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Biomedical subjects

H Krum

Publications and source records attributed to H Krum.

At least 73 records · Page 4Linked to original sources
PubMed1996

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. Compared to patients receiving placebo, patients receiving carvedilol improved significantly as assessed by the parameters described. These changes were paralleled by significant falls in endothelin-1 with carvedilol (-2.1 + 3.8 pg/ml) in comparison to placebo (2.2 + 3.9 pg/ml; p < 0.05 for between-group differences). Changes in endothelin-1 after treatment in both groups correlated significantly with changes in symptom severity, New York Heart Association class, 6-minute walk distance (r = 0.64 to 0.80; p < 0.05), hemodynamic parameters (ejection fraction, right atrial pressure, pulmonary artery diastolic pressure, pulmonary wedge pressure, right atrial pressure, and stroke volume index; r = 0.54 to 0.86; p < 0.05), and neurohormonal parameters (serum aldosterone and plasma norepinephrine (r = 0.74 to 0.76; p < 0.05). By stepwise regression analysis, change in endothelin-1 was an independent, noninvasive predictor of functional and hemodynamic responses to therapy in these patients. These findings suggest that endothelin-1 accurately reflects functional, hemodynamic, and neurohormonal responses to beta-blocker therapy in patients with congestive heart failure. Measurement of endothelin-1 may therefore be a useful, noninvasive approach to the evaluation of clinical response to drug therapy in these patients.

Adrenergic beta-Antagonists↗
PubMed1996

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. The aim of this study was to validate a novel method of quantitative analysis of the Poincaré plot using conventional statistical techniques. 2. Beat-to-beat heart rate variability was measured over a relatively short period of time (10-20 min) in 12 healthy subjects aged between 20 and 40 years (mean 30 +/- 7 years) during (i) supine rest, (ii) head-up tilt (sympathetic activation, parasympathetic nervous system activity withdrawal), (iii) intravenous infusion of atropine (parasympathetic nervous system activity withdrawal), and (iv) after overnight administration of low-dose transdermal scopolamine (parasympathetic nervous system augmentation). 3. The "width' of the Poincaré plot, as quantified by SD delta R-R (the difference between successive R-R intervals), was determined at rest (median 48.9, quartile range 20 ms) and found to be significantly reduced during tilt (median 19.1, quartile range 13.7 ms, P < 0.01) and atropine administration (median 7.1, quartile range 5.7 ms, P < 0.01) and increased by scopolamine (median 79.3, quartile range 33 ms, P < 0.01). Furthermore, log variance of delta R-R intervals correlated almost perfectly with log high-frequency (0.15-0.4 Hz) power (r = 0.99, P < 0.01). 4. These findings strongly suggest that the "width' of the Poincaré plot is a measure of parasympathetic nervous system activity. The Poincaré plot is therefore a quantitative visual tool which can be applied to the analysis of R-R interval data gathered over relatively short time periods.

Adult↗
PubMed1996

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.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

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 0.16 +/- 0.01 and a mean maximal oxygen consumption of 13.6 +/- 0.6 mL.kg-1.min-1 despite digitalis, diuretics, and an angiotensin-converting enzyme inhibitor (if tolerated). After a 3-week, open-label, up-titration period, 49 of the 56 patients were assigned (in a double-blind fashion using a 2:1 randomization) to receive either carvedilol (25 mg BID, n = 33) or matching placebo (n = 16) for 14 weeks, while background therapy remained constant. Hemodynamic and functional variables were measured at the start and end of the study. Compared with the placebo group, patients in the carvedilol group showed improved cardiac performance, as reflected by an increase in left ventricular ejection fraction (P = .005) and stroke volume index (P = .010) and a decrease in pulmonary wedge pressure, mean right atrial pressure, and systemic vascular resistance (P = .003, .002, and .017, respectively). In addition, compared with placebo, patients treated with carvedilol benefited clinically, as shown by an improvement in symptom scores (P = .002), functional class (P = .013), and submaximal exercise tolerance (P = .006). The combined risk of death, worsening heart failure, and life-threatening ventricular tachyarrhythmia was lower in the carvedilol group than in the placebo group (P = .028), but carvedilol-treated patients had more dizziness and advanced heart block. CONCLUSIONS: Carvedilol produces clinical and hemodynamic improvement in patients who have severe heart failure despite treatment with angiotensin-converting enzyme inhibitors.

