Elevation Of Aortic Pressure Research Articles

Mechanisms involved in aortic baroreceptor excitation during drug-induced aortic pressure elevation in intact rabbits

Aortic baroreceptor activity during drug-induced elevation of arterial pressure in intact animals is determined not only by the magnitudes of arterial pressure elevation but also by other mechanisms such as the direct effects of drugs on aortic wall property and on baroreceptors per se. This study aimed to determine the relative contribution of arterial pressure elevation and other mechanisms on aortic baroreceptor activity during intravenous infusion of norepinephrine (NE), phenylephrine (PE) or angiotensin II (Ang II) in intact anesthetized rabbits, all of which were used to assess arterial baroreflex function in vivo. We simultaneously recorded aortic pressure (AP), afferent aortic nerve activity (ANA) and the aortic diameter (AD) during elevation of AP induced by intra-aortic balloon inflation or intravenous infusions of NE, PE, and Ang II. During Ang II-infusion or balloon inflation, AD progressively increased with increases in AP. The relationships among changes in AP, ANA, and AD were similar during balloon inflation and during Ang II infusion which indicated that increases in ANA during Ang II infusion were caused by increases in AD or strain of baroreceptors. In contrast, during NE or PE infusion, ANA increased with no changes or decreases in AD, respectively. The latter results suggest that in intact rabbits increases in ANA during NE or PE infusion resulted from mechanisms other than an increase in strain of baroreceptors, such as the direct excitatory effect on baroreceptors. Thus, different mechanisms were involved in aortic baroreceptor excitation in intact rabbits during elevation of AP caused by the vasopressor drugs, which are commonly used to assess arterial baroreflex function in vivo.

Signal transduction in myocardial hypertrophy.

Transduction of stretch of the ventricular wall into accelerated growth and ultimately hypertrophy of cardiac muscle cells is a cyclic AMP (cAMP) dependent phenomenon. When stretch was induced in isolated perfused rat hearts by an increase in aortic pressure from 60 to 120 mmHg, protein synthesis was accelerated during the second hour of perfusion. Only a brief exposure to higher aortic pressure (2 min) was required to elicit this effect. Elevation of aortic pressure also increased cAMP content. Other interventions that increased cAMP content such as glucagon increased second hour rates of protein synthesis. Stretch of the ventricular wall had a more rapid effect on ribosome formation. During the first hour of perfusion, increased aortic pressure raised rates of 60S ribosomal subunit formation by 38% in the absence of added insulin and 35% in the presence of the hormone. Ribosome formation was also accelerated by addition of glucagon. The muscarinic cholinergic agonist, methacholine blocked the effects of elevated aortic pressure on protein synthesis, ribosome formation, and cAMP content. These studies indicate that stretch of the ventricular wall is transduced into greater cAMP content and that this intracellular messenger is one of the substances responsible for accelerated ribosome formation and protein synthesis.

Increased cyclic AMP content accelerates protein synthesis in rat heart.

Elevation of cyclic AMP (cAMP) content in perfused rat hearts by exposure to glucagon, forskolin, and 1-methyl-3-isobutylxanthine (IBMX) increased rates of protein synthesis during the second hour of perfusion with buffer that contained glucose in the absence of added insulin. When tetrodotoxin was added to arrest contractile activity, glucagon, forskolin, and IBMX still elevated cAMP content and rates of protein synthesis. Perfusion of beating rat hearts at elevated aortic pressure (120 mm Hg vs. 60 mm Hg) also accelerated rates of protein synthesis and raised cAMP content and cAMP-dependent protein kinase activity during the second hour of perfusion. Insulin accelerated rates of protein synthesis in beating hearts during the first and second hour of perfusion but did not increase cAMP content. Elevation of aortic pressure in insulin-treated hearts raised cAMP content but had no further effect on rates of protein synthesis. Perfusion of arrested hearts for as little as 2 minutes at 120 mm Hg resulted in a rapid and sustained increase in cAMP content, cAMP-dependent protein kinase activity, and rate of protein synthesis after 60-120 minutes of additional perfusion at 60 mm Hg. Exposure of arrested hearts to 0.2 mM methacholine, a muscarinic-cholinergic agonist, for 5 minutes before elevation of perfusion pressure blocked the pressure-induced increases in cAMP content, cAMP-dependent protein kinase activity, and rates of protein synthesis. When hearts were removed from pertussis toxin-treated animals, methacholine did not block the effects of forskolin on these same three parameters. These studies indicated that elevation of tissue cAMP by hormone binding, direct activation of adenylate cyclase, or inhibition of phosphodiesterase resulted in acceleration of protein synthesis. Furthermore, the effects of increased aortic pressure to accelerate synthesis appeared to involve a cAMP-dependent mechanism that was independent of changes in contractile activity but could be blocked with a muscarinic-cholinergic agonist. Acceleration of protein synthesis by insulin was not associated with an elevation of cAMP.

