Total Coronary Blood Flow Research Articles

Effects of endothelin-1 and sarafotoxin S6b on regional hemodynamics in the conscious dog

Endothelin, a potent vasoconstrictor, also is capable of producing transient vasodilation in some situations. We examined the changes in regional hemodynamics in response to constant infusions of endothelin-1 (ET-1) at 5, 10, or 20 ng.kg-1.min-1 for 1 h into conscious dogs. The dogs were instrumented with ultrasonic flow probes for measurement of blood flow in the ascending aorta (cardiac output) and in the coronary, mesenteric, renal, and iliac arteries. A compound structurally similar to ET-1, sarafotoxin S6b (S6b), was also infused in identical experiments to determine whether the responses to these two peptides might differ. Basal plasma levels of immunoreactive ET-1 averaged approximately 6 pg/ml. After 55 min of infusion of ET-1 at 5, 10, and 20 ng.kg-1.min-1, plasma immunoreactive ET-1 increased to approximately 55, 130, and 520 pg/ml, respectively. When given at 20 ng.kg-1.min-1, ET-1 increased total peripheral resistance and arterial pressure and decreased cardiac output and heart rate. ET-1 decreased coronary, mesenteric, and renal blood flow but did not change iliac flow. In comparison with ET-1, S6b produced relatively smaller changes in total peripheral resistance, cardiac output, heart rate, and coronary, mesenteric, and renal blood flow. Iliac resistance did not change in response to ET-1, but it increased during infusions of S6b. Similar but less pronounced responses were observed when these peptides were infused at 5 and 10 ng.kg-1.min-1. The regional variability in the hemodynamic response to ET-1 and the difference in regional responses to ET-1 and S6b are consistent with the existence of heterogenous receptor subtypes for these peptides.

Influence of low perfusion pressure on effect of endothelin on coronary vascular bed

The goal of this study was to evaluate the influence of low coronary perfusion pressure on the coronary vasoconstriction induced by endothelin. For this purpose, the circumflex coronary arteries of 12 open-chest dogs were cannulated and perfused at a controlled pressure. Total coronary blood flow was measured with an electromagnetic flowmeter and the transmural distribution of coronary blood flow with the radioactive microspheres technique. In addition, the circumflex coronary artery diameter was measured by sonomicrometry with piezoelectric crystals, and the coronary cross-sectional area was calculated. At a coronary perfusion pressure of 100 mmHg, endothelin induced a marked coronary vasoconstriction and a redistribution of coronary blood flow toward the endocardium. At a low coronary perfusion pressure of 40 mmHg, these effects of endothelin were still present. The constriction of the large coronary artery occurred even with a lower dose of endothelin at a low coronary perfusion pressure compared with the normal perfusion pressure. This was not the case when angiotensin II was given the same way. We conclude that endothelin is a potent coronary vasoconstrictor even at a low perfusion pressure. Thus one may speculate that endothelin plays a role in the coronary spasm which has been shown in patients with angina pectoris.

Coronary reserve in patients with aortic valve disease before and after successful aortic valve replacement

In patients with aortic valve disease and normal coronary angiograms coronary reserve was determined by the coronary sinus thermodilution technique. Three groups of patients were studied: 37 preoperative patients; 18 different patients 12-52 months after aortic valve replacement and seven control subjects with no cardiac disease. Coronary flow ratio (dipyridamole/rest) was diminished in preoperative compared with postoperative patients (1.66 +/- 0.44 vs 2.22 +/- 0.85; P less than 0.05) as well as with controls (2.80 +/- 0.84; P less than 0.01), and corresponding coronary resistance ratio (dipyridamole/rest) was higher in preoperative patients than in both other groups (0.61 +/- 0.17 vs 0.48 +/- 0.14; P less than 0.05 vs 0.37 +/- 0.10; P less than 0.01). Differences in the flow ratio, but not in the resistance ratio, were significant (P less than 0.05) in patients after aortic valve replacement compared with controls. Total coronary sinus blood flow at rest was elevated in preoperative compared with both postoperative patients and controls (252 +/- 99 vs 169 +/- 63; P less than 0.01; vs 170 +/- 35 ml.min-1, P less than 0.05), whereas flows after maximal vasodilation did not differ among the three groups (416 +/- 184 vs 361 +/- 150 vs 488 +/- 235 ml.min-1). Postoperative patients showed a distinct, though not total regression of left ventricular angiographic muscle mass index and wall thickness. Nine of the 18 postoperative patients showed a normal coronary flow reserve and nine showed subnormal response. These two subgroups did not differ with respect to preoperative macroscopic and microscopic measures of hypertrophy. Thus in aortic valve disease, the reduced coronary vasodilator capacity is mainly due to an elevated coronary flow at rest, while the maximal coronary blood flow achieved is identical to that of postoperative patients and controls. With regression of left ventricular hypertrophy, flow at rest decreases and this leads to a distinct improvement of coronary flow reserve.

