Biomedical subjects

S H Taylor

Publications and source records attributed to S H Taylor.

At least 73 records · Page 4Linked to original sources

PubMed1989

Haemodynamic comparison of different routes of nitrate administration in postmyocardial infarction left ventricular failure.

An open randomised parallel group comparison of the haemodynamic effectiveness of three different routes of nitrate administration was undertaken in 36 male patients aged 40-69 years who had developed acute left ventricular failure within 18 h of the onset of myocardial infarction. All patients had electrocardiographic and serum cardiac enzyme changes compatible with transmural myocardial infarction and all had both radiographic and haemodynamic evidence of left ventricular failure. None were hypotensive, all were in sinus rhythm and none were receiving other cardioactive drugs. Control haemodynamic measurements were made over a period of one h, following which patients were randomised to receive either intravenous isosorbide dinitrate (mean dose 12.9 mg; range 7.7-14.9), buccal nitroglycerine (5 mg) or transdermal nitroglycerin (nitro TTS 10). The raised left heart filling pressure was reduced by all nitrate preparations but none significantly changed the heart rate or cardiac output. Systemic arterial pressure and vascular resistance were reduced by i.v. ISDN and buccal NTG but not by a transdermal NTG. The only adverse circulatory reaction was hypotension in the three patients following buccal NTG. Nitroglycerin by the transdermal route appears to be equally effective in reducing the raised left heart filling pressure in patients with postinfarction heart failure without the practical disadvantages of monitoring its intravenous administration or the potential hazard of hypotension with buccal NTG.

Administration, Buccal↗

PubMed1988

Hemodynamic comparison of dopexamine hydrochloride and dopamine in ischemic left ventricular dysfunction.

The hemodynamic dose-response effects of intravenous dopexamine hydrochloride (0.5 to 2.0 micrograms/kg/min) have been compared with dopamine (2.5 to 10 micrograms/kg/min) in 12 patients with ischemic left ventricular dysfunction in an open randomized crossover study. Both drugs increased cardiac output and decreased systemic vascular resistance. Dopexamine hydrochloride appeared to increase heart rate more than dopamine although this did not reach statistical significance. Dopexamine hydrochloride produced small increases in systolic and decreases in diastolic blood pressure, whereas dopamine had a biphasic effect resulting in a decrease in mean blood pressure at low doses and an increase at the highest dose studied. With increasing dosage, there was a trend toward more vasodilator activity with dopexamine hydrochloride than with dopamine. Dopexamine hydrochloride produced fewer adverse effects than dopamine.

Adult↗

PubMed1988

Celiprolol and the heart.

The introduction of beta-adrenoceptor antagonists was a major advance in the treatment of hypertension and coronary artery disease. However, nonselective beta blockade carries distinct circulatory disadvantages, which accounts for the search for an "ideal" beta-blocking drug for use in this extensive therapeutic field. It is possible to define the desirable cardiodynamic profile of a beta-blocking drug. How far does celiprolol meet this function? What questions should we address in attempting to evaluate the effects of celiprolol on the heart? In contrast to propranolol, in the normal heart, celiprolol does not depress left ventricular pumping function. There is little information on the effects of celiprolol on left ventricular function in the hypertensive patient. However, we now know that most patients with hypertension already have advancing coronary artery disease. It is reasonable, therefore, to examine the effects of celiprolol on left ventricular function in patients with coronary disease because these can not only be used to evaluate the possible efficacy of the drug in patients with angina pectoris, but also to extrapolate to their clinical effectiveness in most patients with hypertension. Celiprolol does not depress left ventricular pumping function at rest or during exercise, in contrast to other beta-adrenoceptor antagonists that reduce both heart rate and left ventricular activity. Moreover, celiprolol possesses anti-ischemic properties equivalent to those of atenolol. It does not appear to aggravate the atherogenic profile of the lipids as much as some other cardioselective beta-blocking drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

PubMed1988

Celiprolol in hypertension.

