Faculty Collaboration Database

Prostaglandin redirection by thromboxane synthetase inhibition. Attenuation of myocardial stunning in canine heart. Circulation 1990 Jan;81(1):369-80

Date

01/01/1990

Pubmed ID

2297841

DOI

10.1161/01.cir.81.1.369

Scopus ID

2-s2.0-0025064352 (requires institutional sign-in at Scopus site)   29 Citations

Abstract

We have previously reported that inhibition of thromboxane synthesis results in an improvement in postischemic function in stunned myocardium of dogs. The purpose of the present study was to investigate further the mechanism by which thromboxane synthesis inhibition improves recovery of function in stunned myocardium (15 minutes of coronary occlusion and 3 hours of reperfusion) in barbital anesthetized dogs. The recovery of regional myocardial wall function (percent segment shortening, % SS) following treatment with two doses (0.5 and 10 mg/kg) of a thromboxane receptor blocker, BM 13.505, given prior to coronary occlusion, was not different from that of a control group (3-hour % SS of pretreatment control, PTC, 12 +/- 11) throughout reperfusion (3-hour % SS of PTC with BM 13.505: 0.5 mg/kg 14 +/- 10; 10 mg/kg, 27 +/- 9). In contrast, the specific thromboxane synthetase inhibitor, dazmegrel (3.0 mg/kg), significantly improved % SS throughout reperfusion (3-hour % SS of PTC, 66 +/- 8). In addition, while dazmegrel produced a marked decrease in thromboxane, 6-keto-PGF1 alpha was significantly increased in coronary venous blood throughout the occlusion and reperfusion period. The cyclooxygenase inhibitor, indomethacin, had no beneficial effect on functional recovery (3-hour % SS of PTC, 5 +/- 6), attenuated the dazmegrel induced shunting to prostacyclin, and completely prevented the beneficial effects of dazmegrel on functional recovery (3-hour % SS of PTC, 17 +/- 12). Thus, a redirection to endogenous cardioprotective prostanoids, such as prostacyclin, appears to be responsible for the beneficial effect of thromboxane synthesis inhibition on postischemic recovery in stunned myocardium whereas thromboxane does not appear to be an important mediator of the stunning phenomenon.

Author List

Farber NE, Gross GJ

MESH terms used to index this publication - Major topics in bold

Animals
Coronary Circulation
Dogs
Hemodynamics
Myocardial Reperfusion Injury
Myocardium
Organ Size
Prostaglandins
Thromboxane-A Synthase
Thromboxanes