Decline In Heart Rate Research Articles

The comparison of therapeutic effects of atropine and pralidoxime on cardiac signs in rats with experimental organophosphate poisoning

Organophosphate poisoning causes disturbances in cardiac conduction and potentially fatal severe cardiac rhythm abnormalities. This study investigated the cardiac effects of atropine and pralidoxime in the treatment of organophosphate poisoning in rats. Three groups of 10 adult male Wistar rats were anesthetized with an intraperitoneal injection of ketamine 100 mg/kg and xylazine 10 mg/kg and connected to a computerized electrocardiographic monitor. Each rat was then injected intraperitoneally with the pesticide dichlorvos 70 mg/kg. Sixty seconds after the injection, 10 rats were injected with saline, 10 with pralidoxime mesylate 20 mg/kg, and 10 with atropine 10 mg/kg. During the computerized electrocardiographic monitoring, each rat's heart rate and QT(c) intervals were recorded and analyzed as the injections were administered. The heart rates in all 3 groups did not differ before the dichlorvos was administered, nor at 60 seconds afterward, but in the atropine group, the time elapsed before the first decline in heart rate was significantly longer than that in the control group (P<.05). In addition, the interval before death was significantly longer in the atropine group than in either the control group or the pralidoxime group (P<.05 for both). The QT(c) was almost identical in each of the groups. Atropine has beneficial effects on the heart rate, prolongs the time before the heart rate declines, and delays death but has no effect on the QT(c) interval. Further research about the toxic effects of organophosphate compounds on myocardial cells is warranted.

Post-exercise heart rate, blood pressure and oxygen uptake dynamics in pediatric patients with Fontan circulation: Comparison with patients after right ventricular outflow tract reconstruction

Background Post-exercise heart rate (HR) and oxygen uptake (V˙O 2) recover more slowly in patients with the Fontan circulation, but little is known about the determinants of the delayed recovery. Purpose To evaluate the post-exercise cardiovascular dynamics and clinical profiles in these patients. Methods and results We studied 51 Fontan patients (14±4 years) (atriopulmonary connection, APC=18 and total cavopulmonary connection, TCPC=33) and compared the results with 34 patients after right ventricular outflow tract reconstruction (RVOTR) with identical exercise capacity and arterial baroreflex sensitivity (BRS) (15±4 years) and with 26 controls (14±4 years). There were no differences in post-exercise HR or V˙O 2 declines between the Fontan and RVOTR groups. Although the systolic blood pressure (SBP) decline was delayed in the RVOTR group ( p<0.01), its early decline in the Fontan group was rapid and equivalent to that in controls. In Fontan patients, BRS had a great impact on early HR decline ( p<0.05) and early V˙O 2 decline was determined by peak V˙O 2, age and cardiac index ( p<0.05–0.001). TCPC and lower BRS were the main determinants of the slower SBP decline ( p<0.05). In another study of repeated paired exercise tests before and after Fontan operation, post-exercise SBP decline became greater after the operation ( p<0.07). Conclusions In the Fontan group, post-exercise HR and V˙O 2 declines are markedly delayed and are determined by cardiac vagal nervous activity, exercise capacity and age, respectively. Despite identical impaired hemodynamics and exercise capacity, post-exercise SBP decline is greater in the Fontan group, especially after APC, than in the RVOTR patients.

The protective effects of ligustrazine on ischemia-reperfusion and DPPH free radical-induced myocardial injury in isolated rat hearts.

