Long-term Magnetic Resonance Imaging/Spectroscopy Study of Cariporide in a Canine Cardiac Ischemia/Reperfusion Model

Using both P and H cardiac magnetic resonance techniques, it is possible to monitor the functional (ejection fraction [EF]) and biochemical (pH) status of the heart following a reperfused ischemic insult. This study assessed the effects of Na/H exchange inhibition with cariporide in a closed-chest canine ischemia/reperfusion model. Dogs received 1-mg/kg cariporide treatments for 3 days after occlusion, but were monitored for 10 days. Baseline intracellular pH (±SEM) for the control and treated groups were 7.10 ± 0.03 and 7.14 ± 0.04, respectively, and dropped to 6.25 ± 0.08 and 6.38 ± 0.08 during occlusion. There was a significant increase in pH from occlusion to early reperfusion in the control group (P = 0.03) but, during the same time period, this increase was not seen in the cariporide group. There was a significant (P = 0.01) drug interaction in recovery of EF over the 10-day protocol. Individual time-point analysis revealed significant differences at immediate reperfusion through day 3 (73.9% ± 2.5%, 84.5% ± 3.1%; baseline normalized EF controls and cariporide, respectively). Neither pH nor EF measurements were significantly different between the groups at day 10. Despite early functional and metabolic benefits, infarct size, as measured at day 10, was 13.2% ± 2.2% for the controls and 11.8% ± 2.3% for the cariporide group (NS). Thus there were no long-term cariporide functional or biochemical benefits.