Circulatory effects of intravenous and oral atenolol in acute myocardial infarction.

The hemodynamic dose-response effects of intravenous (0.05 and 0.10 mg/kg) and oral (50 and 100 mg) atenolol were compared in a randomized between-group study of 24 men within seventeen hours of an acute uncomplicated myocardial infarction; 6 subjects were evaluated in each of the four groups. Hemodynamic variables were determined over a one-hour control period, following which the randomized dose of atenolol was administered and measurements repeated at 15 (intravenous therapy only), 30, 60, 90, 120, 180, 240, 300, and 360 minutes. The peak hemodynamic effect was similar and independent of either the dosage or route of administration. In all groups atenolol reduced heart rate and cardiac and stroke volume indices. The pulmonary artery occluded pressure and systemic vascular resistance index were transiently increased. Mean arterial pressure was significantly reduced only in the oral group with the highest pretreatment pressure. Maximum changes developed between fifteen and thirty minutes after intravenous dosing and between two and three hours after oral dosing. However, substantial reductions in cardiac index (-0.6 L/min/m2; p less than 0.05) were already achieved at sixty minutes following oral dosing. The duration of pharmacodynamic activity was for two to three hours following intravenous and for the study duration (four to six hours) after oral dosing. These data confirm the hemodynamic safety of atenolol after acute myocardial infarction.

Haemodynamic dose-response effects of a transdermal nitrate delivery system in acute myocardial infarction with and without left heart failure.

The haemodynamic effects of a transdermal nitroglycerin delivery system (NTG-TTS) were investigated in 67 patients with a recent myocardial infarction. The study objectives were to define the dose-response effects of NTG-TTS and to examine the influence of baseline haemodynamic status on subsequent response. Therefore, patients with normal cardiac function [pulmonary artery occluded pressure (PAOP) less than 18 mm Hg, n = 40] and those with acute heart failure (PAOP greater than 18 mm Hg, n = 27) were studied after one of three regimens (TTS-10, TTS-20, or TTS-40) with the intention of securing 10 evaluable patients in each group. In patients with acute heart failure, all three doses reduced the left ventricular filling pressure with a modest decrease in systemic arterial pressure; cardiac index and heart rate were unaltered. The systemic vascular resistance was significantly reduced from 120 min. In patients with normal left ventricular function, there were small but significant reductions in systemic arterial pressure and vascular resistance with limited increases in heart rate; the cardiac stroke work index was reduced. These results are compatible with actions of NTG-TTS mainly on capacitance vessels; PAOP fell with limited impact on systemic arterial pressure and vascular resistance index. This mode of nitrate delivery resulted in a low incidence of hypotension and side-effects; comparison with other delivery methods in myocardial infarction seems indicated.

Comparative haemodynamic effects of intravenous lignocaine, disopyramide and flecainide in uncomplicated acute myocardial infarction.

A prospective study evaluated the comparative haemodynamic effects of three Class I antiarrhythmics (lignocaine Class 1B, disopyramide Class 1A and flecainide Class 1C) in 30 patients with uncomplicated acute myocardial infarction. Three groups, each of 10 patients, were allocated to lignocaine (Group I) 1.5 mg kg-1 i.v. loading dose over 10 min followed by infusion at 3 mg kg-1 h-1, disopyramide (Group II) or flecainide (Group III), both administered as a 1.0 mg kg-1 i.v. loading bolus over 10 min followed by a 1.6 mg kg-1 h-1 infusion for 120 min. The plasma levels of each drug were in the described therapeutic range. Lignocaine decreased cardiac index (-0.3 l min-1 m-2 (9%); P less than 0.05) and stroke volume index (-5 ml m-2 (11%); P less than 0.01). Systemic blood pressure, heart rate and systemic vascular resistance index were unchanged. There was a small increase (+3 mm Hg (30%); P less than 0.01) in pulmonary artery occluded pressure (PAOP). Both disopyramide and flecainide increased systemic blood pressure; the maximum increases for mean blood pressure were +10 mm Hg (11%) and +4 mm Hg (4%) respectively. Both drugs reduced cardiac index (-0.5 l min-1 m-2 (16%): -0.4 l min-1 m-2 (11%)) and stroke volume index (-11 ml m-2 (25%): -5 ml m-2 (11%)). There were increases in heart rate (+13: +5 beats min-1) pulmonary artery occluded pressure (+2: +3 mm Hg) and systemic vascular resistance index (+696: +275 dyn s cm-5 m2).(ABSTRACT TRUNCATED AT 250 WORDS)

