Adenosine-enhanced ischemic preconditioning: adenosine receptor involvement during ischemia and reperfusion

Abstract

Adenosine-enhanced ischemic preconditioning (APC) extends the cardioprotection of ischemic preconditioning (IPC) by both significantly decreasing myocardial infarct size and significantly enhancing postischemic functional recovery. In this study, the role of adenosine receptors during ischemia-reperfusion was determined. Rabbit hearts (n = 92) were used for Langendorff perfusion. Control hearts were perfused for 180 min, global ischemia hearts received 30-min ischemia and 120-min reperfusion, and IPC hearts received 5-min ischemia and 5-min reperfusion before ischemia. APC hearts received a bolus injection of adenosine coincident with IPC. Adenosine receptor (A(1), A(2), and A(3)) antagonists were used with APC before ischemia and/or during reperfusion. GR-69019X (A(1)/A(3)) and MRS-1191/MRS-1220 (A(3)) significantly increased infarct size in APC hearts when administered before ischemia and significantly decreased functional recovery when administered during both ischemia and reperfusion (P < 0.05 vs. APC). DPCPX (A(1)) administered either before ischemia and/or during reperfusion had no effect on APC cardioprotection. APC-enhanced infarct size reduction is modulated by adenosine receptors primarily during ischemia, whereas APC-enhanced postischemic functional recovery is modulated by adenosine receptors during both ischemia and reperfusion.

Pharmacological and ischemic preconditioning of the human myocardium: mitoKATP channels are upstream and p38MAPK is downstream of PKC

“…These results in the human myocardium are supported by studies in other animal species [23] but contrast with the results reported by Leesar et al [24] in the vivo human heart and by McCully et al [25] in the isolated rabbit heart. In the study by Leesar et al [24] patients undergoing percutaneous transluminal coronary angioplasty were subjected to three 2-minute balloon inflations 5 minutes apart.…”

Acute Hyperglycemia Abolishes Ischemic Preconditioning by Inhibiting Akt Phosphorylation: Normalizing Blood Glucose before Ischemia Restores Ischemic Preconditioning

“…However, other studies seem to favor the use of insulin to restore the preconditioning effect in hyperglycemic patients or animals [16, 17]. It is now well known that activation of adenosine A 1 receptors (A 1 R), either by ischemic preconditioning or by specific agonists, triggers the protective effect against myocardial ischemia/reperfusion injury [18–24]. However, the role of acute hyperglycemia in blocking the A 1 R pathway is largely unknown.…”

Warm ischemic preconditioning improves mitochondrial redox balance during and after mild hypothermic ischemia in guinea pig isolated hearts

“…This imbalance likely has an important role in the triggering mechanisms of ischemic and pharmacological preconditioning (35). Many studies suggest that mitochondrial ATP-sensitive K ϩ (K ATP ) channels open during brief ischemia and also play a key protective role in normothermic I/R injury (5,13,17,24,30,41). Opening of K ATP channels is believed to be a common mechanism of IPC because K ATP channel antagonists attenuate the protection of IPC and K ATP agonists mimic the protection of IPC (18,29).…”