Mechano-electric feedback in right atrium after left ventricular infarction in rats.
Left ventricular myocardial infarction (MI) can lead to alterations in hemodynamic load conditions, thereby inducing right atrial hypertrophy and dilatation associated with phenotypic modulation of cardiomyocytes, electrical abnormalities, rhythm disturbances, and atrial fibrillation. However, there is limited information on the electrophysiological basis for these events. We investigated whether atrial stretch in the setting of chronic MI modulates the electrophysiological properties of cardiomyocytes via "mechano-electric feedback", providing a mechanism for atrial arrhythmia after ventricular infarction. Five weeks after left ventricular MI (n=37), action potentials (AP) were measured in right atrial tissue preparations using a current clamp scheme, and compared to sham-operated rats (SO, n=10). Contractile activity was recorded at a preload of 1 mN, and sustained stretch was applied via a micrometer. In SO, stretch of 1.75 mN shortened repolarization at 50% and prolonged it at 90%. In MI, mechanically-induced electrical alterations were observed at a significantly lower level of stretch than in SO (0.19 mN). Sustained stretch in MI prolonged AP at 90% repolarization giving rise to stretch-activated depolarizations (SAD) near 90% repolarization (SAD90). When reaching threshold for premature APs, electrical phenomena similar to atrial fibrillations were seen in some preparations. Moreover, we observed APs with prolonged duration at 25%, 50%, and 90% repolarization where stretch induced SAD near 50%. Gadolinium used at a concentration to inhibit stretch-activated channels (40microM) suppressed mechanically-induced electrical events. In conclusion, increased susceptibility after MI to mechanical stretch may predispose atrial cardiomyocytes to arrhythmia. These mechano-electrical alterations are sensitive to gadolinium suggesting involvement of stretch-activated ion channels.
Kamkin
A
A
Institute of Physiology, Humboldt-University (Charité), Tucholskystrasse 2, Berlin, 10117, Germany.
Kiseleva
I
I
Wagner
K D
KD
Leiterer
K P
KP
Theres
H
H
Scholz
H
H
Günther
J
J
Lab
M J
MJ
D000818:Animals; D004594:Electrophysiology; D006325:Heart Atria / Q000503:physiopathology*; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology*