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Biomedical subjects

W Kiowski

Publications and source records attributed to W Kiowski.

At least 127 records · Page 7Linked to original sources
PubMed1990

Arterial vasodilator and antihypertensive effects of diltiazem.

The arterial vasodilator properties of the calcium antagonist diltiazem were investigated by measurement of changes of forearm blood flow during brachial artery infusions of eight dosages of diltiazem in eight hypertensive patients. Forearm blood flow increased and calculated forearm vascular resistance decreased dose-dependently (maximum decrease of 83.5 +/- 8.6%). When comparing the effects of calcium influx inhibition by diltiazem with stimulation of the vascular cyclic guanosine monophosphate (GMP) system by sodium nitroprusside, the vasodilation by diltiazem was approximately 1.6 times greater, attesting to its potent arterial vasodilator activity. The clinical efficacy and feasibility of diltiazem monotherapy was evaluated in 40 patients with mild to moderate essential hypertension treated with a slow-release formulation of diltiazem, 90 mg twice daily over 8 weeks, and in a subgroup of 21 patients with two tablets of 90 mg once daily in the morning over a period of 2 weeks. Blood pressure was lowered significantly and to a similar extent by either twice- or once-daily administration of diltiazem. This effect was maintained during open long-term therapy over a mean of 11 months. Heart rate and body weight did not change. Thus, the vasodilator properties of diltiazem can be utilized for effective long-term treatment of hypertension. The possibility of once-daily dosing may prove useful with respect to drug compliance in the long-term treatment of a generally asymptomatic disease such as hypertension.

Adult↗
PubMed1990

[The long-term management of heart transplant patients].

The long-term care of patients following heart transplantation is characterized by the problems associated with long-term immunosuppression. In addition, a specific form of coronary atherosclerosis develops within years in many patients requiring coronary angiography on a yearly basis. The examination of patients after heart transplantation does not reveal characteristic findings, as long as the transplanted heart functions properly and a normally functioning graft allows a functionally almost normal life. The dependence on a specialized center, which may be more or less depending on the clinical course, and the ever present knowledge of the potentially lethal consequences of a graft failure present a severe psychic stress to the patient. This stress is handled more or less well and requires special attention by the treating physicians and, ideally, an intact social environment. The care of patients in a center close to their place of living is less time consuming for the patient and relieves the burden of the transplanting center.

Follow-Up Studies↗
PubMed1990

Place of calcium antagonists in the treatment of hypertension.

The reduction of transmembraneous calcium influx into vascular smooth muscle cells by calcium antagonists leads to a reduction of tension development and vascular tone. Calcium antagonists reduce forearm vascular resistance dose dependently and this effect can be successfully utilized for the treatment of essential hypertension where they act by reducing increased peripheral vascular resistance thereby normalizing the main haemodynamic derangement of hypertensive patients. In contrast to other direct acting vasodilators the antihypertensive effect is not accompanied by sympathetic reflex activation or volume retention making it feasible to use calcium antagonists as monotherapy for hypertensive patients. In view of the well documented efficacy, tolerability and an excellent safety profile calcium antagonists have become drugs of choice for treatment of hypertension in many patients. Although all calcium antagonists have been shown to lower blood pressure they differ with respect to their vasodilating potency and their negative inotropic effects. The development of dihydropyridine calcium antagonists which are potent arterial vasodilators but have little if any negative inotropic effects at clinically used dosages further improves the safety profile of calcium antagonists, particularly when used in hypertensive patients with impaired left ventricular function.

Animals↗
PubMed1989

[Emergency coronary dilatation in acute myocardial infarct with contraindications to thrombolytic therapy: salvage of the myocardium by early intervention].

In 1986/87, emergency-PTCA in acute myocardial infarction was performed in 13 patients in whom thrombolysis was contraindicated. All infarct-related arteries could be opened with PTCA. Patency rate after one week was 94%. Reopening of the vessel resulted in immediate cessation of ischemic chest pain and in stable cardiac rhythm and hemodynamics. Prior cardiopulmonary resuscitation and/or cardiogenic shock did not influence short- or longterm outcome. In nine of eleven patients an improvement of left ventricular function was found after four to six months as compared to one to four weeks after PTCA. The functional result proved to be better if PTCA was performed early; PTCA within 90 minutes was associated with normal left ventricular function. Thus, PTCA is feasible as an emergency procedure in patients with acute myocardial infarction and contraindications to thrombolysis. It can salvage myocardium and improve or prevent severe infarct complications when performed early after onset of pain. Rapid hospital admission through the primary care physician importantly influences the outcome for these patients.