Coronary hemodynamic effects of atrial natriuretic peptide in humans

Studies of the effects of atrial natriuretic peptide on the coronary circulation have yielded conflicting results in animals and have not been fully investigated in human subjects. To further characterize the direct coronary hemodynamic actions of atrial natriuretic peptide in humans and to assess the safety of its administration in patients with coronary artery disease, incremental doses of synthetic atrial natriuretic peptide and nitroglycerin were infused into the left coronary artery in 14 patients, 11 of whom had coronary artery disease.Both agents caused dose-related increases in total coronary sinus blood flow. The largest dose of atrial natriuretic peptide given to all patients (100 μg) increased mean coronary sinus blood flow from 127 ± 7 to 149 ± 9 ml/min (p < 0.05) and decreased coronary vascular resistance from 0.93 ± 0.07 to 0.81 ± 0.05 mm Hg/ml per min (p < 0.05); mean arterial blood pressure and heart rate were not affected by this dose of atrial natriuretic peptide. The greatest changes in coronary sinus blood flow (+25%) and coronary vascular resistance (−18%) after atrial natriuretic peptide administration occurred in the patients with coronary artery disease and no other associated cardiovascular disease. The maximal effects of atrial natriuretic peptide were similar to those of nitroglycerin, and no untoward effects were observed.Thus atrial natriuretic peptide is a direct coronary vasodilator in humans. Its maximal dose effects are similar to those of nitroglycerin and were well tolerated in this small group of patients. The physiologic importance and therapeutic potential of atrial natriuretic peptide in patients with coronary artery disease merit further investigation.

Dynamics of atrial peptide secretion in the coronary circulation of the conscious dog.

The secretion of atrial natriuretic peptide by the heart is not simply the arterial-coronary sinus concentration difference times coronary blood flow, because only a small fraction of total coronary blood flow passes through the atria. We measured coronary sinus and arterial plasma atrial natriuretic factor (ANF) concentrations and blood flow to each part of the heart using the radioactive microsphere technique. Before acute volume expansion, the arterial-coronary sinus ANF difference was 305 +/- 23 pg/ml and rose to 1,009 +/- 220 pg/ml during volume expansion, whereas total coronary blood flow rose from 167 to 465 ml/min. Atrial blood flow rose from 2.9% to 4.6% of total coronary blood flow during volume expansion. ANF secretion rate increased from 51 to 469 ng/min. When divided by atrial weight, ANF secretion rate increased from 4.0 +/- 0.3 to 56 +/- 12 ng/min/g atrial tissue-in other words, from 0.3% to 3.7% of tissue ANF content each minute. Dividing by atrial blood flow indicated that the concentration of ANF leaving atrial tissue was 10,000 to 29,651 pg/ml, and the additional secretion of ANF was determined by the increase in coronary blood flow. Therefore, at least two mechanisms are responsible for altering coronary sinus ANF and circulating ANF: the release rate from atrial myocytes and the washout via changes in atrial blood flow.

Coronary effects of adenosine in conscious man.

Adenosine has been reported to play an important role in several cardiac functions, including the regulation of total and regional myocardial perfusion. This hypothesis is based on extensive investigations in animal models, but very limited information is available on the cardiovascular actions of adenosine in conscious man and the effects of the intracoronary administration of adenosine are unknown. The purpose of this study was to measure total and regional coronary blood flow after bolus injections of 0.1, 0.5, 1.0, and 2.5 mg of adenosine into the left anterior descending coronary branch. A three-thermistor thermodilution catheter was advanced into the coronary sinus to measure simultaneously the great cardiac vein flow and the coronary sinus flow. Six patients with normal coronary angiograms and normal ventricular function completed the study. Intracoronary injections of adenosine were free from significant adverse effect and caused a dose-related increase of great cardiac vein flow. A linear relation was found between flow increment and the log of adenosine dose (y = 18.929x + 74.84, r2 = 0.951). The highest flow, measured after the maximal dose, was almost three times greater than control flow (155 +/- 2 vs 58 +/- 3 ml min-1, P less than 0.001). We also observed a flow response in the territory not directly exposed to adenosine, as indicated by a marked increase of coronary sinus blood flow that was linearly related to the adenosine dose (y = 29.113x = 112.635, r2 = 0.98). These preliminary observations suggest: (1) Intracoronary injections of adenosine in conscious man can be performed without significant adverse effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Diltiazem on Coronary Blood Flow Distribution in Dog Heart Under Ischemia