Effect of higher aortic pressure on ribosome formation and cAMP content in rat heart

Elevation of aortic perfusion pressure from 60 to 120 mmHg in beating and arrested rat hearts raised cAMP content and increased rates of ribosome formation but had no effect on total protein synthesis during 1 h of perfusion. The activity of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase increased as perfusion pressure was elevated in arrested hearts. A regulatory link between increased cAMP content and accelerated ribosome formation was hypothesized to exist. When hearts were arrested with tetrodotoxin and exposed to 0.2 mM methacholine, a muscarinic-cholinergic agonist that blocked pressure-induced increases in cAMP content, elevation of aortic pressure to 120 mmHg failed to increase the rate of ribosome formation. When aortic pressure was maintained at 60 mmHg, exposure of beating hearts to glucagon increased cAMP content and mimicked the effect of elevated aortic pressure to accelerate rates of ribosome formation. These studies support the hypothesis that increased aortic pressure preferentially accelerates rates of ribosome formation by a cAMP-dependent mechanism.

Elevated aortic pressure, calcium uptake, and protein synthesis in rat heart

Elevation of aortic pressure from 60 to 120 mmHg increased the initial rate of 45Ca 2+ uptake and the steady-state level that was achieved. The increase in uptake was as great after the first 10 min of pressure elevation as it was after aortic pressure had been at 120 mmHg for 1 h. When aortic pressure was returned to 60 mmHg for 30 min after 1 h at 120 mmHg, calcium uptake was restored to the control value. Elevation of perfusate Ca 2+ from 0.5 m m to 2.9 and 5.0 m m increased oxygen consumption and decreased creatine phosphate/creatine ratios in hearts supplied glucose but had no effect on the rate of total protein synthesis. When hearts were supplied pyruvate to maintain high energy phosphates, an increase in perfusate Ca 2+ from 0.5 to 2.9 m m did not accelerate total protein synthesis or ribosome formation. These studies provide no support for a role for extracellular Ca 2+ availability in mediating the effects of elevated aortic pressure on total protein synthesis and ribosome formation.

Hemodynamics in humans during conventional and experimental methods of cardiopulmonary resuscitation.

High-fidelity hemodynamic recordings of aortic and right atrial pressures and the coronary perfusion gradient (the difference between aortic and atrial pressure) were made in nine patients during cardiopulmonary resuscitation (CPR). Findings during conventional manual CPR were compared with those during high-impulse CPR (rate, 120 cycles/min with a shorter compression:relaxation ratio) as well as during pneumatic vest CPR with and without simultaneous ventilation and abdominal binding. Aortic peak pressure during conventional CPR averaged 61 +/- 29 mm Hg but varied widely (range, 39-126 mm Hg) among patients. Although the magnitude of improvement was modest, the high-impulse method was the only technique tested that significantly elevated both aortic peak pressure and the coronary perfusion gradient during cardiac arrest. During conventional CPR, aortic pressure rose from 61 +/- 29 to 80 +/- 39 mm Hg during high-impulse CPR, and the gradient rose from 9 +/- 11 to 14 +/- 15 mm Hg, respectively; p less than 0.01. The pneumatic vest method significantly improved peak aortic pressure but not the coronary perfusion gradient. Simultaneous ventilation and chest compression created high end-expiratory pressure and lowered the coronary perfusion gradient. Abdominal binding had no significant hemodynamic effects. This evaluation of experimental resuscitation methods in humans shows that the high-impulse chest compression method augments aortic pressure over levels achieved during conventional CPR methods; however, the improvement in pressure is modest and may not be clinically important. Simultaneous ventilation as well as abdominal binding during CPR were associated with no benefit; in fact, simultaneous ventilation appears to adversely affect cardiac perfusion and, therefore, should not be used during clinical resuscitation.

