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.     

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.     

Central and regional hemodynamic effects of intravenous isosorbide dinitrate, nitroglycerin and nitroprusside in patients with congestive heart failure

A triple crossover random design was used to compare the central and regional hemodynamic effects of intravenous isosorbide dinitrate, nitroglycerin and nitroprusside in 10 patients with low output congestive heart failure. Isosorbide dinitrate and nitroglycerin were infused in dose increments of 0.8 μg/kg body weight per min up to 4.0 μg/kg per min and nitroprusside in increments of 0.4 μg/kg per min up to 2.0 μg/kg per min. The central and regional hemodynamic responses of isosorbide dinitrate and nitroglycerin were similar;both effected a 10 to 35 percent reduction in pulmonary capillary wedge pressure, systemic blood pressure and vascular resistance and pulmonary arterial pressure and resistance with a 7 to 22 percent increase in stroke volume and cardiac output. Nitroprusside elicited a similar decrease in pulmonary capillary wedge pressure with a greater reduction (15 to 45 percent) in systemic blood pressure and resistance and pulmonary arterial pressure and resistance and greater augmentation of stroke volume and cardiac output (20 to 40 percent). Arterial oxygen saturation remained unchanged with isosorbide dinitrate and nitroglycerin and decreased slightly with nitroprusside. None of the drugs altered total body oxygen consumption. All three drugs decreased limb vascular resistance and elevated limb blood flow proportional to the degree of change in systemic vascular resistance and cardiac output. Isosorbide dinitrate and nitroglycerin did not alter renal vascular resistance, so that a mild reduction in renal blood flow was noted as systemic blood pressure decreased. Nitroprusside decreased renal vascular resistance; however, the concomitant decrease in arterial pressure resulted in no net change in renal blood flow. None of the three drugs altered hepatic blood flow or vascular resistance.

In low output congestive heart failure, these three drugs effect similar responses in preload, nitroprusside causing a greater change in afterload. Preferential vasodilation of regional vascular beds was noted with limb flow greater than hepatic and renal flow with isosorbide dinitrate and nitroglycerin and limb flow much greater than renal and greater than hepatic flow with nitroprusside.     

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)     

Effect of nitroprusside, nitroglycerin, propranolol and mannitol on the size of a myocardial infarct

Effects of nitroprusside, nitroglycerin, propranolol and mannitol on the size of infarcted and peri-infarction areas were examined in 276 patients with acute left-ventricular anterior myocardial infarction. The study involved an assessment of electrocardiograms from 35 precordial leads, and the measurement of central venous blood pressure, hemodynamic parameters, serum enzymes, acid-base state and, in some patients, the pressure inside the pulmonary artery, right and left cavities of the heart and the aorta, left-ventricular kinetocardiography, etc. All the drugs examined were shown to have a favourable effect on the size of the peri-infarction area and reduce the extent of myocardial infarction. Indications for each of the drugs have been worked out on a differential basis. A detailed analysis of ECG patterns from multiple chest leads under the action of nitroprusside, nitroglycerin, propranolol and mannitol is presented.     

Hemodynamic changes in patients with myocardial infarct complicated by acute left ventricular failure during combined nitroglycerin and dobutamine therapy

A total of 18 patients with acute myocardial infarction complicated by acute left ventricular failure were examined for their central hemodynamics. Intravenous nitroglycerin was shown to cause positive changes in central hemodynamic parameters, but it failed to normalize the hemodynamics in patients with baseline low blood pressure, as nitroglycerin induced a further reduction in blood pressure. A combined administration of nitroglycerin and dobutamine solutions contributes to hemodynamic normalization and is indicated for patients with acute myocardial infarction complicated by acute left ventricular failure at a baseline low blood pressure.     

