Role of Cerebral Blood Flow in Extreme Breath Holding

The role of cerebral blood flow (CBF) on a maximal breath-hold (BH) in ultra-elite divers was examined. Divers (n = 7) performed one control BH, and one BH following oral administration of the non-selective cyclooxygenase inhibitor indomethacin (1.2 mg/kg). Arterial blood gases and CBF were measured prior to (baseline), and at BH termination. Compared to control, indomethacin reduced baseline CBF and cerebral delivery of oxygen (CDO(2)) by about 26% (p < 0.01). Indomethacin reduced maximal BH time from 339 ± 51 to 319 ± 57 seconds (p = 0.04). In both conditions, the CDO(2) remained unchanged from baseline to the termination of apnea. At BH termination, arterial oxygen tension was higher following oral administration of indomethacin compared to control (4.05 ± 0.45 vs. 3.44 ± 0.32 kPa). The absolute increase in CBF from baseline to the termination of apnea was lower with indomethacin (p = 0.01). These findings indicate that the impact of CBF on maximal BH time is likely attributable to its influence on cerebral H(+) washout, and therefore central chemoreceptive drive to breathe, rather than to CDO(2)

The Central Autonomic Network and Regulation of Bladder Function

The autonomic nervous system (ANS) is involved in the regulation of physiologic and homeostatic parameters relating particularly to the visceral organs and the co-ordination of physiological responses to threat. Blood pressure and heart rate, respiration, pupillomotor reactivity, sexual function, gastrointestinal secretions and motility, and urine storage and micturition are all under a degree of ANS control. Furthermore, there is close integration between the ANS and other neural functions such as emotion and cognition, and thus brain regions that are known to be important for autonomic control are also implicated in emotional functions. In this review we explore the role of the central ANS in the control of the bladder, and the implications of this for bladder dysfunction in diseases of the ANS

Recruitment pattern of muscle sympathetic nerve activity in chronic stable heart failure patients and in healthy control subjects

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

Recruitment pattern of muscle sympathetic nerve activity in chronic stable heart failure patients and in healthy control subjects

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

Recruitment pattern of muscle sympathetic nerve activity in chronic stable heart failure patients and in healthy control subjects

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

High-sugar feeding and increasing cholesterol levels in infants

Hypercholesterolaemia is an important risk factor for cardiovascular disease. Both total and LDL cholesterol levels are three-fold higher at the end of the first year of life and about four-fold higher in adulthood compared with the neonatal period. In the USA, only 25% of infants are exclusively breastfed and simple carbohydrate-rich formulas are preferentially consumed. Spikes in fasting glucose and insulin have been reported in formula-fed infants and are associated with higher levels of proprotein convertase subtilisin/kexin type 9, suggesting a potential link between high simple sugar intake and consequent increase in LDL cholesterol in early childhood

Firing patterns of muscle sympathetic neurons during short-term use of continuous positive airway pressure in healthy subjects and in chronic heart failure patients

The current study tested the hypothesis that modification in central hemodynamics during short-term continuous positive airway pressure (CPAP) application was accompanied by altered firing patterns of sympathetic nerve activity in CHF patients and healthy subjects.Muscle sympathetic nerve activity (MSNA), hemodynamic and ventilatory parameters were obtained from 8 healthy middle aged subjects and 7 CHF patients. Action potentials (APs) were extracted from MSNA neurograms, quantified as AP frequency and classified into different sized clusters. While on CPAP at 10cm H2O, multi-unit MSNA, AP frequency and mean burst area/min increased in healthy middle aged subjects (p\u3c0.05) whereas CPAP had no effect on these variables in CHF patients. In conclusion, 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. © 2013 Elsevier B.V

The Effects of Involuntary Respiratory Contractions on Cerebral Blood Flow during Maximal Apnoea in Trained Divers.

The effects of involuntary respiratory contractions on the cerebral blood flow response to maximal apnoea is presently unclear. We hypothesised that while respiratory contractions may augment left ventricular stroke volume, cardiac output and ultimately cerebral blood flow during the struggle phase, these contractions would simultaneously cause marked 'respiratory' variability in blood flow to the brain. Respiratory, cardiovascular and cerebrovascular parameters were measured in ten trained, male apnoea divers during maximal 'dry' breath holding. Intrathoracic pressure was estimated via oesophageal pressure. Left ventricular stroke volume, cardiac output and mean arterial pressure were monitored using finger photoplethysmography, and cerebral blood flow velocity was obtained using transcranial ultrasound. The increasingly negative inspiratory intrathoracic pressure swings of the struggle phase significantly influenced the rise in left ventricular stroke volume (R (2) = 0.63, P<0.05), thereby contributing to the increase in cerebral blood flow velocity throughout this phase of apnoea. However, these contractions also caused marked respiratory variability in left ventricular stroke volume, cardiac output, mean arterial pressure and cerebral blood flow velocity during the struggle phase (R (2) = 0.99, P<0.05). Interestingly, the magnitude of respiratory variability in cerebral blood flow velocity was inversely correlated with struggle phase duration (R (2) = 0.71, P<0.05). This study confirms the hypothesis that, on the one hand, involuntary respiratory contractions facilitate cerebral haemodynamics during the struggle phase while, on the other, these contractions produce marked respiratory variability in blood flow to the brain. In addition, our findings indicate that such variability in cerebral blood flow negatively impacts on struggle phase duration, and thus impairs breath holding performance