Role of nitrates in acute myocardial infarction.

In patients with acute myocardial infarction, intravenous nitroglycerin lowers left ventricular filling pressure and systemic vascular resistance. At lower infusion rates (less than 50 micrograms/min) nitroglycerin is principally a venodilator, whereas at higher infusion rates more balanced venous and arterial dilating effects are seen. Patients with left ventricular failure demonstrate increased or maintained stroke volumes, whereas patients without failure show a decrease in stroke volume. All hemodynamic subgroups show a decrease in left ventricular filling pressures and a reduction in electrocardiographic evidence of regional myocardial ischemia. Longer-term infusions (24-48 hours) have been shown to result in myocardial preservation, as assessed by global and regional left ventricular function and laboratory indices of infarct size. Comparison of intravenous nitroglycerin and sodium nitroprusside reveals increased intercoronary collateral flow with nitroglycerin, in contrast to a decrease with nitroprusside, compatible with a "coronary steal." Short-term administration of intravenous nitroglycerin with or without chronic administration of long-acting nitrates have been found both to reduce short-term mortality and to have long-term beneficial effects on left ventricular remodeling in patients with anterior transmural infarctions. Current clinical practice would utilize intravenous nitroglycerin as initial therapy for patients receiving intravenous thrombolytic therapy and/or acute percutaneous transluminal coronary angioplasty within 4-6 hours of the onset of symptoms of acute myocardial infarction, in order to optimize intercoronary collateral flow until reperfusion can be accomplished. Patients reaching the hospital greater than 6 hours but less than 14 hours after symptom onset can still benefit from intravenous nitroglycerin for 24-48 hours.(ABSTRACT TRUNCATED AT 250 WORDS)     

Significance of collateral circulation in reversible left ventricular asynergy by nitroglycerin in patients with relatively recent myocardial infarction

To evaluate the functional role of coronary collateral circulation in reversible asynergy of the left ventricle, cineventriculography was performed before and after the administration of sublingual nitroglycerin in 19 patients with complete occlusion of the proximal part of the left anterior descending coronary artery. In nine patients who had significant collateral circulation to the infarct-related coronary artery (group A), there was significant improvement in both the left ventricular ejection fraction (53% to 60%, p less than 0.05) and regional wall motion in the infarct zone (8% to 18%, p less than 0.01 in the anterolateral area) with administration of nitroglycerin. In contrast, in the remaining 10 patients without significant collateral perfusion (group B), there were no detectable changes in either global function (49% versus 50%) or regional wall motion (6% versus 8% in the anterolateral area) before and after nitroglycerin. Changes in heart rate and left ventricular peak systolic and end-diastolic pressures with nitroglycerin were comparable in both groups. These results suggest that angiographically demonstrable collaterals preserve viable myocardium, which can improve its contraction when the supply-demand relationship is favorably affected because of increased collateral flow and/or more favorable loading conditions produced by nitroglycerin.     

Alterations in regional myocardial blood flow after nitroprusside and nitroglycerin in patients with and without significant coronary artery disease

To evaluate vasodilator-induced redistribution of regional myocardial blood flow, intravenous sodium nitroprusside and nitroglycerin were administered in doses producing matched reductions (15%) in mean arterial pressure at constant heart rate. Anterior left ventricular great cardiac vein blood flow (thermodilution) was measured in 14 patients without angiographic anterior collateral supply. Global coronary sinus blood flow remained constant with both nitroprusside and nitroglycerin administration, despite significant reductions in mean arterial pressure. However, nitroglycerin reduced great vein flow by 25 +/- 17% and nitroprusside by 10 +/- 16% (p less than 0.01). Subgroup analysis indicated that the nitroglycerin-nitroprusside regional blood flow differences were more pronounced in patients without significant left anterior descending coronary artery narrowing. Neither vasodilator produced significant differences in arterial-coronary sinus oxygen or lactate contents, calculated myocardial oxygen consumption, left ventricular dP/dt, or electrocardiographic or clinical signs of myocardial ischemia. Despite qualitatively similar hemodynamic effects, comparisons of vasodilator-induced relative reductions in normally supplied anterior left ventricular regional coronary blood flow suggest a mechanism of the reported beneficial effects of nitroglycerin on potentially ischemic myocardial regions.     

Effect of nitroglycerin on coronary collateral function during exercise evaluated by quantitative analysis of thallium-201 single photon emission computed tomography

A noninfarcted, entirely collateral-dependent myocardial region provides an opportunity to assess the effect of nitroglycerin on coronary collateral function during exercise. Stress thallium-201 computed tomography was performed in seven patients with effort angina and no history of myocardial infarction, both before and after nitroglycerin (0.3 mg). All patients had single-vessel disease with total or subtotal (99% with delay) occlusion of proximal left anterior descending coronary artery and well-developed collaterals. The pressure-rate product, mean blood pressure, and heart rate at peak exercise did not differ before and after nitroglycerin. The size of the perfusion defect and the severity of ischemia during exercise estimated by quantitative analysis of thallium-201 single photon emission computed tomography were significantly less after nitroglycerin administration (extent score: 23 +/- 17 vs 7 +/- 9, p less than 0.01; severity score: 20 +/- 22 vs 3 +/- 4, p less than 0.05). The pressure-rate products at peak exercise did not differ before and after nitroglycerin, which suggested that the reduction in perfusion defect size was unlikely to be the result of decreased myocardial oxygen consumption. These results suggest that nitroglycerin improved coronary collateral function during exercise and thus prevented exercise-induced myocardial ischemia.     

The effects of ventricular asynchrony on myocardial perfusion

Asynchronous depolarization and contraction sequence, secondary to intraventricular conduction defects or to permanent right ventricular apical pacing, is associated with adverse effects that may be clinically evident in the failing heart. Experimental and clinical studies have suggested that asynchronous ventricular contraction deteriorates left ventricular performance and induces unfavourable left ventricular remodelling. Although such contraction does not appear to affect resting coronary artery blood flow, it increases endomyocardial pressure during diastole and decreases regional myocardial perfusion in the interventricular septum. The magnitude of these effects may correlate with the duration of the asynchrony. Despite these detrimental effects, there is no evidence that ventricular asynchrony reduces collateral myocardial blood flow, myocardial oxygen consumption or cardiac efficiency, neither in patients with normal coronary arteries, nor in patients with coronary artery disease. Furthermore, in patients with acute ischaemic syndromes, ventricular asynchrony exerts a neutral effect on the ischaemic myocardium. Cardiac resynchronization therapy improves left ventricular systolic and diastolic function without an increase in myocardial oxygen consumption or energy cost. This therapy may decrease the inhomogeneity in regional oxidative metabolism, myocardial perfusion and cardiac efficiency. Further experimental and clinical studies are needed on this area.     

SIN-1 has no direct myocardial anti-ischemic action

Anti-ischemic drugs may develop their cardiac activity via peripheral (reduction in preload and/or afterload) or cardiac (coronary vasculature, myocardial cell metabolism) effects. The aim of the study was to investigate whether SIN-1, the active metabolite of molsidomine, develops a direct myocardial anti-ischemic property. Three groups of seven patients each were treated with 0.4 mg SIN-1 administered via either the intracoronary (IC) or intravenous (IV) route, or with placebo in a double-blind randomized investigation. SIN-1 had no influence on either the ischemic parameters in the surface electrocardiogram (ECG) or the intracoronary ECG. There was also no change in peripheral or central hemodynamics or in the severity of angina following this low IC or IV dosage. There is no evidence of a direct myocardial anti-ischemic response of SIN-1. The well known anti-ischemic activity of SIN-1 or molsidomine has to be attributed to the proven peripheral and cardiac vascular responses.     

Effect of sublingually administered nitroglycerin on regional myocardial blood flow in patients with coronary artery disease.