Effect of calcium uptake increased by elevated aortic pressure on total and ribosomal protein synthesis in rat heart: T. Haneda, H.E. Morgan, and P.A. Watson. Weis Center for Research, Geisinger Clinic, Danville, PA

Effect of calcium uptake increased by elevated aortic pressure on total and ribosomal protein synthesis in rat heart: T. Haneda, H.E. Morgan, and P.A. Watson. Weis Center for Research, Geisinger Clinic, Danville, PA

Segmental vascular responses to acute hypertension in cerebrum and brain stem.

The goal of this study was to examine hemodynamic mechanisms that contribute to regional differences in autoregulation during acute hypertension. We measured blood flow (microspheres) and pressure in pial arteries (approximately 160 microns) of anesthetized cats and calculated resistance of large and small vessels in cerebrum and brain stem. Moderate elevation of aortic pressure increased resistance of both large and small vessels in cerebrum but only small vessels in brain stem. During severe hypertension, resistance of both large and small vessels in cerebrum decreased and blood flow increased markedly. In contrast, in the brain stem large artery resistance did not change, small vessel resistance increased, and blood flow increased only modestly during severe hypertension. Pial artery pressure was 20 mmHg higher in brain stem than cerebrum during control conditions and 30-50 mmHg higher during moderate and severe hypertension. We conclude that resistance of large arteries is less and thus pial artery pressure is higher in brain stem than cerebrum under control conditions. More effective autoregulation in the brain stem than cerebrum during severe hypertension is due to greater resistance of small, not large, cerebral vessels.

Faster ribosome synthesis induced by elevated aortic pressure in rat heart.

An increase in aortic pressure from 60 to 120 mmHg accelerated ribosomal protein synthesis in rat hearts during 1 or 2 h of labeling with 0.4 mM [3H]phenylalanine. When hearts were perfused with buffer that contained 20 mM glucose and normal plasma concentrations of 19 other amino acids without added insulin, ribosomal protein synthesis relative to the rate of total protein synthesis increased from approximately 0.22 to 0.36 and 0.30 as aortic pressure was raised from 60 to 120 mmHg during 1 or 2 h of labeling, respectively. With the addition of insulin, the relative rate of ribosomal protein synthesis averaged 0.33 at an aortic pressure of 60 mmHg and increased to 0.42 when aortic pressure was raised to 120 mmHg. These results indicate that elevation of aortic pressure has a preferential effect on synthesis of new ribosomes. This response appears to be an early and physiologically significant event in cardiac hypertrophy.

Aortic pressure as a determinant of cardiac protein degradation.

Mechanical parameters and intracellular mediators that may control protein degradation were studied in isolated rat hearts subjected to increased aortic pressure. Elevation of aortic pressure from 60 to 120 mmHg in Langendorff preparations provided glucose or pyruvate as substrate decreased the rate of protein degradation during the second hour of perfusion. Intracellular contents of ATP or creatine phosphate or the creatine phosphate/creatine ratio did not indicate that energy depletion accounted for these effects. When ventricular pressure development was prevented by ventricular draining, and hearts were arrested with tetrodotoxin, protein degradation still decreased as aortic pressure was raised. The effect of elevated aortic pressure on proteolysis was unchanged when perfusate calcium concentrations were 0.6, 3.0, or 5.1 mM, or when indomethacin or meclofenamate was added to the perfusion buffer. These results provided no evidence to indicate that intraventricular pressure development or cardiac contraction was responsible for the inhibitory effect of increased aortic pressure on protein degradation. Instead, they suggested that stretch of the ventricular wall, as a consequence of increased aortic pressure, could be the mechanical parameter most closely related to the restraint on proteolysis. No evidence was obtained that the lower rate of degradation depended on energy or calcium availability or prostaglandin synthesis.

Effect of proximal and distal coronary pressure change on the resistance of stenotic coronary segment.

While dynamic changes in the resistance of stenotic coronary segments were recently proposed by several investigators, the mechanisms of these changes are obscure. This study was conducted to correlate changes in coronary pressure distal to the stenosis to dynamic changes in the stenosis resistance in the canine heart. Coronary pressure distal to the stenosis was raised by either proximal aortic pressure elevation or intracoronary blood infusion distal to the stenosis. The pressure rise resulted in a significant fall in the stenosis resistance. Distal coronary pressure drop induced by phlebotomy or removal of blood from the distal coronary bed caused the reverse effects on resistance. Linear regression analysis revealed a close relationship between changes in distal coronary pressure (delta DCP) and those in resistance of the stenotic coronary segment (delta RL) represented by the following equation; delta RL (dyne X cm-5 X sec X 10(-3)) = 0.50 X [delta DCP (mmHg)]-6.0 X 10(-2), r = 0.86, p less than 0.01. The results suggest that dynamic changes in stenosis resistance appear largely to be a function of the pressure changes distal to the stenosis.

