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Biomedical subjects

S Moncada

Publications and source records attributed to S Moncada.

At least 433 records · Page 24Linked to original sources
PubMed1979

Prostacyclin: a solution to some problems of extracorporeal circulation. Experiments in greyhounds.

In cardiopulmonary-bypass experiments in greyhounds the effects of adding prostacyclin, prostacyclin plus heparin, and heparin alone to the extracorporeal circulation were compared. With heparin alone platelet count and function were reduced, the pressure differential across the arterial filters rose, platelet deposits were found on the arterial filters, and plasma-fibrinogen levels fell. Plasma from these dogs was toxic to fetal-mouse hearts in culture. With prostacyclin alone, fibrinogen levels fell, but the platelets were preserved. With a combination of prostacyclin and heparin, platelet count and function were maintained, there was no consumption of fibrinogen, and there was little deposition on the arterial filters.

Animals↗
PubMed1979

The effect of prostacyclin (PGT2) on platelet behaviour. Thrombus formation in vivo and bleeding time.

Prostacyclin (PGI2) infused intravenously into anaesthetized rabbits inhibited electrically-induced thrombus formation in the carotid artery, increased bleeding time and inhibited ex vivo platelet aggregation induced by ADP or arachidonic acid. The increase in bleeding time and the inhibition of ex vivo platelet aggregation lasted for as long as the infusion of PGI2 was maintained but rapidly disappeared after infusion was stopped. Prostacyclin is a more potent inhibitor of platelet function, in vivo than prostaglandin E1 (PGE1) or prostaglandin D2 (PGD2). The effects of prostacyclin on all parameters studied except blood pressure were potentiated by the concomitant administration of theophylline, a phosphodiesterase inhibitor.

Animals↗
PubMed1979

Biotransformation and cardiovascular effects of arachidonic acid in the dog.

The biotransformation and cardiovascular effects of arachidonic acid (AA) were studied in the circulation of anaesthetized dogs. Arterial blood was continuously bioassayed for arachidonate metabolites using the blood-bathed organ technique of Vane. AA (5-10 microgram/ml) infused into an incubation coil of flowing blood was converted into a labile substance which contracted the vascular tissues (rabbit aorta, RbA; rabbit coeliac and mesenteric arteries, RbCA and RbMA; bovine coronary artery, BCA) and the gastrointestinal smooth muscle strips (rat stomach strip, RSS; rat colon, RC). These effects could be mimicked by exogenously generated thromboxane A2 (TXA2). Conversion of AA was inhibited by indomethacin and the selective thromboxane synthetase inhibitor, imidazole (100 microgram/ml). The half-life of TXA2 in blood was 30-47 sec, a similar value to that found in aqueous solutions at 37 degrees C. PGH2 was also converted in blood to other product(s) which contracted RSS and RC, relaxed RbCA and RbMA but had little effect on RbA. Intravenous infusion of AA (50-800 microgram kg-1 min-1) caused effects on the bioassay tissues which could be mimicked by prostacyclin. The AA infusion also induced falls in pulmonary and systemic arterial pressures and bradycardia. All effects were abolished by indomethacin (5 mg/kg) or aspirin (200 mg/kg). Radioimmunoassay confirmed that the major product of intravenously infused AA was 6-oxo-PGF1alpha, the chemical degradation product of prostacyclin. Thus, although AA is transformed to the vasoconstrictor TXA2 when incubated for sufficient time with blood alone, on rapid pulmonary transit it is transformed into a prostacyclin-like substance.

Animals↗
PubMed1979

Use of the rabbit transverse stomach-strip to identify and assay prostacyclin, PGA2, PGD2 and other prostaglandins.

The preparation and use of the rabbit transverse stomachstrip as an isolated assay tissue for prostaglandins is described. The tissue is relaxed by low concentrations of PGE2, PGA2 and PGD2 and contracted by prostacyclin (PGI2) and PGF2alpha. The decomposition product of prostacyclin, 6-oxo-PGF1alpha, has little effect, whereas the endoperoxide PGH2 and thromboxane A2 cause a small contraction. Arachidonic acid also contracts the tissue and this response is abolished by indomethacin. This tissue also responds to low concentrations of histamine, acetylcholine, noradrenaline and bradykinin. In conjunction with other bioassay tissues such as the rat stomach strip and rabbit coeliac artery, the rabbit transverse stomach strip provides a convenient method of detection of identification of known arachidonic acid metabolites.

Animals↗
PubMed1979

The renal haemodynamic and excretory actions of prostacyclin and 6-oxo-PGF1 alpha in anaesthetized dogs.

Intrarenal arterial (i.a.) infusions of prostacyclin (PGI2) at 30-300 ng/min to anaesthetized dogs reduced renal vascular resistance (RVR) and filtration fraction (FF), increased mean renal blood flow (MRBF) but did not alter mean arterial pressure (MAP)or glomerular filtration rate (GFR). The urinary excretion of sodium (UNaV), potassium (UKV) and chloride ions (UC1V) were increased through inhibition of net tubular ion reabsorption. PGI2 (3000 ng/min, i.a.) reduced MAP and increased heart rate. Intravenous (i.v.) infusions of PGI2 (3000 gn/min) reduced MAP, GFR, FF, urine volume and ion excretion, with elevation of heart rate. The measured variables were unaltered by 6-oxo-PGF1 alpha (10,000 ng/min i.a.). Treatment of the dogs with the PG synthetase inhibitor meclofenamic acid (2.5 mg/kg i.v.) did not antagonise the elevation of MRBF to PGI2 (300 ng/min i.a.). Thus the renal effects of PGI2 were due to a direct action rather than through conversion to 6-oxo-PGF1 alpha or through stimulation of endogenous renal PG biosynthesis and release.

Anesthesia↗
PubMed1979

Effects of prostacyclin on coronary circulation, heart rate and myocardial contractile force in isolated hearts of guinea pig and rabbit - comparison with prostaglandin E2.

Infusions of prostacyclin (PGI2) (3 x 10(-10) - 3 x 10(-7)M) into the coronary circulation of isolated hearts from ginea pigs or rabbits resulted in a concentration-dependent decrease in the coronary perfusion pressure (CPP). There was a slight decrease in left ventricular systolic pressure in the heart of the rabbit, whereas the heart rate remained unchanged. PGE2 was without effect on the heart of the rabbit but was as potent as PGI2 in decreasing the CPP in the guinea pig heart. 6-oxo-PGF1 alpha (up to 3 x 10(-6) M) did not affect any of the parameters measured.

Animals↗
PubMed1979

Preparation and biochemical properties of PGH3.

PGH3 was biosynthesised from all-cis-5,8,11,14,17-eicosapentaenoic acid (20:5 omega 3) by an acetone-pentane powder of ram seminal vesicles and its structure was confirmed by GLC-MS after its reduction to PGF 3 alpha. PGH3 was transformed by horse platelet microsomes to TXB3, and by aortic microsomes to delta 17-6-keto-PGF 1 alpha. The structures of these compounds were confirmed by GLC-MS.

Animals↗
PubMed1979

Biosynthesis of prostaglandin (PGI2) and 12L-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE) by pericardium, pleura, peritoneum and aorta of the rabbit.

Prostacyclin generation by pericardium, pleura, peritoneum, aorta and dura mater of the rabbit was assessed as platelet aggregation inhibitory activity in platelet rich plasma. All tissues except the dura mater, were also incubated with labelled (1-14C) arachidonic acid and (1-14C) prostaglandin endoperoxide H2 and the various metabolites formed were identified radiochromatographically. Pericardium, pleura and peritoneum form substantially high amounts of prostacyclin and HETE indicating that these tissues contain both cyclo-oxygenase and prostacyclin-synthetase. They also show considerable lipoxygenase activity.

