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Biomedical subjects

H J Mest

Publications and source records attributed to H J Mest.

At least 91 records · Page 5Linked to original sources
PubMed1987

Trapidil derivatives as potential antiatherosclerotic drugs.

Trapidil, a triazolopyrimidine, and its derivatives are coronary vasodilating drugs. Trapidil reduces the serum level of low density lipoprotein- and very low density lipoprotein-cholesterol and increases the serum level of high density lipoprotein-cholesterol in hyperlipemic patients. The present study demonstrates that trapidil and five different trapidil derivatives inhibit the proliferation of cells cultured from grossly normal intima and fatty streaks of human aorta. The inhibiting effect of trapidil derivatives is about 60%, similar to the standard substance 3-isobutyl-1-methyl-xanthine (MIX). In cells cultured from atherosclerotic plaques trapidil and trapidil derivatives reduced the content of cholesteryl esters by 36% for trapidil and between 47% and 68% for 4 of 5 trapidil derivatives, respectively. The trapidil derivative AR 12463 (5-piperidino-7-[N-(n-amyl)-N-(beta-hydroxyethyl)amino]-s-triazolo[1,5- a]pyrimidine) reduces the free cholesterol content by 29%, but the other trapidil derivatives are without effect on this parameter. Four of five derivatives decrease the content of triglycerides by 53 to 70%. The synthesis of collagen is inhibited by the trapidil derivative AR 12463 (25%). Trapidil and other derivatives have a smaller or no effect on the synthesis of collagen. These effects of trapidil derivatives point to potential antiatherosclerotic properties. The possible mechanisms are discussed.

Arteriosclerosis↗
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

What about the effects of dietary lipids on endogenous prostanoid synthesis? A state-of-the-art review.

The endogenous prostanoid synthesis can principally be influenced by a variation of the polyunsaturated fatty acid supply in food. Withholding an essential fatty acid supply in food for a length of time results in a low rate of formation of prostanoids. However, there is no simple correlation between the amount of prostaglandin precursor fatty acid supplied with food and the biosynthesis of prostanoids in the different organs. A progressive increase of the intake of polyunsaturated fatty acids results in irregular changes in the prostanoid synthesis of the organism. The impact of various parameters should be taken into account, e.g., the period of feeding, the preexperimental state of the organism, the kind of polyunsaturated fatty acid related to a particular family of fatty acids, interactions with other components of food, differences of the species, organ specificities, aspects of chronoperiodicity, interactions of the prostanoids (and polyunsaturated fatty acids, respectively) with other metabolic circuits on a different level of integration, and details in the methods applied in the determination of prostanoids. Above all, care must be taken to prevent too general conclusions being drawn about the influence on the endogenous synthesis of prostanoids by dietary polyunsaturated fatty acids.

Animals↗
PubMed1987

Relevance of eicosanoids for biochemical regulation of cardiac rhythm disturbances.

The balance between the eicosanoids seems to be involved in the biochemical regulation of cardiac rhythm. Under several pathophysiological conditions thromboxane (TX) could be an important factor for the genesis of cardiac arrhythmias. Shifting the balance between the arrhythmogenic TX and the antiarrhythmic prostacyclin (PGI2) in favour of PGI2 by substances influencing the arachidonic acid cascade might by useful for the treatment of arrhythmias. PAF induced toxic arrhythmogenicity seems to be mediated by TX. Therefore the suppression of TX influence can antagonize these arrhythmias, too.

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

The influence of cod-liver oil diet on various lipid metabolism parameters, the thromboxane formation capacity, platelet function and the serum MDA level in patients suffering from myocardial infarction.

The influence of an eicosapentaenoic-acid-rich diet, containing 8.1 g cod-liver oil, given daily for two weeks on various parameters of lipid metabolism, the thromboxane formation capacity, platelet function and the serum MDA level was studied in 16 patients with myocardial infarction. The 18:2, 20:3 and 20:4 fatty acid portions of serum phospholipids were significantly decreased, whereas the 20:5 and 22:6 portions were significantly elevated. Serum total cholesterol, LDL cholesterol and the thromboxane formation capacity were significantly increased. Serum triglycerides, HDL cholesterol, the prostacyclin blocking activity of LDL, and several parameters of platelet function were unchanged, the platelet count was significantly depressed. As compared to those of healthy persons, the serum MDA levels in myocardial infarction patients were significantly increased both before and after cod-liver oil ingestion. A possible correlation between the elevated serum levels of MDA and total cholesterol, LDL cholesterol as well as thromboxane formation capacity and the cod-liver oil treatment in patients with myocardial infarction is discussed.

Cholesterol↗
PubMed1987

[The effect of trapidil and the trapidil derivative AR 12463 on blood pressure and thromboxane formation in spontaneously hypertensive rats].

The trapidil derivative AR 12463 has a much more stronger inhibiting effect than trapidil on different atherosclerotic parameters of the cell cultures obtained from normal intima and fatty streaks of human aorta, on thromboxane (TX) formation and on the aggregation of human platelets in vitro, and on the activity of phosphodiesterase. In addition to these present results, AR 12463 reduced significantly the mean arterial blood pressure of spontaneously hypertensive rats (at a dosage of 20 mg/kg/d administered orally for 2 weeks) in contrast to the same dosage of trapidil. Simultaneously, TX formation is significantly reduced in serum by 48% in aorta thoracica by 29%, and in aorta abdominalis by 19%. Due to these properties, AR 12463 seems to be suitable for a therapeutic and prophylactic strategy in chronic ischemic diseases.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

[The effectiveness of trapidil and trapidil derivatives on drug-induced heart arrhythmias in the rat and guinea pig].

