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.     

Effects of felodipine, a new dihydropyridine vasodilator, on regional myocardial blood flow during acute coronary occlusion in the pig

We studied the effects of felodipine [4-(2,3-dichlorophenyl)-1,4-dihydropyridine-2,6-dimethyl 3,5-dicarboxylic 3-ethylester and 5-methylester] on the coronary vascular bed of pig hearts with an ischemic region in the left ventricle following ligation of the left anterior descending coronary artery. At an infusion rate of 0.12 nmol X kg-1 X min-1, felodipine caused a slight reduction in mean arterial blood pressure and a decrease in coronary vascular resistance in both normal myocardium and partly ischemic myocardium of the border zone. In another series of experiments, felodipine was infused at a higher rate (0.38 nmol X kg-1 X min-1). The resultant decrease in mean arterial blood pressure, which was about 30%, was counterbalanced by inflation of an aortic balloon to keep the afterload and the coronary perfusion pressure constant. In this situation, felodipine caused a pronounced increase in blood flow to all parts of the heart except the central ischemic zone, where blood flow was extremely low. We conclude that felodipine has a coronary vasodilator action which is at least of the same magnitude as its peripheral vasodilator action, and that it markedly increases coronary blood flow in the border zone of an ischemic area.     

Coronary collateral blood flow in acute myocardial ischemia is not increased by dihydropyridine-induced coronary vasodilatation

The effect of two dihydropyridine derivatives, nifedipine and felodipine, on myocardial blood flow distribution 1 h after ligation of the left anterior descending coronary artery (LAD) was studied in open-chest dogs by means of radioactive microspheres. The myocardium normally perfused from the LAD was first labeled with 125I-labeled microspheres injected directly into the LAD before ligation. Microspheres used for blood flow measurements were given in the left atrium. An intravenous infusion rate of 0.3 nmol/kg/min felodipine slightly depressed mean aortic blood pressure (approximately 5 mm Hg) and decreased coronary vascular resistance in normal myocardium. Nifedipine, at three times the dose of felodipine, had a comparable hypotensive effect, but the decrease in coronary vascular resistance was not statistically significant. The two dihydropyridines were also compared in a dose range that was four times higher. The mean arterial blood pressure reduction (approximately 30% for both drugs) was counterbalanced by inflation of an intraaortic balloon to avoid a drastic decrease in afterload and coronary perfusion pressure. Under these circumstances, felodipine and nifedipine decreased coronary vascular resistance and increased blood flow to nonischemic myocardium comparably. However, in severely ischemic, truly collateral-dependent myocardium without admixture of interdigitating healthy myocardium, the blood flow was unaffected after administration of both felodipine and nifedipine. Although felodipine was three times more potent than nifedipine with regard to vasodilatation in the normal myocardium, the difference in vascular selectivity between the two agents did not influence the effect on the "true" collateral blood flow in acute myocardial ischemia.     

Effect of diltiazem on extent of ultimate myocardial injury resulting from temporary coronary artery occlusion in dogs

The calcium antagonist, diltiazem, was evaluated for its ability to reduce the extent of myocardial injury resulting from 90 min of left circumflex (LCX) coronary artery occlusion in anesthetized dogs. Administration of diltiazem (0.75 mg/kg over 10 min, followed by 600 microgram/kg/h for 4 h) was initiated 30 min prior to LCX occlusion. Regional myocardial blood flow (RMBF) was measured with radioactive microspheres 30 min after LCX occlusion, and at 45 min and 24 h after reperfusion. At 24 h, after obtaining hemodynamic and RMBF measurements, excised hearts were processed by perfusion staining to determine the percent of left ventricle (LV) perfused by LCX (area at risk) and infarct size, with triphenyltetrazolium chloride. Infarct size, expressed as a percentage of the area at risk, was significantly lower in the diltiazem-treated group compared to the control group (27 +/- 4 vs. 42 +/- 5%, respectively). The area at risk, expressed as a percentage of left ventricular mass, was similar in both groups [41 +/- 2 and 44 +/- 3% (area at risk-LV)]. In addition, the marked elevation of tissue Ca2+ content in noninfarcted and infarcted myocardium within the area at risk (18 +/- 2 and 42 +/- 8 mumol Ca2+/g) in control animals was attenuated by diltiazem (6 +/- 3 and 18 +/- 8 mumol Ca2+/g). Diltiazem did not increase blood flow to ischemic myocardium during LCX occlusion. However, reflow to the inner layers of formerly ischemic myocardium during reperfusion was significantly greater in diltiazem-treated dogs. Both arterial blood pressure and heart rate were significantly lower in the diltiazem -treated group. In addition, mortality (1 vs. 4) and occurrence of ventricular arrhythmias during reperfusion were lower in diltiazem-treated dogs. The data suggest that diltiazem reduces myocardial ischemic injury by lowering myocardial oxygen demands indirectly via favorable hemodynamic alterations, and directly by limiting transmembrane Ca2+ fluxes during ischemia and reperfusion.     

Effects of pinacidil on myocardial blood flow and infarct size after acute left anterior descending coronary artery occlusion and reperfusion in awake dogs with and without a coexisting left circumflex coronary artery stenosis

To determine whether partial stenosis of a second major coronary artery promoted vasodilator-induced coronary steal and increased infarct size after acute coronary artery occlusion, we produced acute myocardial infarction by 4-h left anterior descending coronary artery occlusion and 20-h reperfusion in awake dogs with and without a mild to moderate stenosis (33-72%) of the proximal left circumflex coronary artery. Dogs were randomized to receive intravenous (i.v.) normal saline or pinacidil, a new antihypertensive agent with a marked coronary dilator property, beginning 40 min after onset of coronary artery occlusion and continuing throughout the occlusion and the first hour of reperfusion. Pinacidil was titrated to decrease mean aortic pressure 25 mm Hg, which resulted in an increase in heart rate (HR), cardiac output (CO), and left ventricular (LV) dP/dt and LVdP/dt/P. Saline infusion had no effects. Blood flows to ischemic and remote myocardium did not differ between dogs with and without coronary stenosis. Pinacidil increased blood flow threefold in normal myocardium, but had no effect on infarct zone myocardial blood flow or infarct size (58 +/- 4% of region at risk vs. 56 +/- 4% in animals receiving normal saline) in dogs without coronary stenosis. In contrast, similar administration of pinacidil in dogs with coronary stenosis reduced infarct size zone myocardial blood flow and increased infarct size (69 +/- 3% vs. 55 +/- 5% in the saline group, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

心内直视手术灌注对冠脉血流量及ST段的影响

目的:观察分析心脏不停跳心内直视手术,灌注对冠脉血流量及ST段缺血改变的影响。方法:选择ASA I-Ⅱ级冠心病(CHD)20例,年龄(9.8±3.3)岁,体重(26.9±4.5)kg,灌注量100 ml/kg,大剂量芬太尼静脉复合麻醉,测量心肺转流插入冠状静脉管后1、5、10、15、20、25分钟的每分钟体外灌注流量,冠脉血流量,记录心电图和平均动脉压(MAP)、中心静脉压(CVP)、肛温(℃)亦同步取样观察血流酸碱气体分析及血浆电解质变化。结果:冠脉血流量在插冠管后1分钟是灌注流量的8％,5分钟后是6.6％以上。ST段在插冠管后1分钟正常,5分钟至20分钟明显上抬或下移,25分钟恢复正常。各时项MAP、CVP,肛温稳定。血液酸碱气体分析,血浆电解质正常范围,灌注流量与ST段无明显相关(P>0.05),冠脉流量与ST段有明显相关(P<0.01)。结论:体外循环心脏不停跳心内直视手术,在灌注流量稳定,冠脉血流量占灌注流量的6.5％以上。ST段缺血改变主要是手术操作,按压心脏,造成冠状动脉血流减少或局部阻塞,心肌顿时缺血所致,只要手术操作熟练完全可以避免。     

实时心肌声学造影评价冠心病介入治疗前后心肌灌注

目的评价冠心病（CHD）经皮冠状动脉介入治疗（PCI）前、后心肌灌注情况。方法由心血管科医师筛选出经冠状动脉造影（CAG）证实冠状动脉正常的健康者和有冠状动脉狭窄的冠心病患者共42例,对人选的冠状动脉狭窄的患者在行PCI术前、后和冠状动脉正常者进行经静脉心肌声学造影（MCE）,通过心肌显影程度定量判断冠状动脉微循环灌注并记录图像,将治疗前、后及冠状动脉正常者的心肌声学造影结果进行对比分析,评价手术疗效,估计患者的预后。结果23例患者PCI术治疗后,相关心肌节段的局部所有毛细血管横截面积之和（A）;血流速度（B）、心肌的血流量（A·B）均较冠状动脉介入前显著增加;PCI术后相关心肌节段组与冠状动脉正常人心肌节段组比较,局部所有毛细血管横截面积之和（A）、血流速度（B）、心肌的血流量（A·B）仍减低;相关分析显示,随访期EF值和室壁运动记分指数较术前明显增加,并与PCI术治疗后A、B、A·B相关性好。结论经静脉心肌声学造影检查能为冠心病诊断治疗领域提供一种准确、无创评价心肌微循环的临床检测手段进一步评价经皮冠状动脉介入治疗对改善心肌梗死患者心肌组织灌注的效果。未经再灌注治疗的心肌梗死或心绞痛患者应尽早行择期PCI术,挽救梗死区的缺血心肌,改善左心室功能。     

