title: Transient pre-ischemic acidosis protects the isolated rabbit heart subjected to 30 minutes, but not 60 minutes, of global ischemia.
abstract: Adenosine released during brief episodes of ischemia, due to the breakdown of ATP, is thought to be an endogenous mediator of ischemic preconditioning. In this study we sought to determine whether protons, also released from ATP during ischemia, may protect the heart from sustained ischemic insult. Experiments were performed in isolated Langendorff-perfused rabbit hearts. Proton release was simulated by a brief transient episode of preischemic acidosis. Before ischemia all hearts underwent 15 min of preischemic perfusion. Control hearts received 15 min perfusion with normal Krebs-Henseleit buffer (KHB; pH 7.39) while the short-term acidosis (STA) group received 5 min of perfusion with normal KHB followed by 5 min of perfusion with acidic buffer (pH 5.97), and then 5 min of perfusion with normal KHB. Both control and STA groups then underwent 30 min of global ischemia. A second pair of control and STA groups were subjected to 60 min of global ischemia. After global ischemia all hearts received 60 min of reperfusion. The time course of functional recovery after 30 min of ischemia was accelerated in the STA group (i.e., developed pressure in the control and STA groups at 15 min into reperfusion averaged 57 +/- 9 and 74 +/- 3 mmHg, respectively; p < 0.05), and a strong trend towards lower release of creatine kinase after 30 min of global ischemia was observed in the STA group (43 +/- 7 U/g dry tissue in the STA group vs. 76 +/- 15 U/g dry tissue in the control group). However, after 60 min of global ischemia no differences in cardiac function at reperfusion were observed between control and STA groups. Our results indicate that in the isolated rabbit heart, brief acidosis affords protection against 30 min but not against 60 min of global ischemia.
authors.affiliation: Heart Institute/Research Good Samaritan Hospital, Los Angeles, CA 90017-2395, USA.
authors.forename: B Z
authors.initials: BZ
authors.lastname: Simkhovich
authors.forename: P
authors.initials: P
authors.lastname: Whittaker
authors.forename: K
authors.initials: K
authors.lastname: Przyklenk
authors.forename: R A
authors.initials: RA
authors.lastname: Kloner
mesh_terms: D000138:Acidosis / Q000378:metabolism*; D000241:Adenosine / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism; D005500:Follow-Up Studies; D006439:Hemodynamics; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D011522:Protons; D011817:Rabbits; D013997:Time Factors
chemical_list: D011522:Protons; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D000241:Adenosine