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Investigating the dual nature of endothelin-1: ischemia or direct arrhythmogenic effect?
1Department of Cardiovascular Surgery, Semmelweis University of Medicine, Budapest, Hungary. tamas.szabo@excite.com
Insights
Endothelin-1 (ET-1) causes ventricular arrhythmias before ischemia. Intracoronary ET-1 reduced coronary blood flow but did not induce ischemia, unlike left anterior descending artery occlusion.
Area of Science:
- Cardiology
- Physiology
Background:
- Endothelin-1 (ET-1) is a potent vasoconstrictor with arrhythmogenic potential.
- Investigating ET-1's role in arrhythmias is crucial for understanding cardiac events.
Purpose of the Study:
- Compare the arrhythmogenic effects of left anterior descending (LAD) artery occlusion versus intracoronary ET-1 administration.
- Elucidate the underlying pathomechanism of ET-1-induced ventricular arrhythmias.
Main Methods:
- Three groups of dogs underwent LAD occlusion or ET-1 infusion.
- Electrophysiological parameters (monophasic action potentials), coronary blood flow, and lactate levels were monitored.
- Infrared imaging assessed epimyocardial temperature changes.
Main Results:
- ET-1 infusion significantly reduced coronary blood flow and epimyocardial temperature.
- ET-1 administration induced ventricular arrhythmias, including ventricular fibrillation, in a dose-dependent manner.
- Ischemic changes (lactate elevation, altered action potentials) were observed only in the LAD occlusion group.
Conclusions:
- ET-1 can trigger severe ventricular arrhythmias independently of significant myocardial ischemia.
- Reduced coronary blood flow by ET-1 may contribute to arrhythmia maintenance.
- ET-1's arrhythmogenic effects manifest earlier than ischemic signs.
Abstract:
Endothelin-1 (ET-1) is a potent vasoconstrictor peptide, which may also elicit severe ventricular arrhythmias. The aims of our study were to compare the effects of total left anterior descending coronary artery (LAD) occlusion to intracoronary (ic.) ET-1 administration and to investigate the pathomechanism of ET-1 induced arrhythmias in 3 groups of anesthetized, open-chest mongrel dogs. In group A (n=10) a total LAD occlusion was carried out for 30 min, followed by a 60 min reperfusion period. In groups B and C ET-1 was administered into LAD for 30 min at a rate of 30 pmol/min (n=6) and 60 pmol/min (n=8). Epi- and endocardial monophasic action potential (MAP) recordings were performed to detect electrophysiologic changes and ischemia Blood samples for lactate measurements were collected from the coronary sinus (CS) and from the femoral artery. Infrared imaging was applied to follow epimyocardial heat emission changes. At the end of the ET-1 infusion period coronary blood flow (CBF) was reduced significantly in groups B and C (deltaCBF30MIN B: 21+/-2%, p<0.05; C: 35+/-2%, p<0.05), paralleled by a significant epimyocardial temperature decrease in group C (deltaT30MIN: -0.65+/-0.29 degrees C, p<0.05). Two dogs died of ventricular fibrillation (VF) in the reperfusion period in group A. Ventricular premature contractions and non-sustained ventricular tachycardic episodes appeared in group B, whereas six dogs died of VF in group C. Significant CS lactate level elevation indicating ischemia was observed only in group A from the 30th min occlusion throughout the reperfusion period (control vs. 30 min: 1.3+/-0.29 vs. 2.2+/-0.37 mmol/l, p<0.05). Epi- and endocardial MAP durations (MAPD90) and left ventricular epicardial (LV(EPI)) upstroke velocity decreased significantly in group A in the occlusion period. ET-1 infusion significantly increased LV(EPI) MAPD90 in group B and both MAPD90-s in group C. In conclusion, ischemic MAP and CS lactate changes were observed only in group A. Although ET-1 reduced CBF significantly in groups B and C, neither MAP nor lactate indicated ischemic alterations. ET-1 induced major ventricular arrhythmias appeared before signs of myocardial ischemia developed, though reduced CBF presumably contributed to sustaining the arrhythmias.
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