Protection of ischemic hearts by Ca2+ antagonists

Insights

Calcium channel blockers like verapamil and diltiazem protect working rat hearts during ischemia by preserving energy stores and reducing calcium overload. Pretreatment before ischemia is crucial for this protective effect.

Area of Science:

  • Cardiology
  • Pharmacology
  • Biochemistry

Background:

  • Global ischemia significantly impairs heart function and energy stores.
  • Calcium channel blockers are known to affect cardiac function and energy metabolism.

Purpose of the Study:

  • To investigate the protective effects of calcium channel blockers (verapamil, diltiazem, nifedipine, bepridil) on isolated rat hearts subjected to global ischemia.
  • To determine the optimal timing and mechanism of action for these protective effects.

Main Methods:

  • Isolated working rat hearts were pretreated with equiactive concentrations of calcium channel blockers before global ischemia.
  • Contractile function, high-energy phosphate (HEP) stores, mitochondrial function, and calcium (Ca2+) overload were assessed post-reperfusion.
  • Lactate production was measured in normal and K+-arrested ischemic hearts.

Main Results:

  • Pretreatment with verapamil, diltiazem, and nifedipine before ischemia enhanced recovery of contractile function and HEP stores.
  • Treatment during reperfusion alone did not improve recovery.
  • Bepridil did not preserve function, HEP, or mitochondrial function and did not reduce Ca2+ overload, with Ca2+ accumulating in mitochondria.
  • Diltiazem reduced lactate production during ischemia.

Conclusions:

  • Calcium channel blockers administered before global ischemia offer significant protection to working rat hearts.
  • The protective mechanisms involve not only energy preservation but also reduction of Ca2+ overload during reperfusion and altered Ca2+ compartmentation during ischemia.
  • Bepridil appears less effective than other tested calcium channel blockers in this model.

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