Adrenergic beta-Antagonists↗
PubMed1995

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.

Adult↗
PubMed1995

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, 5.5-8.8 mmol/L). RESULTS: Pravastatin reduced total cholesterol levels by 22% (from 7.1 +/- 0.29 [SEM] to 5.5 +/- 0.25 mmol/L; P < 0.001) and low-density-lipoprotein cholesterol levels by 32% (from 5.0 +/- 0.32 to 3.4 +/- 0.28 mmol/L; P < 0.001) in four weeks and these levels were maintained for the 12 weeks of therapy. Pre-pravastatin values returned three weeks after stopping therapy. Levels of total cholesterol, cholesterol fractions and triglycerides remained constant or deteriorated in the placebo group. Pravastatin therapy was well tolerated. An integrated coronary risk score showed a 40% reduction in risk. CONCLUSION: This study indicates that pravastatin (combined with captopril) is an effective cholesterol-lowering drug, but that treatment needs to be maintained.

Adult↗
PubMed1995

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. METHODS: We determined sympathetic activity in 26 patients with heart failure by measuring plasma norepinephrine levels and parasympathetic activity from variables of heart period variability derived from 24-h ambulatory electrocardiographic Holter recordings obtained before and after 4 to 8 weeks of digoxin therapy. RESULTS: After digoxin therapy, plasma norepinephrine decreased significantly from a mean +/- SEM of 552 +/- 80 to 390 +/- 37 ng/ml. In addition, the RR interval increased significantly from 719 +/- 19 to 771 +/- 20 ms. High frequency power increased from 84 +/- 24 to 212 +/- 72 ms2, and the root mean square of successive differences in RR interval increased from 20.3 +/- 1.8 to 27.0 +/- 3.4 ms, indicating a substantial increase in parasympathetic activity. Low frequency power, an index of baroreflex activity, was also significantly increased (239 +/- 80 to 483 +/- 144 ms2) by digoxin therapy. CONCLUSIONS: These results indicate 1) that long-term therapy with digoxin acts to ameliorate the autonomic dysfunction of patients with heart failure, and 2) that the short-term neurohormonal effects of digoxin are sustained during prolonged treatment with the drug.

Autonomic Nervous System↗
PubMed1995

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, 1.75 g/kg/day) or no intervention. Alcohol consumption did not affect OBP or 24-mean ABP but appeared to decrease nocturnal systolic and diastolic blood pressure soon after consumption. Although vascular reactivity did not differ between the groups, the blood pressure rise in response to isometric exercise tended to be lower following alcohol. Thus, short-term alcohol ingestion by normotensive 'social' drinkers does not increase office or ambulatory blood pressure.

Adult↗
PubMed1995

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 < 0.05) and also reduced blood pressure (126 +/- 13/67 +/- 9 mm Hg to 104 +/- 25/52 +/- 12 mm Hg) but was without effect on other urodynamic parameters. Because of concerns about hypotensive responses, further studies involving higher doses of levcromakalim should be considered only if the drug was administered intravesically.

Adult↗
PubMed1994

Beta-blockers.

Explore the source record for details and available documents.

Adrenergic beta-Antagonists↗
PubMed1994

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. Two of the 12 patients died of right heart failure and 1 of aspiration; all deaths occurred in the first 2 weeks after LVAD implantation. Of the other 9 patients, 8 improved to New York Heart Association class I and 1 to class II, all of whom were in class IV preoperatively. The 4 patients who underwent exercise testing achieved an exercise oxygen consumption of 15.0 +/- 2.7 mL.kg-1.min-1, which was paralleled by an increase in resting cardiac output from 3.07 +/- 0.9 L.min-1 preoperatively to 5.66 +/- 1.1 L.min-1 at 2 months, and mean arterial pressure from 60 +/- 8 to 91 +/- 10 mm Hg at 2 months, a benefit that was maintained for up to 10 months. End-organ function revealed comparable improvement at 2 months for both creatinine (1.68 +/- 0.7 to 1.0 +/- 0.19 mg.dL-1) and total bilirubin (1.37 +/- 1.17 to 0.54 +/- 0.26 mg.dL-1) levels. Levels of neurohormones were within normal limits. Adverse clinical events after the perioperative period were minimal, and no thromboembolic complications occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Spontaneous endothelin production by circulating mononuclear cells from patients with chronic heart failure but not from normal subjects.

