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Published on: May 22, 2018
Fundamental electrophysiological differences between low-dose intracoronary endothelin-1 infusion and myocardial
1Department of Cardiovascular Surgery, Semmelweis Medical University, Budapest, Hungary. gellac@kkt.sote.hu
Insights
Endothelin-1 (ET-1) directly causes arrhythmias by prolonging action potentials and increasing dispersion, distinct from ischemic effects. This study in canines differentiates ET-1
Area of Science:
- Cardiovascular Physiology
- Cardiac Electrophysiology
- Pharmacology
Background:
- The direct arrhythmogenic potential of endothelin-1 (ET-1) remains unclear.
- Ischemia and ET-1 can both induce cardiac arrhythmias.
- Differentiating direct ET-1 effects from ischemic effects is crucial.
Purpose of the Study:
- To investigate electrophysiological changes during left anterior descending artery (LAD) occlusion and intracoronary ET-1 infusion.
- To distinguish between direct and ischemic arrhythmogenic actions of ET-1.
- To characterize ET-1's role in canine cardiac arrhythmias.
Main Methods:
- Monophasic action potential duration (MAPD90), upstroke velocity (UV), and MAP dispersion (MAPDISP) were recorded in canine ventricles.
- Groups underwent LAD occlusion (Group A) or intracoronary ET-1 infusion at varying rates (Groups B and C).
- Electrophysiological parameters were analyzed to assess local ischemic and direct ET-1 effects.
Main Results:
- LAD occlusion (Group A) decreased MAPD90 and UV, with unchanged MAPDISP and no severe arrhythmias.
- ET-1 infusion (Groups B and C) increased MAPD90 and MAPDISP, with unchanged or slightly decreased UV.
- Early afterdepolarizations (EADs) and severe arrhythmias were observed in ET-1 treated groups (B and C).
Conclusions:
- ET-1 directly promotes arrhythmias through action potential prolongation, increased dispersion, and EAD development.
- The absence of prompt UV and MAPD90 decreases seen in ischemia supports a direct arrhythmogenic mechanism for ET-1.
- ET-1's arrhythmogenic effects are distinct from those induced solely by ischemia.
Abstract:
The supposed direct arrhythmogenic property of endothelin-1 (ET-1) has not yet been clearly proven. Our study aimed to characterize the electrophysiological changes during left anterior descending artery (LAD) occlusion and intracoronary (i.c.) ET-1 infusion, and to differentiate between the supposed direct and ischemic arrhythmogenic actions of ET-1 in a canine model. Changes of monophasic action potential duration (MAPD90) and upstroke velocity (UV) are capable of detecting local ischemic changes. Left and right ventricular endo- (LVEND, RVEND) and epicardial (LVEP, RVEP) monophasic action potentials were recorded. MAPD90, monophasic action potential dispersion (MAPDISP) and UV were determined. In group A (n = 8) 30 min LAD occlusion was followed by a 60 min reperfusion period. In groups B and C ET-1 was administered into the LAD at rates of 30 (n = 8) and 60 pmol/min (n = 10), respectively. In group A after the LAD occlusion both MAPD90 and UV decreased significantly in the LAD region (LVEP and LVEND 18 +/- 3% and 10 +/- 1%, p < 0.05, and 65 +/- 4% and 52 +/- 8%, respectively, p < 0.05; control and 30 min values in all groups), whereas the increase in MAPDISP remained unchanged. No severe arrhythmias were noticed in this group. In group B, both MAPD90 and MAPDISP increased significantly (LVEP and LVEND 11 +/- 4% and 18 +/- 3%, p < 0.05; MAPDISP 200 +/- 40%, p < 0.05), whereas UV remained unchanged at the end of the infusion. Early afterdepolarizations (EADs) were present in three instances. In group C both MAPD90 and MAPDISP increased significantly (LVEP and LVEND 12 +/- 5% and 26 +/- 8%, respectively, p < 0.05; MAPDISP 215 +/- 30%, p < 0.05) and UV decreased slightly in the LAD region. EADs were observed in five instances. Severe arrhythmias were observed in both groups B and C. We concluded that MAP prolongation, increased MAP dispersion and development of EADs all contribute to the arrhythmogenic action of ET-1. The lack of the almost prompt decrease of UV and MAPD90 which was observed in group A in groups B and C strongly supports the probability of a direct arrhythmogenic effect of ET-1.
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