Abhishek et.

al Himalayan Journal of Health Sciences ISSN: 2582 - 0737

Myocardial Infarction
Available online at www.hjhs.co.in
REVIEW ARTICLE
Abhishek Kumar Singh* and Dr Rakesh Kumar Jat
Institute of Pharmacy, Shri Jagdishprasad Jhabarmal Tibrewala University
Jhunjhunu (Rajasthan) India -333001.
DOI 10.22270/hjhs.v6i4.116

ABSTRACT
Myocardial infarction (MI), commonly known as a heart attack is the disease of the blood vessels
supplying the heart muscle (Myocardium) i.e. coronary heart disease. The area of heart muscle that has
either zero flow or so little flow that it cannot sustain cardiac muscle function is said to be infracted and
the overall process is called a myocardial infarction. MI are of two types; transmural and subendocardial.
Mainly it is caused due to oxidative stress and atherosclerosis.Chest pain is the most common symptom of
acute MI and is often described as a sensation of tightness, pressure, or squeezing. Other symptoms
include diaphoresis (an excessive form of sweating), Shortness of breath (dyspnea), weakness, light-
headedness, nausea, vomiting, and palpitations. The most common symptoms of MI in women include
dyspnea, weakness, and fatigue, sleep disturbances. It can be treated by using blockers, diuretics, ACE
inhibitors, calcium channel blockers and nitrates.
Keywords: Myocardial Infarction; Atherosclerosis; Transmural: Subendocardial: Oxidative Stress

1. Introduction either zero flow or so little flow that it

cannot sustain cardiac muscle function is
Myocardial infarction (MI), commonly
said to be infracted and the overall process
known as a heart attack is the disease of
is called a myocardial infarction. (1)
the blood vessels supplying the heart
muscle (Myocardium) i.e. coronary heart
disease. The area of heart muscle that has

Figure 1.1 Myocardial infarction (Source: web-books.com)

Soon after the onset of the infarction, blood flow through anastigmatic channel
the area to become overfilled with stagnant to the infracted area and progressive
blood as a combined effect of collateral dilation of local blood vessels.

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Simultaneously the muscle fibers use the muscle cells begin to swell because of
last vestiges of the oxygen in the blood, diminished cellular metabolism. Within a
causing the hemoglobin to become totally few hours of almost no blood supply, the
de-oxygenated. Therefore, the infracted cardiac muscle cells die. Cardiac muscle
area takes on a bluish-brown. In later requires about 1.3 milliliters of oxygen per
stages, the vessel walls become highly 100 grams of muscle tissue per minute just
permeable and leak fluid; the local muscle to remain alive. (1)
tissue becomes edematous, and the cardiac
CLASSIFICATION:
Myocardial Infarction

NSTEMI STEMI

Non Q-wave MI Q-wave MI

Figure 1.2 Classification of MI.

cancer (malignant neoplasm). (3) Coronary
There are two basic types of MI: heart disease is responsible for 1 in 5
Transmural: associated with deaths in the U.S.This means that roughly
atherosclerosis involving major coronary every 65 seconds, an American dies of a
artery. It can be sub classified into coronary event. (4)
anterior, posterior, or inferior. Transmural In India, cardiovascular disease (CVD) is
infarcts extend through the whole the leading cause of death. (5) The deaths
thickness of the heart muscle and are due to CVD in India were 32% of all
usually a result of complete occlusion of deaths in 2007 and are expected to rise
the area's blood supply.
from 1.17 million in 1990 and 1.59 million
Subendocardial: involves small area in the in 2000 to 2.03 million in 2010. (6)
subendocardial wall of the left ventricle, Although a relatively new epidemic in
ventricular septum, or papillary muscles. India, it has quickly become a major health
Subendocardial infarcts are thought to be a issue with deaths due to CVD expected to
result of locally decreased blood supply, double during 1985-2015. (7-9)
possibly from a narrowing of the coronary
arteries. The Subendocardial area is Legal Implication
farthest from the heart's blood supply and At common law, MI is generally a
is more susceptible to this type of disease, but may sometimes be an injury.
pathology. This has implications for no-fault
Clinically, MI is further sub classified into insurance schemes such as workers'
ST elevation MI versus non ST elevation compensation. A heart attack is generally
MI based on ECG changes. not covered (10); however, it may be a
Epidemiology work-related injury if it results, for
example, from unusual emotional stress or
MI is a common presentation of unusual exertion. (11) Additionally, in
ischemic heart disease. The WHO some jurisdictions, heart attacks suffered
estimated that in 2002, 12.6 percent of by persons in particular occupations such
deaths worldwide were from ischemic as police officers may be classified as line-
heart disease. (2) In the United States, of-duty injuries by statute or policy. In
diseases of the heart are the leading cause some countries or states, a person who has
of death, causing a higher mortality than

