Evaluating transient phenomena by wavelet analysis: early recovery to exercise.

Wavelet analysis (WA) provides superior time-frequency decomposition of complex signals than conventional spectral analysis tools. To illustrate its usefulness in assessing transient phenomena, we applied a custom-developed WA algorithm to laser-Doppler (LD) signals of the cutaneous microcirculation measured at glabrous (finger pulp) and nonglabrous (forearm) sites during early recovery after dynamic exercise. This phase, importantly contributing to the establishment of thermal homeostasis after exercise cessation, has not been adequately explored because of its complex, transient form. Using WA, we decomposed the LD signals measured during the baseline and early recovery into power spectra of characteristic frequency intervals corresponding to endothelial nitric oxide (NO)-dependent, neurogenic, myogenic, respiratory, and cardiac physiological influence. Assessment of relative power (RP), defined as the ratio between the median power in the frequency interval and the median power of the total spectrum, revealed that endothelial NO-dependent (5.87 early recovery; 1.53 baseline; P = 0.005; Wilcoxon signed-rank test) and respiratory (0.71 early recovery; 0.40 baseline; P = 0.001) components were significantly increased, and myogenic component (1.35 early recovery; 1.83 baseline; P = 0.02) significantly decreased during early recovery in the finger pulp. In the forearm, only the RP of the endothelial NO-dependent (1.90 early recovery; 0.94 baseline; P = 0.009) component was significantly increased. WA presents an irreplaceable tool for the assessment of transient phenomena. The relative contribution of the physiological mechanisms controlling the microcirculatory response in the early recovery phase appears to differ in glabrous and nonglabrous skin when compared with baseline; moreover, the endothelial NO-dependent influence seems to play an important role.NEW & NOTEWORTHY We address the applicability of wavelet analysis (WA) in evaluating transient phenomena on a model of early recovery to exercise, which is the only exercise-associated phase characterized by a distinct transient shape and as such cannot be assessed using conventional tools. Our WA-based algorithm provided a reliable spectral decomposition of laser-Doppler (LD) signals in early recovery, enabling us to speculate roughly on the mechanisms involved in the regulation of skin microcirculation in this phase.

A Comparison of Faster Insulin Aspart with Standard Insulin Aspart Using Hybrid Automated Insulin Delivery System in Active Children and Adolescents with Type 1 Diabetes: A Randomized Double-Blind Crossover Trial.

Objective: To evaluate the use of faster acting (FIA) and standard insulin aspart (SIA) with hybrid automated insulin delivery (AID) in active youth with type 1 diabetes. Research Design and Methods: In this double-blind multinational randomized crossover trial, 30 children and adolescents with type 1 diabetes (16 females; aged 15.0 ± 1.7 years; baseline HbA1c 7.5% ± 0.9% [58 ± 9.8 mmol/mol]) underwent two unrestricted 4-week periods using hybrid AID with either FIA or SIA in random order. During both interventions, participants were using the hybrid AID (investigational version of MiniMed™ 780G; Medtronic). Participants were encouraged to exercise as frequently as possible, capturing physical activity with an activity monitor. The primary outcome was the percentage of sensor glucose time above range (180 mg/dL [10.0 mmol/L]) measured by continuous glucose monitoring. Results: In an intention-to-treat analysis, mean time above range was 31% ± 15% at baseline, 19% ± 6% during FIA use, and 20% ± 6% during SIA use with no difference between treatments: mean difference = -0.9%; 95% CI: -2.4% to 0.6%; P = 0.23. Similarly, there was no difference in mean time in range (TIR) (78% and 77%) or median time below range (2.5% and 2.8%). Glycemic outcomes during exercise or postprandial periods were comparable for the two treatment arms. No severe hypoglycemia or diabetic ketoacidosis events occurred. Conclusions: FIA was not superior to SIA with hybrid AID system use in physically active children and adolescents with type 1 diabetes. Nonetheless, both insulin formulations enabled high overall TIR and low time above and below ranges, even during and after documented exercise. Trial Registration Clinicaltrials.gov: NCT04853030.