The effect of sublingually administered nitroglycerin on regional myocardial specific blood flow (in ml/min per 100 g tissue) was evaluated with a xenon-133 washout technique in 31 patients in a resting nonstressed state. Eight patients had normal coronary arteriograms (Group 1), 12 had coronary artery disease without collateral vessels (Group 2) and 11 had coronary artery disease with collateral vessels (Group 3). Although nitroglycerin caused a similar decrease in mean arterial blood pressure and blood pressure-heart rate product in all three groups, the decrease in regional myocardial blood flow was significantly less in Group 3 (-8+/-6% [mean+/-standard error of the mean]) than in Group 1 (-31+/-5%), P less than 0.05); an intermediary decrease occurred in Group 2 (-23+/-5%). Within Group 3, there was a mean increase in regional myocardial blood flow after nitroglycerin in the five patients whose collateral vessels were of a higher angiographic grade and arose from non-stenosed coronary arteries, whereas a reduction was observed in the six patients with none or only one of these findings (+10+/-7% versus -23+/-3%, P less than 0.001). This study suggests that even in the resting state, in some patients with coronary artery disease enhancement of regional myocardial blood flow can occur after sublingual administration of nitroglycerin and is probably mediated through well functioning collateral vessels. It is possible that the drug's effects on both the coronary and systemic circulation may relieve angina in some patients with coronary artery disease.     

Nitroglycerin-resistant coronary spasm treated with intracoronary linsidomine chlorhydrate (SIN-1)

Spontaneous left anterior descending coronary artery spasm occurred in two patients during coronary angiography. After intravenous injection of 0.75 mg of nitroglycerin, the narrowing was unchanged in one patient and only partially relieved in the other. The coronary narrowing completely disappeared after intracoronary injection of 1 mg of the active metabolite of molsidomine, linsidomine chlorhydrate (SIN-1). In the first patient, this injection was performed just prior to the initiation of coronary balloon dilatation, which was then cancelled. Although rare, these two observations demonstrate the limitations of the intravenous use of nitroglycerin during diagnostic coronary angiography and point out the efficacy of intracoronary administration of SIN-1.     

Role of nitroglycerin in acute myocardial infarction

Intravenous nitroglycerin lowers left ventricular filling pressure and systemic vascular resistance in patients with acute myocardial infarction. At lower infusion rates (less than 30 micrograms/min) nitroglycerin acts principally as a venodilator, while at higher infusion rates a balanced venous and arterial dilating effect is seen. Patients with left ventricular failure demonstrate increased or maintained stroke volumes, while patients without failure will show a decrease in stroke volume. All hemodynamic subgroups will show a reduction in left ventricular filling pressures and in electrocardiographic evidence of regional myocardial ischemia. Longer-term infusions (24-48 h) have been associated with a reduction in short-term mortality and evidence of myocardial preservation, as evidenced by improved left ventricular function or indices of infarct size. Studies comparing intravenous nitroglycerin and sodium nitroprusside have revealed increases in intercoronary collateral flow with nitroglycerin, in contrast to decreases with nitroprusside, suggesting a coronary steal with nitroprusside. Current clinical practice would recommend intravenous nitroglycerin as initial adjunctive therapy for patients receiving intravenous thrombolytic therapy and/or acute percutaneous transluminal angioplasty within 4-6 h of the onset of symptoms of acute myocardial infarction, with the goal of optimizing collateral flow until reperfusion can be accomplished. Patients treated later than 6 but less than 12-14 h after symptom onset should still receive intravenous nitroglycerin for 24-48 h with the hope of reducing infarct size. Likewise, congestive heart failure and arterial hypertension complicating acute infarctions as well as postinfarction unstable angina are additional current indications for the use of intravenous nitroglycerin in patients with acute myocardial infarction.     

Mechanisms of action of the organic nitrates in the treatment of myocardial ischemia.

