Effect of propranolol on heart rate variability in patients with end-stage renal disease: a double-blind, placebo-controlled, randomized crossover pilot trial.
BACKGROUND
Low heart rate variability (HRV) is an independent risk factor of cardiac mortality in patients with end-stage renal disease (ESRD). It has been explained by uremic parasympathetic neuropathy. Sympathetic overactivity can also reduce HRV. Our aim was to determine whether there is vagal activity in ESRD patients that is masked by sympathetic activity.


METHODS
The effect of propranolol on HRV was examined in 13 patients with ESRD, aged 20.1 +/- 7.6 years without diabetes. All patients were given intravenous propranolol (0.05 mg/kg) once and placebo once in a randomized, double-blind way, with an interval of 6.6 days (mean, range: 2-9). Propranolol was administered before hemodialysis treatment, after 40 minutes supine resting period. HRV was registered for 10 minutes, during supine, before and after the injection. Patients' HRV data were compared to that of 29 age-matched healthy controls.


RESULTS
Initially, both high-(HFV) and low-frequency (LFV) bands of heart rate variability were lower in ESRD patients compared to controls (p < 0.001 for both). Propranolol resulted in a significant increase of HFV (propranolol: AlgHFV = 0.182 (0.027 - 0.337), placebo: deltalgHFV = -0.029 (-0.128 - +0.070); p = 0.032). Elevation of LFV was not significant. Six patients had an elevated plasma norepinephrine and/or epinephrine level. Plasma dopamine level was elevated in all but 1 patient (mean: 432 pmol/l, 95% CI: 320-543) and showed an inverse relationship with the increase of IgHFV secondary to propranolol (r = -0.66, p = 0.014).


CONCLUSIONS
Low HFV of ESRD patients can be improved by beta-adrenergic blockade. It demonstrates that there is some vagal activity in ESRD that is masked by sympathetic activity. Therefore, altered sympathovagal balance of ESRD patients should be taken into consideration in the assessment of vagal uremic neuropathy.
Tory
K
K
First Department of Pediatrics, Semmelweis University of Budapest, Hungary. torykalman@hotmail.com
Horváth
E
E
Süveges
Z
Z
Fekete
A
A
Sallay
P
P
Berta
K
K
Szabó
T
T
Szabó
A J
AJ
Tulassay
T
T
Reusz
G S
GS
D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D002648:Child; D018592:Cross-Over Studies; D004298:Dopamine / Q000378:metabolism; D004311:Double-Blind Method; D004837:Epinephrine / Q000378:metabolism; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000503:physiopathology* / Q000628:therapy; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010865:Pilot Projects; D011433:Propranolol / Q000494:pharmacology*; D006435:Renal Dialysis; D013564:Sympathetic Nervous System / Q000502:physiology; D014630:Vagus Nerve / Q000502:physiology
D000319:Adrenergic beta-Antagonists; D011433:Propranolol; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine