Comprehensive Pathophysiology of Myocardial Ischemia and Injury Explained

[Music] [Music] namaste i'm dr vijay shiragawan

professor head of pathology department chetnal hospital and research institute and i will be talking to you about the

pathophysiology of myocardial ischemia and injury so the objectives of my topic are definition of ischemic heart disease

determinants and physiology of coronary blood flow pathophysiology of ihd whether ischemic heart disease e to

pathogenesis of the ischemic heart disease atherosclerosis endless changes effects of myocardial ischemia and

non-ischemic myocardial injury so coming before we go on to the actual subject

let us first see how the word ischemia was derived it comes from the greek word ischeme which is to restrain in english

and jaima means blood so ischemia occurs when the blood supply to a tissue is inadequate to meet the tissues metabolic

demands ischemic heart disease is a condition in which there is an inadequate supply of

blood and oxygen to a portion of myocardium it typically occurs when there is an

imbalance between myocardial oxygen supply and demand so before going to the etopathogenesis

and the pathophysiology of ischemic heart disease we need to know certain important features of coronary blood

flow which are very unique to only coronary circulation coronary blood flow is largely regulated

by the need of the cardiac muscle for oxygen and under normal resting conditions the

heart extracts about 70 percent of oxygen in the blood as there is little o2 reserve

the coronary arteries must increase their flow to meet the metabolic needs of the myocardium and it is seen that

coronary blood flow is about 225 ml per minute or it roughly represents about four percent to five percent of the

total cardiac output now there are certain points to know about the determinants of coronary blood

flow there are two major determinants of coronary blood flow one is the metabolic activity of the heart itself and second

is the endothelial cell products which are produced in the circulation the metabolic activity of the heart the

metabolites released from working myocardial cells we all know myocardial cells were 24 into seven so the

metabolites coming from these working myocardial cells that is the potassium ions the lactic acid the carbon dioxide

and adenosine all these act as mediators for vasodilation that accompanies increased cardiac work

of these adenosine is appears to be a critical mediator for local blood flow thus we must remember when there is a

when there is actually a reduction in coronary blood flow and coming to endothelial cell products vasodilators

like nitric oxide prostacyclin and endothelium derived hyperpolarizing factor what is called edhf of these the

nitric oxide is the most important one and most of the other vasodilators also exert their action through nitric oxide

so these endothelial cell also release a very powerful vasoconstrictor called endothelin all these cell products are

important when there is a reduction or increase in the coronary blood circulation

and blood flow in the coronary vessel is actually influenced by three major events happening within the cardiac

muscle one is the iotic pressure the second is the autoregulatory mechanisms and third is compression of these intra

myocardial vessels by the contracting heart muscle which is very unique only to heart

so coming to the iotic pressure as we all know the two main coronary arteries that is the right coronary

artery and the left coronary artery arise in the sinuses behind the two cusp of the iotic valve

during systole when the iotic valve is open the velocity of blood flow and the position of the valve cuts cause the

blood to move rapidly past the coronary artery inlets whereas during diastole when diatic valve is closed the blood

flow and iotic pressure are transmitted directly into coronary arteries coming to the second important influence

that is orthoregulation of coronary blood flow which is also unique to coronary circulation

oxygen delivery during periods of increased metabolic demand depends on the autoregulated change in the vessel

tone and in the diameter so we have already seen the endothelial cell products and the metabolites which

are released during the working cardiac muscle and also in the circulation by the endothelial cells so the when there

is an increased metabolic demand vasodilation produces an increase in blood flow

during decreased demand ways of constriction or return of the vessel to to normal produces a reduction in the

flow these tonal changes result from vasoactive mediators released from the myocardial cells and

the endothelium which we already saw in the last slide here we have the myocardial blood flow

and the endothelial cell and release of these vaso-active mediators release of these

weight vis active mediators one is the basic constricting factor which comes from the

