Sažetak | Study I
Constant sympathetic overactivity is a well known hallmark of chronic heart failure (CHF) that tends to increase with disease severity. One of the common abnormalities of heart function associated with CHF is occurrence of premature ventricular contractions (PVCs) that tend to transiently decrease blood pressure (BP) and cause reflex increase in sympathetic discharge. PVCs that often occur in these patients have been already recognized as a pronounced sympathoexcitatory stimulus that elicits formation of larger bursts of muscle sympathetic nerve activity (MSNA). However, firing pattern of activation of postganglionic sympathetic neurons in CHF patients and in healthy individuals is still poorly investigated. Aim of the Study I in the present Doctoral Dissertation is to evaluate firing properties of postganglionic sympathetic neurons in CHF patients and healthy age- and gender- matched individuals. Second aim is to examine and compare the strategies of SNS activity in CHF patients and in healthy subjects as a response to PVC. PVCs were identified in both groups (CHF and controls) and sympathetic neurograms of sufficient signal-to-noise ratio were obtained using the microneurography. Neurograms of 6 CHF patients and 6 healthy controls were analyzed using action potential (AP) detection software that enables identification of individual sympathetic APs and their amplitude-size classification into different clusters. During sinus rhythm, CHF patients had greater number of APs per burst, higher AP firing frequency and higher number of active clusters of sympathetic neurons compared to healthy controls. PVCs caused an increase in AP firing frequency and in the number of active clusters. However, compared with controls, an increase in burst integral, AP firing frequency, and APs per burst was less in CHF patients. The PVC-induced increase in active clusters per burst was similar between the groups, suggesting that CHF patients retained the sympathetic reserve through the recruitment of larger APs but not through augmentation of already active sympathetic neurons.
Study II
Continuous positive airway pressure (CPAP) application is a novel therapy for patients with chronic heart failure (CHF), a condition often related to sleep disordered breathing. Favorable effects of CPAP include correction of respiratory breathing pattern, improvement in left ventricular function and enhanced exercise tolerance. The data on whether the benefits of CPAP application in CHF patients are direct consequence of ANS responses are still inconsistent. Moreover, firing pattern of sympathetic fibers during various respiratory stimuli in health as well as in heart failure remains to be elucidated. The aim of the Study II is to assess the firing pattern of sympathetic fibers during CPAP application in CHF patients and in healthy age- and gender- matched controls. Microneurography was used to measure muscle sympathetic nerve activity (MSNA) from 8 healthy middle aged individuals and from 7 CHF patients. The same AP detection software was used to extract action potentials (APs) from the recorded neurograms as for the purpose of the Study I. Extracted APs were quantified as AP firing frequency and classified into different clusters based on the size of their peak-to-peak amplitude. Ventilation and various hemodynamic parameters were measured as well. The protocol included CPAP application for 5 minutes at each level of 5 and 10 cmH2O. While on CPAP, stroke volume (SV) and CO (cardiac output) decreased whereas multi- unit MSNA, AP frequency and mean burst area/min increased in healthy middle aged subjects. In contrast, CPAP had no effect on hemodynamics, MSNA or AP parameters. A negative linear correlation was observed between sympathetic and hemodynamic responses to CPAP in control group, but the same was not observed for CHF group. Consequently, it can be concluded that the impact of CPAP on central hemodynamics in healthy individuals elicited a moderate activation of sympathetic neurons through increased AP firing frequency, whereas in CHF patients both hemodynamics and MSNA remained unaltered. |