Previous investigations have suggested that tumor necrosis factor-alpha (TNF-alpha) can contribute to myocardial damage during ischemia-reperfusion. In the present study, we examined whether the cardioprotective effects of ligustrazine are related to inhibition of TNF-alpha production in the rat models of ischemia-reperfusion and 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical-induced myocardial injury. Ischemia for 20 min and reperfusion for 40 min caused a decline in cardiac function (left ventricular pressure, +/- d p/d t(max), heart rate and coronary flow) and an increase in the release of creatine kinase in coronary effluent and the content of TNF-alpha in myocardial tissues. Similarly, perfusion with DPPH (100 nM) for 30 min significantly decreased cardiac function, and increased the release of creatine kinase and the content of TNF-alpha. Ligustrazine at the concentration of 40 or 80 mg/L markedly improved cardiac function and reduced the release of creatine kinase and the content of TNF-alpha in myocardial tissues in hearts subjected to ischemia-reperfusion or DPPH perfusion. These results suggest that the cardioprotection afforded by ligustrazine is related to a reduction of TNF-alpha content by inhibition of free radical production in isolated rat hearts.

Maximal Exercise Function In Children and Adolescents With Cystic Fibrosis Compared With Normal Controls

0460 Persons with cystic fibrosis (CF) have worsening lung function as they age. This results in impaired exercise performance with lowering of peak oxygen consumption (VO2max), peak work (Wmax) and increased minute ventilation (Ve) during exercise. Typically pulmonary function is followed by serial measurements of the Forced Expiratory Volume at 1 second (FEV1) in persons with CF. This method has its limitations because decline in FEV1 can be variable in persons with CF. Methods to determine earlier decline in pulmonary function may improve outcome in persons with CF. Purpose: To compare exercise function and parameters obtained by maximal progressive cycle ergometry in persons with CF and mild lung disease to healthy controls. Methods: Persons with CF and controls had maximal exercise testing performed by cycle ergomertry (Sensormedics 800 cycle ergometer using a 10-watt/minute ramp). The values for VO2, VCO2, Ve, heart rate (HR), end tidal oxygen (ETO2) and end tidal carbon dioxide (ETCO2) were then compared. Results: Similar proportions of males and females were recruited in both groups. Age, Tanner staging and bone age were likewise similar. Persons with CF had lower weight (W), height (H), and Body Mass Index (BMI) compared with controls. FEV1 was similar in both groups and ranged from 82–125% in persons with CF. VO2 and VCO2 were lower in the persons with CF but when adjusted as percent of predicted VO2max, the values were similar. Ve was higher in controls. When adjusted for Body Mass Index, Ve was similar in both groups. Ventilatory equivalent for predicted VO2max (Ve/VO2max predicted) was higher in individuals with CF. ETO2 was higher and ETCO2 lower in individuals with CF. HR declined an average of 43 beats per minute (BPM) in controls and 36 bpm in persons with CF over the first minute. Conclusion: Persons with CF and mild lung disease maintain a higher ratio of Ve to VO2 and VCO2 than normal controls. Because measurements of PaO2 and PaCO2 were not made during our study it is unclear if the relative increase in Ve was voluntarily or involuntarily. If the elevation in Ve was involuntary, it is likely due to V/Q mismatching. If V/Q mismatching is playing a role in this, the HR may remain elevated in recovery to facilitate CO2 excretion. Therefore the rate of HR decline after maximal exercise may be a useful physiologic measurement in persons with CF. Mark Johnson was supported by a grant from the Cystic Fibrosis Foundation

Developmental Patterns of Physiological Response to a Multisensory Intervention in Extremely Premature and High‐Risk Infants

To compare the developmental patterns of heart rate (HR), respiratory rate (RR), and hemoglobin oxygen saturation (SaO2) of premature infants with and without central nervous system (CNS) injury, and evaluate whether a multisensory intervention altered this development. Thirty-seven premature infants born at 23-26 weeks with normal head ultrasounds or at 24-32 weeks and diagnosed with periventricular leukomalacia (PVL) and/or intraventricular hemorrhage (IVH) were studied at 33-35 weeks postconceptional age. Infants were randomly assigned to control and experimental groups. The experimental group infants received auditory, tactile, visual, and vestibular (ATVV) multisensory intervention twice daily from 33 weeks postconceptional age (PCA) until hospital discharge. HR, RR, and SaO2 were continuously monitored during baseline, intervention, and the 30-minute postintervention period. Between 33 and 35 weeks PCA, control group infants with and without CNS injury and experimental group infants without CNS injury had a significant decrease in resting mean HR, whereas RR and SaO2 remained stable. The infants with PVL who received the intervention showed increases in HR even at rest. The absence of a weekly decline in HR for experimental group infants with PVL suggests that PVL may affect maturation of the autonomic nervous system and increase risk of decelerative HR changes and associated clinical compromise. Infants diagnosed with PVL should be closely monitored during procedures or interventions that may be stressful or involve handling. Further research is needed to tailor multisensory interventions for infants with PVL.

