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)     

Effects of intravenous nitroglycerin on left ventricular function and ST segment changes in acute myocardial infarction.

It has been shown previously that 30-minute infusions of intravenous nitroglycerin in patients with acute myocardial infarction are able to lower left ventricular filling pressure and improve left ventricular function while lowering mean arterial pressure by only 7 mmHg (0.9 kPa). A decrease in sigmaST in praecordial ST segment mapping studies during nitroglycerin infusion in patients with anterior infarction suggested a decrease in the extent of myocardial ischaemia. In the present study, 30 patients with acute myocardial infarction received 1- to 3-hour infusions of intravenous nitroglycerin at infusion rates sufficient to lower mean arterial pressure by an average of 22 mmHg (2.9 kPa). An improvement in ventricular function was noted in that subgroup of patients with the msot severe left ventricular dysfunction. All patients with anterior myocardial infarction underwent serial ST segment mapping and, irrespective of the presence or absence of left ventricular failure, showed a decrease in sigmaST during nitroglycerin infusion (P less than 0.005). These findings suggest that infusion of nitroglycerin improves left ventricular function and/or alters left ventricular compliance in patients with left ventricular failure complicating myocardial infarction and furthermore decreases sigmaST in all patients, irrespective of the presence or absence of left ventricular failure, suggesting that the extent of myocardial ischaemia is decreased.     

Intravenous nitroglycerin unloading in acute myocardial infarction.

Low-dose intravenous nitroglycerin infusion can be safely administered during acute myocardial infarction to unload the left ventricle and salvage ischemic myocardium and left ventricular geometry and function. In an experimental conscious dog model, low-dose infusion titrated to decrease mean blood pressure by 10% over the first 6 hours after coronary artery ligation resulted in 51% decrease in infarct size, 54% decrease in preload, and more than 50% increase in collateral blood flow. The same benefits were seen when methoxamine was given to counteract that 10% decrease in blood pressure. Similar short-term nitroglycerin infusion also limited remodeling in the dog model. More important, no myocardial salvage was seen with excessive nitroglycerin-induced hypotension to levels less than 80 mm Hg. Clinically, prolonged low-dose nitroglycerin infusion was evaluated in a prospective, randomized, single-blinded, placebo-controlled study of 310 patients with acute infarction: 154 received nitroglycerin and 156 received placebo. Nitroglycerin was titrated to reduce mean blood pressure by 10% in normotensive patients and up to 30% in hypertensive (blood pressure greater than 140/90 mm Hg) patients, but not to less than 80 mm Hg. Nitroglycerin produced several benefits compared with placebo: (1) smaller creatine kinase infarct size; (2) less regional left ventricular dysfunction, better global ejection fraction, and less infarct expansion and thinning; (3) better clinical functional status and hemodynamics; (4) fewer inhospital complications such as acute left ventricular failure and dilation due to marked infarct expansion, left ventricular thrombus, cardiogenic shock, and infarct extension; and (5) fewer deaths up to 1 year in patients with anterior Q-wave infarction.     

Effects of nitrate therapy on ventricular remodeling and function

The hypothesis that nitrates might effectively limit left ventricular remodeling and improve function after acute myocardial infarction has been tested in experimental and clinical models, with special attention to the pathophystologic evolution of remodeling. In 1 clinical study, before the thrombolytic era, the effects of low-dose intravenous nitroglycerin infusion for the first 48 hours during acute myocardial infarction was evaluated in a prospective, randomized, single-blinded, placebo-controlled study of 310 patients (154 nitroglycerin; 156 placebo). Nitroglycerin proved to be safe and produced several benefits compared with placebo: (1) smaller infarct size; (2) less left ventricular dysfunction; (3) less infarct expansion and thinning; (4) better functional status; (5) fewer in-hospital complications such as left ventricular failure, left ventricular thrombus, cardiogenic shock, and infarct extension; and (6) fewer deaths up to 1 year. Two subsequent clinical studies in the thrombolytic era, with low-dose intravenous nitroglycerin infusion during infarction over the first 48 hours followed by buccal nitrate (eccentric dose regimen) or placebo during healing over 6 weeks postinfarction, indicated that prolonged nitrate therapy effectively limited left ventricular remodeling and improved function further compared with placebo.     

