External pacing does not potentiate allopurinol protection of the heart from liver ischemia-reperfusion -- a study in an isolated perfused liver-heart rat model.
BACKGROUND
We recently demonstrated that isolated paced hearts perfused with modified Krebs-Henseleit solution containing high dose allopurinol (1 mM) were protected from liver ischemia-reperfusion (IR)-induced reperfusion injury. The objective was to study the effects of low dose allopurinol together with external pacing in attenuating myocardial reperfusion dysfunction following liver IR in the same double organ model.


METHODS
Isolated rat livers were perfused with modified Krebs-Henseleit solution (groups 1 and 2, n=8/all groups) or underwent global ischemia (groups 3-6) for 120 minutes. Following a 15-minute conjoint reperfusion of earlier separately isolated liver+heart, the hearts were recirculated alone for additional 45 minutes. The organs of three-group donating animals (groups 2, 4, and 6) were treated with allopurinol 18 hours and 1 hour before the experiment (50 mg x kg(-1) intraperitoneally) and it was also added during perfusion (0.1 mM in Krebs). The hearts in groups 5 and 6 were paced (300 x min(-1)).


RESULTS
The hearts perfused with IR Krebs (group 3) experienced decreased myocardial left ventricular-developed pressure (LVP), heart rate (in the unpaced hearts) and later coronary flow (by 68%, 21% and 32%, respectively); LVP and coronary flow also decreased correspondingly in the IR-paced hearts (group 4). Xanthine oxidase (XO) was high in groups 3 and 4 compared to group 1. IR allopurinol-treated hearts, both unpaced and paced (groups 5 and 6) had normal, similar myocardial performance, while their circulating XO was as low as in group 2 (allopurinol-treated controls).


CONCLUSIONS
External pacing in the double organ, isolated-perfused liver-heart did not ameliorate XO-mediated dysfunction compared to low dose allopurinol. The unexpected delayed coronary insufficiency in myocardial reperfusion injury is discussed.
Weinbroum
A A
AA
The Post-Anesthesia Care Unit, Tel Aviv Sourasky Medical Center, Israel. draviw@tasmc.health.gov.il
Dembo
G
G
Hochhauser
E
E
Rudick
V
V
Vidne
B A
BA
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D066298:In Vitro Techniques; D007511:Ischemia / Q000503:physiopathology*; D008099:Liver / Q000098:blood supply*; D023421:Models, Animal; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D010138:Pacemaker, Artificial; D051381:Rats
D000493:Allopurinol