Coronary Artery Pressure Research Articles

Association between serial measures of systemic blood pressure and early coronary arterial perfusion status following intravenous thrombolytic therapy

Background: Systemic hypotension, at times transient while in other instances more prolonged, is common among patients with myocardial infarction (MI). It also is a characteristic feature for patients experiencing either advanced congestive heart failure or cardiogenic shock. In this group of patients, thrombolytic therapy has failed to exert. favorable impact on their high in-hospital mortality. Although it has been postulated that the success of thrombolytic therapy is directly linked to systemic blood pressure' there is little information available in human subjects. Methods and Results: In a University of Massachusetts Thrombolysis Data Bank Study, 127 patients with MI who were given intravenous thrombolytic therapy (tPA or streptokinase) within 6 hours from symptom onset (4.2 +/- 1.5 hours) had serial systemic blood pressure measurements (at the time of hospital arrival, treatment initiation, and every 30 minutes during the thrombolytic infusion) and underwent coronary angiography within 120 minutes of treatment initiation. All patients received intravenous heparin and oral aspirin. By univariate analysis, disastolic blood pressure below 80 mmHg at the time of treatment initiation was associated with a reduced angiographic coronary perfusion grade [Thrombolysis in Myocardial Infarction (TIMI) flow grade; p + 0.02]. A correlation analysis of tPA-treated patients indicated that a greater maximum change in diastolic blood pressure during treatment correlated inversely with coronary perfusion (r +.24, p < 0.05). By multivariate regression analysis, however, only shorter time to treatment (p + 0.001) and thrombolysis with tPA (p + 0.02) were independent predictors of coronary arterial perfusion grade. Conclusion: Systemic blood pressure (and presumably proximal coronary arterial perfusion pressure) in the ranges investigated in this study is not an independent predictor of coronary reperfusion following intravenous thrombolytic therapy with either tPA or streptokinase. It seems likely, therefore, that properties intrinsic to the ruptured plaque and occlusive thrombus, and potentially the local metabolic environment, either alone or acting synergistically with perfusion pressure, are determinants of thrombolytic success. Further investigation of factors influencing the efficacy of thrombolysis should be undertaken.

Sulfhydryl compounds, captopril, and MPG inhibit complement-mediated myocardial injury.

Factors including complement activation, neutrophil infiltration, and oxygen-derived free radicals have been implicated in the pathogenesis of myocardial tissue injury during ischemia and reperfusion. Certain sulfhydryl-containing compounds have been shown to inhibit complement activation. The sulfhydryl compounds captopril and N-(2-mercaptopropionyl)-glycine (MPG) are antioxidant compounds that previously have been shown to protect the myocardium from ischemia and reperfusion-induced damage. In this study, captopril (an angiotensin-converting-enzyme inhibitor; ACEI) and MPG, and the non-sulfhydryl compound enalaprilat (also an ACEI) were tested for their ability to protect the isolated perfused rabbit heart against complement-induced injury. Both captopril and MPG protected hearts against complement-mediated increases in left ventricular end-diastolic pressure and increases in coronary arterial perfusion pressure in a concentration-dependent manner, whereas enalaprilat was not protective. The ability of these compounds to inhibit complement activation also was tested using an in vitro complement-mediated red blood cell hemolysis assay. These findings offer additional insight as to the mechanism whereby captopril, MPG, and possibly other sulfhydryl compounds, may be acting to provide cytoprotection during myocardial ischemia and reperfusion.

Arterial diastolic pressure augmentation by intra-aortic balloon counterpulsation enhances the onset of coronary artery reperfusion by thrombolytic therapy.

