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Biomedical subjects

P Mentz

Publications and source records attributed to P Mentz.

At least 37 records · Page 2Linked to original sources
PubMed1987

[The effectiveness of trapidil and some derivatives on heart function under in vitro and in vivo conditions].

Cardiac and coronary effects of trapidil (Rocornal) and some derivatives were investigated in isolated heart preparations and rabbit hearts in vivo. All substances showed a comparable increase of the coronary flow. Contrary to the cardiotonic influence of trapidil the trapidil derivates induced a negative inotropic effect, possibly due to a weak calcium antagonism. Heart rate was slightly diminished, but in some cases higher doses caused an acute tachycardia. I.v. application of the substances to rabbits in doses of 10 mg/kg and 30 mg/kg induced an initial depression of blood pressure normalizing within 3-5 min. An increase of the myocardial prostacyclin biosynthesis is only demonstrable under trapidil. The results indicate that the cardiac effects of trapidil derivatives are possibly caused by a direct influence on the contractile system and the membrane potential of the cardiac muscle cell.

Anesthesia↗
PubMed1987

[Thromboxane A2 antagonistic effect of antiangina drugs, with special reference to trapidil and trapidil derivatives].

In isolated perfused guinea pig hearts and in the cardiocirculatory system of anaesthetized rabbits the thromboxane A2-agonist U 46619 shows cardiodepressive effects. The contraction force of isolated auricle preparations from guinea pigs was enhanced. Antianginous drugs (dipyridamole, propranolol, verapamil, nitroglycerin and trapidil) induced a significant inhibition of the U 46619 effects. Oxyfedrine remained ineffective. The efficiency of some derivatives of trapidil was markedly diminished or abolished in comparison with the original substance. Because of the different chemical structure of the active drugs the TXA2-antagonism is regarded to be caused by a functional influence on the cellular membrane and the calcium transport. Nevertheless the inhibition of the TXA2-effects by antianginous drugs seems to be a factor for the therapeutic use of these substances.

Anesthesia↗
PubMed1987

[Chemical synthesis of phenylbutazone hydroperoxide and testing of the substance for heart action under in vitro and in vivo conditions].

Phenylbutazone (4-n-butyl-1,2-diphenyl-pyrazolidine-3,5-dione) 1 is an easily autoxidable substance which forms a crystalline and stable hydroperoxide 3. The decomposition of 3 yields products which were investigated as metabolites of the drug. In isolated heart preparations of guinea pigs and rabbit hearts in vivo the hydroperoxide 3 shows a significantly stronger cardiodepressive and coronary constricting effect compared to phenylbutazone 1, 4-hydroxy-phenylbutazone 4 and the open-ring decomposition product of the hydroperoxide 5. The results indicate the significance of the hydroperoxide 3 for the total efficiency of phenylbutazone and explain the side effects of the substance.

Animals↗
PubMed1986

The influence of lipoproteins (LDL and HDL) on PGI2-formation by isolated aortic preparations of rabbits.

The influence of LDL- and HDL-concentrations of 0.5-2.0 mg/ml and 0.25-1.0 mg/ml respectively, from male and female donors on the formation of PGI2 in isolated aortic preparations was investigated under in vitro conditions. LDL of male donors inhibited endogenous PGI2-formation and the conversion of exogenous PBH2 to PGI2. On the other hand the highest concentration of HDL induced an increase in the basal and in the stimulated PGI2-formation. Lipoproteins of female donors showed no or only a weak stimulating effect on PGI2-formation. Human serum albumin in comparable concentrations of 1-50 mg/ml remained without influence. The importance of the results for cardiovascular diseases is discussed.

Animals↗
PubMed1984

Significance of myocardial prostaglandin biosynthesis and the influence of mechanical loading, endogenous mediators and cardiovascular drugs.

Isolated perfused and electrically driven heart preparations of guinea pigs and tissue from different parts of the rabbit hearts have the capacity to rapidly synthesize prostacyclin (PGI2) and thromboxane (TXB2). Auricles showed a higher PGI2 formation than ventricles. Addition of arachidonic acid or PGH2 markedly enhanced the myocardial PGI2 biosynthesis. After acute pressure overload by a graduated aortic stenosis the PGI2 and TXB2 formation of the myocardium is decreased possibly caused by a diminished availability of substrate, an alteration of enzyme activities or changes in the functional state of the cardiac tissue. Pretreatment with dipyridamole or propranolol again induced an increase of this diminished PGI2 and TXB2 synthesis. The PGI2 formation of electrically driven ventricular strips enhanced with an increased stimulation rate. Ouabain, antianginal drugs (dipyridamole, oxyfedrine, propranolol) and endogenous mediators (norepinephrine, histamine, adenosine) induced a significant rise of the cardiac PGI2 formation. The results suggest that the cardiac prostaglandin biosynthesis is involved in the action of the myocardium indicating heart sufficiency and an adaptability to mechanical loading or drug influence.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

The dependence of cardiac eicosanoid effects on changes of calcium concentration.

