~1II-1111-IIt---c_rit_ic_a_1c_are ~
_
-==:sF
Myocardial Oxygen Supply and Demand* Abbas Ardehali, 1\I.D.;t and Thonms A. Ports, i.\I.D., F.C.C.ff
The supply of oxygen to the myocardium is determined by coronary blood How and oxygen carrying capacity. Coronary blood How is a dynamic process modulated via multiple parameters. Cardiac metabolism is also affected by several factors. Under normal physiologic conditions, the demand is easily met by the supply of oxygen. In fact, there is a significant reserve on the supply side. Under certain pathologic states such as coronary artery disease, the supply
of oxygen may be exhausted and an imbalance between supply and demand occurs which is translated into ischemia. The area of myocardium most susceptible to ischemia is the subendocardium due to mechanical and metabolic forces. In therapy of coronary artery disease, attention should be directed to directional changes in factors influencing supply and demand to improve blood flow to the most susceptible area. (Chest 1990; 98:699-705)
Coronary artery disease remains the most important form of heart disease in the industrialized world. The most common clinical manifestation of coronary artery disease is myocardial ischemia \vhich is characterized by an imbalance bet\veen myocardial oxygen supply and demand. This imbalance is lIsually due to decreased coronary blood flo\\' as a result of critical atherosclerotic obstructive coronary artery disease. With recent advances in technology and evolution of the intravascular Doppler catheter to measure blood 8o~ a great body of new information has become available about coronary blood flo\v in health and diseased states. Better understandin~ of factors influencing myocardial oxygen supply and demand will provide an improved insight into the care of patients with coronary artery disease. This article discusses the factors influencing myocardial oxygen availability and consumption in health and in the presence of coronary artery disease. The factors rendering subendocardiunl most susceptible to ischemia will also be reviewed.
hearts \\'ith the nlost vi~orous level of exercise. 1-2 Ho\\'ever, in the presence of coronary artery disease or abnorlnal left ventricular hypertrophy, all itnbalance bet\\'een supply and deluand IUllY occur \'lith nlinimal exercise or even at rest. Applicatioll of the concept of supply and demand to Illyocardial ()xy~en utilization emphasizes and underlines the physiolowc paralneters that control ()xy~en delivery and COllstnnption by the heart.
SUPPLY ANI) DE~IANI)
Myocardial ischemia can be defined by the concept of supply and demand. The molecular, physiologic, and clinical evidences of ischemia only occur \\,hen delnand outstrips the supply of oxygen to the myocardium. Fortunately, the reserve on the supply side is large enough to nlake ischemia impossible in l10rrual *Cardiovascular Research Institute, and Division of Cardioloh~', Deparhnent of Medicine, University of California. San Francis(.'(). tResearch Fellow, Cardiovascular Research Institute. tProfessor of Medicine (Cardiol()~y), and Director, Cardiac Catherization Lahoratories, Moffitt- L()n~ Ilospital. University of California, San Francisco. Reprint requl!stS: D,: Ardl~hali, Division of Cardiology, .561, San
Francisco c;eneral HOS1Jital, San Fraoci.4ico, California 94110
~'Iyocardial OXYlI.en
Supply
The supply of oxygen to the myocardiulll is determined by the maWlitude of coronary hlood flow and the oxy~en-carryin~capacity of the blood. The latter is compronlised in clinical circumstances such as si~nificant anenlia, hypoxemia, and carhon monoxide poisoning. However, by far, the most illlportant determinant of oxygen supply in most clinical situations is the magnitude of coronary blood 80\v. Blood flo\\' in coronary vessels is governed by the principles of fluid dynamics, narnely: the flo\\' is the result of the pressure gradient across the vascular hed divided hy the resistance. Aortic root pressure minus right atrial pressure or left ventricular diastolic pressure defines the pressure gradient or perfusion pressure. The regulation of the coronary blood OO\V is a cornplex process incorporating several factors. P'fhe Inost irnportant of these are: 1) rnetaholic control; 2) autoregulation; 3) extravascular c()nlpressi\'t.~ fi)rces; 4) diastolic phase in cardiac cycle~ 5) hUllltliral factors; and 6) neural control. ~\Ietabolic control: The changt's in Inetabolic rate of Inyocardial cells are very closely linkllld to blood HO\\,.:l This coupling rnechanisnl aets \\tithin ont. cardiac cycle, and nlaximal coronary dilation or constriction can be elicited \vithin 15 to 20 s... The Inediator (or ll
