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Biomedical subjects

S H Taylor

Publications and source records attributed to S H Taylor.

At least 55 records · Page 3Linked to original sources
PubMed1990

How does posture influence the haemodynamic assessment of a cardiovascular drug? Experience with nicardipine.

The extent to which posture altered the haemodynamic response to slow calcium channel blocker nicardipine was evaluated in 22 male patients with angiographically confirmed coronary artery disease. Patients were randomly allocated to supine or upright posture and an otherwise identical protocol performed in each group. At rest, following a 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 period of 40 min; haemodynamic indices were recorded during the 3-5 min following each 5 min infusion. The exercise effects of the drug, in each posture, were determined by comparison of a control predrug exercise with observations at the same workload following the maximal cumulative dose. Nicardipine reduced resting mean blood pressure (MBP) and systemic vascular resistance index (SVRI) in both postures, the decrease being more pronounced when upright (MBP, -12%, -18%; p less than 0.01: SVRI, -30%, -46%; p less than 0.01). The increases in cardiac index (CI) and stroke volume index (SVI) were higher when upright (29 and 54% vs. 10 and 27%; p less than 0.01). Pulmonary artery occluded pressure (PAOP) increased by 29% when upright, without change when supine. On exercise, the effects for HR, MBP, CI, SI, and SVRI responses were independent of posture; however, a qualitative difference was apparent for PAOP (-17% vs. +14%; p less than 0.05). Thus, although the actions of nicardipine were qualitatively similar, quantitative differences related to posture were confirmed. These differences appeared to relate to posture-related baseline haemodynamic differences between the groups but with similar postnicardipine absolute values.

Adult↗
PubMed1990

Haemodynamic and radionuclide effects of amlodipine in coronary artery disease.

1. The haemodynamic and radionuclide effects of a new long-acting slow-calcium channel blocking agent, amlodipine, were evaluated in 32 patients with coronary artery disease. 2. Haemodynamic measurements in 24 patients were made at rest and 10 to 15 min after 20 mg i.v. amlodipine. Amlodipine significantly reduced systemic arterial blood pressure and vascular resistance index with an increased heart rate and augmented cardiac index. Cardiac stroke volume index rose and stroke work fell without change in pulmonary artery occluded pressure (PAOP). 3. The exercise effects were determined by comparison of measurements during 4 min of supine bicycle exercise at a fixed workload before and after drug treatment. During dynamic exercise, amlodipine reduced systemic arterial pressure and vascular resistance index. Exercise cardiac index, stroke volume index and heart rate were higher. The left ventricular filling pressure was significantly reduced. 4. Radionuclide parameters were studied in 16 patients at rest and on exercise; ejection fraction was unaltered following amlodipine. 5. Pre-therapy haemodynamic values correlated with response following amlodipine for resting mean blood pressure, systemic vascular resistance and exercise PAOP. 6. Thus, the immediate impact of amlodipine in stable coronary artery disease was to reduce left ventricular afterload and thereby improve cardiac pumping performance.

Adult↗
PubMed1990

Pharmacodynamic monitoring during acute intervention in ischaemic heart disease using a new echo-Doppler device.

1. We have utilised a new non-imaging echo-Doppler cardiac output device, using the principle of attenuated compensated volume flow (ACVF), to assess the cardiovascular effects of atenolol and buccal nitroglycerin (NTG) in a placebo-controlled study of 30 patients with coronary disease. 2. Atenolol (4 mg i.v.) reduced heart rate, cardiac output and time-averaged mean aortic velocity (P less than 0.01) and increased systemic vascular resistance (P less than 0.01). 3. Buccal NTG (5 mg) reduced systemic mean arterial pressure (P less than 0.01), cardiac stroke volume (P less than 0.05) and stroke length (P less than 0.01). 4. Thus although both drugs reduced time-averaged aortic velocity (an index of cardiac performance), the concomitant reduction in cardiac stroke length and tachycardia suggested sub-optimal cardiac filling for buccal NTG, whereas for atenolol (with the associated increased systemic vascular resistance but unchanged stroke length) attenuation of sympathetic stimulation at cardiac beta-adrenoceptors. 5. The ACVF method of cardiovascular monitoring should prove useful in human pharmacodynamic studies.

Adult↗
PubMed1990

Haemodynamic dose-response effects of UK-52,046 in ischaemic disease with or without impaired left ventricular function.

1. The haemodynamic effects of a new cardioselective postsynaptic alpha 1-adrenoceptor antagonist UK-52,046, were evaluated in 25 patients with stable coronary disease, with or without impaired left ventricular function. At rest the haemodynamic effects to two dose-response regimens were determined. In an initial eight patients 0.125, 0.125 and 0.25 micrograms kg-1 were administered peripherally at 15 min intervals; the haemodynamic measurements were determined between 10 to 15 min after each dose. In a further 17 patients, the dose regimen was doubled yielding a cumulative dose-regimen of 0.25, 0.5 and 1.0 micrograms kg-1. The exercise effects were determined by comparison of measurements during 4 min of supine sub-maximal bicycle exercise at a fixed workload before and after drug treatment. 2. At rest, the lower dose regimen of UK-52,046 significantly reduced systemic mean arterial blood pressure (-5 mm Hg; P less than 0.05) and increased cardiac index (+0.2 l min-1 m-2, P less than 0.01). The higher dose regimen of UK-52,046 reduced systemic mean arterial blood pressure (-7 mm Hg; P less than 0.01), pulmonary artery occluded pressure (PAOP) (-2 mm Hg, P less than 0.01) and vascular resistance index (-314 dyn s cm-5 m2; P less than 0.05) with an increase in heart rate (+7%, P less than 0.05) and cardiac index (+0.2 l min-1 m-2, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1990

Management of vascular risk factors in the hypertensive patient.

Understanding of the multiple risk factors for premature vascular degeneration is essential for the most effective management of the hypertensive patient. High blood pressure is the most important single predictor of coronary heart disease risk in general clinical practice in the UK. However, hypertension is only a marker of an apparent excess of other risk factors for coronary heart disease among hypertensive patients. The global management of the patient is further complicated for two reasons. First, many of the risk factors are complexly interrelated, either biologically or by lifestyle. Second, the attempted correction of one factor is fraught with the potential for aggravation of the others. The benefits to the coronary and vascular risk profile from lowering blood pressure may be offset, partially or completely, by the aggravation of other risk factors by the antihypertensive drug used. Optimum management of the hypertensive patient can only be achieved when all the risk factors for coronary heart disease in that individual are modified.

Alcohol Drinking↗
PubMed1990

Comparison of central and peripheral haemodynamic effects of dilevalol and atenolol in essential hypertension.

A new non-imaging echo-Doppler cardiac output device that works on the principle of attenuated compensation volume flow (ACVF), has been used to assess the cardiovascular effects of atenolol and dilevalol in 24 patients with essential hypertension. Compared with the baseline, one month of atenolol reduced systemic mean arterial blood pressure (12 mmHg; P less than 0.01), heart rate (-24 bpm; P less than 0.001), aortic velocity integral (-2.1 cm/sec; P less than 0.01) without a change in cardiac output or systemic vascular resistance. Dilevalol reduced systemic mean arterial pressure (-12 mmHg; P less than 0.01) and heart rate (-13 bpm; P less than 0.01), without a change in cardiac output or aortic velocity integral; systemic vascular resistance fell (-149 dyne/sec; P less than 0.01). Thermography and skin thermal clearance techniques were used to assess the effects of each compound on the peripheral circulation; both compounds reduced skin temperature and thermal clearance but the changes were more marked for atenolol than dilevalol. These results suggest that the mechanism of action of dilevalol is, in part, different from atenolol and would be compatible with a direct vasodilator action on the peripheral vasculature.

Analysis of Variance↗
PubMed1989

Hemodynamic assessment of nicardipine alone and with atenolol in coronary artery disease using a modified echo-Doppler device.

