'Physiological' hyperinsulinaemia increases distal artery systolic blood pressure without changing proximal blood pressure.

1. Although epidemiological data links essential hypertension with insulin resistance, 'physiological' insulin concentrations have not had pressor effects in humans. Our previous studies suggested that hyperinsulinaemia might have effects on distal blood pressure which are not detected more proximally.

Effect of endothelin-1 on exercise-induced vasodilation in normal subjects and in patients with heart failure.

Forearm blood flow (ml/min/100 ml) was determined with strain-gauge venous occlusion plethysmography at rest and in response to handgrip exercise in 7 patients with congestive heart failure and in 9 normal subjects before and after regional administration of endothelin-1 in the brachial artery. Administration of endothelin-1 significantly decreased forearm blood flow at rest and during exercise in normal subjects but did not change it at rest or during exercise in patients with congestive heart failure.

Long-term carvedilol therapy increases parasympathetic nervous system activity in chronic congestive heart failure.

To determine the effect of beta blockade on parasympathetic nervous system activity, we assessed RR variability during 24-hour Holter monitoring in 10 patients with congestive heart failure before and after 3 to 4 months of treatment with the beta blocker carvedilol. High-frequency power increased from 26 to 64 ms2, root-mean-square of successive differences in RR interval increased from 14.3 to 23.

Beta-adrenoceptor blockers in chronic heart failure--a review.

There are now considerable clinical trial data to support the use of beta-adrenoceptor blockers in patients with chronic heart failure due to systolic left ventricular dysfunction. Increases in ejection fraction, improved well-being as judged by both patient and physician and reduced progression of ventricular dysfunction have been demonstrated. From meta-analyses of available trial data, a mortality reduction of approximately 30% is obtained when these drugs are added to standard heart failure therapies.

Low-dose but not high-dose captopril increases parasympathetic activity in patients with heart failure.

Parasympathetic nervous activity (PSNA) is an important determinant of the risk of sudden death and outcome in patients with cardiovascular disease, so the effects of drug therapy on PSNA may be of prognostic importance in patients with chronic heart failure (CHF). The angiotensin-converting enzyme (ACE) inhibitors are the only drugs that are reasonably accepted to improve prognosis in such patients. Accordingly we determined PSNA by heart-rate variability (HRV) analysis in nine patients (four women and five men, aged 73.

Critical assessment of calcium antagonists.

Calcium antagonists have been demonstrated to be useful agents in the management of a wide variety of cardiovascular disorders. All calcium antagonists effectively lower blood pressure. Non dihydropyridine compounds (verapamil and diltiazem) are of particular benefit in the treatment of supraventricular arrhythmias and angina.

Exercise-induced vasodilation in forearm circulation of normal subjects and patients with congestive heart failure: role of endothelium-derived nitric oxide.

Objectives: This study was undertaken to investigate the role of endothelium-derived nitric oxide in the regulation of forearm blood flow during exercise in normal subjects and patients with congestive heart failure.

Background: Nitric oxide-mediated vasodilation in response to muscarinic stimulation is impaired in the peripheral circulation of patients with congestive heart failure. Whether nitric oxide-mediated vasodilation during exercise is also impaired in patients with congestive heart failure is unknown.

Poincaré plot of heart rate variability allows quantitative display of parasympathetic nervous activity in humans.

1. Time domain summary statistics and frequency domain parameters can be used to measure heart rate variability. More recently, qualitative methods including the Poincaré plot have been used to evaluate heart rate variability.

ACE inhibitors in cardiovascular disease. Which patient? Which drug? Which dose?

The increasing role of angiotensin converting enzyme (ACE) inhibitor therapy in cardiovascular disease makes it important for the practising clinician to be aware of the specific benefits afforded by these agents. This article covers the use of ACE inhibitors in hypertension, chronic heart failure, post myocardial infarction, diabetic nephropathy and atherosclerosis, with specific reference to clinical trial data and proposed mechanisms of effect.

Non-invasive assessment of baroreflex sensitivity and relation to measures of heart rate variability in man.

1. We have developed a simple noninvasive method to assess the spontaneous baroreflex (BRS; reflex heart rate response to change in systemic blood pressure) in man. The BRS is impaired in many cardiovascular disorders and is known to be of major prognostic significance; however, the invasive nature of traditional BRS assessment has thus far limited its clinical application.

Changes in plasma endothelin-1 levels reflect clinical response to beta-blockade in chronic heart failure.