Nitroglycerin and the long-acting nitrates are widely used in all of the anginal syndromes and have proven effectiveness in relieving or preventing myocardial ischemia. Recent developments into nitrate mechanisms of action provide new insights as to the many anti-ischemic effects of these agents. Important concepts relating to coronary arterial endothelial function are germane to nitrate therapy. Endothelial-derived relaxing factor (EDRF) is presently believed to be nitric oxide (NO), which exerts vasodilatory and/or antiplatelet actions by increasing intracellular cyclic guanosine monophosphate as a result of activation of the enzyme guanylate cyclase. In the setting of coronary atherosclerosis, or even hyperlipidemia without histologic vascular disease, endothelial dysfunction may be present, promoting a vasoconstrictor/proplatelet aggregatory milieu. Nitroglycerin and the organic nitrates are NO donors; NO is the final product of nitrate metabolism, and in the vascular smooth muscle NO induces relaxation, resulting in vasodilation of arteries and veins. In the presence of inadequate EDRF production and/or release, it appears that nitroglycerin may partially replenish EDRF-like activity. Nitrates have long been known to have major peripheral circulatory actions resulting in a marked decrease in cardiac work. Venodilation and arterial relaxation result in a decrease in intracardiac chamber size and pressures, with a resultant decrease in myocardial oxygen consumption. In addition, a variety of direct coronary circulatory actions of the nitrates have been documented. These include not only epicardial coronary artery dilation, but the prevention of coronary vasoconstriction, enhanced collateral flow, and coronary stenosis enlargement. Recent work suggests that the nitrates may also act by preventing distal coronary artery or collateral vasoconstriction, which can reduce blood flow downstream from a total coronary obstruction. Thus, there are many anti-ischemic mechanisms of action by which nitroglycerin and the organic nitrates may be beneficial in both acute and chronic ischemic heart disease syndromes. The unique salutory effects of the nitrates in subjects with left ventricular dysfunction or congestive heart failure make these drugs particularly attractive for patients with abnormal systolic function and intermittent myocardial ischemia. Finally, the emergent role of intravenous nitroglycerin in acute myocardial infarction offers new prospects that nitrate therapy may prove to be beneficial in acute myocardial infarction as well as postmyocardial infarction for the reduction of left ventricular remodeling.     

冠状动脉内注射乌拉地尔对急性心肌梗死心肌灌注和心功能的影响

目的:探讨乌拉地尔对急性心肌梗死(AMI)急诊经皮冠状动脉介入治疗(PCI)患者心肌灌注和心功能的影响。方法:对经急诊PCI治疗的AMI患者54例,随机分为乌拉地尔组、硝酸甘油组和对照组。分别于经皮腔内冠状动脉成形术前冠状动脉内注射乌拉地尔、硝酸甘油、生理盐水。观察PCI术前、术后心肌梗死溶栓试验(TIMI)血流、校正的TIMI帧计数(cTFC)、心肌充血分级(MBG)、ST段回落、心肌坏死指标、左心室射血分数(LVEF)及住院期间主要心血管不良事件(MACE)。结果:乌拉地尔组与硝酸甘油组和对照组相比,PCI后cTFC降低、MBG增加、ST段回落增加、LVEF增加、CK和TnT峰值降低(P均<0.01)。结论:乌拉地尔可改善AMI急诊PCI患者冠状动脉血流、心肌灌注和左心室收缩功能,减少梗死面积,不增加住院期间MACE。     

Efficacy of combined therapy using coronary reperfusion and elective percutaneous transluminal coronary angioplasty for acute myocardial infarction

The effects of elective percutaneous transluminal coronary angioplasty (PTCA) performed one month after coronary reperfusion therapy in patients with acute myocardial infarction (AMI) were observed using exercise Tl-201 myocardial scintigraphy performed before and after PTCA. Myocardial perfusion in Tl-201 scintigraphy was significantly greater in the early (less than 4 hours) and late (4-9 hours) reperfusion groups than in the total occlusion group one month after the onset of AMI. Both reperfusion groups showed significant improvement in myocardial perfusion after elective PTCA; whereas, the total occlusion group showed no significant improvement. In the early reperfusion group, there were no significant differences in myocardial perfusion between those with well developed and those with poorly developed collateral circulations one month after the onset of AMI. However, in the late reperfusion group, myocardial perfusion was greater in those with well developed collateral circulations compared to those with poorly developed collateral circulations. The grade of myocardial perfusion in the late reperfusion group with poorly developed collateral circulations did not differ significantly from that of the total occlusion group. There was significant improvement of myocardial perfusion in the early and late reperfusion groups with well developed collateral circulations after elective PTCA; whereas, no significant improvement was observed in the late reperfusion group with poorly developed collateral circulations. These findings indicate that the time interval from the onset of AMI to reperfusion and the grade of development of collateral circulations are the major determinants of myocardial perfusion after elective PTCA and after reperfusion therapy.     

Effects of nitroglycerin in patients with angina, normal coronary arteries, and left ventricular hypertrophy

The coronary hemodynamic and left ventricular mechanical responses to nitroglycerin were studied in eight patients with angina, normal coronary arteries, and pressure overload left ventricular hypertrophy (POLVH) and in five control subjects. Elevated mean and end-diastolic pressure and end-diastolic meridional stress characterized the POLVH group, although systolic meridional stresses were not significantly different from the control group. Thermodilution coronary sinus flow and estimated myocardial oxygen consumption declined significantly following nitroglycerin in both patient groups. Systolic and diastolic mechanical loads also decreased in both groups, although diastolic tone remained elevated in the patients with POLVH. The decrease in coronary sinus flow in the POLVH group was in excess of that expected from the decrease in systolic mechanical load, which suggests a combination of perfusion pressure-dependent decreases in coronary flow as well as an increased resistance to coronary inflow in these patients. The beneficial clinical response to nitroglycerin may reflect the lowered myocardial metabolic demand as well as the decrease in diastolic myocardial tensile and compressive forces.     

Beneficial actions of nitrates in cardiovascular disease

Nitroglycerin and the long-acting nitrates have been used in cardiovascular medicine for > 100 years. Nitrates are widely utilized for the various anginal syndromes and are also used in congestive heart failure and patients with left ventricular dysfunction. The potential mechanisms for relief of myocardial ischemia with nitrates are multiple. The nitrovasodilators are a related group of drugs that result in the formation of nitric oxide (NO) within vascular smooth muscle cells. NO stimulates the enzyme guanylate cyclase, which results in increases in cyclic guanosine monophosphate and vasodilation. In the presence of atherosclerosis, endothelial dysfunction is ubiquitous and associated with decreased NO availability, probably due to increased destruction of NO by free radical anions. Nitrovasodilators, including the nitrates, supply exogenous NO to the vascular wall and improve the vasodilator state. When nitrates are administered, endothelial-dependent stimuli cause relaxation rather than constriction in the setting of endothelial dysfunction. Nitrates also have antiplatelet effects, and recent evidence confirms that these drugs decrease platelet aggregation and thrombosis formation. This may play an important role in the therapy of acute unstable myocardial ischemia, including unstable angina and myocardial infarction. Nitrate hemodynamic effects have been long known. They are primarily modulated through a decrease in myocardial work that results from smaller cardiac chambers operating with lower systolic and diastolic pressures. These changes are caused by a redistribution of the circulating blood volume away from the heart to the venous capacitance system, with a fall in venous return to the heart. The afterload or arterial effects of nitrates are also useful in decreasing myocardial oxygen consumption. Considerable evidence confirms a variety of mechanisms whereby nitrates increase coronary blood flow, including epicardial coronary artery dilation, stenosis enlargement, enhanced collateral size and flow, improvement of endothelial dysfunction, and prevention or reversal of coronary artery vasoconstriction. These effects help increase nutrient coronary blood flow to zones of myocardial ischemia. Recent data with the nitroglycerin patch confirm that myocardial ischemia is decreased after nitrate administration. Nitroprusside, another nitrovasodilator, is a commonly used intravenous agent for lowering arterial pressure and left ventricular filling pressure. This drug is highly effective for the treatment of acute or severe hypertension and congestive heart failure. However, there are data suggesting that nitroprusside may be deleterious in the presence of acute myocardial ischemia, perhaps by shunting blood away from zones of jeopardized myocardial blood flow. Therefore, nitroprusside cannot be recommended to treat myocardial ischemia; intravenous nitroglycerin should be used in this context.     

Importance of maintaining systemic blood pressure during nitroglycerin administration for reducing ischemic injury in patients with coronary disease. Effects on coronary blood flow, myocardial energetics and left ventricular function.

