Effects of Peripheral Chemoreceptors Deactivation on Sympathetic Activity in Heart Transplant Recipients

Abstract

Abstract-Heart transplantation initially normalizes sympathetic hyperactivity directed at the muscle circulation. However, sympathetic activity increases with time after transplantation and the exact mechanisms responsible for sympathetic control in heart transplant recipients remain unclear. We examined the effects of peripheral chemoreflex deactivation caused by breathing 100% oxygen on muscle sympathetic nerve activity (expressed as number of burst per minute and mean burst amplitude), heart rate, and mean blood pressure in 13 heart transplant recipients, 13 patients with essential hypertension, and 10 controls. Heart transplant recipients disclosed the highest sympathetic activity, whereas it did not differ between controls and patients with essential hypertension (51Ϯ16 versus 37Ϯ14 versus 39Ϯ12 burst/min, respectively; PϽ0.05). Breathing 100% oxygen, in comparison with 21% oxygen, reduced sympathetic activity (Ϫ4Ϯ4 versus Ϫ1Ϯ2 burst/min, PϽ0.01; 85Ϯ9 versus101Ϯ8% of amplitude at baseline, PϽ0.001) and mean blood pressure (Ϫ4Ϯ5 versus ϩ3Ϯ6 mm Hg; PϽ0.05) in heart transplant recipients, decreased sympathetic activity (Ϫ4Ϯ4 versus 0Ϯ3 burst/min, PϽ0.05; 90Ϯ16 versus101Ϯ9% of amplitude at baseline, PϽ0.05) in patients with essential hypertension, but did not reduce sympathetic activity (2Ϯ4 versus 3Ϯ3 burst/min, PϭNS; 95Ϯ11 versus 95Ϯ13% of amplitude at baseline, PϭNS) in control subjects. The sympathetic response to hyperoxia was more marked in heart transplant recipients than in controls (85Ϯ9 versus 95Ϯ11% of baseline amplitude; PϽ0.05). The decrease in sympathetic activity was most evident in patients with the longest time after heart transplantation (rϭϪ0.75, PϽ0.01).In conclusion, tonic chemoreflex activation increases resting muscle sympathetic nerve activity and favors blood pressure elevation after heart transplantation. Key Words: chemoreceptors Ⅲ sympathetic nervous system Ⅲ transplantation C ongestive heart failure is associated with remarkably elevated muscle sympathetic nerve activity (MSNA). 1 Heart transplantation restores a close to normal cardiac function but does not always normalize MSNA. 2-5 Elevated MSNA after heart transplantation is associated with cyclosporine therapy 3 and increases as a function of time after transplantation. 2 Increased peripheral chemoreflex sensitivity has been demonstrated in humans and experimental animals with congestive heart failure. 6 -9 Whether this alteration in chemoreflex function is reversible when cardiac function is restored by heart transplantation is unknown. We hypothesized that increased peripheral chemoreceptor activation, possibly a lingering effect of heart failure, contributes to elevated MSNA in heart transplant recipients (HTRs). Accordingly, we studied the effects of hyperoxia, an intervention that acutely reduces afferent nerve traffic from the peripheral chemoreceptors, on MSNA in HTRs. Because the majority of HTRs are hypertensive 10 and enhanced peripheral chemoreflex sensitivity has been observed in hypertensive humans and in animal m...

Tonic activity of carotid body chemoreceptors contributes to the increased sympathetic drive in essential hypertension

“…Only one study till now has reported that the deactivation of carotid body chemoreceptors may decrease sympathetic activation in systemic hypertension. 18 Hypertensive patient 100 % Oxygen 21 % Oxygen Tonic chemoreflex activation in hypertension M Siński et al However, in this study patients were of an advanced age and on antihypertensive medication, which may influence sympathetic activity. In the recent study by Binggeli et al, 19 the authors used hyperoxic stimuli in hypertensive subjects with and without periodic breathing, and did not find a significant reduction of MSNA in the group without periodic breathing.…”

“…Studies in humans also show that 100% oxygen stimulus inhibits both ventilatory and sympathetic chemoreflex response. 12,13,18,21,28 It is then wise to consider the reduction of MSNA observed in our study as the effect of carotid body inhibition by hyperoxia, but we cannot exclude the role of the local vascular effects. The interpretation of circulatory parameters during hyperoxia in hypertensive subjects need further study.…”

“…Data from previous investigations on the effects of hyperoxia on circulatory hemodynamics are inconsistent. Although some studies did not find any effects of hyperoxia on BP, 18,12 others found a decrease of BP after hyperoxia in heart transplant recipients, 18 chronic renal failure, 21 sleep apnea 12 and hypertension. 16 The reason for such discrepancy remains unknown.…”

“…3,4,7 One study reported no increase in MSNA in hypertensive patients, 18 but the population included subjects of advanced age being treated with antihypertensive medications, which could affect baseline MSNA levels. 20 Another important observation of the present study is that acute hyperoxia-normalized sympathetic activity in hypertensive patients reaching the values observed in control subjects.…”

“…In two studies, 12,13 hyperoxia lowered MSNA in control individuals, but not in the other two. 18,21 The reason for such a discrepancy may be related to control subject selection for the certain study protocol.…”