Haemodynamic dose-response effects of intravenous amrinone in left ventricular failure complicating acute myocardial infarction.

The haemodynamic dose-response effects of intravenous amrinone were measured in 16 male patients, aged 40-65 years, with radiographic and haemodynamic evidence of left ventricular failure 4-18 h after acute myocardial infarction. After a l-h control period to confirm stable haemodynamic baseline variables, patients were randomised to either low-dose (200-400-800 micrograms/kg/h) or high-dose (800-1600-3200 micrograms/kg/h) intravenous amrinone. Each of the three infusions was given consecutively over 30 min (total infusion time 90 min) in each group, and haemodynamic measurements were made at the end of each infusion step. No arrhythmias or other untoward side effects, including haematological changes, were observed during the infusions. In both groups, intravenous amrinone reduced the pulmonary artery-occluded pressure (PAOP) (p less than 0.01), increased the cardiac output (p less than 0.05), and reduced the systemic vascular resistance (p less than 0.05). The reductions in PAOP and systemic arterial diastolic pressure and the increase in heart rate were directly dose-related, but the changes in cardiac output and systemic vascular resistance were not. These results suggest that peripheral vasodilation, particularly of venous capacitance vessels, as well as positive inotropic stimulation, may play a role in the haemodynamic changes induced by intravenous amrinone in acute ischaemic left ventricular failure.

Effects of buccal nitrate on left ventricular haemodynamics and volume at rest and during exercise-induced angina.

A novel approach has been employed to characterize the effects of a cardioactive drug on left ventricular haemodynamics and volume by simultaneously determining cardiac stroke volume (thermodilution) and left ventricular ejection fraction (nuclear probe). The effects of glyceryl trinitrate were evaluated in 12 patients with angiographically proven coronary artery disease at rest and 3, 7, 15 and 30 min following 10 mg buccal nitroglycerin (Suscard) administration. The impact of the drug on left ventricular haemodynamics and volume during exercise-induced angina was determined by repeating exercise 30 min following drug administration, at the workload that reliably induced angina during control exercise. At rest buccal nitroglycerin reduced systemic arterial pressure, cardiac and stroke volume indices, and increased heart rate. The left ventricular ejection fraction (E.F.) increased; its filling pressure together with end-diastolic and end-systolic volumes were significantly reduced. Compared with control supine-bicycle exercise, the drug reduced mean systemic arterial pressure and left ventricular filling pressure without change in cardiac and stroke volume indices. There was a smaller increase in left ventricular volume during exercise, and the fall in E.F. was attenuated. These data demonstrated differential actions of glyceryl trinitrate on left ventricular function related to the physiological state in obstructive coronary artery disease. These techniques appear to hold promise in the evaluation of the effects of other therapies on left ventricular volume in coronary artery disease.

Intravenous amrinone in left ventricular failure complicated by acute myocardial infarction.

