MRI/MRS evaluation of cariporide in a canine long-term model of reperfused ischemic insults. Magnetic resonance imaging/magnetic resonance spectroscopy.
OBJECTIVE
To examine with magnetic resonance imaging (MRI)/magnetic resonance spectroscopy (MRS) the long-term effects of cariporide in a canine cardiac ischemia/reperfusion model.


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).


CONCLUSIONS
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.
Thompson
Kerry
K
Imaging Division, Lawson Health Research Institute, London, Canada. kthompso@lri.sjhc.london.on.ca
Wisenberg
Gerald
G
Sykes
Jane
J
Thompson
R Terry
RT
D000704:Analysis of Variance; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006146:Guanidines / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000473:pathology*; D015424:Reperfusion; D013450:Sulfones / Q000627:therapeutic use*; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D006146:Guanidines; D013450:Sulfones; C093373:cariporide