Because of the controversy concerning the effects on myocardial ischemia of maintaining systemic pressure concomitant with administration of nitroglycerin, this study was undertaken of the actions of nitroglycerin, with and without simultaneous phenylephrine infusion, on coronary blood flow, myocardial energetics and left ventricular function in 17 patients with multivessel coronary artery disease. Five minutes after sublingual administration of 0.4 mg of nitroglycerin, mean arterial pressure, left ventricular filling pressure, cardiac index and coronary sinus blood flow were reduced (P < 0.05) from control values. With mean arterial pressure raised to control level with phenylephrine in 10 patients (Group I), values for coronary sinus blood flow, myocardial perfusion gradient, cardiac efficiency index and ratio of coronary sinus flow/cardiac output all increased (P < 0.05) compared with values in 7 patients receiving only nitroglycerin (Group II) and in patients receiving nitroglycerin before phenylephrine in Group I and with the values in 7 patients who received no phenylephrine. Left ventricular function and coronary vascular resistance were unchanged (P > 0.05) from control values by the addition of phenylephrine to nitroglycerin. Because myocardial oxygen extraction decreased while coronary sinus flow increased, the phenylephrine-induced increase in coronary flow was not due to augmented cardiac oxygen demands. Thus, preservation of systemic pressure concomitant with nitroglycerin enhances myocardial perfusion. From these findings, with greater nitroglycerininduced decreases in mean arterial pressure and coronary flow in patients with acute ischemia, it appears that phenylephrine with nitroglycerin may particularly improve myocardial energetics.     

The effect of some antianginal drugs on the myocardial perfusion in patients with ischaemic heart disease

78 patients with ischaemic heart disease were examined clinically and by exercise test. Their myocardial perfusion was investigated with the aid of perfusion scintigraphy using 201Tl. It was proved that the myocardial 201Tl-scintigraphy accurately detected the presence and localization of ischaemic areas in patients with IHD, with or without a history of myocardial infarction. A combined application of scintigraphy and ergometric exercise test detected with sufficient reliability the zones of transient ischaemia; this is of a great clinical value in patients with negative or equivocal results of the exercise test. The beneficial effects of nitroglycerin, Nitrong, and molsidomine (Corvaton) manifested themselves by reducing the heterogeneity of myocardial perfusion, the extent of the zone of impaired perfusion at rest, and preventing or reducing the ischaemic reaction during exercise.     

Role of coronary collateral vessels during transient coronary occlusion during angioplasty assessed by hemodynamic, electrocardiographic and metabolic changes

The clinical role of collateral vessels was evaluated during transient coronary occlusion by percutaneous transluminal coronary angioplasty in 22 patients with (8) and without (14) collateral vessels. Coronary occlusion pressure, the ratio of mean coronary occlusion pressure to mean aortic pressure and myocardial perfusion pressure at 40 s of balloon inflation were significantly higher in patients with than in patients without collateral vessels. The changes in left ventricular systolic and end-diastolic pressure, maximal rate of rise of left ventricular pressure (peak dP/dt) and maximal rate of fall of left ventricular pressure (negative peak dP/dt) during balloon inflation were less in patients with than in patients without collateral vessels. Myocardial lactate was produced in patients without collateral vessels but not in those with such vessels. Marked ST segment elevation in the electrocardiogram occurred in patients without collateral vessels but either ST segment depression or mild ST segment elevation was observed in patients with collateral vessels. This study indicates that collateral vessels limit myocardial ischemia during coronary occlusion, probably as a result of increased myocardial perfusion pressure.     

Improvement of preservation with cardioplegic solution by nitroglycerin-induced delayed preconditioning is mediated by calcitonin gene-related peptide.