序贯应用硝普钠与硝酸甘油治疗急性左心衰竭的临床观察

目的 探讨序贯应用硝普钠与硝酸甘油治疗急性左心衰竭的临床疗效。方法 将67例急性左心衰竭患者随机分为观察组34例及对照组33例,均予综合基础治疗,同时对照组给予硝普钠治疗,观察组给予硝普钠治疗后及时换用硝酸甘油治疗,对比2组疗效及不良反应。结果 2组治疗后均能有效改善血压、心功能,2组间心功能改善方面比较差异无统计学意义（P〉0．05）;观察组不良反应发生率显著低于对照组（P〈0．05）。结论 在抢救急性左心衰竭过程中,序贯应用硝普钠与硝酸甘油与单一应用硝普钠有同样的治疗效果,且不良反应更少。     

硝普钠并多巴胺治疗重症充血性心力衰竭临床观察

目的：研究硝普钠并多巴胺治疗重症充血性心力衰竭的临床疗效。方法：重症充血性心力衰竭患者64例,在常规治疗（吸氧、洋地黄制剂、利尿剂）的基础上,随机、双盲地给予硝普钠或硝酸甘油,按1：1随机分为硝酸甘油组（对照组）和硝普钠组（治疗组）,两组均联合应用多巴胺,用药前后检查超声心动图评估心功能,监测肝、肾功能,心率,血压变化及预后。结果：与硝酸甘油组比较,硝普钠并多巴胺治疗组患者的临床症状明显改善（93．8％：78．1％,P〈0．01）,治疗后两组收缩压、舒张压明显下降,左室舒张末内径明显缩小,左室射血分数明显加强（P均〈0．01）,且硝普钠组优于对照组（P〈0．05）。结论：使用血管扩张剂硝普钠,联合多巴胺治疗重症充血性心力衰竭有较好的协同作用,可有效地减轻心脏负荷,改善心脏收缩功能,而且患者的耐受性好,较为安全。     

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.     

Afterload reduction and cardiac performance. Physiologic basis of systemic vasodilators as a new approach in treatment of congestive heart failure.

Digitalis and diuretics constitute conventional therapy of congestive heart failure, but systemic vasodilators offer an innovative approach in acute and chronic heart failure of decreasing increased left ventricular systolic wall tension (ventricular afterload) by reducing aortic impedance and/or by reducing cardiac venous return. Thus, vasodilators increase cardiac output (CO) by diminishing peripheral vascular resistance (PVR) and/or decrease increased left ventricular end-diastolic pressure (LVEDP) (ventricular preload) by diminishing venous tone. Concomitantly, there is reduction of myocardial oxygen demand, thereby reliably reducing angina pectoris in coronary disease, and potentially limiting infarct size and ischemia provided systemic arterial pressure remains normal. The vasodilators produce disparate modifications of cardiac function depending upon their differing alterations of preload versus impedance: nitrates principally cause venodilation (decrease LVEDP); nitroprusside, phentolamine and prazosin produce balanced arterial and venous dilation (decrease LVEDP and increase CO) provided left ventricular filling pressure is maintained at the upper limit of normal; whereas hydralazine predominantly effects arteriolar dilation (increases CO). With depressed CO plus highly increased LVEDP and increased PVR, nitrates also induce some increase of CO by reducing PVR. Combined nitroprusside and dopamine synergistically enhance CO and decrease LVEDP. Mechanical counterpulsation aids nitroprusside in acute myocardial infarction. The 30-minute venodilator action of sublingual nitroglycerin is extended for 4 to 6 hours by cutaneous nitroglycerin ointment, by sublingual and oral isosorbide dintrate, and by oral pentaerythritol tetranitrate and sustained-release nitroglycerin capsules. Ambulatory oral vasodilator therapy is provided by long-acting nitrates (relieve pulmonary congestion); hydralazine (improves fatigue); prazosin alone, combined nitrate-hydralazine combined prazosin-hydralazine (improve both dyspnea and fatigue).     

