Search PubMed⌕ Search

Biomedical subjects

S H Taylor

Publications and source records attributed to S H Taylor.

At least 127 records · Page 7Linked to original sources
PubMed1985

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.

Adult↗
PubMed1985

Diuretics in cardiovascular therapy. Perusing the past, practising in the present, preparing for the future.

Diuretics are the mainstay of drug therapy in the treatment of many cardiovascular disorders. However, perusal of knowledge of their haemodynamic activities in heart failure and hypertension reveals major gaps. In left ventricular failure complicating acute myocardial infarction, intravenous frusemide reduces the elevated left heart filling pressure with little change in systemic blood pressure, heart rate or cardiac output, and restores the ability of the left heart to handle an acute increase in filling volume. But there is little knowledge of the haemodynamic effects of other intravenous diuretics, oral diuretics or diuretics other than those acting on the loop of Henle in this emergency clinical situation. Even less information is available on the haemodynamic effects of diuretics in patients in chronic heart failure. In patients with valvular heart disease, parenteral mercury and oral thiazides reduce right heart and pulmonary vascular pressures with variable (dose-dependent?) changes in cardiac output. Information on the effect of loop diuretics, the comparative effects of intravenous versus oral routes of administration and dose-response correlations are all lacking. In hypertension, the dose-blood pressure lowering response relationship of orally administered diuretics is relatively flat. The majority of information relates to oral thiazides; there is little reliable information on the anti-hypertensive efficacy of the loop diuretics. The acute and chronic effects of the majority of commonly used diuretics on cardiac and peripheral vascular functions is unexplained. More is known of their potentially adverse metabolic effects than of their possible circulatory benefits in hypertensive patients. Many unwanted side-effects of these drugs have been described; their potential importance is related directly to the disease state and doses in which they are used. In acute heart failure, their potential danger is probably minimal. In the treatment of chronic heart failure their most sinister potential is in the excessive secretion of potassium and magnesium. In hypertensive patients their long-term administration in high-doses may lead to undesirable metabolic effects that tend to offset their blood pressure lowering activity. Despite their drawbacks, diuretics continue to provide the natural first-line treatment of choice of these common cardiovascular syndromes. But more information on their mechanisms of vascular activities and the differences in non-diuretic activity between different compounds is urgently required.

Angina Pectoris↗
PubMed1985

Haemodynamic studies with muzolimine in left ventricular failure complicating acute myocardial infarction.

This is an interim report of haemodynamic studies with oral muzolimine in male patients under 70 yr with haemodynamically confirmed left ventricular failure complicating acute myocardial infarction. All were in sinus rhythm and without hypotension (SBP 100 mmHg) and were studied by conventional intravascular haemodynamic methods within 18 hr of onset of symptoms of acute myocardial infarction. A preliminary dose-finding study in four patients indicated that both 60 and 120 mg oral muzolimine induced substantial diuresis but only the latter dose was associated with an appreciable reduction in left heart filling pressure within 2 hr. The aims of the main study are to determine the haemodynamic effects of oral muzolimine 120 mg given once daily for 10 days in these high risk patients. Thereafter patients are randomised to continued oral muzolimine or placebo for a period of three months. The effects of such treatment on their haemodynamic profile at rest and during dynamic exercise are being measured by comparison with the 10 day measurements. In the first six patients entered into the main study, 120 mg oral muzolimine resulted in a progressive reduction in the elevated left heart filling pressure without tachycardia or any other major haemodynamic change over 8 hr on both Day 1 and Day 2. These potentially advantageous haemodynamic effects await confirmation from further results in this on-going study.

Aged↗
PubMed1984

Hemodynamic effects of nifedipine during upright exercise in stable angina pectoris and either normal or severely impaired left ventricular function.

