Coronary Pressure-flow Relations Research Articles

Downward shift of coronary pressure-flow relationship following a brief period of ischemia in dogs.

This study was undertaken to test whether a brief period of ischemia affects the coronary pressure-flow relationship during reduction of coronary perfusion pressure (CPP). The left anterior descending coronary artery was cannulated and perfused with blood from the left carotid artery in 40 open-chest dogs. Coronary blood flow (CBF) was measured during intracoronary administrations of papaverine and adenosine. The coronary pressure-flow relationship was assessed during transient reduction of CPP from 100 to 30 mmHg. Coronary hyperemic flow due to adenosine and papaverine was attenuated 30 min after transient 10- and 15-min periods of ischemia. In the group of transient 10-min ischemia, both fractional shortening (FS) and CBF returned to the preischemic values at 30 and 60 min of reperfusion; however, marked decreases in CBF (35 +/- 5 vs. 56 +/- 4 ml.100 g-1.min-1 at CPP = 60 mmHg, P < 0.01) during graded reductions in CPP were observed. The endomyocardial blood flow was reduced relative to the control condition. Furthermore, both FS (6 +/- 1 vs. 14 +/- 1% at CPP = 60 mmHg, P < 0.01) and lactate extraction ratio (-41 +/- 15 vs. 1 +/- 6% at CPP = 60 mmHg, P < 0.05) were decreased. The downward shift of the CPP-CBF relationship and the deterioration of myocardial contractile and metabolic function during reduction of CPP were restored 60 min after the onset of reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary blood flow and myocardial ischaemia in hypertension

The aim of this investigation was to study the coronary pressure-flow relationship in 60 patients with chronic arterial hypertension of diverse aetiologies and in 14 normotensive subjects (control group). The hypertensive cohort included 6 patients with isolated systolic hypertension (ISH), 7 renovascular hypertensive patients with abnormally elevated angiotensin II plasma levels but without electrocardiographic and/or echocardiographic evidence of left ventricular hypertrophy (LVH) and 47 subjects with essential hypertension (EH), 21 of whom had LVH by electrocardiogram and/or echocardiogram. In the hypertensive cohort a Frank-Starling-like curve was found to describe the coronary pressure-flow relationship when the baseline values for coronary sinus blood flow (CBF, intravascular Doppler technique) were plotted against mean aortic pressure (intra-arterial blood pressure). In particular, the descending limb of such a curve represented a critical region where CBF was “inappropriately” low with respect to perfusion pressure. It was thus concluded that this inability of the heart to adapt CBF to its needs might account for the higher propensity to develop myocardial ischaemia encountered in severe essential hypertensive subjects with concomitant LVH and renovascular hypertensive patients.

Effect of exercise on coronary pressure-flow relationship in hypertrophied left ventricle.

