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Biomedical subjects

R C Ahuja

Publications and source records attributed to R C Ahuja.

At least 37 records · Page 2Linked to original sources
PubMed1984

Comparison of haemodynamic dose-response effects of beta- and alpha-beta-blockade in acute myocardial infarction.

The comparative haemodynamic dose-response effects of beta- (propranolol) or alpha- plus beta-blockade (labetalol) were evaluated in a randomised between-group study of 16 patients with an uncomplicated acute myocardial infarction. In equivalent beta-blocking doses both drugs equally reduced myocardial stroke work index and presumably myocardial oxygen requirements. However, although propranolol reduced heart rate and cardiac output, these haemodynamic changes were accompanied by an augmentation of systemic vascular resistance. In contrast, labetalol reduced heart rate, cardiac output without change in systemic vascular resistance. Moreover, concomitant alpha- and beta-blockade with labetalol resulted in lesser depression of cardiac output at equivalent beta-blocking doses to propranolol. These results suggest that the addition of alpha to beta-blockade may attenuate some of the adverse reflex circulatory consequences of pure beta-blockade; the usefulness of this pharmacological approach to the manipulation of the circulation in the early post-infarction period merits further study.

Aged↗
PubMed1984

The effect on left ventricular performance of nifedipine and metoprolol singly and together in exercise-induced angina pectoris.

Clinical concern still exists regarding the potentially deleterious results of the combined negative inotropic effects of cardiac beta-adrenoceptor and slow calcium channel blockade in patients with impaired left ventricular function due to coronary heart disease. The haemodynamic effects of sublingual nifedipine (20 mg) and intravenous metoprolol (10 mg) singly and in combination were therefore studied in 20 patients with severe angina pectoris associated with angiographically documented coronary artery disease. The plasma concentrations of each drug at the time of the haemodynamic measurements were within the range associated with relief of exercise-induced anginal pain. Sitting at rest, nifedipine was associated with reductions in systemic arterial pressure (P less than 0.05), systemic vascular resistance (P less than 0.001), and increases in heart rate (P less than 0.01) and cardiac output (P less than 0.05) without significant change in the left heart filling pressure. In contrast, sitting at rest, metoprolol was associated with reductions in systemic blood pressure (P less than 0.05), heart rate (P less than 0.001) and cardiac output (P less than 0.05) and an increase in left heart filling pressure (P less than 0.01). After both drugs, similar directional changes were observed during upright bicycle exercise compared to the control exercise measurements. In combination, the negative inotropic effects of metoprolol were largely offset by the reduction of the systemic vascular resistance due to nifedipine. Conversely the reflex tachycardia following nifedipine was countered by metoprolol. Thus the combination reduced two of the major determinants of left ventricular oxygen consumption, namely heart rate and systemic blood pressure, at the expense of a small increase in left heart filling pressure. This may have explained the subjective improvement in anginal symptoms noticed by the majority of the patients. The combination of nifedipine and metoprolol was haemodynamically more advantageous both at rest and during exercise than either drug alone in our patients with depressed left ventricular function due to the coronary heart disease.

Adult↗
PubMed1984

Enhanced haemodynamic effects of propranolol in acute myocardial infarction.

To evaluate the possible influence of sympathetic activation on the haemodynamic response to intravenous beta-blockade, the dose-response characteristics of three boluses of propranolol were evaluated in 8 patients with uncomplicated infarction and compared in a similar number of patients with stable angina. Following a control period, when haemodynamic stability was confirmed, propranolol 2, 2 and 4 mg (cumulative dosage 2, 4 and 8 mg) was injected into the central circulation at 15 min intervals. Despite close matching in baseline control haemodynamic variables between the groups, in stable angina, propranolol resulted in dose-related depression of cardiac output without change in systemic blood pressure, whereas following myocardial infarction the drug induced significantly greater falls in cardiac output (P less than 0.05) and a dose-related decrease in systemic blood pressure. Despite the greater effects of propranolol on cardiac output following myocardial infarction, the left ventricular filling pressure was increased to a lesser extent compared with stable angina. The explanation for this observation may reside in a greater susceptibility of the left ventricular wall to increase its compliance, under conditions of high sympathetic stimulation, following beta-blockade. These data support experimental and biochemical evidence of sympathetic activation in myocardial infarction; the hyperadrenergic state conditions an augmented haemodynamic response to competitive antagonism of sympathetic stimulation at cardiac beta-adrenoceptors.

