Thromboxane A2 mediates reperfusion injury after heart preservation.
To assess the role of the eicosanoid thromboxane A2, a potent vasoconstrictor and platelet activator, in reperfusion injury after heart preservation, donor rats (n = 18) were anesthetized, and their hearts were rapidly excised, arrested with cardioplegic solution, and fitted with a left ventricular balloon. Seven hearts were subjected to 45 minutes of ischemia at 15 degrees C, simulating implantation, (group 1) during which the carotid and jugular vessels of support rats were cannulated for ex vivo blood reperfusion. Remaining hearts were preserved in 4 degrees C saline solution for 3 hours followed by 45 minutes at 15 degrees C (group 2, n = 11). Before reperfusion of group 2 hearts, support rats received either vehicle (group 2a, n = 6) or thromboxane A2 receptor antagonist SQ29548 (0.2 mg/kg) (group 2b, n = 5). After 1 hour of reperfusion, left ventricular peak-systolic pressure and end-diastolic pressure were measured in all hearts at incremental ventricular volumes. The slope of the peak-systolic pressure-volume relation and the volume-axis intercept of the end-diastolic pressure-volume relation were also measured. No significant differences were noted in mean peak-systolic pressure, at any left ventricular volume, nor slope of the peak-systolic pressure-volume relation between groups, indicating that neither preservation nor SQ29548 treatment affected systolic contractile performance in this model. Through all left ventricular volume, however, end-diastolic pressure was significantly lower (p < 0.05) in group 2b compared to group 2a, and overall did not differ significantly from group 1.(ABSTRACT TRUNCATED AT 250 WORDS)
Byrne
J G
JG
Division of Cardiac Surgery, Harvard Medical School, Boston, Mass.
Appleyard
R F
RF
Sun
S C
SC
Couper
G S
GS
Cohn
L H
LH
D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006321:Heart / Q000503:physiopathology; D016027:Heart Transplantation; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009926:Organ Preservation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D016277:Ventricular Function, Left
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D013928:Thromboxane A2; C045749:SQ 29548