Left ventricular (LV) hypertrophy (LVH) secondary to chronic pressure overload is associated with increased susceptibility to myocardial hypoperfusion and ischemia during exercise. The present study was performed to determine whether exercise causes alterations in minimum coronary resistance or effective back pressure [coronary pressure at zero flow (Pzf)] that limit maximum myocardial perfusion in the hypertrophied heart. Ascending aortic banding in 7 dogs increased the LV weight-to-body weight ratio to 7.7 +/- 0.3 g/kg compared with 4.6 +/- 0.2 g/kg in 11 normal dogs (P < 0.01). Maximum coronary vasodilation was produced by intracoronary infusion of adenosine. Under resting conditions, the slope of the pressure-flow relationship (conductance) was significantly lower in the LVH animals than in the normal dogs (7.2 +/- 0.8 vs. 11.9 +/- 0.8 x 10(-2) ml.min-1.g-1.mmHg-1; P < 0.01); the slope correlated with the degree of hypertrophy r = 0.74; P < 0.001). The Pzf measured during total coronary artery occlusion (Pzf,measured) was significantly elevated in LVH compared with normal dogs (25.6 +/- 2.2 vs. 13.0 +/- 1.2 mmHg; P < 0.01); Pzf,measured was positively correlated (r = 0.78, P < 0.0005) with LV end-diastolic pressure measured during total coronary artery occlusion (9.0 +/- 1.1 mmHg in normal dogs and 22.2 +/- 3.2 mmHg in LVH dogs; P < 0.01). Graded treadmill exercise to maximum heart rates of 210 +/- 9 and 201 +/- 8 beats/min in normal and LVH animals, respectively, caused similar decreases in the slope of the pressure-flow relationship in LVH (from 7.7 +/- 0.9 to 6.1 +/- 0.8 x 10(-2) ml.min-1.g-1.mmHg-1; P < 0.01) and normal dogs (from 11.9 +/- 0.8 to 10.0 +/- 0.7 x 10(-2) ml.min-1.g-1.mmHg-1; P < 0.01). However, exercise-induced increases in Pzf,measured were significantly greater in the LVH animals (from 25.6 +/- 2.2 to 40.8 +/- 2.1 mmHg; P < 0.01) than in normal animals (from 13.0 +/- 1.2 to 24 +/- 2.1 mmHg; P < 0.01) (P < 0.01 LVH vs. normal). The greater increase in Pzf paralleled a more pronounced increase in LV end-diastolic pressure in the LVH dogs from 22.2 +/- 3.2 to 39.1 +/- 2.7 mmHg) than in normal dogs from 9.0 +/- 1.1 to 14.2 +/- 2.0 mmHg). The results suggest that exaggerated increases in filling pressure during exercise in the hypertrophied left ventricles contributed to impairment of myocardial perfusion during exercise by augmenting the back pressure, which opposes coronary flow.(ABSTRACT TRUNCATED AT 400 WORDS)

744-4 Evidence for Downward-Shift of Coronary Pressure-Flow Relationship Following a Brief Period of Ischemia in Dogs

This study was undertaken to test whether a brief period of ischemia affects the coronary pressure-flow relationship during reduction of coronary perfusion pressure (CPP). The left anterior descending coronary artery was cannulated and perfused with blood from the left carotid artery in 40 open-chest dogs. Coronary blood flow (CBF) was measured during intracoronary administrations of papaverine and adenosine. Coronary pressure-flow relationship was assessed during transient reduction of CPP from 100 to 30 mmHg with 10 mmHg intervals. Coronary hyperemic flow due to adenosine and papaverine was attenuated at 30 min of reperfusion following 10 and 15 min of ischemia. In the group of transient 10 min ischemia, both fractional shortening (FS) and CBF returned to the pre-ischemic values at 30 and 60 min of reperfusion, however, marked decreases in CBF (35 ± 5 vs 56 ± 4 ml/100 g/ml at CPP = 60 mmHg, p &lt; 0.01) during graded reductions in CPP were observed. Furthermore, both FS (6 ± 1 vs 14 ± 1% at CPP = 60 mmHg. p &lt; 001) and lactate extraction ratio (–41 ± 15 vs 1 ± 6% at CPP = 60 mmHg, p &lt; 0.05) were decreased. The endocardial vs. epicardial flow ratio was reduced relative to the control condition. The downward-shift of the coronary perfusion pressure-flow relationship and the deterioration of myocardial contractile and metabolic function during reduction of CPP were restored at 60 min of reperfusion. In contrast, in the group of transient 15 min ischemia, although both baseline FS and coronary hyperemic flow due to adenosine and papaverine remained to be at 30 and 60 min of reperfusion, the coronary perfusion pressure-flow relationship was not shifted. Transient brief period of ischemia can reversibly affect the coronary pressure-flow relationship due to the reduced capability of vascular relaxation, however, the downward-shift of coronary pressure-flow relationship can be blunted by the reduced myocardial contractile force against the coronary resistance vessels.

