Restoration Of Heart Rate Research Articles

Transcranial magnetic stimulation in the assessment of acupuncture effect on exercise-induced fatigue.

Acupuncture as a traditional Chinese medicine therapy relies on unique theories to alleviate fatigue. The aim of this study is to evaluate the effect of acupuncture on exercise-induced fatigue utilizing transcranial magnetic stimulation (TMS). A total of 20 participants with regular exercise habits were recruited for this study. All participants were randomly assigned to receive either acupuncture or sham acupuncture intervention for exercise-induced fatigue. TMS and a heart rate monitor were used to measure the amplitude and latency of motor evoked potential (MEP) as well as heart rate every 5min over a 30-min period. The blood lactic acid (BLA) levels were measured using Lactate Scout+ at baseline, 0min, and 30min after fatigue. Two-way repeated measures analysis of variance was utilized to compare the differences between the effects of acupuncture method and time. Bonferroni post hoc tests were conducted to compare specific differences. Statistical significance was set at p<.05. Interaction effect was observed between acupuncture method and time effect in terms of amplitude (F(1, 38)=5.40, p<.001, η2=0.12) and latency (F(1, 38)=3.78, p=.008, η2=.09) of MEP. The application of acupuncture can promote the recovery of heart rate especially at 30min (p<.05), but which seem insufficient to generate significant difference in BLA (F(1, 38)=0.067, p=.797, η2=0.002). Acupuncture can promote the increase of MEP amplitude, shorten MEP latency, and restore heart rate. Preliminary findings provide novel insights for individuals with exercise habits to alleviate fatigue and enhance sports performance.

2,4'-Dihydroxybenzophenone: A Promising Anti-Inflammatory Agent Targeting Toll-like Receptor 4/Myeloid Differentiation Factor 2-Mediated Mitochondrial Reactive Oxygen Species Production during Lipopolysaccharide-Induced Systemic Inflammation.

The biochemical properties of 2,4'-dihydroxybenzophenone (DHP) have not been extensively studied. Therefore, this study aimed to investigate whether DHP could alleviate inflammatory responses induced by lipopolysaccharide (LPS) and endotoxemia. The results indicated that DHP effectively reduced mortality and morphological abnormalities, restored heart rate, and mitigated macrophage and neutrophil recruitment to inflammatory sites in LPS-microinjected zebrafish larvae. Additionally, the expression of pro-inflammatory mediators, including inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), and interleukin-12 (IL-12), was significantly reduced in the presence of DHP. In RAW 264.7 macrophages, DHP inhibited the LPS-induced inflammatory response by downregulating pro-inflammatory mediators and decreasing the expression of myeloid differentiation primary response 88 (MyD88), phosphorylation of IL-1 receptor-associated protein kinase-4 (p-IRAK4), and nuclear factor-κB (NF-κB). Molecular docking analysis demonstrated that DHP occupies the hydrophobic pocket of myeloid differentiation factor 2 (MD2) and blocks the dimerization of Toll-like receptor 4 (TLR4). A molecular dynamics simulation confirmed that DHP stably bound to the hydrophobic pocket of MD2. Furthermore, the DHP treatment inhibited mitochondrial reactive oxygen species (mtROS) production during the LPS-induced inflammatory response in both RAW 264.7 macrophages and zebrafish larvae, which was accompanied by stabilizing mitochondrial membrane potential. In conclusion, our study highlights the therapeutic potential of DHP in alleviating LPS-induced inflammation and endotoxemia. The findings suggest that DHP exerts its anti-inflammatory effects by inhibiting the TLR4/MD2 signaling pathway and reducing the level of mtROS production. These results contribute to a better understanding of the biochemical properties of DHP and support its further exploration as a potential therapeutic agent for inflammatory conditions and endotoxemia.