IMPROVED LEFT VENTRICULAR FUNCTION DURING NITROPRUSSIDE INFUSION IN ACUTE MYOCARDIAL INFARCTION

In 15 patients with acute myocardial infarction intravenous infusion of the potent vasodilator, nitroprusside, produced an average 50% fall in the elevated left ventricular filling pressure and a modest reduction in arterial pressure (average 15·5%) without a change in heart-rate. Careful dose adjustment in several patients resulted in a significant fall in left ventricular filling pressure with little or no change in arterial pressure. Cardiac output consistently rose during nitroprusside infusion in patients with clinical signs of left ventricular failure or shock and a low control cardiac index, whereas output changed little in those patients with normal control cardiac index. A fall in pressure-time per minute as well as the fall in left ventricular filling pressure indicated a reduction in myocardial oxygen consumption during the vasodilator infusion. Drug infusion was usually accompanied by subjective improvement, including relief of dyspnœa and of chest pain, and reduction in ventricular irritability. These data suggest that vaso dilator therapy, by reducing left ventricular afterload, can improve left ventricular performance in patients with acute myocardial infarction. Such treatment may be a rational approach to the management of patients with heart-failure, pulmonary œdema, or early shock.     

Nitroglycerin in acute myocardial infarction

Nitroglycerin is an effective agent for reducing preload and afterload in acute myocardial infarction. Until two decades ago, it was considered to be contra-indicated in acute myocardial infarction because of fear of hypotension and reflex tachycardia. Recent animal studies indicated that prolonged low dose infusion during early stages of acute infarction, titrated to decrease mean arterial pressure by 10% but not below 80 mmHg, produced marked increase in collateral blood flow and decrease in infarct size. However, higher doses to further decrease blood pressure offset the beneficial effect on collateral flow and infarct size. More importantly, clinical studies have confirmed that low dose intravenous nitroglycerin is safe therapy during acute myocardial infarction for improving left ventricular performance, limiting infarct size and reducing infarct related complications.     

Arterial pressure as a determinant of left ventricular filling pressure after acute myocardial infarction

Left ventricular filling pressure has been used as a clinical guide to left ventricular function in patients with acute myocardial infarction. However, the contribution of spontaneous or induced changes in arterial pressure to left ventricular filling pressure has not been emphasized. In 26 patients left ventricular filling pressure and arterial pressure were monitored simultaneously for 1 to 5 days after acute myocardial infarction. Ventricular filling pressure averaged 20.7 mm Hg on day 1 and decreased to 12.7 by day 5. Systolic arterial pressure decreased from 146.6 to 107.4 mm Hg during this same period. These changes were significant for treated (P < 0.001) as well as untreated patients (P < 0.01). Fluctuations in arterial pressure occurring spontaneously or induced by isometric exercise, sublingual administration of nitroglycerin or infusion of nitroprusside were accompanied by similar changes in left ventricular filling pressure. These data indicate that a change in arterial pressure may be the most important determinant of a change in left ventricular filling pressure during the first few days after acute myocardial infarction.     

Comparative haemodynamic effects of transdermal vs intravenous nitroglycerin in acute myocardial infarction with elevated pulmonary artery wedge pressure

The comparative haemodynamic effects of transdermal and intravenous nitroglycerin were evaluated in 16 patients with haemodynamic and radiographic left heart failure following a recent myocardial infarction. After the control period patients were randomized to transdermal (10 mg(24 h)-1) or intravenous (mean dose: 40 +/- 9 micrograms min-1) nitroglycerin. Haemodynamic parameters were recorded after 0.5,1,2,6,12,18 and 24 h during administration of the drug and 2 h after drug discontinuation. After the washout period the alternate system of nitroglycerin administration was adopted, according to a cross-over design. No differences were found in baseline measurements. Transdermal nitroglycerin reduced the pulmonary artery wedge pressure after 0.5 h (from 21 +/- 5 to 16 +/- 5 mmHg; P less than 0.05). The peak effect occurred at 2 h (12 +/- 5 mmHg). The improvement was sustained over 24 h. Transdermal nitroglycerin also significantly reduced mean pulmonary arterial and right atrial pressures (from 28 +/- 3 to 20 +/- 5 mmHg and from 6 +/- 3 to 2 +/- 2 mmHg at peak effect, respectively). Cardiac index increased from 2.5 +/- 0.6 to 2.8 +/- 0.8 l min-1 m-2 (P less than 0.05). There was no change in heart rate. Similar haemodynamic changes were observed after the intravenous infusion of nitroglycerin. Thus transdermal nitroglycerin is a safe and effective treatment of acute myocardial infarction with signs of left ventricular failure when an intravenous nitroglycerin infusion cannot be properly implemented.     

Effects of intravenous nitroglycerin on hemodynamics and ischemic injury in patients with acute myocardial infarction.

