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Biomedical subjects

J Swies

Publications and source records attributed to J Swies.

17 recordsLinked to original sources
PubMed1992

Cardioprotection by molsidomine and iloprost in myocardial ischemia in anaesthetized cats.

In ten anaesthetized open chest cats the ligation of left descending coronary artery (LLDCA) resulted in 80 percent of mortality with survival time of 40.9 +/- 8.6 min. The death of animals was preceded by premature ventricular contractions which occurred with frequency 7.3 +/- 0.6/min after 2.1 +/- 0.3 min following LLDCA. Molsidomine as a dose of 20 micrograms/kg given i.v. to 10 cats 15 min before LLDCA affected none of the above characteristics of acute myocardial ischemia. The pretreatment with iloprost (2 micrograms/kg given i.v. to 10 cats) diminished frequency of premature ventricular contractions and elongated a period of time required for their occurrence after LLDCA, however, iloprost was also unable to diminish mortality of LLDCA cats. Only a combined administration of molsidomine and iloprost significantly diminished mortality among LLDCA cats down to 20 percent and doubled their survival time as compared to the controls. It is concluded that NO-donors (molsidomine) exert permissive effect towards the cardioprotective action of prostacyclin analogues (iloprost) in cats with myocardial ischemia. LLDCA cats pretreated with molsidomine + iloprost enjoyed a more complete cardioprotection than those pretreated with a high dose (3000 units/kg i.v.) of superoxide dismutase.

Animals↗
PubMed1990

Occlusion and reperfusion-induced arrhythmias in rats: involvement of platelets and effects of calcium antagonists.

The role of blood platelets in ischemia- and reperfusion-induced arrhythmias and the efficacy of three calcium blocking drugs (verapamil, diltiazem, and nicardipine) in preventing the arrhythmias were investigated. Using anesthetized rats, we measured platelet count (Pc) continuously in vivo with a Technicon autocounter. Thromboxane B2 (TxB2) and 6-keto-PGF1 alpha levels in blood from coronary sinus were determined by radioimmunoassay (RIA). Myocardial ischemia and arrhythmias were monitored from lead I ECG during and after occlusion of the left anterior descending coronary artery (LAD) for 7 min. Ischemia-induced arrhythmias were mainly ventricular ectopic contractions (VECs), whereas reperfusion produced VECs, ventricular tachycardia (VT), and reversible and irreversible ventricular fibrillation (VF). Both ischemia and reperfusion decreased platelet count and increased TxB2 level in blood from the coronary sinus. The effects of the CEBs were determined at two dose levels (0.1 and 0.3 mg/kg). Each calcium entry blocker (CEB), at both dose levels, significantly inhibited ischemia-induced arrhythmias. Verapamil and diltiazem significantly reduced reperfusion-induced VECs, prevented VT and irreversible VF, and reduced the number of animals with reversible VF. Nicardipine in preventing arrhythmias was not very effective at either dose. The CEBs also inhibited both ischemia- and reperfusion-induced decreases in PC with a moderate increase (up to 7%) as compared with levels in sham-operated controls. The CEBs also significantly reduced TxB2 levels in blood from the coronary sinus. These results indicate that ischemia and postischemic reperfusion both induce platelet aggregation in rats. Aggregating platelets release biologically active substances including thromboxane A2 (TxA2) which exacerbates existing ischemia and facilitates generation of arrhythmias. CEBs inhibit platelet aggregation and TxA2 release and enhance PGI2 synthesis, thereby preventing arrhythmias.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Kallikrein-thrombolytic and hypotensive action in cats--preliminary results.

An intravenous injection of kallikrein produced hypotensive and thrombolytic effects in anesthetized cats, using the blood superfused tendon technique. The thrombolytic action of kallikrein was mediated by an unstable substance. The generation of this substance was abolished by either acetylsalicylic acid (ASA) or aprotonin and enhanced by captopril. The hypotensive action of kallikrein was only partially inhibited by ASA. It is proposed that both these pharmacological effects of kallikrein are mediated by bradykinin which in turn releases prostacyclin from the endothelium. However, in contrast to the thrombolytic effect of kallikrein which is totally mediated by prostacyclin the hypotensive action of kallikrein depends not only on prostacyclin but also on another endothelium-derived vasorelaxant, e.g. EDRF.

Animals↗
PubMed1989

Prostacyclin and the mechanism of action of defibrotide.