Effect of intracoronary infusion of diltiazem (1 microgram/min) on regional myocardial blood flow (RMBF) was studied using 15-microns radioactive microspheres in 11 excised cross-circulated canine left ventricles. With total coronary blood flow (CBF) and heart rate (HR) held constant, regional ischemia was induced by ligating the left anterior descending coronary artery (LAD). Diltiazem at the dose used had no effects on ventricular Emax before and after LAD ligation. RMBF expressed by the counts divided by the counts averaged in all segments in each layer significantly (p less than 0.05) increased under diltiazem only in the low-flow region that had less than 50% RMBF before diltiazem; from 21% (+/- 12%) to 35% (+/- 18%) in the epicardial, from 22% (+/- 12%) to 32% (+/- 18%) in the midwall, and from 24% (+/- 10%) to 31% (+/- 12%) in the endocardial layers. We conclude that the beneficial effect of diltiazem on the ischemic heart involves a direct action on the coronary vascular system and does not necessarily depend on the concomitant changes in hemodynamics.

Improvement of myocardial function by trifluoperazine, a calmodulin antagonist, after acute coronary artery occlusion and coronary revascularization

Activation of an intracellular calcium-calmodulin complex may play an important role in myocardial injury induced by ischemia and reperfusion. Trifluoperazine, a calmodulin antagonist, was used before ischemia to enhance myocardial preservation by preventing intracellular calcium accumulation. The experimental model used an isolated in situ pig heart (19 control animals and 15 trifluoperazine-treated animals) subjected to occlusion of the left anterior descending coronary artery for 60 minutes followed by 60 minutes of hypothermic potassium crystalloid cardioplegic arrest and 60 minutes of reperfusion. Myocardial segmental function measured by ultrasonic crystals showed that active systolic segment shortening was abolished in the distribution of the left anterior descending artery after 60 minutes of occlusion irrespective of the treatment, whereas that not in the distribution of the left anterior descending artery increased by about 15% in both groups of animals. Restoration of systolic segment shortening in the distribution of the left anterior descending artery 60 minutes after reperfusion was 12% and 42% of baseline levels in untreated and trifluoperazine-treated animals, respectively (p less than 0.01). This improvement in segmental function by trifluoperazine was reflected in significantly (p less than 0.05) better global myocardial contractility and compliance and in significantly (p less than 0.01) greater total coronary blood flow and myocardial oxygen consumption. Trifluoperazine also increased myocardial creatine phosphate content in the distribution of the left anterior descending artery (p less than 0.01) during reperfusion, and creatine kinase release was reduced (p less than 0.05). Our results suggest that trifluoperazine improved regional myocardial function after acute occlusion of the left anterior descending artery and reperfusion and that global cardiac performance was thereby improved. The beneficial effects of trifluoperazine may be exerted by prevention of myocardial injury associated with the calcium-calmodulin complex in ischemic and reperfused myocardium.

Homogeneous distribution and pressure dependent reduction of coronary blood flow in right ventricular free wall during coronary hypoperfusion in anaesthetised open chest dogs.