Adult↗
PubMed1989

Experimental and clinical experience with the calcium antagonist diltiazem in hypertension.

The arterial vasodilator properties of the calcium antagonist diltiazem were investigated by measurement of changes in forearm blood flow during brachial artery infusions of eight dosages of diltiazem in eight patients with mild to moderate hypertension. Forearm blood flow increased and calculated forearm vascular resistance decreased dose dependently. Comparison with the vascular effects of verapamil did not show any difference between the two drugs, attesting to their powerful vasodilator action. The clinical efficacy and feasibility of diltiazem monotherapy was evaluated in 40 patients with mild to moderate essential hypertension who were treated with a retarded formulation of 90 mg of diltiazem twice daily over 8 weeks. A subgroup of 21 patients were treated with two tablets of 90 mg of diltiazem once daily in the morning over 2 weeks. Blood pressure was lowered significantly as a result of either mode of diltiazem administration. This effect was maintained during open long-term therapy over a mean of 11 months. Heart rate and body weight did not change. Thus, the vasodilator properties of diltiazem can be utilized for effective long-term treatment of hypertension. The possibility of once-daily administration may prove useful for long-term treatment of a generally asymptomatic disease such as hypertension.

Diltiazem↗
PubMed1989

Effects of calcium antagonists on atherogenesis.

Calcium antagonists are able to reduce the development of atherosclerotic lesions in many animal models of atherosclerosis. Although the precise mechanisms of their antiatherogenic effects are unknown studies have shown interference with several pathogenetic mechanisms of the atherosclerotic disease process, namely preservation of endothelial integrity, reduced smooth muscle cell migration and proliferation, increased low density lipoprotein uptake and degradation in smooth muscle cells and reduced synthesis of matrix components. Many of these effects are unrelated to their blocking effects on voltage-dependent slow calcium channels, and most effects have been observed with very high concentrations only. Furthermore, differing calcium antagonists seem to influence these mechanisms differently but available data are difficult to interpret because of differences in study design and models used. With the exception of data on calcium antagonists for secondary prevention after myocardial infarction and their influence on the rate of restenosis after percutaneous transluminal angioplasty, no data are available in man with respect to a possible influence on atherosclerosis. Results from on-going studies designed to address specifically this issue must be awaited to answer the question whether the experimental findings can be extended to human atherosclerosis.

Animals↗
PubMed1989

The vasodilating effect of atrial natriuretic peptide in normotensive and hypertensive humans.

Atrial natriuretic peptide (ANP) infused intra-arterially into the forearm results in a dose-dependent vasodilator response of rapid onset. The maximal forearm vasodilator response to ANP amounts to about 60% of the maximal forearm vasodilator response to sodium nitroprusside and combined infusion of ANP and sodium nitroprusside has an additive vasodilator effect. ANP-induced vasodilation is greater than that of postjunctional alpha 1- or alpha 2-adrenoceptor blockade or of beta 2-adrenoceptor stimulation but is smaller than due to calcium entry blockade. ANP-induced vasodilation can easily be overcome by norepinephrine and to a lesser extent by angiotension II (Ang II). The similarity of the dose-response relationships for vasodilation and for natriuresis suggests that ANP may be equally effective on its renal and vascular targets. In patients with essential hypertension, intra-arterial infusion of ANP produced a greater vasodilator response than in normotensives and this was inversely related to plasma renin activity, suggesting greater vasodilator responsiveness to ANP in low-renin hypertension. ANP caused vasodilation in humans but this may become less apparent when ANP is infused into the systemic circulation because of cardiovascular sympathetic reflex mechanisms blunting ANP vasodilation. Although the role of ANP in circulatory disease states is unclear, it appears that it could serve a physiological function as an endogenous vasodilator (and natriuretic) principle for volume homeostasis in humans.

Atrial Natriuretic Factor↗
PubMed1989

Compensatory and adaptive mechanisms in congestive heart failure.