The early establishment of infarct artery reperfusion by intravenous thrombolytic therapy has improved survival after acute myocardial infarction. Investigations of reperfusion have focused on the effects of specific thrombolytic agents, anticoagulation, and platelet inhibition. However, little attention has been given to the relation of arterial blood pressure to thrombolysis, a factor that probably affects thrombolytic agent delivery to the obstructing thrombus. The effect of arterial diastolic pressure augmentation by intra-aortic balloon counterpulsation (IABP) on reperfusion after intravenous thrombolytic therapy was studied in a canine model. A critical left anterior descending coronary artery stenosis was created by an occluder. Acute thrombosis immediately proximal to the occluder was formed by local injection of a blood and thrombin mixture into a segment of the artery that had intimal damage (groups 1 through 3). Continuous coronary blood flow velocity was measured by an epicardial Doppler probe. Group 1 (n = 7) served as control. Group 2 (n = 6) received an intravenous, front-loaded recombinant tissue-type plasminogen activator (rTPA) regimen (1.25 mg/kg total dose, 15% as bolus, 50% in the first 30 minutes, and 35% for the following 60 minutes). Group 3 (n = 6) received the same rTPA regimen with IABP beginning at the start of rTPA administration. Coronary blood flow velocity, arterial pressure, and heart rate were observed for 150 minutes after the start of thrombolytic therapy. Five animals did not undergo coronary thrombosis (group 4) and had coronary blood flow velocity determined before and after IABP at baseline and after creation of critical stenosis. Mean systolic arterial blood pressure and heart rate were not statistically different between groups. Peak augmented diastolic pressure by IABP was 97.9 +/- 1.3% of systolic pressure in group 3 dogs. Spontaneous reperfusion did not occur in any group 1 dogs. All animals treated with rTPA reperfused. Reperfusion occurred in group 3 (13.1 +/- 2.1 minutes) earlier than in group 2 (39.2 +/- 9.4 minutes, P = .02). Overall duration of arterial patency did not differ between group 2 (81.4 +/- 16.6 minutes) and group 3 (94.9 +/- 15.3 minutes, P = .52). Reocclusions occurred with similar frequency (P = .85) in groups 2 and 3. In group 4, IABP did not increase baseline coronary blood flow velocity. This study demonstrates that augmentation of diastolic arterial pressure by IABP enhances thrombolysis, leading to faster reperfusion. This effect appears to be unrelated to an increase in coronary blood flow and may be due to an effect of the augmented diastolic blood pressure wave on the obstructing thrombus. These findings suggest that the time to reperfusion by rTPA may be blood pressure dependent. The relation of arterial blood pressure to successful thrombolysis may have important implications for future treatment strategies for myocardial infarction.

Volatile Anesthetics and Coronary Collateral Circulation

In this chapter, a study demonstrates that isoflurane and a new volatile anesthetic, sevoflurane, do not abnormally redistribute collateral blood flow away from an area distal to a total coronary artery occlusion. Vasodilation in the region supplied by the stenotic artey causes a decrease in coronary artery pressure distal to the stenosis. Agents that produce coronary vasodilation can act at one or more regions in the coronary vasculature. Arterioles are the primary vessels controlling resistance in the coronary circulation, and, thus, arteriolar dilators such as adenosine, dipyridamole, and chromonar are capable of producing maximal increases in flow and a redistribution of flow away from collateraldependent zones. Volatile anesthetics, including isoflurane, enflurane, and halothane, have been shown to cause coronary vasodilation, primarily of small resistance vessels. This property makes these agents potential candidates for the production of coronary steal. Volatile anesthetics also depress sinoatrial (SA) node and cardiac conduction tissue function in vitro . Volatile anesthetic-induced reductions in myocardial contractility, left ventricular afterload, and heart rate contribute to a reduction in myocardial oxygen consumption and lead to a concomitant increase in coronary vascular resistance via metabolic autoregulation. Thus, the sum of indirect and direct effects in vivo determines the observed alterations in coronary blood flow and vascular resistance. In the present investigation, sevoflurane has been shown to increase coronary collateral blood flow during maintenance of heart rate and arterial pressure at levels observed in the conscious state. In contrast, coronary collateral blood flow remains constant with correction of heart rate and blood pressure during isoflurane or desflurane anesthesia.

Afferent discharges from coronary arterial and ventricular receptors in anaesthetized dogs.