BLUEFIN'S COLD HEART HITS ROCK BOTTOM

Cruising the planet's oceans, bluefin tuna are true giants of the deep;Barbara Block describes them as `majestic fish'. Yet very little was known about the physiology or habits of these gentle giants, as working with the fish in captivity seemed impossible. But being situated in Monterey allowed Block and her lab to establish a collaboration with their next-door neighbour,the Monterey Bay Aquarium, to build a unique facility housing bluefins weighing up to 50 kg. For the first time, Block and her students could begin studying these enigmatic creatures in ways they had only dreamed of before.One of the main questions that puzzled Block about the bluefin was the fish's ability to forage and breed in waters ranging from the tropics to the poles (p. 881). Block explains that unlike other teleosts, whose body temperature is in equilibrium with their surrounding water, tunas are significantly warmer as they retain heat in many tissues thanks to complex counter-current heat-exchanging blood vessels. Yet the fish breathe through gills that constantly chill their blood and hearts to ambient temperature. How could the fish's heart function over such a wide thermal range?Keen to know how bluefin's hearts weather the enormous temperature range,Block and her team set out to sea in a fishing boat to collect juvenile fish. Sailing 500 miles into the Pacific Ocean, the scientists successfully caught more then 20 juvenile bluefins, transferring them to an onboard storage tank,ready for the long journey back to Monterey and their new home in the Tuna Research and Conservation Center's massive tanks.Back on land, Jason Blank, Jeffery Morrissette, Thomas Williams and Block prepared to begin testing the fish's cardiac function. Block explains that`keeping the heart going is a challenge' and adds that the experiments are limited by diffusion, so they must be done on small fish. It took the team almost a year to master the experimental techniques they would need to successfully test the fish's cardiac function, but by then the fish had grown too large for their hearts to be sustained by the perfusion technique. The team had to wait another year before the juvenile bluefins returned to the Mexican coast, and then they were ready to continue making cardiac recordings.Gently dropping the temperature from 30°C to 2°C, Blank and Morrissette saw the fish's heart rate decline from over 150 beats min–1 at 30°C to 13 beats min–1 at 2°C. While the strength of the fish's maximal heart beat was relatively unaffected by the massive temperature change, the dramatic fall in heart rate caused the bluefin's maximal cardiac output to plummet from 106 ml kg–1 min–1 at 25°C to 18.1 ml kg–1 min–1 at 2°C. Most surprisingly,the bluefin's heart continued functioning at temperatures where other tuna hearts failed. And when Block and her team began investigating the cellular basis of the heart's thermal tolerance, Ana Landeira found that the heart tissue expressed high levels of SERCA 2, one of the pump proteins responsible for regulating the heart's contraction, `fitting nicely with the organismal study' Block adds.Block suspects that it is the bluefin heart's exceptional thermal tolerance that permits the creature's nomadic lifestyle, allowing it to exploit environments that are simply too cold for other tuna species. And it could also explain some of the fish's intriguing diving behaviour. The fish seem able to descend to enormous depths where the temperature is barely above freezing. Block suspects that even the bluefin's heart can't tolerate such low temperatures for long, so the fish `bounce' back to warm in waters at the surface.

Effect of hypervolemia on heart rate during 4 days of prolonged exercises.