endothelial cell called endothelin and the other laser dilating factors which we already saw that is the nitric oxide

the carbon dioxide the adenosine which i told you very clearly the potassium neons the lactic acid so these are

important mediators which regulate the coronary blood flow either during increased metabolic demand or during

decreased demand coming to the third influence of the coronary blood flow that is the coronary

resistance so 75 percent of the total coronary resistant flow occurs across three sets of arteries that is the large

epicardial arteries that is r1 the second is the pre rt roller vessels called the r2 and the third is the

arteriolar intra myocardial capillary vessels r3 during sisterly the contracting cardiac

muscle has a squeezing effect on the intra myocardial vessels that is the r3 vessel while at the same time producing

an increase in the intraventricular pressure that pushes against and compresses these subendocardial vessels

as a result the blood flow to the subendocardial muscle is greatest during diastole this one must remember while uh

by knowing about the ischemic heart disease now coming to

what is that which produces ischemia in the cardiac muscle we should know that the an imbalance in

the myocardial oxygen supply and demand can result in myocardial ischemia and its related consequences oxygen supply

is determined by the coronary arteries the capillary inflow and the ability of the hemoglobin to transport and deliver

oxygen to the heart muscle as you see here the myocardial o2 supply depends on the

depends on the coronary vessel patency the ventricular wall compression the diastolic filling time whereas the

myocardial o2 demand what we call as mvo2 is determined by the three important factors one is the heart

rate the second is lv contractility and systolic pressure or what is called myocardial wall stress or tension

these factors together maintain the myocardial o2 balance so depending on which is dominant the ischemia sets in

coming to the most important thing the heart rate the influence of heart rate and oxygen demand heart rate is the most

important factor in myocardial o2 demand for two important reasons one is that as the heart rate increases the myocar

oxygen consumption or demand also increases and the sub endocardial coronary blood flow is reduced because

of the decreased diastolic filling time with increased heart rate so these two points we must remember before

understanding the pathophysiology of ischemic heart disease as diastole becomes shortened when the

heart rate increases the myocardial flow can be greatly reduced during sustained periods of tachycardia

second important factor one must remember is the myocardial contractility and o2 demand in the entrance

myocardial contractility is the intrinsic ability of the heart muscle to shorten and generate force

and this myocardial incontactility reflects the interaction between the calcium ions and the contractile protein

which you will which you must have seen in the physiology of the cardiac muscle or the action potential that is the

actin and the myosin proteins of the muscle fibers so with increased myocardial

contractility the rate of change in the wall stress is increased which in turn increases myocardial oxygen uptake so

the demand is increased now so the factors that increase contractility are exercise sympathetic

nervous system stimulation and the inotropic agents which we use all these increases the myocardial oxygen demand

coming to the third point the lv wall stress that is the left ventricular wall stress and the oxygen demand we all

know that left ventricular wall stress is the average tension that individual muscle fibers must generate to contract

effectively against a developed intraventricular pressure it is proportional to the product of the

intraventricular pressure and ventricle radius divided by the thickness of the ventricle wall so at a given pressure

the wall stress is increased by an increase in the radius of the ventricle that is ventricular dilation what is

called pre-load and by a decrease in the wall thickness so what is afterload after load is the load against which the

heart must contract to eject blood so an increase in the wall stress either as preload or afterload increases the

myocardial oxygen demand now we have already seen the points which favor increase

myocardial oxygen demand now what are those factors which reduces coronary blood flow

to induce ischemia so there are five important factors which reduce

coronary blood flow including decreased iotic diastolic pressure as we already saw the coronary blood flow is

influenced by iotic pressure so decreased iotic diastolic pressure will definitely reduce the coronary blood

flow the second important point here is increased intraventricular pressure and myocardial contraction just now we saw

and our point of interest today here is coronary artery stenosis this is a very important factor which directly reduces

coronary blood flow which can be further subdivided into what is called fixed coronary stenosis where atherosclerosis

