Ws. Mcmahon et al., CELLULAR BASIS FOR IMPROVED LEFT-VENTRICULAR PUMP FUNCTION AFTER DIGOXIN THERAPY IN EXPERIMENTAL LEFT-VENTRICULAR FAILURE, Journal of the American College of Cardiology, 28(2), 1996, pp. 495-505
Objectives. The present study examined left ventricular (LV) and myocy
te contractile performance and electrophysiologic variables after long
term digoxin treatment in a model of LV failure. Background. A fundam
ental therapeutic agent for patients with chronic LV dysfunction is th
e cardiac glycoside digoxin. However, whether digoxin has direct effec
ts on myocyte contractile function and electrophysiologic properties i
n the setting of chronic LV dysfunction remains unexplored. Methods. L
eft ventricular and isolated myocyte function and electrophysiologic v
ariables were examined in five control dogs, five dogs after the devel
opment of long-term rapid pacing (rapid pacing, 220 beats/min, 4 weeks
) and five dogs with rapid pacing given digoxin (0.25 mg/day) during t
he pacing period (rapid pacing and digoxin). Results. Left ventricular
ejection fraction decreased in the dogs with rapid pacing compared,vi
th that in control dogs (30 +/- 2% vs. 68 +/- 3%, p < 0.05) and was hi
gher with digoxin than that in the rapid pacing group (38 +/- 3%, p =
0.038), Left ventricular end diastolic volume increased in the rapid p
acing group compared with the control group (84 +/- 6 ml vs, 59 +/- 7
ml, p < 0.05) and remained increased with digoxin (79 +/- 6 ml). Isola
ted myocyte shortening velocity decreased in the rapid pacing group co
mpared with the control group (37 +/- 1 mu m/s vs. 59 +/- 1 mu m/s, p
< 0.05) and increased with digoxin compared,vith rapid pacing (46 +/-
1 mu m/s, p < 0.05). Action potential maximal upstroke velocity was di
minished in the rapid pacing group compared with the control group (13
5 +/- 6 V/s vs, 163 +/- 9 V/s, p < 0.05) and increased with digoxin co
mpared with rapid pacing (155 +/- 12 V/s, p < 0.05). Action potential
duration increased in the rapid pacing group compared with the control
group (247 +/- 10 vs. 216 +/- 6 ms, p < 0.05) and decreased with digo
xin compared with rapid pacing (219 +/- 12 ms, p < 0.05). Conclusions.
In this model of rapid pacing induced LV failure, digoxin treatment i
mproved LV pump function, enhanced isolated myocyte contractile perfor
mance and normalized myocyte action potential characteristics. This st
udy provides unique evidence to suggest that the cellular basis for im
proved LV pump function with digoxin treatment in the setting of LV fa
ilure has a direct and beneficial effect on myocyte contractile functi
on and electrophysiologic measures.