Dynamics of special endurance of athletes aged 13-15 years under the influence of the program of the Cossack duel

Background and Study Aim. National sports are gradually spreading around the world and becoming international. One of such sports is the Cossack duel - a national martial art in Ukraine. In addition to the purely sports component, this sport has national traditions of educating healthy youth. The purpose of the study is to identify the impact of the Cossack duel program on the special endurance of athletes aged 13-15 year.&#x0D; Material and methods. Athletes (n = 6, age - 13-15 years) of the Cossack duel department of the sports school № 6 (Kharkiv, Ukraine) took part in the study. The children's parents agreed to participate in the study. The study was conducted with athletes of the basic training group on the Cossack duel (sports school №6, Kharkiv, Ukraine) for two years. At the beginning, a preliminary test of the level of special endurance of athletes was conducted. In the end, the final testing of the level of special endurance development of young athletes was conducted. SPSS was used to process the test results. The confidence level is 0.05.&#x0D; Results. It is established that for two years of using the author's program the density of shock actions of athletes has increased significantly. This is manifested in an increase in the number of blows to the bag with his hands and feet (p˂0.001). It was found that the load of maximum intensity during one round caused significant changes in the cardiovascular system. These indicators were almost indistinguishable (0.7%). The process of restoring heart rate has become more advanced. After 60 sec. recovery difference was 13.2%, and after 120 sec. - 16.1%.&#x0D; Conclusions. One of the main factors in the training of athletes in the Cossack duel is special endurance. Among the effective methods of improving special endurance are interval and interval-circle training methods. To control the development of special endurance of athletes, it is advisable to use a 1.5 - minute test with the performance of shock actions with hands and feet on a punching bag. Criteria for assessing special endurance should be the intensity of the kicks, heart rate. It is necessary to remember the harmonious upbringing of the individual, to apply health-preserving technologies, to pay great attention to the upbringing of young people in the spirit of respect for national traditions.

Can Restoration of Heart Rate in ESRD Lower Brain Natriuretic Peptide?

Can Restoration of Heart Rate in ESRD Lower Brain Natriuretic Peptide?

Стан серцево-судинної системи кваліфікованих спортсменок з настільного тенісу на етапі змагальної діяльності

The condition of the cardiovascular system is one of the important criteria for assessing the impact of sports training on the human body. According to the indicators characterizing the state of the cardiovascular system, it is possible to trace the changes associated with fluctuations in the level of training, as well as to identify signs of overload as early as possible. The study of adaptive reactions of the cardiovascular system in athletes under physical activity is an important indicator for sports practice. The purpose of the study was to investigate the quantitative criteria for assessing the state of the cardiovascular system and approaches to correct the functional state of qualified athletes specializing in table tennis. Materials and methods. Studies of heart rate variability, quantitative and qualitative indicators that sufficiently reflect the autonomic functions of the body were used in order to assess the state of autonomic regulation in highly qualified athletes. Systematic physical activity causes a significant restructuring of the cardiovascular system and leads to morphofunctional changes in the mechanisms of the heart. Depending on the autonomic regulation of heart rhythm, there are different ways of myocardial adaptation processes. The balance of sympathetic and parasympathetic links of autonomic rhythm regulation is reflected in the activation of the left ventricle. Results and discussion. Adaptive changes of the cardiovascular system to competitive and training loads in the competitive period in qualified athletes are characterized by a significant decrease in heart rate (from 84.75±1.74 beats / min to 74.8±0.38 beats / min). In addition, a significantly faster process of restoring heart rate was established after exercise in the group of qualified athletes, compared with athletes of the category 1 at 4 (p &gt;0.05) and 5 (p &gt;0.05) minutes, respectively. According to the indicators of autonomic regulation of heart rhythm, activation of the parasympathetic link prevails in athletes of the category 1 in comparison with qualified athletes activation (according to high-frequency component, p &lt;0.05). Significantly higher rates of individual parts of the body compared to low-skilled athletes were found out: the hormonal system (the indicator responsible for the hormonal part of the body – very low-frequency component) and the nervous system (indicators of the sympathetic nervous system – low frequency component). There are significantly higher values of the magnitude of the heart rate spectrum and high-frequency component at p &lt;0.05, which indicates a higher power of all units of the parasympathetic regulation in the category 1 in relation to masters of sports and candidates masters of sports. Conclusion. Systematic physical activity causes a significant restructuring of the cardiovascular system and leads to morphofunctional changes in the mechanisms of the heart. Depending on the autonomic regulation of heart rhythm, there are different ways of myocardial adaptation processes. The balance of sympathetic and parasympathetic links of autonomic rhythm regulation is reflected in the activation of the left ventricle. The analysis showed that the spectral characteristics of heart rate variability significantly differ between groups of athletes with different dominance that are observed only in terms of high-frequency component, which in turn led to a change in the sympathetic-vagal balance

