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Department of Integrative Physiology, University of North Texas Health Science Center, Fort Worth, Texas 76107
1To whom requests for reprints should be addressed at Department of Integrative Physiology, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107. E-mail: pzong{at}hsc.unt.edu
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Abstract |
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 Top Abstract IntroductionAssessing Right Coronary Venous...Resting Right Coronary Blood...Contributions of Flow Reserve...Transmural Distribution of Right...Right Coronary AutoregulationRight Ventricular Systolic...ConclusionsReferences |
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Key Words: right ventricle • myocardial oxygen consumption • oxygen extraction reserve • coronary circulation • contractile function
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Introduction |
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TopAbstractIntroductionAssessing Right Coronary Venous...Resting Right Coronary Blood...Contributions of Flow Reserve...Transmural Distribution of Right...Right Coronary AutoregulationRight Ventricular Systolic...ConclusionsReferences |
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...phasic coronary blood flow, autoregulation, and the effects of sudden increases in ventricular pressure on transmural perfusion are very different in vessels that perfuse the right and left ventricles. These basic differences in the regulation of perfusion to the right and left ventricles will affect the responses of their respective vascular beds to a variety of physiological and pathological stimuli. (pp. 339–340) All too often, these differences are ignored by investigators and clinicians. Discrepancies in the regulation of perfusion to the right and left ventricles deserve much more attention than they have been given in the past. (p. 343)
Although Marcus’ caveat was published in 1983, relatively few subsequent investigations have specifically addressed right coronary physiology or interactions between right coronary function and right ventricular function. Such investigations have been limited, to some degree, by technical difficulties in manipulating and measuring right coronary hemodynamic variables and in collecting right coronary venous samples to investigate relationships between mechanisms of right coronary vasoregulation and right ventricular metabolism. These technical difficulties have posed significant challenges for investigations in anesthetized, open-chest animal models (2) and have been overcome only recently by our laboratory in the instrumented, conscious canine model (3–8).
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Assessing Right Coronary Venous PO2 and Right Ventricular O2 Extraction |
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TopAbstractIntroductionAssessing Right Coronary Venous...Resting Right Coronary Blood...Contributions of Flow Reserve...Transmural Distribution of Right...Right Coronary AutoregulationRight Ventricular Systolic...ConclusionsReferences |
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Kusachi et al. (10) sampled right and left coronary venous blood from anesthetized, open-chest dog hearts and reported that O2 extraction was lower in the right ventricle (51%) than in the left ventricle (60%). They also reported that mean right ventricular myocardial O2 consumption was less than half that of the left ventricle (4.0 compared with 8.6 ml O2/min/100 g). Similar findings of lower resting right coronary flow and lesser right ventricular myocardial O2 consumption were reported by Saito et al. (11–13) and Takeda et al. (14). These findings are not surprising, considering the much lower afterload imposed on the right ventricle. We also measured O2 extraction by right ventricular myocardium of the anesthetized, open-chest dog heart and examined the effects of altering right coronary perfusion pressure on right ventricular O2 extraction (15–17). With normal right coronary artery perfusion pressure, right ventricular O2 extraction was ~45%. The extraction of O2 fell to ~32% as right coronary pressure was elevated to 120 mm Hg and rose to ~56% as right coronary pressure was reduced to 40 mm Hg.
Whereas studies on anesthetized, open-chest dogs have provided information on right ventricular O2 extraction and O2 consumption under various conditions (10–17), there has been concern that anesthesia and the acute effects of extensive open-chest surgery may have produced artifacts. Anesthesia reduces right ventricular O2 demand (3) and may alter right coronary tone (18), so mechanisms of O2 demand/supply balance might be affected. For example, the extent and ability to recruit flow and O2 extraction reserves are most likely different in the conscious state. Clearly, a need existed to extend these studies to the intact right coronary circulation of the conscious animal.
The left coronary circulation drains primarily to the coronary sinus, which can be catheterized in humans and in relatively large, anesthetized, or conscious experimental animals (19, 20). In contrast, samples of right coronary venous blood must be collected from small, superficial veins on the surface of the right ventricle. Owing to their small size and fragility, obtaining blood from these veins is difficult, especially in the conscious state. This problem is most likely responsible for our lesser understanding of right ventricular O2 balance.
A novel procedure developed in this laboratory has enabled us to collect right coronary venous blood from conscious dogs (4). Briefly, a coronary venous catheter is inserted into one branch of a bifurcated superficial right ventricular vein draining the perfusion territory of the right coronary artery. The side holes of this small diameter catheter are positioned in a stream of flowing blood from the other branch of the bifurcation. We found that PO2 of blood collected from the right coronary venous catheter decreased during partial constriction of the right coronary artery and rose during the reactive hyperemia after release of the constriction (4). These findings, along with observation of the catheter position at autopsy, demonstrated that the catheter remained in place and provided samples of right coronary venous blood.
It is essential that samples of right coronary venous blood do indeed originate in the right ventricle and not be contaminated by blood from other sources. Two possible sources of contamination are blood retrogradely drawn from the right atrium and blood originating from tissue supplied by arteries other than the right coronary artery. In our initial study, the PO2 of the sampled blood averaged 27.7 ± 1.0 mm Hg during resting conditions. Although this value is higher than that measured in coronary sinus blood (19, 20), it is consistent with data from anesthetized dogs (15, 17, 21). Furthermore, this value is much less than the PO2 of mixed venous blood in the right atrium, which indicates little or no contamination of the sample with atrial blood. To further investigate whether there was contamination from right atrial blood, radioactive microspheres were infused iv in three instrumented, conscious dogs and one anesthetized dog (5) while blood samples were collected from the right atrium and the right coronary vein. Because circulating microspheres were trapped in the pulmonary circulation, any radioactivity within the right coronary venous samples would have come from right atrial contamination. Radioactivity detected in the right coronary venous blood samples was less than 0.1% of that in atrial blood. These data demonstrated that right atrial blood was not withdrawn into the venous samples.
The possibility of contamination by blood from sources other than the right coronary artery was explored in an earlier canine study in our laboratory by Murakami et al. (16). They infused Evans blue dye (Sigma Chemical, St. Louis, MO) intravenously while perfusing the right coronary artery with dye-free blood from a reservoir that was isolated from the systemic circulation. Blood samples were collected from the systemic circulation and from a right coronary vein with right coronary perfusion pressure reduced to 80 mm Hg and normal systemic arterial pressure. Analysis of optical density of the right coronary venous plasma and that of the systemic plasma indicated that the left coronary contribution to right coronary venous drainage was 1.2%. Under normal conditions, there would be no disparity between right and left coronary perfusion pressures, so these data show that contamination of right coronary venous samples with blood from other coronary sources would be negligible. This new technique for collecting right coronary venous blood from the conscious dog has been used by our laboratory to examine factors responsible for right ventricular O2 balance under a number of conditions, as described next.
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Resting Right Coronary Blood Flow and Vascular Conductance |
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TopAbstractIntroductionAssessing Right Coronary Venous...Resting Right Coronary Blood...Contributions of Flow Reserve...Transmural Distribution of Right...Right Coronary AutoregulationRight Ventricular Systolic...ConclusionsReferences |
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Consistent with a much lesser right ventricular systolic pressure, right coronary flow, unlike left coronary flow, is not impeded by systolic contraction (1, 26). As a consequence, right coronary flow is sustained throughout the cardiac cycle (23), and the subendocardial region of the right ventricle is not as dependent on diastolic flow (26) as the left ventricular subendocardium (26). However, because significant right coronary perfusion occurs in systole, diastolic right coronary conductance must be correspondingly reduced to lessen excessive right ventricular perfusion.