丹参酮、纳络酮对缺血再灌注心肌局部血流量的影响

目的：观察丹参酮、纳络酮对缺血再灌注心肌局部血流量的影响。方法：用结扎冠状动脉左前降支的方法复制犬心肌缺血再灌注模型，心肌局部血流量用氢气清除法测定。结果：丹参酮、纳络酮均能明显增加正常及部分再灌注心肌血流量，丹参酮主要增加缺血周围区血流量，纳络酮可增加缺血中心区及周围区血流量。结论：丹参酮、纳络酮均能缩小缺血区范围，纳络酮还能减轻缺血程度。     

ET-A receptor activity restrains coronary blood flow in the failing heart

Circulating levels of the potent vasoconstrictor peptide endothelin-1 (ET-1) are increased in congestive heart failure (CHF). Coronary blood flow and myocardial oxygen consumption (MVO2) are decreased in some models of CHF. This study tested the hypothesis that ET-1 induced coronary vasoconstriction limits oxygen availability in the failing heart. The effects of selective ET-A receptor blockade with BQ610 (5 microg/min, intracoronary) and selective ET-B receptor blockade with BQ788 (5 microg/min, intracoronary) on coronary blood flow were examined at rest and during graded treadmill exercise in 8 dogs in which congestive heart failure (CHF) had been produced by rapid ventricular pacing for three to four weeks. In animals with CHF, ET-B receptor blockade caused no change in left ventricular (LV) pressure or coronary blood flow. In contrast, ET-A blockade with BQ610 resulted in modest significant increases of coronary blood flow at rest (from 22.4 +/- 2.1 to 27.9 +/- 3.0 mL/min) and during two exercise stages (from 26.9 +/- 2.0 to 30.7 +/- 1.9 during stage 1 exercise and from 28.5 +/- 2.0 to 31.7 +/- 1.3 mL/min during stage 2; all P < 0.05), with an upward shift in the relationship between coronary flow and rate-pressure product. The increase in coronary flow produced by ET-A blockade was not associated with an increase of either myocardial oxygen uptake or LV dP/dt. Thus, although ET-A receptor blockade caused a modest increase in coronary flow, this did not result in an increase of MVO2, implying that ET-A-mediated coronary vasoconstriction did not limit oxygen uptake by the failing heart.     

Effect of intracoronary diltiazem on ST-segment elevation and myocardial blood flow during pacing-induced ischemia

This study was performed to determine if diltiazem can reduce the severity of pacing-induced ischemia independently of its peripheral hemodynamic effects and of increases in ischemic region blood flow. Twelve anesthetized dogs were subjected to atrial pacing and had their left anterior descending coronary arteries (LAD) occluded gradually until ischemia ensued (greater than 10 mV epicardial ST-segment elevation). Cessation of pacing resulted in abolition of ST-segment elevation. ST-segment elevation, as well as peripheral and coronary hemodynamics, was measured during 5-min periods of pacing + LAD stenosis before and 0, 30, and 60 min after treatment with intracoronary (just distal to the stenosis) saline or 1.8 micrograms/kg diltiazem. Myocardial blood flow was measured using radioactive microspheres during pacing, pacing + stenosis, and pacing + stenosis + drug treatment at 60 min. Diltiazem significantly reduced ST-segment elevation approximately 50% at 0, 30, and 60 min compared with elevations seen in animals treated with saline as well as predrug values. No changes in blood pressure, heart rate, or LAD flow occurred with diltiazem. Overall ischemic tissue flow and its transmural distribution were not different with diltiazem compared with saline treatment. Thus, diltiazem can decrease the severity of pacing-induced ischemia independently of its peripheral effects and of increased ischemic region blood flow.     

Importance of myocardial blood flow changes in the protective action of diltiazem in a new model of myocardial ischaemia.