Locomotor-Respiratory Entrainment upon Phonated Compared to Spontaneous Breathing during Submaximal Exercise.

Recently, increased attention to breathing techniques during exercise has addressed the need for more in-depth study of the ergogenic effects of breathing manipulation. The physiological effects of phonation, as a potential breathing tool, have not yet been studied. Thus, the aim of this study was to investigate the respiratory, metabolic and hemodynamic responses of phonated exhalation and its impact on locomotor-respiratory entrainment in young healthy adults during moderate exercise. Twenty-six young, healthy participants were subjected to peak expiratory flow (PEF) measurements and a moderate steady cycling protocol based on three different breathing patterns (BrP): spontaneous breathing (BrP1), phonated breathing pronouncing "h" (BrP2) and phonated breathing pronouncing "ss" (BrP3). The heart rate, arterial blood pressure, oxygen consumption, CO2 production, respiratory rate (RR), tidal volume (VT), respiratory exchange ratio and ventilatory equivalents for both important respiratory gasses (eqO2 and eqCO2) were measured (Cosmed, Italy) simultaneously during a short period of moderate stationary cycling at a predefined cadence. To evaluate the psychological outcomes, the rate of perceived exertion (RPE) was recorded after each cycling protocol. The locomotor-respiratory frequency coupling was calculated at each BrP, and dominant coupling was determined. Phonation gradually decreased the PEF (388 ± 54 L/min at BrP2 and 234 ± 54 L/min at BrP3 compared to 455 ± 42 L/min upon spontaneous breathing) and affected the RR (18.8 ± 5.0 min-1 at BrP2 compared to 22.6 ± 5.5 min-1 at BrP1 and 21.3 ± 7.2 min-1 at BrP3), VT (2.33 ± 0.53 L at BrP2 compared to 1.86 ± 0.46 L at BrP1 and 2.00 ± 0.45 L at BrP3), dominant locomotor-respiratory coupling (1:4 at BrP2 compared to 1:3 at BrP1 and BrP2) and RPE (10.27 ± 2.00 at BrP1 compared to 11.95 ± 1.79 at BrP1 and 11.95 ± 1.01 at BrP3) but not any other respiratory, metabolic or hemodynamic measures of the healthy adults during moderate cycling. The ventilatory efficiency was shown to improve upon dominant locomotor-respiratory coupling, regardless of BrP (eqO2 = 21.8 ± 2.2 and eqCO2 = 24.0 ± 1.9), compared to the other entrainment coupling regimes (25.3 ± 1.9, 27.3 ± 1.7) and no entrainment (24.8 ± 1.5, 26.5 ± 1.3), respectively. No interaction between phonated breathing and entrainment was observed during moderate cycling. We showed, for the first time, that phonation can be used as a simple tool to manipulate expiratory flow. Furthermore, our results indicated that in young healthy adults, entrainment, rather than expiratory resistance, preferentially affected ergogenic enhancement upon moderate stationary cycling. It can only be speculated that phonation would be a good strategy to increase exercise tolerance among COPD patients or to boost the respiratory efficiency of healthy people at higher exercise loads.

Training History, Cardiac Autonomic Recovery from Submaximal Exercise and Associated Performance in Recreational Runners.

