Muammar M. Kabir

Respiratory pattern in awake rats: effects of motor activity and of alerting stimuli.

Our aim was to assess the impact of motor activity and of arousing stimuli on respiratory rate in the awake rats. The study was performed in male adult Sprague-Dawley (SD, n=5) and Hooded Wistar (HW, n=5) rats instrumented for ECG telemetry. Respiratory rate was recorded using whole-body plethysmograph, with a piezoelectric sensor attached for the simultaneous assessment of motor activity. All motor activity was found to be associated with an immediate increase in respiratory rate that remained elevated for the whole duration of movement; this was reflected by: i) bimodal distribution of respiratory intervals (modes for slow peak: 336+/-19 and 532+/-80 ms for HW and SD, p<0.05; modes for fast peak 128+/-6 and 132+/-7 ms for HW and SD, NS); and ii) a tight correlation between total movement time and total time of tachypnoea, with an R(2) ranging 0.96-0.99 (n=10, p<0001). The extent of motor-related tachypnoea was significantly correlated with the intensity of associated movement. Mild alerting stimuli produced stereotyped tachypnoeic responses, without affecting heart rate: tapping the chamber raised respiratory rate from 117+/-7 to 430+/-15 cpm; sudden side move--from 134+/-13 to 487+/-16 cpm, and turning on lights--from 136+/-12 to 507+/-14 cpm (n=10; p<0.01 for all; no inter-strain differences). We conclude that: i) sniffing is an integral part of the generalized arousal response and does not depend on the modality of sensory stimuli; ii) tachypnoea is a sensitive index of arousal; and iii) respiratory rate is tightly correlated with motor activity.

Cardiorespiratory Phase-Coupling Is Reduced in Patients with Obstructive Sleep Apnea

Cardiac and respiratory rhythms reveal transient phases of phase-locking which were proposed to be an important aspect of cardiorespiratory interaction. The aim of this study was to quantify cardio-respiratory phase-locking in obstructive sleep apnea (OSA). We investigated overnight polysomnography data of 248 subjects with suspected OSA. Cardiorespiratory phase-coupling was computed from the R-R intervals of body surface ECG and respiratory rate, calculated from abdominal and thoracic sensors, using Hilbert transform. A significant reduction in phase-coupling was observed in patients with severe OSA compared to patients with no or mild OSA. Cardiorespiratory phase-coupling was also associated with sleep stages and was significantly reduced during rapid-eye-movement (REM) sleep compared to slow-wave (SW) sleep. There was, however, no effect of age and BMI on phase coupling. Our study suggests that the assessment of cardiorespiratory phase coupling may be used as an ECG based screening tool for determining the severity of OSA.

Global Electric Heterogeneity Risk Score for Prediction of Sudden Cardiac Death in the General Population: The Atherosclerosis Risk in Communities (ARIC) and Cardiovascular Health (CHS) Studies.

Background— Asymptomatic individuals account for the majority of sudden cardiac deaths (SCDs). Development of effective, low-cost, and noninvasive SCD risk stratification tools is necessary. Methods and Results— Participants from the Atherosclerosis Risk in Communities study and Cardiovascular Health Study (n=20 177; age, 59.3±10.1 years; age range, 44–100 years; 56% female; 77% white) were followed up for 14.0 years (median). Five ECG markers of global electric heterogeneity (GEH; sum absolute QRST integral, spatial QRST angle, spatial ventricular gradient [SVG] magnitude, SVG elevation, and SVG azimuth) were measured on standard 12-lead ECGs. Cox proportional hazards and competing risks models evaluated associations between GEH electrocardiographic parameters and SCD. An SCD competing risks score was derived from demographics, comorbidities, and GEH parameters. SCD incidence was 1.86 per 1000 person-years. After multivariable adjustment, baseline GEH parameters and large increases in GEH parameters over time were independently associated with SCD. Final SCD risk scores included age, sex, race, diabetes mellitus, hypertension, coronary heart disease, stroke, and GEH parameters as continuous variables. When GEH parameters were added to clinical/demographic factors, the C statistic increased from 0.777 to 0.790 (P=0.008), the risk score classified 10-year SCD risk as high (>5%) in 7.2% of participants, 10% of SCD victims were appropriately reclassified into a high-risk category, and only 1.4% of SCD victims were inappropriately reclassified from high to intermediate risk. The net reclassification index was 18.3%. Conclusions— Abnormal electrophysiological substrate quantified by GEH parameters is independently associated with SCD in the general population. The addition of GEH parameters to clinical characteristics improves SCD risk prediction.

