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Biomedical subjects

H Darius

Publications and source records attributed to H Darius.

At least 91 records · Page 5Linked to original sources
PubMed1991

[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. Platelet aggregation and thromboxane synthesis are dose- dependently inhibited after oral intake of ASA (0, 10, 30, 100 or 500 mg/d) Additional intake of the antianginal agent and nitric oxide donator Molsidomine (8 mg) results in a synergistic platelet inhibitor effect characterized by a significantly delayed aggregation response. In a group of patients with coronary artery stenoses platelet activity was markedly enhanced, when compared to healthy individuals. During physical exercise platelet activity was even further enhanced and plasma t-PA-activity was increased by a factor of 2.2. The stimulation of the endogenous fibrinolytic system was markedly reduced when compared to healthy subjects. Following successful coronary angioplasty 393 patients were randomized to receive either molsidomine (2 x 8 mg/d) or ASA (1 x 500 mg/d) plus nifedipine (3 x 20 mg/d). Coronary angiography performed after the 6 month treatment period revealed a restenosis rate of 29% in the molsidomine group and of 33% in patients treated with ASA + nifedipine. This difference was not statistically significant.

Angioplasty, Balloon, Coronary↗
PubMed1990

[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. Beside hemodynamic reasons the effects of SIN-I on circulating blood cells and collateral perfusion are discussed as mechanisms of action. The effects of molsidomine (2 X 8 mg/d) on restenosis rate after initially successful coronary angioplasty were studied in 393 patients in a prospective, randomized and controlled trial. 29% of patients treated with molsidomine experienced restenosis at control coronary angiography at six months. The control group receiving nifedipine (3 X 20 mg/d) and acetylsalicylic acid (1 X 500 mg/d) showed a restenosis in 33% of patients. Therefore, molsidomine seems as effective as nifedipine and acetylsalicylic acid in treating patients after coronary angioplasty.

Angioplasty, Balloon, Coronary↗
PubMed1989

[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. +25%; p less than 0.0001 resp. p less than 0.0001). Heart rate did not change significantly (84 +/- 2 min-1 resp. 88 +/- 4 min-1). The enddiastolic volume index, determined by two-dimensional echocardiography, did not change significantly (104 +/- 10 ml/m2 resp. 112 +/- 3 ml/m2), the endsystolic volume index increased from 57 +/- 10 ml/m2 to 75 +/- 13 ml/m2 (+32%; p less than 0.01), the ejection fraction fell from 47 +/- 4% to 36 +/- 4% (p less than 0.001). In the RAO-equivalent view the maximal jet-length, determined by color-coded Doppler echocardiography, increased from 2.6 +/- 0.2 cm to 3.9 +/- 0.3 cm (+50%; p less than 0.001), the maximal jet-area rose from 3.4 +/- 0.6 cm2 to 7.0 +/- 1.0 cm2 (+106%; p less than 0.001); in the parasternal long axis view the maximal jet-length increased from 2.3 +/- 0.2 cm to 3.5 +/- 0.3 cm (+52%; p less than 0.001), the maximal jet-area from 2.6 +/- 0.5 cm2 to 4.9 +/- 0.8 cm2 (+89%; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

[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 0.2 mV was significantly prolonged from 44 to 55-62 seconds. Simultaneously, SIN-1 reduced the significant rise in left ventricular end-diastolic pressure observed during dilatation. One minute after SIN-1 was injected, no effect was noted or on the increase in left ventricular volume indices or on the reduction of ejection fraction associated with dilatation. The maximum anti-ischaemic effect of SIN-1 was obtained 5 minutes after the injection. As regards the mechanism of action of the drug, a decrease in parietal tension through reduction of left ventricular preload should be considered. In addition, strong inhibition of platelet aggregation and adenosine triphosphate secretion was demonstrated in high platelet content plasma and whole blood 2 hours after an oral 16 mg dose of molsidomine. The antiplatelet effect of molsidomine may contribute to its anti-ischaemic effect by reducing both platelet adherence at the site of dilatation and the release of vasoconstrictor and pro-aggregant mediators.

Adenosine Triphosphate↗
PubMed1987

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. Myocardial creatine kinase activity was significantly reduced by approximately 25% in the ischemic areas of hearts from rats receiving vehicle. This reduction in myocardial creatine kinase activity was totally abolished by infusion of iloprost. Total phospholipid content was significantly reduced by 10% in ischemic areas of hearts obtained from vehicle infused animals. Iloprost infusion also prevented the loss of total phospholipids in the ischemic areas. The data show that coronary artery ligation is associated with a significant loss of total membrane phospholipids in ischemic regions of rat myocardium, characterized by significant decreases in phosphatidylcholine, phosphatidylethanolamine and cardiolipin. The decrease in cardiac phosphatidylcholine and phosphatidylethanolamine content was prevented by iloprost, whereas the decrease in cardiolipin content was unaltered. Infusion of the prostacyclin analog iloprost almost totally inhibited the ischemia induced loss of phospholipids, suggesting that this may be an important component of its cytoprotective mechanism of action.

Animals↗
PubMed1987

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. Myocardial contractile force and oxygen consumption were not affected. The superoxide anion generation of stimulated granulocytes was modestly antagonized by NIL. NIL (0.5 microgram/kg/min intravenously, i.v.) protected the left ventricular myocardium of cats subjected to 5 h of coronary artery ligation from ischemic injury, as evidenced by the reduction in ischemia-induced ST-segment elevation, prevention of the large increase in plasma creatinine kinase (CK), and loss of myocardial CK and free amino nitrogen. These effects and the extent of cardiac protection by NIL were comparable to those of PGI2 (0.2 microgram/kg/min), whereas PGE2 (1.5 microgram/kg/min) was less effective. The data demonstrate a combination of PGI2-like and PGE2-like activities for NIL in vitro and a significant cardioprotective action of NIL in vivo.