Hemodynamic dose-response effects of intravenous amrinone were studied in 22 male patients aged 38 to 62 years with left ventricular failure occurring within 18 hours of acute myocardial infarction. After hemodynamic confirmation of a raised left-sided cardiac filling pressure--pulmonary artery occluded pressure greater than 20 mm Hg--patients were randomized to either low-dose infusion of amrinone (200 micrograms/kg/hr for 30 minutes, 400 micrograms/kg/hr for 30 minutes and then 800 micrograms/kg/hr for 30 minutes) or high-dose infusion of the drug (800, 1,600 and 3,200 micrograms/kg/hr sequentially, each for 30 minutes). Hemodynamic measurements were obtained at 1 hour before amrinone and at the end of each infusion step. Low-dose infusion of amrinone resulted in a progressive increase in cardiac output (p less than 0.05) and stroke volume (p less than 0.05) and progressive reductions in pulmonary artery occluded pressure (p less than 0.01) and systemic vascular resistance (p less than 0.05). Systemic blood pressure and heart rate were unchanged. High-dose infusion resulted in a similar increase in cardiac output (p less than 0.05) but no change in stroke volume owing to associated tachycardia (p less than 0.01). There was a significantly greater decrease in pulmonary artery occluded pressure compared with the low-dose infusion (p less than 0.05), and systemic arterial diastolic and mean pressures were also decreased (p less than 0.05). The decrease in systemic vascular resistance was of a similar order to that induced by the low-dose infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic dose-response effects of flecainide in acute myocardial infarction with and without left ventricular decompensation.

We evaluated the hemodynamic effects of the class I antiarrhythmic flecainide in 20 patients within 18 hours of an acute myocardial infarction. Equal numbers of patients with normal (group 1) or decompensated (group 2) ventricular function were studied. Both groups received flecainide, 1 mg/kg, as an intravenous bolus over 10 minutes, followed by infusion (1.6 mg/kg/hr) over the next 120 minutes. Plasma concentrations increased linearly with the cumulative flecainide dosage in both groups. There was no difference between the groups in the plasma levels reached, which were within the recognized antiarrhythmic range for flecainide (200 to 1000 ng/ml) throughout the infusion. The hemodynamic effects of flecainide for each group were decreases in systolic blood pressure (maximum 3% fall in group 1 and 8% fall in group 2), cardiac index (9% fall in group 1 and 18% fall in group 2), stroke volume index (13% fall in group 1 and 23% fall in group 2), stroke work index (14% fall in group 1 and 27% fall in group 2), with an increased heart rate (8% rise in group 1 and 5% rise in group 2), pulmonary artery occluded pressure (27% rise in group 1 and 21% rise in group 2), and systemic vascular resistance (11% rise in group 1 and 18% rise in group 2). Diastolic and mean arterial blood pressures did not change. Our data demonstrate that flecainide induced significant cardiodepression in both groups of patients. These effects were not significantly greater in patients with adequately controlled heart failure. These data suggest that the mild negative inotropic properties of flecainide in patients with recent myocardial infarction are comparable to those described for other class I antiarrhythmics.

Comparative haemodynamic effects of nicardipine and verapamil in coronary artery disease.

The haemodynamic relevance of the disparate electrophysiological and structural differences between agents blocking the slow-calcium channels in patients with exercise-induced angina pectoris is controversial. We therefore evaluated the effects of single intravenous and equivalent hypotensive doses of nicardipine (7.5 mg) or verapamil (16 mg) in a randomized single-blind study of 30 patients with angiographically documented coronary artery disease. The randomization process achieved comparable distribution of 15 patients with similar demographic data and cardiac function to each drug. Patients were evaluated at rest and during four minutes upright bicycle exercise at an individually titrated symptom-limited load in both control and post-drug assessments; the reproducibility of the haemodynamics during such tests has been previously demonstrated. Both nicardipine and verapamil induced similar reductions in systemic mean arterial blood pressure and vascular resistance; the reduction in afterload resulted in increased resting cardiac index and stroke volume index on each agent. The magnitude of the former increase was greater following nicardipine (p less than 0.05). The pulmonary artery occluded pressure (PAOP) increased following verapamil (p less than 0.01) without change following nicardipine. During dynamic exercise, neither drug improved cardiac stroke volume index, the PAOP was significantly higher following verapamil compared with nicardipine (p less than 0.05). Analysis of the cardiac performance curve demonstrated its significant depression following verapamil but not following nicardipine. Thus clear haemodynamic advantages were present, both at rest and during exercise-induced angina, for nicardipine; whether such haemodynamic effects will be reflected in symptomatic terms should be critically evaluated.