This study investigated the effect of prolonged exertion on cardiac parasympathetic (cPS) reorganization and associated aerobic performance in response to repeated short-lasting submaximal exercise bouts (SSE) performed for 7 days following prolonged exertion. In 19 recreational runners, heart rate (HR) and HR variability (HRV) indices (lnRMSSD, lnHF, and lnLF/HF) were monitored pre- and post-submaximal graded cycling performed on consecutive days following a half-marathon (HM) and compared with the baseline, pre-HM values. Additionally, HR recovery (HRR), aerobic performance, and rate of perceived exertion (RPE) were determined. HR, HRV indices, and HRR were tested for correlation with exercise performance. A significant time effect was found in HR, HRR, and HRV indices as well as in aerobic performance and RPE during the study period. Most of the measured parameters differed from their baseline values only on the same day following HM. However, HRR and HR measured in recovery after SSE were additionally affected one day following the half-marathon yet in opposite directions to those recorded on the same day as the HM. Thus, postSSE HR and HRR exhibited a bivariate time response (postSSE HR: 102 ± 14 bpm; p < 0.001; 82 ± 11 bpm; p = 0.007 vs. 88 ± 11 bpm; HRR in 30 s after SSE cessation: 14.9 ± 4.9 bpm; p < 0.001; 30.1 ± 13.3 bpm; p = 0.006 vs. 24.4 ± 10.8 bpm), potentially indicating a cPS dysfunction phase on the same day and cPS rebound phase one day following HM reflected also in consecutive changes in aerobic power. Correlations were found between the changes in measured cardiac indices with respect to baseline and the changes in aerobic performance indices throughout the study period. The effect of exercise history on cPS reorganization is more pronounced in response to SSE than at rest. Accordingly, we conclude that SSE performed repeatedly on a daily basis following prolonged exertion offers a noninvasive tool to evaluate the impact of training history on cPS recovery and associated aerobic power output in recreational athletes.

Cardiac autonomic modulation induced by doxorubicin in a rodent model of colorectal cancer and the influence of fullerenol pretreatment.

The very effective anticancer drug doxorubicin (DOX) is known to have cardiotoxic side effects, which could be accompanied by autonomic modulation. Autonomic disbalance might even be an initiating mechanism underlying DOX-induced cardiotoxicity and can be studied noninvasively by the analysis of heart rate variability (HRV). A number of strategies have been assessed to predict chemotherapy-induced cardiac dysfunction while HRV, a potential detecting tool, has not yet been tested. Thus, we aimed to determine the effect of DOX treatment on HRV in a rat model of colorectal cancer. While pretreatment with fullerenol (Frl) acts protectively on DOX-induced cardiotoxicity, we aimed to test the effect of Frl pretreatment on DOX-induced HRV alterations. After the induction of colorectal cancer, adult male Wistar rats were treated with saline (n = 7), DOX (1.5 mg/kg per week, n = 7) or DOX after pretreatment with Frl (25 mg/kg per week, n = 7) for three weeks (cumulative DOX dose 4.5 mg/kg). One week after treatment rats were anaesthetized, standard ECG was measured and HRV was analyzed in time and frequency domain. During autopsy the intestines and hearts were gathered for biochemical analysis and histopathological examination. DOX treatment significantly decreased parasympathetically mediated high-frequency component (p<0.05) and increased the low-frequency component of HRV (p<0.05), resulting in an increased LF/HF ratio (p<0.05) in cancerous rats. When pretreated with Frl, DOX-induced HRV alterations were prevented: the high-frequency component of HRV increased (p<0.01), the low-frequency decreased (p<0.01), LF/HF ratio decreased consequently (p<0.01) compared to DOX only treatment. In all DOX-treated animals, disbalance of oxidative status in heart tissue and early myocardial lesions were found and were significantly reduced in rats receiving Frl pretreatment. Autonomic modulation accompanied the development of DOX-induced cardiotoxicity in rat model of colorectal cancer and was prevented by Frl pretreatment. Our results demonstrated the positive prognostic power of HRV for the early detection of DOX-induced cardiotoxicity.

The measurement of cutaneous blood flow in healthy volunteers subjected to physical exercise with ultrasound Doppler imaging and laser Doppler flowmetry.

