Electromechanical impairment of human auricle and rat myocardial strip subjected to exogenous oxidative stress.
OBJECTIVE
Animal myocardial dysfunction induced by remote ischemia-reperfusion (IR) was shown to be partly accomplished via a direct effect of the pro-oxidant xanthine oxidase (XO). This direct remote effect was not tested in humans. We now assessed the performance of human auricles in the presence of solutions containing XO and/or allopurinol and compared them to those of rat myocardial strips.


METHODS
Human and rat specimens (n=64) were separately exposed for 2h to Krebs-Henseleit solution that either (1) exited from rat livers that were earlier perfused for 2h (control-human or control-rat), (2) exited from livers that were earlier made ischemic for 2h (IR-human, IR-rat), (3) contained xanthine (X) 3.8 microM + XO 3 mU ml(-1) (X+XO-human, X+XO-rat), or (4) exited from post 2h-ischemic livers and contained 100 microM allopurinol (human or rat IR + allopurinol groups).


RESULTS
Unlike the unchanged electromechanical performance in the control and IR+allopurinol auricles and strips, the rates of contraction, maximal force of contraction and working index of either preparation were reduced by 75-98% (P<0.01) when exposed to the IR reperfusate or to the X+XO-enriched Krebs. The basal amplitudes of contraction in these four latter groups increased twofold (P<0.01). XO activity was similarly low in the control and in the IR+allopurinol groups, but four- to 45-fold (P<0.001) higher in the IR and the X+XO groups, both in the rat and human organs. The reduced glutathione was reduced by approximately 50% (P<0.01) in either preparation in the IR and the X+XO groups compared to the control and IR+allopurinol groups.


CONCLUSIONS
Remotely and exogenously originated oxidative burst directly induces electromechanical dysfunction and disrupts oxidant/antioxidant balance in human auricles as it does in the rat myocardial strip.
Ben Abraham
Ron
R
Departments of Anesthesiology and Critical Care, Tel Aviv Sourasky Medical Center and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Matza
Menachem
M
Marmor
Sylvia
S
Rudick
Valery
V
Frolkis
Inna
I
Shapira
Itzhak
I
Weinbroum
Avi A
AA
D000368:Aged; D000493:Allopurinol / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D020517:Atrial Appendage / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D018920:Coculture Techniques; D004594:Electrophysiology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007511:Ischemia / Q000378:metabolism; D008099:Liver / Q000098:blood supply / Q000378:metabolism; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress; D051381:Rats; D017382:Reactive Oxygen Species / Q000494:pharmacology; D013997:Time Factors; D014969:Xanthine Oxidase / Q000494:pharmacology*
D016877:Oxidants; D017382:Reactive Oxygen Species; D000493:Allopurinol; D014969:Xanthine Oxidase; D005978:Glutathione