The lesser resting conductance of the right coronary circulation might be due, at least in part, to accentuated sympathetic-mediated constriction of the right coronary vasculature. However, Zong et al. (7) recently demonstrated that this mechanism is not an important determinant of resting right coronary tone because blockade of 
-adrenergic receptors with phentolamine produced no significant increases in resting right coronary flow or conductance. This new finding for the right coronary circulation is consistent with prior reports that sympathetic vasoconstrictor tone does not restrict resting left coronary flow (45–48).
Although the lower flow in the right ventricular myocardium is consistent with its lower O2 demand, the metabolic regulation of right coronary flow has not been delineated. Furthermore, there are interesting differences in the metabolic regulation of the right and left coronary flow at rest. For example, right coronary venous PO2 is appreciably higher than left coronary venous PO2 at rest (4–8, 46, 49), so metabolic control mechanisms must not be regulating flow to achieve the same myocardial PO2, assuming that coronary venous PO2 is a valid index of tissue PO2. In any case, the lower resting right coronary conductance does not sufficiently restrict flow to force the right ventricle to extract the same percentage of O2 as the left ventricle.
Because right coronary venous PO2 is higher than for the left ventricle and right coronary conductance is lower than for the left ventricle, it is tempting to suggest that coronary conductance is directly or indirectly controlled by tissue PO2. However, this seems to not be the case for the right coronary circulation, at least at high PO2 values. Experiments in our laboratory demonstrated that right coronary venous PO2 can fall from 30 mm Hg to 20 mm Hg with no change in right coronary conductance as the right coronary O2 extraction reserve is mobilized during exercise (5). However, when right coronary venous PO2 reached ~20 mm Hg, further declines were closely associated with increased right coronary conductance. In this lower range of PO2 values, both right and left coronary conductances were similarly sensitive to changes in venous PO2 (Fig. 1
; Refs. 5–7, 20, 46, 50).
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Contributions of Flow Reserve and O2 Extraction Reserve to Right Ventricular O2 Supply When Right Ventricular O2 Consumption Is Increased |
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TopAbstractIntroductionAssessing Right Coronary Venous...Resting Right Coronary Blood...Contributions of Flow Reserve...Transmural Distribution of Right...Right Coronary AutoregulationRight Ventricular Systolic...ConclusionsReferences |
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Exercise increases myocardial O2 demand, and the effect of exercise on right coronary blood flow has been studied in several animal species (22, 30, 37, 42). In dogs, Ball et al. (22) found that myocardial blood flow in the right ventricle increased linearly with heart rate during graded treadmill exercise and remained uniformly distributed across the right ventricular free wall. Bauman et al. (38) also examined exercise-induced increases in canine right coronary flow and found similar left and right coronary flow reserves during exercise. In ponies, Manohar (30) and Parks and Manohar (28) found that maximal exercise produced large increases in right coronary blood flow that were uniformly distributed across the right ventricular free wall. As a percentage, the increase in right coronary flow (921%) exceeded the increase in left coronary flow (419%), but these values largely reflected the lesser resting right coronary flow (30). At maximal exercise, flow values were similar in right and left ventricular free walls. Similar findings were later reported in horses (37). In swine, Duncker et al. (42) also found that exercise produced a greater percentage increase in right coronary blood flow (307%) than in left coronary blood flow (172%) which, as in ponies, reflected a lesser resting right coronary flow as well as a slightly larger flow during exercise.
In ponies, horses, and swine, exercise causes large increases in pulmonary artery pressure (30, 37, 42), which elevates right ventricular work and requirements for right coronary blood flow (24, 25). In contrast, the effects of exercise on human and canine pulmonary artery and right ventricular systolic pressures are much less pronounced (5, 60, 61). None of the earlier studies of right coronary blood flow during exercise sampled right coronary venous blood to compute right ventricular myocardial O2 consumption, so these studies could not relate changes in right coronary flow and conductance to changes in right ventricular myocardial O2 consumption. Also, these earlier studies could not determine the relative contributions of increased right coronary blood flow and right ventricular O2 extraction in meeting elevated right ventricular O2 requirements during exercise.