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suffered from a MI may be prevented from oxidase, aldehyde oxidase and membrane-
participating in activity that puts other associated NADPH oxidases. In addition,
people's lives at risk, for example driving a phagocytic cells, including macrophages
car or flying an airplane. (12) and monocytes, increase their O2 uptake
when stimulated and release large amounts
2. Causes
of O2·‒ into the extracellular fluid through
1) Oxidative Stress the action of NADPH oxidase. Although
Oxidative stress is caused by an O2·‒ is not particularly reactive, having a
imbalance between the production of low second-order rate constant with
reactive oxygen and a biological system's biomolecules, it is capable of diffusing
ability to readily detoxify the reactive through relatively large distances through
intermediates or easily repair the resulting the cell where, in the presence of Fe and
damage. All forms of life maintain a Cu, a metal-catalysed Haber-Weiss
reducing environment within their cells. reaction is thought to occur resulting in the
This reducing environment is preserved by formation of the highly reactive hydroxyl
enzymes that maintain the reduced state radical (OH· ). (14)
through a constant input of metabolic Other radicals include the lipid peroxy-
energy. A particularly destructive aspect of (LOO·) radical, and alkoxy- radicals (LO·).
oxidative stress is the production of Other molecules, including peroxynitrite
reactive oxygen species (ROS), which (ONOO‒), hypochlorous acid (HOCl‒),
include free radicals and peroxides. and hydrogen peroxide (H2O2) are not
Disturbances in this normal redox state can radicals but have strong oxidant properties
cause toxic effects through the production and are, therefore, included as ROS. (15)
of peroxides and free radicals that damage Another relevant group of molecules are
all components of the cell, including the reactive nitrogen species (RNS)
proteins, lipids and DNA. In humans, including nitric oxide (NO·), the nitrogen
oxidative stress is involved in many dioxide radical (NO2·), and the
diseases, such as atherosclerosis, MI. (13) nitrosonium cation (NO+). Peroxynitrite is
considered both an ROS and RNS and is
ROS are metabolites of oxygen that can formed by the near diffusion-limited
either strip electrons away from other reaction between O2·‒ and NO. RNS are
molecules (oxidize), donate electrons to important, because they often react with
molecules (reduce), or react with and and modify proteins and other cellular
become part of molecules (i.e., oxidative structures and alter function of these
modification). A particularly important targets. (16,17)
radical for cardiovascular biology is In addition to ROS-forming enzymes,
superoxide (O2·‒), which is formed by the mammalian cells produce myriad
one-electron reduction of oxygen. (O2·‒) is molecules and enzymes that remove ROS.
important because it can serve as both an Some of these are small molecules, such as
oxidant and as a reductant in biologic the thiol-containing tripeptide glutathione.
systems and is a progenitor for other ROS. Others are enzymes that catalyze removal
Endogenous production of free radicals of ROS, such as the superoxide dismutases
occurs during normal aerobic metabolism. (SODs), which catalyze dismutation of
Activated oxygen intermediates are O2·‒ to H2O2 and water; catalase, which
formed by stepwise reduction of O2 to converts H2O2 to oxygen and water; the
water and by secondary reactions with glutathione peroxidases, which use H2O2
protons and transition metals such as Fe and glutathione as co-substrates to form
and Cu. The superoxide anion (O2·‒) is water and glutathione disulfide;
produced by many cell redox systems thioredoxin; and others. (18)
including ischemia-derived xanthine

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Sources of reactive oxygen/nitrogen react with metal ions, metalloproteins, and

species: O2·‒ to form reactive nitrogen species.
Perhaps the best characterized of these
NAD(P)H oxidases (Nox)
reactions is the combination of NO and
The phagocytes, including neutrophils, O2·‒ to generate ONOO−. Among the most
monocytes, and macrophages, contain a abundant biological targets for ONOO− is
plasma membrane-bound multicomponent carbon dioxide (CO2). The reaction of
oxidase that utilizes NADPH-derived ONOO− with CO2 is complex and initially
electrons and Activation of the oxidase in produces nitrosoperoxycarbonate which
phagocytic cells results in large amounts homolyzes to form a pair of caged radicals
of O2·‒ over short periods that appear to be that may then diffuse apart to become free
involved in host defense. NAD(P)H radicals, or recombine to form nitro
oxidases in vascular cells are subject to carbonate (O2NOCO2), which decomposes
activation by specific agonists that include to nitrite and CO2. The formation of free
angiotensin II, thrombin, platelet-derived nitrogen dioxide (•NO2) readily leads to
growth factor, tumor necrosis factor-α, protein tyrosine nitration and lipid
interleukin-, and, for endothelial cells, peroxidation. (19-21)
mechanical forces (including shear stress)
Myeloperoxidase
and vascular endothelial growth factor.
(19,20) Myeloperoxidase is the only human
enzyme that generates HOCl; chlorinated
Xanthine oxidase
biomolecules are considered specific
Xanthine oxidase is an iron–sulfur markers of MPO-mediated oxidation
molybdenum flavoprotein with multiple reactions. Myeloperoxidase can yield a
functions that exists in two forms, xanthine number of products, including 3-
dehydrogenase and xanthine oxidase, the chlorotyrosine, chlorohydrins from
former being predominant. The oxidation cholesterol and fatty acids, and tyrosyl
of xanthine or hypoxanthine to uric acid is radicals, with the latter species able to
associated with NADH production by the participate in single electron oxidation
dehydrogenase, whereas the oxidase reactions, including the oxidation of LDL.
generates O2·‒. The dehydrogenase is Another activity of myeloperoxidase and
readily converted into the oxidase by HOCl is to convert L-tyrosine into
proteolysis or by reversible oxidation of phydroxyphenylacetaldehyde which can
thiol groups. Xanthine oxidase contributes react with amino phospholipids and the ε-
to impaired •NO bioactivity observed with amino groups of protein lysine residues.
hypercholesterolemia, heavy smoking, and The product of these reactions may be
coronary disease. (21) subsequently modified by
Nitric oxide synthases myeloperoxidase to generate a variety of
reactive aldehyde residues. Furthermore,
A relative cofactor deficiency for L-serine is readily converted by
enzyme catalysis allows the enzyme to myeloperoxidase to Ne- (carboxymethyl)
reduce molecular oxygen rather than lysine, a well-characterized advanced
transfer electrons to Larginine, thereby glycation end-product. Thus,
generating O2·‒ by the oxygenase domain myeloperoxidase and HOCl can generate a
of the enzyme through dissociation of a series of secondary oxidation products that
ferrous–dioxygen complex that is normally may oxidize biomolecules, including LDL,
stabilized by tetrahydrobiopterin. In rendering them capable of converting
atherosclerosis and diabetes there is macrophages into foam cells. (19,20)
evidence that vascular tetrahydrobiopterin
levels may be depressed. Nitric oxide may Mitochondrial respiration

