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Biomedical subjects

W Kiowski

Publications and source records attributed to W Kiowski.

At least 109 records · Page 6Linked to original sources
PubMed1992

Endothelin-induced vasoconstriction and calcium antagonists.

Endothelial cells can produce contracting factors; endothelin, a 21-amino acid peptide, is one of the most potent of these factors, which can control local vascular tone. The peptide is formed from its precursor, big endothelin, via the activity of the endothelin converting enzyme. The basal production of the peptide is stimulated by epinephrine, angiotensin II, arginine vasopressin, transforming growth factor beta, thrombin, interleukin-1 and the calcium ionophore A23187. In vascular smooth muscle cells, endothelin binds to its specific receptor (ETA-receptor and possibly ETB-receptor) which activate phospholipase C and lead to the formation of inositol trisphosphate, diacylglycerol and increased intracellular calcium levels. In certain blood vessels, the endothelin receptor is linked to voltage-operated calcium channels via a Gi-protein. This linkage may explain why calcium antagonists inhibit endothelin-induced contractions in certain, but not other blood vessels. In large conduit arteries, such as the human internal mammary artery, endothelin-induced contractions are primarily mediated by release of intracellular calcium and hence, calcium antagonists do not markedly affect the response. In contrast, in the human forearm circulation, calcium antagonists of different classes do prevent endothelin-induced contractions. Similarly, in mesenteric resistance arteries of the rat, calcium antagonists can reverse endothelin-induced contraction suggesting that calcium antagonists are particularly potent in inhibiting endothelin-induced contraction in resistance arteries, where peripheral vascular resistance and hence, blood pressure is regulated.

Animals↗
PubMed1991

Circulatory abnormalities and compensatory mechanisms in heart failure.

Knowledge of the basic alterations of central hemodynamics in congestive heart failure has failed to explain many aspects of this important syndrome. Increasing attention has recently been paid to compensatory and adaptive mechanisms occurring after the initial 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 congestive heart failure has been further elucidated, and the role of the vasodilating atrial natriuretic peptide is undergoing further definition. New results further clarify the mechanisms leading to breathlessness and muscular fatigue in congestive heart failure, with emphasis shifting from the traditional concept of the importance of increased filling pressures to changes to the peripheral circulation and exercising muscles. Although progress has been made in understanding of the pathophysiology of congestive heart failure, many aspects are still poorly understood and await clarification.

Blood Circulation↗
PubMed1991

Coronary vasodilatation and improved myocardial lactate metabolism after angiotensin converting enzyme inhibition with cilazapril in patients with congestive heart failure.

The effects of angiotensin converting enzyme inhibition on systemic and coronary hemodynamics and on myocardial lactate metabolism were investigated before and 2 and 6 hours after cilazapril at rest and during supine submaximal exercise in 10 patients with New York Heart Association class II or III chronic congestive heart failure. Angiotensin converting enzyme inhibition, indicated by a significant increase in plasma renin activity, resulted in significant reductions in blood pressure and systemic vascular resistance. Myocardial oxygen demand decreased (resting double product 10.9 +/- 3.7 vs 12.2 +/- 3.8 mm Hg beats/min 10(-3); p less than 0.05), but coronary sinus blood flow remained unchanged and calculated coronary resistance decreased (0.45 vs 0.5 units, rest 6 hours; p less than 0.05) suggesting coronary vasodilatation. Changes in coronary vascular resistance were directly related to changes in systemic vascular resistance (r = 0.75, p less than 0.5). Myocardial lactate extraction increased at rest (47 +/- 60 vs 134 +/- 132 mumol/min; p less than 0.5) and during exercise (27 +/- 54 vs 491 +/- 317 mumol/min; p less than 0.05) both in patients with coronary artery disease (n = 5) and idiopathic dilated cardiomyopathy (n = 5). Resting lactate production was converted to lactate extraction in two patients with coronary artery disease. Neither plasma catecholamine nor atrial natriuretic peptide concentrations changed significantly. The results suggest coronary vasodilation and improved aerobic myocardial metabolism by angiotensin converting enzyme inhibition in patients with congestive heart failure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Assessment of the extent of jeopardized myocardium during acute coronary artery occlusion followed by reperfusion in man using technetium-99m isonitrile imaging.

We tested the feasibility of technetium-99m methoxyisobutyl isonitrile (Tc-MIBI) imaging for delineating jeopardized myocardium during acute coronary occlusion and reperfusion in man. This new perfusion agent was injected in 25 patients during elective percutaneous transluminal coronary angioplasty (PTCA) of a single-vessel left anterior descending (LAD) coronary artery stenosis. Distinct perfusion defects were present on "occlusion" images but not on "open vessel" images obtained 20 to 24 hours later in 21 patients (84%). The extent and severity of perfusion defects were significantly smaller in patients with distal versus proximal LAD occlusions (3.4 +/- 1.2 versus 5.2 +/- 1.5 segments; p less than 0.001). The only factor that was significantly related to the presence or absence of such "ischemic" perfusion defects was the absence or presence of visible collateral vessels to the LAD (p less than 0.03). The site of occlusion, presence of wall motion abnormalities, or occlusion time did not influence the results significantly. Thus the myocardial area at risk could be visualized and quantitated by Tc-MIBI imaging even after occlusion times as short as 15 seconds, but functioning collateral vessels are capable of protecting jeopardized myocardium in this setting.

Adult↗
PubMed1991

Treatment of mitral stenosis.

In patients with mitral stenosis the need for therapeutic intervention can be assessed by clinical and non-invasive data. Mitral valve replacement is indicated when marked dyspnoea on mild exertion, dyspnoea at rest or pulmonary oedema, haemoptysis, atrial fibrillation, recurrent systemic emboli or right ventricular failure occur in a patient with a mitral valve area of less than 1.5 cm2, as measured by Doppler echocardiography. This treatment will entail life-long anticoagulation in the majority of patients. Closed commissurotomy is no longer considered a valid therapeutic alternative due to its limited success rate but open commissurotomy and balloon valvotomy may be performed in patients with no significant calcification of valve cusps and no major concomitant mitral regurgitation. Preservation of the subvalvular apparatus and left ventricular geometry can be considered the most important advantages of these techniques. More severe chronic symptoms are generally required as indication for mitral valve replacement because of the additional long-term imponderabilities imposed by an implanted artificial device. Therefore, in patients with mitral stenosis different symptoms and clinical findings will eventually lead to different interventions.

Catheterization↗
PubMed1991

Endothelin-1-induced vasoconstriction in humans. Reversal by calcium channel blockade but not by nitrovasodilators or endothelium-derived relaxing factor.

The vascular effects of endothelin-1 (ET) in humans were investigated by brachial artery infusions of ET into 25 healthy volunteers. Forearm blood flow increased from a mean +/- SD value of 2.3 +/- 1.5 to 2.5 +/- 1.5 ml/min/100 ml forearm tissue (n = 25, p less than 0.05) in response to low dose (0.5 ng/min/100 ml forearm tissue) ET infusion and decreased to 1.78 +/- 1.3 and 1.1 +/- 0.9 ml/min/100 ml forearm tissue (p less than 0.001) during higher dosages (25 and 50 ng/min/100 ml forearm tissue). Sodium nitroprusside (0.6 micrograms/min/100 ml forearm tissue, n = 6), acetylcholine (16 micrograms/min/100 ml forearm tissue, n = 7), nifedipine (6 micrograms/min/100 ml forearm tissue, n = 6), and verapamil (80 micrograms/min/100 ml forearm tissue, n = 6) were infused alone and in combination with ET to evaluate the interactions between ET-induced vasoconstriction and stimulation of vascular muscle cyclic GMP levels by sodium nitroprusside, release of endothelium-derived relaxing factor by acetylcholine, and blockade of voltage-operated calcium channels by nifedipine and verapamil. Neither the vasodilator nor the vasoconstrictor response to ET was influenced by sodium nitroprusside or acetylcholine. In contrast, both calcium antagonists converted ET-induced vasoconstriction (e.g., delta forearm vascular resistance to ET 50 ng/min/100 ml forearm tissue, 151 +/- 100% and 164 +/- 92% in verapamil and nifedipine groups, respectively) to vasodilation (-35 +/- 12% and -21 +/- 16%, p less than 0.05). Our results demonstrate both ET-induced vasodilation (at low dosages) and vasoconstriction (at high dosages) in resistance vessels of normal humans. Blockade of voltage-operated calcium channels prevented ET-induced vasoconstriction and unmasked the vasodilator effect of high ET dosages. In human resistance vessels, blockade of voltage-operated Ca2+ channels but not cyclic GMP-dependent vasodilation may be an effective tool to inhibit ET-induced vasoconstriction.

Adult↗
PubMed1991

Endothelial function in humans. Studies of forearm resistance vessels.

