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Biomedical subjects

H Krum

Publications and source records attributed to H Krum.

At least 19 recordsLinked to original sources
PubMed1998

The effect of an endothelin-receptor antagonist, bosentan, on blood pressure in patients with essential hypertension. Bosentan Hypertension Investigators.

BACKGROUND: Endothelin is a powerful vasoconstrictor peptide derived from the endothelium. We evaluated the contribution of endothelin to blood-pressure regulation in patients with essential hypertension by studying the effect of an endothelin-receptor antagonist, bosentan. METHODS: We studied 293 patients with mild-to-moderate essential hypertension. After a placebo run-in period of four to six weeks, patients were randomly assigned to receive one of four oral doses of bosentan (100, 500, or 1000 mg once daily or 1000 mg twice daily), placebo, or the angiotensin-converting-enzyme inhibitor enalapril (20 mg once daily) for four weeks. Blood pressure was measured before and after treatment. RESULTS: As compared with placebo, bosentan resulted in a significant reduction in diastolic pressure with a daily dose of 500 or 2000 mg (an absolute reduction of 5.7 mm Hg at each dose), which was similar to the reduction with enalapril (5.8 mm Hg). There were no significant changes in heart rate. Bosentan did not result in activation of the sympathetic nervous system (as determined by measurement of the plasma norepinephrine level) or the renin-angiotensin system (as determined by measurements of plasma renin activity and angiotensin II levels). CONCLUSIONS: An endothelin-receptor antagonist, bosentan, significantly lowered blood pressure in patients with essential hypertension, suggesting that endothelin may contribute to elevated blood pressure in such patients. The favorable effect of treatment with bosentan on blood pressure occurred without reflexive neurohormonal activation.

Adult↗
PubMed1998

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.

Adult↗
PubMed1998

Efficacy and safety of carvedilol in patients with chronic heart failure receiving concomitant amiodarone therapy. Australia/New Zealand Heart Failure Research Collaborative Group.

BACKGROUND: The beta-blocker/vasodilator carvedilol is found to have beneficial effects in patients with chronic heart failure. However, the safety and efficacy of this agent in the presence of concomitant amiodarone therapy has not been previously determined. METHODS AND RESULTS: We retrospectively analyzed the Australia/New Zealand Carvedilol Heart Failure Research Collaborative Group study of 415 patients with mild to moderate ischemic heart failure where amiodarone was administered as part of the treatment therapy (in 52 patients). After the open-label carvedilol run-in, patients received carvedilol (target dose 25 mg twice daily) or placebo for an average of 19 months. The main adverse events during this double-blind period were worsened heart failure, hypotension/dizziness, bradycardia/atrioventricular block, and aggravation of angina. By Chi square analysis, carvedilol and amiodarone together were not associated with a greater overall incidence of adverse effects than either drug alone. The beneficial effects of carvedilol on left ventricular ejection that were observed in the main trial were preserved in the presence of amiodarone. CONCLUSIONS: Carvedilol is a useful additional therapy for patients with chronic heart failure already receiving amiodarone. Carvedilol can be added to amiodarone in these patients without expectation of increased adverse effects or loss of clinical efficacy.

Adrenergic beta-Antagonists↗
PubMed1998

Drug administration in patients with diabetes mellitus. Safety considerations.

Diabetes mellitus is associated with alterations in a number of key metabolic pathways. Despite theoretical concerns, clinically significant alterations in the pharmacokinetic properties of commonly prescribed drugs are relatively uncommon. Indeed, dose adjustment is rarely required in the setting of well controlled diabetes mellitus. However, significant alterations in drug handling may occur in the context of poor metabolic control or in the presence of complications such as nephropathy. Metformin use may be complicated by lactic acidosis. Fortunately, this is a rare occurrence providing that the agent is not used in circumstances in which it is contraindicated. Indeed, the risk of death from metformin-related lactic acidosis is similar in magnitude to the risk of death related to hypoglycaemia in sulphonylurea-treated patients. The novel hypoglycaemic agent troglitazone may be associated with abnormalities in liver function in approximately 2% of patients. Discontinuation of treatment is followed by normalisation of liver enzyme levels. Current prescribing information recommends frequent monitoring of liver function tests and immediate cessation of therapy if abnormalities develop. In addition to disturbances in intermediary metabolism, diabetes mellitus may also lead to chronic microvascular and marcovascular complications. Thus, in addition to the use of drugs for the control of blood glucose, patients with diabetes mellitus are likely to be prescribed medication for associated conditions such as cardiovascular disease. Such medication includes the ACE inhibitors which are contraindicated in patients with bilateral renal artery stenosis. This complication may be theoretically more common in patients with diabetes mellitus because of accelerated atherosclerosis. However, in clinical practice this is an uncommon occurrence in the absence of clinical features that should alert the treating clinician that an individual patient might be at high risk. Although caution should also be used with beta-blocker therapy in patients with diabetes mellitus, current evidence suggests that, like ACE inhibitors, these drugs may be particularly useful in this patient group.

Acarbose↗
PubMed1998

New and emerging drug treatments for hypertension.

BACKGROUND: Existing antihypertensive therapies are effective in lowering blood pressure, however, they are associated with adverse effects that may contribute to medication non-compliance. Furthermore, morbidity and mortality benefits have not been established with commonly used agents such as ACE inhibitors and calcium channel blockers. OBJECTIVE: Newer antihypertensive therapies offer similar efficacy with fewer adverse effects and may be of benefit in a number of concomitant disease states. DISCUSSION: This article examines the promise of the newer therapies: angiotensin II antagonists, T-type calcium channel blockers, dual metalloprotease inhibitors and endothelin receptor antagonists.

