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Biomedical subjects

A Beitz

Publications and source records attributed to A Beitz.

25 records · Page 2Linked to original sources

Influence of iloprost on eicosanoid generation and lipid levels in experimental myocardial ischemia in dogs.

Anaesthetized mongrel dogs were subjected to occlusion of a coronary artery. The resulting myocardial infarction was observed for three hours. One hour after occlusion, infusion of the stable prostacyclin analogue iloprost or saline was started. In the control group myocardial infarction was associated with an increase of the ratio TXB2/6-keto-PGF1a which was abolished by iloprost treatment. After occlusion in the control group, the atherosclerosis index (TC-HDLC): HDLC was increased, but in the iloprost-treated group it was significantly decreased. The results of this study suggest that the administration of iloprost is able to prevent changes in eicosanoid metabolism and lipoprotein pattern after coronary artery occlusion in dogs.

6-Ketoprostaglandin F1 alpha↗

Influence of drugs on the TXA2/PGI2 balance and on the atherogenic index in myocardial ischemia in dogs.

The effect of drugs on eicosanoid production and on the development of atherogenic index was investigated in canine myocardial ischemia. Iloprost, verapamil, the trapidil derivative AR 12463 or 0.9% NaCl solution were administered 60 min after coronary artery ligation in anaesthetized dogs. Both iloprost and AR 12463 reduced the thromboxane A2/prostacyclin (TXA2/PGI2) ratio in coronary sinus plasma in comparison to controls. The atherogenic index was significantly decreased in the iloprost as well as in the AR 12463-treated group in comparison to the control group. Verapamil had no influence on the investigated parameters.

Animals↗

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↗

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↗

Low density lipoproteins of male donors decrease prostacyclin (PGI2) and enhance thromboxane (TXA2) release from rat aortas perfused under pulsatile pressure.

The influence of low density lipoproteins (LDL)-cholesterol (1.69 +/- 0.08 mg/ml) and of high density lipoproteins (HDL)-cholesterol (0.62 +/- 0.09 mg/ml), respectively, on the levels of 6-oxo-PGF1 alpha and TXB2 in the perfusates of rat aortas perfused under pulsatile pressure was studied. After passage through the aortas the concentration of LDL-cholesterol was significantly decreased in the perfusates, whereas the HDL-cholesterol level was unchanged. In comparison to controls, perfused with lipoprotein free solution, the concentration of 6-oxo-PGF1 alpha was significantly decreased more than 50% by LDL and the TXB2 level was enhanced significantly by approximately 50%. This results in a significant rise of the TXB2/6-oxo-PGF1 alpha ratio in the perfusates. HDL did not significantly change the ratio of these eicosanoids in the perfusates. These results suggest that this concentration of LDL enhanced the formation of the proaggregatory TXA2 and decreased the formation of the antiaggregatory PGI2 in rat aortas perfused under pulsatile pressure. The proaggregatory action of an elevated level of LDL during the development of atherosclerosis in men may be also mediated by changes in the metabolism of eicosanoids of the vessel wall.

Animals↗

Thromboxane B2 (TXB2) formation in clotting whole blood of healthy and diabetic humans in vitro.

We investigated the ability of platelets from two groups of diabetics type I and two groups of healthy volunteers matched of age to generate thromboxane B2 (TXB2) during spontaneous clotting of whole blood. The serum concentration of TXB2, reflecting the ability of the platelets to generate TXA2 during clotting, was measured by gas liquid chromatography. Platelets from old diabetics with more than 40 years duration of diabetes mellitus formed significantly less TXB2 than those from old healthy controls. Platelets from juvenile diabetics (9 years duration of disease) formed nearly the same amount of TXB2 as those from young healthy volunteers. The importance of these results is discussed.

Adult↗

The trapidil derivative AR 12456 protects against serum hyperlipidemia in guinea pigs.

The administration of the trapidil derivative AR 12465 (5 mg/kg body weight) intraperitoneally to hypercholesterolemic guinea pigs caused a stronger reduction in serum total cholesterol (TC) than trapidil (20 mg/kg, i.p.) or a vehicle injection (saline with 5% ethanol i.p.). The stronger reduction of TC is caused by a lower level in the sum of all beta-migrating lipoproteins and an enhanced level of high-density lipoprotein. The levels of free and esterified cholesterol were not changed in kidney and left cardiac ventricle, but significantly enhanced (P less than 0.05) in the liver of all groups fed a cholesterol-rich diet. The elevation in liver cholesterol was higher in the group treated with AR 12456 than in the group treated with trapidil or with vehicle. The treatment with AR 12456 diminished the ratio TXB2/6-keto-PGF1 alpha for the capacity of aorta to form these prostanoids. In conclusion, our data show that AR 12456 has a strong antilipidemic action in guinea pigs fed a cholesterol-rich diet.

3',5'-Cyclic-AMP Phosphodiesterases↗