Celiprolol is a third-generation, beta-adrenoceptor antagonist with ancillary pharmacologic properties that are potentially advantageous in the treatment of hypertension. Celiprolol provides 24-hour control of blood pressure and in formal clinical trials has been found superior to a placebo and of equal efficacy to other commonly used beta-blocking drugs. It has also been found to be equally as effective as enalapril in lowering the resting blood pressure and superior in controlling the increases in blood pressure and heart rate during exercise. Celiprolol is known to exert a beneficial effect on the atheroprotective components of the risk factors for coronary heart disease, such as cholesterol triglyceride, and fibrinogen. Therefore the primary attributes of beta-blockade are uniquely advanced by celiprolol's ancillary pharmacologic activities.

Adrenergic beta-Antagonists↗

PubMed1988

Pharmacotherapeutic stature of doxazosin and its role in coronary risk reduction.

In hypertension the primary pathophysiologic abnormality is a generalized increase in the peripheral vascular resistance as a result of concentric narrowing of the systemic arterioles, as a result of alpha 1-receptor stimulation. Such stimulation is attenuated by the selective alpha 1-inhibitor doxazosin. The pharmacologic attributes of doxazosin are translated into direct relaxation of the peripheral arteriolar resistance vessels and venous capacitance system, particularly those with a high alpha-adrenoceptor population. The direct effects of such vascular dilatation are immediately beneficial to the heart in reducing systemic and pulmonary vascular pressures that reduce left ventricular wall stress and myocardial oxygen consumption. In clinical studies doxazosin has been found to have a plasma half-life of 19 to 22 hours, of which a single daily dose is sufficient to control hypertension. The antiatherogenic changes in the blood lipid profile resulting from long-term treatment with doxazosin can also be expected to advance its primary prevention potential in hypertensive patients, which is in marked contrast to the potentially disadvantageous changes in the blood lipid profile that follow treatment with beta-blockers and thiazide diuretics. The therapeutic efficacy of doxazosin has been confirmed, irrespective of hypertension severity, age and race of the patient, or the presence of renal impairment or diabetes mellitus. Its side-effect profile is not substantially different from that of placebo or other antihypertensive drug treatment. Given its unique actions regarding antihypertensive efficacy, together with favorable effects on blood lipids, doxazosin probably holds more promise for the prevention of precocious coronary heart disease in hypertensive patients than any other currently available antihypertensive agent.

Adrenergic alpha-Antagonists↗

PubMed1988

A comparison of doxazosin and enalapril in the treatment of mild and moderate essential hypertension.

The antihypertensive efficacy and safety of doxazosin, a selective alpha 1-adrenoceptor antagonist, were compared with that of the angiotensin-converting enzyme inhibitor enalapril in an 18-week double-blind, parallel-group trial. Sixty-seven hypertensive patients entered the three-phase study, which involved a 4-week placebo washout period, a 10-week titration period with doxazosin, 1 to 16 mg, or enalapril, 10 to 40 mg once daily followed by a 4-week maintenance period. The target response was a standing diastolic blood pressure less than or equal to 90 mm Hg. In the 62 efficacy evaluable patients the mean final daily dose of doxazosin was 5.6 mg and 25.5 mg for enalapril. The percentages of therapeutic successes were 74% in the doxazosin- and 81% in the enalapril-treated groups; the proportions in whom standing diastolic blood pressure less than or equal to 90 mm Hg were 55% and 61%, respectively. Both sitting and standing blood pressures were significantly reduced at all visits during the 14-week treatment period in both groups. Twelve patients receiving doxazosin reported 14 adverse events and nine patients administered enalapril reported 19 adverse events; therapy was stopped in three patients in each group because of side effects. The overall assessment of efficacy was excellent or good for 71% of the doxazosin-treated and 67% of the enalapril-treated patients, respectively. Toleration of therapy was excellent or good for 91% of the doxazosin-treated and 88% of the enalapril-treated patients, respectively. No clinically significant changes were observed in the serum lipids, plasma biochemistry, or hematologic profiles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

PubMed1988

Is the measurement of cardiac output useful in clinical practice?

