Ischemic preconditioning in human and rat ventricle

Abstract

The signal transduction of ischemic preconditioning involves activation of endogenous receptor-based systems, including alpha 1-adrenoceptors and adenosine receptors. Whereas preconditioning protects against ischemia-reperfusion injury, it is unknown whether this protective strategy might be useful clinically. Furthermore, human atrium has been successfully preconditioned, but it is unknown whether human ventricle can be functionally protected against hypoxia-reoxygenation. To study these questions, isolated rat ventricle and human ventricular trabeculae were suspended in an organ bath and subjected to 30 min of hypoxia and 60 min of reoxygenation. In the rat ventricle, preconditioning was induced by 5 min of rapid pacing at 3 Hz in hypoxic buffer without glucose (simulated ischemia), alpha 1-adrenoceptor stimulation (phenylephrine), or adenosine receptor stimulation (adenosine). In the human trabeculae the effects of preceding simulated ischemia and alpha 1-adrenoceptor and adenosine receptor stimulation were examined against hypoxia-reoxygenation. In the rat, pretreatment with simulated ischemia and alpha 1-adrenoceptor and adenosine receptor stimulation improved recovery of developed tension (56 +/- 3, 56 +/- 4, and 58 +/- 2%, respectively) compared with control trabeculae (25 +/- 2%) after hypoxia-reoxygenation (P < 0.05). In human trabeculae, simulated ischemic preconditioning and alpha 1-adrenoceptor and adenosine receptor stimulation augmented recovery of developed tension (65 +/- 5, 59 +/- 6, and 60 +/- 3%, respectively) compared with control (29 +/- 2%) after hypoxia-reoxygenation (P < 0.05). We conclude that functional cardioadaptation (preconditioning) against hypoxia-reoxygenation injury in rat and human myocardium exists and that alpha 1-adrenergic and adenosine receptor signaling participate in conferring this protection.

Cardiac Alpha1-Adrenergic Receptors: Novel Aspects of Expression, Signaling Mechanisms, Physiologic Function, and Clinical Importance

“…However, pharmacology and knockouts argue against the results seen in certain cardiac transgenics. Specifically, studies with a 1 -agonists in mouse (Chan et al, 2008;Dash et al, 2011) and human (Cleveland et al, 1996Galinanes, 2001, 2002), as well as in loss-of-function mouse models (O'Connell et al, , 2006Huang et al, 2007) as reviewed above, support a 1 -mediated cardioprotective effects.…”

“…a 1 -Adrenergic Receptor-Mediated Preconditioning in Humans. In human atrial and ventricular muscle strips, a 1 -ARs mediate ischemic preconditioning through activation of PKC, p38 MAPK, and opening of mitochondrial K-ATP channels (Cleveland et al, 1996Galinanes, 2001, 2002).…”

Clinical Importance of Ischemic Preconditioning

“…Köpek miyokardının ardından insan miyokardı da dahil olmak üzere çeşitli canlıların farklı dokuları da çalışma materyali olarak kullanılmıştır (4)(5)(6)(7) . Murry (1) , köpek koroner arterinin 40 dk.…”

Organ preconditioning: the past, current status, and related lung studies

“…The protective effect of PC in the heart can be assessed by limiting infarct size, reducing myocardial stunning, preventing arrhythmias, or accelerating the recovery of myocardial function after ischemia (Muller et al, 1990;Tamura et al, 1997;Cleveland et al, 1996;Sun et al, 1995;Shiki and Hearse, 1987;Pomerantz et al, 2000).…”

“…PC also plays an important role in the field of heart transplantation, in which attenuation of injuries related to the hypothermic ischemia of the donor heart during harvest and preservation is very important. There have been both in vitro (Cleveland et al, 1996) and in vivo (Karck et al, 1996) studies to prove the protective effects of ischemic PC against the I/R injuries related to heart graft preservation.…”