Aged↗
PubMed1984

The effects on left ventricular performance of nifedipine and verapamil in exercise-induced angina pectoris.

The differences between slow calcium blocking agents with respect to effects on heart rate, myocardial contractility and atrioventricular conducting time are well described; the relevance of such differences to the treatment of patients with impaired left ventricular function due to coronary heart disease is uncertain. The haemodynamic effects of equivalent hypotensive doses of nifedipine and verapamil were therefore compared in 20 patients with severe angina pectoris associated with angiographically documented coronary artery disease. The plasma concentrations of nifedipine (mean 57 +/- 19; range 27-77 ng/ml) and verapamil (mean 147 +/- 14; range 117-260 ng/ml) at the time of the haemodynamic measurements were of an order usually associated with substantial pharmacodynamic activity. Sitting at rest nifedipine resulted in reduction in systemic arterial pressure (P less than 0.05) and vascular resistance (P less than 0.01); both the heart rate (P less than 0.01) and cardiac output (P less than 0.05) increased without any significant change in the left heart filling pressure. In contrast, verapamil, which similarly reduced systemic blood pressure (P less than 0.05) and vascular resistance (P less than 0.01), increased cardiac output (P less than 0.05) and left heart filling pressure (P less than 0.05) without any change in heart rate. During upright bicycle exercise both drugs attenuated the angina induced in all subjects during the control exercise period. Despite reductions in systemic blood pressure and vascular resistance the cardiac output was unaltered on either drug at the same workload as in the control assessment. The reduction in exercise blood pressure following nifedipine induced a reflex tachycardia; this was not present, despite the similar hypotensive action, after verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Comparative haemodynamic dose-response effects of intravenous propranolol, acebutolol and penbutolol in angina pectoris.

The relevance of the ancillary pharmacological properties of intrinsic sympathomimetic activity (ISA) and cardioselectivity to the haemodynamic profile following intravenous beta-blockade was examined in a randomised study of propranolol (16 mg), acebutolol (160 mg) or penbutolol (4 mg) in 30 patients with stable angina pectoris. Haemodynamic measurements were undertaken at rest and during four minutes steady-state supine bicycle exercise (25 to 50 W), load limited to the angina threshold, before and after each drug. The randomised groups were statistically similar for major haemodynamic and clinical variables. The plasma concentrations achieved for each drug were in the therapeutic range. At rest, propranolol resulted in greater reductions in resting cardiac output and greater increase in pulmonary artery occluded pressure compared with acebutolol and penbutolol. During the sympathetic stimulus of dynamic exercise, penbutolol resulted in less depression of exercise cardiac performance than either acebutolol or propranolol. These observations are compatible with previous studies which suggested that the possession of ISA by a beta-blocking drug offset the depression of cardiac performance following intravenous beta-blockade; the benefits of ISA on haemodynamic profile appeared maximum at rest and were reduced or abolished during dynamic exercise.

Acebutolol↗
PubMed1984

Haemodynamic dose-response effects of i.v. verapamil in coronary artery disease.

As an aid to clinical therapeutic decisions, the haemodynamic dose-response effects following intravenous verapamil were evaluated in ten male patients with angiographically confirmed and stable coronary artery disease. Sitting at rest, following a control period with four i.v. boluses of saline, four equivalent boluses of verapamil (logarithmic cumulative dosage; 2, 4, 8 and 16 mg) were administered at four minute intervals; haemodynamic variables were recorded two to four minutes following each i.v. injection. The haemodynamic effects of the drug during upright bicycle exercise were evaluated by comparison of measurements made during a control steady-state exercise period with observations made at the same upright exercise workload (25 to 75 W) immediately following the maximum cumulative dose (16 mg). Following the four i.v. boluses, the plasma verapamil concentrations showed a log-linear increase (r = 0.82; p less than 0.001); the levels achieved (26 +/- 2 to 147 +/- 14 micrograms/l) were within the range at which substantial pharmacodynamic activity has been shown to be present. At rest, compared with control measurements after saline, these plasma concentrations of verapamil were associated with linear decreases in systemic vascular resistance (maximum delta SVR -720 dyne X s X cm-5/m2; p less than 0.01) and blood pressure (maximum delta MBP -8 mmHg; p less than 0.05) and linear increases in cardiac index (maximum delta CI +0.4 l/min/m2; p less than 0.05) and in pulmonary artery occluded pressure (maximum delta PAOP +3 mmHg; p less than 0.05). There was no significant trend of change in the heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Haemodynamic advantages of isosorbide dinitrate over frusemide in acute heart-failure following myocardial infarction.