979-36 Role of Endogenous Adenosine in Coronary Pressure-Flow Relationship In Dogs

There have been conflicting evidence for the role of adenosine in coronary pressure flow relationship; although adenosine release increases when coronary perfusion pressure (CPP) is reduced, adenosine deaminase does not affect changes in coronary blood flow (CBF). To examine the role of endogenous adenosine in coronary pressure flow relationship, responses of CBF were observed during a stepwise reduction of CPP by 10 mmHg with and without 8-phenyltheophylline (8PT). In 32 dogs, the left anterior descending coronary artery was perfused from the carotid artery, where CBF was measured. According to the reduction of CPP, adenosine concentration detected in coronary venous blood was increased (CPP = 100 mmHg:7 ± 2, 8O mmHg:25 ± 3, 70 mmHg:53 ± 5, 40 mmHg:165 ± 11 pmollml), Administration of 8PT reduced CBF by 8 ± 3% at CPP = 100 – 70 mmHg, and by 34 ± 7% at CPP = 60-40 mmHg. When CPP was altered between 100 and 70 mmHg, 8PT markedly reduced (p &lt; 0,001) fractional shortening (FS) and lactate extraction ratio (LER) (FS:9,8 ± 1.2 vs. 23.6 ± 1.2%, LER:-6,5 ± 1.9 vs. 26.7 ± 1.9% at CPP = 70 mmHg). Interestingly, 8PT markedly reduced End/Epi flow ratio by 35 ± 4% at CPP = 70 mmHg. Thus we conclude that when CPP is reduced, endogenous adenosine favors endocardial myocardial flow and preserves myocardial contractile and metabolic function.

Impaired endothelium-dependent vasodilation of coronary resistance vessels in severely stunned porcine myocardium.

The effect of stunning on endothelium-dependent responses of resistance vessels in vivo remains of interest. We utilized the coronary pressure-flow relationship during maximal vasodilation in anesthetized swine to identify subtle changes in flow reserve within stunned myocardium. Prior to and following stunning, the coronary pressure-flow relationship during maximal doses of intracoronary adenosine was compared with that of the endothelium-dependent vasodilator ATP. In 11 anesthetized swine, 30 min of partial LAD occlusion and 40 min of reperfusion reduced fractional shortening from 16 +/- 4% to 6 +/- 5% (p < 0.05). This caused a rightward shift of the coronary pressure-flow relationships during infusions of either adenosine or ATP, suggestive of increased extra vascular compressive forces. With adenosine, the slope of the linear portion of the relationship (i.e., coronary pressures > 30 mmHg) was 1.31 +/- 0.54 ml/min-mmHg at baseline and 1.30 +/- 0.55 ml/min-mmHg following stunning (NS). With ATP however, the slope decreased from 1.34 +/- 0.48 ml/min-mmHg at baseline to 1.08 +/- 0.47 ml/min-mmHg following reperfusion (p < 0.05), indicating an attenuation of endothelium-dependent vasodilator capacity. In five of the animals, the slope of the pressure-flow relationship during intracoronary nitroprusside was unchanged post-stunning, which is similar to the adenosine results. In conclusion, the data support the hypothesis that endothelium-dependent vasodilation of resistance vessels in the intact animal is altered within severely stunned myocardium. The rightward shift of the coronary pressure-flow relationships with both classes of vasodilators suggest that extra vascular factors may also play a role in limiting coronary flow reserve.

Increased protection of the ischemic myocardium by decreased aortic pressure.

The elevation of aortic pressure increases myocardial oxygen consumption and increases the blood supply to the myocardium. It is not obvious whether elevated systemic arterial pressure would enhance or diminish myocardial protection during acute myocardial ischemia. This report reviews previously published data on the effects of aortic pressure elevation on the coronary pressure-flow relationship, and on the ischemic myocardium in the dog. The shift of the maximally-dilated coronary pressure-flow line to the right on the pressure-flow diagram is an indication of the deterioration of the oxygen supply/demand ratio caused by aortic pressure elevation. The only maneuver recognized for protecting the ischemic myocardium is early reperfusion. In patients with de novo acute myocardial ischemia, we propose that myocardial protection can be enhanced by reduction of systemic blood pressure until coronary reperfusion therapy is initiated.

Compliance of isolated porcine coronary small arteries and coronary pressure-flow relations.

