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Am J Physiol Heart Circ Physiol (February 14, 2002). doi:10.1152/ajpheart.01055.2001
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Articles in PresS, published online ahead of print February 14, 2002
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.01055.2001
Submitted on December 3, 2001
Accepted on February 12, 2002

Myocardial preconditioning factors evoke mesenteric ischemic tolerance via opioid receptors and KATP channels

Eric W Dickson1*, Robert J Tubbs2, William A Porcaro2, Won Jae Lee3, David J Blehar2, Robert E Carraway4, Chad E Darling2, and Karin Przyklenk5

1 Emergency Medicine, University of Massachusetts Medical School, Worcester, MA, USA; Physiology, University of Massachusetts, Worecester, MA, USA; Anesthesiology, University of Massachusetts, Worcester, MA, USA
2 Emergency Medicine, University of Massachusetts Medical School, Worcester, MA, USA
3 Emergency Medicine, Kangnam Saint Mary's Hospital, Seoul, Korea, Democratic People's Rep; Emergency Medicine, University of Massachusetts Medical School, Worcester, MA, USA
4 Physiology, University of Massachusetts, Worecester, MA, USA
5 Cardiology, Heart Institute Good Samaritan Hospital, University of Southern California, Los Angeles, CA, USA

* To whom correspondence should be addressed. E-mail: dicksone{at}ummhc.org.

We have shown that a reverse-phase concentrate generated from the effluent of preconditioned (PC) rabbit hearts evokes a cardioprotective effect in virgin acceptor hearts. Using a model of sustained (1 hour) simulated ischemia in isolated, spontaneously contracting rabbit jejunum, our current aims were to: (1) determine whether protective factor(s) released from PC hearts can improve ischemic tolerance in non-cardiac tissue; and (2) obtain preliminary insight into the mediator(s) involved in triggering and eliciting this remote protection. Recovery of contractile force following reoxygenation (our index of ischemic tolerance) was enhanced in jejunal segments pre-treated with concentrate generated from PC hearts (33±3%* of baseline) versus segments that received no concentrate (21±2%) and segments treated with concentrate from normoxic hearts (16±3%; *p<.01). Protection achieved with PC concentrate was attenuated by co-administration of naloxone or glibenclamide, thereby implicating the involvement of opioids and ATP-sensitive potassium channels. Moreover, evaluation of purified sub-fractions of the crude PC concentrate identified a specific bioactive fraction that may participate in triggering the improved jejunal ischemic tolerance.




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