Defibrotide (DEF) is a product of the controlled hydrolysis of DNA from mammalian lungs. In vitro DEF (1-2000 micrograms/ml) neither inhibited the aggregation of human, rabbit and cat platelets nor released PGI2 from cultured porcine aortic endothelial cells. Preincubated with platelet preparations, DEF (10 micrograms/ml) lowered the IC50 for the anti-aggregatory action of PGI2 from 2.1-6.5 nM to 0.6-2.4 nM. In vivo DEF (2-20 mg/kg i.v. or 0.1-10 micrograms/ml locally o.t.) dispersed platelet thrombi in the extracorporeal circulation of anaesthetized heparinized cats. In contrast to an immediate and reversible action of PGI2 (0.3-3 micrograms/kg i.v. or 1-3 ng/ml locally o.t.), the delayed and irreversible dispersion of thrombi by DEF in vivo was inhibited by aspirin (50 mg/kg i.v.), indomethacin (10 mg/kg i.v.) or dexamethasone (2 mg/kg i.v.). After pretreatment with these drugs DEF, although deprived of its own effect on thrombi, still enhanced their dispersion by exogenous and endogenous PGI2. Similarly, at its subthreshold effective concentration (10 ng/ml, o.t.) DEF potentiated the thrombolytic action of PGI2 (1 microgram/kg, i.v.), dazoxiben (1 mg/kg, i.v.) and nicotinamide (100 mg/kg i.v.). It is concluded that DEF potentiates the action of PGI2 on platelets. In vivo DEF may facilitate an interaction between platelets and endothelium, leading to augmented generation of PGI2 or of its biologically active products, which are endowed with fibrinolytic properties.

Animals↗
PubMed1987

On the mechanism of thrombolytic action of thromboxane synthetase inhibitors.

Using our in vivo model for studying drugs which prevent deposition of thrombi or dissipate thrombi formed in extra-corporeal circulation over a collagen strip superfused with arterial blood of anaesthetized and heparinized cats, we have found that dazoxiben--a thromboxane synthetase inhibitor--possesses not only antithrombotic but also thrombolytic potency in vivo (ED50 = 3.8 mg/kg i.v.). The thrombolytic potency of dazoxiben was antagonized by aspirin at a dose of 50 mg/kg i.v. Moreover, dazoxiben stimulated the generation of prostacyclin in isolated rat aortic slices incubated in platelet rich plasma, but not in platelet poor plasma. It is suggested that the thrombolytic potency of thromboxane synthetase inhibitors after their systemic administration is associated with the release of prostacyclin and/or prostacyclin-stable metabolites by the vascular endothelium owing to feeding of prostacyclin synthetase with prostaglandin endoperoxides accumulated in platelets following the inhibition of thromboxane synthetase.

Animals↗
PubMed1987

On the mechanism of antithrombotic action of flavonoids.

Flavonols (quercetin and rutin) and flavanes (cyanidol and meciadonol) were studied for their effect on non-enzymatic lipid peroxidation, lipoxygenase and cyclo-oxygenase activities, binding to albumin and platelet membranes. These biochemical properties of four flavonoids were compared with respect to their antithrombotic action in vivo and their efficacy at influencing the platelet-endothelium interaction in vitro. All four flavonoids inhibited the ascorbate-stimulated formation of malondialdehyde by boiled rat liver microsomes (quercetin greater than rutin approximately cyanidol approximately meciadonol) and inhibited platelet lipoxygenase activity (quercetin greater than cyanidol greater than meciadonol greater than rutin) whereas only flavonols, but not flavanes, stimulated cyclo-oxygenase and were bound to platelet membranes. The same two flavonols dispersed platelet thrombi which were adhering to the rabbit aortic endothelium in vitro (EC50 for quercetin was 80 nM and for rutin 500 nM) and prevented platelets from aggregation over blood-superfused collagen strip in vivo (ED50 for quercetin was 5 nmol/kg and for rutin 33 nmol/kg i.v.). Cyanidol and meciadonol were not effective as anti-thrombotic agents. It is concluded that activated platelets adhering to vascular endothelium generate lipid peroxides and oxygen-free radicals which inhibit endothelial biosynthesis of prostacyclin and destroy endothelium-derived relaxing factor (EDRF). Flavonols are anti-thrombotic because they are selectively bound to mural platelet thrombi and owing to their free radical scavenging properties resuscitate biosynthesis and action of endothelial prostacyclin and EDRF. Thus, flavonols release the thrombolytic and vasoprotective endothelial mediators only in these vascular segments which are covered by a carpet of aggregating platelets.

Albumins↗
PubMed1987

Nitrendipine-stimulated release of prostacyclin-like substance in normal and atherosclerotic animals.