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Conventional wisdom dictates that up to on. Cholesterol does not dissolve in water.
1–2% of electron flow through the Cholesterol can move in the bloodstream
respiratory chain may be diverted to only by being transported by LDL. (1, 20)
molecular oxygen. Thus; one must The initial damage to the blood vessel wall
consider the mitochondrion as a potential results in a "call for help," an
major intracellular source of reactive inflammatory response. Monocytes enter
oxygen species. Mitochondrial oxidant the artery wall from the bloodstream, with
production is controlled, in part, by the platelets adhering to the area of insult.
expression of a mitochondrial Mn- This may be promoted by redox signaling
containing superoxide dismutase located in induction of factors such as VCAM-1,
the mitochondrial matrix. (19-21) which recruit circulating monocytes. The
monocytes differentiate macrophages
2) Atherosclerosis
which ingest oxidized LDL, slowly turning
Atherosclerosis is the condition in into large "foam cells" - so-described
which an artery wall thickens as the result because of their changed appearance
of a buildup of fatty materials such as resulting from the numerous internal
cholesterol. It is a chronic inflammatory cytoplasmic vesicles and resulting high
response in the walls of arteries, in large lipid content. Unfortunately, these white
part due to the accumulation of blood cells are not able to process the
macrophage white blood cells and oxidized-LDL, and ultimately grow then
promoted by low density lipoproteins rupture, depositing a greater amount of
(plasma proteins that carry cholesterol and oxidized cholesterol into the artery wall.
triglycerides) without adequate removal of This triggers more white blood cells,
fats and cholesterol from the macrophages continuing the cycle. Eventually, the artery
by functional high density lipoproteins becomes inflamed. The cholesterol plaque
(HDL). Complications of atherosclerosis causes the muscle cells to enlarge and
are chronic, slowly progressive and form a hard cover over the affected area.
cumulative. Most commonly, soft plaque This hard cover is what causes a narrowing
suddenly ruptures causing the formation of of the artery, reduces the blood flow and
a thrombus that will rapidly slow or stop increases blood pressure. (23)
blood flow, leading to death of the tissues
fed by the artery. This catastrophic event is 3. Symptoms of MI
called an infarction. One of the most The onset of symptoms in MI is usually
common recognized scenarios is called gradual, over several minutes, and rarely
coronary thrombosis of a coronary artery, instantaneous. Chest pain is the most
causing MI. Even worse is the same common symptom of acute MI and is often
process in an artery to the brain, described as a sensation of tightness,
commonly called stroke. (22) pressure, or squeezing. Other symptoms
include diaphoresis (an excessive form of
Atherosclerosis develops from low-density
sweating), Shortness of breath (dyspnea),
lipoprotein molecules (LDL) becoming
weakness, light-headedness, nausea,
oxidized by free radicals, particularly
vomiting, and palpitations. The most
oxygen free radicals (ROS). When
common symptoms of MI in women
oxidized LDL comes in contact with an
include dyspnea, weakness, and fatigue,
artery wall, a series of reactions occur to
sleep disturbances. In women, chest pain
repair the damage to the artery wall caused
may be less predictive of coronary
by oxidized LDL. The LDL molecule is
ischemia than in men. (24)
globular shaped with a hollow core to
carry cholesterol throughout the body to Approximately one fourth of all MI are
generate brain tissues, vitamin D, and so silent, without chest pain or other

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symptoms. (25) These cases can be the ability of platelets to aggregate varies
discovered later on electrocardiograms or according to a circadian rhythm, although
at autopsy without a prior history of they have not proven causation. (33)
related complaints. A silent course is more Some investigators theorize that this
common in the elderly, in patients with increased incidence may be related to the
diabetes mellitus and after heart circadian variation in cortisol production
transplantation, probably because the affecting the concentrations of various
donor heart is not connected to nerves of cytokines and other mediators of
the host. (26) inflammation. (34)
Risk factors for atherosclerosis are
4. Risk factors
generally risk factors for MI:
Heart attack rates are higher in
association with intense exertion, be it  Diabetes (with or without insulin
psychological stress or physical exertion, resistance) - the single most important
especially if the exertion is more intense risk factor for ischaemic heart disease
than the individual usually performs. (IHD)
Quantitatively, the period of intense  Tobacco smoking
exercise and subsequent recovery is  Hypercholesterolemia (more
associated with about a 6-fold higher MI accurately hyperlipoproteinemia,
rate (compared with other more relaxed especially high LDL and low HDL)
time frames) for people who are physically  High blood pressure
very fit. (27) For those in poor physical  Family history of IHD
condition, the rate differential is over 35-  Obesity (35) (defined by a body mass
fold higher. (27) One observed mechanism index of more than 30 kg/m², or
for this phenomenon is the increased alternatively by waist circumference or
arterial pulse pressure stretching and waist-hip ratio).
relaxation of arteries with each heart beat  Age: Men acquire an independent risk
which, as has been observed with factor at age 45, Women acquire an
intravascular ultrasound, increases independent risk factor at age 55; in
mechanical "shear stress" on atheromas addition individuals acquire another
and the likelihood of plaque rupture. (27) independent risk factor if they have a
Acute severe infection, such as first-degree male relative (brother,
pneumonia, can trigger MI. A more father) who suffered a coronary
controversial link is that between vascular event at or before age 55.
Another independent risk factor is
Chlamydophila pneumoniae infection and
acquired if one has a first-degree
atherosclerosis. (28) While this
intracellular organism has been female relative (mother, sister) who
suffered a coronary vascular event at
demonstrated in atherosclerotic plaques,
age 65 or younger.
evidence is inconclusive as to whether it
can be considered a causative factor. (28)  Hyperhomocysteinemia (high
Treatment with antibiotics in patients with homocysteine, a toxic blood amino
proven atherosclerosis has not acid that is elevated when intakes of
demonstrated a decreased risk of heart vitamins B2, B6, B12 and folic acid
attacks or other coronary vascular are insufficient)
diseases. (29)  Stress (occupations with high stress
There is an association of an increased index are known to have susceptibility
incidence of a heart attack in the morning for atherosclerosis)
hours, more specifically around 9 a.m. (30-  Alcohol Studies show that prolonged
32) Some investigators have noticed that exposure to high quantities of alcohol
can increase the risk of heart attack.

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Males are more at risk than females. accumulation of hydrogen ions and lactate,
(27) resulting in intracellular acidosis and
inhibition of residual energy metabolism.
5. Mechanism of MI
(36) Impaired contraction with persistent
Fatty acids are the main fuel for the electrical activity develops in association
healthy heart, supplying approximately 60- with alterations in ion transport systems in
80% of the energy. Myocardial ischemia the sarcolemma and organellar
dramatically alters fuel metabolism. (20) membranes. (37) Reduced aerobic ATP
Sudden occlusion of a major branch of a formation stimulates glycolysis and an
coronary artery shifts aerobic or increase in myocardial glucose uptake and
mitochondrial metabolism to anaerobic glycogen breakdown. At the same time
glycolysis within seconds. A decreased ATP inhibits Na+, K+-ATPase,
compensatory increase in anaerobic increasing intracellular Na+ and Cl-,
glycolysis for ATP production leads to the leading to cell swelling. (38)

Figure 1.3 Myocardial infarction.