Knowledge of the basic alterations of central hemodynamics in congestive heart failure (CHF) has failed to explain many aspects of this important syndrome. Increasing attention has recently been paid to compensatory and adaptive mechanisms occurring after the initiating insult. Thus, new insights have been gained into the pathophysiology of contraction of hypertrophied myocardium and changes of adrenergic receptors in the myocardium due to chronically increased cardiac sympathetic tone. The role of the renin-angiotensin-aldosterone system in early and advanced CHF has been further elucidated and the role of the vasodilating and natriuretic atrial natriuretic peptide is undergoing further definition. New results further clarify the mechanisms leading to breathlessness and muscular fatigue in chronic CHF with emphasis shifting from the traditional concept of the importance of increased filling pressures to changes to the peripheral circulation and the exercising muscles. Although progress has been made in the understanding of the pathophysiology of CHF, many aspects are still poorly understood and await clarification.

Adaptation, Physiological↗
PubMed1989

Mechanisms of action and clinical use of calcium antagonists in hypertension.

Calcium antagonists are potent arterial vasodilators that do not lead to relevant chronic sympathetic reflex activation and sodium and volume retention. This favorable hemodynamic profile renders them suitable for monotherapy of hypertension in which they can reduce the calcium influx-dependent functional component of elevated vascular resistance that may be enhanced by altered vascular muscle cation handling and increased intracellular free calcium concentrations. Clinical studies have proved their efficacy, safety, and good tolerability alone or in combination with other drugs in uncomplicated hypertension in which they are particularly effective in older, low renin, and possibly, black patients. These properties and their efficacy in the treatment of severe and accelerated hypertension or hypertensive emergencies make them a valuable addition to already available drug therapy.

Animals↗
PubMed1988

Effects of vasodilators on the coronary circulation in congestive heart failure.

Pressure or volume overload of the myocardium increases the wall stress, particularly of the subendocardium, and leads to hypertrophy. Even though cardiac hypertrophy is viewed as a beneficial compensatory process that normalizes wall stress, the increased muscle mass carries with it the need of increased blood supply. Overall flow per unit mass is similar at rest in hypertrophic and normal hearts but a reduction of flow to the subendocardium and an increase in minimal coronary vascular resistance have been described. Thus, the potential exists for a vasodilator-induced steal mechanism shunting blood away from potentially ischemic areas. Angiotensin-converting enzyme inhibitors reduced myocardial oxygen consumption and coronary blood flow in parallel manner in some studies, indicating preserved coronary autoregulation, but there is also some evidence of a coronary vasodilator effect. Calcium antagonists reduce coronary vascular resistance and improve the myocardial demand-supply ratio, but the clinical usefulness of the newer compounds with supposedly little or no negative inotropic effects remains to be established. Hydralazine improved the myocardial oxygen demand-supply ratio in patients with dilated cardiomyopathy, but metabolic function may deteriorate more often after hydralazine than after angiotensin-converting enzyme inhibitors in patients with coronary heart disease. Similar observations have been made using alpha-adrenergic blockers. Although progress has been made in the understanding of the coronary circulation and the influence of vasodilators in congestive heart failure, many questions await clarification using refined or new methodology.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Antihypertensive monotherapy with nitrendipine in general practice.

Efficacy and feasibility of antihypertensive monotherapy with the calcium antagonist nitrendipine were investigated in a 6-week open trial in 768 patients with mild to moderate essential hypertension from 191 practicing internists and general practitioners. Previous antihypertensive therapy (n = 501) was withheld for 1 week and therapy then started with nitrendipine 20 mg q.d. If diastolic blood pressure before tablet intake in the morning stayed above 90 mm Hg or fell less than 10 mm Hg, the dose could be doubled to the maximum dose of 20 mg b.i.d. Alternatively, if blood pressure control was good, the dose could be halved to 10 mg q.d. One hundred thirty-four patients discontinued therapy prematurely because of unwanted effects mostly characteristic with dihydropyridines (headaches, flushes, and ankle edema) and mostly within the first 3 weeks. In 72% of the remaining 634 patients, the goal blood pressure was achieved by nitrendipine monotherapy (10 mg q.d. in 8%, 20 mg q.d. in 87%, and 20 mg b.i.d. in 5%) and diastolic blood pressure was between 90 and 95 mm Hg in another 3%. Reductions of blood pressure did not result in changes of heart rate or weight. Nitrendipine was effective in patients of all age groups but patients older than 65 years showed a significantly greater fall of systolic and mean arterial pressure than middle aged or young patients. Nitrendipine's efficacy under conditions of general practice and the high proportion of patients responding to once daily administration appear well suited for first-line therapy of uncomplicated hypertension. The incidence of side effects might have been smaller if therapy had started with a smaller dose.

