Influence of strain, age, origin, and anesthesia on the cardioprotective efficacy by local and remote ischemic conditioning in an ex vivo rat model

Abstract

BackgroundLocal ischemic preconditioning (IPC) and remote ischemic conditioning (RIC) induced by brief periods of ischemia and reperfusion protect against ischemia‐reperfusion injury.MethodsWe studied the sensitivity to IR‐injury and the influence of strain, age, supplier, and anesthesia upon the efficacy of IPC and RIC in 7‐ and 16‐weeks‐old Sprague‐Dawley and Wistar rats from three different suppliers. The influence of sedation with a hypnorm and midazolam mixture (rodent mixture) and pentobarbiturate was compared.ResultsIPC attenuated infarct size in both 7‐weeks‐old Sprague–Dawley (48.4 ± 17.7% vs. 20.3 ± 6.9, p < 0.001) and 7‐weeks‐old Wistar (55.6 ± 10.9% vs. 26.8 ± 5.0%, p < 0.001) rats. Infarct size was larger in 16‐weeks‐old Sprague–Dawley rats, however, IPC still lowered infarct size (78.8 ± 9.2% vs. 58.3 ± 12.3%, p < 0.01). RIC reduced infarct sizes in 7‐weeks‐old Sprague–Dawley (75.3 ± 11.8% vs. 58.6 ± 8.9%, p < 0.05), but not in 7‐weeks‐old Wistar rats (31.7 ± 17.6% and 24.0 ± 12.6%, p = 0.2). In 16‐weeks‐old Sprague–Dawley rats, RIC did not induce protection (76.4 ± 5.5% and 73.2 ± 14.7%, p = 0.6). However, RIC induced protection in 16‐weeks‐old Wistar rats (45.2 ± 8.5% vs. 14.7 ± 10.8%, p < 0.001). RIC did not reduce infarct size in 7‐weeks‐old Sprague–Dawley rats from Charles River (62.0 ± 13.5% and 69.4 ± 10.4% p = 0.3) or 16‐weeks‐old Wistar rats from Janvier (50.7 ± 11.3 and 49.2 ± 16.2, p = 0.8). There was no difference between sedation with rodent mixture or pentobarbiturate.ConclusionThe cardioprotective effect of IPC is consistent across rat strains independent of age, strain, and supplier. RIC seems to be less reproducible, but still yields protection across different rat strains. However, age, animal supplier, and anesthetics may modulate the sensitivity of IR‐injury and the response to RIC.