Adrenergic beta-Antagonists↗
PubMed1998

Effect of endothelin-1 on endothelium-derived vascular responsiveness in man.

1. Endothelium-dependent vasodilatation via nitric oxide in response to muscarinic stimulation is decreased in chronic heart failure while basal release of nitric oxide may be increased. As production of the endothelium-derived vasoconstrictor endothelin-1 is increased in chronic heart failure, endothelin-1 may act in an autocrine manner to modulate these effects. 2. To test this, we determined whether prolonged endothelin infusion in normal subjects would reproduce the alterations in basal and stimulated nitric oxide release observed in patients with chronic heart failure. Basal nitric oxide production was determined by measurement of forearm blood flow using strain gauge venous occlusion plethysmography before and after brachial artery infusion of a nitric oxide synthase inhibitor (NG-monomethyl-L-arginine). Stimulated nitric oxide production was determined by brachial artery infusion of acetylcholine. As metabolic vasodilatation is thought to be mediated in part via nitric oxide and is decreased in chronic heart failure, forearm blood flow during peak reactive hyperaemia was also measured. Studies were then repeated during brachial artery infusion of endothelin-1 and a non-specific vasoconstrictor, noradrenaline. 3. Neither basal nor stimulated nitric oxide production was altered by endothelin-1 and noradrenaline infusion. However, absolute forearm blood flow responses to peak reactive hyperaemia were decreased during infusion of endothelin-1 in comparison to noradrenaline. These data suggest that increased endothelin-1 may not contribute greatly to altered basal and stimulated nitric oxide production in patients with chronic heart failure but may contribute to impaired metabolic vasodilatation, by mechanisms presumably unrelated to altered nitric oxide production.

Acetylcholine↗
PubMed1997

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 23.7 ms2, and percentage of absolute differences >50 ms between successive normal RR intervals increased from 0.8% to 4.7%, all p <0.01, indicating a substantial increase in parasympathetic modulation of RR intervals.

Adrenergic beta-Antagonists↗
PubMed1997

'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. Therefore, we used non-invasive techniques to determine the acute effects of insulin on proximal and distal blood pressure. 2. Blood pressure was measured in the finger (Finapres) and arm (Dinamap monitor) during a two-stage euglycaemic clamp. Values obtained during the insulin infusion were compared with a control infusion. 3. Plasma insulin concentrations were 7.0 +/- 1.0 mu-units/ml at baseline and remained within the accepted post-prandial 'physiological' range during low- and high-dose insulin infusions (28.9 +/- 2.1 and 101.7 +/- 6.8 mu-units/ml respectively). From a baseline value of 130 +/- 3 mmHg, finger systolic blood pressure rose by 9.9 +/- 1.9 mmHg during the low-dose infusion (compared with 7.5 +/- 2.7 mmHg in control, P < 0.05) and by 21.9 +/- 2.3 mmHg during the high-dose infusion (compared with 14.6 +/- 3.1 mmHg in control, P < 0.01). Compared with control, insulin did not have an additional effect on arm pressures. 4. Although finger systolic pressure was increased by hyperinsulinaemia, this occurred in the absence of a change in mean blood pressure or in arm pressures. These data therefore suggest that insulin augmented pulse wave reflection. This novel haemodynamic effect of insulin could contribute to the association of insulin resistance with essential hypertension.

Adult↗
PubMed1997

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. Furthermore, reductions in cardiovascular morbidity associated with decreased hospitalization rates suggest pharmacoeconomic benefits with these agents. This review addresses the following issues regarding beta-adrenoceptor blockers in chronic heart failure: the known adverse effects of chronic sympathetic activation in heart failure, the theoretical benefits of blockade of this neurohormonal system, the current clinical database of beta-adrenoceptor blockers in heart failure and practical issues regarding the administration of these agents to these patients.

Adrenergic beta-Agonists↗
PubMed1997

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 73.6 +/- 6 yrs) with heart failure (NYHA Classes II-III) and in sinus rhythm. HRV was determined during 20-40 min supine rest at baseline and then at 2-weekly intervals during incremental dosing of oral captopril, 12.5 mg b.i.d., 25 mg b.i.d., and 50 mg b.i.d. Poincaré plot and conventional time- and frequency-domain measures were used to analyze the data. Low-dose captopril (12.5 mg b.i.d.) resulted in an increase in SD delta RR (16.0 +/- 6.6 to 22.0 +/- 9.1 ms; p < 0.05). We previously validated this as a measure of PSNA. Higher dose captopril (25 mg b.i.d.) also produced an increase in PSNA activity (16.0 +/- 6.6 to 18.7 +/- 7.8 ms), although this failed to reach statistical significance. However, the highest dose of captopril (50 mg b.i.d.) reduced PSNA activity to near-baseline values, as shown by measures of HRV in both the time and frequency domains. These data suggest that only a low dose of captopril augments PSNA in patients with heart failure. Dosing of ACE inhibitors may be important in optimizing their benefit in CHF.

Aged↗
PubMed1997

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. Epidemiological data have raised concerns regarding the use of rapid acting dihydropyridine agents in the treatment of hypertension and ischaemic heart disease. Slow release agents provide sustained therapeutic benefits with fewer side effects than standard dihydropyridine preparations.

Calcium Channel Blockers↗