Preconditioning effects of steroids and hyperoxia on cardiac ischemia—reperfusion injury and vascular reactivity

Kaljusto, Mari-Liis; Stensløkken, Kåre-Olav; Mori, Tomohisa; Panchenko, Andrey; Frantzen, Marthe-Lise; Valen, Guro; Vaage, Jarle
March 2008
European Journal of Cardio-Thoracic Surgery;Mar2008, Vol. 33 Issue 3, p355
Academic Journal
Abstract: Objective: Corticosteroids and hyperoxia protect the heart against ischemia–reperfusion injury and may attenuate vascular reactivity. We hypothesized that (1) combining these two pretreatments induces an additive cardioprotection, (2) protection depends on activation of survival kinases and/or heat shock proteins, and (3) these interventions would change vascular reactivity into a more relaxed state. Methods: Male rats were randomized (n =10 in each group): 1. control, 2. dexamethasone (3mg/kg) injected 24 and 12h before harvesting the hearts, 3. 60min of hyperoxia (90–95% O2) immediately before harvest, 4. combination of dexamethasone and hyperoxia as in groups 2 and 3. The hearts were Langendorff-perfused and exposed to 30min of global ischemia and reperfused for 120min. Cardiac function was monitored and infarct size determined. Isometric tension to vasoconstrictive and vasodilatory agents was measured in femoral artery rings. Phosphorylation of survival kinases (protein kinase B/AKT, extracellular signal-regulated kinases (ERK1/2), the stress-activated/c-Jun NH2 terminal kinases (SAPK/JNK) and p38 MAPK), adenosine monophosphate dependent kinase (AMPK) and expression of heat shock protein 72 (HSP72) in hearts was evaluated by immunoblotting. Results: Infarct size was attenuated in all pretreated groups versus controls: 29% reduction in the combined group (p <0.01), 23% in hyperoxia group (p <0.05) and 31% in dexamethasone group (p <0.01). There was no significant difference between the treated groups. Combined pretreatment improved postischemic left ventricular end diastolic pressure compared to all other groups (p <0.001 vs controls, p =0.002 vs dexamethasone, p =0.005 vs hyperoxia). Combined pretreatment improved left ventricular developed pressure and coronary flow compared to controls (p <0.001 for both) and hyperoxia (p =0.0047 and p =0.0024, respectively). Combined pretreatment enhanced endothelium-independent relaxation (p =0.0032) compared to controls. Excepting ERK1/2 phosphorylation in the combined group during early reperfusion, there was no increased phosphorylation of the survival kinases AKT, p38, JNK, or AMPK and no increase of HSP72 expression. Conclusion: Combined pretreatment by hyperoxia and dexamethasone improved postischemic heart function, but did not reduce infarct size compared to single pretreatment groups. Except of a possible role of ERK1/2, protection depended neither on survival kinases nor heat shock protein 72.


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