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Biomedical subjects

S H Taylor

Publications and source records attributed to S H Taylor.

At least 145 records · Page 8Linked to original sources
PubMed1984

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

The haemodynamic dose-response effects of the slow channel blocking agent nicardipine were evaluated in 10 male patients with angiographically confirmed coronary artery disease. At rest, following a similar control saline period, four doses of the drug (log cumulative dosage: 1.25, 2.5, 5.0 and 10.0 mg) were administered by i.v. infusion over a total duration of 40 min; haemodynamic variables were recorded in the 3-5 min following each 5 min infusion. During steady-state exercise the haemodynamic effects of the drug were evaluated by comparison of a control exercise period with observations made at the same workload (200-500 kpm) following the maximum cumulative dose (10 mg). Following the four i.v. infusions, the plasma nicardipine level increased log-linearly with the infused dose (r = 0.68). Compared with control measurements at rest after saline, these plasma concentrations (35 +/- 8 to 141 +/- 24 micrograms/l) resulted in a linear decrease in systemic blood pressure and vascular resistance with significant increase in cardiac index (maximum delta CI + 1.6 l min(-1) m(-2); P less than 0.01), stroke index (maximum delta SI + 11 ml/m2; P less than 0.01) and in pulmonary artery occluded pressure (maximum delta PAOP + 2 mm Hg; P less than 0.01). There was a significant increase in heart rate; the stroke work index was unchanged. During upright bicycle exercise the reduction in systemic blood pressure was accompanied by an increased exercise cardiac output without change in stroke index. The exercise pulmonary artery occluded pressure was unchanged compared with control observations, the stroke work index fell significantly (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Alpha- and beta-blockade in angina pectoris.

Angina pectoris encompasses a clinically diverse group of syndromes in which the common factor is myocardial ischaemia resulting from an imbalance between oxygen requirement and delivery. Anginal pain is most frequently precipitated by exercise, but may occur without any apparent cause at rest. Fixed obstructions in the coronary vessels, often attended by thickening of the overlying coronary artery media, are the most frequent cause of ischaemic cardiac pain. The resulting myocardial fibrosis impairs efficient filling and emptying of the ventricles, further aggravating the functional embarrassment resulting from the reduced coronary blood flow. In stable coronary heart disease the increased energy demands during exercise are associated with the rapid development of a haemodynamic profile characteristic of acute left ventricular failure. This results in further substantial increases in pressure work, wall stress and oxygen consumption of the left ventricle. The reflex sympathoadrenal consequences of these primary haemodynamic changes lead to further mechanical and electrical embarrassment of the ischaemic heart. Increased stimulation of beta 1- and beta 2-receptors in the heart increases heart rate and contractility and thereby myocardial oxygen demand. Increased stimulation of alpha-receptors in the peripheral veins and arteries indirectly increases left ventricular oxygen demand still further by increasing preload and afterload, respectively. The reduced blood flow to the endocardium enhances its sensitivity to increased sympathoadrenal stimulation and facilitates initiation of arrhythmias. Blockade of all adrenergic activity, particularly in the myocardium, coronary arteries and peripheral blood vessels should, therefore, help alleviate the myocardial ischaemia. There is a rational argument for the use of alpha-blockade in coronary heart disease, particularly in conjunction with beta-blockade. Attenuation of the risk of coronary spasm and ventricular arrhythmias and reduction of pressure work and left ventricular afterload are amongst the potential attributes of alpha-blockade. Alone, however, their utility is severely limited by the risks of hypotension and reduction in coronary perfusion pressure and reflex oxygen-wasting tachycardia. Alone, alpha-adrenoceptor antagonists have no place in the treatment of angina pectoris. beta-Adrenoceptor blocking drugs competitively inhibit catecholamines at both cardiac and peripheral vascular beta-adrenergic receptors. Their main advantage is that they reduce many of the important determinants of myocardial oxygen consumption, particularly by reducing the heart rate during exercise.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1984

Secondary prevention after myocardial infarction: facts and fallacies.