The immediate haemodynamic effects of intravenous frusemide (1 mg/kg) and intravenous isosorbide dinitrate (50-200 micrograms/kg/h) were compared in a prospective, randomised, between-group study in 28 men with radiographic and haemodynamic evidence of left ventricular failure following acute myocardial infarction. The diuresis induced by frusemide reduced the left heart filling pressure and cardiac output and transiently raised systemic blood-pressure. In contrast, isosorbide dinitrate was accompanied by a reduction in systemic blood-pressure and peripheral resistance with the result that the cardiac output was not decreased despite a large fall in the pulmonary vascular and left heart filling pressures. These results indicate that reduction of excessive preload by venodilatation may be haemodynamically superior to that induced by diuresis in terms of both reducing myocardial oxygen consumption and maintaining peripheral perfusion. The influence of these contrasting treatments on the prognosis of these high-risk patients warrants further study.

Acute Disease↗
PubMed1983

Comparative haemodynamic dose-response effects of intravenous propranolol and pindolol in patients with coronary heart disease.

To determine whether the depression of left ventricular pumping activity associated with beta-blockade alone could be offset by a substantial degree of partial agonist activity, the haemodynamic dose-response effects of intravenous propranolol and pindolol were compared in a randomised between-group saline controlled study in twenty patients with angiographically proven coronary artery disease. The intravenous doses of propranolol (2-16 mg) and pindolol (0.2-1.6 mg) used were selected on the basis of published reports of equivalence in terms of exercise blockade of chronotropic beta-adrenoceptors. Following four intravenous boluses of each drug, administered according to a cumulative log-dosage schedule, there was a log-linear increase in the plasma concentrations of each drug. The range of plasma concentrations achieved were those which have been shown to be associated with substantial attenuation of sympathetic stimulation of cardiac beta-adrenoceptors. At rest propranolol resulted in dose-related linear reductions in heart rate and cardiac output and linear increases in left heart filling pressure and systemic vascular resistance compared with saline-controlled measurements. The only statistically significant change at rest after pindolol was a small increase in the left heart filling pressure. The calculated systemic vascular resistance was increased after propranolol but unchanged after pindolol. During supine bicycle exercise the systolic blood pressure increased less after propranolol than after saline or pindolol. The increments in all other measured haemodynamic variables during exercise were equally influenced by the two drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Haemodynamic effects of frusemide and its influence on repetitive rapid volume loading in acute myocardial infarction.

The haemodynamic effects of intravenous frusemide (1 mg/kg) were studied in 22 male patients with left ventricular failure following acute myocardial infarction. Radiographic pulmonary oedema was present in all patients and their average left heart filling pressure was 20 mmHg. Bolus injection of the drug was followed by immediate increases in systemic arterial pressure (P less than 0.05) and heart rate (less than 0.05); these declined to pre-injection values after 60 min. Following frusemide there were progressive reductions in left heart filling pressure (P less than 0.01), thermodilution cardiac output (P less than 0.01) and stroke volume (P less than 0.05) and a progressive increase in the derived systemic vascular resistance (P less than 0.05). There was an average diuresis of 860 ml during the 90 min following the frusemide injection. The influence of frusemide on left ventricular performance was studied by comparing the circulatory effects of passive leg raising in the control period with those at 30, 60 and 90 min after the drug. In the control period this manoeuvre increased left heart filling pressure, but not heart rate, cardiac output, stroke volume or systemic vascular resistance. Ninety minutes after frusemide, but not before, passive leg raising resulted in a significant increase in cardiac output (P less than 0.01) and stroke volume at a similar increment in filling pressure and a significant reduction in the systemic vascular resistance (P less than 0.05). These circulatory actions of intravenous frusemide are compatible with initial arteriolar constriction and venodilatation followed by depletion of blood volume with subsequent change in left ventricular pumping performance.

Adult↗
PubMed1983

Beta-blockade in ischaemic heart disease--influence of concomitant ISA or alpha-blockade on haemodynamic profile.

