Abstract 18151: Remote Ischemic Preconditioning with - but not Without - Metabolic Support Protects Against Ischemia-Reperfusion Injury in the Newborn Piglet In-vivo
Introduction: While remote ischemic preconditioning (rIPC) protects the mature heart against ischemia-reperfusion (IR) injury, the effect of rIPC on the neonatal heart is controversial. In contrast to the mature heart, the neonatal heart relies almost solely on carbohydrate metabolism, which is modified by rIPC in the mature heart. Glucose-insulin (GI) infusion stimulates glycolysis and provides myocardial substrate supplementation, which may compensate for adverse metabolic effects induced by rIPC in the immature heart. Hypothesis: rIPC combined with GI improves cardiac function and reduces infarcts size compared to control (no pretreatment) or rIPC alone after IR injury in neonatal piglet in-vivo.
Methods: 32 newborn (1-4 days old; 0.8-1.3 kg.) piglets were randomized into 4 groups: control, rIPC, GI and GI+rIPC. GI and GI+rIPC groups received insulin in 20% glucose at a rate of weight (in kg)*5 ml/h corresponding to 100 mU/kg/h continuously from 40 minutes prior to ischemia. rIPC and GI+rIPC groups underwent four cycles of 5 minutes limb ischemia followed by 5 minutes reperfusion obtained by tourniquet occlusion of the right hind limb. Myocardial IR was induced by 40 min tourniquet occlusion of the left anterior descending artery followed by 2 h reperfusion. Left ventricular pressure was measured using 3F Millar high fidelity microtip catheters. Interstitial lactate was measured using microdialysis and infarct size measured using triphenyltetrazolium chloride staining.
Results: Systolic recovery (dP/dt max as % of baseline) after 2h reperfusion was improved in GI+rIPC (84.7±5.3%) compared to control (71.2±4.9%, p<0.05) and rIPC (33.9±12.9%, p<0.01) but not different from GI (82.9±8.1%, p=0.67). Lactate levels (% of baseline) were lower in GI+rIPC (85.5±4.9%) compared to control (125.1±9.1%, p<0.01) and rIPC (233.9±31.1%, p<0.01). Infarct size relative to area at risk was 12.7±1.1% in GI+rIPC compared to 16.4±1.5% in control (p=0.06), 18.1±0.8% in rIPC (p<0.01) and 24.1±2.1% in GI.
Conclusion: rIPC+GI, but neither rIPC nor GI alone protects the neonatal porcine heart against IR injury in-vivo. rIPC alone appears to have detrimental metabolic and functional effects that are compensated by simultaneous metabolic support with GI infusion.
- © 2012 by American Heart Association, Inc.