In 24 patients with acute myocardial infarction intravenous nitroglycerin in 2 different dosages was administered and the effect on hemodynamics and extent of myocardial ischemia was investigated. According to the initial left ventricular filling pressure (LVFP) the patients were divided in Group I: LVFP below 20 mm Hg (13 patients) and in Group II: LVFP above 20 mm Hg (11 patients). Following an infusion of 3 mg of nitroglycerin in the first and 6 mg in the second hour, a significant decrease (P less than 0.0001) in the filling pressure (in Group I from 15 +/- 4 to 9 +/- 3 (+/-1 SD) and in Group II from 28 +/- 11 to 16 +/- 7 mm Hg) was observed. The mean arterial pressure decreased in both groups by an average of 9 mm Hg. The changes in the heart rate were minimal. The cardiac output decreased in Group I from 4.4 +/- 1.0 to 3.9 +/- 0.8 1/min (P less than 0.005) whereas in the group with left ventricular failure it increased significantly from a lowered initial value (3.4 +/- 1.0 to 4.0 +/- 1.1 1/min) (P less than 0.001). By using precordial mapping for estimation of ischemic injury in 12 patient sigma ST elevation decreased from 14.6 +/- 11.9 to 12.2 +/- 9.8 mV at a dose of 3 mg/h (P less than 0.03). The dose of 6 mg/h, however, was less effective on the extent of myocardial ischemia than 3 mg/h. Thus, the dosage of nitroglycerin may be critical in respect to infarct size, despite the beneficial hemodynamic effects of the drug.     

Heart failure in acute myocardial infarction: comparing infusions of nifedipine and nitroglycerin]

The impact of intravenous infusion of nifedipine and nitroglycerin on invasive central hemodynamic parameters and microcirculation was compared in 94 patients with acute myocardial infarction complicated by heart failure. The artery dilating effects of nifedipine were associated with baseline peripheral vascular tone, so the comparison was made separately in the groups with and without vasoconstriction. Nifedipine seems to be beneficial in the management of heart failure due to acute myocardial infarction in patients with systemic vasoconstriction. In patients with severe pulmonary congestion and normal left ventricular afterload, the intravenous vasodilators are preferable.     

Nitrates in myocardial infarction

Summary Until two decades ago nitroglycerin was contraindicated in acute myocardial infarction (MI). Studies in the canine model demonstrated that low-dose intravenous (IV) infusion, carefully titrated to decrease mean blood pressure by 10% but not below 80 mmHg, during early stages of acute MI produced marked reduction of left ventricular (LV) preload, improvement in regional perfusion, and limitation of infarct size and remodeling. However, more IV nitroglycerin to decrease blood pressure further resulted in a paradoxical J-curve effect, with hypoperfusion and increased infarct size. Clinical studies have confirmed that low-dose IV nitroglycerin infusion for the first 48 hours after acute MI is safe, not only for improving performance in LV failure, but also for limiting ischemic injury, infarct size, remodeling, and infarct-related complications, including deaths in-hospital and up to 1 year. Recent studies suggest that more prolonged therapy with nitrates spanning the healing phase of acute anterior Q-wave MI can further limit LV remodeling and preserve function. Preliminary results of the recently completed ISIS-4 megatrial suggest, however, that long-term nitrate in patients with suspected MI in the 1990s does not improve survival significantly.     

Intravenous streptokinase in acute myocardial infarction (I.S.A.M.) trial: serial evaluation of left ventricular function up to 3 years after infarction estimated by radionuclide ventriculography. I.S.A.M. Study Group

The Intravenous Streptokinase in Acute Myocardial Infarction (I.S.A.M.) trial was a prospective, placebo-controlled, double-blind multicenter trial of high-dose short-term intravenous streptokinase in acute myocardial infarction administered within 6 h after the onset of symptoms. Global and regional left ventricular ejection fractions were determined by radionuclide ventriculography in a subset of 120 patients 3 days, 4 weeks, 7 months, 18 months and 3 years after acute myocardial infarction. In patients with anterior myocardial infarction, left ventricular ejection fraction was higher in the streptokinase than in the placebo group 3 days after acute infarction (49 +/- 14% vs. 40 +/- 11%, p = 0.02). This difference of about 10% units in ejection fraction persisted during the 3 year follow-up period. Among streptokinase-treated patients, regional left ventricular ejection fraction was higher within the infarct zone as well as in remote myocardium throughout the follow-up period. Among patients with inferior infarction, no significant differences between the treatment and control groups were demonstrable with respect to global and regional left ventricular ejection fraction. Thus, intravenous administration of streptokinase within 6 h after the onset of symptoms of acute myocardial infarction preserves left ventricular function over a period of greater than or equal to 3 years in patients with acute anterior myocardial infarction. It improves regional myocardial function within the infarct zone as well as in remote areas. In patients with acute inferior myocardial infarction, benefit from intravenous streptokinase is of only minor degree.     