1. Previous work has shown that increases in aortic root pressure result in reflex vasodilation, and that this response is likely to result mainly from stimulation of receptors in the coronary arteries, although contribution from left ventricular receptors was not excluded. This investigation was undertaken to resolve this question and to determine the afferent nerve fibres likely to be involved in this reflex. 2. In chloralose-anaesthetized dogs a perfusion circuit was used which allowed us to change the pressures in: (a) the aortic root, coronary arteries and the left ventricle; (b) aortic root and coronary arteries at constant ventricular pressure; and (c) the left ventricle with mean (although not pulse) aortic pressure constant. Electrophysiological recordings were made from slips dissected from the vagus nerve which responded with an increase in discharge to either combined increases in the pressures, or to aortic root injections of veratridine. 3. Recordings were made from twenty-one vagal afferents. On the basis of their conduction velocities, eleven were classified as non-myelinated and ten as myelinated. 4. Three non-myelinated afferents responded to veratridine injections only, three to both veratridine and combined aortic root and ventricular pressure changes, and five to pressure changes only. Responses to pressure occurred only when ventricular systolic pressure exceeded 30 kPa. 5. None of the myelinated afferents responded to veratridine. All showed increases in discharge to combined increases in mean aortic root, coronary arterial and left ventricular systolic pressures, which would be graded over a range similar to that which caused reflex changes. All were more sensitive to changes in mean coronary pressure than to changes in ventricular systolic pressure. 6. We conclude that myelinated vagal afferent nerve fibres, which respond predominantly to changes in mean coronary arterial pressure, are likely to be responsible for the vasodilation to the changes in mean aortic root pressure previously reported. These fibres are probably attached to coronary arterial mechanoreceptors.

Muscarinic receptor subtypes mediating vasodilation and vasoconstriction in isolated, perfused simian coronary arteries.

Using the cannula insertion method, we investigated the vascular responses of isolated simian coronary artery to acetylcholine (ACh). When the preparation was partially precontracted by 20 mM KCl, ACh and carbachol induced vasodilation dose dependently in coronary artery with endothelium, but ACh and carbachol contracted the coronary artery after removal of the endothelium by 1 mg saponin. A selective M1 receptor agonist 4-[N-(3-chlorophenyl)carbamoyloxy]-2-butinyltrimethylammonium++ + chloride (McN-A-343) did not affect the perfusion pressure of the precontracted coronary arteries significantly. Both these responses to ACh were inhibited by the M3 receptor antagonist 4-dipheny-lacetoxy N-methylpiperidine methobromide (4-DAMP) in a dose-dependent manner, but not by a selective M2 receptor antagonist AF-DX 116 (11-[[2-[(diethylamino)methyl]-1-piperidinyl] acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzo-diazepine-6-one). A selective M1 receptor antagonist pirenzepine did not affect ACh-induced vasoconstriction significantly and inhibited the vasodilation partially only at the highest dose (100 nmol). The effects of three antagonists on the vasodilative responses to carbachol were also studied and almost the same results were observed. Removal of the endothelium did not affect sodium nitroprusside (SNP)-induced vasodilation significantly. Pirenzepine, AF-DX 116, and 4-DAMP did not affect the action of isoproterenol. These data suggest that the vasodilation elicited by ACh is mediated by release of endothelium-derived relaxing factors (EDRF) consequent to the activation of M3 receptors on endothelial cells, and the constriction is mediated by stimulation of M3 receptors on smooth muscle cells in isolated simian coronary arteries.

Reflex responses to stimulation of mechanoreceptors in the left ventricle and coronary arteries in anaesthetized dogs.

1. Previous work has shown that physiological increases in mean aortic root pressure, which change the pressure in both the coronary circulation and the left ventricle, result in reflex vasodilatation. This study was undertaken to attempt to localize the reflexogenic area mainly responsible for the reflex. 2. In anaesthetized, artificially ventilated dogs, cannulae connected to perfusion systems were inserted in the ascending aorta, left ventricular apex and left atrium. This allowed us to change the pressures in: (a) the aortic root including both the coronary arteries and the left ventricle; (b) aortic root and coronary arteries, at constant ventricular pressure; and (c) in the ventricle, with mean (although not pulse) aortic pressure constant. Aortic and carotid baroreceptors were perfused at constant pressure and reflex responses were determined from changes in perfusion pressures (flows constant) to a vascularly isolated hindlimb and to the remainder of the systemic circulation. 3. Combined changes in mean aortic root (coronary arterial) and ventricular systolic pressures consistently resulted in decreases in perfusion pressures. A change in only mean aortic root (coronary arterial) pressure, with ventricular pressure constant, also resulted in decreases in perfusion pressures and these were only a little smaller than those to the combined stimulus. Changes in ventricular systolic pressure resulted in responses averaging only about 30% of those to the combined stimulus. 4. Setting mean aortic root or ventricular systolic pressures at different levels did not affect the responses to changes in pressures in the other region. 5. These results show that physiological increases in pressure in the aortic root and coronary arteries, in the absence of changes in pressure in the left ventricle, cause reflex vasodilatation. The relatively small response occurring when ventricular pressure was changed could be due either to a contribution from ventricular receptors or to a change in the stimulus to coronary receptors resulting from changes in the ventricular or aortic pulse. 6. We conclude that the reflex effects of increases in mean aortic root pressure are due mainly to stimulation of coronary arterial baroreceptors.