Compliance of small arteries is important for the interpretation of arterial pressure-flow relations. Six coronary small arteries (mean diameter 189 +/- 46 microns) were cannulated. Pressure-cross-sectional area (CSA) relations were obtained from isolated vessels by slowly varying pressure between 10 and 120 mmHg. Subsequently, small pressure variations were superimposed on constant mean pressures of 10, 30, and 50 mmHg with frequencies of 0.1-10 Hz. Normalized compliance (C0) was calculated as the compliance divided by the CSA at 50 mmHg. In vessels without tone, static C0 was 27.5 +/- 8.9, 6.4 +/- 1.1, and 3.8 +/- 1.0 x 10(-3) mmHg-1 at 10, 30, and 50 mmHg, respectively. At a frequency of 0.1 Hz, C0 decreased to one-third of static C0 at any pressure. Under these conditions, the phase shift between pressure and CSA was rather constant and ranged from -21 to -5 degrees. In four small arteries, smooth muscle tone was induced by the administration of acetylcholine. Activation decreased dynamic C0 by 60%. Two models of coronary input impedance were evaluated: the first model includes viscoelastic properties of the arterial wall and the second takes into account the blood inertia effect. The second model predicts much better the wall mechanics of single small arteries. The viscoelastic model overestimates the frequency dependence of compliance by a factor of 2 and the phase lag by a factor of 4. Moreover this model predicts a strong frequency dependence of induction of tone on compliance and phase lag, whereas this dependence is absent in the experimental results.

Acute tamponade alters subendo- and subepicardial pressure-flow relations differently during vasodilation.

Instantaneous diastolic left coronary artery pressure-flow relations (PFR) shift during acute tamponade as pressure surrounding the heart increases. Coronary pressure at zero flow (Pf = 0) on the linear portion of the PFR is the weighted mean of the different myocardial waterfall pressures, the distribution of which varies across the left ventricular wall during diastole. However, instantaneous PFR measured in large epicardial coronary arteries cannot be used to estimate Pf = 0 in the different myocardial tissue layers. During coronary vasodilatation in a capacitance-free model, myocardial PFR differs from subendocardium to subepicardium. Therefore, we studied the effects of acute tamponade during maximal pharmacology induced coronary vasodilatation on myocardial PFR in in situ anesthetized dogs. Tamponade reduced cardiac output, aortic pressure, and coronary blood flow. Results demonstrate that different mechanisms influence distribution of myocardial blood flow during tamponade. Subepicardial vascular resistance is unchanged and the extrapolated Pf = 0 is increased, thereby shifting PFR to a higher intercept on the pressure axis. Subendocardial vascular resistance is increased while the extrapolated Pf = 0 remains unchanged. Results indicate that in the setting of acute tamponade with coronary vasodilatation different mechanisms regulate the distribution of myocardial blood flow: in the subepicardium only outflow pressure increases, whereas in the subendocardium only vascular resistance increases.

Maximal vascular conductance in right ventricular myocardial circulation.

With acutely increasing right ventricular (RV) hypertension, failure eventually occurs because of RV ischemia. This study examines the effects of RV hypertension on the diastolic right coronary circulation. Conscious dogs instrumented to measure right coronary artery pressure and blood flow were studied after maximal coronary vasodilation with chromonar. Diastolic coronary pressure-flow relations, described by slope (conductance) and zero-flow, pressure axis intercept (Pf = 0), were generated before and during RV hypertension. Diastolic Pf = 0 increased from 11.8 +/- 6.5 to 17.1 +/- 7.1 (means +/- SD, P < 0.01) Torr, with no change in conductance. During RV hypertension, RV diastolic pressure increased. To examine possible mechanisms for the increase in Pf = 0, pressure-flow relations were generated before and after volume loading, without systolic hypertension. Diastolic Pf = 0 increased from 15.5 +/- 3.1 to 20.8 +/- 4.1 Torr, suggesting that changes in Pf = 0 with RV hypertension were mediated by increased filling pressures. Pressure flow relations were derived from mean right coronary flow and RV driving pressure before and during RV hypertension. Under these conditions, Pf = 0 is close to zero; the use of RV driving pressure provides a method for calculating maximal right coronary conductance.

