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

BACKGROUND: Local ischemic preconditioning (IPC) and remote ischemic conditioning (RIC) induced by brief periods of ischemia and reperfusion protect against ischemia-reperfusion injury. METHODS: We 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. RESULTS: IPC 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. CONCLUSION: The 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.

Induced functional modulations of isolated large mammalian hearts.

In this study we used Visible Heart® methodologies featuring cyclic temperature modulation of porcine hearts in order to establish characteristic temperature responses. This isolated and perfused model is a more predictable and modifiable analog for human heart preservation and isolates the response of the cardiac tissue. We comprehensively monitored isolated porcine hearts undergoing temperature change and demonstrated optimization of isolated cardiac function under mild hypothermia. We tracked metrics of cardiac function as continuous variables during temperature changes (~ 31 to 39 °C), eliciting a well-defined reduction in metabolic demand and in heart rate modulation. Optimization of function appeared to occur around 34.7 ± 0.9 °C (n = 13). Cardiac response was further investigated in the presence of active pacing in order to assess pacing capture and the heart's functional response without a means of regulating rate. Our results may have direct clinical implications for emerging heart preservation methods prior to transplantation, as well as benefits for investigators using isolated heart models for preclinical device testing. Clinically, this porcine model is a basis for finding new ways to extend the window of viability for transplantable organs, thereby restoring or improving graft function and potentially enhancing recipient outcomes.

Guidelines for experimental models of myocardial ischemia and infarction.

Myocardial infarction is a prevalent major cardiovascular event that arises from myocardial ischemia with or without reperfusion, and basic and translational research is needed to better understand its underlying mechanisms and consequences for cardiac structure and function. Ischemia underlies a broad range of clinical scenarios ranging from angina to hibernation to permanent occlusion, and while reperfusion is mandatory for salvage from ischemic injury, reperfusion also inflicts injury on its own. In this consensus statement, we present recommendations for animal models of myocardial ischemia and infarction. With increasing awareness of the need for rigor and reproducibility in designing and performing scientific research to ensure validation of results, the goal of this review is to provide best practice information regarding myocardial ischemia-reperfusion and infarction models. Listen to this article's corresponding podcast at ajpheart.podbean.com/e/guidelines-for-experimental-models-of-myocardial-ischemia-and-infarction/.