Under conscious resting conditions, the left ventricle extracts ~75% of the O2 delivered by coronary arterial blood, so left ventricular O2 extraction reserve is quite limited (20, 62, 63). Thus, increases in left ventricular O2 demand, as occur during exercise, must be met primarily by increasing left coronary flow (20, 22, 58, 59, 62–66). With both a large flow reserve and a large O2 extraction reserve, the right ventricle has two options to increase its O2 supply when O2 demand increases. Hart et al. (5) measured, for the first time, right ventricular myocardial O2 consumption and its determinants, right ventricular O2 extraction, and right coronary flow during exercise. They then evaluated the respective roles of the right coronary flow reserve and the right ventricular O2 extraction reserve in balancing right ventricular O2 demand and supply. Initially, the right ventricular O2 extraction reserve was preferentially used (Fig. 2). During the first level of exercise (4 mi/hr), the increase in O2 extraction provided 82% of the incremental increase in O2 supply. An increase in right coronary blood flow provided only 18%. Right coronary conductance did not increase until the right ventricular O2 extraction had increased to ~75%. In this process, right coronary venous PO2 decreased to ~20 mm Hg without concomitant right coronary vasodilation.
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) and, concomitantly, large increases in coronary blood flow (Fig. 3; Refs. 20, 22, 58, 59, 62–66). The fact that conductance increases in both right and left coronary circulations when coronary venous PO2 falls below 20 mm Hg suggests that this is a critical value for the activation of a powerful vasodilator mechanism (Fig. 1). Despite much research, mostly applied to the left coronary circulation, this mechanism has not been delineated.
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The mechanism responsible for increased right coronary flow during pulmonary hypertension was further explored by analysis of O2 supply variables as functions of right ventricular myocardial O2 consumption before and after nitric oxide synthesis blockade with N
-nitro-L-arginine. After nitric oxide synthesis blockade, the right coronary flow and conductance responses to changes in right ventricular myocardial O2 consumption were 21% and 50% less, respectively. This attenuated right coronary flow response to pulmonary hypertension forced the right ventricle to use its O2 extraction reserve, as reflected by the reductions in right coronary venous PO2 at any measured right ventricular myocardial O2 consumption. Thus, nitric oxide is required for the right coronary hyperemic response to acute pulmonary hypertension, as well as for regulating resting right coronary blood flow.
To reconcile the different findings of relative contributions of right coronary flow and O2 extraction to right ventricular O2 supply during exercise and pulmonary hypertension, Zong et al. (6, 7) suggested that an augmented, sympathetic-mediated vasoconstrictor tone blunts metabolically mediated dilator mechanisms during exercise and forces the right ventricle to mobilize its O2 extraction reserve. During acute pulmonary hypertension experiments, arterial pressure did not fall (6). Therefore, in the absence of an error signal, it seems unlikely that sympathetic-mediated vasoconstrictor tone was increased.
To further investigate control of right coronary blood flow during exercise, Zong et al. (7) examined right ventricular O2 balance during graded treadmill exercise before and during -adrenergic blockade with phentol-amine. During exercise, -adrenergic blockade increased right coronary flow and conductance responses to increased right ventricular myocardial O2 consumption by 25% and 60%, respectively. Before -adrenergic blockade, hyperemia provided 39%–66% of the additional O2 consumed by the right ventricle during graded exercise. After -adrenergic blockade, hyperemia contributed 74%–85%. In contrast, smaller increases in left coronary flow have been reported by Gorman et al. (22%; Ref. 46), Heyndrickx et al. (14%; Ref. 48), Huang and Feigl (6%; Ref. 67), Strader et al. (21%; Ref. 68), and Bache et al. (16%; Ref. 69).
