Autonomic function and myocardial repolarisation. Studies in renal diseases and in spinal cord injury

Abstract

Both experimental and clinical evidence indicates that cardiac parasympathetic markers such as baroreflex sensitivity (BRS) and heart rate variability (HRV) have significant prognostic value. Furthermore, increased myocardial repolarisation lability reflected by increased QT variability index (QTVI) has been identified as a predictor for sudden cardiac death. The present study explored sympathetic and parasympathetic interaction in high spinal cord injury, which results in divided influence upon the two divisions with intact vagal activity and loss of supraspinal control to the entire or the major part of the sympathetic division. Autonomic response during perturbation caused by autonomic dysreflexia (AD) was also investigated. Autonomic function and myocardial repolarisation dynamics were evaluated in renal diseases, including renovascular hypertension (RVH) and end-stage renal disease (ESRD). Moreover, method reproducibility of spontaneous BRS and temporal QTVI measurements were assessed.Spontaneous BRS was used to estimate cardiac parasympathetic modulation in patients with RVH, patients with ESRD, spinal cord injured and healthy subjects. In subgroups, HRV was also measured. Isotope dilution with total body norepinephrine (NE) spillover was performed to assess overall sympathetic nerve activity in patients with RVH, spinal cord injured and healthy controls. Temporal QT variability reflecting myocardial repolarisation, and method reproducibility of BRS and temporal QTVI was measured in patients with ESRD and healthy volunteers. The findings indicate that in the chronic stage after the spinal cord injury, despite low peripheral sympathetic activity, autonomic balance is re-established at the cardiac level, as evidenced by normal BRS and heart rate at rest. During AD, the hypertensive reaction may be partly attributable to renal vasoconstriction and pronounced generalised sympathetic activation, which was counterbalanced by vagal activation at the cardiac level. In patients with RVH, BRS was reduced, whereas total body NE spillover was increased compared to healthy controls, indicating autonomic dysfunction encompassing both the parasympathetic and the sympathetic division. In the ESRD population, the impaired cardiac parasympathetic modulation demonstrated by reduced BRS and HRV, and increased myocardial repolarisation lability were further deteriorated in the diabetic subgroup. Method reproducibility over time of BRS and QTVI was moderate, suggesting that the biological variation should be taken into consideration when interpreting results from longitudinal studies. Taken together, investigations of spinal cord injured subjects add to our understanding of sympathetic and parasympathetic interaction striving to maintain cardiovascular homeostasis Despite moderate reproducibility over time, BRS and QTVI can be useful tools for identification of cardiac autonomic and repolarisation disturbances. Moreover, the present studies established impaired autonomic function with increased sympathetic and reduced parasympathetic activity, and increased myocardial repolarisation lability in RVH and ESRD. These disturbances may contribute to increased cardiovascular morbidity and mortality.