Coronary pressure-flow relationship and exercise: contributions of heart rate, contractility, and alpha 1-adrenergic tone

We examined the impeding effects of exercise on coronary blood flow by analyzing exercise-induced changes in the pressure-flow relationship during maximal coronary vasodilation with adenosine in chronically instrumented dogs and assessed the individual contributions produced by heart rate, contractility, and alpha 1-adrenergic vasoconstriction. Treadmill exercise that increased heart rate from 118 +/- 6 beats/min at rest to 213 +/- 8 beats/min (P < 0.01) decreased maximum coronary blood flows by decreasing the slope of the linear part of the pressure-flow relationship for coronary pressures > or = 30 mmHg (slopeP > or = 30) from 12.3 +/- 0.9 to 10.9 +/- 0.9 ml.min-1 x g-1 x mmHg-1 (P < 0.01) and increasing the measured coronary pressure at zero flow (P zf,measured) from 12.6 +/- 1.2 to 23.3 +/- 2.0 mmHg (P < 0.01). Atrial pacing at 200 beats/min caused an increase of P zf,measured from 15.0 +/- 1.6 to 18.3 +/- 2.1 mmHg (P < 0.05) with no change in slopeP > or = 30. While pacing continued, infusion of dobutamine (20 micrograms.kg-1 x min-1 i.v.) increased contractility to levels similar to those during exercise but caused no significant change in coronary blood flow, as a decrease of the slopeP > or = 30 was compensated for by a slight decrease in P zf,measured. alpha 1-Adrenergic blockade with intracoronary prazosin (10 micrograms/kg) did not prevent the exercise-induced increase of P zf,measured but abolished the decrease of the slopeP > or = 30. When the increases in heart rate, contractility, and alpha 1-adrenergic vasoconstriction were prevented, exercise still increased P zf,measured from 15.8 +/- 2.1 to 21.8 +/- 2.6 mmHg (P < 0.05) but had no effect on the slopeP > or = 30. This residual increase in P zf,measured correlated with the concomitant increase in left ventricular filling pressure. In conclusion, exercise-induced decreases of maximum coronary blood flow were explained by increases in heart rate, alpha 1-adrenergic vasoconstriction, and left ventricular filling pressure, with a minimal contribution of contractility.

Accounting for the Gregg effect in tetanised coronary arterial pressure-flow relationships

Myocardial contraction shifts the diastolic coronary pressure-flow relationship to lower flows at any given pressure, the amount of shift being determined primarily by the contractile level. A portion of this shift may be attributable to the Gregg effect. The purpose of this study was to quantify the influence of the Gregg effect and thereby demonstrate the pure effect of activation at a constant contractile level on the pressure-flow relationships. It was first shown in beating canine interventricular septa that transverse stiffness induced by small high frequency indentations transverse to the plane of the tissue was an index of contractility. At constant perfusion pressure and preload, there was an inverse relationship between peak transverse stiffness and contractile level (induced by graded doses of 2,3-butanedione monoxime) for both isotonic and auxotonic contractions. A Gregg effect was next verified by showing a linear dependence between transverse stiffness and perfusion pressure during ryanodine induced tetanizations. Finally, the relationship between changes in flow and transverse stiffness was determined from diastole to tetany at two contractile levels. These relationships suffice to quantify the Gregg effect. Correcting for the Gregg effect from the transverse stiffness measurements obtained concomitantly with previously reported pressure-flow data in six specimens showed the following: using a linear fit to the pressure-flow data, the mean slope of the diastolic pressure-flow relationships decreased from 0.88 to 0.81 and 0.74 ml.min-1 x mmHg-1 during tetanisation at normal and reduced contractile levels, respectively. Correcting for the Gregg effect decreased the tetanised slopes to intermediate values of 0.85 and 0.79 ml.min-1 x mmHg-1, respectively. A small but clearly discernible portion of the shift in tetanised pressure-flow relationships is attributable to the Gregg effect. Similar conclusions pertained when quadratic regressions were fitted to the pressure-flow data.

Coronary Blood Flow Autoregulation and Flow Heterogeneity in the Stunned Heart.