Effects of nicardipine on cardiac volume at rest and during exercise-induced angina.

The action of nicardipine on cardiac volume, both at rest and during exercise-induced angina, was evaluated in 12 patients with angiographically-proven coronary artery disease. Nicardipine given to patients at rest reduced systemic vascular resistance and mean arterial pressure and increased heart rate and cardiac index. The left ventricular filling pressure, ejection fraction (EF), end-diastolic and end-systolic volumes were unchanged. During supine bicycle exercise, the reduction in systemic arterial blood pressure following nicardipine increased cardiac and stroke index and attenuated the rise in left ventricular filling pressure observed in the control exercise. The effects of nicardipine on EF, end-diastolic and end-systolic cardiac volumes were dependent on the baseline cardiac reserve. In patients with EF less than 50%, nicardipine improved EF and left ventricular exercise volumes.

Is the intrinsic sympathomimetic activity (ISA) of beta-blocking compounds relevant in acute myocardial infarction?

The relevance of the intrinsic sympathomimetic activity (ISA) of beta-blocking compounds to the clinical therapeutics of acute myocardial infarction was evaluated in 20 patients with an uncomplicated acute myocardial infarction by comparing the haemodynamic effects of equivalent beta-blocking doses of propranolol (non-cardioselective; no ISA) and pindolol (non-cardioselective; 50% ISA). Consecutive eligible male patients admitted to a Coronary Care Unit were randomised following a 1 h control period to two separate studies. In Study 1 the short-term dose-response effects of propranolol (1-8 mg) or pindolol (0.1-0.8 mg) were assessed. In Study 2 comparison of the effects of single i.v. propranolol (8 mg) and pindolol (0.8 mg) doses was undertaken over 6 h. Haemodynamic variables and thermodilution cardiac output were subsequently recorded to compare the effects of each drug on the circulation. The plasma concentrations of propranolol and pindolol were in the recognised therapeutic range. Both drugs were clinically well-tolerated, the changes induced in haemodynamic variables following each drug demonstrated effective beta-blockade. Within the limits of the experimental protocol, these data did not suggest definite haemodynamic advantage for ISA of pindolol in acute myocardial infarction. These findings are perhaps due to sympathetic activation in acute myocardial infarction attenuating the haemodynamic impact of ISA.

Haemodynamic effects of intravenous nicardipine during upright exercise in patients with stable angina pectoris.

The immediate haemodynamic effects, at rest and during exercise, of 2.5 and 10mg intravenous nicardipine were measured in 20 male patients with uncomplicated angina pectoris due to angiographically confirmed coronary artery disease. At rest, both doses of nicardipine resulted in reductions in the systemic arterial pressure and vascular resistance and increases in heart rate and cardiac output. The changes were greater after the larger than after the smaller dose of nicardipine. During exercise, neither dose of nicardipine resulted in a substantial change in the haemodynamic profile, except that after the larger dose heart rate and cardiac output were higher than in the control study. These results indicate that the major overall haemodynamic effect of intravenous nicardipine is dilatation of the systemic arteriolar resistance vessels associated with reflex increase in cardiac pumping activity.

Haemodynamic effects of nicardipine in acute myocardial infarction.

The haemodynamic dose-response effects of the slow-calcium channel blocker nicardipine were evaluated in fifteen male patients with uncomplicated acute myocardial infarction. Following a 1 hr control period, during which the stability of base-line control haemodynamic variables was confirmed, four i.v. boluses of 1.25, 1.25, 2.5 and 5.0 mg of the drug (cumulative dosage 1.25, 2.5, 5.0 and 10.0 mg) were administered at 15 min intervals. The plasma concentrations achieved are within the previously described therapeutic range (greater than 20 micrograms/l). Nicardipine resulted in linear reductions in systemic arterial pressure and vascular resistance, and dose-related increases in heart rate, cardiac and stroke output without change in the left heart filling pressure. Intravenous nicardipine did not induce any depression of left ventricular pumping performance in our patients in the early stages of uncomplicated myocardial infarction.