forms a very important most of the time it is atherosclerotic block which forms a fixed coronary stenosis second is an

acute block change on the atherosclerotic block that is the rupture and hemorrhage can also produce

a reduction in the coronary blood flow and third is when there is a thrombosis as a complication of the atheromatous

block can also reduce coronary blood flow finally vasoconstriction also contributes to reduction in the coronary

blood flow and fourth important point in coronary blood flow reduction is iotic valve

stenosis and regurgitation and increased right atrial pressure so now having known that fixed coronary stenosis acute

block change coronary artery thrombosis and vasoconstriction are major contributing factors towards reduction

in coronary blood flow and towards ischemia of the myocardium so now let's go after knowing all these

important factors about the dynamics of coronary blood flow and the imbalance between the myocardial oxygen demand and

the supply now let us go on to the ischemic heart disease which is synonymous with coronary artery disease

the term coronary artery disease or ischemic heart disease describes heart disease caused by impaired coronary

blood flow so this ischemic heart disease is a broad term encompassing several closely

related syndromes caused by myocardial ischemia which is an imbalance between the cardiac blood supply what is called

as perfusion and myocardial oxygen and nutritional requirements that is the myocardial metabolic demands of the

myocardium and something which is very unique about cardiac myocyte is that these cardiac

myocytes generate energy almost exclusively through mitochondrial oxidative phosphorylation

and hence the cardiac function is strictly dependent upon the continuous flow of oxygenated blood through the

coronary arteries it is seen that in more than 90 percent of the cases ischemic heart disease is a consequence

of coronary artery disease due to atherosclerosis now coming to the causes of ischemic

heart disease as we already saw in the previous slide more than 90 percent of the cases ischemic heart disease is a

consequence of reduced coronary blood flow due to obstructive atherosclerotic vascular disease

less frequently ischemic heart disease can also result from increased demand that is hypertension or diminish blood

volume as seen in hypotension or shock and diminished oxygenation example due to pneumonia or congestive heart failure

also when there is a diminished oxygen carrying capacity example due to anemia or carbon monoxide

poisoning there are certain risk factors for coronary artery disease so some of the

major risk factors here i will be telling you are one is cigarette smoking elevated blood pressure that is

hypertension elevated serum total and low density lipoprotein cholesterol that is ldl cholesterol and also presence of

low serum hdl that is high density lipoprotein cholesterol diabetes a very important metabolic condition and

advancing age so these are some of the major risk factors for coronary artery disease out of which individuals with

diabetes and metabolic syndrome are at very particularly increased risk for coronary artery disease or ischemic

heart disease so now coming to the actual ego pathogenesis of ischemic heart disease

which can be divided into three important stems one as i already told you more than 90 percent it is coronary

atherosclerosis so it is not merely coronary atherosclerosis all the time producing ischemic heart disease

it is super added changes within the atherosclerotic block that is for example acute changes in block as

rupture or hemorrhage and sometimes coronary artery thrombosis superimposed on this atherosclerotic block and local

platelet aggregation all these are considered to be super added changes which also result in

ischemia then there are non-atherosclerotic causes in about 10 percent of the people

where vasospasm stenosis of coronary ostria arteritis which is an inflammation of the artery embolism and

thrombotic diseases compression aneurysms and trauma these are other non-atherosclerotic causes which can

result in ischemic heart disease in less than 10 percent of individuals now coming to the actual pathogenesis

because we know that in 90 personal cases ethic atherosclerosis is the cause so now let's go on to

see about the atherosclerotic pathogenesis leading to ischemic heart disease

as i already told you ischemic heart disease is a consequence of pre-existing what is called a fixed atherosclerotic

occlusion coronary arteries and new superimposed thrombosis or vasospasm on the fixed atherosclerotic block these

atherosclerotic narrowing can affect any of the coronary arteries particularly in the descending order it