An early increase in cytosolic Ca2+ also damaged by per oxidative damage from
develops due to multifactorial changes in free radicals and toxic oxygen species.
transport systems in the sarcolemma and (41)
sarcoplasmic reticulum. Ca2+-induced
6. Pathophysiology
activation of proteases causes alterations in
contractile proteins, decreased sensitivity A MI occurs when an atherosclerotic
to Ca2+, and sustained impairment of plaque slowly builds up in the inner lining
contractility despite the elevated cytosolic of a coronary artery and then suddenly
Ca2+ . (39) ruptures, totally occluding the artery and
Ultra structurally, reversibly injured preventing blood flow downstream.
myocytes are edematous and swollen from The most common triggering event is the
the osmotic overload. The cell size is disruption of an atherosclerotic plaque in
increased with a decrease in the glycogen an epicardial coronary artery, which leads
content. (40) Increased cytosolic Ca2+ and to a clotting cascade, sometimes resulting
mitochondrial impairment cause in total occlusion of the artery.
phospholipase activation and release of Atherosclerosis is the gradual buildup of
lysophospholipids and free fatty acids, cholesterol and fibrous tissue in plaques in
which are incorporated within the cell and the wall of arteries (in this case, the

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coronary arteries), typically over decades. When a severe enough plaque rupture
Blood stream column irregularities visible occurs in the coronary vasculature, it leads
on angiography reflect artery lumen to MI (necrosis of downstream
narrowing as a result of decades of myocardium).
advancing atherosclerosis. Plaques can If impaired blood flow to the heart lasts
become unstable, rupture, and additionally long enough, it triggers a process called
promote a thrombus (blood clot) that the ischemic cascade; the heart cells in the
occludes the artery; this can occur in territory of the occluded coronary artery
minutes. die (chiefly through necrosis) and do not
grow back.

Figure 1.4 the inner lining of a coronary artery

A collagen scar forms in its place. Recent However, ventricular tachycardia usually
studies indicate that another form of cell results in rapid heart rates that prevent the
death called apoptosis also plays a role in heart from pumping blood effectively.
the process of tissue damage subsequent to Cardiac output and blood pressure may fall
MI. (42) As a result, the patient's heart will to dangerous levels, which can lead to
be permanently damaged. This Myocardial further coronary ischemia and extension of
scarring also puts the patient at risk for the infarct.
potentially life threatening arrhythmias, The cardiac defibrillator is a device that
and may result in the formation of a was specifically designed to terminate
ventricular aneurysm that can rupture with these potentially fatal arrhythmias. The
catastrophic consequences. device works by delivering an electrical
Injured heart tissue conducts electrical shock to the patient in order to depolarize
impulses more slowly than normal heart a critical mass of the heart muscle, in
tissue. The difference in conduction effect "rebooting" the heart. This therapy
velocity between injured and uninjured is time dependent, and the odds of
tissue can trigger re-entry or a feedback successful defibrillation decline rapidly
loop that is believed to be the cause of after the onset of cardiopulmonary arrest.
many lethal arrhythmias. The most serious
7. Diagnosis Criteria
of these arrhythmias is ventricular
fibrillation (V-Fib/VF), an extremely fast WHO criteria
and chaotic heart rhythm that is the leading WHO criteria (43) have classically been
cause of sudden cardiac death. Another life used to diagnose MI; a patient is diagnosed
threatening arrhythmia is ventricular with MI if two (probable) or three
tachycardia (V-Tach/VT), which may or (definite) of the following criteria are
may not cause sudden cardiac death. satisfied:

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Clinical history of ischaemic type chest Electrocardiograph

pain lasting for more than 20 minutes The electrocardiogram (ECG or EKG,
Changes in serial ECG tracings abbreviated from the German
Change in serum cardiac biomarkers such Elektrokardiogramm) is a graphic
as creatine kinase-MB fraction and recording of electric potentials generated
troponin I. by the heart. The signals are detected by
The WHO criteria were refined in 2000 to means of metal electrodes attached to the
give more prominence to cardiac extremities and chest wall and are then
biomarkers. (44) According to the new amplified and recorded by the
guidelines, a cardiac troponin, myoglobin electrocardiograph. ECG leads actually
rise accompanied by typical symptoms, display the instantaneous differences in
pathological Q waves, ST elevation or potential between these electrodes. (45)
depression or coronary interventions are
diagnostic of MI.

Figure 1.5 Electrocardiogram –I

The clinical utility of the ECG derives infarction has refocused particular
from its immediate availability as a attention on the sensitivity and specificity
noninvasive, inexpensive, and highly of ECG signs of myocardial ischemia. (46)
versatile test. In addition to its use in Many cardiac abnormalities alter the
detecting arrhythmias, conduction heart‟s electrical activity, and cause
disturbances, and myocardial ischemia, changes in the ECG. Since the electrical
electrocardiography may reveal other activity of both atria and ventricles is
findings related to life-threatening reflected in the ECG, the test is of
metabolic disturbances (e.g., particular value in defining cardiac
hyperkalemia) or increased suspectibity to rhythm. Diseases which result in changes
sudden cardiac death (e.g., QT in the myocardial muscle mass will alter
prolongation syndromes). The advent of the ECG. Diseases which cause death of
coronary thrombolysis or angioplasty in heart muscle and replacement by scar
the early therapy of acute myocardial tissue (such as MI) will be reflected in

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characteristic changes in morphology of alterations in the repolarization of muscle

the QRS complex. Inadequate blood cells, which will be reflected in
supply to heart muscle resulting from characteristic changes in the ST-T wave
coronary artery disease may cause portion of the electrocardiogram.