The immediate effects of sublingual nifedipine (20 mg) were evaluated in 18 men with stable, exercise-related angina pectoris and angiographically confirmed coronary artery obstructions, stratified at the time of left ventricular (LV) angiography according to the degree of LV dysfunction supine at rest (Group 1: n = 9, left ventricular end-diastolic pressure [LVEDP] less than 20 mm Hg; Group 2: n = 9, LVEDP greater than 20 mm Hg). At rest, in the upright posture in both groups, nifedipine reduced the systemic vascular resistance (p less than 0.01). The systemic arterial mean (p less than 0.05) and diastolic (p less than 0.01) pressures were reduced despite an increase in the cardiac output (p less than 0.05). Heart rate was increased only in Group 1 (p less than 0.05). Pulmonary artery occluded pressure was unchanged in both groups. During upright bicycle exercise in all patients, compared to control measurements, systemic arterial pressure (p less than 0.01) and vascular resistance (p less than 0.05) were similarly reduced, while exercise cardiac output response and LV filling pressure did not change after nifedipine. Heart rate was increased in Group 1 (p less than 0.05) and decreased in Group 2 (p less than 0.05). Stroke volume during exercise after nifedipine decreased 1 ml/m2 in Group 1 (p greater than 0.05) and increased 2 ml/m2 in Group 2 (p greater than 0.05) compared to control measurements; the between-group difference in the exercise heart rate and stroke volume responses after nifedipine were significant at the 5% level.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

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.

Adrenergic beta-Antagonists↗
PubMed1984

Hemodynamic trial of sequential treatment with diuretic, vasodilator, and positive inotropic drugs in left ventricular failure following acute myocardial infarction.

The circulatory effects induced by two sequential intravenous treatment programs with a diuretic, arteriolar or venodilator , and a positive inotropic drug were studied in a randomized between-group trial in 20 male patients with radiographic and hemodynamic evidence of left ventricular (LV) failure following acute myocardial infarction (AMI). Furosemide induced a substantial diuresis in both groups of patients, in association with reductions in LV filling pressure (p less than 0.01) and cardiac output (p less than 0.05), without significant change in heart rate or systemic arterial pressure. The addition of isosorbide dinitrate was followed by reductions in the systemic arterial (p less than 0.01) and LV filling pressures (p less than 0.01) without significant change in the heart rate or cardiac output. Hydralazine after furosemide reduced systemic vascular resistance (p less than 0.01), but the fall in mean blood pressure (p less than 0.01) was limited by the increase in cardiac output (p less than 0.01); heart rate was also increased (p less than 0.01) and LV filling pressure fell (p less than 0.05). The final addition of the beta-1 adrenoceptor agonist, prenalterol, increased systemic arterial systolic pressure (p less than 0.05), cardiac output (p less than 0.05), and heart rate (p less than 0.01), and reduced systemic vascular resistance (p less than 0.01) in both groups; these changes were greatest in those pretreated with furosemide and isosorbide dinitrate. In both treatment pathways compared with control the reductions in systemic vascular resistance and left heart filling pressure were accompanied by increases in heart rate and cardiac output without substantial changes in systemic blood pressure. Which of these hemodynamic pathways offers the optimum prognosis awaits further study.

Adrenergic beta-Agonists↗
PubMed1984

Rest and exercise hemodynamic effects of sequential alpha-1-adrenoceptor (trimazosin) and beta-adrenoceptor (propranolol) antagonism in essential hypertension.

The efficacy of acute beta blockade in essential hypertension is limited by reflex vasoconstriction. The aim of this study was to determine whether the latter response was modified by prior selective alpha-1-adrenoceptor blockade. A single-blind, within-patient, placebo-controlled evaluation of the immediate hemodynamic effects of sequential alpha-1 (trimazosin)- and beta (propranolol)-adrenoceptor blockade was undertaken in 10 men (34 to 58 years) with previously untreated essential hypertension. The study commenced with a 4-minute control period of constant-load (600 to 900 kpm/min) upright bicycle exercise, and measurements were made before (control) and 30 minutes after intravenous trimazosin (2 mg/kg) and exercise was then repeated; measurements at rest were again made 4 minutes after intravenous propranolol (0.2 mg/kg) before a final exercise period. Trimazosin at rest reduced systolic and diastolic arterial pressure and systemic vascular resistance without change in heart rate, cardiac output, or left ventricular (LV) filling pressure. During upright bicycle exercise the reductions in blood pressure were sustained without change in their rest-to-exercise increments. Other circulatory variables did not differ from control values. At rest the addition of propranolol further reduced systolic arterial pressure. Heart rate and cardiac output fell and systemic vascular resistance increased to its pretreatment control value. During exercise the changes at rest were sustained and the rest-to-exercise increments in blood pressure, heart rate, and cardiac output were reduced. LV filling pressure was significantly increased. In conclusion, alpha-1-adrenoceptor blockade modified the adverse effects of acute beta blockade at rest but not during exercise.