Reduction of S-T segment elevation with infusion of nitroprusside in patients with acute myocardial infarction

The effect of infusion of sodium nitroprusside on S-T segment elevation was evaluated in 12 patlents with acute anterior myocardial infarction. Precordial 35 lead S-T segment maps were obtained in each patient immediately before and 10 minutes after infusion of 53 μ/min (range 20 to 100 μg/min) of nitroprusside. The following measurements were made from each S-T map: ∑ST (total S-T elevation in all leads), NST (number of leads with S-T elevation greater than 1 mm) and $\text{ST}$ (average S-T elevation in leads with more than 1 mm elevation). After administration of nitroprusside, evidence of myocardial ischemic injury as assessed by S-T mapping decreased in association with reduction of the myocardial oxygen consumption index of pressure-time per minute. Group mean values diminished significantly for ∑ST (41.7 to 28.6 mm, P <0.001), NST (20.3 to 14.6, P <0.001) and $\text{ST}$ (1.6 to 1.2 mm, P <0.005). Pressure-time per minute decreased from 2,690 to 2,372 mm Hg-sec/min (P <0.001). Because there was no significant relation (P >0.05) between reductions in S-T elevation and lower indexes of myocardial oxygen consumption, it is suggested that nitroprusside may possess a separate action of augmenting regional blood flow to ischemic myocardium. Evaluation with the precordial S-T mapping technique suggested that intravenous administration of nitroprusside was associated with evidence of reduced ventricular ischemic injury in patients with acute myocardial infarction. This effect appears to be related to reduction of myocardial oxygen demand by the peripheral cardiac unloading mechanisms of nitroprusside as well as to a possible direct action of the drug in improving regional blood flow to ischemic heart muscle.     

硝普钠和硝酸甘油治疗急性左心衰竭临床疗效比较

目的观察硝普钠和硝酸甘油治疗急性左心衰竭的临床疗效。方法选择2009年1月至2011年12月云南省第二人民医院心内科住院治疗的急性左心衰竭患者120例,随机分为硝普钠组和硝酸甘油组各60例,观察两组的临床疗效。结果治疗后两组患者的收缩压、舒张压、心率及尿量均优于治疗前（P〈0．05）。治疗后硝普钠组患者在收缩压、舒张压、心率及尿量改善方面优于硝酸甘油组（P〈0．05）。硝普钠组总有效率为93．3％,硝酸甘油组为78．3％（P〈0．05）。硝普钠改善心衰症状所需的时间更短。两组患者均未见明显的药物不良反应。结论在抢救急性左心衰时硝普钠较硝酸甘油更有优势。     

Afterload reduction in the management of postinfarction ventricular septal defect

The primary goal in the medical management of ventricular septal defect complicating myocardial infarction is to support cardiac function and control symptoms, if possible, for a period of 4 to 6 weeks. If the patient survives this period, surgical correction of the defect is technically easier and safer. In many cases, however, cardiac function is severely compromised, intractable biventricular failure develops, early operation is necessary and the likelihood of successful repair is diminished.

We recently treated two such patients by means of afterload reduction with nitroprusside. In one patient, sublingually administered isosorbide dinitrate was later used, and prolonged survival was achieved after surgery. Hemodynamic investigations in both cases demonstrated that nitroprusside improved cardiac output without necessarily decreasing mean arterial pressure. The effect of nitroprusside on pulmonary blood flow and left to right shunt was variable: One patient demonstrated a decrease in the ratio of pulmonary to systemic blood flow, and the other did not. We conclude that afterload reduction with either intravenous or oral agents is a potentially useful measure in the management of patients with ventricular septal defect complicating myocardial infarction.     

Effect of nitroprusside on regional myocardial blood flow in coronary artery disease. Results in 25 patients and comparison with nitroglycerin.

The effect of nitroprusside on regional myocardial specific blood flow (RMBF) was evaluated in 25 patients with the xenon-133 washout technique. Six patients were normal (group 1), six patients had coronary artery disease without collateral vessels (group 2), and thirteen patients had coronary artery disease with collateral vessels (group 3). In group 1, RMBF was unchanged following nitroprusside. RMBF decreased significantly in both group 2 and group 3, including seven patients in group 3 with high-grade collateral vessels. The results were compared to the effect of nitroglycerin in 31 patients previously studied using the same technique. Mean arterial pressure and pressure-rate product were comparably reduced by both drugs. In contrast to the findings with nitroprusside, after sublingual nitroglycerin RMBF decreased markedly in normals and increased in patients with coronary artery disease and high-grade collaterals. The data suggest that nitroprusside may primarily affect resistance vessels within the coronary circulation, as opposed to the effect of nitroglycerin on conductance vessels. Thus, nitroprusside could result in redistribution of blood flow away from ischemic areas and potentially increase ischemic injury in some patients with coronary artery disease.     