We have used a modified noninvasive echo-Doppler cardiac output device, based on the principle of attenuated compensation volume flow, to assess the cardiovascular effects of the slow-calcium antagonist nicardipine in coronary disease. The dose-response effects of 2.5, 5.0 and 10.0 mg intravenous nicardipine were determined in 8 patients with angina. Dose-related decreases were seen in systemic mean arterial pressure (p less than 0.01) after administration of nicardipine. Cardiac pumping indexes were improved, as evident from linear increases in cardiac stroke volume (p less than 0.001), stroke length (p less than 0.01) and time-averaged mean velocity (p less than 0.01). The echo-Doppler device was also used to assess beta-blocking/nicardipine combination therapy in patients with angina. When nicardipine was given after the cardioselective beta blocker atenolol the reduction in heart rate and cardiac output after atenolol was reversed compared with a group that received atenolol followed by placebo. Cardiac performance improved and the 35% reduction in systemic vascular resistance was associated with markedly increased cardiac index (p less than 0.01), augmentation of time-averaged mean velocity (p less than 0.01) and cardiac stroke length (p less than 0.05). These data are consistent with previous invasive studies of nicardipine, either alone or when combined with beta blockade in coronary disease. The data also suggest that nicardipine/beta-blocking combination is safe in patients with coronary heart disease and that the echo-Doppler method of cardiovascular monitoring will prove useful in human pharmacodynamic studies.

Adult↗
PubMed1989

Clinical pharmacotherapeutics of doxazosin.

Doxazosin is the latest in a series of highly selective postsynaptic alpha 1-adrenoceptor inhibitors. It is readily absorbed, with high bioavailability and a relatively long plasma half-life, neither of which property is influenced by age. This accounts for the prolonged pharmacologic activity of doxazosin following a single oral dose. Its prime pharmacodynamic activity resides in its ability to counter sympathetic vasoconstriction of the systemic arteriolar resistance vessels and venous capacitance system, which enables the drug to target the major pathophysiologic abnormality in hypertension, i.e., the generalized systemic arteriolar constriction. The widespread vasodilation induced by doxazosin relieves both cardiac preload and afterload and, consequently, reduces left ventricular wall stress and myocardial oxygen consumption. In hypertension, doxazosin reduces blood pressure both at rest and during exercise by reduction of systemic vascular resistance without precipitating substantial reflex cardiac stimulation. The effects are maximal on the standing blood pressure between two and four hours after ingestion; due to doxazosin's relatively slow absorption, postural hypotension is infrequent. Its antihypertensive activity is maintained over 24 hours following a single oral dose, and the optimal dose range is 2 to 8 mg once daily. The antihypertensive efficacy of doxazosin has been shown to be comparable with that of other alpha-adrenoceptor inhibitors, beta-blocking drugs, diuretics, calcium antagonists, and angiotensin-converting enzyme inhibitors. In contrast to other conventional antihypertensive drugs, a unique feature of alpha-adrenoceptor-inhibiting drugs, including doxazosin, is their ability to reduce the plasma concentrations of triglycerides, total cholesterol, and low-density lipoprotein cholesterol and to increase high-density lipoprotein cholesterol concentration. This contrasts with the opposite effect on lipid levels induced by hydrochlorothiazide and atenolol seen in comparative studies. Side effects show no predilection for any organ system, and the overall incidence of such effects compares well with those of other commonly used antihypertensive drugs. This unique combination of antihypertensive efficacy and favorable effect on blood lipid levels indicates that once-daily treatment with doxazosin holds considerable promise in the treatment of hypertension, both from the point of view of its antihypertensive efficacy and also from its primary preventative potential.

Adrenergic alpha-Antagonists↗
PubMed1989

Effects of nicorandil on left ventricular hemodynamics and volume at rest and during exercise-induced angina pectoris.

The hemodynamic effects of nicorandil (20 mg) were compared with placebo in a double-blind study of 20 patients with angiographically proved coronary artery disease at rest before and 7, 15, 30 and 60 minutes after oral dosing. The impact of the drug on left ventricular (LV) hemodynamics and volume during exercise-induced angina was determined by repeating exercise 60 minutes after drug administration, at the same work load that reliably induced angina during control predrug exercise. At rest, nicorandil reduced all components of systemic arterial pressure without change in cardiac or stroke volume indexes or heart rate. Pulmonary artery occluded pressure was reduced without change in LV ejection fraction or systemic vascular resistance index. Effects were evident at 7 minutes and peaked at 30 minutes with attenuation at 60 minutes. Compared with control supine bicycle exercise, the drug (at 60 minutes) reduced mean systemic arterial pressure and LV filling pressure without change in cardiac stroke volume indexes and heart rate. There was a smaller increase in LV ejection fraction. These data suggested greatest impact on LV function during exercise when substantial decreases in filling pressure occurred at maintained cardiac pumping indexes.