Animals↗
PubMed1987

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., sudden death, myocardial ischemia, circulatory shock). It does so because it propagates its own formation by activating platelets and constricting blood vessels, thus activating more TxA2 and trapping it locally within an ischemic or hypoxic region. TxA2 concentrations in the extracellular fluid of lymph of ischemic regions may be much higher than that occurring in nonischemic, normally perfused regions. Specific and potent Tx receptor antagonists (TxRA) have recently become available for study. The TxRA are useful tools in the study of the pathophysiology of Tx-dependent disease processes and have been found to be effective in a variety of ischemic disorders including circulatory shock, myocardial ischemia, and sudden cardiopulmonary death. Moreover, inasmuch as early work indicates that these agents are both safe and effective in humans, Tx receptor antagonists may be employed as therapeutic agents in several cardiovascular disease states. Further investigation is necessary to clarify the role of TxRA as therapeutic agents.

Animals↗
PubMed1987

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 +/- 0.5% in one pass through the heart. Short-term infusion of either leukotriene (LT) D4 (0.02-0.5 nmol) or norepinephrine (NE; 0.06-0.6 mumol) released significant quantities of ATP from isolated rat hearts in a dose-dependent manner. In contrast, equipotent vasoconstrictor doses of arginine vasopressin (AVP; 20 and 60 microU) failed to release ATP. The amount of ATP released by LTD4 and NE declined by 50 to 60% with each consecutive challenge. LTD4-induced vasoconstriction and ATP release were totally abolished by the LT receptor antagonist FPL-55,712, whereas the NE-induced coronary vasoconstriction and ATP release were totally blocked by the alpha adrenergic blocking agent phentolamine. The coronary vasoconstriction induced by NE was followed by a slight coronary vasodilation, which was inhibited by the beta adrenergic blocking agent timolol without influencing ATP release. The LTD4- and NE-induced release of ATP appears to be receptor mediated and may play a role in the regulation of coronary vascular tone.

Adenosine Triphosphate↗
PubMed1986

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.v. to six patients at doses of 0.5, 1.0, 2.0 or 3.0 ng/kg X min for 4 h, with an interval of 2-3 days between the infusions. During iloprost infusion, systolic and diastolic arterial blood pressure, heart rate and blood flow in the affected limb remained unchanged. In contrast, there was a considerable, dose-dependent inhibition of ADP- and thrombin-induced platelet aggregation and secretion ex vivo at doses of 0.5-2.0 ng/kg X min iloprost, indicating that iloprost reduced platelet stimulation by 50%-70%. The antiplatelet action of iloprost remained unchanged during infusion but ceased with 2 h after administration had ended. The agent was tolerated by the patients without unacceptable side-effects at doses up to 2 ng/kg X min. It is concluded that iloprost administered i.v. at doses of 1-2 ng/kg X min in patients with stage II-III PAOD does not involve haemodynamic side-effects and might be considered an effective antiplatelet agent.

Adult↗
PubMed1986

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. Increases in CPP induced by arginine vasopressin and leukotriene D4 were not altered by SQ-29,548. We conclude that SQ-29,548 is a very potent and specific TxA2 receptor antagonist in the coronary vasculature of the rat heart.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1986

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. The results reported here demonstrate that the histamine- and leukotriene-independent component of guinea pig anaphylaxis in vivo and in isolated lung parenchymal strips in vitro is mediated by PAF-acether. However, PAF-acether is not responsible for the anaphylaxis-induced thrombocytopenia.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1986

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. Plasminogen activator was infused at a rate of 500 IU X kg-1 X min-1 for the first 30 minutes of reperfusion. The marked increase in plasma creatine kinase activity during reperfusion was significantly lower in plasminogen activator-treated cats at 4, 5 and 6 hours, with 7.7 +/- 1.5 X 10(-3) IU X mg protein-1 (n = 8) in the plasminogen activator group versus 17.8 +/- 3.5 X 10(-3) IU X mg protein-1 (n = 7) in the vehicle group at 6 hours (mean +/- SEM). The area at risk in the two ischemic groups was not different, being 14.6 +/- 1.5 and 16.6 +/- 1.4% of total left ventricular mass for the treated and untreated groups, respectively. However, the mass of necrotic tissue determined histochemically was significantly lower in the plasminogen activator-treated group, accounting for 29.5 +/- 3.9% of the area at risk compared with 46.8 +/- 4.2% of area at risk in cats receiving only the vehicle (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

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. The bronchoconstrictor effects induced by immunological challenge were also totally inhibited when the leukotriene receptor antagonist FPL-55,712 was used to replace BW-755C or another PAF receptor antagonist, alprazolam was used to replace kadsurenone. Ovalbumin challenge in sensitized guinea pigs in vivo resulted in airway constriction, circulatory failure and an abrupt fall in continuously measured platelet count by 75 +/- 12%, followed by death of all animals within 5-8 min. Pretreatment with diphenhydramine, BW-755C and kadsurenone (or alprazolam) improved survival to 64% (i.e., 7 of 11 animals) compared to a survival rate of 0% (i.e., 0 of 8 vehicle treated controls). Despite the improved survival, the severe thrombocytopenia was unaltered with the combined therapy. PAF, histamine and peptide leukotrienes appear to act in concert in mediating the anaphylaxis-induced airway constriction and circulatory failure in guinea pigs, but are not apparently responsible for the accompanying thrombocytopenia.

Alprazolam↗