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Background: While remote ischemic preconditioning (rIPC) protects the mature heart against ischemia-reperfusion (IR) injury, the effect on the neonatal heart is not known. The neonatal heart relies almost solely on carbohydrate metabolism, which is modified by rIPC in the mature heart. We hypothesized that rIPC combined with metabolic support with glucose-insulin (GI) infusion improves cardiac function and reduces infarct size after IR injury in neonatal piglets in-vivo. Methods and results: 32 newborn piglets were randomized into 4 groups: control, GI, GI+rIPC and rIPC. GI and GI+rIPC groups received GI infusion continuously from 40min prior to ischemia. rIPC and GI+rIPC groups underwent four cycles of 5min limb ischemia. Myocardial IR injury was induced by 40min occlusion of the left anterior descending artery followed by 2h reperfusion. Myocardial lactate concentrations were assessed in microdialysis samples analyzed by mass spectrometry. Infarct size was measured using triphenyltetrazolium chloride staining. Systolic recovery (dP/dtmax as % of baseline) after 2h reperfusion was 68.5±13.8% in control, 53.7±11.2% in rIPC (p <0.05), and improved in GI (83.6±18.8%, p <0.05) and GI+rIPC (87.0±15.7%, p <0.01). Conclusion: rIPC+GI protects the neonatal porcine heart against IR injury in-vivo. rIPC alone has detrimental metabolic and functional effects that are abrogated by simultaneous GI infusion. [ABSTRACT FROM AUTHOR]

1. Previously, we found that administration of high-dosel-glutamate during postischaemic reperfusion improves haemodynamic recovery and enhances glycogen resynthesis. In the present study, we investigated whether the same effect occurs in an insulin-free model and whether glutamate administration reduces infarct size. Further, we studied whether the cardioprotective effect of glutamate depends on preserved glutamate transamination and KATP channel activity. 2. In a rat isolated, insulin-free, perfused heart model, we compared the effects of administration ofl-glutamate (10 mmol/L) during either 45 min no-flow regional ischaemia plus 120 min reperfusion or reperfusion alone on infarct size and left ventricular (LV) recovery. The effect of glutamate on glycogen metabolism was studied in a model of 30 min global no-flow ischaemia and 60 min reperfusion. In both models, the effects of inhibition of glutamate transamination and KATP channel activity were examined by adding amino-oxyacetate (an aminotransferase inhibitor; 0.1 mmol/L) and glibenclamide (a KATP blocker; 10 mmol/L), respectively. 3. Administration ofl-glutamate reduced infarct size by 60% ( P < 0.01) and improved postischaemic LV function (developed pressure and rate pressure product; P < 0.05).l-Glutamate increased glycogen content after 60 min reperfusion by 65% ( P < 0.01). Amino-oxyacetate, as well as glibenclamide, abolished the glutamate-mediated reduction in infarct size, haemodynamic improvement and glycogen resynthesis during reperfusion. 4. In conclusion,l-glutamate administration from the start of postischaemic reperfusion exerts cardioprotective effects, including reduced infarct size, improved haemodynamic recovery and enhanced glycogen resynthesis. These effects depend on preserved transamination of glutamate and KATP channel activity, but not on insulin administration. [ABSTRACT FROM AUTHOR]

1. l-Glutamate and glutamine have been suggested to have cardioprotective effects. However, the issue is controversial and the metabolic mechanisms underlying a beneficial effect are not well understood. 2. In the present study we investigated the effects ofl-glutamate and glutamine on haemodynamic recovery, the rate of de novo glycogen synthesis and myocardial glucose uptake during postischaemic reperfusion. 3 . Hearts from male Wistar rats (250–300 g) were divided into three groups as follows: (i) control ( n = 12); (ii)l-glutamate ( n = 12); and (iii) glutamine ( n = 12). Hearts were mounted in a Langendorff preparation and perfused with oxygenated Krebs’–Henseleit solution at 80 mmHg and 37C. Global ischaemia for 20 min was followed by 15 min reperfusion, during whichl-glutamate (50 mmol/L) or glutamine (20 mmol/L) were administered. Left ventricular developed pressure (LVDP), de novo synthesis of glycogen using [14C]-glucose and myocardial glucose uptake usingd-[2-3H]-glucose were measured. 4. l-Glutamate and glutamine increased postischaemic LVDP ( P < 0.01 vs control hearts for both).l-Glutamate and glutamine increased de novo glycogen synthesis by 78% ( P < 0.001) and 55% ( P < 0.01), respectively. At the end of reperfusion, total myocardial glycogen content was increased by bothl-glutamate and glutamine (5.7 ± 0.3 and 6.2 ± 0.7 mmol/g wet weight, respectively; P < 0.05 and 0.01, respectively) compared with that in control hearts (3.6 ± 0.4 mmol/g wet weight). Neitherl-glutamate nor glutamine affected myocardial glucose uptake during reperfusion. 5 . Improved postischaemic haemodynamic recovery afterl-glutamate and glutamine supplementation during reperfusion is associated with increased de novo glycogen synthesis, suggesting a favourable modulation of intracellular myocardial carbohydrate metabolism. [ABSTRACT FROM AUTHOR]