CHEST I 98 I 3 I SEPTEMBER, 1990
699
mediators) responsible for the coupling of nlyocardial nletaholic rate to coronary vascular resistance remains unkno\\'n. The putative mediator is constantly produced by the myocardium, is released into the interstititlln, and cleared by the blood flo\\~ This Inetabolite may act as a potent coronary vasodilator. When the nlyocardial nletabolisnl exceeds a previously established steady state, the production of this substrate increases, and it Inay accumulate. A higher anlount of mediator induces coronary vasodilation, facilitates clearance, and the steady state concentration of this substrate is re-established. Several nlediators have been proposed that may fulfill the above requirements: adenosine, molecular oxygen, H +, carbon dioxide, K+, etc. Adenosine is the byproduct of utilization of ATP which stores hi~h ener~y phosphate (Fig 1). Myocardial metabolisnl releases adenosine \vhich, under steady states, is constantly cleared by blood flow. 5 With increased nletabolic rates or decreased blood fl()~ adenosine accunlulates, induces vasodilation, causes an increase in blood flow, and the steady-state concentration of adenosine is restored. 6 The role of molecular ()xy~en as a mediator for metabolic control has also been studied extensively.7.N Diminished molecular oxygen tension has a directly vasodilatory effect on smooth nluscle cells and on the tone of precapillary sphincters of vascular beds. It is important to emphasize that variation of blood flow is not only mediated via chan~es in the caliber of presently open capillaries, but also through recruitment ofclosed microvascular beds. 9 Although adenosine was used as the exemplifying InediatoT, it seems likely that metabolic control of coronary blood flo\\' is mediated via multiple a~ents and there Inay be a cascade of messengers involved in this coupling reaction.
Autoregulation: As is true in the central nervous system, blood flow in coronary arteries remains con-
stant over a wide range of perfusion pressures (60-160 mm Hg). In other words, as the driving pressure changes, coronary resistance also changes in the reciprocal manner to keep blood flow constant. Coronary autoregulation was first described by Mosher et al. 1O The mechanism and the mediator(s) responsible for translation of changes in perfusion pressure into alterations in coronary vascular resistance to maintain blood flow constant remains unknown. However, several hypotheses have been proposed. II ~lyogenic factors-the shear forces of perfusion pressure on vascular smooth muscles may mediate constriction. As perfusion pressure increases, the distending pressure on the vessel wall musculature causes reHex spasm, and returns blood flow to the previous steady state level. This phenomenon cannot explain coronary autoregulation in its entirety.12 Metabolic controls-this potential mechanism of autoregulation shares the principles of metabolic control of blood flow, namely: maintenance of a set-point concentration of a metabolite (or metabolites) is the goal of the regulatory system. If the concentration of this substance decreases as a result of increased perfusion pressure and blood flo~ vascular smooth muscles constrict and coronary blood flow is limited until the previously established concentration of the above metabolite is reached. Adenosine was noted as the prototypic agent under metabolic control of blood flow, however, as previously noted, there seems to be a variety of potential mediators that work in concert. Whatever the mechanism of coupling between perfusion pressure and coronary blood flow may be, the importance of this interaction becomes most prominent when the perfusion pressure exceeds 160 or falls below 60 mm Hg. Under the latter situation, coronary arteries become maximally dilated and totally dependent on perfusion pressure. In the presence of significant coronary artery disease, the perfusion pressure distal to an atherosclerotic plaque may fall below this
MYOCARDIAL
CEll
t. VASODILATION
~
(1) (2) ADENOSINE ---... INOSINE ---... HVPOXANTHINE
INTERSTITIUM
WASH OUT VIA CAPILLARV
700
,-
ADENOSINE DEAMINASE
2-
NUCLEOSIDE PHOSPHOHVLASE
FIGURE 1. Role of adenosine as a metabolic mediator of