Investigations were performed in isolated heart preparations of guinea pigs to prove the dependence of myocardial eicosanoid effects (PGE1, PGF2a, PGI2, U 46619) on concentration and fluxes of calcium ions. In auricles the increase of cardiac performance by eicosanoids was more evident, when calcium ions were reduced in the medium. In isolated perfused hearts a continuous perfusion of eicosanoids showed a cardiodepressive effect. The coronary flow was increased by PGE1 and PGI2, but decreased by U 46619. The actions of prostaglandins were diminished, but the U 46619 influence increased with rising calcium concentrations. The antiaggregatory effect of PGI2 was decreased by calcium. Furthermore the calcium antagonist verapamil opposed Ca2+-fluxes and the cardiac and coronary effects of prostaglandins. The results indicate that eicosanoids induce cardiac and vascular effects by changes in the membrane calcium fluxes and/or the intracellular concentration and distribution of calcium ions.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1984

[The importance of increased prostaglandins and prostacyclin for the effect of oxyfedrin in isolated guinea pig heart preparations].

In isolated perfused heart preparations of guinea pigs coronary dilating and positive inotropic doses of oxyfedrine induce a significant increase of the release of prostaglandin-like substances (PLS) and prostacyclin (PGI2). Indometacin as an inhibitor of prostaglandin biosynthesis (140 mumol/l) enhances after a 10 min lasting perfusion contraction force and coronary flow of the hearts but inhibits PGI2-formation. Under these conditions oxyfedrine loses its positive influence on inotropism, coronary flow and PGI2-efflux. Indometacin (140 mumol/l) also completely abolishes the increase of cardiac performance of isolated auricle preparations by oxyfedrine (50 mumol/l). These findings agree with former results and indicate an involvement of the PLS- and PGI2-biosynthesis in the antianginal efficacy of oxyfedrine.

Animals↗
PubMed1984

Regulatory action of cholesterol esters on the eicosanoid metabolism.

The influence of cholesterol esters (CE) on the formation of prostacyclin (PGI2) and thromboxane A2 (TXA2) depends on the concentration of the added CE and the fatty acid, esterified in the CE. Our results demonstrate that the formation of eicosanoids depends on the CE composition in the microenvironment of the enzymes. Therefore we suggest that the influence of elevated CE levels on the development of atherosclerosis may be also mediated by their influence on the eicosanoid metabolism.

Animals↗
PubMed1984

Drug induced inhibition of the cardiac effects of U 46619 as a thromboxane A2-like agonist.

U 46619 (11,9-epoxymethano-PGH2) appears to be a selective and stable thromboxane-like agonist. In isolated preparations the substance (3.10(-9) - 3.10(-6) mol/l) induced an increase of cardiac performance of auricles and a decrease of contraction force and coronary flow of perfused hearts of guinea pigs. Intravenous infusion of U 46619 (10 micrograms/kg/min) to rabbits caused a marked reduction of heart contractility and blood pressure and the death of the animals within 10 minutes. Antianginal drugs, especially dipyridamole, propranolol, trapidil and verapamil, significantly reduced the TXA2 agonistic effects in auricles and anesthetized rabbits. The results indicate that some antianginal drugs inhibit TXA2 effects in the cardiocirculatory system. This may be regarded as an important factor for the therapeutic use of these substances.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1983

Myocardial biosynthesis of prostaglandins with special consideration of prostacyclin and the influence of dipyridamole and propranolol.

Experiments with isolated perfused hearts of guinea pigs and rats showed that cardiac action is linked to formation of prostaglandinlike substances (PLS) and prostacyclin (PGI2). Perfusion of the hearts with arachidonic acid or pretreatment with a linoleic-acid-supplemented diet significantly increased the content of PLS and PGI2 and exerted an economic effect on the heart performance. Dipyridamole induced a marked increase in the coronary flow and PGI2 formation of the hearts but decreased the enhanced myocardial PGI2 biosynthesis after perfusion with arachidonic acid. Propranolol also caused a rise in PGI2 efflux but did not show any influence on PGI2 formation after arachidonic acid. Dipyridamole and propranolol prevent decreased PGI2 formation after acetylsalicylic acid, supporting the view that a combination of these drugs exerts a preventive effect in patients with angina pectoris and heart infarction.

Animals↗
PubMed1983

Influence of cardiovascular drugs on platelet aggregation.