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).     

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.     

Comparative hemodynamic effects of intravenous nitroprusside and oral prazosin in refractory heart failure

Beneficial effects of vasodilator therapy in heart failure have been amply described. Afterload reduction with intravenous nitroprusside improves hemodynamic values in patients with left ventricular dysfunction. The oral vasodilator prazosin was given to 10 patients with refractory heart failure, and its hemodynamic effects were compared with those of intravenous nitroprusside in the same patients. With prazosin, heart rate remained unchanged, mean arterial pressure decreased 13 percent (P < 0.01), left ventricular filling and mean pulmonary arterial pressures decreased 31 and 24 percent, respectively (both P < 0.01) and cardiac index and left ventricular stroke work increased by 31 and 30 percent, respectively (both P < 0.01). Resistance levels in the systemic and pulmonary vascular beds declined by 29 and 27 percent, respectively (both P < 0.01). The hemodynamic changes appeared 1 hour after administration of a single dose of oral prazosin and persisted for 6 hours.Intravenous infusion of nitroprusside resulted in similar changes in heart rate and arterial pressure but greater reduction in left ventricular filling and mean pulmonary arterial pressures (P < 0.05). Left ventricular stroke work index increased more with nitroprusside (P < 0.01); however, changes in cardiac index and systemic and pulmonary vascular resistance levels were identical. Further, systolic pressure-heart rate product (index of myocardial oxygen demand) decreased significantly with oral prazosin as well as nitroprusside. These results suggest that prazosin has salutary effects on cardiovascular hemodynamics in heart failure, probably because of its vasodilator properties. These effects are qualitatively similar to those observed with intravenous infusion of nitroprusside. However, quantitatively, intravenous nitroprusside is slightly more potent.     

Value of the replacement of intravenous trinitrin by oral trinitrin in the acute phase of myocardial infarction complicated by regressive left ventricular insufficiency

Left ventricular failure is a common complication of the acute phase of myocardial infarction. The most appropriate current treatment, when an increase in preload is the predominant or sole feature, involves nitroglycerin by infusion combined in varying degrees with diuretics. The aim of this study was to assess the value of maintenance treatment following intravenous nitroglycerin based upon a long acting nitrate derivative designed to achieve a hemodynamic result. Twenty patients with a mean age of 62 and with left ventricular failure during the acute phase of a myocardial infarction were studied. They were all treated with IV nitroglycerin using an automatic pump syringe. Pulmonary artery diastolic pressure, cardiac output, blood pressure and heart rate were measured hourly for six hours then every 6 hours. When PADP fell to below 18 mmHg, maintenance treatment with placebo or long acting nitroglycerin was given double-blind (10 patients were given long acting nitroglycerin and 10 patients the placebo). Pulmonary artery pressures, blood pressure and heart rate were measured every 2 hours for 8 hours, then at 12 and 24 hours. No significant difference was found in heart rate, blood pressure, cardiac output nor PADP (10 +/- 3.5 mmHg cf. 12 +/- 2.8 mmHg; NS) between the two groups. In total, maintenance treatment with long acting nitrate derivatives following IV nitroglycerin for hemodynamic purposes in patients with an acute myocardial infarction complicated by regressive cardiac failure would no appear to be necessary.     

Effect of reperfusion therapy for acute myocardial infarction on ventricular function and heart failure

Thrombolytic therapy reduces mortality and improves ventricular function in acute myocardial infarction. We review the short- and long-term effects of reperfusion after acute myocardial infarction on left ventricular function and heart failure. The beneficial effects of reperfusion may be achieved by immediate limitation of infarct size or through delayed improvement in ventricular remodeling. Infarct size is dependent on the area at risk, the time delay to reperfusion, the completeness and persistence of reperfusion, and collateral blood flow. The main prognostic parameters after myocardial infarction are vessel patency, infarct size, and ventricular volume and function. Initial infarct size and patency of the infarct-related artery are independent predictors of ventricular volume and function, as well as of survival in the long-term following acute myocardial infarction. The beneficial effects of a patent infarct-related artery are only evident if normal flow is achieved and maintained, and are dependent on the degrees of the residual stenosis. Thrombolytic therapy reduces the incidence of in-hospital congestive heart failure, and this improvement is sustained for at least 5 years. As only a fraction of patients with acute myocardial infarction currently receive thrombolytic therapy, heart failure after myocardial infarction can be reduced by administering thrombolytic therapy earlier to more patients with evolving acute myocardial infarction.     

