This study demonstrated two unique observations: first, CHF patients with CSA who undergo heart transplantation may have persistent CSA beyond the peritransplant period (> 6 months) despite normalization of heart function and sympathetic activity. Second, CSA severity is attenuated and the cycle length plus ventilation:apnea ratio are altered in appearance, similar to that seen with idiopathic nonhypercapnic CSA, a condition characterized by normal heart function, after successful heart transplantation. Therefore, mechanisms other than heart dysfunction and heightened sympathetic activation are likely for the development or persistence of CSA.
Although our observations of apnea type changing from central to obstructive following transplantation confirms previous observations, we observed it to occur only in the group with pretransplant CSA.
While hyperventilation, related to heightened central and peripheral chemoreceptor function, is the physiologic entity which underpins CSA, the precise factors which contribute to the altered che-mosensitivity are unknown. In CHF, it is assumed that circulating norepinephrine or possibly loss of endothelial production of nitric oxide are responsible for the changes in chemosensitivity. Alternatively changes to chemoreceptor function may result from increased pulmonary vagal afferent stimulation, due to elevated pulmonary vascular pressures, in some patients but not in all.
Importantly, the change in the pattern of CSA, namely shortening of the cycle length with successful transplantation, indicates that CSA may occur despite normalization of heart function. The current study would suggest that factors other than heart dysfunction and sympathetic activity are responsible.
An alternative explanation is that medications that are required after heart transplantation affect che-mosensitivity. Cyclosporin has been shown to contribute to hypertension through mechanisms of direct renal vasoconstriction, rather than via elevations in sympathetic nerve activity, while its effect on chemosensitivity is not known. Swings of heightened systemic BP could contribute to the brief central apneas; however, we believe this mechanism is unlikely to be responsible for persistent CSA in our study, as no patient in the control group, matched for medications, acquired CSA.