Heart and Vessels

, Volume 7, Issue 4, pp 189–195 | Cite as

Moderation of myocardial ischemia reperfusion injury by calcium channel and calmodulin receptor inhibition

  • Yataka Kimura
  • Richard M. Engelman
  • John Rousou
  • Joseph Flack
  • Jaisimha Iyengar
  • Dipak K. Das
Originals
Received:
Revised:
Accepted:

Summary

Intracellular Ca2+ accumulation is implicated in the pathogenesis of myocardial reperfusion injury. To study approaches designed to modify Ca2+ uptake during coronary revascularization after acute infarction, a pig heart surgical infarct model (left anterior descending artery occlusion for 60 min) was subjected to 60 min hypothermic potassium cardioplegic arrest, followed by 60 min of global reperfusion. Four groups of six hearts each were studied in a randomized manner, i.e., cardioplegia alone (control), cardioplegia + 10 µM diltiazem (Ca2+ slow channel blocker), cardioplegia + 10 µM trifluoperazine (TFP), (a Ca2+-calmodulin antagonist), and cardioplegia + diltiazem (10 µM) + TFP (10 µM). Left ventricular contractility (global and segmental), metabolism (coronary blood flow and O2 consumption), and creatine kinase generation were measured during reperfusion. Both the Ca2+ channel blocker, diltiazem, and the calmodulin antagonist, TFP, improved myocardial global and regional function as well as myocardial metabolism. While diltiazem better restored global and regional contractility, trifluoperazine had a greater effect on coronary blood flow and myocardial oxygen consumption. Enzyme release and lipid peroxidation were equally moderated by both drugs. From this study it can be concluded that Ca2+ influx does play a role in ischemic and reperfusion injury. The mechanisms of its effect are complex, but can be successfully antagonized by Ca2+ blockers as well as by calmodulin antagonists, with improved myocardial preservation.

Key words

Myocardial reperfusion injury Ca2+ Channel blockers Calmodulin antagonists Myocardial infarction 
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Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • Yataka Kimura
    • 1
    • 2
  • Richard M. Engelman
    • 1
    • 2
  • John Rousou
    • 1
    • 2
  • Joseph Flack
    • 1
    • 2
  • Jaisimha Iyengar
    • 1
    • 2
  • Dipak K. Das
    • 1
    • 2
  1. 1.Cardiovascular Division, Department of Surgery, Surgical Research CenterUniversity of Connecticut School of MedicineFarmingtonUSA
  2. 2.Baystate Medical CenterSpringfieldUSA

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