The effect of diltiazem was studied in a new model of myocardial ischaemia in which in addition to a critical constriction of the left circumflex branch (LCX), the left anterior descending coronary artery (LAD) was suddenly occluded. This model is probably more relevant to the clinical situation in which multivessel coronary artery disease is common. In this model diltiazem exerted a beneficial effect, manifested by an increase in myocardial blood flow (MBF) within the stenosed area of the LCX; by a marked reduction of the enhanced preload (LVEDP); by a diminution of the inhomogeneity of electrical activation and by a decrease in ST-segment elevation. Diltiazem also caused a significant reduction both in the number of extrasystoles and in the incidence of ventricular fibrillation. Increased MBF within the stenosed area was associated with enhanced blood flow to the ischaemic myocardium, i.e. diltiazem directed flow to the ischaemic zone by improvement of the collateral circulation. The beneficial electrophysiological changes caused by diltiazem are probably at least partly due to the drug-induced improvement of myocardial blood supply to the ischaemic area.     

The effect of diltiazem on ST-segment elevation and myocardial blood flow distribution during pacing-induced ischemia

The purpose of this study was to determine if diltiazem can reduce the severity of pacing-induced ischemia independently of increases in overall and microregional ischemic blood flow. Sixteen anesthetized dogs were subjected to atrial pacing and had their left anterior descending coronary arteries (LAD) occluded until significant ST-elevation occurred. Cessation of pacing resulted in abolition of ST-segment elevation. ST-elevation as well as hemodynamics were measured during 5 min periods of pacing + LAD stenosis before, and 10, 40 and 70 min after treatment with intracoronary (i.c., just distal to the stenosis) diltiazem (1.8 micrograms/kg), i.v. diltiazem (180 micrograms/kg) or saline. Myocardial blood flow was measured using radioactive microspheres under baseline conditions, pacing, pacing + stenosis, and pacing + stenosis + drug (70 min post-drug). Both i.c. and i.v. diltiazem significantly and similarly reduced pacing-induced ST-elevation at 40 and 70 min post-drug with the highest measured reductions occurring for both at 70 min (50-60% reduction). Overall ischemic regional myocardial blood flow was unaffected by i.c. and i.v. diltiazem. Diltiazem given i.v. resulted in reduced flow in the lightly ischemic region and increased flows in the subepicardial half of the severely ischemic region. Diltiazem given i.c. resulted in a reduced subepicardial flow in the lightly ischemic region with no other changes occurring in the other regions. Thus, both i.c. and i.v. diltiazem can reduce the severity of pacing-induced ischemia and, in the doses given, in an equivalent fashion. Diltiazem also seems to be able to reduce severity of ischemia in a manner independent of increases in ischemic region flow and in fact can reduce flow in marginally ischemic tissue.     

Collateral blood flow following acute coronary artery occlusion: comparison of a new intracellular calcium antagonist (KT-362) and diltiazem

The effects of a new intracellular calcium antagonist, KT-362 (150 and 300 micrograms/kg per min), on hemodynamics and collateral function (retrograde pressure and flow, radioactive microspheres) distal to an acute coronary artery occlusion were studied in anesthetized dogs and compared with the effects of the structurally related classical calcium channel blocker, diltiazem (15 and 30 micrograms/kg per min), and a saline-treated control group. In the saline series, there were no changes in systemic hemodynamics or coronary collateral blood flow over the 90-min ischemic period. KT-362 reduced mean aortic pressure, heart rate, and dP/dt whereas diltiazem only decreased aortic blood pressure. When blood pressure was controlled by a distal aortic cuff, heart rate was significantly reduced in both groups and dP/dt was reduced in the KT-362 series and increased in diltiazem-treated dogs. In both drug-treated groups, retrograde pressure and flow were significantly increased only when aortic pressure was controlled. Regional myocardial tissue blood flow in the nonischemic or ischemic region did not change significantly after KT-362 treatment despite its hypotensive actions, and in the presence of a constant aortic pressure, transmural collateral blood flow and the ischemic/nonischemic blood flow ratio tended to increase. In contrast, diltiazem treatment resulted in a significant decrease in the ischemic/nonischemic blood flow ratio in the absence of blood pressure control. In the presence of constant aortic pressure, blood flow to the nonischemic area was markedly increased by diltiazem whereas subendocardial blood flow was significantly increased in the ischemic area.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of molsidomine and nitroglycerin on the regional blood flow in the normal and acutely ischemic myocardium (author's transl)]