The impact of exercise-induced sympathetic vaso-constriction on O2 balance in the right and left coronary circulations can be compared by plotting right and left coronary venous PO2 as functions of myocardial O2 consumption (7). Figure 4A shows that the right coronary vasodilation caused by -adrenergic blockade significantly elevated venous PO2 at any exercise-induced increase in right ventricular O2 consumption. This effect of -adrenergic blockade on venous PO2 was much less in the left coronary circulation (Fig. 4B). To further investigate the role of adrenergic mechanisms in regulating right coronary flow, additional experiments were conducted on anesthetized, open-chest dogs with constant right coronary perfusion pressure and ß-adrenergic blockade. The right coronary flow response to intracoronary norepinephrine was shifted to the left compared with that measured in the left coronary circulation, which is consistent with observations in the conscious, exercising dogs (7). Thus, it is evident that during exercise, physiologic modulation of coronary conductance by sympathetic vasoconstrictor tone and its effect on O2 delivery by the coronary circulation is more pronounced in the right ventricle. However, right ventricular O2 balance can still be maintained by using the large right ventricular O2 extraction reserve.
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Besides the role of nitric oxide in regulating right coronary blood flow under various conditions, the effect of nitric oxide on right ventricular metabolism was also investigated (21, 43, 44). Setty et al. (43) demonstrated in anesthetized dogs that nitric oxide has a depressive effect on right ventricular O2 demand when changes in right coronary flow are avoided by maximal dilation with adenosine. During norepinephrine-induced increases in right ventricular mechanical performance and right ventricular O2 consumption, nitric oxide acts to lessen myocardial O2 demand and, thus, contributes to the right ventricular O2 demand/supply balance by increasing right ventricular O2 utilization efficiency (21). In another study, Setty et al. (44) found that nitric oxide improved right ventricular O2 utilization efficiency in hypoperfused myocardium.
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Transmural Distribution of Right Coronary Blood Flow |
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TopAbstractIntroductionAssessing Right Coronary Venous...Resting Right Coronary Blood...Contributions of Flow Reserve...Transmural Distribution of Right...Right Coronary AutoregulationRight Ventricular Systolic...ConclusionsReferences |
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-adrenergic blockade in the left circumflex region of the left ventricle decreased the ratio of subendocardial to subepicardial flow during exercise. They concluded that enhanced -adrenergic coronary vasoconstriction is beneficial by redistributing left coronary flow toward the subendocar-dium, the region of the left ventricular wall most vulnerable to underperfusion. Morita et al. (71) demonstrated that -adrenergic–mediated left coronary vasoconstriction reduced systolic retrograde coronary flow. Thus, reduction of to-and-fro flow oscillations in arterial vessels that penetrate the left ventricular wall might result in more flow to the subendocardium during exercise. However, in anesthetized dogs, Baumgart et al. (72) could detect this effect only when the coronary vasculature had been previously dilated maximally and the cardiac sympathetic nerves were stimulated. Also, Dodd-o and Gwirtz (73) reported that -adrenergic coronary vasoconstriction does not affect left ventricular transmural blood flow distribution during exercise.
Whether sympathetic vasoconstriction is important for maintaining flow to the subendocardium of the right ventricle was tested by Zong et al. (7). They concluded that adequate right ventricular subendocardial flow is not dependent on sympathetic vasoconstrictor tone because -adrenergic blockade did not alter the transmural distribution of right coronary blood flow either at rest or during exercise (7). Because the right ventricular wall is much thinner than the left ventricular wall, and the right coronary circulation is subjected to lesser myocardial tissue pressures than the left coronary circulation, to-and-fro flow oscillations of right coronary flow would likely be minimal, so vasoconstrictor tone might not be required to direct adequate blood flow to the right ventricular subendocardium.
In the left ventricular free wall, flow to subendocardium is reduced to a greater extent than is flow to subepicardium during severe coronary hypotension (74–77), while the coronary flow reserve in that region also falls (77). In contrast to the left coronary circulation, as right coronary artery perfusion pressure was decreased from 100 mm Hg to 40 mm Hg, subepicardial and subendocardial flows were similarly reduced (31). This finding is consistent with differences in the left and right coronary artery phasic flow patterns (1, 23) because right ventricular subendocardial perfusion is much less dependent on diastolic flow.