Dependence of protein synthesis on aortic pressure and calcium availability.

Increased aortic pressure accelerated protein synthesis in control-beating and arrested-drained hearts supplied with either glucose or pyruvate. Elevation of perfusion pressure from 60 to 120 mm Hg increased oxygen consumption in control-beating but not in arrested-drained preparations. Energy availability, as assessed by adenylate energy charge or creatine phosphate/creatine ratio, or both, was increased in arrested-drained hearts supplied with glucose and perfused at 60 and 120 mm Hg aortic pressure. In control-beating or arrested-drained hearts supplied with pyruvate, energy availability was not improved by elevation of aortic pressure from 60 to 120 mm Hg. An increase of perfusate calcium concentration from 0.5 to 5.0 mM in control-beating Langendorff preparations supplied with glucose and perfused at an aortic pressure of 90 mm Hg doubled oxygen consumption and decreased energy availability, but had no effect on the rate of protein synthesis. In arrested-drained hearts supplied with either glucose or pyruvate and calcium concentrations ranging from 0.5 to 5.0 mM, the rates at 120 mm Hg aortic pressure were 11-25% higher than at 60 mm Hg. These findings provide no evidence to implicate increased oxidative metabolism, energy availability, or extracellular calcium concentration as important factors in the mechanism that accounts for the effects of increased aortic pressure on protein synthesis.

Aortic pressure, substrate utilization and protein synthesis.

An increase in aortic pressure from 60 to 120 mmHg in Langendorff perfused hearts increased oxygen consumption, glucose utilization, pyruvate oxidation and protein synthesis. These changes were not prevented by insertion of a ventricular drain that prevented intraventricular pressure development. Arrest of the heart with tetrodotoxin markedly reduced oxygen consumption; under these conditions an elevation of aortic pressure did not increase oxygen consumption. Elevation of aortic pressure in arrested-drained preparations supplied either glucose or pyruvate as oxidizable substrate increased protein synthesis to a comparable extent. Energy availability, as assessed by measurements of the creatine-P/creatine ratio, increased as aortic pressure was raised in hearts provided glucose, but not pyruvate, suggesting that greater energy availability was not the factor linking higher aortic pressure to faster rates of synthesis. These results focus attention on stretch of the ventricular wall, as the mechanical factor responsible for the effects of aortic pressure on several metabolic activities of the heart.

Nitroprusside infusion in experimental acute myocardial infarction with systemic hypertension: Effects on systemic hemodynamics and regional myocardial blood flows

The effects of graded doses of nitroprusside on regional myocardial blood flow were studied in awake, acutely hypertensive dogs with acute myocardial infarction. Acute systemic hypertension was produced by infusing a mixture of norepinephrine and epinephrine for 80 minutes after coronary artery occlusion. The increase in aortic pressure produced by catecholamine infusion was accompanied by increases in heart rate, left ventricular (LV) enddiastolic pressure, first derivative of LV pressure (dP/dt), dP/dt at an LV developed pressure of 50 mm Hg (dP/dt/P) and pressure-rate product, but total peripheral vascular resistance did not change significantly. Two graded doses of nitroprusside were then infused, each for 25 minutes, beginning 30 minutes after the onset of coronary artery occlusion. The smaller dose of nitroprusside returned aortic pressure to control levels and significantly reduced total peripheral vascular resistance and LV enddiastolic pressure, but did not affect cardiac output, heart rate, LV dP/dt, dP/dt/P and pressure-rate product. Regional blood flow increased to both the ischemic and normal myocardium. The larger dose of nitroprusside further reduced aortic pressure and total peripheral vascular resistance and LV enddiastolic pressure and significantly increased heart rate and cardiac output. However, LV dP/dt, dP/dt/P and pressure-rate product remained unchanged. Regional blood flow to normal myocardium increased, but the increase in ischemic endocardial blood flow produced by the smaller dose of nitroprusside was no longer significant when the larger dose was administered. These changes were not produced by administration of normal saline solution. It is concluded that, in a setting of elevated filling pressures, return of elevated aortic pressure to normal levels by nitroprusside may improve perfusion to the ischemic myocardium. This increase in subendocardial blood flow to ischemic regions was probably a result of increased collateral flow caused, at least in part, by the vasodilator action of the drug and by the decrease in LV filling pressure.