Relationship of coronary perfusion pressure with total and regional myocardial blood flow in right ventricular free wall was studied in 10 anaesthetised open chest dogs. The right coronary artery was perfused by an autoperfusion system from the carotid artery. Total coronary blood flow into the perfused area was measured by an extracorporeal electromagnetic flow probe. Critical perfusion pressure of the right coronary artery, defined as the lowest pressure level below which the regional wall motion deteriorated, was 39(SEM1) mm Hg. Reactive hyperaemia was noted at 60(2) mm Hg, a level well above the critical perfusion pressure. There was an inverse linear relation between the level of reactive hyperaemia and perfusion pressure. Regional myocardial blood flow was measured by a tracer microsphere technique at control condition, just above and below the critical perfusion pressures and during coronary occlusion. This correlated closely with values obtained by an electromagnetic flow probe (r = 0.94, p less than 0.001) and both values were dependent on the level of perfusion pressure. Endocardial to epicardial flow ratio remained at unity at any level of coronary perfusion pressure. Thus the level of coronary perfusion pressure was a major determinant of the regional myocardial blood flow into the right coronary artery, and autoregulation of the regional myocardial blood flow was not apparent across the wall, despite the presence of a reactive hyperaemia.

Reduction of systolic coronary blood flow in experimental left ventricular outflow tract obstruction

In aortic valvular stenosis, coronary reserve has been shown to be markedly diminished despite normal coronary arteries. To gain further insight into this phenomenon, we examined the effects of an acute subaortic valvular obstruction on coronary blood flow (CBF) in seven open-chest anesthetized dogs. Transient subaortic obstruction was produced by inflating a catheter-tip balloon in the left ventricular (LV) outflow tract. The degree of obstruction, a 26 ± 3 mm Hg gradient across the aortic valve, was adjusted to achieve an elevation of LV pressure while maintaining a constant aortic pressure (coronary perfusion pressure). In seven dogs with intact coronary vasomotor tone, systolic left anterior descending CBF decreased from 20 ± 9 ml/min during the control period to 13 ± 3 ml/min during subaortic obstruction ( p < 0.001). Diastolic CBF increased from 52 ± 9 to 58 ± 10 ml/min ( p < 0.05), and total CBF remained unchanged. In three dogs with maximal coronary vasodilation, systolic CBF decreased during subaortic obstruction, diastolic CBF remained unchanged, and total CBF decreased. The present data suggest that elevation of LV intracavitary pressure above coronary perfusion pressure can reduce systolic CBF and lead to an autoregulatory compensation that taxes coronary flow reserve.

Mechanisms of Enhanced Canine Subendocardial Perfusion

The purpose of these experiments was to determine the effects of adenosine triphosphate (ATP) and sodium nitroprusside, two compounds used to produce controlled hypotension during surgery, on regional myocardial blood flow. Intracoronary drug infusions in open chest, anesthetized dogs were used to study the direct actions of these agents on the coronary circulation as well as to avoid systemic hemodynamic effects. The actions of the endothelium-dependent and -independent vasodilators, ATP and nitroprusside, respectively, were studied before and after administration of quinacrine (an inhibitor of phospholipase A2), which blocks formation and/or release of endothelium-derived relaxing factor (EDRF). Both vasodilators produced significant increases in transmural blood flow of the drug-perfused zone. Only ATP, the endothelium-dependent vasodilator, altered the distribution of myocardial blood flow. Perfusion to the subendocardium was preferentially increased by ATP, resulting in an increase in the subendocardial-to-subepicardial flow ratio. Quinacrine markedly inhibited the increase in endo/epi produced by ATP without changing total flow. These data suggest that ATP increases total coronary blood flow by a mechanism that is independent of EDRF, but the selective redistribution of blood flow to the subendocardium is dependent on EDRF. Nitroprusside, an endothelium-independent vasodilator, produces no redistribution of myocardial blood flow.

Improved distribution of regional oxygenation in denervated ischemic dog myocardium.

The role of the adrenergic nervous system in the response to coronary artery occlusion has been examined using surgical and chemical denervation techniques. Experiments were conducted on four groups of dogs (n = 18): 1) untreated controls; 2) intrapericardial denervation immediately prior to coronary ligation; 3) surgical denervation 2 weeks prior to the experiment; and 4) chemical sympathectomy 5 days prior to the experiment with 6-hydroxydopamine (50 mg/kg). Small artery and vein O2 saturations were obtained microspectrophotometrically and combined with radioactive microsphere blood flow determinations to calculate regional myocardial O2 consumption in open chest dogs. Denervation significantly reduced the preocclusion heart rate from 165 +/- 16 beats/min in the control to 114 +/- 13 in the chronic surgically denervated and to 137 +/- 15 in the chemically sympathectomized groups. After 2 hours of occlusion, the O2 consumption and flow were similar in the nonischemic area except for lower values in the surgically denervated group. Total coronary blood flow and O2 consumption in the occluded regions were not significantly affected by chronic denervation. However, significant elimination of areas with low venous O2 saturation (less than 20%) were found in the ischemic myocardium of the chronically denervated groups as compared with the control or with the acutely denervated dogs. The mean venous O2 saturation was found to be significantly higher in all regions of these two groups as compared with the control. The O2 extraction was also lowered. Thus, chronic denervation reduced microregional heterogeneity of oxygenation in the ischemic myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Relations of preoperative hemodynamics and coronary blood flow to improved left ventricular function after valve replacement for aortic regurgitation