is left anterior descending order what is left anterior descending artery which is called the lad the second is the left

circumflex artery third is a right coronary artery a all these can be in single or in combination

clinically significant blocks tend to occur with the first several centimeters of the origin

of either the ladder that is the left anterior descending artery and the left circumflex artery and almost along the

entire length of the right coronary artery sometimes the secondary branches are

also involved that is the diagonal branches of left anterior descending artery are the obtuse marginal branches

of the left circumflex artery and the posterior descending branch of the right coronary artery

now coming to atherosclerosis as such what is atherosclerosis as the name suggests atherosclerosis is a pathologic

process by which cholesterol and calcium block accumulate within the arterial wall

over time the fat and the calcium build up narrows the artery and blocks the blood flow through it producing ischemia

or ischemic heart disease now anthrogenesis or what is called formation of this atherosclerotic block

can be divided into five key steps one is the endothelial dysfunction so to start an atherosclerotic block there

must be an endothelial dysfunction and second is after there is an endothelial dysfunction there must be

formation of lipid layer or what is called fatty streak within the intima of the vessel as we all know the vessel

wall has three important layers that is the intima which is the innermost the second is the media and third is the

tunica adventitia so the after when there is an endothelial dysfunction the second important key step is

formation of a lipid layer or what is called deposition of fat as fatty streak within the intima

now the next step is that migration of the leukocytes that is some of the wbcs and the smooth muscle cell

into the vessel wall that is from the tunica media the smooth muscle will migrate into the intima towards the

fatty streak or towards the accumulation of the lipid and also migration of wbcs from the

circulation into the intima or into the area of fatty strain then the fourth step is that now that

there is leukocytes and smooth muscle cells into the area of the fatty stick or the

vessel wall there is form cell formation what is this foam cell formation form cells are nothing but macrophages which

have imbibed the fat present within the vessel wall so these foam cell formation is the major determinant for the

atherosclerotic block and its consequences now once this foam cell formation occurs along with the smooth

muscle migration and the wbc migration there is now degradation of the extracellular matrix resulting in

what is called the fibrosis so these are the five major steps involved in formation of atherosclerotic block

then what are the contributive factors towards the pathogenesis of ischemic heart disease after the formation of a

atherosclerotic block it has been said that and has also been proved that inflammation plays an essential role at

all stages of atherosclerosis right from the inception to the block rupture as we already saw in the previous slide that

migration of leukocytes and some of the endothelial cell products producing endothelial cell dysfunction these are

the initial events of inflammation which starts the formation of atherosclerotic blocker and

propagates further then second major event is supposed to be the thrombosis thrombosis is

associated with an eroded or ruptured block which triggers the acute coronary syndrome

even a partial luminal occlusion by a thrombus can cause an infarction of the innermost zone of the myocardium may not

be the entire myocardium by the innermost layer of the myocardium producing what is called sub-endocardial

infarct sometimes the mural thrombi in a coronary artery can also embolize and

these small embolic can be found in the distal intramyocardial circulation

and as you see these emboli are going along the distal mental circulation there will be associated

micro infarcts in the myocardium then i already told you vasospasm or vasoconstruction

vasoconstriction which is caused by the adrenergic agonist local platelet and endothelial product directly compromises

the lumen diameter producing ischemia or reduction in coronary blood flow so the three major

contributing factors here are inflammation thrombosis which also embolizes and vasoconstriction

during the formation of atherosclerotic block now what are the evidences to say that

inflammation is a cause of ischemic heart disease in physiological conditions leukocytes are not activated

by endothelial this is normal whereas when there is inflammation there is a change in the interaction between

the endothelium and the leukocytes so severe that it leads to endothelial expression of addition molecules that

bind to leukocytes maintaining and enhancing a local inflammatory response this local inflammation produces

proteolytic enzymes making atherosclerotic cap prone to rupture and

the evidence which says is that there is apparent correlation between inflammatory markers that is the c