Plasma levels of endothelin-1 are elevated in patients with chronic heart failure; however, it is unknown whether changes in plasma endothelin-1 levels accurately reflect clinical response to therapy in these patients. To determine this, we measured plasma endothelin-1 in addition to functional, hemodynamic, and other neurohormonal parameters as part of a double-blind, placebo-controlled study of the beta-blocker vasodilator carvedilol in patients with moderate to severe chronic heart failure. Patients were assigned (2:1 randomization) to receive carvedilol (25 mg twice daily, n = 10) or placebo (n = 5) for 14 weeks, with evaluations made before and after therapy.

Double-blind, placebo-controlled study of the long-term efficacy of carvedilol in patients with severe chronic heart failure.

Background: Clinical trials have shown that beta-adrenergic blocking drugs are effective and well tolerated in patients with mild to moderate heart failure, but the utility and safety of these drugs in patients with advanced disease have not been evaluated.

Methods And Results: We enrolled 56 patients with severe chronic heart failure into a double-blind, placebo-controlled study of the vasodilating beta-blocker carvedilol. All patients had advanced heart failure, as evidenced by a mean left ventricular ejection fraction of 0.

Role of endothelin in the exercise intolerance of chronic heart failure.

In conclusion, plasma levels of the endothelial-derived vasoconstrictor endothelin-1 (but not those of other neurohormonal vasoconstrictor factors), measured during exercise correlated closely with objective variables of exercise capacity in patients with heart failure. These findings suggest that endothelin-1 may contribute to exercise intolerance in patients with heart failure, perhaps by limiting the ability of the peripheral vasculature to dilate during exercise.

The effects of short-term alcohol intake on clinic and ambulatory blood pressure in normotensive 'social' drinkers.

Office blood pressure (OBP), ambulatory blood pressure (ABP), and vascular reactivity were measured in 12 normotensive 'social' drinkers (mean alcohol consumption of 9.7 +/- 3.1 g/day) after 4 days of alcohol consumption (1 g/kg/day) and compared with the effects of an isocaloric substitute (sucrose, 1.

Efficacy of pravastatin in combination with captopril in hypertensive patients.

Objective: To determine the efficacy of pravastatin in the treatment of primary hypercholesterolaemia in patients being treated with captopril for hypertension.

Design: A double-blind parallel group study comparing 12 weeks of pravastatin therapy (20-40 mg/day) with placebo.

Participants: 25 patients (age, 37-73 years) with mild-to-moderate hypertension and hypercholesterolaemia (total cholesterol level, 5.

Effect of long-term digoxin therapy on autonomic function in patients with chronic heart failure.

Objectives: This study was conducted to determine the effect of long-term digoxin therapy on autonomic function in patients with mild to moderate chronic heart failure.

Background: Chronic heart failure is characterized by increased sympathetic activity and decreased parasympathetic activity. Intravenous digitalis has been found to reduce sympathetic activity immediately in these patients, but whether short-term neurohormonal effects are sustained during long-term oral therapy has not been assessed.

The effect of levcromakalim (BRL 38227) on bladder function in patients with high spinal cord lesions.

The effects of the potassium channel opener levcromakalim (BRL 38227) 7.5 micrograms kg-1 were examined on urodynamic variables and blood pressure during inflow and voiding cystometry in six high spinal cord lesion patients. Levcromakalim administration significantly increased the duration of bladder contraction (197 +/- 128 s to 267 +/- 167 s, P < 0.

Potential of left ventricular assist devices as outpatient therapy while awaiting transplantation.

Left ventricular assist devices (LVADs) increasingly are being used as a bridge to transplantation. We studied changes in New York Heart Association class, mean arterial pressure, resting cardiac output, end-organ function, exercise oxygen consumption, and exercise cardiac output in 12 LVAD recipients. In addition, resting levels of neurohormonal factors were evaluated 4 to 16 weeks after implantation.

Short term effects of pravastatin on blood pressure in hypercholesterolaemic hypertensive patients.

In this study, which was primarily designed to determine the lipid-lowering efficacy of pravastatin in the setting of background antihypertensive therapy with ACE inhibitors and calcium antagonists, we took the opportunity to examine whether pravastatin interacts with antihypertensive therapy to produce additional falls in blood pressure. This may help clarify the mechanism of action of pravastatin's rapid beneficial effects on cardiovascular morbidity. We treated 25 hypertensive hypercholesterolaemic patients with 12 weeks of either pravastatin or placebo in this double blind, placebo controlled parallel group study.