Nitrendipine (Bayotensin) is a dihydropyridine derivative that appears to preferentially dilate peripheral vessels by a cellular mechanism similar to those found with other calcium blocking agents. In this study nitrendipine when infused (0.2-0.3 mg/kg i.v.) into anaesthetized cats caused a release of a substance disaggregating platelet clumps which had adhered to blood superfused collagen strip. The appearance of this unstable disaggregating substance was prevented by the pretreatment of cats with acetylsalicylic acid (50 mg/kg i.v.). In atherosclerotic rabbits nitrendipine stimulated release of prostacyclin-like substance without effect on proaggregatory concentrations of arachidonic acid and adenosine diphosphate. In rats nitrendipine inhibited the development of atherosclerotic changes in the aorta evoked by the atherogenic diet with ergocalciferol (vitamin D2). It is suggested that nitrendipine may promote formation of prostacyclin in arteries and inhibit the development of atherosclerosis.

Animals↗
PubMed1985

The influence of molsidomine and its active metabolite SIN-1 on fibrinolysis and platelet aggregation.

Molsidomine and its active metabolite SIN-1 were examined in humans and animals for platelet suppressant and fibrinolytic activities. Following oral administration of molsidomine at doses of 6 or 15 mg/kg to rabbits, their blood platelets in PRP ex vivo required higher threshold concentrations of ADP, AA and thrombin to be aggregated. Unlike molsidomine, SIN-1 when infused (10 and 20 micrograms/kg i.v.) into anaesthetized cats caused a release of a substance disaggregating platelet clumps which had adhered to blood superfused collagen strip. The appearance of this unstable disaggregating substance was prevented by the pretreatment of cats with aspirin (50 mg/kg i.v.). It is suggested that SIN-1 may promote formation of a PGI2-like substance. In humans shortening of euglobulin clot lysis time was observed 60 min after a single ingestion of 2 mg of molsidomine. This fibrinolytic effect of molsidomine was not abolished by the pretreatment of patients with aspirin. Neither molsidomine nor SIN-1 activated fibrinolysis in preformed euglobulin clots in vitro.

Adenosine Diphosphate↗
PubMed1985

Stimulatory cholinergic effect on the release of antiaggregatory activity into the circulation of cat and man and its modification by beta-adrenergic antagonists.

The release of PGI2-like activity into the circulation in response to cholinergic agonists and modification of this response by beta-adrenergic antagonists was investigated in anaesthetized cats and healthy humans. Antiaggregatory activity in the arterial blood was continuously assayed by measuring platelet aggregation on blood superfused collagen strip. In some of the human experiments, after the administration of the drugs, the conversion of [14C]-arachidonate to [14C]-prostaglandins in the pulmonary vascular bed was studied. Cholinergic agonists stimulated the release of PGI2-like activity into the circulation, which effect was potentiated in cats by beta-adrenergic antagonists. In humans the latter agents did not stimulate the conversion of [14C]-arachidonate to prostaglandins in the pulmonary circulation and, moreover, inhibited the stimulatory cholinergic effect. The results suggest that an interplay between cholinergic and beta-adrenergic mediators may be involved, although in a different way in cats and in humans, in the release of PGI2-like activity into the systemic circulation.

Acetylcholine↗
PubMed1978

Lungs as a generator of prostacyclin--hypothesis on physiological significance.

In vivo anti-platelet de-aggregatory activity of exogenous prostacyclin is enhanced after its passage through the pulmonary circulation of anaesthetized cats, probably because of a concomitant generation of endogenous prostacyclin by the lungs. Evidence is also presented that perfused lungs of guinea pigs and rats spontaneously release considerable amounts of prostacyclin. It is therefore postulated that a continuous biosynthesis of prostacyclin by pulmonary endothelium is a general physiological phenomenon, while the generation of thromboxane A2 by lungs occurs in response to pathological stimuli. Coronary and cerebral arteries are supposed to benefit from this hormonal function of the lungs.

Animals↗
PubMedDate not supplied

On the mechanism of antiaggregatory effect of myricetin.

Myricetin at a dose of 3.6 micrograms/kg iv was found to inhibit the cat blood platelet aggregation in vivo. It disaggregated platelet thrombi in vitro at a concentration of 60 nM. This flavonoid bound to platelet membranes and prevented prostacyclin synthase against oxygen free radicals owing to its antioxidant properties. Myricetin inhibited soybean lipoxygenase when linoleic acid was used as a substrate.

Animals↗
PubMedDate not supplied

Haemodynamic changes accompanying lung oedema produced by iv injection of adrenaline or vasopressin into rats.

The blood pressure was investigated in the common left carotid artery (LC), in the left atrium (LA), in the pulmonary artery (PA) and in the right atrium (RA). After adrenaline injection the blood pressure rised rapid and simulatneously in all four regions. After vasopressin injection the blood pressures rised sequence in LC, in LA and PA. The blood pressure in RA in this time was unchanged. These results indicate that primary causes of the lung oedema after adrenaline or vasopressin are different.

Animals↗