Figure 1.6 Electrocardiogram (47)

From left to right the first deflection seen The QRS wave complex follows the PR
in Figure 1.6 is labeled a P-wave. It segment. It represents ventricular
represents the voltage change at the body‟s depolarization, lasts approximately 80-100
surface caused by the depolarization of the milliseconds, and has amplitude of 0.5-1.0
atria. Atrial depolarization is usually millivolts. The QRS depolarization is
complete in about 0.1 seconds. Therefore, much greater in amplitude than the P-wave
the P-wave usually spans about 2.5 complex because of the greater muscular
millimeters. A P-wave typically stands 1-2 mass of the ventricle, and the greater
millimeters tall (0.1-0.2 millivolts). synchronization of depolarization by the
Once the P-wave is completed, an high speed ventricular conduction system.
isoelectric segment follows during which At the completion of the QRS complex,
no surface potential is visible using another segment of zero voltage normally
ordinary equipment. During this time the follows: the ST segment. It corresponds to
cardiac action potential passes through the the plateau period of the action potential
AV node and ventricular conduction during which the ventricles remain
system. depolarized. It typically lasts 150
The interval from the beginning of the P- milliseconds, but is a function of heart
wave to the beginning of the QRS complex rate.
is called the PR interval and is normally no The T-wave follows the ST-segment, and
longer than 0.2 seconds in adults (Figure corresponds to ventricular repolarization.
1.6). Cellular repolarization is a much slower
A wave corresponding to atrial process than depolarization. Also,
repolarization occurs, but is ordinarily repolarization does not appear to propagate
buried in the QRS complex, and is not from cell to cell. Rather, individual cells
identifiable in the ECG. repolarize independently depending on
their individual plateau duration. Whereas

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depolarization spreads from endocardium Depolarization of the heart is the

to epicardium, repolarization normally initiating event for cardiac contraction.
proceeds in the opposite direction (the The electric currents that spread through
action potentials of epicardial cells are the heart are produced by three
shorter than those of endocardial cells). components: cardiac pacemaker cells,
Normal T-wave duration is 0.15-0.20 specialized conduction tissue, and the
seconds, and normal amplitude in the limb heart muscle itself. The ECG, however,
leads is less than 0.6 millivolts (48) records only the depolarization
(stimulation) and repolarization (recovery)
Electrophysiology
potentials generated by the atrial and
ventricular myocardium.

Figure 1.7 Electrocardiogram –II (43)

P wave is 110 milliseconds or less in segment depression may indicate atrial
duration; the first two-thirds are from right injury or pericarditis.
atrial depolarization, the last two-thirds QRS complex is 120 milliseconds or less
from left atrial depolarization. In healthy in duration. The QRS complex
person, the P wave is upright in lead II and corresponds to the depolarization of the
biphasic in lead V1; the first, positive ventricles. Because the ventricles contain
deflection is larger than the second, more muscle mass than the atria, the QRS
negative one. complex is larger than the P wave. In
PR interval is 120–200 milliseconds in addition, because the His/Purkinje system
duration. A short PR interval may indicate coordinates the depolarization of the
an accessory pathway, which allows early ventricles, the QRS complex tends to look
ventricular depolarization („pre- "spiked" rather than rounded due to the
excitation‟). A long PR interval reflects increase in conduction velocity. The
slow conduction through the AV node and duration, amplitude, and morphology of
bundle of His, and may indicate a the QRS complex is useful in diagnosing
conducting tissue disease predisposing to cardiac arrhythmias, conduction
bradyarrhythmia through high-grade AV abnormalities, ventricular hypertrophy,
block. A PR interval of over 200 ms may myocardial infarction, electrolyte
indicate a first degree heart block. PR derangements, and other disease states.

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Q waves can be normal (physiological) or Inverted (or negative) T waves can be a

pathological. Normal Q waves, when sign of coronary ischemia, left ventricular
present, represent depolarization of the hypertrophy. Tall or "tented" symmetrical
interventricular septum. For this reason, T waves may indicate hyperkalemia. Flat
they are referred to as septal Q waves. Q T waves may indicate coronary ischemia
waves greater than 1/3 the height of the R or hypokalemia. The earliest
wave, greater than 0.04 sec (40 ms) in electrocardiographic finding of acute
duration, or in the right precordial leads myocardial infarction is sometimes the
are considered to be abnormal, and may hyper acute T wave, which can be
represent myocardial infarction. distinguished from hyperkalemia by the
broad base and slight asymmetry.
RT segment connects the QRS complex
and the T wave and has duration of 80 QT interval is 0.30 and 0.44 seconds in
to120 millisecond. It starts at the J point duration. The QT interval is important in
and ends at the beginning of the T wave. the diagnosis of long QT syndrome and
However, since it is usually difficult to short QT syndrome. The QT interval
determine exactly where the ST segment represents on an ECG the total time
ends and the T wave begins, the needed for the ventricles to depolarize and
relationship between the RT segment and repolarize.
T wave should be examined together. U wave is not always seen. It is typically
ST segment is isoelectric. „Physiological‟ small, and, by definition, follows the T
ST elevation is usually restricted to leads wave. U waves are thought to represent
V1 to V3/4. Flat, down sloping or repolarization of the papillary muscles or
depressed ST segments may indicate Purkinje fibers. Prominent U waves are
coronary ischemia. ST segment elevation most often seen in hypokalemia, but may
may indicate myocardial infarction. be present in hypercalcemia,
thyrotoxicosis, or exposure to digitalis,
T wave represents the repolarization (or
epinephrine, and Class 1A and 3
recovery) of the ventricles. The interval
antiarrhythmics, as well as in congenital
from the beginning of the QRS complex to
long QT syndrome and in the setting of
the apex of the T wave is referred to as the
intracranial hemorrhage. An inverted U
absolute refractory period. The last half of
wave may represent myocardial ischemia
the T wave is referred to as the relative
or left ventricular volume overload. (26,44)
refractory period.
Sequential changes of acute MI (44)

Figure 1.8 Sequential changes of acute MI.