reactive protein homocysteine and the susceptibility to develop isd and worse prognosis so these are some of

the evidences to say that inflammation plays a major role in development of ischemic heart disease in

atherosclerotic diseases then there is also called as role of

oxidized ldl i already said increased presence increased serum level of low density lipoprotein is a major risk

factor so it is not merely low density lipoprotein it is the oxidized low density

lipoprotein which has a fundamental role in the entire process of atherogenesis from the block formation to plot

destabilization this aux ldl what is called oxidized ldl induces endothelial dysfunction in the

initial stage then it stimulates the generation of what is called free radicals that is the

reactive oxygen species which are known to produce destructive changes within the cell

and this oxidized ldl also inhibits nitric oxide synthesis so we have lost the vasodilation also

one of the major potent vasodilator and this oxidized ldl enhances monocyte addition to activated endothelial

endothelial cells thus propagating inflammation and it induces vascular smooth muscle

cells what is called the vs mcs smcs for migration and proliferation so there is accumulation of

atherosclerotic block now and also this oxidized ldl is avidly ingested by the macrophages as i already

told you resulting in foam cell formation and oxidized ldl may also induce

apoptosis that is program cell death and necrosis of the vascular endothelial cells and also the vascular smooth

muscle cells and macrophages so these are the changes which are initiated by the oxidized ldl so it plays a

fundamental role or a very important role in the entire process of atherogenesis

this oxidized ldl increased levels relate to block instability with a positive correlation with myocardial

ischemic severity now coming to the last point the role of vasos passion i told you it is

inflammation the thrombosis and the vasoconstriction in the basospasm the vasospasm can be initiated by several

factors that is vasomotor tone at rest segment epicardial coronary hyperactivity

and an organic stenosis so we already have an organic stenosis in atherosclerosis so this rhizospasm

appears at the sites of significant atherosclerotic stenosis both in acute and chronic settings

spasm of these atherosclerotic lesions may provoke myocardial ischemia both in early and advanced stages of disease

through activation of what is called a downstream vasospastic effector

which is called as rock that is the rho associated protein kinase which is in which increases the

expression of inflammation related molecules also increases the incidence of thrombosis and fibrosis

and this rock the and which is a novel biomarker that is rho associated protein kinase

is probably involved in the pathophysiology of angina pectoris coronary vesospasm hypotension and also

pulmonary hypertension so this is one of a novel biomarker which can be used as a diagnostic marker for ischemic heart

disease as well and coming to role of aging in pathogenesis i told increased aging is

an important risk factor for atherosclerosis so this aging is a physiological mechanism and an

independent cardiovascular risk factor its pathogenic role is strongly influenced by genetic predisposition and

environmental features as well aging is responsible for endothelial layer integrity loss

arterial stiffness loss of vessels elasticity and reduced vascular adaptability to physical forces

related to currently blood flow so these are some of the major factors in aging which contributes to increased

atherogenesis and also increased ischemic heart disease it promotes an increased expression of

cyclogenesis that is cox 1 and 2 thromboxane a2 1 will brand factor and factor 8 all these promoting aggregation

and hyper hyper coagulative state and

inflammation per se response is enhanced with aging so aging plays a major role in

pathogenesis of ischemic heart disease either with or without atherosclerotic

lesion now we need to know something about coronary

microvascular dysfunction though we know atherosclerotic block and non-atherosclerotic

diseases can produce ischemia there is important pathophysiological mechanism within the coronary microvascular

dysfunction which is related to ischemia this coronary microvascular dysfunction what is called a cmd represents a common

pathophysiological mechanism for type 2 myocardial infarction we know there are about type 4 types of myocardial

infarction so the cmd that is the coronary microvascular dysfunction

determines an increase in the flow resistance leading to myocardial ischemia

in response to reduced perfusion pressure the term microvascular angina

for those patient population was used for the first time in 1985 referring to ischemia triggered by an altered