In this study of the limits of reversibility of left ventricular function after aortic valve replacement for aortic regurgitation, measurements were made of pre- and postoperative coronary blood Row and left ventricular volumes. Eighteen patients who had undergone aortic valve replacement for pure aortic regurgitation using the Björk-Shiley valve or the Bicerval valve were restarted an average of 8 ± 3 months after surgery.Postoperative left ventricular end-systolic and end-diastolic volumes returned to near normal values. The slight left ventricular wall thickening apparent before surgery remained unchanged after surgery and, consequently, left ventricular mass, though somewhat reduced, remained abnormally high. Ejection fraction, which was low preoperatively, returned to normal postoperatively. Total coronary sinus blood flow decreased after surgery, but coronary sinus blood flow per 100 g of left ventricular mass increased. This recovery of coronary flow per unit mass was believed to cause the improvement in left ventricular function.A significant correlation was found between postoperative systolic function and preoperative left ventricular endsystolic and end-diastolic volumes, wall thickness and, especially, left ventricular mass, the latter indicating that, if preoperative left ventricular mass is <350 g/m2, postoperative improvement of systolic function is attainable. Another significant correlation was indicated by measurements of coronary sinus blood flow per 100 g of left ventricular mass. If this is >35 ml/min before surgery, a postoperative improvement in systolic function to within the normal range may be expected.

Muscarinic Receptor Subtypes Mediating Myocardial Blood Flow Redistribution

Selective M1 and M2 muscarinic receptor antagonists pirenzepine and AF-DX 116, respectively, were administered to open-chest, pentobarbital-anesthetized dogs to determine the muscarinic receptor subtype responsible for the preferential vasodilation of subendocardial blood vessels during intracoronary methacholine infusion. There were no changes in systemic hemodynamics responsible for the myocardial blood flow redistribution produced by methacholine. Selective M1 receptor blockade with pirenzepine attenuated increases in transmural perfusion and prevented the redistribution of blood flow favoring the subendocardium during methacholine infusion. M2 receptor blockade with AF-DX 116 also attenuated the increase in transmural perfusion produced by methacholine but did not selectively block increases in subendocardial blood flow. These results support the hypothesis that M1 muscarinic coronary receptors are responsible for the redistribution of blood flow to the subendocardium (increased endo/epi) during cholinergic coronary vasodilation, whereas M2 receptors mediate an increase in total coronary blood flow. In additional experiments in isolated rabbit aorta, AF-DX 116 was 0.38 times less potent than pirenzepine with respect to endothelium-dependent muscarinic vasodilation but 1.47 times more potent with respect to endothelium-independent muscarinic vasoconstriction. This suggests that differences exist in the receptors found on the vascular smooth muscle and endothelium and that the preferential distribution of blood flow to the subendocardium may be due to stimulation of M1 receptors located on the vascular endothelium.

Distribution of a neutral cardioplegic vehicle during the development of ischemic myocardial contracture