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Abhishek et.al Himalayan Journal of Health Sciences ISSN: 2582 - 0737

Control, normal appearances are shown Myoglobin (Mb) has low specificity for
in the lead, which, as can be seen by its myocardial infarction and is used less than
QRS morphology, lies facing the left the other markers.
ventricle. Cardiac markers or cardiac enzymes are
The typical, convex upwards S-T elevation proteins from cardiac tissue found in the
is shown occurring within hours of the blood. These proteins are released into the
onset of symptoms of infarction. At this bloodstream when damage to the heart
stage, there is no change in the QRS occurs, as in the case of MI. Depending on
complex. the marker, it can take between 2 to 24
The appearances within days of the onset hours for the level to increase in the blood.
are shown. There is loss of R wave height, Additionally, determining the levels of
abnormal Q waves (in this case in both cardiac markers in the laboratory - like
depth and duration) have developed, and many other lab measurements - takes
there is T wave inversion. The loss of R substantial time. Cardiac markers are
wave height and the abnormal Q waves therefore not useful in diagnosing a MI in
prove infarction. The S-T segment and T the acute phase. Also these enzyme levels
wave changes indicate that the event is are not elevated immediately following a
recent. heart attack, patients presenting with chest
Resolution of the S-T segment change is pain are generally treated with the
shown. In other respects, the appearances assumption that a MI has occurred and
are similar to c. The loss of R wave height then evaluated for a more precise
and the abnormal Q waves prove diagnosis. (50) The clinical presentation
infarction. The normal S-T segment and results from an ECG are more
indicates that the event is not very recent appropriate in the acute situation. Now a
(i.e. not within days) but T wave changes day‟s novel cardioprotective “urocortins”
indicate that the event is relatively recent and “endoglin” determination is used as a
(within weeks). novel prognostic marker after AMI.
Restoration of an upright T wave is shown, (51,52)
but this is otherwise similar to d. The loss
Histopathology
of R wave height and the abnormal Q
waves prove infarction. The normal S-T
segment indicates that the event is not very
recent (i.e. not within days) and the normal
T wave that the event is relatively old (not
within weeks).
Cardiac Marker
Medical tests that are often referred to
Figure 1.9 Microscopy image (magn. ca
as cardiac markers include (1, 49):
100x, H&E stain) from autopsy specimen
Cardiac troponin (the most sensitive and of myocardial infarct (7 days post-
specific test for myocardial damage) infarction).
Creatine kinase (CK, also known as Histopathological examination of the heart
phosphocreatine kinase or creatine may reveal infarction at autopsy. Under
phosphokinase) the microscope, MI presents as a
Aspartate transaminase (AST, also called circumscribed area of ischemic,
Glutamic Oxaloacetic Transaminase coagulative necrosis (cell death). On gross
(GOT/SGOT) or aspartate examination, the infarct is not identifiable
aminotransferase (ASAT)). within the first 12 hours. (53)
Lactate dehydrogenase (LDH)

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Abhishek et.al Himalayan Journal of Health Sciences ISSN: 2582 - 0737

infiltrated with neutrophils, then with

lymphocytes and macrophages, who
phagocytes ("eat") the myocytes debris.
The necrotic area is surrounded and
progressively invaded by granulation
tissue, which will replace the infarct with a
fibrous (collagenous) scar (which are
Figure 1.10 Micrograph of a MI (ca. 40x
typical steps in wound healing). The
H&E stain) with prominent contraction
interstitial space (the space between cells
band necrosis.
outside of blood vessels) may be infiltrated
Although earlier changes can be discerned
with red blood cells. (53)
using electron microscopy, one of the
These features can be recognized in cases
earliest changes under a normal
where the perfusion was not restored;
microscope are so-called wavy fibers. (54)
reperfused infarcts can have other
Subsequently, the myocytes cytoplasm
hallmarks, such as contraction band
becomes more eosinophilic (pink) and the
necrosis. (56)
cells lose their transversal striations, with
8. Treatment of MI
typical changes and eventually loss of the
cell nucleus. (55) The interstitium at the
margin of the infracted area is initially
Table 1.1 Treatment of MI (56)
Class of drug Action Drug
Beta blockers heart‟s workload↓ Nadolol, Metoprolol, Pindolol,
Bisoprolol etc.
Diuretics Rid body of excess fluid and Hydrochlorothiazide, Chlorothiazide,
salt Furosemide,
Triamterene,Spironolactone etc
ACE inhibitors Prevent blood vessel Benazepril, Lisinopril, Captopril,
constriction Ramipril, Fosinopril, Moexipril.
Calcium channel prevent blood vessel Verapamil, Diltiazem, Nifedipine.
blockers constriction by blocking
calcium ions
Nitrates Help relax the myocardium Nitroglycerin, Isosorbide dinitrate.
and blood vessels
9. Discussion medical therapy after acute myocardial
infarction. Relevant to this discussion is
Beta-blockers, angiotensin-converting–
the observation that ACE inhibitors block
enzyme (ACE) inhibitors, and aldosterone
only 13 percent of the total production of
antagonists have been shown to reduce the
angiotensin II in the human heart because
overall risk of death as well as the risk of
of the existence of ACE-independent
major nonfatal cardiovascular events when
pathways (e.g, chymase, cathepsin, and
they are administered to patients with
kallikrein) that convert angiotensin I to
acute myocardial infarction who also have
angiotensin II. (59)
left ventricular systolic dysfunction,
clinical evidence of heart failure, or both. These observations provided the impetus
(57,58) However, there remains a sizable for the development of angiotensin-
subgroup of patients in whom clinical receptor antagonists that offer more
heart failure worsens despite optimal complete protection against angiotensin II

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Abhishek et.al Himalayan Journal of Health Sciences ISSN: 2582 - 0737