Late thrombolytic therapy preserves left ventricular function in patients with collateralized total coronary occlusion: primary end point findings of the Second Mount Sinai-New York University Reperfusion Trial

The change in left ventricular ejection fraction from preintervention to predischarge was prospectively assessed in 393 patients with acute myocardial infarction. Within 12 h of symptom onset (mean 6.3 +/- 2.7 h), patients were randomly assigned to a double-blind intracoronary infusion of streptokinase, nitroglycerin, both streptokinase and nitroglycerin or conventional therapy without acute cardiac catheterization. Treatment effects were also assessed in prospectively defined angiographic subsets. There was a significant interaction between streptokinase and nitroglycerin (p less than 0.01), resulting in an increase in ejection fraction of 3.9 percentage units in the combined treatment arm (p less than 0.001). Patients with collateral flow to a totally obstructed infarct-related artery showed a significant improvement over those without collateral flow in the streptokinase (5.4 +/- 2.5%) and streptokinase-nitroglycerin (10.6 +/- 2.7%) arms, but not in the nitroglycerin arm. Time to treatment did not influence the change in ejection fraction. In patients with initial subtotal occlusion, thrombolytic therapy was of no short-term benefit because ejection fraction increased by 6% in all three intervention arms. These findings indicate that relatively late thrombolytic therapy results in significant myocardial salvage in those patients with collateralized total coronary occlusion. This benefit is potentiated by concomitant nitroglycerin therapy.     

Hemodynamic responsiveness to short- and long-acting vasodilators in left ventricular failure

Vasodilators acutely reduce afterload and improve hemodynamics in congestive heart failure. Intravenous nitroprusside reduces left ventricular filling pressure and increases cardiac output while modestly reducing blood pressure and not changing heart rate in patients with heart failure in whom this response is characteristic. Comparably reduced blood pressure during nitroprusside infusion in normal subjects or hypertensive patients without failure results in a decrease in cardiac output and tachycardia. Long-acting vasodilators are also effective in patients with congestive heart failure. Nitrates, predominant venodllators, decrease left ventricular filling pressure as much as nitroprusside does, but increase cardiac output less. Hydralazine, an arterial dilator, increases cardiac output similarly to nitroprusside but decreases filling pressure less. Combining hydralazine with nitrates results in hemodynamic effects almost identical to those of nitroprusside. The quinazoline derivatives, trlmazosin and prazosin, are also effective vasodilators, which act on both arteries and veins in patients with congestive heart failure. The hemodynamic response to vasodilators is influenced by the underlying hemodynamic status, as the change in cardiac output is directly related to base line ventricular filling pressure as well as systemic vascular resistance, and inversely related to the base line cardiac output. Response to vasodilators does not appear to be altered by age, diabetes, acute myocardial infarction or the cause of congestive myocardiopathy.     

Hemodynamics, circulating catecholamines and response to intravenous nitrate therapy in a specific subset of acute myocardial infarction: the hypertensive-hyperkinetic-coronary-active group

A specific subset of acute myocardial infarction was defined and named 'the hypertensive-hyperkinetic-coronary-active' subgroup. This subgroup included patients with acute myocardial infarction without pump failure or hypovolemia who continued to have hypertension and tachycardia, after relief of pain and who also had at least two recurrent ischemic episodes in the first days after a transmural event. Fifteen patients belonging to this group (group A) were studied in comparison with 15 other patients with acute myocardial infarction complicated by pump failure (group B). The alterations in hemodynamics, in circulating catecholamine levels and the clinical course during an intravenous infusion of isosorbide dinitrate were evaluated and the data obtained in the two groups were compared. The patients in group A had tachycardia, hypertension and upper normal filling pressures (pulmonary capillary wedge pressures: 15.8 +/- 1.8 mm Hg). They had high levels of circulating catecholamines (1,343 +/- 407 ng/l), a cardiac output of 5.9 +/- 0.6 liters/min and stroke work index of 78 +/- 11 (mean +/- SD). The effect of intravenous nitrates on the left ventricular function curves of the two groups was the following: a marked shift downward and slight shift to the left in group A, as opposed to a moderate but significant shift upward and marked shift to the left in group B. The episodes of recurrent ischemia subsided in 13 out of 15 patients from group A. It appears therefore that the hyperkinetic patients with acute infarction are characterized by a hypersympathetic response, a typical hemodynamic profile and a particular response to nitrate therapy directionally opposite to the changes obtained in patients with acute infarction complicated with failure.