Analysis of conditioning with dexmedetomidine under endothelial dysfunction in isolated perfused hearts

Cardioprotective strategies such as pharmacological conditioning have not yet successfully undergone bench-to-bedside transfer, which is probably due to inhibition of cardioprotection by comorbidities or associated pathological changes. Endothelial dysfunction (ED) is closely associated with most cardiovascular diseases and their typical comorbidities. Therefore, cardioprotective strategies should be examined under ED. It was previously demonstrated that dexmedetomidine (DEX) maintains its cardioprotective properties against ischemia/reperfusion (I/R) injury under hyperglycaemia in the setting of pre-but not postconditioning, using a constant pressure Langendorff system. Under ED, cardioprotection by DEX preconditioning is also maintained using a constant flow mode, whereas this has not yet been investigated for postconditioning. Because DEX has vasoconstrictive properties, different haemodynamic conditions might influence the cardioprotective potential of DEX. Therefore, it was investigated whether pre- and postconditioning protocols with DEX used in constant pressure mode are transferable to constant flow mode and whether the cardioprotective effect of DEX is maintained under ED. The cardioprotective effect against I/R injury of pre- and post-treatment with 3 nM DEX on isolated-perfused hearts of male Wistar rats was analysed in constant flow mode. ED was induced by perfusion with Krebs-Henseleit buffer containing 60 mM KCl. Heart function was assessed via pressure measurements in the left ventricle (LV) and infarct size (IS) via triphenyltetrazolium-chloride staining. In constant flow mode, pre- and post-treatment with DEX has no effect on IS and heart function compared with hearts treated with vehicle both under ED and under physiological conditions. In DEX pre-treated hearts under ED, LV developed pressure is increased and contractility is improved after 60 min of reperfusion. Pre- and post-treatment with DEX is not cardioprotective with the protocol used, while DEX pre-treatment under ED has improving effects on heart function. Different hemodynamic conditions may modulate the cardioprotective properties of DEX, possibly due to its vasoconstrictive properties.