Aortic perfusion pressure as a determinant of cardiac protein synthesis.

Mechanical parameters and intracellular mediators that may control protein synthesis have been studied in isolated rat hearts subjected to increased aortic pressure or induced to perform cardiac work. Elevation of aortic pressure from 60 to 120 mmHg in Langendorff preparations with glucose, glucose plus insulin, or pyruvate raised the rate of protein synthesis during the 2nd h of perfusion. These effects involved faster rates of both peptide chain initiation and elongation. In working hearts supplied glucose or glucose plus insulin, higher rate of synthesis were observed in both the 1st and 2nd h of perfusion, compared with Langendorff preparations perfused at 60 mmHg. Intracellular levels of glucose 6-phosphate, ATP/ADP ratio, adenylate energy charge, or creatine phosphate/creatine did not correlate with the rate of protein synthesis in beating control hearts. When ventricular pressure development was prevented by ventricular draining and hearts were arrested with tetrodotoxin, protein synthesis still increased as a function of perfusion pressure. Oxygen consumption increased as aortic pressure was raised in beating-drained hearts but was unaffected in arrested-drained hearts. These results indicate that intraventricular pressure development, cardiac contraction, oxygen consumption, glucose 6-phosphate, energy availability, and coronary flow could be dissociated from the stimulatory effect of higher aortic pressures on protein synthesis and suggested that stretch of the ventricular wall, as a consequence of increased aortic pressure, could be the mechanical parameter most closely related to the increase in protein synthesis.

Influence of vasopressin and angiotensin on baroreflexes in the dog.

Cardiovascular responses to step-changes of carotid sinus pressure were evaluated at normal and elevated levels of plasma arginine vasopressin in anesthetized neurohypophysectomized dogs (n = 12). Arginine vasopressin influenced autonomic function in two ways: first, maximum carotid reflex gain increased; second, cardiac output was decreased. The enhancement of reflex strength was observed only in response to decreases of intrasinus pressure below the equilibrium point (pressures of between 60 and 105 mm Hg). Aortic pressure rose twice as high for a given decrease of intrasinus pressure, elevations of total peripheral resistance responses were triple those observed at normal plasma arginine vasopressin. In this way, arginine vasopressin more than doubled the ability of the carotid reflexes to return a drop in arterial pressure to normal. Arginine vasopressin enhancement of reflex gain was not observed with elevations of intrasinus pressures above the equilibrium point. Elevation of aortic pressure expected from the vasoconstrictor actions of infused arginine vasopressin were buffered by associated reductions in cardiac output. Vagally mediated bradycardia was consistently observed with elevated arginine vasopressin, but the reflex response of heart rate to step-changes of intrasinus pressure was unchanged. Time control studies in five neurohypophysectomized dogs indicated no significant change in carotid reflex response over the 3- to 4-hour protocol. Comparison of reflex responses in anephric dogs (n = 8) at low and elevated levels of angiotensin II indicated that this vasoactive peptide did not significantly alter reflex responsiveness. We conclude that arginine vasopressin enhances the ability of the carotid reflexes to normalize decreases of arterial pressure, but buffers a rise in pressure from its own vasoactive properties by initiating a fall of cardiac output.

Influences of the alteration in aortic pressure on regional myocardial function and regional myocardial blood flow in partial coronary artery occlusion.

This study was designed to simultaneously evaluate the effects of alterations in aortic pressure (AoP) on regional myocardial function and regional myocardial blood flow (MBF) in anesthetized dogs with partial coronary occlusion. Regional myocardial function was assessed by both segment-length and tension gauges. The left circumflex coronary artery flow was reduced to 50 to 70% by a constrictor. When systolic aortic pressure (AoPS) fell from 103.6 +/- 7.4 to 72.5 +/- 4.9 mmHg following nitroprusside infusion, systolic shortening (SS) markedly depressed from 0.63 +/- 0.17 to 0.09 +/- 0.20 mm (p less than 0.01), developed tension (DT) decreased by 30% (p less than 0.01), and MBF assessed with tracer microspheres decreased from 0.61 +/- 0.13 to 0.36 +/- 0.11 ml/min/Gm (p less than 0.01) in ischemic regions. In non-ischemic regions SS was enhanced from 0.78 +/- 0.16 to 0.89 +/- 0.15 mm (p less than 0.05), but DT and MBF showed no changes. An elevation of AoPS from 106.4 +/- 5.6 to 143.3 +/- 6.9 mmHg following methoxamine infusion brought about enhanced SS from 0.42 +/- 0.15 to 0.48 +/- 0.09 mm (p less than 0.05), a 50%-increase in DT (p less than 0.01), and was associated with an increase in MBF from 0.66 +/- 0.03 to 1.19 +/- 0.07 ml/min/Gm (p less than 0.01) in ischemic regions. These results indicate that, in partial coronary occlusion, a fall of AoP induces redistribution of blood flow away from ischemic regions and aggravates the function of the ischemic myocardium, while an elevation of AoP may produce beneficial effects upon the ischemic myocardium.