Aged↗
PubMed1988

Hemodynamic and counterregulatory effects of calcium antagonists in hypertension.

Increased systemic vascular resistance in essential hypertension depends on increased calcium influx. Calcium antagonists lower cytosolic free calcium concentrations mainly through a reduction of transmembraneous calcium influx and are potent arterial vasodilators. Dihydropyridine calcium antagonists are pharmacologically more potent with respect to arterial vasodilatation than verapamil- or diltiazem-type calcium antagonists and have less or no clinically detectable negative inotropic effects, but this seems to be of importance only in patients with reduced cardiac function. All calcium antagonists lower high blood pressure through a reduction of elevated systemic vascular resistance without clinically relevant activation of sympathetic reflexes or the renin-angiotensin-aldosteron system. However, subtle changes of sympathetic nervous system activity may codetermine the acute and chronic blood pressure response. They do not lead to volume retention because of improved intrarenal hemodynamics and a diuretic effect. Interference with angiotensin and sympathetically mediated vasoconstrictor mechanisms probably also contributes to their antihypertensive effect. This hemodynamic profile is similar for all calcium antagonists but the degree of acute sympathetic stimulation seems to be greater for dihydropyridines. Their overall favorable hemodynamic and neurohumoral profile and their proven efficacy and lack of serious side effects have made calcium antagonists a valuable addition to the armanentarium available for monotherapy of hypertension.

Animals↗
PubMed1988

Calcium antagonists and their potential for antihypertensive therapy.

Calcium antagonists are potent arterial vasodilators devoid of relevant chronic sympathetic reflex activation and sodium and volume retention. This favorable hemodynamic profile of action renders them suitable for monotherapy of hypertension where they act to reduce an enhanced, calcium-influx-dependent vasoconstrictor mechanism which may be brought about by altered smooth muscle cation handling and increased intracellular free calcium concentrations. Clinical studies have proved their efficacy, safety, and good tolerability alone or in combination with other drugs in uncomplicated hypertension where they are particularly effective in older and low-renin and possibly black patients. These properties and their efficacy in the treatment of severe and accelerated hypertension or hypertensive emergencies make them a valuable addition to already available drug therapy.

Calcium↗
PubMed1988

Reduction in early recurrence of variceal bleeding by propranolol.

Survival after variceal bleeding depends greatly on the outcome of the immediate posthaemorrhagic period. This may in turn depend on the recurrence of bleeding. We therefore prospectively evaluated the influence of propranolol on the recurrence of variceal haemorrhage during the early period after the acute bleeding episode. Twenty consecutive patients with acute variceal haemorrhage and liver disease were randomly assigned to treatment either with propranolol or placebo orally for 14 days. Propranolol significantly decreased the rate of recurrence of variceal haemorrhage during this early period (p = 0.0028; 95% confidence interval in the placebo group, 90 +/- 20%; in the beta blocker group, 20 +/- 26%). Whereas a recurrence of variceal bleeding occurred in 9 of 10 patients in the placebo group, only 2 of 10 rebled during treatment with propranolol. These results suggest that propranolol may prevent rebleeding in the crucial early period after acute haemorrhage from oesophageal varices.

Acute Disease↗
PubMed1988

Age and the platelet serotonin vasoconstrictor axis in essential hypertension.

This review addresses the question of whether platelet-derived serotonin locally released at the resistance vessel wall may contribute via selective 5-hydroxytryptamine (5-HT) receptors to vasoconstriction and whether this chain of events is enhanced with age and high blood pressure. In platelets from animals and humans, both age and hypertension are associated with greater shape change and aggregation responses, reduced serotonin uptake and content, and increased release. Removal of the endothelium, age, and high blood pressure enhance vasoconstrictor responses to serotonin. In the presence of endothelial damage and arteriosclerotic vascular disease, particularly with reduced blood flow in areas of stenosis, platelets may aggregate, resulting in high local 5-HT concentrations and 5-HT-induced vasoconstriction. Since alpha 1-adrenoceptor-mediated vasoconstriction is independent of age, the age-related antihypertensive efficacy of the 5-HT2-receptor antagonist ketanserin (with alpha 1-blocking property) helps to define pharmacologically 5-HT2-receptor-mediated platelet aggregatory and vasoconstrictor mechanisms. 5-HT2-receptor antagonists represent a new antihypertensive tool with the potential of reducing thromboembolic complications and vascular damage, particularly in older patients.

Aging↗