Adult↗
PubMed1989

The efficacy of amlodipine in myocardial ischemia.

Calcium antagonists are among the most potent and efficacious drugs used in the treatment of angina pectoris. Amlodipine, a new member of this family of dihydropyridines, has a unique pharmacokinetic profile with high bioavailability and an extended period of pharmacodynamic activity. In formal randomized, double-blind, placebo-controlled trials with exercise tests carried out 24 hours after administration, amlodipine was significantly more effective than the placebo and comparable in efficacy with the calcium antagonist diltiazem and the beta-blocking drug nadolol. In addition to extending exercise capacity in patients with angina pectoris, amlodipine significantly reduces ECG evidence of myocardial ischemia. Amlodipine has also been found to be effective in reducing the anginal attack rate in patients with vasospastic angina. From the evidence available, it is concluded that once-daily treatment with amlodipine in the dose range of 5 to 10 mg is effective in improving exercise capacity and reducing anginal attack rate in patients with chronic stable angina pectoris and also those with vasospastic angina.

Adrenergic beta-Antagonists↗
PubMed1989

Therapeutic targets and expectations for the treatment of heart failure.

Drug therapy for heart failure holds considerable promise. Direct support of cardiac pumping activity with positive inotropic drugs provides a specific correction for the failing myocardium. Vasodilatation of the systemic arteriolar resistance and venous capacitance systems affords a different but equally rational remedy. Volume and pressure load on the heart is reduced and this augments the pharmacodynamic effects of drugs with positive inotropic activity. For this reason, drugs possessing both pharmacodynamic attributes are an important development in heart failure. The precise clinical targets at which heart failure therapy must be aimed are: (i) relief of symptoms and improvement in quality of life; (ii) reduced risk of morbid events, particularly ventricular arrhythmias; and (iii) extension of survival. Whilst the pathophysiological targets for drug intervention are the same at all stages of the syndrome, expectations of benefit are likely to depend on the stage at which therapy is instituted. In early or mild heart failure, when the patient is not markedly impaired by symptoms, the most that can be expected from treatment is a marginal improvement in quality of life but a major improvement in survival expectancy. In contrast, treatment of severe heart failure may be expected to improve the quality of life substantially by relieving the oppressive symptoms of the advanced syndrome, but only a relatively small increase, if any, in survival. Nevertheless, when the syndrome is terminal, improvement in quality of life carries a clinical priority far in excess of prolonged survival.

Cardiotonic Agents↗
PubMed1989

Nitrate therapy for left ventricular failure complicating acute myocardial infarction: a haemodynamic comparison of intravenous, buccal, and transdermal delivery systems.

The haemodynamic effects of three different methods of nitrate administration [intravenous (i.v.) isosorbide dinitrate (ISDN) and buccal and transdermal nitroglycerin (NTG)] were evaluated in 36 patients with acute left ventricular failure due to a recent myocardial infarction. Similar reductions in pulmonary artery occluded pressure (p less than 0.01) followed all three regimens without change in heart rate and cardiac and stroke volume indices. Significant reductions in systemic arterial pressure and vascular resistance followed both ISDN and buccal NTG but not transdermal NTG. A disadvantage of the buccal NTG delivery was an abrupt and, on occasion, inappropriate reduction in blood pressure. The more gradual and controlled reduction of systemic blood pressure with substantial falls in pulmonary artery occluded pressure following ISDN infusion suggest that in the context of myocardial infarction this method of nitrate delivery may have safety advantages; however, when invasive haemodynamic monitoring facilities are not available, transdermal delivery may offer a practical alternative.

Administration, Buccal↗
PubMed1989

A comparison of the efficacy and safety of quinapril with that of enalapril in the treatment of mild to moderate essential hypertension.

