M J Child | PubMed Health

PubMed1996

Cellular basis for improved left ventricular pump function after digoxin therapy in experimental left ventricular failure.

OBJECTIVES: The present study examined left ventricular (LV) and myocyte contractile performance and electrophysiologic variables after long-term digoxin treatment in a model of LV failure. BACKGROUND: A fundamental therapeutic agent for patients with chronic LV dysfunction is the cardiac glycoside digoxin. However, whether digoxin has direct effects on myocyte contractile function and electrophysiologic properties in the setting of chronic LV dysfunction remains unexplored. METHODS: Left ventricular and isolated myocyte function and electrophysiologic variables were examined in five control dogs, five dogs after the development 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 the pacing period (rapid pacing and digoxin). RESULTS: Left ventricular ejection fraction decreased in the dogs with rapid pacing compared with that in control dogs (30 +/- 2% vs. 68 +/- 3%, p < 0.05) and was higher with digoxin than that in the rapid pacing group (38 +/- 3%, p = 0.038). Left ventricular end-diastolic volume increased in the rapid pacing group compared with the control group (84 +/- 6 ml vs. 59 +/- 7 ml, p < 0.05) and remained increased with digoxin (79 +/- 6 ml). Isolated myocyte shortening velocity decreased in the rapid pacing group compared with the control group (37 +/- 1 microns/s vs. 59 +/- 1 microns/s, p < 0.05) and increased with digoxin compared with rapid pacing (46 +/- 1 microns/s, p < 0.05). Action potential maximal upstroke velocity was diminished in the rapid pacing group compared with the control group (135 +/- 6 V/s vs. 163 +/- 9 V/s, p < 0.05) and increased with digoxin compared 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 digoxin compared with rapid pacing (219 +/- 12 ms, p < 0.05). CONCLUSIONS: In this model of rapid pacing-induced LV failure, digoxin treatment improved LV pump function, enhanced isolated myocyte contractile performance and normalized myocyte action potential characteristics. This study provides unique evidence to suggest that the cellular basis for improved LV pump function with digoxin treatment in the setting of LV failure has a direct and beneficial effect on myocyte contractile function and electrophysiologic measures.

Action Potentials↗

PubMed1995

LV and myocyte structure and function after early recovery from tachycardia-induced cardiomyopathy.

Left ventricular (LV) function and mass were measured in six conscious dogs at weekly intervals during the progression of tachycardia-induced dilated cardiomyopathy (DCM) and during a 1-mo recovery period from DCM (post-DCM). LV end-diastolic volume and LV wall stress increased and LV ejection fraction decreased with each week of pacing. Despite the increased LV wall stress, LV mass did not change during the progression of tachycardia DCM. One week post-DCM resulted in an improved LV ejection fraction and normalization of neurohormonal profiles. However, 1 wk post-DCM was accompanied by a 26% increase in LV mass and persistent LV chamber dilation. Isolated myocyte function was examined and compared with that in six normal control dogs. Myocyte percent and myocyte velocity of shortening were 19 and 32% lower, respectively, in the post-DCM group compared with controls. Thus termination of the tachycardia subsequent to the development of DCM resulted in persistent LV chamber dilation and abnormalities in myocyte contractile function. The improved LV pump function with early recovery from tachycardia-induced DCM was mediated by LV hypertrophy and a subsequent reduction in LV wall stress rather than a normalization of LV geometry and myocyte contractile function.

Animals↗