by directly blocking the angiotensin type I in hypertension. 1st edition. Abingdon (UK): Taylor
& Francis Medical Books; 2006.
receptor. 14. Duthie GG, Wahle KWJ, James WPT. Oxidants,
antioxidants and cardiovascular disease. Nutrition
Acknowledgements Research Reviews. 1989;2:51-62.
We would like to convey our sincere 15. Sawyer DB, Siwik DA, Xiao L, Pimentel DR, Singh
K, Colucci WS, et al. Role of oxidative stress in
gratitude towards the HJHS Journal for myocardial hypertrophy and failure. J. Mol. Cell.
publishing our article. Cardiol. 2002;34:379-388.
16. David GH, Maria CG. Oxidative Stress and Hyper
Financial Disclosure statement: The tension. Med. Clin. N. 2009;93:621-635.
author received no specific funding for this 17. Scandalios JG. Oxidative stress responses- what
have genome-scale studies taught us? Genome
work. Biology. 2002; 3(7):1019.1-1019.6
18. Wassmann S, Wassmann K, Nickenig G.
Conflict of Interest Regulation of antioxidant and oxidant enzymes in
vascular cells and implications for vascular disease.
The authors declare that there is no Curr Hypertens Rep. 2006;8(1):69-78.
conflict of interest regarding the 19. Mainzen PS, Karthick M. Preventive effect of rutin,
publication of this article. a bioflavonoid, on lipid peroxides and antioxidants
in ISO-induced myocardial infarction in rats.
References Preventive Effect of Rutin on Lipids, Lipoproteins,
and ATPases in Normal and Isoproterenol-Induced
1. Mohan H. Textbook of Pathophysiology. 5th Ed. Myocardial Infarction in Rats. J Biochem Molecular
New Delhi: Jaypee Brothers medical publishers (p) Toxicology. 2007;21;1: 701-707.
ltd; 2005. 20. Stocker R, Keaney FK. Oxidative stress and
2. Robert Beaglehole, et al. The World Health Report atherosclerosis. In: Loscalzo J. editor; Molecular
2004 - Changing History. World Health mechanisms of atherosclerosis. London and New
Organization; 2004. pp. 120–4. York: Taylor & Francis Group Pvt ltd; 2005. p. 83-
3. "Cause of Death - UC Atlas of Global Inequality". 114.
Center for Global, International and Regional 21. Gaetani G, Ferraris A, Rolfo M, Mangerini R,
Studies (CGIRS) at the University of California Arena S, Kirkman H, et al. Predominant role of
Santa Cruz; 2006 Dec 7 catalase in the disposal of hydrogen peroxide within
4. "Deaths and percentage of total death for the 10 human erythrocytes. Blood. 1996; 87(4):1595-1599.
leading causes of death: United States, National 22. Allen PB, Renu V. Pathophysiology of Acute
Center of Health Statistics; 2002-2003 Myocardial Infarction. Med Clin N Am.
5. Mukherjee AK. (1995). "Prediction of coronary 2007;91:553-572.
heart disease using risk factor categories". J Indian 23. Prof. Roger G. Mark. Clinical Electrocardiography
Med Assoc 93 (8): 312–5. PMID 8713248. and Arrhythmias. Massachusetts Institute of
6. Ghaffar A, Reddy KS and Singhi M. "Burden of Technology. Quantitative Physiology: Organ
non-communicable diseases in South Asia". BMJ. Transport Systems. 2004:1-7.
2004; 328 (7443): 807–810. 24. McSweeney JC, Cody M, O'Sullivan P, Elberson K,
doi:10.1136/bmj.328.7443.807. PMID 15070638. Moser DK, Garvin BJ, et al. Women's early warning
7. Rastogi T, Vaz M, Spiegelman D, Reddy KS, symptoms of acute myocardial infarction.
Bharathi AV, Stampfer MJ, Willett WC and Circulation. 2003; 108(21): 2619-23.
Ascherio1 A. "Physical activity and risk of coronary 25. Kannel WB. Silent myocardial ischemia and
heart disease in India". Int. J. Epidemiol. infarction: insights from the Framingham Study.
2004;33(4):1-9. Cardiol. Clin. 1986;4(4):583-91.
doi:10.1093/ije/dyh042. PMID 15044412 26. Davis TM, Fortun P, Mulder J, Davis WA, Bruce
8. Gupta R. "Escalating Coronary Heart Disease and DG. Silent myocardial infarction and its prognosis
Risk Factors in South Asians". Indian Heart in a community-based cohort of Type 2 diabetic
Journal.2007;214-17. patients: the Fremantle Diabetes Study.
9. Gupta R, Misra A, Pais P, Rastogi P and Gupta VP. Diabetologia. 2004; 47(3):395-399.
"Correlation of regional cardiovascular disease 27. Wilson PW, D'Agostino RB, Levy D, Belanger AM,
mortality in India with lifestyle and nutritional Silbershatz H, Kannel WB. "Prediction of coronary
factors" (PDF). International Journal of Cardiology. heart disease using risk factor categories".
2006; 108(3):291–300. Doi: Circulation. 1998;97(18):1837-47. PMID 9603539.
10.1016/j.ijcard.2005.05.044. PMID15978684. 28. Saikku P, Leinonen M, Tenkanen L, Linnanmaki E,
10. Workers' Compensation FAQ. Prairie View A&M Ekman MR, Manninen V, Manttari M, Frick MH,
University. 2006 Nov 22. Huttunen JK. "Chronic Chlamydia pneumoniae
11. SIGNIFICANT DECISIONS Subject Index. Board infection as a risk factor for coronary heart disease
of Industrial Insurance Appeals; 2006 Nov 22 in the Helsinki Heart Study". Ann Intern Med. 1992;
12. "Classification of Drivers' Licenses Regulations". 116(4):273-8. PMID 1733381.
Nova Scotia Registry of Regulations; 2000 May 24. 29. Andraws R, Berger JS, Brown DL. "Effects of
13. Harrison DG, Dikalov S. Oxidative events in cell antibiotic therapy on outcomes of patients with
and vascular biology. In: Re RN, DiPette DJ, coronary artery disease: a meta-analysis of
Schriffrin EL, et al, editors. Molecular mechanisms

© 2021 HJHS Journal 2021; 6(4) Page 30

Abhishek et.al Himalayan Journal of Health Sciences ISSN: 2582 - 0737

randomized controlled trials". JAMA. 2005;293 (11):801-11. doi:10.1136/jcp.55.11.801. PMID