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Right Coronary Autoregulation |
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TopAbstractIntroductionAssessing Right Coronary Venous...Resting Right Coronary Blood...Contributions of Flow Reserve...Transmural Distribution of Right...Right Coronary AutoregulationRight Ventricular Systolic...ConclusionsReferences |
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The absence of effective autoregulation in the right coronary circulation contrasts markedly with the potent autoregulation often found in the left coronary circulation (15, 77, 79–86). Most studies of coronary autoregulation have been conducted in anesthetized dogs. However, Bian et al. (3) evaluated right coronary autoregulation in conscious dogs that were chronically instrumented to measure right coronary flow and right coronary pressure as a hydraulic occluder on the right coronary artery was inflated. These dogs were then anesthetized and right coronary autoregulation was again assessed. In the conscious state, right coronary autoregulatory closed loop gain (Gc) was 0.59–0.27 (Gc = 1 if changes in pressure have no effect on flow) as right coronary pressure was reduced from 100 mm Hg to 40 mm Hg. In the anesthetized state, Gc was not significantly less than in the conscious state at right coronary pressure >50 mm Hg, so previously reported poor right coronary autoregulation was not an artifact due to anesthesia.
In contrast to the reports of absence or weak autoregulation by the right coronary artery as previously described, Guth et al. (34) reported a marked autoregulatory capacity within the right coronary artery perfusion territory of anesthetized swine. In this study, the pressure-flow relationship of the right ventricle showed nearly perfect autoregulation down to a right coronary pressure of 30 mm Hg, with a significant decrease in blood flow observed only at 20 mm Hg. Regional contractile function of the right ventricle was well maintained until right coronary pressure was reduced below 30 mm Hg. Interestingly, autoregulation was poor in the right atrium.
The potent right coronary autoregulation observed by Guth et al. (34) in swine may reflect a species difference. Another explanation for this potent right coronary auto-regulation is elevated sympathetic stimulation of the right coronary circulation. In their experiments, the right coronary artery was perfused by an extracorporeal circuit that withdrew blood from a carotid artery. The other carotid artery was also catheterized to measure arterial blood pressure. Bilateral ligation of the carotid arteries would have unloaded the carotid baroreceptors, resulting in a reflex increase in sympathetic drive to the right ventricle (2). This may have enhanced baseline right coronary vasoconstriction in this animal model and blunted the potency of the metabolic vasodilators released under conditions of reduced right coronary perfusion pressure. Interestingly, an earlier study by Jones et al. (87) showed that sympathetic-mediated coronary vasoconstriction increased the efficiency of left coronary blood flow autoregulation. Increased sympathetic activity may have also helped sustain right ventricular contractile function as perfusion pressure was reduced.
Tani et al. (33) used a canine model in which the right and left circumflex coronary arteries were perfused from a single pressure reservoir. They also found significant autoregulatory capacity in the right coronary circulation, and the pressure at the lower end of the autoregulatory range was lower in the right than in the left circumflex coronary artery. However, different size cannulae were likely required to perfuse the left and right coronary circulations. This factor and the differences in left and right coronary artery flows would have made it impossible for a common reservoir to simultaneously perfuse these arteries at identical pressures. If more pressure were dissipated in a smaller diameter right coronary cannula, any change in the reservoir pressure would have altered right coronary perfusion pressure less than left coronary perfusion pressure. Under these circumstances, right coronary flow would have changed less than left coronary flow, leading the investigators to conclude that right coronary autoregulatory capability exceeded left coronary autoregulatory capability.