The derivation of the "cardiac output" in man is fraught with difficulties whatever principle of measurement is used. The theories underlying the principles involved are sound; the problem arises in their application to the measurement in man. Of equal moment are the immense practical difficulties in applying the techniques available. Together these difficulties frequently give rise to unacceptable errors in the derivation of the "cardiac output". There is no "gold standard" of measurement; all methods have inherent difficulties in their application to man. If intense attention is paid to the practice of any one of the techniques available, then it is possible to reduce the variability of the measurement to acceptable proportions, but the conditions necessary to obtain such narrow ranges of variability in the human subject rarely obtain in routine clinical practice. These realizations apply to the techniques available at present, and it is difficult to imagine that there will be further development of the invasive methods available which would negate these. In contrast, it is possible that refinement of some of the non-invasive techniques now being introduced will allow reasonably reliable measurement of the cardiac output with greater facility than is possible at present. Finally, this brings into question the whole objective of the utility of measurement of cardiac output in practice. Frequently it is measured without due deference to its usefulness. Doubtless there are situations in which the measurement of cardiac output may be of scientific, if not of individual clinical benefit, for example the influence of drugs in hypertension and heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Output↗

PubMed1988

Cardiovascular consequences of heart failure.

The cardiac and reflex neuroendocrine consequences of heart failure are reviewed. The mechanisms responsible for the many neuroendocrine reflexes that result as a consequence of heart failure are considered particularly in relation to their pathophysiological interactions. The lack of knowledge regarding quantitative changes occurring in the various circulatory reflexes activated by heart failure and the paucity of knowledge of the immediate and long-term effects of pharmacotherapeutic interventions on these reflexes are highlighted.

Atrial Natriuretic Factor↗

PubMed1988

Sympathetic (alpha-beta) or calcium channel blockade for hypertensive myocardial infarction? A haemodynamic comparison of labetalol and nifedipine.

The haemodynamic impact of alpha- and beta-adrenoceptor blockade (labetalol) was compared with that of slow-calcium channel blockade (nifedipine) in 32 patients with sustained elevation of systemic arterial pressure (systolic blood pressure greater than 160; diastolic blood pressure greater than 95 mmHg) following a recent myocardial infarction (6-22 h). Patients with normal (pulmonary artery occluded pressure; (PAOP less than 18 mmHg; n = 16) or impaired (PAOP greater than 18 mmHg; n = 16) left ventricular function were randomized to labetalol (1 mg/kg i.v. 15 min) or nifedipine (20 mg sublingually) and haemodynamic profile was measured over 2 h. Both drugs equally reduced mean systemic arterial pressure (P less than 0.01 versus pretreatment control), and presumably left ventricular afterload; however, the heart rate (P less than 0.01) and cardiac index (P less than 0.01) increased after nifedipine, contrasting with reductions in both variables following labetalol (P less than 0.01). The elevated left ventricular filling pressure was reduced by both labetalol (P less than 0.05) and nifedipine (P less than 0.01) but the reduction was greater following nifedipine (-2 mmHg versus -5 mmHg, P less than 0.05). Thus both compounds were equally effective hypotensive agents. Labetalol consistently reduced cardiac stroke work and double product, important determinants of myocardial oxygen requirements; however, nifedipine afforded some improvement in cardiac performance in patients with left ventricular dysfunction.

Adrenergic alpha-Antagonists↗

PubMed1988

Left ventricular failure complicating acute myocardial infarction--problems and potential of nonthrombolytic therapy.

Despite recent advances, problems in the treatment of acute myocardial infarction still remain. In the earliest stages of the syndrome thrombolysis holds substantial if not absolute promise but many patients present too late for it to be effective. In these latter individuals and those in whom thrombolysis was not successful, the major mortality risk is concentrated in those with left ventricular failure. Many drugs, including diuretics, vasodilators, ACE inhibitors and positive inotropes, singly or in combination, may be used to manipulate the circulation and correct partially or completely the abnormal circulatory profile. Despite such haemodynamic efficacy the impact of drug therapy on the high morbidity and mortality risk of patients with acute myocardial infarction complicated by left ventricular failure is still unknown.

Cardiotonic Agents↗

PubMed1988

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.

Administration, Oral↗

PubMed1988

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.

Administration, Cutaneous↗

PubMed1988

Pharmacological and therapeutic properties of an ideal beta-blocker.

With hindsight it is now possible to define some of the additional pharmacological characteristics which enhance the pharmacodynamic and therapeutic efficacy of a drug whose primary purpose is to antagonize competitively sympathetic stimulation of the heart. The ideal pharmacokinetic profile for a beta-blocker includes ready and unimpeded absorption; a predominantly hydrophilic distribution; a relatively long duration of pharmacological activity and alternative routes of elimination. The ideal pharmacodynamic activity of such a drug involves a number of factors, including the essential element of beta 1-adrenoceptor selectivity. In addition, moderate beta 2-adrenoceptor agonist activity and mild stimulation of myocardial contractibility afford enhanced haemodynamic efficacy. The intrinsic ability to relax vascular and bronchial smooth muscle are also highly desirable ancillary pharmacodynamic properties. From the therapeutic aspect, a drug administered with the primary objective of reducing myocardial ischaemia in patients with a coronary heart disease, or of lowering blood pressure in patients with hypertension, should not only prove effective in clinical practice, but should also be shown to have beneficial haemodynamic properties and a minimum of undesirable pharmacological effects. The unique pharmacological profile of celiprolol appears to allow fulfillment of many of these desirable objectives.

Adrenergic beta-Antagonists↗

PubMed1988

Influence of drug therapy on survival following acute myocardial infarction.

The treatment of the patient with acute myocardial infarction remains a complex field of endeavour. Undoubtedly thrombolytic therapy, if instituted sufficiently early, holds considerable promise for the immediate prevention of myocardial necrosis. Alone, however, without further endeavours to remove the offending obstruction that precipitated clot formation in the coronary arteries, the procedure is only temporarily palliative. The long-term results of thrombolysis plus coronary angioplasty or bypass surgery are awaited but are unlikely to be universally successful or universally applicable. Moreover for the foreseeable future it is probable that the majority of patients will continue to present with established myocardial infarction. The prognosis of these patients is dominated by the presence or absence of left ventricular failure complicating the acute event. In those without such a sinister complication the evidence available suggests that early treatment with beta-blocking drugs or nitrates may enhance their prognosis although the most that can be expected is that the chances of survival will be improved in only one patient for every 150 treated. Moreover it is impossible to predict the patient who will benefit from such treatment and the improvement in length of life-span that this single beneficiary may expect. The major mortality risk of acute myocardial infarction resides in patients who have lost a substantial amount of muscle which has resulted in pump failure of the left ventricle. Both the short-term and long-term mortality rates in these patients is high. A range of drugs exist with which it is possible to ameliorate the hemodynamic evidence of left ventricular failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents↗

PubMed1988

Drug therapy of chronic heart failure.

Chronic heart failure is an irremediable terminal syndrome. The inability of the heart to pump sufficient blood to meet the demands of metabolically active tissues is aggravated by reflex increases in peripheral vasoconstriction induced by the sympathoadrenal and renin-angiotensin-aldosterone systems. Vasoconstriction is partially attenuated by atrial natriuretic hormone, prostaglandin, and bradykinin. The aim of therapy is to improve the pumping performance of the heart and reduce arterial and venous constriction in the hope that this will reduce symptoms and improve the quality of life. Many drugs achieve such benefits, at least initially. Inotropic drugs increase cardiac pumping activity, and drugs acting directly on arteries and veins improve cardiac function by reducing afterload and preload. ACE inhibitors suppress angiotensin II formation, reducing its vasoconstrictive action, its ability to increase aldosterone secretion and the consequent salt retention and expansion of plasma volume. Since the proportionate role played by various hemodynamic factors in individual patients is unknown, it is likely that most benefit will be achieved by a combined therapeutic approach.