Altered cardio-respiratory response to spontaneous cortical arousals in children with upper airway obstruction

OBJECTIVE Upper airway obstruction (UAO) during childhood is associated with cardiovascular morbidity. The aim of this study was to investigate the cardio-respiratory response to cortical arousal during sleep in children with UAO. METHODS Standard paediatric overnight polysomnography (PSG) was conducted in 40 children with UAO (25M, 7.5±2.7yrs) prior to and 6 months following adenotonsillectomy. For comparison a control group of 40 normal, sex and age matched children (21M, 7.5±2.6yrs) underwent two PSGs without intervention at the same time points. RESULTS Heart rate and respiratory rate were measured during spontaneous and respiratory arousals in stage 2 and REM sleep 15s prior to and 15s immediately following cortical arousal onset. Cortical arousal was associated with a significant increase in heart and respiratory rate in both groups of children. UAO children, however, showed a significantly higher heart rate response in stage 2 sleep (-17.5±6.0 vs. -14.4±4.8%; p<0.05), a lower pre-arousal baseline respiratory rate (stage 2: 17.1±1.4 vs. 18.2±1.7 BPM; p<0.01) and a prolonged increase in respiratory rate compared to control children. Cardiac and respiratory arousal responses were not significantly different from controls following adenotonsillectomy in the UAO children. CONCLUSIONS UAO in children is associated with an altered cardiorespiratory response to spontaneous arousal from sleep, which may indicate early signs of autonomic dysfunction. Surgical treatment of UAO appears to reverse these outcomes.

Cardiorespiratory response to spontaneous cortical arousals during stage 2 and rapid eye movement sleep in healthy children

Arousal from sleep is associated with transient and abrupt cardiorespiratory changes, and elevated arousals associated with sleep disorders may trigger adverse cardiovascular sequela. In this paper, we provide the first data in children on cardiorespiratory responses to cortical arousal. Heart rate and ventilatory responses to arousal from stage 2 and rapid eye movement (REM) sleep were investigated in 40 normal, healthy Caucasian children (age: 7.7 ± 2.6 years; body mass index z‐score: 0.30 ± 0.8). All children underwent overnight polysomnography studies. Cortical arousals were scored according to standard criteria. Heart rate changes were assessed over 30 s, starting 15 s prior to cortical arousal onset. Breathing rates were quantified three breaths before and after arousal onset. Arousals from stage 2 as well as REM sleep resulted in an R–R interval shortening of about 15%, independent of age and gender. The R–R interval shortening initiated at least 3 s before the cortical arousal onset. The breathing interval immediately after cortical arousal onset was significantly shortened (P < 0.001). In conclusion, cortical arousals in children are associated with an increase in breathing rate and significant heart rate accelerations, which typically precede the cortical arousal onset.

Global Electric Heterogeneity Risk Score for Prediction of Sudden Cardiac Death in the General Population

Background— Asymptomatic individuals account for the majority of sudden cardiac deaths (SCDs). Development of effective, low-cost, and noninvasive SCD risk stratification tools is necessary. Methods and Results— Participants from the Atherosclerosis Risk in Communities study and Cardiovascular Health Study (n=20 177; age, 59.3±10.1 years; age range, 44–100 years; 56% female; 77% white) were followed up for 14.0 years (median). Five ECG markers of global electric heterogeneity (GEH; sum absolute QRST integral, spatial QRST angle, spatial ventricular gradient [SVG] magnitude, SVG elevation, and SVG azimuth) were measured on standard 12-lead ECGs. Cox proportional hazards and competing risks models evaluated associations between GEH electrocardiographic parameters and SCD. An SCD competing risks score was derived from demographics, comorbidities, and GEH parameters. SCD incidence was 1.86 per 1000 person-years. After multivariable adjustment, baseline GEH parameters and large increases in GEH parameters over time were independently associated with SCD. Final SCD risk scores included age, sex, race, diabetes mellitus, hypertension, coronary heart disease, stroke, and GEH parameters as continuous variables. When GEH parameters were added to clinical/demographic factors, the C statistic increased from 0.777 to 0.790 (P=0.008), the risk score classified 10-year SCD risk as high (>5%) in 7.2% of participants, 10% of SCD victims were appropriately reclassified into a high-risk category, and only 1.4% of SCD victims were inappropriately reclassified from high to intermediate risk. The net reclassification index was 18.3%. Conclusions— Abnormal electrophysiological substrate quantified by GEH parameters is independently associated with SCD in the general population. The addition of GEH parameters to clinical characteristics improves SCD risk prediction.