Therapeutic research into secondary prevention after myocardial infarction has a disappointing cost-benefit record. Many unrecognised biological problems have complicated apparently simple clinical trials. Inadequacies in design have also contributed to the low rate of success in demonstrating a statistically convincing and clinically worthwhile prophylactic benefit of any of the drugs so far tested. The potential hazards of long-term preventive drug treatment have yet to be defined. The projected economic impact on the community of successful secondary prevention is not encouraging. In the present state of knowledge, arguments for the long-term prophylactic drug therapy of asymptomatic survivors of myocardial infarction are difficult to sustain.

Adrenergic beta-Antagonists↗
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↗
PubMed1984

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.

Adult↗
PubMed1984

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.

Blood Pressure↗
PubMed1984

Nitrates in acute myocardial infarction.

Nitrates produce a more efficacious early haemodynamic profile than other drugs currently available for the treatment of patients with left ventricular failure following acute myocardial infarction. Given by intravenous infusion their venodilator activity rapidly results in a substantial reduction in the excessive left ventricular preload. Their arterial dilator effects result in a less marked but advantageous reduction in the reflex increase in left ventricular afterload. The haemodynamic consequences are a reduction in left ventricular global dysfunction, wall stress and myocardial oxygen consumption and enhanced subendocardial perfusion. These beneficial haemodynamic attributes may reduce infarct size and contribute to a reduction in the potential to develop arrhythmias. Nitrates form the first-line treatment of choice in this clinical emergency, but may be combined with advantage in some situations with diuretics and arteriolar dilators. Nitrates offer potential but less certain advantages in the prophylactic treatment of uncomplicated myocardial infarction.

Blood Pressure↗
PubMed1983

Intrinsic sympathomimetic activity: clinical fact or fiction?

The therapeutic importance of the ancillary pharmacologic property of partial agonist activity, or intrinsic sympathomimetic activity (ISA), of a beta-adrenoceptor antagonist is controversial. Its pharmacologic definition and accepted physiologic potential are now joined by convincing evidence that ISA may have important therapeutic implications. The ability to support basal cardiac functions while preventing the potential hazards of random sympathetic stimulation is an important attribute of this property, particularly in the damaged heart. The beneficial effects of ISA on peripheral blood flow, systemic vascular resistance and left ventricular afterload are established. Although all beta-blocking drugs are contraindicated in patients with asthma, ISA appears to be at least as important as cardioselectivity in offsetting some of the increase in airway resistance that results from beta blockade alone both at rest and during exertion. These pharmacodynamic consequences of ISA may explain the lesser reduction in exercise tolerance afforded by beta-blocking drugs with ISA than by those without. ISA may also enhance the primary oxygen-sparing effects of beta blockade in the ischemic myocardium by reducing coronary resistance, enhancing coronary blood flow, and reducing anaerobic metabolism. The adverse effects of beta-blocking drugs on blood lipids and carbohydrate metabolism also appear to be largely negated in drugs with ISA. The risks of rebound effects from abrupt withdrawal are significantly less in drugs with ISA than in those without.

Adrenergic beta-Agonists↗
PubMed1983

Oxprenolol in clinical practice.

Oxprenolol is a potent noncardioselective beta-adrenoceptor blocking drug with partial agonist activity of proved efficacy and high tolerability in patients at risk of various cardiovascular disease syndromes. The drug rapidly relieves angina and attenuates the electrocardiographic evidence of myocardial ischemia. It is a potent antihypertensive drug that not only reduces the blood pressure at rest but also prevents the surges associated with exercise and psychic stress. Oxprenolol has substantial benefit in the alleviation of many of the somatic sequelae of psychic stress and anxiety. The drug also suppresses the cardiovascular and metabolic effects of cigarette smoking. In the field of primary prevention, oxprenolol has attributes that could be expected to reduce the long-term cardiovascular complications of high blood pressure. In the secondary prevention, it reduces the further incidence of sudden death in patients in whom administration is started in relatively small doses within a few weeks after acute myocardial infarction. In the 15 years that the drug has been available for clinical prescription, it has established a reputation for high clinical tolerability.