_
-==:sF
Myocardial Oxygen Supply and Demand* Abbas Ardehali, 1\I.D.;t and Thonms A. Ports, i.\I.D., F.C.C.ff
The supply of oxygen to the myocardium is determined by coronary blood How and oxygen carrying capacity. Coronary blood How is a dynamic process modulated via multiple parameters. Cardiac metabolism is also affected by several factors. Under normal physiologic conditions, the demand is easily met by the supply of oxygen. In fact, there is a significant reserve on the supply side. Under certain pathologic states such as coronary artery disease, the supply
of oxygen may be exhausted and an imbalance between supply and demand occurs which is translated into ischemia. The area of myocardium most susceptible to ischemia is the subendocardium due to mechanical and metabolic forces. In therapy of coronary artery disease, attention should be directed to directional changes in factors influencing supply and demand to improve blood flow to the most susceptible area. (Chest 1990; 98:699-705)
Coronary artery disease remains the most important form of heart disease in the industrialized world. The most common clinical manifestation of coronary artery disease is myocardial ischemia \vhich is characterized by an imbalance bet\veen myocardial oxygen supply and demand. This imbalance is lIsually due to decreased coronary blood flo\\' as a result of critical atherosclerotic obstructive coronary artery disease. With recent advances in technology and evolution of the intravascular Doppler catheter to measure blood 8o~ a great body of new information has become available about coronary blood flo\v in health and diseased states. Better understandin~ of factors influencing myocardial oxygen supply and demand will provide an improved insight into the care of patients with coronary artery disease. This article discusses the factors influencing myocardial oxygen availability and consumption in health and in the presence of coronary artery disease. The factors rendering subendocardiunl most susceptible to ischemia will also be reviewed.
hearts \\'ith the nlost vi~orous level of exercise. 1-2 Ho\\'ever, in the presence of coronary artery disease or abnorlnal left ventricular hypertrophy, all itnbalance bet\\'een supply and deluand IUllY occur \'lith nlinimal exercise or even at rest. Applicatioll of the concept of supply and demand to Illyocardial ()xy~en utilization emphasizes and underlines the physiolowc paralneters that control ()xy~en delivery and COllstnnption by the heart.
SUPPLY ANI) DE~IANI)
Myocardial ischemia can be defined by the concept of supply and demand. The molecular, physiologic, and clinical evidences of ischemia only occur \\,hen delnand outstrips the supply of oxygen to the myocardium. Fortunately, the reserve on the supply side is large enough to nlake ischemia impossible in l10rrual *Cardiovascular Research Institute, and Division of Cardioloh~', Deparhnent of Medicine, University of California. San Francis(.'(). tResearch Fellow, Cardiovascular Research Institute. tProfessor of Medicine (Cardiol()~y), and Director, Cardiac Catherization Lahoratories, Moffitt- L()n~ Ilospital. University of California, San Francisco. Reprint requl!stS: D,: Ardl~hali, Division of Cardiology, .561, San
Francisco c;eneral HOS1Jital, San Fraoci.4ico, California 94110
~'Iyocardial OXYlI.en
Supply
The supply of oxygen to the myocardiulll is determined by the maWlitude of coronary hlood flow and the oxy~en-carryin~capacity of the blood. The latter is compronlised in clinical circumstances such as si~nificant anenlia, hypoxemia, and carhon monoxide poisoning. However, by far, the most illlportant determinant of oxygen supply in most clinical situations is the magnitude of coronary blood 80\v. Blood flo\\' in coronary vessels is governed by the principles of fluid dynamics, narnely: the flo\\' is the result of the pressure gradient across the vascular hed divided hy the resistance. Aortic root pressure minus right atrial pressure or left ventricular diastolic pressure defines the pressure gradient or perfusion pressure. The regulation of the coronary blood OO\V is a cornplex process incorporating several factors. P'fhe Inost irnportant of these are: 1) rnetaholic control; 2) autoregulation; 3) extravascular c()nlpressi\'t.~ fi)rces; 4) diastolic phase in cardiac cycle~ 5) hUllltliral factors; and 6) neural control. ~\Ietabolic control: The changt's in Inetabolic rate of Inyocardial cells are very closely linkllld to blood HO\\,.:l This coupling rnechanisnl aets \\tithin ont. cardiac cycle, and nlaximal coronary dilation or constriction can be elicited \vithin 15 to 20 s... The Inediator (or ll