Effects of nitroprusside on myocardial blood flow and oxygen consumption in conscious lambs with an aortopulmonary left-to-right shunt

We studied the effect of vasodilation on regional myocardial blood flow and oxygen consumption of the left ventricular free wall by infusing 10 micrograms/kg/min sodium nitroprusside into 7-week-old conscious lambs with and without aortopulmonary left-to-right shunts. Resting myocardial oxygen consumption in the 13 shunt lambs was significantly higher than in the nine control lambs (989 +/- 104 [+/- SEM] vs. 432 +/- 41 mumol/min/100 g left ventricle). This was achieved by a significantly higher left ventricular myocardial blood flow (294 +/- 33 vs. 143 +/- 16 ml/min/100 g left ventricle) because the arteriovenous oxygen concentration difference across the left ventricular free wall was similar in shunt and control lambs. Infusion of nitroprusside did not significantly change myocardial oxygen consumption and regional myocardial blood flows at 10 and 50 minutes after the onset of the infusion. This occurred despite a substantial drop in aortic and left atrial pressures and stroke volume, which decreases wall stress as well as external work of the left ventricle. Heart rate, however, increased significantly. We postulate that, during infusion of nitroprusside, the potential decrease in myocardial oxygen consumption due to a decrease in wall stress and external work of the left ventricle is neutralized by the consequences of the increased heart rate. In view of this and because of its hemodynamic effects, we do not consider sodium nitroprusside useful in the treatment of circulatory congestion in patients with left-to-right shunts, normal arterial pressures, and normal systemic blood flows.     

Comparison of coronary hemodynamic effects of nitroprusside and sublingual nitroglycerin with anterior descending coronary arterial occlusion

This study compares the coronary hemodynamic effects of an infusion of nitroprusside and of sublingual nitroglycerin in the same patients. The coronary hemodynamic responses of the anterior left ventricular (LV) region to both drugs were studied in 9 patients whose anterior descending branch of the left coronary artery was filled by collaterals. Before and during administration of each drug (given in doses designed to produce similar changes in LV diastolic pressure), heart rate, LV and aortic pressure, and anterior regional flow, oxygen delivery and lactate metabolism were measured. Given in this manner, as expected, both drugs decreased the double product of heart rate and systolic pressure. Concomitant with these changes, anterior regional blood flow increased or decreased modest amounts or did not change with either drug. Similar directional flow changes or no change occurred in 6 patients and directionally different changes in the other 3 patients. The ratio of mean aortic pressure or of the double product to anterior regional flow consistently decreased during the administration of both drugs. Additionally, anterior regional myocardial oxygen uptake remained similar during both drug periods compared with control values. Anterior region lactate extraction was abnormal (less than 10%) in 4 of the 9 patients during the initial control period. Lactate extraction was usually normal during both the nitroprusside and the nitroglycerin periods. In general, coronary hemodynamic values were remarkably similar during both of these periods. Thus, although relative differences in systemic arterial and venous dilation were obtained with nitroprusside and nitroglycerin, similar and beneficial coronary hemodynamic changes generally occurred.     

Comparative evaluation of the efficacy of nitrosorbide and nitroglycerin in acute myocardial infarct patients

Intravenous isosorbide dinitrate and nitroglycerin administered within early hours of myocardial infarction have a marked antianginal effect, stabilize the size of necrotic focus and promptly control acute left-ventricular insufficiency. Unlike nitroglycerin, isosorbide dinitrate has a more lasting action and does not affect heart rate and arterial blood pressure. It can therefore be used more extensively in patients with acute myocardial infarction.     