Respiratory timing and variability during sleep in children with sleep-disordered breathing

Sleep-disordered breathing (SDB) in children is assessed by quantification of hypopnea and apnea events. Little is known, however, about respiratory timing and breath-to-breath variability during sleep. The aim of this study was to investigate respiratory parameters across sleep stages in children with SDB before and after treatment compared with healthy children. Overnight polysomnography (PSG) was conducted in 40 children with SDB prior to and 6 mo following adenotonsillectomy. For comparison, a control group of 40 healthy sex- and age-matched children underwent two PSGs at equivalent time points but without intervention. The following variables were measured breath by breath during obstruction-free periods in stage 2 nonrapid eye movement (NREM), stage 4 NREM, and REM sleep: inspiratory time (Ti), expiratory time (Te), total time (Ttotal), inspiratory duty cycle (DC; =Ti/Ttotal), respiratory frequency (fR), and SD of the parameters Ti, Te, fR, and DC. Variability in waveform morphology was also computed using the residue of respiratory patterns. The severity of SDB was relatively mild in the study cohort (obstructive apnea hypopnea index: baseline, 5.1 ± 9.4 vs. 0.1 ± 0.2, P < 0.001; follow-up, 0.3 ± 0.3 vs. 0.8 ± 1.0, P < 0.01). Compared with healthy controls, children with SDB showed significantly longer Ti and Te and a lower fR at the baseline study. These differences were not significant after adenotonsillectomy. Sleep stages were associated with significant differences in all of the respiratory measures in both groups of children. In conclusion, children with relatively mild SDB showed prolonged inspiration and expiration indicative of chronic narrowing of the upper airway. Treatment of SDB normalizes respiratory timing. Documentation of these parameters may aid in both understanding and management of children with SDB.

Electrophysiologic Substrate and Risk of Mortality in Incident Hemodialysis

The single leading cause of mortality on hemodialysis is sudden cardiac death. Whether measures of electrophysiologic substrate independently associate with mortality is unknown. We examined measures of electrophysiologic substrate in a prospective cohort of 571 patients on incident hemodialysis enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease Study. A total of 358 participants completed both baseline 5-minute and 12-lead electrocardiogram recordings on a nondialysis day. Measures of electrophysiologic substrate included ventricular late potentials by the signal-averaged electrocardiogram and spatial mean QRS-T angle measured on the averaged beat recorded within a median of 106 days (interquartile range, 78-151 days) from dialysis initiation. The cohort was 59% men, and 73% were black, with a mean±SD age of 55±13 years. Transthoracic echocardiography revealed a mean±SD ejection fraction of 65.5%±12.0% and a mean±SD left ventricular mass index of 66.6±22.3 g/m2.7 During 864.6 person-years of follow-up, 77 patients died; 35 died from cardiovascular causes, of which 15 were sudden cardiac deaths. By Cox regression analysis, QRS-T angle ≥75° significantly associated with increased risk of cardiovascular mortality (hazard ratio, 2.99; 95% confidence interval, 1.31 to 6.82) and sudden cardiac death (hazard ratio, 4.52; 95% confidence interval, 1.17 to 17.40) after multivariable adjustment for demographic, cardiovascular, and dialysis factors. Abnormal signal-averaged electrocardiogram measures did not associate with mortality. In conclusion, spatial QRS-T angle but not abnormal signal-averaged electrocardiogram significantly associates with cardiovascular mortality and sudden cardiac death independent of traditional risk factors in patients starting hemodialysis.

Joint symbolic dynamics for the assessment of cardiovascular and cardiorespiratory interactions

Beat-to-beat variations in heart period provide information on cardiovascular control and are closely linked to variations in arterial pressure and respiration. Joint symbolic analysis of heart period, systolic arterial pressure and respiration allows for a simple description of their shared short-term dynamics that are governed by cardiac baroreflex control and cardiorespiratory coupling. In this review, we discuss methodology and research applications. Studies suggest that analysis of joint symbolic dynamics provides a powerful tool for identifying physiological and pathophysiological changes in cardiovascular and cardiorespiratory control.

Joint symbolic analyses of heart rate, blood pressure, and respiratory dynamics

INTRODUCTION The dynamics of cardiovascular variables are modulated by respiration. The aim of this study was to assess baroreflex function in normal subjects based on the joint symbolic dynamics of heart rate, blood pressure and respiration. METHODS ECG, continuous blood pressure and respiration were recorded in ten healthy subjects during rest in the supine position and upon standing. Beat-to-beat time series of heart rate, systolic blood pressure and respiratory phase were extracted and transformed into binary symbol sequences. Words of length two that were reflective of baroreflex activity were statistically analysed with respect to the respiratory phase. RESULTS Symbolic analysis showed a significant influence of the respiratory phase on the occurrence of baroreflex patterns. Upon standing, the frequency of baroreflex words increased and the effect of respiration appeared to be reduced. CONCLUSIONS Symbolic dynamics provide a simple representation of cardiovascular dynamics and may be useful for assessing baroreflex function.