MRI/MRS evaluation of cariporide in a canine long‐term model of reperfused ischemic insults

Abstract

Purpose: To examine with magnetic resonance imaging (MRI)/magnetic resonance spectroscopy (MRS) the longterm 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 ϭ 10) and cariporide (N ϭ 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 Ͻ 0.05) and at days 3 and 10 postreperfusion (P Ͻ 0.0005). Functional recovery of the myocardium was significantly improved immediately upon reperfusion (percent of baseline: 63.5% Ϯ 3.5% for controls, 90.5% Ϯ 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 Ϯ 0.08, 0.58 Ϯ 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.

Biomedical imaging in the safety evaluation of new drugs

“…While electrical activities of the heart can be monitored in clinical trials by ECG, due to delayed release of serum markers of cardiac damage, structural histopathology, such as cardiomyocyte inflammation, degeneration and necrosis lack conventional early biomarkers. For investigative studies, imaging can provide valuable information in assessing myocardial perfusion and myocardial viability (Wassmuth et al 2001, Thompson et al 2003.…”