Merit of anisodamine combined with opioid δ-receptor activation in the protection against myocardial injury during cardiopulmonary bypass

Biomed Res Int. 2013:2013:212801. doi: 10.1155/2013/212801. Epub 2013 Dec 10.

Abstract

Myocardial ischemia/reperfusion (MIR) injury easily occurrs during cardiopulmonary bypass surgery in elderly patients. In an attempt to develop an effective strategy, we employed a pig model of MIR injury to investigate the maximum rate of change of left ventricular pressure, left ventricular enddiastolic pressure, and left intraventricular pressure. Coronary sinus cardiac troponin T (TnT) and adenosine-triphosphate (ATP) content in myocardium were measured. The ultrastructures for MIR injury were visualized by transmission electron microscopy (TEM). The role of δ-opioid receptor activation using D-Ala2, D-Leu5-enkephalin (DADLE) in both early (D1) and late (D2) phases of cardioprotection was identified. Also, the merit of cardioprotection by DADLE in combination with anisodamine, the muscarinic receptor antagonist (D+M), was evaluated. Glibenclamide was employed at the dose sufficient to block ATP-sensitive potassium channels. Significant higher cardiac indicators, reduced TnT and increased ATP contents, were observed in D1, D2, and D+M groups compared with the control group. DADLE induced protection was better in later phase of ischemia that was attenuated by glibenclamide. DADLE after the ischemia showed no benefit, but combined treatment with anisodamine showed a marked postischemic cardioprotection. Thus, anisodamine is helpful in combination with DADLE for postischemic cardioprotection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Cardiopulmonary Bypass / adverse effects*
  • Cell Shape / drug effects
  • Coronary Sinus / drug effects
  • Coronary Sinus / metabolism
  • Coronary Sinus / pathology
  • Coronary Sinus / physiopathology
  • GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
  • Heart Function Tests
  • Myocardial Reperfusion Injury / blood
  • Myocardial Reperfusion Injury / drug therapy*
  • Myocardial Reperfusion Injury / etiology*
  • Myocardial Reperfusion Injury / prevention & control*
  • Myocardium / enzymology
  • Myocardium / pathology
  • Myocardium / ultrastructure
  • Protein Kinase C / metabolism
  • Receptors, Opioid, delta / metabolism*
  • Solanaceous Alkaloids / pharmacology
  • Solanaceous Alkaloids / therapeutic use*
  • Sus scrofa
  • Troponin / blood

Substances

  • Receptors, Opioid, delta
  • Solanaceous Alkaloids
  • Troponin
  • anisodamine
  • Adenosine Triphosphate
  • Protein Kinase C
  • GTP-Binding Protein alpha Subunits, Gi-Go