MRI/MRS evaluation of cariporide in a canine long-term model of reperfused ischemic insults. Magnetic resonance imaging/magnetic resonance spectroscopy

J Magn Reson Imaging. 2003 Jan;17(1):136-41. doi: 10.1002/jmri.10222.

Abstract

Purpose: To examine with magnetic resonance imaging (MRI)/magnetic resonance spectroscopy (MRS) the long-term effects of cariporide in a canine cardiac ischemia/reperfusion model.

Materials and methods: Twenty-two beagles underwent a 2-hour occlusion followed by 10 days of reperfusion. Cine MRI and (31)P MRS were performed to monitor function and metabolism of the heart in the control (N = 10) and cariporide (N = 12) groups. Radioactively labeled microspheres were injected to determine coronary blood flow, and contrast-enhanced ex vivo MRI assessed infarct volumes.

Results: Cariporide produced a significant reduction vs. controls, in intracellular pH, during ischemia (P < 0.05) and at days 3 and 10 postreperfusion (P < 0.0005). Functional recovery of the myocardium was significantly improved immediately upon reperfusion (percent of baseline: 63.5% +/- 3.5% for controls, 90.5% +/- 7.2% for cariporide) and at day 3, but not by day 10. Normalized infarct ratios (IRs) were similar for controls and cariporide (0.58 +/- 0.08, 0.58 +/- 0.06, respectively).

Conclusion: Cariporide augments early functional recovery, while delaying normalization of intracellular pH following ischemia/reperfusion, but confers neither long-term functional or metabolic protection nor, most importantly, myocardial salvage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Anti-Arrhythmia Agents / therapeutic use*
  • Disease Models, Animal*
  • Dogs
  • Female
  • Guanidines / therapeutic use*
  • Magnetic Resonance Imaging*
  • Magnetic Resonance Spectroscopy*
  • Myocardial Ischemia / drug therapy*
  • Myocardial Ischemia / pathology*
  • Reperfusion*
  • Sulfones / therapeutic use*
  • Time Factors

Substances

  • Anti-Arrhythmia Agents
  • Guanidines
  • Sulfones
  • cariporide