This twenty-eight-week double-blind study in patients with mild to moderate essential hypertension showed quinapril (10, 20, and 40 mg/day) to be similarly effective to enalapril at the same doses in producing clinically significant reductions in sitting DBP. Hydrochlorothiazide could be safely added to quinapril therapy in nonresponders. Quinapril and enalapril were well tolerated. Both agents can safely be administered as first-line therapy.

Adult↗
PubMed1989

Comparative effects of atenolol and cicloprolol on cardiac performance in coronary heart disease.

Cicloprolol is a new cardioselective beta-blocking agent with partial agonist activity (intrinsic sympathomimetic activity, ISA). Its haemodynamic profile was compared with that of atenolol (cardioselective; no ISA) in a comparative dose-response study of 24 ischaemic patients with diminished cardiac reserve. Following a stable control period, equivalent intravenous (i.v.) beta-blocking boluses of atenolol (1, 1, 2, and 4 mg) or cicloprolol (0.025, 0.025, 0.05, and 0.1 mg/kg) were randomly administered and haemodynamics and left ventricular ejection fraction were determined at rest and during bicycle exercise. At rest, atenolol reduced heart rate (HR) and cardiac index; diastolic blood pressure (DBP), systemic vascular resistance index (SVRI), and pulmonary artery occluded pressure (PAOP) increased without change in mean arterial pressure (MAP). Cicloprolol increased left ventricular ejection fraction, reduced its end-diastolic volume, and tended to reduce filling pressure without change in other variables. During exercise, atenolol reduced ejection fraction and increased SVRI; in contrast, cicloprolol did not significantly alter these parameters. Attenuation of exercise tachycardia and cardiac index increase was similar after each agent. Thus, the cardiac performance assessed from left ventricular stroke index or ejection fraction/filling pressure relationships was less depressed after cicloprolol as compared with atenolol. The relevance of such haemodynamic differences to exercise ability or quality of life during sustained therapy warrants examination.

Adrenergic beta-Antagonists↗
PubMed1989

Celiprolol and risk factor reversal in hypertension.

beta-Blockers reduce hypertension effectively and safely. However, their overall efficacy is a balance between their influence on blood pressure and their influence on other important risk factors. Thus, whereas a drug may ameliorate the primary blood pressure marker of the syndrome, this effect may be negated by enhancement of aggressive cofactors. The evolution of the beta-blockers exemplifies how this potentially dangerous conflict may be counteracted. The latest "third-generation" agents, such as celiprolol, not only achieve their primary objective of lowering blood pressure, but also have the potential to simultaneously reverse some of the deleterious cofactors. For example, celiprolol reduces the threat of atheroma by lowering serum cholesterol, and enhances the efficacy of myocardial oxygen utilization in heart failure by reducing plasma triglyceride metabolism. Its ability to reduce fibrinogen and its lack of effect on glucose metabolism are additional positive factors. Celiprolol also provides the combined pharmacodynamic advantages of vasodilatation and inotropic support of the heart, and it attenuates the myocardial oxygen-wasting effects of sympathoadrenal stimulation. These attributes all make a positive contribution to cardiovascular risk reversal in the hypertensive patient.

Adrenergic beta-Antagonists↗
PubMed1989

Pharmacotherapeutic profile of ibopamine in heart failure.

Heart failure is a complex cardiovascular syndrome affording many pharmacotherapeutic targets. Ibopamine affords a unique pharmacological profile for the treatment of this complex syndrome by virtue of its ability to stimulate DA-1 and DA-2 receptors in the vasculature in combination with its beta 2-agonist activity. The drug has been shown to improve the Frank-Starling relationship in the failing heart and augment cardiac output and ejection fraction at the same time that cardiac filling pressure is reduced. Concomitantly, the drug has been shown to attenuate the activated neuroendocrine responses activated in heart failure. Clinically, ibopamine has been shown to improve exercise tolerance, reduce the patient's symptom score, and NYHA classification, and reduce the requirement for additional anti-heart failure drugs. The influence of ibopamine on survival in heart failure awaits pragmatic tests, but the results of open monitoring studies are promising in this respect. Ibopamine does not appear to have any substantial adverse reactions that would inhibit its use in patients in heart failure. The unique pharmacotherapeutic profile of ibopamine affords a new pharmacologic vista for the treatment of patients with chronic heart failure.

Adrenergic beta-Agonists↗