CHEST I 98 I 3 I SEPTEMBER, 1990
699
mediators) responsible for the coupling of nlyocardial nletaholic rate to coronary vascular resistance remains unkno\\'n. The putative mediator is constantly produced by the myocardium, is released into the interstititlln, and cleared by the blood flo\\~ This Inetabolite may act as a potent coronary vasodilator. When the nlyocardial nletabolisnl exceeds a previously established steady state, the production of this substrate increases, and it Inay accumulate. A higher anlount of mediator induces coronary vasodilation, facilitates clearance, and the steady state concentration of this substrate is re-established. Several nlediators have been proposed that may fulfill the above requirements: adenosine, molecular oxygen, H +, carbon dioxide, K+, etc. Adenosine is the byproduct of utilization of ATP which stores hi~h ener~y phosphate (Fig 1). Myocardial metabolisnl releases adenosine \vhich, under steady states, is constantly cleared by blood flow. 5 With increased nletabolic rates or decreased blood fl()~ adenosine accunlulates, induces vasodilation, causes an increase in blood flow, and the steady-state concentration of adenosine is restored. 6 The role of molecular ()xy~en as a mediator for metabolic control has also been studied extensively.7.N Diminished molecular oxygen tension has a directly vasodilatory effect on smooth nluscle cells and on the tone of precapillary sphincters of vascular beds. It is important to emphasize that variation of blood flow is not only mediated via chan~es in the caliber of presently open capillaries, but also through recruitment ofclosed microvascular beds. 9 Although adenosine was used as the exemplifying InediatoT, it seems likely that metabolic control of coronary blood flo\\' is mediated via multiple a~ents and there Inay be a cascade of messengers involved in this coupling reaction.
Autoregulation: As is true in the central nervous system, blood flow in coronary arteries remains con-
stant over a wide range of perfusion pressures (60-160 mm Hg). In other words, as the driving pressure changes, coronary resistance also changes in the reciprocal manner to keep blood flow constant. Coronary autoregulation was first described by Mosher et al. 1O The mechanism and the mediator(s) responsible for translation of changes in perfusion pressure into alterations in coronary vascular resistance to maintain blood flow constant remains unknown. However, several hypotheses have been proposed. II ~lyogenic factors-the shear forces of perfusion pressure on vascular smooth muscles may mediate constriction. As perfusion pressure increases, the distending pressure on the vessel wall musculature causes reHex spasm, and returns blood flow to the previous steady state level. This phenomenon cannot explain coronary autoregulation in its entirety.12 Metabolic controls-this potential mechanism of autoregulation shares the principles of metabolic control of blood flow, namely: maintenance of a set-point concentration of a metabolite (or metabolites) is the goal of the regulatory system. If the concentration of this substance decreases as a result of increased perfusion pressure and blood flo~ vascular smooth muscles constrict and coronary blood flow is limited until the previously established concentration of the above metabolite is reached. Adenosine was noted as the prototypic agent under metabolic control of blood flow, however, as previously noted, there seems to be a variety of potential mediators that work in concert. Whatever the mechanism of coupling between perfusion pressure and coronary blood flow may be, the importance of this interaction becomes most prominent when the perfusion pressure exceeds 160 or falls below 60 mm Hg. Under the latter situation, coronary arteries become maximally dilated and totally dependent on perfusion pressure. In the presence of significant coronary artery disease, the perfusion pressure distal to an atherosclerotic plaque may fall below this
MYOCARDIAL
CEll
t. VASODILATION
~
(1) (2) ADENOSINE ---... INOSINE ---... HVPOXANTHINE
INTERSTITIUM
WASH OUT VIA CAPILLARV
700
,-
ADENOSINE DEAMINASE
2-
NUCLEOSIDE PHOSPHOHVLASE
FIGURE 1. Role of adenosine as a metabolic mediator of
