[Modification of thrombocyte function in diagnostic and therapeutic interventions in cardiology].

In patients with coronary heart disease platelet activity may be pathologically increased. Administration of platelet inhibitor drugs is an established treatment principle. The interactions between platelet activation, platelet inhibitor drugs like acetylsalicylic acid (ASA) or molsidomine and the endogenous fibrinolysis were studied in three trials.

[Effect of molsidomine on fibrinolytic activity: a double-blind, randomized study].

The influence of molsidomine on endogenous fibrinolytic activity was studied in a double-blind, randomized, placebo-controlled trial involving 12 male healthy volunteers. When measured 3 h after oral intake of molsidomine (16 mg, slow-release formulation) the activity of tissue plasminogen activator (t-PA) in plasma was significantly increased from 1.1 +/- 0.

[Acute and chronic effects of molsidomine in therapeutic coronary angioplasty].

The effects of the molsidomine metabolite SIN-I (0.5 mg) on tolerance to ischemia were studied in twelve patients during coronary angioplasty of the LAD. SIN-I resulted in a significant prolongation of time to ST-segment alteration one, five and ten minutes after intracoronary injection.

[Influence of angiotensin-induced change in afterload on hemodynamics in mitral valve insufficiency. A 2-dimensional and color-coded Doppler echocardiography study].

This study assesses the consequences of angiotensin I-induced afterload-stress on mitral regurgitation by two-dimensional and color-coded Doppler echocardiography. During continuous intravenous infusion of angiotensin I in increasing doses of 0.5, 2, and 4 micrograms/min, blood pressure increased significantly from 119 +/- 7/73 +/- 3 mm Hg up to 145 +/- 8/91 +/- 4 mm Hg (+22% resp.

[Anti-ischemic effects of SIN-1, a molsidomine metabolite, during coronary angioplasty and antiplatelet effects in humans].

The effects of SIN-1, the biologically active metabolite of molsidomine, on tolerance of ischaemia during percutaneous transluminal coronary angioplasty were studied in 12 patients. Following an intracoronary injection of SIN-1 0.5 mg, the time required for the ST segment to be depressed by at least 0.

Cardiovascular actions in vitro and cardioprotective effects in vivo of nileprost, a mixed type PGI2/PGE2 agonist.

Cardiovascular, platelet- and neutrophil-inhibitory effects of the chemically stable prostacyclin analog nileprost (5-cyano-16-methyl-PGI2) (NIL, ZK 34798) were studied in vitro and in a feline model of acute myocardial ischemia in vivo. Isolated bovine coronary arteries were relaxed by NIL at low concentrations (less than 3 microM), whereas higher concentrations produced a marked vasoconstriction. NIL inhibited human platelet aggregation and reduced the coronary vascular resistance of Langendorff-perfused rabbit hearts.

Protective actions of a stable prostacyclin analog in ischemia induced membrane damage in rat myocardium.

Myocardial ischemia leads to the damage of cellular membranes and release of intracellular enzymes. We studied the influence of the prostacyclin analog, iloprost, on alterations in membrane phospholipid content and composition in rat myocardium during ischemia. Infusion of iloprost (100 ng/kg/min) or its vehicle started 20 min after coronary artery ligation, and the hearts were analyzed after 6 h.

Pharmacologic modulation of ATP release from isolated rat hearts in response to vasoconstrictor stimuli using a continuous flow technique.

A new method is described for continuously recording ATP release in isolated perfused hearts by a bioluminescence technique that makes possible the study of the dynamics of ATP release in terms of coronary vascular regulation. Infusion of exogenous ATP in isolated perfused rat hearts resulted in a clearance of 97.8 +/- 0.

A pharmacological approach to thromboxane receptor antagonism.

Thromboxane A2 (TxA2) appears to be an important mediator of ischemia and hypoxia. Despite its short half-life and the fact that it may not circulate in the blood until its values become quite high, TxA2 contributes to the pathogenesis of cardiopulmonary diseases (e.g.

Beneficial effects of tissue-type plasminogen activator in acute myocardial ischemia in cats.

Tissue-type plasminogen activator is a new thrombolytic agent that dissolves intravascular thrombi in coronary and peripheral vessels with less pronounced systemic lysis than that produced by streptokinase. Plasminogen activator was shown to induce reperfusion, and to salvage ischemic myocardium, by lysing experimentally induced coronary artery thrombi. The effect of a melanoma cell-derived tissue-type plasminogen activator was studied in cat myocardium rendered ischemic by coronary artery ligation for 2 hours and reperfused for another 4 hours.