Tone-dependent coronary arterial-venous pressure differences at the cessation of venous outflow during long diastoles.

The origin and magnitude of the back pressure opposing diastolic coronary inflow remain controversial. The arterial pressure at which coronary inflow stops during a prolonged diastole, ie, "zero-flow pressure," is higher than coronary venous pressure. However, because of capacitive discharge as distending pressure falls, flow at the microcirculatory level exceeds inflow, and coronary outflow ceases later than inflow. If coronary arterial pressure continues to exceed venous pressure at the point of venous flow cessation, zero-flow pressure cannot be an artifact of capacitive discharge. Coronary inflow and outflow, arterial pressure, and right atrial pressure have been measured during long diastoles in closed-chest dogs chronically instrumented with volumetric flow probes on the great cardiac vein or coronary sinus as well as the circumflex artery. Although venous outflow continued for 1 to 4 seconds after arterial inflow ceased, coronary artery pressure at the point of venous flow cessation (Pfv = 0) always exceeded right atrial pressure (13 +/- 1.3 mm Hg [SEM] vs 6 +/- 0.7 mm Hg, P < .001). When vasomotor tone was augmented using vasopressin, the diastolic pressure-flow relation shifted to the right, with Pfv = 0 increasing to 21 +/- 2.4 mm Hg despite an unchanged right atrial pressure (6 +/- 0.5 mm Hg). Transcoronary pressure differences persist when venous outflow stops and are larger when vasomotor tone is augmented. Measurements of zero-flow pressure that exceed venous pressure cannot be considered an artifact of continuing capacitive discharge after the cessation of arterial inflow. Diastolic coronary back pressure exceeds right atrial pressure and is tone dependent.

Preliminary observations on blood flow in the coronary arteries of two school sharks (Galeorhinus australis)

Coronary arterial blood flow and pressure, intraventricular blood pressure, and ventral aortic blood velocity were measured in two anaesthetized school sharks (Galeorhinus australis) in order to examine the phasic relationships between these flows and pressures. Maximum instantaneous flow recorded in the ventral coronary artery was 0.37 mL∙min−1∙kg−1 body mass (estimated 0.63 mL∙min−1∙g−1 ventricular mass). The average mean coronary blood flow was estimated as 0.28 mL∙min−1∙g−1 ventricular mass during periods of high coronary blood flow. On average, 86% of coronary flow occurred during diastole. Coronary arterial flow began during the last quarter of ventricular systole. Coronary blood flow peaked when intraventricular pressure fell to just below zero immediately after ventricular systole. Coronary blood flow fell slightly as diastole continued and reflected the small fall in coronary arterial pressure. Coronary flow reversed briefly during isovolumic ventricular contraction. Increases in the proportion of the cardiac cycle occupied by ventricular diastole, which occur during hypoxic bradycardia, have the potential to more than double coronary blood flow provided coronary arterial pressure is maintained.

Effect of changes in aortic pressure and in coronary arterial pressure on left ventricular geometry and function Anrep vs. gardenhose effect.