In anaesthetized dogs regional myocardial blood flow (radioactive particle distribution technique) and several haemodynamic parameters were measured before and after acute ligation of left descending coronary artery. By injection of N-carboxy-3-morpholino-sydnonimine ethylester (molsidomine, Corvaton) or infusion of nitroglycerin it was tried to influence blood flow of the infarcted areas of the myocardium. 1. Ligation of the coronary artery induces myocardial infarction of anterior wall, predominantly restricted to the endocardial portions of the heart muscle. 2. Molsidomine and also nitroglycerin do not change overall blood flow of the heart in the sense of vasodilation. 3. In the infarcted area the ratio: blood flow of endocardial layers to blood flow of epicardial layers, is improved by molsidomine. 4. The positive effect of molsidomine becomes clearer in the border zone of infarction. Nitroglycerin remains without effect. 5. The effects of the compound molsidomine are explained by stronger action on extravascular factors of colonary vascular resistance (decrease in enddiastolic pressure).     

Effects of intracoronary nifedipine on blood flow and segment shortening in normal and ischemic myocardium: potentiation by ischemia of the negative inotropic effect

The effects of intracoronary nifedipine on myocardial blood flow (flow probe or microspheres) and regional function (ultrasonic crystals in subendocardium) were examined both in the normal myocardium and in myocardium made ischemic by a partial coronary occlusion in the open-chest anesthetized dog. In a first group of experiments (n = 7), without ischemia, nifedipine infused into the left anterior descending coronary artery (LAD) during a 1-min period (doses 0.75-8 nmol/kg body weight) decreased coronary vascular resistance with a maximal effect at 4 nmol/kg. Systolic segment shortening was decreased from 10.7 to 7.4% (p less than 0.05) by 6 nmol/kg, whereas lower doses had no effect. In a second experimental group (n = 7), a partial LAD occlusion was applied to decrease subendocardial segment shortening by about 50%. Nifedipine (2 nmol/kg) injected into the partially occluded LAD induced a marked segmental bulging during early systole and systolic segment shortening was eliminated (from 4.2 to -3.1%, p less than 0.02) in the LAD-dependent myocardium. Concomitant with the decreased regional function, nifedipine caused a transmural redistribution of myocardial blood flow in the ischemic area, the endocardial/epicardial blood flow ratio increasing from 0.49 to 0.61 (p less than 0.02). It is concluded that ischemia potentiates the direct depressant effect of nifedipine on myocardial regional function.     

The effects of propranolol and acebutolol on left ventricular function and coronary haemodynamics in the conscious dog with myocardial ischaemia.

1 The cardiovascular effects of the beta-adrenoceptor blocking drugs, propranolol and acebutolol, on regional coronary blood flow and left ventricular function have been investigated in the conscious dog with developing myocardial infarction. 2 Propranolol (1 to 1.5 mg/kg) or acebutolol (4 to 5 mg/kg) were administered intravenously 2 to 3 h after occlusion of the left anterior descending coronary artery. 3 Propranolol or acebutolol administration resulted in a relative increase in flow to the ischaemic area of the myocardium, particularly to the subendocardium. 4 Propranolol produced a greater reduction in heart rate and myocardial contractility than acebutolol. 5 These results demonstrate that beta-adrenoceptor blocking drugs reduce myocardial oxygen consumption and increase coronary flow to the ischaemic area of the myocardium after coronary artery occlusion in the conscious dog.     

Electrophysiologic effects of bretylium tosylate on the canine heart during coronary artery occlusion and reperfusion

The electrophysiologic and antiarrhythmic actions of bretylium tosylate were studied after acute coronary artery occlusion and reperfusion in pentobarbital-anesthetized dogs. Three groups of animals were studied: Group I (n = 8) served as saline controls, Group II (n = 7) received bretylium tosylate (10 mg/kg i.v.) 60 min prior to coronary artery occlusion, and Group III (n = 5) received bretylium tosylate (30 mg/kg i.v.) in three divided doses over the 24 h prior to coronary artery occlusion. In Groups II and III the effective refractory period of the nonischemic myocardium was not altered by bretylium before or during the occlusion period, nor was it influenced by bretylium during the subsequent reperfusion period. In Group I the effective refractory period of the ischemic myocardium decreased 24 +/- 3.0% after coronary occlusion and increased 12 +/- 3% above the preocclusion level on reperfusion. In Group II the effective refractory period of the ischemic myocardium decreased 28 +/- 3.2% after coronary occlusion but did not overshoot preischemic levels on reperfusion. In Group III the effective refractory period decreased 15 +/- 3.8% following coronary occlusion and did not overshoot preocclusion levels during reperfusion. The ventricular activation times of the normal and ischemic myocardium were not affected by bretylium tosylate during occlusion or reperfusion in Group II or III. Significant reperfusion arrhythmias were observed only in Groups I and II. These data suggest that bretylium tosylate exerts its antiarrhythmic actions in ischemic myocardium by reducing the dispersion of cardiac refractoriness produced by coronary artery occlusion and, consequently, abolishing the abrupt change in cardiac refractoriness that follows coronary artery reperfusion. These antiarrhythmic actions of bretylium are pronounced in the chronically treated group, suggesting an electrophysiologic basis of the delayed antiarrhythmic actions of bretylium.     