Antiplatelet effects of intravenous iloprost in patients with peripheral arterial obliterative disease. A placebo-controlled dose-response study.

The dose-dependent inhibition of platelet aggregation by the chemically stable, prostacyclin-mimetic, iloprost, was studied in patients suffering from stage II-III peripheral arterial obliterative disease (PAOD). The study was designed as a randomized placebo-controlled cross-over trial. Iloprost was administered i.

Antagonism of thromboxane actions in the isolated perfused rat heart.

The effects of SQ-29,548, a novel thromboxane A2 (TxA2) receptor antagonist, were studied in the isolated perfused rat heart. SQ-29,548 at concentrations of 2.5 to 50 ng/ml antagonized the increase in coronary perfusion pressure (CPP) in response to the thromboxane agonist, 9,11-methanoepoxy PGH2.

In vivo anti-platelet properties of anipamil, a calcium channel blocker, in the rabbit.

The anti-platelet actions of anipamil, a new calcium channel blocker were studied in anesthetized rabbits using continuous on-line techniques to measure platelet count and platelet secretion by ATP release. Anipamil, at a dose of 0.5 mg/kg twice daily for three days, prior to challenge with collagen (100 micrograms/kg) or arachidonic acid (1.

Role of platelet-activating factor-acether in mediating guinea pig anaphylaxis.

The pathophysiology of anaphylaxis is very complex, and the sequelae of events are not fully explained in terms of the effects of histamine and peptide leukotrienes alone. Platelet-activating factor (1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine, PAF-acether) has been detected in animals undergoing anaphylaxis. Injection of synthetic PAF-acether induces similar effects, including bronchoconstriction, respiratory arrest, systemic hypotension, neutropenia, and thrombocytopenia.

Cardioprotective actions of a new calcium channel blocker in acute myocardial ischemia.

The ability of anipamil, a calcium channel blocker, to protect ischemic myocardial tissue was investigated in pentobarbital anesthetized cats. Two bolus injections of anipamil (1.0 mg/kg i.

[Organic nitrates and prostaglandins in the cardiovascular system].

The beneficial effect of organic nitrates in acute myocardial ischemia is commonly explained by their hemodynamic actions, especially the dilatation of venous capacitance vessels. Recent studies have shown an inhibition of platelet function by organic nitrates ex vivo but not in vitro. Antiplatelet activities of organic nitrates might represent an additional mechanism, independent of vascular actions which might eventually involve stimulation of prostacyclin formation by the vessel wall.

Inhibition of the platelet activating factor mediated component of guinea pig anaphylaxis by receptor antagonists.

The role of platelet activating factor (PAF) and its inhibition by specific receptor antagonists was studied in hypersensitivity reactions in guinea pig lung parenchymal strips and in guinea pigs in vivo. Immunological challenge of isolated lung parenchymal strips with ovalbumin resulted in a contractile response of 184 +/- 16 mg (n = 38). Pretreatment of the strips with a combination of the antihistamine diphenhydramine, the dual lipoxygenase and cyclooxygenase product synthesis inhibitor BW-755C, and the PAF receptor antagonist kadsurenone totally inhibited the increase in tension.

Anti-ischemic actions of a new thromboxane receptor antagonist during acute myocardial ischemia in cats.

Thromboxane A2 (TxA2) production increases significantly during acute myocardial ischemia. Since TxA2 induces platelet aggregation, coronary vasoconstriction, and has a direct cytolytic effect, thromboxane receptor antagonism would be expected to be beneficial in acute myocardial ischemia. Thirty minutes after ligation of the left anterior descending coronary artery (LAD) in anesthetized cats, the TxA2 receptor antagonist BM-13,177 or its vehicle was given as a bolus injection at 20 mg/kg, followed by continuous infusion of 20 mg/kg/hr for 4.

Antiaggregatory effects of thromboxane receptor antagonists in vivo.

The antiaggregatory and antisecretory effects of two newly developed thromboxane receptor antagonists, BM-13,177 and SQ-29,548, were studied in an in vivo model of platelet activation. Arterial platelet count and whole blood ATP concentrations were measured continuously on-line in the arterial blood of anesthetized rabbits. Injections of collagen decreased peripheral platelet count by 25% of initial value.

Beneficial effects of a new potent and specific thromboxane receptor antagonist (SQ-29,548) in vitro and in vivo.

SQ-29,548, a newly synthetized thromboxane receptor antagonist, was investigated for its effects on platelet and vascular thromboxane receptors in vivo and in vitro. Arachidonic acid (AA)-induced sudden death in rabbits was dose-dependently inhibited by SQ-29,548 at doses ranging from 0.2 to 2 mg/kg.