Chronic Disease↗

PubMed1987

Coronary artery disease risk factor management in the hypertensive patient.

Recent advances in understanding the relation of risk factors to coronary artery disease (CAD) have initiated a change in the approach to managing the hypertensive patient. Reduction of elevated blood pressure still remains a major therapeutic priority. However, the risk of cardiovascular morbidity is also related to hypercholesterolemia, hyperuricemia, hyperglycemia, hyperfibrinogenemia and obesity; all aggravate the risk of CAD in the patient with high blood pressure. Life-style is also important: cigarette smoking, high alcohol consumption and lack of physical exercise all predispose to precocious atheromatous CAD. Thus, the most favorable prognosis in terms of reducing CAD risk is accomplished by reducing elevated systemic arterial pressure while simultaneously improving all other risk factors. The method by which blood pressure is lowered is an important consideration. The ancillary metabolic activities of antihypertensive drugs now available differ widely. Diuretics and beta blockers, for example, have potentially adverse metabolic effects, whereas agents such as selective alpha 1-adrenoceptor inhibitors appear to beneficially affect several metabolic cofactors influencing the CAD risk profile. The impact of such drug-induced metabolic changes on overall prognosis of the hypertensive patient remains to be clarified. In the absence of other contraindications, however, it is sensible to use drugs that do not increase the metabolic predilection to precocious CAD.

Antihypertensive Agents↗

PubMed1987

Role of cardioselectivity and intrinsic sympathomimetic activity in beta-blocking drugs in cardiovascular disease.

The significance of ancillary properties of beta blockers continues to be the focus of considerable clinical investigation. Beta 1-selective blocking agents, such as acebutolol, inhibit cardiac beta 1 receptors, but have less influence on bronchial and vascular beta 2 receptors. Certain beta 1-selective blocking drugs, including acebutolol, have intrinsic sympathomimetic activity (ISA), also termed partial agonist activity. This property produces slight cardiac stimulation, which can be blocked by propranolol. Drugs with mild or moderate ISA have proven to be as clinically effective as beta blockers lacking this property. Additionally, drugs with ISA possess potential therapeutic benefits, particularly for patients with coronary artery disease. The hemodynamic influences of cardioselectivity and ISA on left ventricular function, heart rate, cardiac output, left-sided heart filling pressure and myocardial oxygen consumption in patients with coronary artery disease are now clearly defined.

Adrenergic beta-Antagonists↗

PubMed1987

Efficacy of a new calcium antagonist PN 200-110 (isradipine) in angina pectoris.

Angina pectoris is one of the major syndromes against which to test the therapeutic effectiveness of any new calcium antagonist. An interim analysis of the efficacy and safety of a new dihydropyridine calcium antagonist (PN 200-110 [isradipine]) in patients with confirmed coronary artery disease is reported. The study was carried out in 3 centers; 50 patients of an anticipated 96 have completed the double-blind comparative phases in 3 separate studies. Preliminary results from the placebo-controlled study indicate that PN 200-110 was significantly more effective than placebo in reducing the anginal attack rate and glyceryl trinitrate consumption in the 15 patients so far enrolled. Dose-response comparisons against nifedipine in 21 patients and against isosorbide dinitrate in 14 patients demonstrate that PN 200-110 has a similar antianginal efficacy profile to both drugs. No significant change in any of the monitored safety factors was noted in any of the patients taking PN 200-110. The side-effects profile compared favorably with that of nifedipine. These interim results suggest that PN 200-110 will prove to be an effective and safe drug for the treatment of angina pectoris.

Angina Pectoris↗