Sudden increases in aortic pressure (AoP, mm Hg) are associated with increases in left ventricular (LV) function which persist even after diastolic volume has returned to its initial value (Anrep effect). Likewise, increases in coronary arterial pressure (CAP, mm Hg) are associated with improved LV function (gardenhouse effect). In situ, increases in AoP are paralleled by increases in both CAP and coronary blood flow, i.e., oxygen supply. We investigated the individual contributions of AoP and CAP increases on function (peak systolic pressure: LVPmax, mm Hg; dP/dtmax, mm Hg/s; end-diastolic pressure: LVPed, mm Hg) and end-diastolic geometry (inner diameter: IDed, mm; wall thickness: WTed, mm; sonomicrometry). CAP-induced increases in coronary flow were prevented by admixing dextran to the perfusate. The experiments were performed on isolated, saline-perfused, working rabbit hearts. Increasing CAP from 60 to 80 mm Hg (n = 11) resulted in improved function: LVPmax 89 +/- 3 vs. 94 +/- 3, dP/dtmax 1160 +/- 50 vs. 1250 +/- 50, LVPed 17 +/- 1 vs. 16 +/- 1 (mean +/- SEM). IDed decreased from 9.96 +/- 0.25 to 9.64 +/- 0.33 and WTed increased from 6.02 +/- 0.16 to 6.15 +/- 0.17. In a second series, AoP was increased from 60 to 80 (n = 9). Both LVPmax, dP/dtmax and LVPed increased (90 +/- 4 vs. 97 +/- 3, 1170 +/- 70 vs. 1270 +/- 90 and 18 +/- 1 vs. 19 +/- 1). IDed increased from 9.76 +/- 0.39 to 9.99 +/- 0.37 and WTed decreased from 6.08 +/- 0.22 to 5.86 +/- 0.25. After additionally increasing CAP to 80, function further improved (LVPmax: 101 +/- 3, dP/dtmax: 1310 +/- 80) while LVPed decreased (18 +/- 1). This time, IDed decreased to 9.71 +/- 0.36 and WTed increased to 6.03 +/- 0.26. Increases in CAP improve LV function via the gardenhose effect and likely do not depend on simultaneous increases in coronary flow or oxygen supply. On the other hand, increases in AoP alone improve systolic function via the Frank-Starling mechanism. Increases in both pressures together amplify this effect. Increases in CAP and in AoP have opposing effects on IDed and WTed. In conclusion, the homeometric Anrep effect--at least in part--can be viewed as synergistic action of the Frank-Starling mechanism and the gardenhose effect for this experimental model.

Direct coronary and cerebral vascular responses to dexmedetomidine. Significance of endogenous nitric oxide synthesis.

Dexmedetomidine activates alpha 2-adrenergic receptors in the central nervous system and in the peripheral vasculature. In vivo dexmedetomidine has been found to cause alterations in coronary and cerebral blood flows and arterial pressure by stimulation of vascular smooth muscle alpha 2 receptors. The direct vasoconstrictor effects of alpha 2-adrenergic agonists may be opposed by release of endothelium-derived relaxing factor believed to be nitric oxide. A functional endothelium was demonstrated recently in canine coronary collateral vessels. The objective of the current study was to assess the direct effect of dexmedetomidine on isolated canine proximal and distal coronary arteries, coronary collateral vessels, and middle cerebral arteries. Responses were measured in tissue baths in the presence of indomethacin 10(-5) M and in the absence and presence of NG nitro-l-arginine methyl ester (L-NAME), an inhibitor of vascular nitric oxide synthesis. Dexmedetomidine (3 x 10(-8) to 3 x 10(-3.9) M) caused constriction (3.9, 5.5, 72.8, and 2.3% for proximal and distal coronary arteries, middle cerebral arteries, and coronary collateral vessels, respectively, expressed as a percentage of KCl-induced contraction) in all vessels. This constriction was enhanced by the presence of L-NAME in all vessels except cerebral arteries. The selective alpha 2-adrenergic antagonist atipamezole (10(-4) M) abolished the response to low but not high concentrations of dexmedetomidine in middle cerebral arteries, proximal coronary arteries, and coronary collateral vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of inotropic effect of endothelin-1 in vivo.

