Effect of streptomycin on wall-stress-induced arrhythmias in the working rat heart.
OBJECTIVE
To assess whether streptomycin, an inhibitor of mechano-sensitive cation channels, has an effect on arrhythmias-induced by an increase of ventricular wall stress in the rat heart.


METHODS
The isolated working rat heart preparation was used. Arrhythmias were induced by increasing the afterload (i.e., aortic pressure) against which the left ventricle (LV) pumped for 20 s. This led to an increase of LV pressure, stretch of the LV and an increase in LV wall stress. The number of ventricular premature beats induced by each afterload step was compared in the absence and presence of streptomycin, a compound known to block mechano-sensitive cation channels in the heart.


RESULTS
Perfusion with 200 microM streptomycin caused a significant reduction in wall-stress-induced arrhythmias. The effect of streptomycin on arrhythmias reached steady-state within 10 min of application. In the presence of streptomycin, arrhythmias elicited by a 40 mmHg afterload increase were reduced to 38% of control. Arrhythmias induced by an 80 mmHg afterload increase were reduced to 61% of control. Complex arrhythmias (ventricular tachycardia) induced by an afterload increase were also reduced in the presence of 200 microM streptomycin. There was no change in inotropic state with streptomycin, as assessed either by cardiac output or by maximum developed LV pressure. Streptomycin 50 microM (a typical therapeutic plasma concentration in patients) had no effect on wall-stress-induced arrhythmias.


CONCLUSIONS
The results were inconsistent with streptomycin acting by modulating inositol phosphate production, or altering the level of intracellular calcium or inotropic state. The anti-arrhythmic effect of streptomycin appears more consistent with inhibition of mechano-sensitive cation channels, suggesting that these ion channels might be involved in causing wall-stress-induced arrhythmias.
Salmon
A H
AH
Department of Physiology, School of Medical Sciences, University of Bristol, UK.
Mays
J L
JL
Dalton
G R
GR
Jones
J V
JV
Levi
A J
AJ
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D006352:Heart Ventricles; D007473:Ion Channels / Q000187:drug effects*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D013307:Streptomycin / Q000494:pharmacology* / Q000627:therapeutic use*; D013314:Stress, Mechanical
D007473:Ion Channels; D013307:Streptomycin