We used an anesthetized swine model of regionally "stunned" myocardium to determine the effect of stunning on coronary autoregulation and blood flow heterogeneity. In 18 domestic swine, stunning was accomplished by reducing blood flow to the left anterior descending coronary artery (LAD) by approximately 75% of baseline for 15 min and restoring it to normal for 1 hour. We quantified coronary autoregulation using both the slope of coronary pressure-flow curves and an autoregulation index. We quantified blood flow heterogeneity using radioactive microspheres to determine the variability in flow (dispersion index) among forty 200 mg segments of myocardium from the center of the stunned, LAD-perfused left ventricle. Before and after stunning, we measured autoregulation, myocardial blood flow and flow heterogeneity, as well as hemodynamic indices of myocardial oxygen demand. Fifteen min of ischemia and 1 hour of reperfusion produced both a 46% reduction in mechanical function, and a 7% drop in systemic arterial pressure, but not change in heart rate or rate pressure product. Myocardial oxygen consumption was 15% reduced and myocardial blood flow 16% reduced in the stunned myocardium when measured at one hour of reperfusion. Fifteen min after reperfusion, the slope of the coronary pressure flow plots and the coronary venous oxygenation were increased whereas the autoregulation index decreased. These findings all indicate reduced autoregulation during early reperfusion. However, after one hour of reperfusion, the slope of the coronary pressure-flow relation (0.41 +/- 0.19 vs. 0.48 +/- 0.26 ml.100 g-1.min-1.mmHg-1) and the autoregulation index (0.43 +/- 0.16 vs. 0.30 +/- 0.32) were unchanged from control measurements (p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of tetanic myocardial contraction on coronary pressure-flow relationships.

Cardiac contraction causes a decrease in coronary flow. Despite many studies, it is still not clear what mechanism or mechanisms are responsible for this flow decrease. The phasic nature of myocardial contraction and the complexities intrinsic to intact heart preparations make it difficult to elucidate the mechanisms. We therefore studied coronary pressure-flow relationships during steady-state (tetanic) contractions in the maximally vasodilated isolated canine interventricular septum to see whether waterfall-type behavior is present. Using ryanodine and electrical stimulation allowed the production of reproducible and reversible tetani. This preparation minimizes the difficulties associated with transmural variations and also the effects of intramyocardial capacitance. Two separate protocols were performed to delineate the pressure-flow relationships in the passive and tetanized states. The first compared diastolic and tetanized pressure-flow relationships. In the second protocol, 2,3-butanedione monoxime was added to obtain an intermediate contractile level, thus allowing the comparison of two contractile states. Both the diastolic and tetanized pressure-flow relationships were curvilinear in the low-pressure range. Linear and nonlinear fits to the data showed that the primary effect of contraction was a shift of the pressure-flow relationships to higher pressures at a given flow. This effect was graded by the level of contractility and was independent of developed stress. Although other mechanisms may also be operative, these results support the presence of waterfall behavior in the coronary vascular bed.

Modulation of coronary autoregulatory responses by nitric oxide. Evidence for flow-dependent resistance adjustments in conscious dogs.

The present study tested the hypothesis that nitric oxide production in coronary resistance vessels is an important mechanism affecting the regulation of myocardial perfusion in unanesthetized dogs. We inhibited nitric oxide synthesis with the arginine analogue N omega-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg) and maintained the compressive determinants of myocardial blood flow constant by ventricular pacing. L-NAME did not affect resting coronary blood flow and reduced the receptor-mediated increase in flow to intracoronary acetylcholine (100 micrograms/min IC) from 143 +/- 20% (mean +/- SEM) under control conditions to 31 +/- 10% after L-NAME (P < .001). Coronary autoregulatory relations were determined as steady-state coronary pressure was reduced by inflating a hydraulic occluder. Initial resistance adjustments over the autoregulatory plateau were not affected by L-NAME. Closed-loop autoregulatory gain was 0.84 +/- 0.09 under control conditions versus 0.78 +/- 0.07 after L-NAME (P = NS). As coronary pressure was reduced further, however, the critical pressure at which myocardial ischemia began (lower autoregulatory break point) increased from 45 +/- 3 mm Hg under control conditions to 61 +/- 2 mm Hg (P < .001) after L-NAME. In addition, the slope of the coronary pressure-flow relation below the autoregulatory break point was reduced (1.0 +/- 0.2 versus 0.58 +/- 0.09 mL.min-1.mm Hg-1 after L-NAME, P < .05), reflecting a reduction in the maximal conductance recruitable during ischemia. In concert with the effects of L-NAME on autoregulatory responses during ischemia, peak reactive hyperemic flow to a 30-second coronary occlusion was also reduced (from 200 +/- 22 to 166 +/- 24 mL/min after L-NAME, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary pressure-flow relation in left ventricular hypertrophy. Importance of changes in back pressure versus changes in minimum resistance.

