Vanhoutte and Bowditch phenomena in heart failure: their relation toischemia-reperfusion impact

Abstract

Aim: Evaluation of both 15,16-epoxyeicosatrien (15,16-EET) induced coronaro dilation and Bowditch’s staircase in experimental heart failure (HF) as well as their influence on ischemic contracture and functional recovery of isolated heart during reperfusion.Material and methods:HF was reproduced by doxorubicin administration in rat (16mg/kg in 2 weeks). Vanhoutte’s phenomenon was estimated by coronary flow raising rate in isovolumic isolated heart perfused by Langendorff method during action of15,16-EET (10-4 M). Bowditch’s staircase was assayed by electrically induced heart rate (HR) rise till maximal level suitable to left ventricle (LV) systolic pressure elevation(LVSP). Ischemic contracture was appreciated by LV end-diastolic pressure (LVEDP)at the end of global 20 min ischemia period followed by 30 min period of reperfusion when LVSP dynamics has been recorded. Likewise, ischemia-reperfusion impact was attested in condition of 15,16-EET action during pre-ischemia (20 min) and reperfusion as well as after maximal HR reaching.Results:Coronarodilation effect of 15,16-EET has not been compromised in HF,because the coronary flow increased like in control comparatively to basal value(13,2±1,2% vs 13,9±1,1%). However, Bowditch’s staircase was earlier interrupted in comparison to control according to maximal HR matching to positive slope of LSD: 285±22,6 vs 372±29,4 1/min (p<0,05). Maximal ischemic LVEDP was significantly higher in HR: 47,6±3,3 vs 24,9±1,8 mmHg (p<0,001). On the other hand LVSP was at the end of reperfusion lower than control: 72,4±6,5 vs112,3±7,5 mmHg (p<0,01). Remarkably, 15,16-EET action before ischemia and during reperfusion notably improved dynamics of LVEDP and LVEDP in both control and HF (in the last even more evidently). Relative diminution of LVEDP measured14,3±1,4% in HF and 12,5±1,2% in control, and LVESP increment: 15,1±1,5%vs 13,7±1,3%. If the ischemia-reperfusion onset started after frequency pacingischemic contracture and functional LV recovery worsened similarly in both control and HF series: LVEDP increased by 19-20% while LVSP decreased by 17-18%.Conclusions:1. Derived (in cytochrome P450 biochemical way) from arachidonic acid 15,16-EET increases coronary flow in HF similarly to control and could be an important factor of coronary regulation by hyperpolarization mechanism in cases of endothelium dependent compromised coronary reactivity.2. 15,16-EET mitigates ischemia-reperfusion impact in HF while HR elevationworsens ischemic contracture and LV contraction recovery in reperfusion.