Adult↗
PubMed1984

Prevention of carcinomatosis and bloody malignant ascites in the rat by an inhibitor of angiogenesis.

It has previously been shown that protamine sulfate is an angiogenesis inhibitor. Regional infusion of protamine into the peritoneal cavity is now reported to prevent the growth of intraperitoneal vascularized tumor masses in rats. Walker 256 carcinoma was implanted directly into the liver or into the peritoneal cavity of rats. Hepatic implants grew in the liver with metastases to the wound and mesentery. Injected tumor cells grew as solid tumor masses in the mesentery. Bloody ascites developed after 7 days. Animals received an intraperitoneal infusion of protamine or saline. Protamine significantly inhibited growth of solid tumors in the mesentery (P less than 0.001). Histology showed tumor cells growing only in monolayer but without vascularization. Ascites was not bloody. In saline-treated animals large vascularized tumors grew in the peritoneal cavity and ascites became bloody.

Animals↗
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 circulatory response to lifting and carrying and its modification by beta-adrenoceptor blockade.

The circulatory effects of lifting and holding weighted suitcases of 5, 10 and 15 kg, and carrying the same suitcases at two different walking speeds were evaluated in 6 normal subjects before and after beta-adrenoceptor blockade with 160 mg oxprenolol. Lifting and holding induced significant weight-induced increments in systolic and diastolic blood pressure which were not attenuated by beta-blockade. There was a significant increase in heart rate only on lifting the 15 kg weight which was attenuated by oxprenolol. Dynamic exercise (walking) with the same weighted suitcases resulted in rate and speed related increase in systolic pressure and heart rate, the magnitude of which was greater than that of lifting alone. The isometric pressor response was attenuated when walking and carrying at 2 mph, but completely abolished by the metabolic and heat induced vasodilatation when walking at 4 mph. Following beta-blockade both the absolute blood pressure and the systolic pressor and heart rate responses to combined lifting and carrying were attenuated. The diastolic pressor response induced by lifting, which was offset in the control period by the vasodilation induced by dynamic exercise was progressively attenuated proportionate to the load carried following beta-blockade; presumably this reflected systemic vasoconstriction to maintain mean perfusion pressure in the presence of central beta-blockade. These observations suggest that the isometric component which predominates at slow walking speeds when carrying weights between 5 and 15 kg is completely suppressed by the vasodilatation at fast walking speeds. Beta-blockade, while reducing heart rate and systolic pressor response to the same stimuli, leads to an augmented systemic vascular resistance which is particularly evident at high metabolic workloads.

Adult↗
PubMed1984

Dose-response effects of cardioselective beta blockade in coronary artery disease.

The hemodynamic dose-response effects of intravenous acebutolol, a cardioselective beta-adrenoceptor antagonist with intrinsic sympathomimetic activity, were evaluated in 12 male subjects with angiographically confirmed coronary artery disease. At rest after a saline solution control period, four doubling intravenous boluses of acebutolol (logarithmic cumulative dosage of 20, 40, 80, and 160 mg) were injected at 4-min intervals; hemodynamic variables were recorded 2 to 4 min after each injection. Hemodynamic effects of the drug during steady-state exercise were evaluated by comparison of a control exercise period with observations made at the same workload (25W to 50W) after the maximum cumulative dose (160 mg). After the four intravenous boluses, plasma acebutolol concentrations rose in log-linear fashion and levels achieved (0.6 to 3.5 micrograms/ml) were within the range at which substantial pharmacodynamic activity is usually present (i.e., 0.02 to 0.2 microgram/ml). Compared with control measurements at rest after saline solution injection, these plasma concentrations of acebutolol resulted in a quadratic reduction in heart rate (maximum delta HR, -4 bpm) and a linear increase in pulmonary artery occluded pressure (maximum delta PAOP, +3 mm Hg) without change in systemic arterial pressure. There was a small reduction in cardiac output (delta cardiac index [CI], -0.2 l/min/m2). During steady-state supine bicycle exercise, there were significant reductions in systolic blood pressure (delta SBP, -15 mm Hg, or 9%) HR (-9 bpm or -9%), cardiac output (delta CI, -1.0 l/min/m2, or -18%), and increase in PAOP (+8 mm Hg, or +38%).(ABSTRACT TRUNCATED AT 250 WORDS)

Acebutolol↗
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↗