Cardioprotective Effects of Combined Therapy with Hyperbaric Oxygen and Diltiazem Pretreatment on Myocardial Ischemia-Reperfusion Injury in Rats

Cell Physiol Biochem. 2016;38(5):2015-29. doi: 10.1159/000445561. Epub 2016 May 9.

Abstract

Background/aims: In this study, we examined whether the combination of hyperbaric oxygen (HBO) and diltiazem therapy provided a cardioprotective effect on myocardial ischemia-reperfusion injury (MIRI) rat model.

Methods: Sixty healthy Sprague-Dawley rats were randomly divided into sham, IR, diltiazem (5 mg/kg), HBO (0.25 MPa, 60 min) and combination therapy (HBO plus diltiazem) groups. MIRI model was established by ligating the left anterior descending for 30 min, followed by 60 min of reperfusion.

Results: The results show that HBO and diltiazem preconditioning significantly improves cardiac function and myocardial infarction area, increases nitric oxide, endothelial nitric oxide synthase and ATPase (Na+-K+-ATPase and Ca2+-Mg2+-ATPase) activity and decreases levels of oxygen stress, myocardial enzymes and endothelin-1. Notably, HBO and diltiazem preconditioning significantly increased Bcl-2 protein expression and decreased Bax protein and caspase-3 mRNA expression.

Conclusions: These data indicate that combination therapy protected against heart MIRI by reducing oxygen stress damage, correcting energy metabolism, improving endothelial function and inhibiting cell apoptosis.

MeSH terms

  • Animals
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Combined Modality Therapy
  • Diltiazem / pharmacology
  • Diltiazem / therapeutic use*
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Endothelin-1 / genetics
  • Endothelin-1 / metabolism
  • Female
  • Heart / diagnostic imaging
  • Hyperbaric Oxygenation*
  • Ischemic Preconditioning
  • Male
  • Myocardial Infarction
  • Myocardial Reperfusion Injury / metabolism
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / therapy*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type III / metabolism
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Up-Regulation / drug effects
  • bcl-2-Associated X Protein / metabolism

Substances

  • Endothelin-1
  • Protective Agents
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Nitric Oxide
  • Nitric Oxide Synthase Type III
  • Caspase 3
  • Sodium-Potassium-Exchanging ATPase
  • Diltiazem