Effect of ATP and molsidomine combination on contractile function of isolated adult and old rat hearts during adequate coronary perfusion, at ischemia and reperfusion

Abstract. Pathology of the cardiovascular system occupies a major place in the structure of diseases of the elderly and old patients. Metabolic disturbances are very important in ischemic damages of myocardium in the elderly and old people. So, drugі with metabolic mechanism of action is very ppromising in the treatment of elderly patients with cardiovascular diseases. The relevance of this study is determined by the feasibility of using drugs of metabolic action, which have a beneficial effect on the metabolism of cardiomyocytes, improve blood supply to the myocardium, increase its contractile function. The effect of ATP-molsidomine combination on myocardial contractility in different age animals was stuiesy in vitro experiments. The experiments on the isolated hearts from adult and old rats have shown that combined use of ATP and molsidomine did not significantly affect the contractility of the isolated hearts of adult rats under different perfusion regimes. In old rats, the use of ATP-molsidomine combination had a positive effect on the contractile function of the myocardium under the influence of damaging factors (ischemia, reperfusion): prevented a decrease of left ventricular developing pressure and its first derivative (velocity of pressure rise and velocity of pressure decline) and accelerated its growth during reperfusion. Co-administration of ATP and molsidomine during ischemia had a positive effect on the heart rhythm and restored heart rate at the reperfusion period in adult and old rats. The results of the study indicate a positive effect of the ATP-molsidomine combination on the myocardial contractility in old rats. Combined use of ATP and molsidomine exerted a favourable influence on the heart rhythm under damaging factors both in the adult and old animals. Key words: ATP; molsidomine; isolated rat heart; myocardial contractility; ageing

Erythrocyte transfusion restored heart rate variability in children with thalassemia major

Thalassemia major (TM) is a severe transfusion-dependent anemia. Regular erytrocyte transfusion is required for the treatment of thalassemia patients. However, repeated transfusion may result in impairements in heart function. In this study, we aimed to investigate short-term effects of erythrocyte transfusion on autonomic control of heart in children with thalassemia major. For that purpose heart rate variability (HRV), which is a non-invasive method used to evaluate the effects of the autonomic nervous system on the heart rhythym, was measured before and after erythrocyte transfusion and compared to the healthy controls. Children diagnosed with TM (n = 17) and sex and age matched healthy children (HC, n = 30) were included in the study. HRV values of TM patients were measured 5 min before erythrocyte transfusion (BET, n = 17) and 5 min after erythrocyte transfusion (AET, n = 17). Parameters of time-domain and frequency-domain of HRV were evaluated in all participants. Heart rate (HR) was higher in the BET than AET (P = 0.002) but there was no difference between AET and HC groups (P > 0.05). HRV parameters were lower in BET than AET (P < 0.05) but there were no statistical difference between AET and HC (P> 0.05). The data suggest that, in thalassemia major patients, erythrocyte transfusion restores HR and HRV parameters to the levels observed in healthy controls and, thus, in short-terms, appears to be beneficial for the autonomic control of the heart.

PEMULIHAN SUHU TUBUH DAN DENYUT JANTUNG DENGAN METODE SPORT MASSAGE DAN STRETCHING STATIS SETELAH BERENANG

The aim of this study was to discover the difference in effectiveness between sports massage, stretching, and conventional recovery in healing body temperature and heart rate after swimming based on the gender of the child. This study used an experimental method with a 2x3 factorial design involving independent variables in the form of the effectiveness of conventional sports massage, stretching, and recovery, and the dependent variables in the form of body temperature and heart rate. We were found that the stretching technique was more effective in restoring body temperature. Meanwhile, conventional massage and recovery techniques are more effective in restoring heart rate. During the Covid-19 pandemic, trainees needed a faster recovery using sports massage and/or conventional recovery methods, to speed up recovery from fatigue and accelerate fitness improvement.

Differential effects of bicarbonate on severe hypoxia- and hypercapnia-induced cardiac malfunctions in diverse fish species.

We tested in six fish species [Pacific lamprey (Lampetra richardsoni), Pacific spiny dogfish (Squalus suckleyi), Asian swamp eel (Monopterus albus), white sturgeon (Acipenser transmontanus), zebrafish (Danio rerio), and starry flounder (Platichthys stellatus)] the hypothesis that elevated extracellular [HCO3-] protects spontaneous heart rate and cardiac force development from the known impairments that severe hypoxia and hypercapnic acidosis can induce. Hearts were exposed in vitro to either severe hypoxia (~ 3% of air saturation), or severe hypercapnic acidosis (either 7.5% CO2 or 15% CO2), which reduced heart rate (in six test species) and net force development (in three test species). During hypoxia, heart rate was restored by [HCO3-] in a dose-dependent fashion in lamprey, dogfish and eel (EC50 = 5, 25 and 30mM, respectively), but not in sturgeon, zebrafish or flounder. During hypercapnia, elevated [HCO3-] completely restored heart rate in dogfish, eel and sturgeon (EC50 = 5, 25 and 30mM, respectively), had a partial effect in lamprey and zebrafish, and had no effect in flounder. Elevated [HCO3-], however, had no significant effect on net force of electrically paced ventricular strips from dogfish, eel and flounder during hypoxia and hypercapnia. Only in lamprey hearts did a specific soluble adenylyl cyclase (sAC) inhibitor, KH7, block the HCO3--mediated rescue of heart rate during both hypoxia and hypercapnia, and wasthe only species where we conclusively demonstrated sAC activity was involved in the protective effects of HCO3- on cardiac function. Our results suggest a common HCO3--dependent, sAC-dependent transduction pathway for heart rate recovery exists in cyclostomes and a HCO3--dependent, sAC-independent pathway exists in other fish species.

Piperlonguminine a new mitochondrial aldehyde dehydrogenase activator protects the heart from ischemia/reperfusion injury

BackgroundDetoxification of aldehydes by aldehyde dehydrogenases (ALDHs) is crucial to maintain cell function. In cardiovascular diseases, reactive oxygen species generated during ischemia/reperfusion events trigger lipoperoxidation, promoting cell accumulation of highly toxic lipid aldehydes compromising cardiac function. In this context, activation of ALDH2, may contribute to preservation of cell integrity by diminishing aldehydes content more efficiently. MethodsThe theoretic interaction of piperlonguminine (PPLG) with ALDH2 was evaluated by docking analysis. Recombinant human ALDH2 was used to evaluate the effects of PPLG on the kinetics of the enzyme. The effects of PPLG were further investigated in a myocardial infarction model in rats, evaluating ALDHs activity, antioxidant enzymes, oxidative stress markers and mitochondrial function. ResultsPPLG increased the activity of recombinant human ALDH2 and protected the enzyme from inactivation by lipid aldehydes. Additionally, administration of this drug prevented the damage induced by ischemia/reperfusion in rats, restoring heart rate and blood pressure, which correlated with protection of ALDHs activity in the tissue, a lower content of lipid aldehydes, and the preservation of mitochondrial function. ConclusionActivation of ALDH2 by piperlonguminine ameliorates cell damage generated in heart ischemia/reperfusion events, by decreasing lipid aldehydes concentration promoting cardioprotection.

N-acetylcysteine Restored Heart Rate Variability and Prevented Serious Adverse Events in Transfusion-dependent Thalassemia Patients: a Double-blind Single Center Randomized Controlled Trial.

Regular blood transfusions in transfusion-dependent thalassemia (TDT) patients can lead to iron overload, causing oxidative stress and sympathovagal imbalance, resulting in increased cardiac complications. We hypothesized that administrating of N-acetylcysteine (NAC) prevents serious adverse events including cardiac complications in TDT patients by reducing systemic oxidative stress and balancing cardiac sympathovagal control. This study was double-blind, randomized control trial, investigating in 59 Thai TDT patients. After randomization, the participants were divided into two groups. The control group received standard care of TDT patient plus placebo, whereas the intervention group received 600 mg of NAC orally for six months. Serum 8-isoprostane, TNF-alpha, IL-10, 24-hour ECG monitoring, echocardiograms and the incidence of thalassemia-related complications were collected. At baseline, no significant difference in any parameters between the control and the intervention groups. At the end of intervention, the incidence of serious adverse events (i.e. infection, worsening thalassemia) was significantly higher in the control group when compared with the intervention group (24.1% vs. 3.3%, p=0.019) (Chi-square test; absolute risk reduction=20.8%, number needed to treat=4.8). The control group also had significantly lower time-dependent HRV parameters, compared with the intervention group (p=0.025 and 0.030, independent t-test). Treatment with NAC restored HRV and reduced serious adverse event in TDT patients, however, no difference in cardiac complications could be demonstrated. NAC could prevent serious adverse events in TDT patients. The proposed mechanism might be the balancing of sympathovagal control.