Smolich et al. (32, 35) reduced aortic pressure and, thus, right coronary artery perfusion pressure, with a large arteriovenous shunt and found potent right coronary autoregulation. This reduction in systemic arterial pressure would have activated the baroreflex, which may have enhanced right coronary autoregulation as in the experiments of Guth et al. (34). Furthermore, opening an arteriovenous shunt increases both right ventricular venous return and right ventricular O2 demand. Thus, when right coronary perfusion pressure was reduced by opening the shunt, an increase in right ventricular myocardial O2 consumption would sustain right coronary flow and make right coronary autoregulation appear to be potent. This was confirmed by Gaugl et al. (36) who observed augmented right ventricular myocardial O2 consumption at lower right coronary perfusion pressure when an arteriovenous shunt was opened. In the same dogs, selective changes in right coronary perfusion pressure produced corresponding changes in coronary blood flow (i.e., right coronary autoregulation was ineffective).
As previously mentioned, implicit in the definition of autoregulation is the assumption that changes in coronary perfusion pressure do not produce changes in O2 demand. For the right coronary circulation, this prerequisite of constant myocardial O2 consumption was absent over the entire range of pressures (i.e., 40 mm Hg–160 mm Hg) examined by Yonekura et al. (15). Furthermore, when autoregulation was abolished in the maximally dilated right coronary circulation, graded increases in coronary perfusion pressure increased both right coronary blood flow and right ventricular myocardial O2 consumption (43). Because changes in perfusion pressure have a marked effect on right ventricular myocardial O2 consumption (15, 16, 43), the corresponding changes in right coronary flow may reflect appropriate metabolic autoregulation, although pressure-flow autoregulation is attenuated. In fact, when the change in right ventricular myocardial O2 consumption was taken into account, a "corrected" right coronary autoregulatory gain could be computed, which agreed well with left coronary autoregulatory gain (15). In contrast, left coronary circulations with potent autoregulation had essentially constant myocardial O2 consumption as left coronary perfusion pressure was varied (83, 85, 86).
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Right Ventricular Systolic Stiffness and Right Ventricular Function |
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TopAbstractIntroductionAssessing Right Coronary Venous...Resting Right Coronary Blood...Contributions of Flow Reserve...Transmural Distribution of Right...Right Coronary AutoregulationRight Ventricular Systolic...ConclusionsReferences |
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Systolic stiffness is an important determinant of ventricular internal work, so changes in systolic stiffness affect the internal to external work ratio and impact on ventricular O2 utilization efficiency (17, 86, 91, 92). Systolic stiffness can be estimated from the ratio of isometric force (
F) and nearby segment shortening (SL) during ventricular ejection (39, 93). Bian and Downey (39) estimated changes in systolic ventricular stiffness during decreased right coronary pressure in intact, ejecting canine hearts. The F decreased as right coronary pressure was decreased from baseline, although the SL was unchanged. Thus, right ventricular systolic stiffness (F/SL) fell. This may account for the remarkable ability of the right ventricle to maintain external work and cytosolic energetics in the face of moderately reduced coronary blood flow and also reduced right ventricular myocardial O2 consumption (17). In contrast, there is a tight relationship between left coronary flow and left ventricular mechanical function as left coronary flow is reduced (92, 94, 95).
Reduced systolic stiffness at low coronary perfusion pressure would improve the ratio of external to total work. This would decrease myocardial O2 demand as O2 supply is reduced, so the ventricular O2 demand/supply balance could be maintained. Maintenance of this balance was evident from the absence of lactate production (39, 40, 44). We have observed marked changes in right coronary vascular volume that correlated with right ventricular myocardial O2 consumption (96), as we have reported for left coronary circulations with impaired autoregulation (86). Thus, we propose that in the poorly autoregulating right coronary circulation, reduced coronary pressure unloads the coronary hydraulic skeleton and reduces right ventricular systolic stiffness.
A comparison of the data from both ventricles shows that right ventricular systolic stiffness is much less than left ventricular stiffness (39, 90), as is consistent with the thinner right ventricular wall. Because baseline right ventricular systolic stiffness is so low, changes in coronary pressure produce proportionally greater changes in right ventricular stiffness compared with the left ventricle. This may explain why changes in coronary perfusion pressure produce more marked changes in myocardial O2 consumption in the right ventricle than in the left ventricle.
