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DOI: 10.1055/s-0034-1367389
Epinephrine application in ischemia-reperfusion injury-induced ventricular dysfunction promotes myocardial mitochondrial dysfunction
Objectives: Epinephrine-application in acute myocardial insufficiency increases the myocardial oxygen demand, impacting on clinical outcome. We analyzed the impact of epinephrine on healthy and failing myocardium during ischemia reperfusion injury.
Methods: Wistar rats were divided into 4 groups consisting of controls (IR0-30) and animals receiving IR (IR15/30), epinephrine (IR0/30 Epi) and the combination of both (IR15/30 Epi). During pressure-controlled Langendorff reperfusion left ventricular performance was recorded (LVPmax, LVPdp/dtmax). After reperfusion myocardium was analyzed regarding mitochondrial function (electron transport chain, Ca2+-mMTP-opening), marker enzymes (CK/MB, HFABP, Cyr61) and redox states (GSH, NOx) and injury due to ROS or inflammation (TBARS, MPO).
Results: Compared to IR0/30 in IR15/30 myocardial performance deteriorated and was significantly enhanced in IR0/30 Epi (P = .037). During IR epinephrine significantly improved LVdp/dtmax (P = .011) and LVPmax (P = .06). Analysis of SSM- and IFM-fraction of mitochondria revealed adverted IR-dysfunction of SSM-complexes I-V, II-V and II-IV in presence of epinephrine (P < .001, P < .01, P < .05). Ca2+-induced swelling was performed in presence of 50 µmol (w/o 5 µmol pyruvate) and 100 µmol Ca2+. In IR15/30 SSM susceptibility towards Ca2+-induced swelling increased, in presence of epinephrine swelling was inhibited significantly (P < .001). Regarding IFM results remained less significant.
HFABP determined from eluate demonstrated insignificantly increased damage in IR0/30 Epi and foremost in IR15/30 Epi, CK/MB was elevated in both groups undergoing IR. Cyr61tissue was insignificantly suppressed in IR15/30 Epi. A significant loss of GSH occurred during ischemia in presence of Epinephrine (P < 0.005). TBARS was high in IR15/30 Epi (P>.05) and MPO increased in IR15/30 with or without Epi (P = .037).
Conclusions: Epinephrine-treatment of IR-induced LV-failure exacerbates myocardial mitochondria and tissue injury.