The endothelium is increasingly recognized as a modulator of vascular tone, and evidence also is accumulating for an important role of the endothelium in humans in vivo. Endothelial release of prostacylin appears to regulate hyperemic blood flow after ischemia and muscle exercise, and the potent vasodilating properties of endothelium-derived relaxing factor (EDRF) are well established. Tonic release of EDRF plays an important role in the regulation of vascular tone in normal subjects, and a reduction of EDRF release in response to muscarinergic stimulation has been described in subjects with uncomplicated hypertension and also in hyperlipidemic patients. These observations point toward an early disturbance of endothelial function in disorders known as risk factors for the development of atherosclerosis. Furthermore, altered EDRF release and responsiveness to stimuli may be involved in the disturbed regulation of peripheral vascular tone in congestive heart failure. The physiological role of the vasoconstricting peptide endothelin-1 is not yet defined, but the study of the vascular actions of the peptide in humans has shown a vasodilating effect (for low dosages or when the vasconstricting effects are blocked), as well as a marked and long-lasting vasoconstricting effect. Although the mechanisms leading to vasodilation are not clear in humans, endothelin-1-induced vasoconstriction appears to be completely dependent on the activity of voltage-operated calcium channels and can be blocked by organic calcium antagonists but not by nitrovasodilators or EDRF. Further clarification of the role of the endothelium will provide a better understanding of circulatory physiology and pathophysiology and eventually may lead to the development of new therapeutic modalities.

Endothelins↗
PubMed1991

Cilazapril in congestive heart failure. A pilot study.

The haemodynamic effects of a single dose of cilazapril 2.5 or 5 mg were studied in 33 patients with stable chronic congestive heart failure who were receiving digitalis and diuretics. Subsequently, a double-blind comparison of the haemodynamic and clinical effects of 3 months' treatment with cilazapril 1.25 to 5 mg daily or placebo in 24 evaluable patients revealed that the acute haemodynamic improvement produced by a single dose of cilazapril was maintained in patients receiving repeated administration of the drug, but not in those randomly allocated the placebo. Acute cilazapril significantly decreased mean arterial pressure, systemic vascular resistance, pulmonary capillary wedge pressure, pulmonary artery pressure and right atrial pressure, while cardiac index and stroke volume index increased at rest and during submaximal exercise. After 3 months' treatment 11 of 13 cilazapril recipients improved their New York Heart Association (NYHA) class compared with 2 of 11 patients treated with placebo. This functional improvement was paralleled by a patient-perceived improvement in general well-being.

Adult↗
PubMed1991

Effect of antiarrhythmic therapy on mortality after myocardial infarction.

In an attempt to improve survival of patients with coronary artery disease and high-grade ventricular ectopic activity, several studies using different antiarrhythmic drugs were undertaken. A meta-analysis of all randomized controlled trials using type I antiarrhythmic agents showed that the treatment effect was much more likely to be adverse than beneficial. In contrast to these studies, the pooled results of major secondary prevention trials using beta-blocking agents could demonstrate a significant reduction in the sudden death rate by an average of 24% during observation periods of 9-36 months. In the beta-blocker trials, however, patients with contraindications for this type of drug, such as overt congestive heart failure or chronic obstructive lung disease, were excluded. In these patients a type III antiarrhythmic drug, such as amiodarone, may have a place, and in fact, the Basel Antiarrhythmic Study of Infarct Survival, a prospective, controlled, randomized trial using low-dose amiodarone as an antiarrhythmic agent, could demonstrate a 60% reduction in sudden death rate and a 74% reduction in arrhythmic events incidence during the first year after myocardial infarction. Therefore, in patients with repetitive ventricular ectopic activity after myocardial infarction and adequate left ventricular function, a therapeutic attempt with beta-blockers without intrinsic sympathomimetic activity seems advisable. Beside beta-adrenergic blockade, low-dose amiodarone is an alternative, especially in patients with impaired left ventricular function or other contraindications for beta-blockers.

Anti-Arrhythmia Agents↗
PubMed1991

[Percutaneous transluminal coronary angioplasty].

Since its first application in a patient, PTCA has undergone a tremendous evolution: Based on growing experience and due to technical developments, indications have been markedly extended. Despite the fact that PTCA has been used in more risky situations, the primary success rate has risen and the rate of severe complications has dropped. This evolution is shown based on the Basel experience and on data from Switzerland. The problem of restenosis, however, has not been solved and remains the main problem to be looked for during follow-up of these patients.

Aged↗
PubMed1990

Arterial vasodilator effects of the dihydropyridine calcium antagonist amlodipine alone and in combination with verapamil in systemic hypertension.