The vasoconstrictive peptide endothelin-1 (ET-1) has been reported to exert a very important positive inotropic effect in vitro. To assess the effect of ET-1 on myocardial contractility in vivo, we compared the effect of intracoronary infusion of 10(-8) M ET-1 (constant coronary blood flow) to that of 10(-8) M dobutamine in 8 swine. ET infusion did not produce changes in segmental shortening (control vs. drug, mean +/- SD): 33.8 +/- 14.3 vs. 30.8 +/- 12.1%, shortening velocity: 10.3 +/- 4.3 vs. 10.7 +/- 4.5 mm/s, or maximum +dP/dt: 1,691 +/- 701 vs. 1,772 +/- 773 mm Hg/s, whereas dobutamine infusion induced an important increase in these measurements; segmental shortening: 36.9 +/- 14 vs. 48.4 +/- 18.8%, shortening velocity: 10.1 +/- 2.6 vs. 14.7 +/- 4.5 mm/s, and maximum +dP/dt: 2,041 +/- 567 vs. 2,389 +/- 765 mm Hg/s (all p less than 0.05). Mean myocardial blood flow assessed by microspheres was unchanged by ET-1 despite a marked increase in coronary artery pressure (88.6 +/- 12.9 vs. 157 +/- 8.8 mm Hg, p less than 0.001). Regional infusion of ET-1 at a dose provoking extensive coronary vasoconstriction does not induce any change in regional or global myocardial function in swine.

Dynamic response of coronary regulation to heart rate and perfusion changes in dogs.

The rate of change of coronary adjustment in the anesthetized dog to a step change in heart rate (HR) and in perfusion was analyzed. The left main coronary artery was perfused either at constant pressure (CP) or at constant flow (CF). Coronary arterial pressure and flow were continuously measured and averaged per beat, after which their ratio, being an index of coronary resistance in steady state, was calculated. The rate of change of pressure-to-flow ratio was quantified by t50, the time required to establish half of the completed response. The t50 values for the dilating responses at CP were 5.5 +/- 0.4 (SE) s for an increase in HR and 5.5 +/- 0.1 s for a decrease in perfusion. At CF these values were 9.3 +/- 0.9 and 9.7 +/- 1.6 s, respectively. The t50 values for the constricting responses with CP were 6.6 +/- 0.5 s for a decrease in HR and 6.2 +/- 0.2 s for an increase in perfusion. At CF these values were 12.2 +/- 1.5 and 10.8 +/- 2.2 s. The responses in the dog are faster than in the goat. Furthermore, the directional sensitivity in responses with perfusion changes, observed earlier in goats, is normally absent in dogs.

Retrograde coronary flow is limited by time-varying elastance.

The study examined the influence of left ventricular pressure (PLV) on coronary arterial flow and pressure. In eight anesthetized open-thorax goats with cannulated and artificially perfused left main coronary artery, the PLV was disturbed by aortic occlusions. In the constant pressure perfusion (CPP) protocol the response of systolic arterial inflow on a change in PLV was studied with fixed perfusion pressure and at several perfusion pressure levels. Similarly, in the constant flow perfusion (CFP) protocol the response of systolic perfusion pressure was examined with fixed levels of perfusion flow and repeated for several flow levels. The results show an early systolic response determined by PLV for both protocols. Midsystolic responses were almost absent in the CPP protocol but present in the CFP protocol. At CPP, the effect of a change of PLV on arterial flow in mid systole was only 20% of that on early systolic flow with intact coronary tone and 33% with adenosine-induced vasodilation. At CFP the pulsations in perfusion pressure were 30% of PLV pulsations, both with intact tone and vasodilation; in contrast with the CPP results, no difference for this value was found in different stages of systole. We suggest that stiffness of cardiac muscle determines the influence of PLV on coronary flow. The difference in mid systolic relations between the CPP and CFP protocols is explained by the difference in time constants induced by the perfusion system. The results are best explained by a synthesis between the intramyocardial pump model and the elastance concept.

Does systolic subepicardial perfusion come from retrograde subendocardial flow?