Clinical evidence-guided network pharmacology analysis reveals a critical contribution of \u03b21-adrenoreceptor upregulation to bradycardia alleviation by Shenxian-Shengmai

BackgroundShenxian-Shengmai (SXSM) Oral Liquid is a CFDA-approved patent Chinese Herbal medicine, which has been clinically used for the treatment of bradycardia. However, its active components and action mechanism remain to be established. The present study aimed to evaluate the efficacy of SXSM on bradycardia and to identify the possible active components and their pharmacological targets for this action.MethodsA literature-based meta-analysis was performed to evaluate the clinical efficacy of SXSM on bradycardia, which was confirmed by a rat ex vivo cardiac model. Network pharmacology analysis was then conducted to reveal the potential targets of SXSM active components and their anti-arrhythmia mechanisms. Finally, the identified drug-target interaction was confirmed by immunofluorescence assay in cardiomyocyte.ResultsMeta-analysis of the available clinical study data shows that Shenxian-Shengmai Oral Liquid has a favorable effect for bradycardia. In an ex vivo bradycardia model of rat heart, SXSM restored heart rate by affecting Heart rate variability (HRV) which is associated with autonomic nervous system activity. A drug-target-pathway network analysis connecting SXSM components with arrhythmia suggested that a prominent anti-arrhythmia mechanisms of SXSM was via β1-adrenergic signaling pathway, which was subsequently validated by immunofluorescence assay showing that SXSM indeed increased the expression of ADRB1 in cultured cardiomyocytes.ConclusionBy combining approaches of clinical evidence mining, experimental model confirmation, network pharmacology analyses and molecular mechanistic validation, we show that SXSM is an effective treatment for bradycardia and it involves multiple component interacting via multiple pathways, among which is the critical β1-adrenergic receptor upregulation. Our integrative approach could be applied to other multi-component traditional Chinese medicine investigation where ample clinical data are accumulated but advanced mechanistic studies are lacking.

Responses of Aquatic Organisms to Cyanobacteria and Elodea in Microcosms.

The aim of the present study is investigation of the impact of mass development of cyanobacteria and Elodea on population characteristics (abundance, biomass, fecundity) and "health" parameters (the state of embryos, heart rate, and thermal resistance) of aquatic invertebrates in experiments with controlled conditions. In July-August 2018, in four variants of microcosms, the conditions were modeled characteristic of the coastal zone of the Rybinsk Reservoir in the period of mass development of cyanobacteria. Mass species were placed in microcosms of planktonic (with domination (80%) Daphnia longispina) and bottom animals (Unio pictorum, Gmelinoides fasciatus, Asellus aquaticus), as well as Elodea canadensis. In the variants with cyanobacteria, the toxic microcystins LR were revealed (24-53% of the sum of toxins, or from 6.6-66.5 μg/L). The presence of cyanobacteria (Aphanizomenon flos-aquae, Microcystis aeruginosa, and Gloeoitrichia spp.) influenced structural parameters of plankton: the quantity to green algae decreased, small-sized crustaceans increased. Influence of cyanobacteria caused reliable changes in parameters of aquatic animal from those of the control: thermal resitance of mollusks and amphipods decreased, time of restoration of heart rate after loads (salinity test) in mollusks increased; in amphipods, individual fecundity decreased, frequency of abnormalities and of mortality of embryos increased. The presence of Elodea intensified these effects. Thus, mass development of cyanobacteria and Elodea influences ecological-physiological parameters of aquatic animals, decreasing their adaptivity to natural stresses and deteriorating the quality of the progeny.

CARDIOVASCULAR SYSTEM REACTIVITY TO PHYSICAL ACTIVITY DEPENDENCE ON THE CORTISOL SALIVARY CONTENT AT CHILDREN

Aim of the study - to estimate the indicators of the central haemodynamics of children of the first class in Gorno-Altaysk when conducting one-stage functional Martinet - Kushelevsky’s test depending on the level of salivary cortisol. Material and methods. An object of the research was the students of the first class of schools No. 7, 8 and 12 of Gorno-Altaysk (78 children, including 33 boys and 45 girls in the age of 7-8 years). Content of salivary cortisol and indicators of the central haemodynamics were determined when performing one-stage functional Martinet - Kushelevsky’s test (heart rate, arterial blood pressure, systolic and minute blood volume). The type of cardiovascular system reaction, the reaction quality indicator and blood circulation efficiency were defined on the basis of restoration dynamics of heart rate and arterial pressure. Correlation analysis of cardiovascular system indicators and level of salivary cortisol was carried out. Results and discussion. Cortisol level at the examined children didn’t go beyond reference values. The normotonical type of cardiovascular system reaction to physical activity was noted at 54 % of children (42 of 78), atypical types of reaction were revealed at the others: asthenic at 38 % (30 of 78), dystonic at 6 % (5 of 78) and step-type at 1 % (1 of 78). The indicator values of reaction quality of examined children demonstrate that cardiovascular system adaptation to physical activity at children is carried out due to insignificant increase in pulse pressure and excessive increase in heart rate. The performance indicator of low circulation values are caused by significant increase in heart rate in relation to the systolic pressure (the rate of circulation value is lower than optimum level at 61 % of children). Restoration of heart rate after loading at the examined children took place for the 3rd minute however the mode of this indicator restoration is of decremental character being a sign of cardiovascular system unstable condition. The positive correlation of average degree between the salivary cortisol level and HR indicators of both after physical activity and during restoration is revealed ( p < 0,05). Therefore, the cardiovascular system of children with rather high rates of free cortisol in saliva is notable for the bigger reactivity to physical activity. Conclusion. The atypical type of cardiovascular systems reaction to standard physical activity and the decremental nature of HR restoration is revealed at 46 % examined children of the first class of general education institutions No. 7, 8 and 12 of Gorno-Altaysk. The significant increase in HR after physical activity is revealed at children with higher level of salivary cortisol.

Translational medicine. Improving cardiac rhythm with a biological pacemaker.

Heart muscle cells in a large animal model are reprogrammed to restore heart rate and function

Heart rate variability during exertional heat stress: effects of heat production and treatment

We assessed the efficacy of different treatments (i.e., treatment with ice water immersion vs. natural recovery) and the effect of exercise intensities (i.e., low vs. high) for restoring heart rate variability (HRV) indices during recovery from exertional heat stress (EHS). Nine healthy adults (26 ± 3 years, 174.2 ± 3.8 cm, 74.6 ± 4.3 kg, 17.9 ± 2.8 % body fat, 57 ± 2 mL·kg·(-1) min(-1) peak oxygen uptake) completed four EHS sessions incorporating either walking (4.0-4.5 km·h(-1), 2 % incline) or jogging (~7.0 km·h(-1), 2 % incline) on a treadmill in a hot-dry environment (40 °C, 20-30 % relative humidity) while wearing a non-permeable rain poncho for a slow or fast rate of rectal temperature (T re) increase, respectively. Upon reaching a T re of 39.5 °C, participants recovered until T re returned to 38 °C either passively or with whole-body immersion in 2 °C water. A comprehensive panel of 93 HRV measures were computed from the time, frequency, time-frequency, scale-invariant, entropy and non-linear domains. Exertional heat stress significantly affected 60/93 HRV measures analysed. Analyses during recovery demonstrated that there were no significant differences between HRV measures that had been influenced by EHS at the end of passive recovery vs. whole-body cooling treatment (p > 0.05). Nevertheless, the cooling treatment required statistically significantly less time to reduce T re (p < 0.001). While EHS has a marked effect on autonomic nervous system modulation and whole-body immersion in 2 °C water results in faster cooling, there were no observed differences in restoration of autonomic heart rate modulation as measured by HRV indices with whole-body cold-water immersion compared to passive recovery in thermoneutral conditions.

