Endothelin-B receptors and ventricular arrhythmogenesis in the rat model of acute myocardial infarction.
The arrhythmogenic effects of endothelin-1 (ET-1) are mediated via ETA-receptors, but the role of ETB-receptors is unclear. We examined the pathophysiologic role of ETB-receptors on ventricular tachyarrhythmias (VT/VF) during myocardial infarction (MI). MI was induced by coronary ligation in two animal groups, namely in wild-type (n = 63) and in ETB-receptor-deficient (n = 61) rats. Using a telemetry recorder, VT/VF episodes were evaluated during phase I (the 1st hour) and phase II (2-24 h) post-MI, with and without prior beta-blockade. Action potential duration at 90% repolarization (APD90) was measured from monophasic epicardial recordings and indices of sympathetic activation were assessed using fast-Fourier analysis of heart rate variability. Serum epinephrine and norepinephrine were measured with radioimmunoassay. MI size was similar in the two groups. There was a marked temporal variation in VT/VF duration; during phase I, it was higher (p = 0.0087) in ETB-deficient (1,519 +/- 421 s) than in wild-type (190 +/- 34 s) rats, but tended (p = 0.086) to be lower in ETB-deficient (4.2 +/- 2.0 s) than in wild-type (27.7 +/- 8.0 s) rats during phase II. Overall, the severity of VT/VF was greater in ETB-deficient rats, evidenced by higher (p = 0.0058) mortality (72.0% vs. 32.1%). There was a temporal variation in heart rate and in the ratio of low- to high-frequency spectra, being higher (<0.001) during phase I, but lower (p < 0.05) during phase II in ETB-deficient rats. Likewise, 1 h post-MI, serum epinephrine (p = 0.025) and norepinephrine (p < 0.0001) were higher in ETB-deficient (4.20 +/- 0.54, 14.24 +/- 1.39 ng/ml) than in wild-type (2.30 +/- 0.59, 5.26 +/- 0.67 ng/ml) rats, respectively. After beta-blockade, VT/VF episodes and mortality were similar in the two groups. The ETB-receptor decreases sympathetic activation and arrhythmogenesis during the early phase of MI, but these effects diminish during evolving MI.
Department of Cardiology, University of Ioannina, 1 Stavrou Niarxou Avenue, 45110 Ioannina, Greece.
Dimitrios L
DL
Oikonomidis
Dimitrios G
DG
Tsalikakis
Giannis G
GG
Baltogiannis
Alexandros T
AT
Tzallas
Xanthi
X
Xourgia
Maria G
MG
Agelaki
Aikaterini J
AJ
Megalou
Andreas
A
Fotopoulos
Apostolos
A
Papalois
Zenon S
ZS
Kyriakides
Theofilos M
TM
Kolettis
D000200:Action Potentials; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000818:Animals; D002395:Catecholamines / Q000097:blood; D004562:Electrocardiography; D006339:Heart Rate; D009203:Myocardial Infarction / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D051381:Rats; D044023:Receptor, Endothelin B / Q000235:genetics / Q000378:metabolism*; D017180:Tachycardia, Ventricular / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D018487:Ventricular Dysfunction, Left; D014693:Ventricular Fibrillation / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control
D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D044023:Receptor, Endothelin B