We aimed to evaluate hemodynamic parameters in the cutaneous microcirculation during recovery to graded dynamic exercise performed on a cycloergometer by using two distinctive methods: high-frequency ultrasound Doppler flowmetry (UDF) and laser Doppler fluxmetry (LDF). Regarding UDF, the medium linear blood flow velocity (Vam) was estimated, expressed in absolute units (cm/s) whereas blood flow assessed by LDF was registered in arbitrary perfusion units (PU). We compared the corresponding perfusion values obtained by UDF and LDF, respectively, every 20 s during recovery period to physical exercise. Three types of microvascular blood flow dynamics were recorded: blood flow with an occasional paroxysm, a pulsatile blood flow pattern, and a shunting-type blood flow pattern. In the first type, the reaction time of registration and the direction of changes of UDF and LDF values coincided in 77.7%, exhibiting high correlation (r = 0.77; p≤0.001). In the second type, the direction of changes of UDF and LDF showed 85.0% similarity and a moderate correlation (r = 0.66; p = 0.0015), whereas in the third type, there was also a moderate correlation (r = 0.53, p = 0.0024). Our pilot experiments have shown that UDF could be regarded as a comparable substitutional method to LDF for studying skin microcirculation.

Resting heart rate variability and heart rate recovery after submaximal exercise.

PURPOSE: Aerobic training accelerates Heart Rate Recovery after exercise in healthy subjects and in patients with coronary disease. As shown by pharmacological autonomic blockade, HRR early after exercise is dependent primarily on parasympathetic reactivation. Thus, accelerated HRR early after exercise in endurance-trained athletes may be attributed to augmented parasympathetic reactivation. In the present study, we tested the hypothesis that the HRR early after submaximal exercise is related to the pre-exercise parasympathetic modulation. METHODS: Thirty endurance-trained athletes (20 males, 50 ± 7 years) and thirty control subjects (20 males, 52 ± 6 years) performed a submaximal exercise on a cyclo-ergometer. Pre-exercise resting short-term heart rate variability (HRV) parameters in time and frequency-domains were correlated with HRR during the first 30 s, 1 and 2 min after cessation of exercise. RESULTS: We found that HRR was statistically significantly faster in athletes than in controls at all examination time points (p < 0.05). HF, SDNN and RMSSD were statistically significantly higher in athletes than in controls (p < 0.05), but other resting HRV parameters were not statistically different between groups. After 30 s, 1 and 2 min of recovery, HRR correlation with total power, HF, HFnu and RMSSD was positive, while the correlation with LF/HF was negative for small and positive for larger values. The opposite was true for SDNN. CONCLUSIONS: These findings support the hypothesis that HRR early after submaximal exercise is related to resting parasympathetic modulation in the middle-aged subjects. In addition, they suggested an optimal range of HRV for maximal HRR after exercise.

Alteration of skin laser-Doppler flux response to local cooling in gestational hypertension.

PURPOSE: The pathophysiology of the pregnancy-induced hypertension is still poorly understood, especially with regard to the central autonomic nervous system control and peripheral vascular factors. METHODS: Our study therefore aimed to investigate simultaneously the responses of blood pressure, heart rate, heart rate variability (HRV), and laser-Doppler (LD) flux to local cooling in healthy non-pregnant women (N = 12), in pregnant women with normal pregnancy (N = 16) and in women with gestational hypertension (N = 10). RESULTS: The direct and indirect LD flux responses to local cold exposure were diminished in normotensive pregnant females (Dunnett's test, p < 0.05) when compared to non-pregnant females with normal menstrual cycle, but not in females with pregnancy-induced hypertension. In addition, blood pressure increased and heart rate decreased during cold exposure only in normotensive pregnant females, but not in pregnant hypertensive females (paired t test, p < 0.05). Simultaneously calculated heart rate variability total power of HRV and LF power values typically increased during local cold provocation test in non-pregnant females and in normotensive pregnant females (paired t test, p < 0.05). In hypertensive pregnant females HRV indices remained unchanged. CONCLUSION: Our results indicate that the cardiovascular reactivity adaptation seen in normal pregnancy is absent in gestational hypertension.

Protective effects of fullerenol C60(OH)24 against doxorubicin-induced cardiotoxicity and hepatotoxicity in rats with colorectal cancer.