1. Plasma endothelin-1 (ET-1) levels are increased in chronic heart failure (CHF). Because chronic immunologic activation occurs in CHF and mononuclear cells (MNC) are capable of ET-1 production, the possible contribution of circulating MNC to the increased plasma ET-1 levels in CHF patients was investigated. 2. Unseparated MNC (10(7)/mL) from eight CHF patients spontaneously produced ET-1 (1.54 +/- 0.37 pg/100 mL). After separation of MNC into monocytes (10(6)/mL) and lymphocytes (10(7)/mL) at ratios approximating those in the circulationg, ET-1 was spontaneously produced by CHF lymphocytes (0.81 +/- 0.26 pg/100 mL), and after macrophage colony stimulating factor (MCSF) stimulation by CHF monocytes (0.56 +/- 0.08 pg/100 mL). In contrast, there was neither spontaneous nor MCSF-induced production of ET-1 in six normal subjects. 3. It was concluded that heightened ET-1 production by MNC may contribute to increased plasma levels in CHF patients. Because unseparated MNC produced greater ET-1 than lymphocytes and monocytes separately, contact between these MNC subtypes may be necessary for maximal ET-1 production.

Adult↗
PubMed1994

A risk-benefit assessment of carvedilol in the treatment of cardiovascular disorders.

Carvedilol is a nonselective beta-adrenoceptor blocking vasodilator drug that may be a promising new agent in the management of cardiovascular disease. The rationale for the development of agents of this type is that the alpha-blocking component may overcome the direct vasoconstrictor consequence of beta 2-blockade, whilst the beta-blocker component may inhibit the reflex tachycardia that occurs following alpha-blockade. In clinical trials published to date, carvedilol has been demonstrated to be effective as an antihypertensive agent as monotherapy and also as additional therapy in those patients whose blood pressure cannot be controlled on other standard agents. It is also effective in the management of angina. Carvedilol has beneficial haemodynamic effects in patients with congestive heart failure. beta-Blocker vasodilator drugs of this type may be particularly useful in this condition as the vasodilator component of the drug may overcome the initial negative inotropy of the beta-blocker. In addition, carvedilol possess potentially useful pharmacological actions. In particular, the drug has antimitogenic and free radical scavenging effects that may make it a useful therapy in the long term management of atherosclerotic vascular disease. Its metabolic profile is also favourable, presumably on the basis of its alpha-blocking properties. Thus, beta 2-mediated adverse effects on peripheral vascular tone, glycaemic control and lipid status appear to be offset by the alpha-blocking property of the drug. Carvedilol thus far appears to be well tolerated, with postural dizziness the major adverse effect, especially in the elderly. As with nonselective beta-blockers, carvedilol is contraindicated in patients with asthma.

Adrenergic beta-Antagonists↗
PubMed1994

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. Placebo treatment did not alter plasma lipids, whereas 12 weeks' treatment with pravastatin reduced total cholesterol by 27% (from 7.1 +/- 0.27 to 5.2 +/- 0.18, p < 0.001 compared with placebo) and low density lipoprotein cholesterol by 35% (from 4.9 +/- 0.36 to 3.2 +/- 0.17, p < 0.001). There were no changes in systolic or diastolic blood pressure either following 12 weeks' treatment or 3 weeks' withdrawal of pravastatin. Thus, pravastatin remains efficacious as a lipid lowering agent in the presence of antihypertensive therapy but does not enhance the blood pressure lowering action of these drugs. Therefore it is unlikely that blood pressure reduction is the mechanism by which pravastatin mediates its reported short term effects on cardiovascular morbidity.

Blood Pressure↗