To examine the influence of cardiac contraction on systolic coronary flow and transmural blood flow distribution, we measured phasic blood flow velocity in distal extramural coronary arteries by Doppler velocimeter and regional myocardial blood flow by radiolabeled microspheres while the heart was beating and during prolonged diastoles in 12 dogs. A servo-controlled coronary perfusion circuit allowed mean coronary pressure to be selected and maintained during beating and diastolic conditions. In epicardial arteries just proximal to their entrance into the myocardium, blood flow was either negligible or reverse in direction during systole. When the heart was beating, subepicardial blood flow was 24.2 +/- 12.3% higher than during asystole (5.05 +/- 0.91 and 4.11 +/- 0.79 ml.min-1.g-1 for beating and prolonged diastoles, respectively; P less than 0.01). In the subendocardium, flow was 49.8 +/- 14.7% lower in the beating condition than during prolonged diastoles (4.23 +/- 1.46 and 8.26 +/- 1.71 ml.min-1.g-1 for beating and asystole, respectively; P less than 0.01). When heart rate was increased stepwise from 60 to 150 beats/min, subendocardial flow fell approximately linearly; flow to the superficial layer was relatively unaffected. In beating hearts, lowering mean left main coronary artery (LMCA) pressure from 80 to 50 mmHg resulted in more systolic reverse flow and a fall in inner-to-outer flow ratio from 0.82 +/- 0.18 to 0.66 +/- 0.34 (P less than 0.05). Because mean LMCA pressure was held constant when the heart was stopped, differences in regional blood flow between beating and diastolic conditions were primarily due to cardiac contraction. Because little or no blood entered the myocardium from the extramural arteries during systole, we conclude that the decrease in subendocardial flow and the increase in subepicardial flow were caused by retrograde pumping of blood from the deep layer to the superficial layer of the left ventricle. Systolic retrograde flow to the subepicardium may help explain this layer's relative protection from ischemia.

Reflex vascular responses to changes in left ventricular pressures, heart rate and inotropic state in dogs.

Dogs were anaesthetized with chloralose, artificially ventilated and the chests widely opened. Left ventricular mechanoreceptors, including those in or near the coronary arteries, were stimulated by changing the pressure in the aortic root. The pressures distending the left atrium and the aortic and carotid baroreceptors were controlled. Reflex vascular responses were assessed from changes in perfusion pressures to a hind limb and to the rest of the systemic circulation, which were perfused independently at constant flows. Physiological increases in peak left ventricular and coronary arterial pressures resulted in vasodilatation in both regions. These responses were not influenced by changes in the heart rate. Stimulation of the left cardiac sympathetic nerves resulted in increases in peak ventricular pressure and in the maximal rate of change of pressure (dP/dtmax). This also resulted in increases in perfusion pressures (vasoconstriction) at all levels of peak ventricular pressure although there was little effect on the responses to changes in ventricular pressure. Sympathetic stimulation had little effect on the relationship between perfusion pressures and aortic root pressure. Increases in ventricular filling also resulted in vasoconstriction at all levels of peak ventricular pressure. Increases in filling, however, did not affect the relationship between either perfusion pressure and aortic root pressure. Conversely, decreases in left ventricular filling, by bypassing some of the left atrial blood, resulted in vasodilatation at all levels of peak ventricular pressures but had no effect on the perfusion pressures at any aortic root pressure. The combination of sympathetic stimulation with decreased ventricular filling resulted in little effect on perfusion pressures or on their responses to changes in either aortic root or ventricular systolic pressures. We conclude that the vascular responses to stimulation of left ventricular mechanoreceptors are not enhanced by sympathetic stimulation, decreases in ventricular filling or the combination of the two. The apparent effects of each of these interventions alone on the relationships between perfusion pressures and ventricular, but not aortic root, pressure, could be explained if the receptors responsible were sensitive more to changes in aortic root and coronary arterial pressures than to pressure changes in the ventricle itself.

The effects of ionic and nonionic radiographic contrast media on coronary hyperemia in patients during coronary angiography