During prolonged ischemic cardiac arrest successful myocardial protection depends upon uniform delivery of cardioplegic solutions to all regions of the heart. Accordingly, we studied the regional and transmural distribution of a neutral crystalloid (dextran-saline) solution during normothermic (37 degrees C) ischemia in 18 isolated blood-perfused dog hearts (isovolumic left ventricle). In the baseline state, coronary perfusion pressure was 100 mmHg. At the onset of ischemia and every 15 min throughout ischemia, we infused 100 ml of crystalloid solution (37 degrees C) at a perfusion pressure of 100 mmHg and the distribution of crystalloid solution was assessed (radioactive microsphere technique). The hearts were reperfused after 60 min (n = 9) or 90 mins (n = 9) of ischemia. In the baseline pre-arrest state the left ventricle (LV) received 67 +/- 1.0% of the total coronary blood flow; the LV subendocardial to subepicardial flow ratio was 1.33 +/- 0.18, the LV end diastolic pressure was 7.5 +/- 0.4 mmHg, and mean transmural myocardial adenosine triphosphate (ATP) was 16.4 +/- 1.1 microM/g DW. At the onset and throughout the first 45 mins of ischemia (n = 9), regional and transmural distribution of the crystalloid solution was similar to that of coronary blood flow during the baseline state; there was no change in LV end diastolic pressure, but there was a moderate fall in ATP content (7.26 +/- 1.6 micron/g DW). After 75 mins of ischemia (n = 9), despite the development of ischemic contracture (LV end diastolic pressure exceeded 20 mmHg in all 9 hearts) and marked ATP depletion (2.76 +/- 0.5 microM/g DW), there was an increase in crystalloid solution delivery to the LV as a whole and the subendocardium in particular (the LV received 82 +/- 2.0% and the subendocardial to subepicardial flow ratio was 1.75 +/- 0.1). Even in a subgroup with severe contracture during ischemic arrest (LV end diastolic pressure greater than 60 mmHg, n = 4) there was no reduction in crystalloid solution delivery. Thus, the presence of ischemic contracture does not preclude delivery of crystalloid solution to the LV subendocardium.

Myocardial blood flow and VO2 in conscious lambs with an aortopulmonary shunt.

We measured myocardial blood flow (QLVFW) and O2 consumption of the left ventricular free wall (VO2, LVFW) in 13 chronically instrumented, 7-wk-old lambs with an aortopulmonary left-to-right shunt (S) and in 10 control lambs without a shunt (C). The measured VO2, LVFW was compared with the calculated values obtained by two predictive indexes, the rate-pressure product (RPP) and the pressure-work index (PWI). Measured VO2, LVFW in S lambs was significantly higher than in C lambs [983 +/- 104 (SE) vs. 475 +/- 57 mumol X min-1 X 100 g LV-1, P less than 0.001]. This was achieved by the significantly higher QLVFW (294 +/- 33 vs. 145 +/- 15 ml X min-1 X 100 g LV-1, P less than 0.002), since the arteriovenous O2 difference across the left ventricular free wall was similar in both groups of lambs. Total coronary blood flow per unit body mass in S lambs was higher than in C lambs (14.1 +/- 1.5 vs. 5.6 +/- 0.6 ml X min-1 X kg-1, P less than 0.001), not only because of the increased VO2, LVFW per unit muscle mass, but also because of the increased total heart weight (102.4 +/- 6.4 vs. 81.2 +/- 4.9 g, P less than 0.02). Correct estimation of VO2, LVFW by means of the RPP and the PWI was only possible in C lambs. In S lambs the estimated values were significantly lower than the measured ones.(ABSTRACT TRUNCATED AT 250 WORDS)

Regional Coronary Hemodynamics during Isoflurane???Nitrous Oxide Anesthesia in Patients with Ischemic Heart Disease

The effects of 1.5 MAC isoflurane-nitrous oxide anesthesia on central hemodynamics, regional coronary blood flow, myocardial oxygenation, and lactate balance were investigated in 13 patients with coronary artery disease. Mean arterial pressure was reduced 45% mainly because of systemic vasodilation. Great cardiac venous flow (GCVF) decreased, whereas total coronary sinus blood flow (CSF) was unchanged. Total coronary resistance and resistance in the area drained by the GCVF decreased as did myocardial oxygen extraction, demonstrating coronary vasodilation. The GCVF/CSF ratio did not decrease despite the reduction in resistance to left ventricular ejection. Seven patients had ECG and metabolic indications of myocardial ischemia (lactate extraction reduced from 22 +/- 5% to 7 +/- 3%, P less than 0.02 for the group). Changes in GCVF and oxygen consumption in the corresponding area correlated closely (r = 0.943). However, the regression line was shifted to the left and three patients, who became ischemic, had an increase in GCVF despite unchanged or decreased myocardial oxygen demand. It is concluded that isoflurane may cause coronary blood flow redistribution with regional myocardial ischemia in patients with coronary artery disease.

