Digoxin did not reduce overall mortality, but it reduced the rate of hospitalization both overall and for worsening heart failure. These findings define more precisely the role of digoxin in the management of chronic heart failure.

Enalaprilat augments both arterial and cardiopulmonary baroreflex control of sympathetic activity in heart failure. These augmented inhibitory influences are associated with a reduction in sympathetic outflow and may contribute to the beneficial effects of angiotensin-converting enzyme inhibitors in heart failure.

The purpose of this study was to determine if arterial baroreflex control of sympathetic nerve traffic is impaired in heart failure. We recorded renal nerve activity during changes in arterial pressure while simultaneously recording from aortic baroreceptor afferent fibers in 10 dogs with heart failure induced by rapid ventricular pacing and in 10 sham animals. Sensitivity of the aortic baroreceptors (percent change in nerve activity per millimeters mercury change in mean arterial pressure) was reduced in the heart failure group (heart failure, 2.3 +/- 0.3; sham, 3.6 +/- 0.4, p = 0.02). Despite the reduced sensitivity of aortic baroreceptors in heart failure, there was no difference in the baroreflex gain of renal nerve activity (heart failure, -5.5 +/- 1.4; sham, -5.8 +/- 1.3, p = NS). These values tended to decrease in both groups after vagotomy. The relation between baroreceptor input and renal sympathetic output, or central baroreflex gain (percent change in renal nerve activity divided by percent change in aortic nerve activity) was similar in both groups before vagotomy (heart failure, -2.4 +/- 0.6; sham, -2.3 +/- 0.5, p = NS). Vagotomy reduced central gain in the sham group (-0.9 +/- 0.1, p = 0.03) but not in the heart failure group (-1.7 +/- 0.5, p = NS), suggesting that the contribution of vagal afferents in the baroreflex arc is reduced in heart failure. Baroreflex control of R-R interval was attenuated in heart failure when assessed by blood pressure elevation but not reduction, indicating abnormal parasympathetic but preserved cardiac sympathetic mechanisms in heart failure. Thus, dogs with heart failure exhibit reduced sensitivity of aortic baroreceptors but preserved baroreflex control of renal nerve activity. Reduced baroreceptor sensitivity with preservation of baroreflex control of sympathetic nerve activity may contribute to the sympathoexcitatory state known to exist in heart failure.

Recent reports suggested that exercise intolerance associated with congestive heart failure (CHF) may be due to changes in peripheral limb muscle function. Our purpose was to determine whether CHF also elicits alterations in diaphragmatic function. CHF was induced in dogs by rapid ventricular pacing for a period of 4-6 wk. After signs of CHF developed, dogs were anesthetized and an acute study was performed to assess diaphragm function. Diaphragm strips were dissected in situ in the left costal diaphragm, the phrenic artery supplying these strips was cannulated, and strips were perfused with arterial blood at arteriovenous pressure gradient of 90 mmHg. Diaphragm strength and fatiguability were then determined, and phrenic flow response to transient arterial occlusion was assessed. A group of nonpaced normal dogs was similarly studied and served as controls. We found that CHF dogs had a significant reduction in diaphragm strength. For example, tetanic force in response to 100 Hz of stimulation was 25.5 +/- 1.0 N/cm2 in control dogs but only 19.6 +/- 1.9 kg/cm2 in CHF dogs (P < 0.02). In addition, CHF dogs had increased diaphragm fatiguability. Diaphragm force fell to 27 +/- 3% of its baseline value during a 30-min fatigue trial in CHF dogs but only to 44 +/- 4% in control dogs (P < 0.01). CHF dogs also had a altered phrenic arterial hyperemic response to arterial occlusion and a reduction in phrenic arterial blood flow achieved during the fatigue trial. We conclude that development of CHF is associated with significant alterations in diaphragmatic function, causing a marked increase in fatiguability.