GABA‐A receptor inhibition reverses autoresuscitation defects in serotonin (5‐HT)‐deficient Pet‐1−/− mice

Autoresuscitation is compromised in serotonin (5‐HT)‐deficient Pet‐1−/− mice during a critical developmental period (P7‐10). We hypothesized that the autoresuscitation defects of Pet‐1−/− mice can be restored by antagonizing GABAA receptors. We gave an intracerebroventricular injection of either gabazine (2 uL of 20uM) or saline to Pet‐1−/− pups (n=5 and 7, respectively) and wild‐type littermates (WT; n=14 and 7) at P8. We tested autoresuscitation over 10 asphyxic episodes. We determined survival, delay to gasping, and time required for the recovery of heart rate and normal breathing. ~60% of WT animals survived all 10 episodes, while no Pet‐1−/− animals survived beyond 4 episodes (median=2). Lower survival in Pet‐1−/− was associated with a 7‐fold increase in the delay to the first gasp and a 3‐fold increase in the time required to restore heart rate upon return to room air. Gabazine completely reversed the autoresuscitation defects of Pet‐1−/− mice (P&lt;0.001 for gasp delay and cardio‐respiratory recovery). The median number of asphyxic episodes survived by gabazine‐treated Pet‐1−/− mice was 4, with 2 of 5 surviving to the 8th episode. Based on these data we suggest that pharmacological inhibition of the GABA system could help reduce SIDS in infants that can be identified as being 5‐HT deficient.This research was supported by a Parker B. Francis Fellowship (KJC) and NIH grant HL28066, (PI, E. E. Nattie)

Failed heart rate recovery at a critical age in 5-HT-deficient mice exposed to episodic anoxia: implications for SIDS

Mice deficient in the transcription factor Pet-1⁻/⁻ have a ∼70% deficiency of brainstem serotonin [5-hydroxytryptamine (5-HT)] neurons and exhibit spontaneous bradycardias in room air at postnatal day (P)5 and P12 and delayed gasping in response to a single episode of anoxia at P4.5 and P9.5 (Cummings KJ, Li A, Deneris ES, Nattie EE. Am J Physiol Regul Integr Comp Physiol 298: R1333-R1342, 2010; and Erickson JT, Sposato BC. J Appl Physiol 106: 1785-1792, 2009). We hypothesized that at a critical age Pet-1⁻/⁻ mice will fail to autoresuscitate during episodic anoxia, ultimately dying from a failure of gasping to restore heart rate (HR). We exposed P5, P8, and P12 Pet-1⁻/⁻ mice and wild-type littermates (WT) to four 30-s episodes of anoxia (97% N₂-3% CO₂), separated by 5 min of room air. We observed excess mortality in Pet-1⁻/⁻ only at P8: 43% of Pet-1⁻/⁻ animals survived past the third episode of anoxia while ∼95% of WT survived all four episodes (P = 0.004). No deaths occurred at P5 and at P12, and one of six Pet-1⁻/⁻ mice died after the fourth episode, while all WT animals survived. At P8, dying Pet-1⁻/⁻ animals had delayed gasping, recovery of HR, and eupnea after the first two episodes of anoxia (P < 0.001 for each); death ultimately occurred when gasping failed to restore HR. Both high- and low-frequency components of HR variability were abnormally elevated in dying Pet-1⁻/⁻ animals following the first episode of anoxia. Dying P8 Pet-1⁻/⁻ animals had significantly fewer 5-HT neurons in the raphe magnus than surviving animals (P < 0.001). Our data indicate a critical developmental window at which a brainstem 5-HT deficiency increases the risk of death during episodes of anoxia. They may apply to the sudden infant death syndrome, which occurs at a critical age and is associated with 5-HT deficiency.