vasoregulation of the coronary microcirculation a pre-existing

transient or permanent microvascular dysfunction may contribute to the development and prognosis of what is

called acute coronary syndrome or ischemic heart disease or otherwise coronary artery disease

now coming to diagrammatic representation of how atherosclerotic block reduces

ischemic heart disease as i already told you you can see in the right side that you can see that this is a normal blood

vessel and inside the normal blood as well you see it is very clear and the wall is uniform and the

thickness of the wall is also uniform whereas when there is atherosclerotic block i already told you how

atherosclerotic block is formed first there is a what is called an endothelial dysfunction

and second there is what is called deposition of this lipid or the fatty streak and then there is migration of

leukocytes from the blood circulation also these smooth muscle cells from the tunica media into the intima where there

is fat deposition and there is what is called as release of proteolytic enzymes and also

there is extracellular matrix degradation producing what is called atherosclerotic block this is the block

and there is a cap here and this block yellow color this representation of the lipid or the fat which is there that is

the foam cell formation and these are the smooth muscle cells the leukocytes and the extracellular matrix which are

seen as a cap of the atherosclerotic block and now you see the lumen is slightly reduced not slightly it is

partly reduced so this is a partially blocked blood vessel so fixed obstructions that occlude less

than 70 percent of a coronary vessel lumen typically are asymptomatic even with exertion

but lesions that occlude more than 70 percent of a vessel lumen resulting in critical stenosis causes chest pain on

exertion and this is called a stable angina as i already told you the risk factors these are the steps which we

already discussed and what happens is when there is accumulation of this atherosclerotic

block initially there is an expansion of the outer wall to maintain the internal diameter but once there is a 40 percent

stenosis the inner diameter begins to narrow producing occlusion what is this acute block change we saw

fixed block now let's go on to the complications of this fixed block what

is called as acute block change in most patients there is unstable angina infarction and

sudden cardiac death these occur because of an abrip block change followed by thrombosis this is termed as acute

coronary syndrome so blocks that contain large atheromatic scores that is the yellow color the

central yellow lipid core and have thin overlying fibrous gaps are more prone for bleeding and rupture and therefore

they are termed as vulnerable blocks and the adrenergic search promotes the block change so a fixed stenosis that

occludes 90 percent or more of a vascular lumen can lead to symptoms even at rest one of the forms of unstable

angina whereas i told in the previous slide if it is 70 percent and less a fixed stenosis will not produce angina

even at exertion whereas once it crosses to 90 percent even at rest it is going to produce chest pain and that is called

as unstable angina so when you look at this diagram you can see the progression of atromatis block

this is a normal vessel wall and here you see there is mild deposition of fat which is called as fatty streak this is

a very very initial stage most of us will be in the stage only when we start developing or aggregating more lipid and

when there is a complication that people go in for angina so as age progresses over time there is a buildup of this fat

and all also the extracellular matrix along with smooth muscle cells and the inflammatory cells most important all

these contribute to a formation of fibro fatty block what is called as an advanced or vulnerable block so as the

core increases the vulnerability increases so you can see here the what are the complications of these

acute block change or advanced vulnerable block one is aneurysm and rupture you can see that there is a

rupture of the vessel here there is an aneurysmal formation what is animismal formation it is a dilatation of the

vessel wall and it can also have superimposed thrombosis like this you can have a

thrombosis because of local platelet aggregation and endothelial products which promotes

thrombothrombogenic material thrombogenic mediators and promoting formation of thrombosis this can

embolize and give to further complications and sometimes what happen there is entire

lumen which is occluded by the block and this is called as critical stenosis so all these lead

to myocardial infarction and unstable angina so this is the vulnerable blocker so what are the changes in block as

already mentioned it can be rupture ulceration or erosion of the blocks leading to occlusive thrombosis

hemorrhage into a block is another important complication which results from the rupture of the overlying