Improvement of preservation with cardioplegic solution by nitroglycerin-induced delayed preconditioning was studied in the isolated rat heart. The isolated rat heart was arrested using St. Thomas Hospital solution, and then reperfused with normothermic Krebs-Henseleit solution for 40 min after a 4-h hypothermic ischemic period. Heart rate, coronary flow, left ventricular pressure and the maximum value of the first derivatives of left ventricular pressure (+/-dp/dt(max)) were recorded, and plasma concentrations of CGRP-like immunoreactivity (CGRP-LI) and nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha) in myocardial tissues, and creatine kinase in coronary effluent were measured. Delayed preconditioning was induced by i.v. injection of nitroglycerin 24 h before the experiment. Nitroglycerin (60 microg/kg or 120 microg/kg) caused an improvement of cardiac function, a decrease in the release of creatine kinase in coronary effluent and a decrease in the content of TNF-alpha in myocardial tissues. Nitroglycerin significantly increased plasma concentrations of CGRP and NO. After pretreatment with capsaicin, which depletes neurotransmitters in sensory nerves, or methylene blue, a selective guanylate cyclase inhibitor, the protection and the elevated release of CGRP induced by nitroglycerin were abolished. The present study suggests that improvement of preservation with cardioplegic solution by nitroglycerin-induced delayed preconditioning is due to stimulation of CGRP release in the rat heart, and that the protection of CGRP-mediated nitroglycerin is related to inhibition of TNF-alpha production.     

Paradoxical deterioration of left ventricular asynergy after administration of nitroglycerin

The effects of nitroglycerin on segmental asynergy were studied by 2-dimensional echocardiography. Forty-five patients with coronary artery disease and segmental wall motion abnormality at rest were examined, 31 with Q-wave and 14 with only ST-T abnormalities. Left ventricular (LV) echocardiograms were recorded from the LV apex in 4 planes, obtained by systematically rotating the transducer at 45 degrees intervals around the mitral office, using a mechanical device. Sixteen LV segments were analyzed in each patient on real-time display by 2 observers independently. The wall motion analysis was classified as normal, hypokinetic, akinetic or dyskinetic. Of 720 segments, 596 were agreed on by 2 observers in the assessment of wall motion before and after administration of nitroglycerin: 334 segments (56%) showed no change in wall motion, 206 (35%) showed improvement of wall motion and 56 (9%) showed worsening of myocardial asynergy after nitroglycerin. These data suggest that administration of nitroglycerin may result in unexpected worsening of segmental asynergy. This may be secondary to an adverse effect of a decrease in perfusion pressure in critically occluded arteries or may represent a coronary steal phenomenon.     

Effects of molsidomine on global and regional left ventricular function at rest and during exercise in patients with angina pectoris

Although the antianginal properties of molsidomine are well-established, little is known about its effects on global and regional left ventricular dysfunction secondary to myocardial ischemia. In the present study, left ventricular performance was assessed by radionuclide ventriculography at rest and during exercise in 15 patients with coronary artery disease (CAD) and angina pectoris before and after the administration of 2 mg molsidomine sublingually. Gated blood pool studies were performed for evaluation of left ventricular ejection fraction (LVEF) and regional wall motion by analyzing amplitudes and phases of the first Fourier coefficient of regional time–activity curves. In contrast to normal subjects, during the control study period LVEF in patients with CAD decreased from 50.9% at rest to 42.7% during exercise (p<0.01). After molsidomine the resting values of LVEF increased slightly from 50.9% to 55.7% (p<0.05). Exercise values of LVEF increased from 42.7% to 51.3% (p<0.01). This is usually associated with amelioration of anginal pain and ischemic ST depression in the precordial ECG (0.15 mV vs. 0.09 mV; p<0.01). Before molsidomine, regional wall motion deteriorated from rest to exercise in 11 of 15 patients. These wall motion abnormalities usually expressed themselves as newly developed regions of left ventricular dysfunction (8 patients) or as accentuation of pre-existing contraction disturbances (3 patients). After molsidomine, regional wall motion did not show consistent changes at rest. Comparison during exercise showed enhanced regional function in 10 of the 15 patients after administration of the drug. At rest a slight but significant increase in heart rate was measured following molsidomine, whereas exercise heart rate remained unchanged. Only minor changes in systolic blood pressure occurred after molsidomine (rest, 143 mmHg vs. 134 mmHg; p<0.05; exercise, 177 mmHg vs. 174 mmHg; p>0.10). In conclusion, assessment of left ventricular performance at rest and during exercise in patients with CAD revealed significant improvement of global and regional left ventricular function, indicating reduction of myocardial ischemia. These effects may result primarily from reduction of left ventricular wall tension.