β-Adrenoceptor Blocker Carvedilol Provides Cardioprotection via an Adenosine-Dependent Mechanism in Ischemic Canine Hearts

Abstract

Background-Carvedilol is a ␤-adrenoceptor blocker with a vasodilatory action that is more effective for the treatment of congestive heart failure than other ␤-blockers. Recently, carvedilol has been reported to reduce oxidative stress, which may consequently reduce the deactivation of adenosine-producing enzymes and increase cardiac adenosine levels. Therefore, carvedilol may also have a protective effect on ischemia and reperfusion injury, because adenosine mediates cardioprotection in ischemic hearts. Methods and Results-In anesthetized dogs, the left anterior descending coronary artery was occluded for 90 minutes, followed by reperfusion for 6 hours. Carvedilol reduced the infarct size (15.0Ϯ2.8% versus 40.9Ϯ4.2% in controls), and this effect was completely reversed by the nonselective adenosine receptor antagonist 8-sulfophenyltheophylline (45.2Ϯ5.4%) or by an inhibitor of ecto-5Ј-nucleotidase (44.4Ϯ3.6%). There were no differences of either area at risk or collateral flow among the various groups. When the coronary perfusion pressure was reduced in other dogs so that coronary blood flow was decreased to 50% of the nonischemic level, carvedilol increased coronary blood flow (49.4Ϯ5.6 to 73.5Ϯ7.5 mL · 100 g Ϫ1 · min

Comparative Effects of Carvedilol vs Bisoprolol for Severe Congestive Heart Failure - Special Reference to Atrial Fibrillation -

“…Asanuma et al reported that carvedilol suppressed the frequency of ventricular fibrillation and death through reducing infarct size after ischemia reperfusion injury. 26 This report supports our results that the number of patients died from ACS was lower in the carvedilol group than that in the bisoprolol group. Thus, the dosages of the 2 β-blockers in our study could be sufficient to improve HF.…”

Pathophysiology of myocardial reperfusion injury: preconditioning, postconditioning, and translational aspects of protective measures

“…Indeed, many reports show that the blockade of the ␤-adrenoceptor will protect the myocardium from prolonged ischemia-reperfusion. However, possible pharmacological mechanisms other than hemodynamic benefits are under discussion (9,180,238).…”

Effect of atenolol pre-treatment in heart damage in a model of intestinal ischemia-reperfusion

“…The actions of beta-blocker were different in the lipophilicity, cardioselectivity, and vasodilatation. Drugs, such as carvedilol, metoprolol and labetalol are lipid solubility and have peripheral vasodilators effects; other drugs, such atenolol and practolol are not lipid solubility and not have peripheral vasodilator effects, moreover possess cardiac selectivity 10,28,29 .…”

“…Atenolol, a beta-1-selective blocker, is implicating with cross-talk between adrenoceptors and adenosine receptors to promote cardioprotection and other cytoprotective effects 29 . Campos et al 30 where AT attenuated the motor and neural dysfunctions in rat small bowel caused by ischemia-reperfusion.…”