To test the hypothesis that the depression of cardiac performance induced by competitive blockade of sympathetic stimulation at beta-adrenoceptors could be attenuated by the addition of a high level of intrinsic sympathomimetic activity (ISA) or concomitant alpha- and beta-blockade, the haemodynamic dose-response effects of propranolol (non-cardioselective, no ISA), pindolol (non-cardioselective, high ISA) and labetalol (non-cardioselective, alpha-blocker) were compared in a randomized study of 30 patients with stable coronary artery disease. Following 4 intravenous (i.v.) doses of each drug given according to a logarithmic cumulative dosage schedule, changes in circulatory variables were measured 2-4 min following each i.v. bolus and during bicycle exercise following the maximum dose of each drug. At rest propranolol induced dose-related reductions in heart rate, cardiac output and increases in pulmonary artery occluded pressure and systemic vascular resistance. The only change in resting haemodynamic variables following pindolol was a small dose-related increase in pulmonary artery occluded pressure. Labetalol induced dose-related falls in systemic blood pressure and vascular resistance with linear increase in cardiac output and pulmonary artery occluded pressure. During exercise the depression of cardiac output and increase in pulmonary artery occluded pressure which occurred in patients randomized to propranolol was effectively attenuated in the pindolol and labetalol groups. These observations on cardiac performance following beta-blockade in ischaemic heart disease suggest a rational basis for the use of compounds with added vasodilator or intrinsic sympathomimetic properties.

Adult↗
PubMed1983

Haemodynamic dose-response effects of intravenous labetalol in acute myocardial infarction.

The haemodynamic consequences of combined alpha- and beta-adrenoceptor blockade with intravenous labetalol were evaluated in 21 males with either high (n = 6), normal (n = 9) or low (n = 6) systemic arterial pressure, 4-17 hours after acute myocardial infarction without heart failure. Labetalol 190 +/- 18 mg (range 62-300 mg) infusion resulted in dose-related falls in systolic (P less than 0.01) and diastolic (P less than 0.05) arterial pressure in all patients. The rate of pressure reduction per mg of infused labetalol was directly proportional to the control systolic arterial pressure. Cardiac output (thermodilution) was reduced (P less than 0.05) with low dose labetalol (39 +/- 5 mg) without change on continued infusion. Left heart filling pressure (pulmonary artery occluded pressure) was unchanged throughout infusion in all patients. In conclusion, the vasodilating properties of labetalol appeared to offset the beta-blocker induced depression of cardiac function. The increased sensitivity to the effects of labetalol in those patients with hypertension may be related to excessive alpha-adrenoceptor mediated vasoconstriction in this patient group.

Dose-Response Relationship, Drug↗
PubMed1983

Management of acute heart failure following myocardial infarction: hemodynamic advantages of isosorbide dinitrate over frusemide.

The immediate hemodynamic effects of intravenous frusemide (1 mg/kg) and intravenous isosorbide dinitrate (50-200 micrograms/kg/h) were compared in a prospective, randomized, between-group study in 28 men with radiographic and hemodynamic evidence of left ventricular failure following acute myocardial infarction. The diuresis induced by frusemide reduced the left-heart filling pressure and cardiac output and transiently raised systemic blood pressure. In contrast, isosorbide dinitrate was accompanied by a reduction in systemic blood pressure and peripheral resistance, with the result that the cardiac output was not decreased despite a large fall in the pulmonary vascular and left-heart filling pressures. The results indicate that reduction of excessive preload by venodilatation may be hemodynamically superior to that induced by diuresis in terms of both reducing myocardial oxygen consumption and maintaining peripheral perfusion. The influence of these contrasting treatments on the prognosis of these high-risk patients warrants further study.

Adult↗
PubMed1982

Haemodynamic advantages of combined alpha-blockade and beta-blockade over beta-blockade alone in patients with coronary heart disease.

The acute haemodynamic effects of beta-blockade with propranolol and combined alpha-blockade and beta-blockade with labetalol were compared in a randomised study in 12 patients with coronary artery disease proved by angiography. Propranolol induced significantly greater depression of left ventricular function both at rest and during exercise than labetalol. This difference was probably attributable to the vasodilator activity of labetalol and the associated reduction in afterload offsetting the haemodynamic disadvantages of blockade of cardiac beta-adrenoceptors alone. The haemodynamic advantages of combined alpha-blockade and beta-blockade over beta-blockade alone may thus have therapeutic implications for the use of these treatments in patients with coronary heart disease.

Adult↗