Quantitative data on the afterload dependence of left ventricular dp/dtmax in isolated canine hearts.

In 15 canine heart-lung preparations the effect of an increase in aortic pressure on left ventricular dP/dtmax was tested. Abrupt elevation of aortic pressure by 20-80 mm Hg during diastole without change in enddiastolic pressure did not influence left ventricular dP/dtmax in the following heart beat. Left ventricular circumference increased slightly. Stepwise elevation of aortic pressure from 60 to 130 mm Hg (LVEDP maintained constant) resulted in an augmentation of the steady-state values of dP/dtmax by only 42 mmHg/s per 10 mmHg pressure rise. If the enddiastolic pressure was not maintained constant, the increase in dP/dtmax was 77 mm Hg/s per 10 mm Hg pressure rise. Aortic pressure alterations exhibit a slight but significant influence on left ventricular contractility in the steady-state phase, while an acute effect is not detectable, thus demonstrating that a sudden increase in coronary perfusion pressure is without immediate effect on the cardiac performance.

Increased adenosine formation by rat myocardium with acute aortic constriction

Based primarily on the observations that adenosine release by the heart is inversely related to oxygen supply to the myocardium, it has been proposed that adenosine serves as a metabolic regulator of coronary vascular resistance. The present study was undertaken to determine to what extent adenosine formation is influenced by increases in mean aortic pressure, which is known to elevate myocardial oxygen requirements. In pentobarbital-anesthetized rats, aortic pressure and aortic blood flow were measured during control periods and during constriction of the thoracic aorta. The hearts were frozen in situ and assayed for adenosine and its breakdown products, inosine and hypoxanthine. In a control group of 16 rats, cardiac adenosine levels were 3.6±0.2 nmol/g tissue. In a second group of seven rats, aortic constriction elevated aortic pressure by 108% without a reduction in cardiac output, and tissue adenosine levels were 5.6±0.8 nmol/g ( P < 0.005). The experimental group also demonstrated an increase in the sum of hypoxanthine, inosine and adenosine from 8.2±0.8 nmol/g observed in controls to 17.2±1.7 nmol/g ( P < 0.001). In contrast, no significant difference was observed in adenosine, inosine and hypoxanthine contents of hearts allowed to recover after release of aortic constriction compared to hearts in parallel time-control experiments. These results suggest a direct relationship between myocardial oxygen consumption and the formation of adenosine during acute aortic constriction.

ALTERED VENTRICULAR FUNCTION DURING SEPTAL AND RIGHT VENTRICULAR ISCHEMIA IN ANESTHETIZED DOGS

The purpose of this study was to determine the effect of right and septal coronary arterial ligation on ventricular function. Regional myocardial flow was measured using 9 micron radioactive microspheres. Following septal coronary ligation septal flow decreased 45.6% from control; following right coronary arterial ligation right ventricular free wall flow fell 41.2% indicating nearly equivalent degrees of ischemia were produced. Although ventricular systolic pressures and stroke volumes remained stable during septal and right coronary arterial ligations, right ventricular function was significantly depressed as evidenced by a fall in right ventricular peak dP/dt by 19% and 14% respectively, and a significant (P < 0.05) shift in the Frank-Starling function curve to the right. Septal coronary arterial ligation did not cause a significant shift in the left ventricular function curves. Following selective ligation, elevation of aortic pressure significantly increased coronary flow to the septum but failed to increase flow to the right or left ventricular free walls. The fact that left coronary arterial flow failed to increase with greater left ventricular pressure loads indicates loss of coronary autoregulation. This suggests that acute ischemia in one region may result in significant coronary vasoconstriction in a nonischemic region. The acute changes in right ventricular function demonstrate that contraction of the ventricular septum contributes more to right ventricular than left ventricular performance.