fibrous crab or of the thin walled neovascularized vessels and third complication is atheroembolism

this results from the block rupture with discharge of atherosclerotic debris into the bloodstream now finally aneurysm

formation atheroma induced pressure by ischemic atrophy of the media with loss of elastic tissue is the cause for the

aneurysmal dilatation of the vessel wall as i already told you vulnerable blocks have three important histologic

hallmarks compared to a stable block that is one is the larger lipid core which is more than 40 percent of the

total lesion area a very thin fibrous cap that is 65 to 150 micrometer and many number of inflammatory cells are

the leukocytes most important so what is stabilizing and what is destabilizing when there is more lipid and

inflammatory cells it is it is called as destabilizing block where there is increased lipid content and a very thin

fibrous cap with large number of inflammatory cells whereas when there is increased smooth muscle cell migration

with increased collagen deposition there there is a thick thick fibrous gap and a less of core mate that is your lipid

core more collagen leading to stabilization of the block so when it is stabilization it is a stable angina and

the patient will not have any ontoward events whereas when it is destabilizing patients individuals can go for changes

in the vulnerable block leading to unstable angina and myocardial infarction as well

so knowing all these things what are the manifestations of ischemic heart disease manifestations may include one or more

of the following cardiac syndromes that is angina pectoris literally called as chest pain where ischemia induces pain

but it is insufficient to cause myocyte death whereas the second important cardiac

syndrome is myocardial infarction where the severity or duration of ischemia is sufficient enough to cause myocyte death

and the third complication is chronic ischemic heart disease with congestive heart failure where there is progressive

cardiac decompensation which occurs after an acute episode of myocardial infarction or it can be

secondary to repeated small ischemic insults to the cardiac myocyte and finally you have sudden cardiac

death which is a consequence of myocardial infarction but most commonly resulting from a lethal arrhythmia

without any myocyte necrosis so far we have been seeing ischemic injury to the myocardium now let's go on

to see about acute acute non-ischemic myocardial injury where acute myocardial injury that is the rays and fall in the

biomarkers mainly the cardiac troponin in the absence of primary ischemic cause that is in the absence of myocardial

infarction is the only evidence to say that there is acute non-ischemic myocardial injury here also the patients

will come with chest pain now what is chronic myocardial injury chronic myocardial injury where the cardiac

troponin more than 99th percentile without an acute change is termed as chronic myocardial ingenie so why is it

we should understand this because type 2 myocardial infarction may arise in the context of various acute myocard acute

medical and surgical conditions that are similarly associated with non-ischemic myocardial injury making the

differentiation between type 2 myocardial infarction and acute non-ischemic myocardial injury

challenging in a very common clinical setting that is why one must know that there can be an acute non-ischemic and

chronic myocardial injury so this is myocardial injury in the absence of ischemia which is categorized

acute or chronic non-ischemic myocardial injury so we have myocardial injury which could be acute or chronic

and this acute could be non-ischemic or ischemic when it is ischemic we know it is either a type 1 myocardial infarction

or a type 2 myocardial infarction in type 1 myocardial infarction it is increased block instability and

inflammation in type 2 myocardial infarction the triggers demand ischemia that is the hypertension

microcirculatory dysfunction are the two major triggers which demand ischemia coming to acute non-ischemic injury here

the trigger is a direct myocardial toxicity where there is contraction banned necrosis without any

ischemic changes and in any chronic injury to myocardium there is an increased risk of stroke

also it perpetuates atherosclerosis inflammation and fibrosis so with all these i would like to summarize saying

that myocardial ischemia is directly dependent on an impairment of the crosstalk between

myocardial energy state and coronary blood flow atherosclerosis being the major

etiological factor in more than 90 percent of the cases and

recently it is known that coronary macro vascular and microvascular disease may represent just a portion of the

multifaceted pathophysiology of myocardial ischemia my references are mainly from

robbins and cotron pathological basis of disease thank you for a patient hearing