These results indicate that the IP receptor does not modulate myocardial ischemia/reperfusion injury at baseline and that targeted disruption of the IP gene completely abrogates the infarct-sparing effect of late PC, providing, for the first time, molecular genetic evidence for an obligatory role of IP in the cardioprotection conferred by late PC. The gene discussed is PTGIR; the disease is myocardial ischemia.