The arterial vasodilator properties of the dihydropyridine calcium antagonist amlodipine were compared with the effects of vascular muscle cyclic guanosine monophosphate production by sodium nitroprusside and with the effects of a combined infusion of amlodipine and the nondihydropyridine calcium antagonist verapamil in 8 untreated patients with primary hypertension. Arterial vasodilation was assessed by measurement of changes of forearm blood flow by mercury in Silastic strain-gauge plethysmography during brachial artery drug infusions. Forearm blood flow increased during amlodipine infusions (0.4 to 45 micrograms/min/100 ml forearm tissue) from 2.9 +/- 1.7 to a maximum of 23.6 +/- 7.6 ml/min/100 ml (687%), while sodium nitroprusside caused an increase from 3.0 +/- 1.8 to 16.2 +/- 5.4 ml/min/100 ml (449%), attesting to the importance of transmembrane calcium influx for the maintenance of vascular tone. The addition of verapamil 40 micrograms/min/100 ml to an infusion of amlodipine 44.5 micrograms/min/100 ml resulted in a further increase of forearm blood flow, from 23.6 +/- 7.6 to 34.4 +/- 9.8 ml/min/100 ml (p less than 0.05). The precise mechanisms of this finding have yet to be elucidated but may be due to interactions of the effects of the binding of these 2 chemically and pharmacologically different calcium antagonists to distinct binding sites at calcium channels. The clinical relevance of this observation for the treatment of coronary artery disease and systemic hypertension needs further study.

Amlodipine↗
PubMed1990

[The treatment of ischemia in acute myocardial infarction].

Rapid reestablishment of myocardial blood supply is the ideal in the treatment of acute myocardial infarction. Thrombolysis and, in selected cases, percutaneous transluminal coronary angioplasty (PTCA) or coronary bypass surgery may limit the extent of myocardial necrosis and improve survival. An open, infarct-related artery after thrombolysis carries a better prognosis, but it remains to be established whether the persistent lesion needs to be treated by PCTA or surgery in all patients. Early intravenous beta blockade reduces inhospital mortality by approximately 15% in patients without thrombolysis, while calcium antagonists, despite their theoretical promise and in vitro results, are not effective in the early phase of acute myocardial infarction. Only diltiazem seems to reduce the incidence of reinfarction in patients with non-Q-wave infarction. Aspirin reduces mortality in patients with unstable angina pectoris and in patients with acute myocardial infarction with or without concomitant thrombolysis.

Adrenergic beta-Antagonists↗
PubMed1990

[Antihypertensive therapy and prevention of hypertensive complications].

Arterial hypertension is one of the most important risk factors for the high cardiovascular morbidity and mortality. The efficacy of treatment is undisputed in patients with severe or accelerated hypertension. For the majority of patients suffering from mild to moderate hypertension the usefulness of treatment is not as well established although the potential benefit would be greatest. In this group the reduction of cerebrovascular complications has been demonstrated whereas reduction of morbidity and mortality for ischemic heart disease has remained controversial, indicating that reduction of blood pressure alone may not sufficiently reduce the risk for coronary complications. In contrast to cerebrovascular disease ischemic heart disease depends probably on several risk factors other than hypertension. For prevention of ischemic heart disease these other factors therefore need to be considered extensively.

Age Factors↗
PubMed1990

Direct vascular and myocardial effects of nisoldipine.

The effects of the dihydropyridine calcium antagonist nisoldipine on vascular smooth muscle and myocardium were investigated by brachial artery infusions and measurements of forearm blood flow and by intracoronary infusions and measurements of maximal rate of rise of left ventricular pressure (dP/dtmax). Brachial artery infusions (0.1 to 16 micrograms/min/1,000 ml tissue) in 10 patients with essential hypertension increased forearm blood flow and decreased calculated forearm vascular resistance dose dependently (maximal reduction of forearm vascular resistance 88%). A comparison with the vascular effects of verapamil indicated that the vasodilator potency of nisoldipine is approximately 40- to 50-fold greater in this model supporting similar results from in vitro experiments. Coronary artery infusions of nisoldipine (12, 24 and 48 micrograms over 3 minutes each) in 9 patients undergoing diagnostic left-sided cardiac catheterization did not change dP/dtmax. This lack of effect on left ventricular contractility was similar in patients with normal or impaired left ventricular function. Even though the coronary artery concentrations during the infusion are unknown, the highest intracoronary dose was comparable to the highest brachial artery infusion. Since the coronary vasculature has been found to be at least as sensitive to nisoldipine as the peripheral vasculature, it can be assumed that nisoldipine has no negative inotropic effect even in dosages that probably induced marked vasodilation. Thus, for nisoldipine and possibly other new dihydropyridine calcium antagonists, the concept of a dissociation between peripheral vasodilatation and direct myocardial effects also seems to apply to human circulation and the heart.

