Leukotrienes D4 and E4 produced in myocardium impair coronary flow and ventricular function after two hours of global ischaemia in rat heart.
OBJECTIVE
Leukotrienes D4 and E4 are potent coronary vasoconstrictors and myocardial depressants. The aim was to investigate the contribution of myocardial leukotrienes to impairment of coronary flow and recovery of contractile function in rat hearts subjected to 2 h of global ischaemia.


METHODS
Rat hearts were mounted on a working Langendorff apparatus and perfused with oxygenated Krebs-Henseleit solution at 37 degrees C for 30 min. Hearts were then arrested with either standard potassium crystalloid cardioplegic solution (n = 6), or with cardioplegic solution containing the leukotriene D4, E4 receptor antagonist Ly171883 (n = 6). Arrested hearts were maintained at 15 degrees C for 2 h, then rewarmed to 37 degrees C during 30 min working reperfusion. Coronary effluent was analysed by radioimmunoassay for leukotriene C4, D4, E4, and F4 levels. Immediately prior to cardiac arrest, and again after 30 min reperfusion, coronary flow, and aortic outflow and pressure were measured.


RESULTS
Postischaemic leukotriene levels were increased compared to preischaemic levels in both groups [pooled measurements: 133.3 (SD 136.4) v 20.7(17.8) pg.0.1 ml-1, p < 0.05]. Postischaemic coronary vascular resistance was increased by 80% in controls (p < 0.001) compared to 19% (p = NS) in treated hearts. In addition, functional recovery was significantly greater in treated hearts compared to controls [82(3)% v 53(3)% for coronary flow; 79(3)% v 50(2)% for cardiac output; 82(4)% v 54(3)% for stroke work].


CONCLUSIONS
Leukotrienes are endogenously produced by the heart, and this production is significantly increased after global ischaemia and reperfusion. Reversal of significantly increased coronary vascular resistance coupled with improved functional recovery in hearts treated with LY171883 demonstrates an important contribution of endogenously produced leukotrienes to coronary vascular impairment and functional stunning of the globally ischaemic, reperfused heart.
Division of Cardiac Surgery, Brigham and Women's Hospital, Boston, MA 02115.
C C
CC
Lee
R F
RF
Appleyard
J G
JG
Byrne
L H
LH
Cohn
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D003326:Coronary Circulation / Q000502:physiology*; D006352:Heart Ventricles / Q000503:physiopathology; D017999:Leukotriene E4; D015289:Leukotrienes / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013189:SRS-A / Q000031:analogs & derivatives / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
D000098:Acetophenones; D015289:Leukotrienes; D013189:SRS-A; D013777:Tetrazoles; D017999:Leukotriene E4; C044660:LY 171883