Perfusion abnormalities in the pressure-overloaded hypertrophied left ventricle could result from an increase in minimum coronary resistance or an increase in effective back pressure due to increased extravascular compressive forces. Since the pressure-flow relation of the maximally vasodilated coronary bed allows dissociation of minimum resistance (inverse slope [1/alpha PF]) and back pressure (pressure at zero flow [Pf = 0]), the present study was undertaken to examine the coronary pressure-flow relation in left ventricular hypertrophy (LVH). Ascending aortic banding in eight dogs at 6-8 weeks of age (LVH group) increased the left ventricular to body weight ratio to 8.7 +/- 0.6 g/kg as compared with 4.8 +/- 0.2 g/kg in nine normal dogs (p < 0.05). Maximum coronary vasodilation was produced by infusion of adenosine (1 mg/kg per minute i.v.). The slope of the coronary pressure-flow relation (alpha PF) was 5.8 +/- 0.5 10(-2) (ml/min per gram)/mm Hg in the LVH group and 9.3 +/- 0.6 10(-2) (ml/min per gram)/mm Hg in the normal group (p < 0.05). alpha PF was significantly correlated with the left ventricular to body weight ratio but not with coronary pressure, suggesting that the degree of hypertrophy and not exposure to high coronary pressure was responsible for the observed decrease in alpha PF. Pf = 0 was 24.1 +/- 2.6 mm Hg in the LVH group and 11.7 +/- 1.2 mm Hg in the normal group (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary pressure-flow regulation in the stunned myocardium.

In this study, we used a swine model to study coronary autoregulation in the stunned myocardium. In 18 domestic swine, the left anterior descending coronary artery was cannulated and flow to this artery controlled via an extracorporeal perfusion circuit. Stunning was induced by reducing pump flow to approximately 25% of the baseline value for 15 minutes followed by 1 hour of reperfusion. This ischemia/reperfusion protocol reduced systolic shortening to approximately 50% of control, at 1 hour of reperfusion. Neither the slope of the coronary pressure-flow relation (0.41 +/- 0.19 vs 0.48 +/- 0.26 mL/100 g per min per mmHg) nor an autoregulation index (0.43 +/- 0.16 vs 0.30 +/- 0.32) was significantly changed at 1 hour reperfusion (p > 0.05) compared to baseline. These findings argue against the hypothesis that the mechanical dysfunction of the stunned myocardium is due to suboptimal perfusion caused by poor coronary autoregulation.

Ultra-pure polymerized bovine hemoglobin blood substitute: effects on the coronary circulation.

The effects of stroma-free hemoglobin (SFHgb) on the coronary circulation remain unclear. An intact canine model utilizing intracoronary adenosine to abolish the confounding effect of autoregulation was used to study maximal myocardial oxygen delivery during progressive hemodilution with polymerized bovine SFHgb. The circumflex coronary artery was instrumented with a flow probe, hydraulic constrictor, and proximal and distal catheters for adenosine infusion and distal pressure measurement, respectively. This preparation was used to generate diastolic coronary pressure-flow relations during maximal vasodilation. Maximal coronary conductance and maximal myocardial oxygen delivery were determined in two groups of 7 dogs each following hemodilution, first with 6% hetastarch (Control), followed by further hemodilution with ultra-pure, polymerized, bovine SFHgb. After hemodilution with SFHgb, maximal coronary flow increased slightly without evidence of coronary vasoconstriction. Since hemodilution with this material increases oxygen carrying capacity, maximal oxygen delivery is greater than Control, despite the very low canine hematocrit. These findings suggest: 1) SFHgb can provide adequate oxygen delivery to the myocardium despite extreme degrees of hemodilution, and 2) in this intact model, there is no evidence of adverse coronary vasomotion.