Regional coronary vasoconstriction after combined beta-adrenergic and calcium channel blockade in patients with coronary artery disease

The beta-adrenergic and calcium channel blocking drugs, which individually and combined have proven efficacious in the treatment of angina pectoris, appear to have opposing effects on coronary artery vasomotion. Previous studies have shown that beta-adrenergic blockade may potentiate and calcium channel blockade reverse coronary vasoconstriction during adrenergic cold stimulation in patients with coronary artery disease. To assess the coronary hemodynamic effects of combined drug therapy, thermodilution coronary sinus and great cardiac vein flow and mean arterial pressure were measured during serial cold pressor testing, both before and after 0.1 mg/kg of intravenous propranolol and again after the addition of 10 mg of sublingual nifedipine in 21 patients (9 without [group A1] and 12 with [group A2] greater than 50% narrowing of the left anterior descending coronary artery). In an additional 15 patients (6 patients without [group B1] and 9 with [group B2] left anterior descending artery stenosis), serial cold pressor testing was performed reversing the drug order. Despite significant increases in mean arterial pressure (p less than 0.01) during cold pressor testing, coronary sinus resistance responses after propranolol plus nifedipine were not statistically significant for any group. However, regional coronary resistance responses differed between patients with and without left anterior descending artery stenosis. In group A1, great cardiac vein resistance was unchanged after propranolol plus nifedipine. In group A2, great cardiac vein flow decreased significantly after propranolol plus nifedipine from 8 +/- 17 to -4 +/- 12% (p less than 0.01 versus control), and great cardiac vein resistance increased from 4 +/- 21 to 15 +/- 19% (p less than 0.01 versus control). A similar significant response was observed for groups B1 and B2. Regional coronary vasoconstriction during adrenergic stimulation after combined drug therapy was only observed in patients with significant left anterior descending artery stenosis. These data suggest that in some patients with severe coronary artery disease, combined beta-adrenergic and calcium channel blockade modified regional coronary responses to adrenergic stimulation with an inhomogeneous distribution of blood flow to potentially ischemic regions without affecting total coronary blood flow. These data also imply that an improvement in anginal symptoms after combined drug therapy may be due primarily to mechanisms that reduce myocardial oxygen demand rather than to improved myocardial oxygen supply.

Effect of intracoronary nitroglycerin on myocardial blood flow and distribution in pacing-induced angina pectoris: Quantitative assessment by single-photon emission tomography

Changes in regional coronary flow after administration of intracoronary nitroglycerin were assessed by measuring total coronary blood flow (using coronary sinus flow catheters) and its regional distribution (by quantitative single-photon emission tomography of injected radioactive microspheres). After pacing to angina, 10 patients with coronary artery disease received serial selective left coronary injections of technetium-99m microspheres, 40 μg of nitroglycerin, and indium-111 microspheres. Significant changes in coronary flow distribution were determined by subtracting prenitroglycerin from postnitroglycerin tomographic profiles. Perfusion of each myocardial segment was classified as normal mildly, moderately or severely compromised, based on upstream coronary anatomy. The overall increase in coronary flow was 23% in the normal territories and 33%, 44% and 15% (p < 0.05), in the mildly, moderately and severely compromised territories, respectively, compared with control values. Thus, intracoronary nitroglycerin increased coronary blood flow to all perfusion territories. The increase in distribution of coronary flow was greatest in the mildly and moderately compromised regions and the least in the most severely compromised regions; this is probably a reflection of the underlying coronary reserve.

Effects of intubation on coronary blood flow and myocardial oxygenation.

Effects on haemodynamics and myocardial oxygenation of endotracheal intubation were examined in 17 patients after halothane induction and 12 after 1 mg X kg-1 of IV morphine. Six patients having each anaesthetic were pretreated with IV propranolol (0.1 mg X kg-1) 45 minutes earlier. Arterial and intracardiac pressures, cardiac output and total coronary sinus blood flow (CSBF), both by thermodilution, were determined plus arterial-coronary differences of oxygen, haemoglobin and lactate. Blood pressure (BP), heart rate and CSBF were recorded continuously during intubation. The subjects were candidates for coronary bypass grafts, but had good ventricular function (mean ejection fraction 0.68 +/- 0.13 SD). From their reduced levels after induction, BP, cardiac index and systemic vascular resistance increased to awake levels following intubation. Mean CSBF in nonbetablocked patients increased to awake level along with BP. More myocardial oxygen was extracted and consumed after intubation, but lactate extraction continued: these data are evidence of adequate oxygen supply. Induction with either halothane or morphine effectively prevented the hypertensive response to intubation. Acute beta blockade led to less increase in heart rate from intubation.