Angina Pectoris↗
PubMed1983

Oxprenolol in the treatment of hypertension in the elderly.

Controversy continues to surround the value of drug treatment of hypertension in the elderly. Epidemiologic evidence implicates hypertension as a major risk factor in the precocious development of stroke and coronary heart disease in the elderly subject as clearly as it is implicated in the younger person. The hemodynamic and neuroendocrine profiles of the older patient with essential hypertension are similar to those of younger patients in the stable phase of the disease. However, the arterial ravages induced by many years of sustained hypertension render the circulation of the elderly subject more sensitive to pharmacologic intervention. The benefit-risk ratio of most antihypertensive drugs appears to be inversely related to age. Diuretics reduce the blood pressure at rest but have no influence on the increases in systolic pressure during normal activity; in addition, they carry potentially serious metabolic hazards in the elderly hypertensive patient. Centrally acting drugs likewise lower the blood pressure at rest without influencing the high systolic pressures induced by exercise. They also enhance the tendency to endogenous depression. Adrenergic-neurone blocking drugs and alpha-adrenoceptor antagonists are contraindicated because of the frequency of impaired cardiovascular reflexes in the elderly. The beta-blocking drugs can reduce the risk of coronary and cerebrovascular disease in the older patient with hypertension. They appear to be well tolerated, but because of their impaired metabolic handling in many elderly patients they should probably be used in smaller doses than those prescribed in younger patients. The influence of antihypertensive treatment on cardiovascular morbidity and mortality in the elderly hypertensive patient is not known.

Adrenergic beta-Antagonists↗
PubMed1983

Hemodynamic comparison of primary venous or arteriolar dilatation and the subsequent effect of furosemide in left ventricular failure after acute myocardial infarction.

The hemodynamic effect of venous dilatation (intravenous isosorbide dinitrate [ISDN]) and arteriolar dilatation (intravenous hydralazine), both as firstline treatment and then combined with intravenous furosemide, were evaluated in a randomized, between-group comparison in 20 men with severe acute left-sided cardiac failure after myocardial infarction (MI). Both ISDN (50 to 200 micrograms/kg/hour) (Group 1) and hydralazine (0.15 mg/kg) (Group 2) reduced systemic arterial pressure (p less than 0.05) and vascular resistance (p less than 0.05). Pulmonary artery occluded pressure was reduced (p less than 0.01) only by ISDN, whereas heart rate (p less than 0.01), cardiac output (p less than 0.01) and stroke volume (p less than 0.05) were increased only after hydralazine. After ISDN, furosemide (1 mg/kg) decreased left-sided cardiac filling pressure by 1 mm Hg (p greater than 0.05), whereas after hydralazine, furosemide in a similar dose reduced pulmonary artery occluded pressure by 5 mm Hg (p less than 0.01). In both groups of patients, furosemide transiently increased systemic arterial pressure (p less than 0.05). Cardiac output was reduced (p less than 0.05) and systemic vascular resistance increased (p less than 0.05) in Group 1 patients after furosemide. Similar changes in both variables in Group 2 patients did not attain statistical significance. In conclusion, ISDN-induced venous dilatation is preferable to primary arteriolar dilatation by hydralazine as first-line treatment in acute left-sided cardiac failure. However, hydralazine and furosemide in combination were equally effective in reducing pulmonary artery occluded pressure and increasing cardiac output. The influences of each regimen on prognosis await further investigation.

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

Sulphinpyrazone and renal function following myocardial infarction.

The effects of sulphinpyrazone 800 mg daily on renal excretory function were studied in a double-blind placebo-controlled randomised trial of incremental and full doses of the drug in 28 patients with plasma urea concentration less than 10 mmol/l in the period 2-28 days following uncomplicated acute myocardial infarction. Sulphinpyrazone in both dosage regimens increased uric acid excretion and lowered plasma urate concentration. There was no evidence that the drug reduced glomerular filtration rate or damaged the renal tubules. These results suggest that sulphinpyrazone in the doses used in this study is not contraindicated in patients early after acute myocardial infarction even though they may have a moderate rise in the blood urea.

Adult↗