Nitric oxide is an important determinant of coronary flow in the isolated blood perfused rat heart.

Many vasoactive substances are involved in the regulation of vasomotor tone and some of them, like nitric oxide (NO), are derived from the endothelium. Nitric oxide is able to relax preconstricted coronary resistance vessels almost completely. However, it is not clear what the contribution of NO is to vasomotor tone in the intact blood perfused heart. The aim of the present study was to evaluate the contribution of NO to coronary pressure-flow relations. We used isovolumically beating, donor supported, blood perfused isolated rat hearts. We measured pressure-flow relations under control conditions, after blocking endothelial NO production with NG-nitro-L-Arginine (LNNA) and after administration of L-Arginine (L-Arg) in order to overrule the blocking effect. Administration of LNNA at a perfusion pressure of 105 mm Hg resulted, after about 40 min, in a significant (Wilcoxon's signed-rank test, (n = 8) p < 0.05) reduction of coronary flow to 47 +/- 5% (mean +/- SEM) of control and a reduction of developed isovolumic left-ventricular pressure to 62 +/- 4% of control. L-Arg returned flow to 60 +/- 7% of control which is a significant increase with respect to LNNA (p < 0.05). L-Arg did not increase the left-ventricular pressure. The entire perfusion pressure-flow relation (pressure range 65-125 mm Hg) was significantly shifted downwards after LNNA with respect to control. Pressure-flow relations after L-Arg were in between those during control and after block of NO production. L-Arg alone was found to have no effect on flow and left-ventricular pressure (n = 2) and both LNNA and L-Arg were found to have no effect on contractility of isolated trabeculae (n = 6), thus, coronary blood flow reduction after LNNA administration is mainly the result of inhibition of endothelial NO production. At a perfusion pressure of 105 mm Hg reactive hyperemia is still present after LNNA and subsequent L-Arg administration, indicating that endothelial NO is not the only factor involved in flow regulation. We conclude that endothelium-derived NO is involved in the control of coronary flow in the blood perfused rat heart.

Tone-dependent waterfall behavior during venous pressure elevation in isolated canine hearts.

We examined the "vascular waterfall" hypothesis, which proposes that coronary flow is unaffected by elevations in outflow pressure until the latter reaches a critical threshold level, in 29 isolated canine hearts. In fibrillating hearts vasodilated with adenosine or carbocromen, coronary flow and the coronary pressure-flow relation were not affected by changes in great cardiac vein pressure (PGCV) below a threshold value of 11 +/- 0.9 (mean +/- SEM) mm Hg. Further elevations of PGCV reduced flow and shifted the pressure-flow relation to the right, increasing its pressure-axis intercept (Pf=0). When vasomotor tone was augmented with vasopressin, threshold PGCV increased to 25 +/- 2.7 mm Hg (p less than 0.001). Once again, the pressure-flow relation was unaffected by changes in PGCV below the threshold value and shifted to the right when this value was exceeded. The amount by which spontaneous values of Pf=0 exceeded threshold values of PGCV was greater when vasomotor tone was augmented than during vasodilation. Pf=0 continued to exceed PGCV when the latter was raised above the threshold level. Both Pf=0 and threshold values of PGCV were less during a long diastole than during ventricular fibrillation. We reached the following conclusions. 1) During changes in PGCV below a threshold value, the coronary circulation exhibits traditional waterfall behavior. 2) The threshold pressure for altering waterfall behavior is affected by vascular tone and mechanical activity. 3) Pf=0 remains above PGCV when the latter is increased above the threshold value needed to alter flow.