The purpose of this study was to compare the differential effects of ionic, high-osmolar meglumine diatrizoate; ionic, low-osmolar ioxaglate meglumine; and nonionic, low-osmolar iohexol (all radiographic contrast agents) on coronary blood flow velocity and hyperemic responses during diagnostic coronary angiography. Coronary flow velocity and arterial pressure were measured at baseline and during maximal hyperemia after contrast media were randomly injected (4 to 6 ml into left coronary artery) in 22 patients with the use of a Judkins-style 20 MHz Doppler-tipped angiographic catheter. Contrast media-induced hyperemic responses were compared to those induced with intracoronary nitroglycerin (200 μg) and papaverine (10 mg). There were no significant differences in systolic, diastolic, or mean arterial pressure measurements among the three contrast agents. The increase in mean coronary flow velocity during hyperemia was 118 ± 93%, 133 ± 73%, and 136 ± 86% for iohexol, ioxaglate meglumine, and diatrizoate, respectively ( p = NS among agents vs 264 ± 109% for papaverine; p < 0.05 for all). Coronary vasodilatory reserve (calculated as the ratio of hyperemic to basal mean flow velocity) was also similar among agents. It was comparable to the coronary vasodilatory reserve with nitroglycerin (2.1 ± 1.0 to 2.2 ± 1.1) and significantly less than that with papaverine (3.3 ± 2.2, p < 0.05). These data indicate that the clinical advantages of nonionic or low-osmolar contrast media are not mechanistically related to significant attenuation of the coronary hyperemic response.

Mechanical effects of coronary perfusion in the passive canine left ventricle.

Mechanical effects of coronary perfusion on passive left ventricular filling were studied in seven isolated potassium-arrested dog hearts subjected to static pressure loading. With the use of a biplane video method, midanterior epicardial deformations were measured before, during, and after perfusion of the coronary circulation with a cardioplegic solution. During perfusion, there was a highly significant reduction (P less than 0.001) in ventricular compliance; the mean cavity volume change decreased by 50% at a filling pressure of 12 mmHg. The loss of compliance was reversible and increased with coronary artery pressure. The magnitudes of the principal epicardial extensions, determined by homogeneous strain analysis, also decreased significantly (P less than 0.001) by an average of 30-40% at ventricular pressures of 4-12 mmHg. But there was no change in the pattern of epicardial deformations. These findings, and similar significant falls in epicardial in-plane rotation (P less than 0.05) and angular translation (P less than 0.001), suggest that the main mechanical effect of the coronary circulation is homogeneous and uniform and is, therefore, probably associated with the microcirculation. We propose that this effect may be modeled by treating the myocardium as a porous elastic medium swollen with an incompressible fluid rather than by an increase in ventricular wall thickness due to filling of the coronary vessels.

Relationship between coronary blood flow and perfusion pressure during reactive hyperemia: A case report in an awake unanesthetized woman with normal coronary arteries

The linear relationship between coronary blood flow and mean arterial pressure during reactive hyperemia is presented for the first time in an awake unanesthetized woman with normal coronary arteries during systemic hypotension induced by pharmacologic vasodilation. This case demonstrates the critical dependence of coronary flow reserve on simultaneous perfusion pressure.

Effect of graded reductions of coronary pressure and flow on myocardial metabolism and performance: A model of “hibernating” myocardium

The term “hibernating” myocardium has been applied to chronic left ventricular dysfunction without angina or ischemic electrocardiographic changes in patients with coronary artery disease that is reversed by therapy that increases myocardial blood flow. To investigate the relation between coronary blood flow and ventricular function experimentally, graded reductions in coronary artery pressure were produced in isolated perfused rat hearts as contractile performance (peak systolic pressure and its first derivative [dp/dt]) and metabolic variables were measured using phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy.As coronary pressure and flow were reduced, significant reductions in myocardial oxygen consumption and contractile performance were observed, which returned to control levels when coronary artery pressure and flow were restored to baseline values. Two phases of metabolic abnormality were observed. With modest reductions in coronary perfusion, proportionate reductions in myocardial oxygen consumption and contractile behavior were accompanied by a slight reduction in creatine phosphate but no significant lactate production. With greater reductions in coronary artery pressure and flow, creatine phosphate decreased more, adenosine triphosphate levels and myocardial pH decreased significantly and myocardial lactate production increased. The balanced reductions in myocardial contractility and oxygen consumption without metabolic abnormalities traditionally associated with “ischemia” observed in the first phase provides evidence in normal hearts for resetting of the myocardial contractile behavior and oxygen consumption in the presence of reduced coronary flow (that is, hibernating myocardium). The data suggest that reductions in adenosine diphosphate and the index of the reduced form of nicotinamide adenine dinucleotide (NADH) (lactate formation) do not explain the coupling between coronary artery pressure and flow and myocardial oxygen consumption as contractile performance decreases.