Trapidil and some selected derivatives of trapidil were investigated in ouabain induced arrhythmia in guinea-pigs and in aconitine induced arrhythmia in rats. In both models trapidil exerted a marked antiarrhythmic effect. Investigations on ouabain induced arrhythmia showed that three derivatives were more effective than trapidil concerning the threshold for premature ventricular beats and flutter. One derivative only was able to decrease the sensitivity for fibrillation in the same order of magnitude as trapidil. On aconitine induced arrhythmia all derivatives of trapidil were less effective in elevating the threshold of arrhythmia than trapidil itself, but three derivatives showed antiarrhythmic properties.

Aconitine↗
PubMed1986

Influence of a cod liver oil diet in healthy and insulin-dependent diabetic volunteers on fatty acid pattern, inhibition of prostacyclin formation by low density lipoprotein (LDL) and platelet thromboxane.

Ten healthy and twenty diabetic volunteers (type 1) received 15 capsules (à 450 mg) cod liver oil for 2 weeks daily in addition to a "normal" diet. The levels of eicosapentaenoic acid in the plasma phospholipids of both groups were increased after the treatment. The inhibition of the prostacyclin formation by LDL was diminished when the LDL was isolated after the treatment in comparison to LDL taken in the same concentration and from the same donors before it. The thromboxane B2 (TXB2) synthesis capacity of clotting whole blood, thrombin-induced TXB2 formation by platelets as well as the 15(S)-hydroxy-11 alpha,9 alpha-epoxymethano-5Z, 13E-prostadienoic acid-induced platelet aggregation were not altered by the treatment in healthy volunteers, whereas in diabetics the TXB2 formation capacity of clotting whole blood was decreased after the treatment in comparison with before it.

Adult↗
PubMed1986

[Is there a renaissance for trapidil?].

In a survey experimental and clinical investigations on Trapidil (Rocornal) are briefly demonstrated. The great number of recent investigations, particularly by Japanese authors, render it necessary anew to think over the application of Trapidil in the GDR. Apart from possibilities of the treatment of the ischaemic heart disease, the survey shows further possible indications, such as inhibitions or the aggregation of thrombocytes, improvement of the microcirculation and treatment of hyperlipidaemias. It was made evident that Trapidil induces no steal phenomenon and thus a restriction as an antianginal pharmacon it not justified. A renaissance for Trapidil indicates itself.

Angina Pectoris↗
PubMed1986

[Significance of eicosanoids for arteriosclerosis and the effect of lipoproteins on prostanoid formation].

In a review the possible relevance of the eicosanoid system for arteriosclerosis is outlined. Particularly the interdependence between prostacyclin and thromboxane regarding the development of arteriosclerosis is discussed. Own findings show the influence of lipoproteins on the synthesis of prostacyclin or thromboxane in different biological material. On the one hand, HDL stimulates the synthesis of prostacyclin, whereas LDL inhibits it; both of them were sampled from human volunteers. On the other hand, the synthesis of thromboxane is inhibited by HDL and stimulated by LDL. The results indicate the close relationship between the lipoprotein and the eicosanoid hypotheses of arteriosclerosis.

Animals↗
PubMed1986

[Changes in blood pressure and serum lipids with fish diets in patients with mild essential hypertension].

14 male patients with moderate essential hypertension were treated in the cross-comparison with a mackerel and herring diet, respectively, for two weeks. The mackerel diet contained double as much eicosapentaenic (EPA) and docosahexaenic acid (DHA) as the herring diet which served as control. In the serum triglycerides particularly DHS, in the cholesterol esters above all EPA were enriched. In the phospholipids the increase of the two fatty acids was approximately the same. At the end of the mackerel period the serum triglycerides, the total and LDL-cholesterol, the activity of the lecithin-cholesterol-acyl-transferase (CALT) and the serum sodium were significantly decreased. On the other hand, the HDL-cholesterol and the uric acid in the serum significantly increased. Under influence of the herring diet the parameters mentioned appeared only slightly changed. After the mackerel diet also a significantly lower systolic blood pressure was found. The systolic and diastolic blood pressure during a standardized psychophysiological stress test was more diminished at the end of the mackerel period than after the herring diet. The plasma renin activity (PRA) was increased after the mackerel diet. Its increase under the stress test could no more be proved at the end of the mackerel diet. In similar way the stress-conditioned increase of thromboxane B2 could no more be observe both after mackerel and after herring diet. When the results should confirm themselves in long-term studies, a mackerel diet in practicable dosage can be recommended as non-medicamentous treatment of moderate hypertension.

Blood Pressure↗
PubMed1986

Endogenous lipoproteins modify the thromboxane formation capacity of platelets.

A significantly negative correlation was demonstrated between HDL-cholesterol levels of serum and the thromboxane B2 (TXB2) formation in clotted whole blood, whereas a significantly positive correlation was estimated between the LDL cholesterol or apolipoprotein B (apo B) levels and the TXB2 formation in clotted whole blood. Similar relationships were observed between the HDL and apo B serum levels and the thrombin-induced malondialdehyde formation in platelet-rich plasma. The levels of HDL2 cholesterol, total cholesterol, apo A-I and of triglycerides were not significantly correlated with the TXB2 or malondialdehyde formation in both systems. The results in this study support the hypothesis that the TXB2 formation may be modulated by endogenous lipoproteins: high level of LDL stimulates and high level of HDL inhibits the TXB2 formation.

Adult↗