Adult↗
PubMed1990

Use of nifedipine in hypertension and Raynaud's phenomenon.

The reduction of transmembranous calcium influx into vascular smooth muscle cells by calcium antagonists leads to a reduction of tension development and vascular tone. Nifedipine reduces forearm vascular resistance dose-dependently when infused into the brachial artery in patients with essential hypertension, attesting to its potent arterial vasodilator effects. This effect can be successfully utilized for the treatment of essential hypertension, where nifedipine acts by reducing increased peripheral vascular resistance, thereby normalizing the main hemodynamic 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 nifedipine as monotherapy for hypertensive patients. Although the pathophysiologic disturbances leading to vasospasm are not clear, blockade of slow calcium channels is also effective for the treatment of Raynaud's phenomenon, reducing attack frequency, digital pain, and functional disability in many patients, particularly those with primary Raynaud's phenomenon.

Adult↗
PubMed1990

Effect of antiarrhythmic therapy on mortality in survivors of myocardial infarction with asymptomatic complex ventricular arrhythmias: Basel Antiarrhythmic Study of Infarct Survival (BASIS)

In view of the high risk of sudden cardiac death and the prognostic importance of complex ventricular ectopic activity, the effects of prophylactic antiarrhythmic treatment were investigated prospectively in patients with persisting asymptomatic complex arrhythmias after myocardial infarction. End points were total mortality and arrhythmic events (sudden death, sustained ventricular tachycardia and ventricular fibrillation). Of 1,220 consecutively screened survivors of myocardial infarction, 312 had Lown class 3 or 4b arrhythmia on 24 h electrocardiographic recordings before hospital discharge and consented to the study. They were randomized to individualized antiarrhythmic treatment (Group 1, n = 100), treatment with low dose amiodarone, 200 mg/day (Group 2, n = 98) or no antiarrhythmic therapy (Group 3 [control group], n = 114). During the 1 year follow-up period, 10 patients in Group 1 died, as did 5 in Group 2 and 15 in Group 3. On the basis of an intention to treat analysis, the probability of survival of patients given amiodarone was significantly greater than that of control patients (p less than 0.05). In addition, arrhythmic events were significantly reduced by amiodarone (p less than 0.01). These effects were less marked and not significant for individually treated patients (Group 1). These findings suggest that low dose amiodarone decreases mortality in the 1st year after myocardial infarction in patients at high risk of sudden death.

Amiodarone↗
PubMed1990

Indirect evidence for release of endothelium-derived relaxing factor in human forearm circulation in vivo. Blunted response in essential hypertension.

In isolated blood vessels, acetylcholine releases endothelium-derived relaxing factor (EDRF). In vivo, the vasodilator action of acetylcholine may be mediated by EDRF, but prostacyclin or prejunctional inhibition of adrenergic neurotransmission may also be involved. Therefore, we investigated whether acetylcholine releases EDRF in humans in vivo and, if so, whether the response altered in essential hypertension. Acetylcholine was infused into the brachial artery, and forearm blood flow measured by venous occlusion plethysmography. In control subjects, acetylcholine (0.02-16 micrograms/min/100 ml tissue) increased flow from 2.4 +/- 5.0 to 20.6 +/- 5.2 ml/min/100 ml tissue (n = 14; p less than 0.05) and decreased forearm vascular resistance from 42.0 +/- 4.1 to 6.0 +/- 1.4 units (p less than 0.03), a response comparable to that of sodium nitroprusside (0.6 micrograms/min ml tissue). Acetylsalicylic acid (500 mg i.v.) given to block vascular prostacyclin production did not alter the response (n = 14). alpha-Adrenoceptor blockade by phentolamine (12 micrograms/min/100 ml tissue) did not prevent the increase in flow evoked by acetylcholine. In hypertensive patients, the decrease in forearm vascular resistance induced by acetylcholine but not evoked by sodium nitroprusside was reduced as compared with controls (14.5 +/- 3.1 and 6.1 +/- 1.6 units, respectively; n = 8; p less than 0.05). Thus, the vascular effects of acetylcholine in the human forearm circulation are independent of prostaglandins and adrenergic neurotransmission and therefore are most likely to be mediated by EDRF; the acetylcholine-induced release of EDRF is blunted in patients with essential hypertension.

Acetylcholine↗