The effects of fullerenol C60(OH)24 (Frl) at doses of 25, 50, and 100mg/kg/week (for a time-span of 3 weeks) on heart and liver tissue after doxorubicin (Dox)-induced toxicity in rats with colorectal cancer were investigated. In the present study, we used an in vivo Wistar male rat model to explore whether Frl could protect against Dox-induced (1.5mg/kg/week for 3 weeks) chronic cardio- and hepato- toxicity and compared the effect with a well-known antioxidant, vitamin C (100mg/kg/week for 3 weeks). According to macroscopic, microscopic, hematological, biochemical, physiological, pharmacological, and pharmacokinetic results, we confirmed that, at all examined doses, Frl exhibits a protective influence on the heart and liver tissue against chronic toxicity induced by Dox.

Left ventricular end-diastolic pressure-volume relationship in septic rats with open thorax.

To estimate changes in compliance, we evaluated the effects of sepsis on the end-diastolic pressure-volume relationship (EDPVR) in the left ventricle of rats that had undergone an open thorax procedure. Sepsis was induced in male Wistar Hannover rats (n = 7; 240 to 270 g) by intraperitoneal administration of a slurry of cecal contents; control rats (n = 7) were given 5% dextrose only. On the third day after induction of sepsis, left ventricular (LV) pressure and LV dimensions were recorded simultaneously in animals of both groups. Using a micromanometer and ultrasonic crystals, measurements were obtained at baseline and during the increase of afterload. Blood samples were taken for determination of complete blood count, white blood cell differential count, and lactate concentration, and for bacteriologic examination. Septic rats lost weight, and developed changes in body temperature, ascites, and abscesses in the abdominal and thoracic cavities, gram-negative bacteremia, and increase in heart rate. On the third day after induction of sepsis, LV EDPVR decreased, compared with that in the control rats (regression coefficients: control group, 8.41 to 23.95; sepsis group, 3.94 to 7.92). Myocardial compliance in the left ventricle increased on the third day of sepsis in the open-thorax rat model, as evidenced by the downward shift of LV EDPVR in rats with sepsis, compared with controls.

The reversible displacement of the passive diastolic p-V curve in the isolated guinea pig left ventricle.

We studied viscoelastic behaviour of the isolated diastolic guinea pig left ventricle (LV), manifested in changes of the hysteresis loop of the pressure-volume (p-V) diagram, produced by acute volume loading. Specifically, we investigated how the width of the hysteresis depends on the way LV volume loading, and whether changes in the hysteresis width are reversible. Each of 11 LV was instrumented with a catheter for injection and withdrawal of saline, and a micromanometer (Millar, 2F) to measure LV pressure. LV were loaded by the computer controlled injection of saline in 6-8 sequential injection steps of 100 µl each with a pause of 5 s, followed by a similar withdrawal pattern. In protocol A (N=5), a 100 µl higher maximal LV volume (LVVmax) was reached during injection than in the control run, and in protocol B (N=6), the time spent at LVVmax was longer (20 vs. 5 s pause). In both protocols a reproducible displacement of the passive p-V curve during volume unloading was observed, reflected in the increase of the hysteresis width by 23±8 % in protocol A, and 12±3 % in protocol B. Reversible displacement of the passive diastolic p-V curve after large aperiodic volume change suggests participation of reversible phenomena, like extracellular fluid filtration, and may in part provide an answer to the phenomenon of preconditioning.

Non-invasive beat-to-beat determination of changes in the small artery compliance after smoking.

We investigated the response of the small arterial compliance on smoking in 5 occasional smokers before, during and after inhaling the first cigarette in the day. For this purpose we used a non-invasive method based on interpretation of the oscillometric signal from the finger cuff coupled to the signal from photoplethysmograph. This system enables on-line determination of the finger artery compliance as function of transmural pressure (ptm) between 0 and 120 mmHg, where each heart beat is presented by a set of compliance values in the range of the pulse pressure reduced by the cuff pressure. This procedure allowed construction of time course of the arterial compliance. When comparing the compliance value at ptm of 40 mmHg, we found its fluctuations around the steady value during the rest and immediate lowering of the compliance after smoking, accompanied by the increase of blood pressure and heart rate.