Abstract 1900: Preconditioning in Cynomolgus Monkey Heart Protects Against Both Ischemic and Reperfusion Injury
Ischemic preconditioning (IPC) and postconditioning (IPoC) are equally cardioprotective in some species tested but IPoC has been less protective in others. Although IPoC decreases infarct size in humans, no comparable data exist for IPC making a comparison impossible. We therefore compared IPoC and IPC in sub-human primate hearts which would be expected to most closely mimic that of humans. Cynomolgus monkeys underwent a 90-min occlusion of a coronary artery and 4h of reperfusion. In IPC 2 cycles of 10-min coronary occlusion/10-min reperfusion preceded the 90-min occlusion, and in IPoC 6 cycles of 30-sec reperfusion/30-sec coronary reocclusion were performed immediately after the 90-min occlusion. The regression line for the infarct-risk zone plot was very linear (r=0.99) and intersected the risk zone axis at 0.82 cm3. Collateral flow averaged only 6.6% of preocclusion flow and did not influence infarction. In control monkeys 44% of the risk zone infarcted indicating cynomolgus myocardium is much more resistant to infarction than that of rabbits or rats. While IPC reduced infarct size to near zero (2.4±0.9% infarction of risk zone), IPoC was much less protective (27.5±4.8% infarction of risk zone). Increasing the number of IPoC cycles to 10 did not increase salvage. When wortmannin was administered at the end of the ischemic period to block any protection that IPC might elicit during reperfusion, infarct size increased to only 28%. These findings suggest that only half of IPC’s protection in monkey heart derives from prevention of cell death during reperfusion. The other half of IPC’s salvage would have derived from suppression of cell death during the prolonged ischemic period. If human heart is similar to cynomolgus heart, then interventions applied at reperfusion such as IPoC may be much less effective than would be predicted from the non-primate animal studies. Effective clinical salvage may require cardioprotective interventions that target both the ischemic phase as well as reperfusion injury.