Influence of the thromboxane synthetase inhibitor HOE 944, prostacyclin and indomethacin on reperfusion arrhythmias, cardiodynamics and metabolism in isolated ischemic rat hearts.
We investigated the influence of the thromboxane (TX) synthetase inhibitor HOE 944 (6-(5-Methylimidazol-1-yl)methyl-2-naphthoic acid-Hydrochloride), prostacyclin (PGI2) and indomethacin on reperfusion arrhythmias in isolated perfused ischemic rat hearts. HOE 944, PGI2 and indomethacin were perfused in a concentration of 1 x 10(-6), 5 x 10(-8) and 1 x 10 (-6) mol/l respectively (in vitro). In another set up rats were pretreated p.o. with a daily dose of 30 mg/kg for 7 days (ex vivo). Acute regional myocardial ischemia was induced in isolated working rat hearts by occlusion of the left coronary artery. Reperfusion commenced upon release of this occlusion which was invariably associated with ventricular fibrillations (VF). Perfusion with 1 x 10(-6) mol/l HOE 944 did not affect these arrhythmias. In contrast hearts from HOE 944 pretreated rats were protected against fibrillations (p less than 0.01). PGI2 perfusion was also protective against VF (p less than 0.01) whereas indomethacin perfusion aggravated VF. In the ischemic period cardiodynamics like left ventricular pressure (LVP), dp/dt max and coronary flow (CF) were improved in HOE 944 pretreated rat hearts. In the venous effluent the enzyme activities of lactate dehydrogenase (LDH) and creatine kinase (CK) as well as lactate production were decreased in the ischemic and reperfusion period. Myocardial tissue levels of ATP were distinctly increased and lactate levels decreased in HOE 944 pretreated rats, whereas glycogen and creatine phosphate did not change.(ABSTRACT TRUNCATED AT 250 WORDS)
Linz
W
W
Hoechst AG, Frankfurt/M.
Lau
H H
HH
Beck
G
G
Schökens
B A
BA
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology* / Q000517:prevention & control; D003327:Coronary Disease / Q000503:physiopathology*; D011464:Epoprostenol / Q000494:pharmacology / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology* / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D007093:Imidazoles; D009281:Naphthalenes; C059526:6-(5-methylimidazol-1-yl)methyl-2-naphthoic acid hydrochloride; D011464:Epoprostenol; D013930:Thromboxane-A Synthase; D007213:Indomethacin