Benefit of nanocarrier of magnetic magnesium in rat malathion-induced toxicity and cardiac failure using non-invasive monitoring of electrocardiogram and blood pressure

Medical management in acute organophosphate (OP) poisoning is not always successful because of tissue hypoxia which results in a reduction of heart contractility and cell damage. This study reports improvement of malathion (MAL)-induced cardiac failure by a nanocarrier of magnetic isotope of Mg (PMC16). A rat model of acute MAL poisoning was set up. PMC16 nanoparticle at doses of 0.05, 0.1, 0.2 LD50 = 896 mg/kg) were administered intravenously (iv) 30 minutes after a single intraperitoneal (ip) injection of MAL (0.25 LD50= 207 mg/kg). Atropine (AT; 40 mg/kg, ip) plus pralidoxime (PAM; 40 mg/kg, ip) and magnesium sulfate (MgSO₄; 600 mg/kg, iv) were used as standard therapy or controls. Anesthetized animals were monitored for heart rate, electrocardiogram, blood pressure, and blood oxidative stress biomarkers like cellular lipid peroxidation, total thiol molecules, antioxidant power, gamma glutamil transpeptidase, and acetylcholinesterase (AChE) as a marker of OP toxicity. Results indicated that after MAL administration, heart rate and BP decreased and R-R duration increased. PMC16 markedly restored BP at all doses as compared with MgSO₄. PMC16 at the dose of 0.05 LD50 significantly increased BP in comparison to AT + PAM. PMC16 restored heart rate at dose of 0.2 LD50 and reduced lipid peroxidation at dose of 0.05 LD50 as compared to MgSO₄. PMC16 also improved total antioxidant power at all doses when compared to AT + PAM and reduced GGT activity at dose of 0.2 LD50 but did not affect total thiol molecules. MgSO₄ could improve MAL-induced reduction of total antioxidant power. After 24 h, PMC16 significantly improved MAL-suppressed AChE activity at doses of 0.05 and 0.1 LD50. PMC16 at all doses significantly recovered MAL-induced arrhythmia when compared to standard therapies. It is concluded that PMC16 is able to control OP-induced cardiac failure and toxicity.

Influence of Rehydration Mode Following Exercise Dehydration on Blood Pressure and Heart Rate Restoration

Rehydration (REHY) is widely used by athletes to recover from exercise. The ideal method of REHY following exercise dehydration (EXDE) to facilitate physiologic return to baseline is unknown. PURPOSE: To examine the efficacy of the most common modes of REHY on cardiovascular and fluid perturbations following EXDE. METHODS: Twelve non-heat-acclimatized trained subjects (23±4y, 81.3±3.7kg, 180±6cm, 56.9±4.4mL.min-1.kg-1, 7.8±3.0 % body fat) completed 20-h fluid restriction and 2-h EXDE (cycling and walking) to -4% body mass loss followed by REHY to -2% body mass loss in a randomized, cross-over design. REHY methods included no fluid (NF), ad libitum (AL), metered oral (OR), intravenous (IV), and a combination of IV and OR (IV+OR) of ½-normal saline (0.45% NaCl). REHY occurred for 30min and subjects were subsequently observed during recovery for 30 more min (total of 60min). Seated and standing blood pressure (BP) were measured and mean arterial pressure (MAP) calculated every 15min throughout REHY. Heart rate (HR), plasma [AVP], and thirst perception were recorded throughout REHY. RESULTS: Subjects reached -4.32 ± 0.22% body mass following EXDE and then were REHY to -2.13 ± 0.47% body mass for controlled trials. Seated systolic BP more closely approximated resting BP for IV+OR compared to OR (p=.015). Subjects showed, independent of time, greater seated systolic BP and MAP during REHY with IV+OR over OR (p≤.011). Upon standing, IV+OR demonstrated greater BP than NF (p=.012) and OR (p=.031). Drop in systolic BP from seated to standing significantly diminished over time in all trials (p≤.036), without trial differences (p>.05). IV and IV+OR effectively reduced HR more than NF at REHY30 and REHY60 (p<.05). Subjects demonstrated superior decreases in plasma [AVP] with IV+OR versus NF at REHY 60 (.003) and showed a strong trend for a decrease compared to OR at REHY 60 (.054). AL thirst was less than all other trials at REHY15 (p=.043). All trials except IV were decreased in thirst compared to NF from REHY30 through REHY60 (p≤.049). CONCLUSION: BP and plasma [AVP] approximated resting values faster with IV+OR REHY compared to other trials. Components of cardiovascular physiology returned to baseline most efficiently with combined IV+OR REHY rather than a single method following EXDE.