Petra Zubin Maslov
dr. sc. ZUBIN MASLOV PETRA dr. med.
: "ACTIVATION PATTERN OF MUSCLE SYMPATHETIC NERVOUS SYSTEM IN PATIENTS WITH CHRONIC STABLE HEART FAILURE AND HEALTHY CONTROLS"
Doctoral dissertation full text
prof. dr. sc. DUJIĆ ŽELJKO
Qualifying research publications:
Zubin MP, Breskovic T, Shoemaker JK, Olson TP, Johnson BD,
Eterovic D, Dujic Z. Firing patterns of muscle sympathetic neurons during short-term use of continuous positive airway pressure in healthy subjects and in chronic heart failure patients. Respir Physiol Neurobiol 2013;187(2):149-56
IF (JCR 2013) 1.967
Maslov PZ, Breskovic T, Brewer DN, Shoemaker JK, Dujic Z.
Recruitment pattern of sympathetic muscle neurons during premature ventricular contractions in heart failure patients and controls. Am J Physiol Regul Integr Comp Physiol. 2012;303(11):R1157-64
IF (JCR 2012) 3.284
Summary (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
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.
Summary 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 multiunit
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
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