Abstract

Introduction: The amplitude spectral area (AMSA) of ventricular fibrillation (VF) has been shown to track the myocardial energy state and to predict the effect of defibrillation. We measured AMSA in a rat model of VF and assessed the effects of α-methylnorepinephrine (α-MNE) - a selective peripheral α 2 -adrenoreceptor agonist - given to increase the coronary perfusion pressure without myocardial β 1 -adrenoceptor stimulation and the effects of zoniporide (ZNP) - an inhibitor of the sodium-hydrogen exchanger isoform-1 - given to protect mitochondrial bioenergetic function from reperfusion injury. Methods: VF was electrically induced in 48 rats and left untreated for 8 minutes. Chest compression was then started and defibrillation attempted 8 minutes later. Rats were randomized to receive a 3-mg/kg bolus of ZNP or 0.9% NaCl control (Ctr) before starting chest compression and a 100-μg/kg bolus of α-MNE or 0.9% NaCl control (Ctr) at 2 minutes of chest compression yielding four groups of 12 rats each; ZNP/α-MNE, ZNP/Ctr, Ctr/α-MNE, and Ctr/Ctr. Results: AMSA (mV·Hz; mean±SEM) was 34.9±1.5 at minute one after induction of VF and decreased to 2.6±0.2 at minute eight. With chest compression, AMSA gradually increased attaining different levels among groups (p<0.001). At minute seven of chest compression, AMSA was the highest with ZNP/α-MNE (29.9±2.5; p=0.012 vs Ctr/α-MNE and p<0.001 vs Ctr/Ctr) followed by ZNP/Ctr (24.1±2.5; p=0.016 vs Ctr/Ctr), Ctr/α-MNE (18.9±2.3), and Ctr/Ctr (12.9±2.6). Survival at 240 minutes differed among groups (p=0.007) with the highest survival with ZNP/α-MNE. Analysis of the independent effects of the interventions revealed that AMSA at minute seven was significantly higher with ZNP (27.2±2.6 vs 16.2±1.6; p<0.001) but not with α-MNE (22.9±2.1 vs 18.6±2.8; p=1.000). Survival was significantly higher with ZNP (18/24 vs 7/24; p=0.004) but not with α-MNE (12/24 vs 13/24; p=1.000). Conclusions: AMSA was the highest when ZNP was combined with α-MNE; a combination that also resulted in the highest 240-minute survival. This effect was primarily linked to ZNP without excluding a positive interaction with α-MNE. Accordingly, AMSA may also serve to assess the myocardial effects of metabolic interventions during cardiac resuscitation.

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