(21):2641-7. 12401816
doi:10.1001/jama.293.21.2641. PMID 15928286. 43. Gillum RF, Fortmann SP, Prineas RJ, Kottke TE.
30. Muller JE, Stone PH, Turi ZG, et al. "Circadian International diagnostic criteria for acute
variation in the frequency of onset of acute myocardial infarction and acute stroke. Am. Heart.
myocardial infarction". N. Engl. J. Med. 1985;313 J. 1984; 108:150-158.
(21):1315-22. PMID 2865677 44. Alpert JS, Thygesen K, Antman E, Bassand JP.
31. Beamer AD, Lee TH, Cook EF, et al. "Diagnostic Myocardial infarction redefined a consensus
implications for myocardial ischemia of the document of The Joint European Society of
circadian variation of the onset of chest pain". Am. Cardiology/American College of Cardiology
J. Cardiol. 1987; 60(13):998-1002. Committee for the redefinition of myocardial
doi:10.1016/0002-9149(87)90340-7. PMID infarction. J Am Cell Cardiol. 2000; 36(3):959-69.
3673917. 45. Kasper DL, Braunwald E, Fauci AS, Hauser SL,
32. Cannon CP, McCabe CH, Stone PH, et al. Longo DL, Jameson JL, et al. Harrison‟s Principles
"Circadian variation in the onset of unstable angina of Internal Medicine, Vol II, 16th Ed. New Delhi:
and non-Q-wave acute myocardial infarction (the McGraw-Hill Medical Publishing Division; 2005.
TIMI III Registry and TIMI IIIB)". Am. J. Cardiol. 46. Goldschlager N, Gold man MJ. Principles of
1997; 79(3):253-8. Clinical Electrocardiography. 13th ed. New Delhi:
doi:10.1016/S0002-9149(97)00743-1. McGraw Hill Co-Inc.; 1989.
33. Tofler GH, Brezinski D, Schafer AI, et al. 47. Prof. Roger G. Mark. Clinical Electrocardiography
"Concurrent morning increase in platelet and Arrhythmias. Massachusetts Institute of
aggregability and the risk of myocardial infarction Technology. Quantitative Physiology: Organ
and sudden cardiac death". N. Engl. J. Med. Transport Systems. 2004:1-7.
1987;316(24):1514-8. 48. Davey P. ECG. Medicine. 2006; 34(4):128-135.
PMID 3587281. 49. Ross GE, Bever F, Uddin Z, Devireddy L, Gardin J.
34. Fantidis P, Perez De Prada T, Fernandez-Ortiz A, et Common scenarios to clarify the interpretation of
al. "Morning cortisol production in coronary heart cardiac markers. J. Am. Osteopath. Assoc. 2004;
disease patients". Eur. J. Clin. Invest. 104(4):165-176.
2002;32(5):304–8. 50. Braunwald E, Antman EM, Beasley JW, Califf RM,
doi:10.1046/j.1365-2362.2002.00988.x. PMID Cheitlin MD, Hochman JS et al. ACC/AHA 2002
12027868. guideline update for the management of patients
35. Yusuf S, Hawken S, Ounpuu S, Bautista L, Franzosi with unstable angina and non–ST-segment elevation
MG, Commerford P, Lang CC, Rumboldt Z, Onen myocardial infarction: a report of the American
CL, Lisheng L, Tanomsup S, Wangai P Jr, Razak F, College of Cardiology/American Heart Association
Sharma AM, Anand SS; INTERHEART Study Task Force on Practice Guidelines (Committee on
Investigators. "Obesity and the risk of myocardial the Management of Patients With Unstable Angina).
infarction in 27,000 participants from 52 countries: J. Am. Coll. Cardiol. 2002; 40:1366-1374.
a case-control study". Lancet 2005;366(9497):1640- 51. Boonprasert P, Lailerd N, Chattipakorn N.
9. Urocortins in heart failure and ischemic heart
doi:10.1016/S0140-6736(05)67663- disease. Int. J. Cardiol. 2008; 127:307-312.
5.PMID16271645 52. Cruz-Gonzalez I, Pabon P, Rodriguez-Barbero A,
36. Barar FSK. Essentials of Pharmacotherapeutics. 3rd Martin-Moreiras J, Pericacho M, Sanchez PL et al.
Ed. New Delhi: S. Chand; 2004. Identification of serum endoglin as a novel
37. Thandroyen FT, Bellotto D, Katayama A, Hagler prognostic marker after acute myocardial infarction.
HK, Willerson JT and Buja LM et al. Subcellular J.Cell.Mol.Med. 2008; 12(3):955-961.
electrolyte alterations during progressive hypoxia 53. Rubin's Pathology - Clinicopathological
and following reoxygenation in isolated neonatal rat Foundations of Medicine. Maryland: Lippincott
ventricular myocytes. Circulation Research. 1992; Williams & Wilkins. 2001. p.546. ISBN 0-7817-
71(1):106-119. 4733-3
38. Vandana SP, Suresh RN. Cardioprotective activity 54. Eichbaum FW. "'Wavy' myocardial fibers in
of Ginkgo biloba Phytosomes in isoproterenol- spontaneous and experimental adrenergic
induced myocardial necrosis in rats: A biochemical cardiopathies" Cardiology 1975; 60(6): 358–65.
and histoarchitectural evaluation. Experimental and PMID 782705.
Toxicologic Pathology. 2008; 60:397-404. 55. S Roy. Myocardial infarction. Retrieved November
39. Stanley WC. Cardiac energetics during ischaemia 28, 2006.
and the rationale for metabolic interventions. Coron 56. Fishbein MC. "Reperfusion injury". Clin Cardiol.
Artery Dis. 2001; 12 Suppl 1:S3-7. 1990; 13(3):213-7.
40. Virmani R, Forman MB, Kolodgie FD. Myocardial doi:10.1152/ajpheart.00270.2002
reperfusion injury. Histopathological effects of 57. Pfeffer MA, Braunwald E, Moye LA, et al. Effect of
perfluorochemical. Circulation. 1990; 81(3 Suppl captopril on mortality and morbidity in patients with
IV):57-68. left ventricular dysfunction after myocardial
41. Buja LM. Myocardial ischemia and reperfusion infarction. N Engl J Med. 1992;327:669-77.
injury. Cardiovasc Pathol. 2005; 14(4):170-5. 58. Pitt B, Remme W, Zannad F, et al. Eplerenone, a
42. Krijnen PA, Nijmeijer R, Meijer CJ, Visser CA, selective aldosterone blocker, in patients with left
Hack CE, Niessen HW. "Apoptosis in myocardial ventricular dysfunction after myocardial infarction.
ischaemia and infarction". J Clin Pathol. 2002; 55

© 2021 HJHS Journal 2021; 6(4) Page 31

Abhishek et.al Himalayan Journal of Health Sciences ISSN: 2582 - 0737

N Engl J Med. 2003;348:1309-21. [Erratum, N Engl

J Med 2003;348:2271.]
59. Urata H, Healy B, Stewart RW, Bumpus FM,
Husain A. Angiotensin II-forming pathways in
normal and failing human hearts.Circ Res.
1990;66:883-90.

© 2021 HJHS Journal 2021; 6(4) Page 32