All vasodilatory drugs reported in this chapter possess an antiaggregatory effect on platelets, some of them with a synergistic effect on prostacyclin-induced inhibition of aggregation. Thus, the question seems valid whether the antiaggregatory effect represents one part of their antianginal and antihypertensive action. Some vasodilators stimulate the biosynthesis of prostacyclin and/or other vasodilating prostaglandins. This stimulation could be linked not only to the antiaggregatory but also to the vasodilating action. The influence on prostaglandin biosynthesis, however, is not obligatory for all vasodilators, as nitroglycerin proves. Trapidil inhibits the biosynthesis and the effect of thromboxane A2, as our own experiments and those by Ohnishi et al. (7) have shown. This effect could be favorable in patients with heart infarction. Lefer et al. (5) have demonstrated a fivefold increase in thromboxane release after experimental ligation of the coronary artery in the cat. Pinane thromboxane, a thromboxane antagonist, almost completely abolished all deleterious consequences of ischemia. Whether trapidil is also able to inhibit thromboxane biosynthesis and activity under clinical conditions of heart infarction will be the topic of further investigations.

Animals↗
PubMed1983

[The modification of the biosynthesis and effect of thromboxane A2 and prostacyclin by trapidil (Rocornal)].

The influence of the antianginal drug trapidil on the biosynthesis of thromboxane A2 (TXA2) and/or prostacyclin (PGI2), metabolites of arachidonic acid (AA), was investigated in rabbit and human platelet rich plasma (PRP), in homogenates of rabbit spleen and of rat lung and in aortic preparations of rats and rabbits, respectively. Trapidil showed a marked inhibition of the AA-induced aggregation and TXA2 biosynthesis in rabbit and human PRP. The TXA2 inhibition by trapidil was not demonstrable in damaged platelets and seems to require intact cells. In homogenates of rat lungs, trapidil remained without effect on the TXA2 and PGI2 synthesis. In rabbit spleen homogenates the drug induced an inhibition of the formation of both AA metabolites. In contrast to Japanese authors we could not observe any increase in PGI2 release in rat aortic preparation. The PGI2 release from isolated perfused guinea pigs hearts was enhanced; on the other hand, the PGI2 efflux from rabbit hearts remained unchanged. The antiaggregatory effect of PGI2 on the ADP-induced aggregation was strengthened by trapidil, showing an overadditive effect in rabbit PRP. The aggregation inducing effect of the prostaglandin endoperoxide analog U-46619 was inhibited by trapidil. A possible clinical significance of the inhibitions of the synthesis and effect of TXA2 for therapy of ischemic heart disease is discussed.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1981

[Stimulation of prostacyclin biosynthesis as a possible mechanism of action of dipyridamole (author's transl)].

In microsomes of pig aorta, isolated perfused hearts of guinea-pigs, rabbit vessel preparations and homogenates of rat lungs 2,6-bis-[bis-(beta-hydroxyethyl)-amino]-4,8-dipiper-idino-pyrimido-[5,4-d]pyrimidine (dipyridamole) application caused a marked stimulation of prostacyclin biosynthesis. The oxygen incorporation into arachidonic acid indicating cyclooxygenase and lipoxydase activity under the influence of lyophilised ram vesicle microsomes was increased by dipyridamole. The formation of malondialdehyde and thromboxane A2 in platelet rich plasma of rabbits remained uninfluenced. On the other side the formation of thromboxane A2 was moderately inhibited in homogenates of guinea-pig lungs. The arachidonic acid-induced thrombus formation and following death of rabbits remained uninfluenced. The results indicate that dipyridamole causes a relatively specific alteration of the prostaglandin metabolism stimulating the biosynthesis of prostacyclin but without effect or only moderate inhibition of the formation of thromboxane A2. These effects could be looked upon as an important mechanism for the cardiovascular action of the drug.

Animals↗
PubMed1978

Influence of coronary vasodilators on prostaglandin E, F2alpha, I2, and adenosine metabolism.

We investigated the influence of oxyfedrine, verapamil, prenylamine, sodium nitrite, nitroglycerin, papaverine and carbochromen on the release of prostaglandins (PG) and adenosine from Langendorff heart preparations of guinea pigs and rabbits and on the PG biosynthesis in the heart and renal medulla of rabbits, in the bovine seminal vesicle homogenate, and in the rat stomach fundus. Oxyfedrine stimulated the release of PGE and PGF2alpha from the Langendorff hearts and increased the PG biosynthesis in all organs investigated. Compared with the other drugs, oxyfedrine showed the strongest stimulation of PGI2-synthesis in the rat stomach fundus. Prenylamine depressed the PG biosynthesis in all organs investigated but increased the PGE release from Langendorff hearts. Nitroglycerin, verapamil and, to some degree, also carbochromen increased the PGI2 synthesis in rat stomach fundus. Sodium nitrite was without influence on the PG release from Langendorff hearts and on the PG biosynthesis. Papaverine did not influence the PGI2 synthesis. Independently of the PG release, oxyfedrine, prenylamine and sodium nitrite increased the adenosine efflux from the rabbit hearts.

Adenosine↗