Left ventricular mechanical function is very sensitive to reductions in left coronary blood flow (94, 95). However, global right ventricular function is much less sensitive to changes in right coronary flow. Because the canine right coronary artery does not supply the interventricular septum (97), it is not surprising that complete occlusion of the right coronary artery has been reported to have little effect on right ventricular systolic pressure of dogs (98). However, in swine, as in humans, the right coronary artery supplies portions of the left and right ventricles (1). Thus, proximal right coronary artery occlusion will have a greater effect on cardiac function in these species. Clearly, evaluation of the relationship between right coronary flow and right ventricular function relation requires direct assessment of function in the right ventricular perfusion territory of the right coronary artery, as by measuring regional right ventricular segment shortening.
Bian et al. (3) and Bian and Downey (39) implanted a pair of piezoelectric crystals in the midmyocardium of the right coronary artery perfusion territory to measure myocardial segment lengths. They found that right ventricular function was unchanged until right coronary pressure was reduced to <50 mm Hg in both conscious and anesthetized dogs (Fig. 5). Consistent with ineffective right coronary autoregulation, right coronary flow fell with right coronary pressure. However, right ventricular function did not fall until right coronary flow fell by ~34% in conscious dogs and ~56% in anesthetized dogs. Because the right ventricle has much greater O2 extraction reserve compared with the left ventricle (5–8, 10, 13, 14, 16, 49, 58, 62, 63), it is tempting to attribute the maintenance of right ventricular function with reduced flow to mobilization of this O2 extraction reserve. However, we previously found that right ventricular O2 extraction increased only from 44% to 55% as right coronary pressure was reduced from 80 mm Hg to 40 mm Hg (16), although right ventricular myocardial O2 consumption significantly fell. Faced with a moderate decrease in right coronary pressure and a corresponding decrease in right coronary flow, the right ventricle decreases its O2 demand with little or no decrement in right ventricular function. This theory is further supported by another report from our laboratory that right ventricular function and high-energy phosphates were well maintained as right coronary pressure was reduced to 60 mm Hg, although right coronary flow fell 45% (17). These findings are consistent with our view that ventricular systolic stiffness decreases as coronary pressure is reduced and that this reduction in internal cardiac work permits maintenance of normal cardiac external work and cytosolic energetics during moderate coronary hypoperfusion (39, 90, 99).
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Although the right ventricle can sustain its contractile function during brief periods of right coronary hypoperfusion, Yi et al. (41) noted both reduced right ventricular function and O2 consumption by 15 mins of hypoperfusion at a right coronary pressure of 40 mm Hg. A reduction in O2 demand of the underperfused right ventricular myocardium might allow it to remain viable despite limited O2 supply, as has been described for hibernating left ventricular myocardium (100). Yi et al. (41) also found that low-dose dobutamine significantly increased contractile function and O2 utilization efficiency of the hypoperfused right ventricle. Thus, the decrease in right ventricular function during hypoperfusion was an adaptation to reduced right coronary flow and not the direct effect of ischemia.
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Conclusions |
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TopAbstractIntroductionAssessing Right Coronary Venous...Resting Right Coronary Blood...Contributions of Flow Reserve...Transmural Distribution of Right...Right Coronary AutoregulationRight Ventricular Systolic...ConclusionsReferences |
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-adrenergic vasoconstriction during exercise, with no effect on transmural right coronary flow distribution Considering these important differences in factors impacting the myocardial O2 demand/supply balance, generalizations about right coronary physiology should not be made from left ventricular observations. The physiology of the right ventricle and its coronary circulation merit much further investigation.
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Footnotes |
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2 Current Address: Department of Physiology, Louisiana State University Health Science Center, New Orleans, Louisiana 70112 
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References |
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TopAbstractIntroductionAssessing Right Coronary Venous...Resting Right Coronary Blood...Contributions of Flow Reserve...Transmural Distribution of Right...Right Coronary AutoregulationRight Ventricular Systolic...ConclusionsReferences |
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, different from prior, less strenuous condition (P < 0.05). (Reproduced from Ref. 