Animals↗
PubMed1979

Responses of human and baboon arteries to prostaglandin endoperoxides and biologically generated and synthetic prostacyclin: their relevance to cerebral arterial spasm in man.

1 Isolated strips of human or baboon basilar, middle cerebral, vertebral or common carotid arteries were set up in an isolated organ bath or in a superfusion cascade system. 2 These arteries relaxed to prostacyclin but contracted to prostaglandin endoperoxide (PGH2). 3 Human and baboon isolated arteries also generated prostacyclin from exogenous endoperoxide (PGH2). 4 Human arteries generated prostacyclin 36 h post-mortem but not 40 h post-mortem. The biologically generated prostacyclin relaxed the basilar artery and overcame the contractile effects of PGH2. 5 Thromboxane A2-like activity generated during human platelet aggregation by arachidonic acid caused contractions of the human basilar artery. 6 Prostacyclin reversed contractions of human basilar arteries caused by an unidentified vasoconstrictor factor in cerebrospinal fluid obtained from patients with cerebral arterial vasospasm after subarachnoid haemorrhage following rupture of cerebral arterial aneurysms. 7. The above vasospasm may be due at least in part to disordered physiological control of the calibre of cerebral arteries caused by diminished synthesis of prostacyclin.

Animals↗
PubMed1979

Elimination of prostacyclin (PGI2) and 6-oxo-PGF1 alpha in anaesthetized dogs.

The plasma concentration of 6-oxo-PGF1 alpha was measured by radioimmunoassay after constant rate infusion of 6-oxo-PGF1 alpha or prostacyclin (PGI2) into anaesthetized dogs. A steady-state plasma concentration was rapidly attained with both compounds. After termination of the infusions, the concentration of 6-oxo-PGF1 alpha declined according to a bi-exponential process. The steady-state plasma concentrations of 6-oxo-PGF1 alpha obtained after infusion of 6-oxo-PGF1 alpha and PGI2 were approximately 10 times higher than the corresponding steady-state level of PGF2 alpha measured after infusion of PGF2 alph into the same dogs. The data presented suggest that PGI2 and 6-oxo-PGF1 alpha are eliminated more slowly than PGF2 alpha, probably because they are not taken up and metabolized in the lungs as rapidly as PGF2 alpha.

Animals↗
PubMed1979

Prostacyclin, thromboxane A2 interactions in haemostasis and thrombosis.

Prostacyclin and thromboxane A2 are products of arachidonic acid which play a role in the regulation of haemostatic plug and thrombus formation. Aspirin inhibits the synthesis of both compounds but is more active in blocking TXA2 formation; based on this, aspirin is suggested to have an anti-thrombotic effect. Other possible approaches to the development of anti-thrombotic drugs are discussed.

Animals↗
PubMed1979

The role of prostacyclin in vascular tissue.

Prostacyclin (PGI2) generated by the vascular wall is a potent vasodilator, and the most potent endogenous inhibitor of platelet aggregation so far discovered. Prostacyclin inhibits platelet aggregation by increasing cyclic AMP levels. Prostacyclin is a circulating hormone continually released by the lungs into the arterial circulation. Circulating platelets are, therefore, subjected constantly to prostacyclin stimulation and it is via this mechanism that platelet aggregability in vivo is controlled. Moreover, phosphodiesterase inhibitors such as dipyridamole or theophylline exert their antithrombotic actions by potentiating circulating prostacyclin. The prostacyclin:thromboxane A2 ratio is important in the control of thrombus formation; manipulation of this ratio by small doses of aspirin (which will inhibit mainly platelet cyclooxygenase), a selective inhibitor of thromboxane formation, or the dietary use of a fatty acid like eicosapentaenoic acid (which would be the precursor for a delta17-prostacyclin (PGI3) but is transformed by the platelets into nonaggregating thromboxane A3) might have beneficial effects as antithrombotic therapies. Prostacyclin has interesting potential for clinical application in conditions where enhanced platelet aggregation is involved or to increase biocompatibility of extracorporeal circulation systems.

Animals↗