Direct and reflex cardiostimulating effects of hydralazine

Increased cardiac output and heart rate after administration of hydralazine have been attributed to reflex activation of the cardiac sympathetic nerves secondary to the decrease in arterial pressure. However, some studies suggest that hydralazine has an additional direct cardiostimulatory effect. The present study was designed to investigate this possibility. Mean arterial pressure, percent change in myocardial contractile force using a Walton-Brodle strain gauge and heart rate were measured in eight open chest dogs anesthetized with sodium pentobarbital. After intravenous administration of hydralazine, 20 mg, myocardial contractile force increased on average by 27 percent and heart rate by 7 percent; mean arterial pressure decreased less than 10 percent. The same reduction of mean arterial pressure with sodium nitroprusside resulted in increases of only 10 percent in myocardial contractile force and 2 percent in heart rate. The differences between the drugs were statistically significant for heart rate (P < 0.05) and myocardial contractile force (P < 0.01). After reductions in mean arterial pressure exceeding 10 percent, the increases in heart rate and myocardial contractile force with either hydralazine or sodium nitroprusside were insignificantly different. Direct injection of 0.8 mg of hydralazine into a coronary artery in four dogs consistently increased myocardial contractile force in the area perfused whereas administration of sodium nitroprusside even in large doses exerted no local inotropic activity. The local effect of hydralazine was blocked by intravenous administration of propranolol. These results suggest that the increase in myocardial contractile force and heart rate after administration of hydralazine is the result not only of a reflex response to a decrease in blood pressure, as occurred with sodium nitroprusside, but also of direct beta adrenergic stimulation of myocardium.     

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.     

Isosorbide dinitrate for the relief of severe heart failure after myocardial infarction.

Severe congestive heart failure secondary to myocardial infarction remains a difficult management problem. Although intravenous vasodilators and mechanical assist devices have been reported to improve the depressed hemodynamic function, these interventions are limited to the intensive care unit and cannot be used for long-term management. This study evaluates the hemodynamic and symptomatic response to sublingual administration to isosorbide dinitrate (5 to 10 mg) in seven consecutive patients with severe congestive heart failure after anterior wall myocardial infarction. Serial measurements of mean right atrial and pulmonary arterial end-diastolic pressure, mean blood pressure, heart rate and cardiac output were obtained during the control period and during the 4 hours after administration of isosorbide dinitrate. The peak response occurred approximately 30 minutes after drug administration with an 83 percent reduction in mean right atrial pressure (from 6 to 1 mm Hg, P less than 0.02), a 36 percent reduction in pulmonary arterial end-diastolic pressure (from 25 to 16 mm Hg, P less than 0.0001) and a 6 percent reduction in mean blood pressure (from 94 to 88 mm Hg (P less than 0.05). There were small but statistically not significant increases in cardiac index (from 2.3 to 2.6 liters/min per m2 and stroke work index (from 26 to 32 gm/beat per m2). The total systemic vascular resistance was reduced by 5 percent from 1,605 to 1,518 dynes sec cm-5 (P less than 0.10). The baseline heart rate of 105 beats/min was not significantly changed. The reduction in pulmonary arterial end-diastolic pressure became statistically significant (P less than 0.05) between 15 and 30 minutes after administration of isosorbide dinitrate and remained significant for 3 to 4 hours. This reduction of pulmonary arterial end-diastolic pressure to less than 22 mm Hg was associated with relief of the patients' pulmonary symptoms. The response to nitroglycerin (0.4 mg) was similar in magnitude but of much shorter duration (approximately 15 minutes for nitroglycerin versus 4 hours for isosorbide dinitrate in patients with and without congestive heart failure. The slope (calculated by dividing the change in cardiac index or stroke work index by the change in pulmonary arterial end-diastolic pressure) was significantly (P less than 0.05) depressed in the patients with congestive heart failure. These data demonstrate that the symptomatic pulmonary venous hypertension can be effectively relieved by isosorbide dinitrate without further compromising left ventricular function.