Comparative effects of two slow channel calcium entry blockers, FR 34235 and nifedipine, on true coronary collateral blood flow

The effect of a new dihydropyridine calcium entry blocker, FR 34235, on coronary collateral blood flow was compared with that of nifedipine in anesthetized dogs following acute ligation of the left anterior descending coronary artery. A special technique was used to separate true coronary collateral blood flow from overlap flow due to interdigitation of normally perfused tissue contained within the ischemic region. During infusion of doses of both agents, which produced nearly equivalent decreases (15-20 mm Hg) in mean arterial pressure, flow was significantly increased in normal myocardium; however, no change in collateral perfusion to ischemic myocardium was observed. When blood pressure was returned to control by an aortic cuff, blood flow to the normal region further increased. Transmural flow to the ischemic region was also significantly increased by both compounds. Nifedipine increased collateral flow primarily to the subepicardium, whereas FR 34235 increased collateral perfusion to the subepicardium, midmyocardium, and subendocardium. These results suggest that dihydropyridine calcium entry blockers may increase collateral blood flow to ischemic myocardium if drug-induced hypotension is minimized. In addition, FR 34235 has a more favorable effect on the transmural distribution of blood flow than nifedipine.     

The slow-channel calcium blocking agent, nitrendipine, and coronary collateral blood flow

The effects of a new dihydropyridine slow-channel calcium blocking agent, nitrendipine, on hemodynamics and myocardial blood flow in normal and ischemic areas distal to either an acute or chronic coronary artery occlusion were studied in anesthetized dogs. Nitrendipine produced significant and dose-related decreases in mean aortic blood pressure and increases in flow through the nonobstructed coronary artery. In acute coronary artery occlusion experiments, only small changes in perfusion of the ischemic zone were observed following nitrendipine. On the other hand, in dogs with a chronic coronary artery occlusion and well-developed collateral circulation, nitrendipine produced significant and dose-related increases in subepicardial perfusion within the central ischemic zone. No change in subendocardial blood flow during drug-induced hypotension was observed, but when aortic pressure was held constant, there was an increase in subepicardial, subendocardial, and overall transmural myocardial perfusion. The data demonstrate that nitrendipine improves oxygen supply to collateral-dependent myocardium via an increase in coronary collateral blood flow in a model of chronic coronary occlusion.     

Effects of diltiazem and propranolol on irreversibility of ischemic cardiac function and metabolism in the isolated perfused rat heart

Ischemia was induced by lowering the afterload pressure of the perfused working rat heart, and continued until the heart was reperfused by raising the after load. After ischemia, the following changes were observed: decreases in the pressure-rate product (peak aortic pressure X heart rate) and coronary flow; depletion of adenosine triphosphate and creating phosphate; and accumulation of lactate. When the heart was exposed to ischemia for more than 20 min, reperfusion of the ischemic heart could not restore the pressure-rate product and the tissue adenosine triphosphate completely, suggesting that irreversible ischemic damage occurred. Diltiazem (2.41 X 10(-6), 1.21 X 10(-5), and 2.41 X 10(-5) M) or propranolol (1.69 X 10(-5) and 3.38 X 10(-5) M) was provided for the heart 5 min before the onset of ischemia. In the presence of diltiazem or propranolol, the levels of adenosine triphosphate and creatine phosphate were preserved even after 20 min of ischemia. Reperfusion with the normal perfusate after 20 min of ischemia. Reperfusion with the normal perfusate after 20 min of ischemia with the buffer containing diltiazem or propranolol recovered the pressure-rate product that had been decreased by ischemia, depending on the concentration of diltiazem or propranolol provided. These results indicate that diltiazem, as well as propranolol, delays the onset of irreversible ischemic damage of the heart, suggesting their protective effects on the ischemic myocardium.