Pharmacological modulation of b-adrenoceptors as a new cardioprotective strategy for therapy of myocardial dysfunction induced by ischemia and reperfusion

Acta Cir Bras. 2019;34(5):e201900505. doi: 10.1590/s0102-865020190050000005. Epub 2019 Jun 3.

Abstract

Purpose: To evaluate the cardioprotective response of the pharmacological modulation of β-adrenergic receptors (β-AR) in animal model of cardiac ischemia and reperfusion (CIR), in spontaneously hypertensive (SHR) and normotensive (NWR) rats.

Methods: CIR was induced by the occlusion of left anterior descendent coronary artery (10 min) and reperfusion (75 min). The SHR was treated with β-AR antagonist atenolol (AT, 10 mg/kg, IV) 5 min before CIR, and NWR were treated with β-AR agonist isoproterenol (ISO, 0.5 mg/kg, IV) 5 min before CIR.

Results: The treatment with AT increased the incidence of VA, AVB and LET in SHR, suggesting that spontaneous cardioprotection in hypertensive animals was abolished by blockade of β-AR. In contrast, the treatment with ISO significantly reduced the incidence of ventricular arrhythmia, atrioventricular blockade and lethality in NWR (30%, 20% and 20%, respectively), suggesting that the activation of β-AR stimulate cardioprotection in normotensive animals. Serum CK-MB were higher in SHR/CIR and NWR/CIR compared to respective SHAM group (not altered by treatment with AT or ISO).

Conclusion: The pharmacological modulation of β-AR could be a new cardioprotective strategy for the therapy of myocardial dysfunctions induced by CIR related to cardiac surgery and cardiovascular diseases.

Publication types

  • Evaluation Study

MeSH terms

  • Adrenergic beta-1 Receptor Antagonists / pharmacology*
  • Adrenergic beta-Agonists / pharmacology*
  • Animals
  • Atenolol / pharmacology*
  • Biomarkers / blood
  • Blood Pressure / drug effects
  • Cardiotonic Agents / pharmacology*
  • Creatine Kinase, MB Form / blood
  • Heart Function Tests
  • Isoproterenol / pharmacology*
  • Male
  • Myocardial Reperfusion Injury / blood
  • Myocardial Reperfusion Injury / drug therapy*
  • Myocardial Reperfusion Injury / physiopathology
  • Rats, Inbred SHR
  • Receptors, Adrenergic, beta / drug effects*
  • Reproducibility of Results
  • Time Factors
  • Treatment Outcome

Substances

  • Adrenergic beta-1 Receptor Antagonists
  • Adrenergic beta-Agonists
  • Biomarkers
  • Cardiotonic Agents
  • Receptors, Adrenergic, beta
  • Atenolol
  • Creatine Kinase, MB Form
  • Isoproterenol