The aim was to evaluate the cardiodynamic adjustment during 4 days of prolonged exercises and to check if the plasma volume (PV) expansion which is observed generally during such events plays a role in this adaptation. Thirteen subjects exercised 5 hours per day on a cycle ergometer alternately with a treadmill for 4 days (D1 to D4) (6 x 50 min sessions per day). The individual cycle ergometer load and the treadmill speed were unchanged during each exercise session and throughout all the sessions, and corresponded to a moderate exercise intensity: 58 - 63 % of peak oxygen uptake (VO (2)peak). Heart rate (HR) was recorded every 15 s during each exercise session and VO (2) was measured from the expired air at the beginning and the end of each exercise session. Relative PV changes were measured from haematocrit and haemoglobin changes in the morning before the exercise bouts. No significant changes of VO (2) were observed between the first and the last exercise session i. e. for cycling: 2.1 +/- 0.2 l/min and for running: 2.4 +/- 0.3 l/min. Between the first and the last day, HR decreased from 143 to 129 bpm for cycle (p < 0.0001) and from 147 to 137 bpm (p = 0.01) for treadmill. As compared to D1, PV increased gradually from D2 (+ 1.8 % +/- 4.7 %) to D4 (+ 8.5 % +/- 4.7 %). The individual PV increases were significantly correlated with cycling HR decreases from D1 to D4 (r (2) = 0.40, p = 0.02). In conclusion, the 4 days' prolonged exercise induced a HR decrease during submaximal exercise without VO (2) drift. Here we suggested that this HR decline could be in part linked to the transient PV expansion.

Haemodynamic Response to TENS Applied to the Upper Thoracic Nerve Roots in Normal Subjects

This study investigated the haemodynamic response to the 90-minute application of 85 Hz transcutaneous electrical nerve stimulation (TENS) to the T1 and T5 nerve roots. Comparison was made between 20 healthy subjects who had TENS stimulation and a separate group of 20 healthy subjects who rested for 90 minutes. Pulse and blood pressure were measured just prior to the start of TENS stimulation, after 30 minutes of stimulation, and after 90 minutes of stimulation (immediately after stopping TENS) or at completion of the rest time depending on group allocation. The rate pressure product was calculated from the pulse and systolic blood pressure data. Multivariate repeated measures analysis showed a significant group effect for TENS ( p = 0.048). Univariate repeated measures analyses showed a significant group by time effect due to TENS on systolic blood pressure over the 90-minute time period ( p = 0.028). Separate group repeated measures ANOVA showed a significant decline in heart rate ( p = 0.000), systolic blood pressure ( p = 0.013) and rate pressure product ( p = 0.000) for the TENS group, while the control resting group showed a significant decline in heart rate only ( p = 0.04). The application of 85 Hz TENS to the upper thoracic nerve roots causes no adverse haemodynamic effects in healthy subjects.

The Effects of Cold-Water Immersion on Power Output and Heart Rate in Elite Cyclists

The purpose of this study was to examine the effects of cold-water immersion on power output, heart rate, and time to peak power in 10 well-trained cyclists. The Compu-trainer Professional Model 8001 computerized stationary trainer was used to evaluate maximum power, average power, and time to peak power during a simulated cycling sprint. The heart rate was measured using a Polar heart rate monitor. Subjects performed 2 maximum-effort sprints (for approximately 30 seconds) separated by either an experimental condition (15 minutes of cold-water immersion at 12° C up to the level of the iliac crest) or a control condition (15 minutes of quiet sitting). All subjects participated under both control and experimental conditions in a counterbalanced design in which 5 subjects performed the experimental condition first and the other 5 subjects performed the control condition first. Each condition was separated by at least 2 days. The time to peak power was not different between the 2 conditions. Maximum and average powers declined by 13.7 and 9.5% for the experimental condition but only by 4.7 and 2.3% for the control condition, respectively. The results also demonstrated a significantly greater decline in maximum heart rate after cold-water immersion (8.1%) than under the control condition (2.4%). Average heart rate showed a decrease of 4.2% under the experimental condition, as compared with an increase of 1.5% under the control condition. The major findings of this study suggest that a relatively brief period of cold-water immersion can manifest significant physiological effects that can impair cycling performance.

Heart rate recovery after treadmill exercise testing and risk of cardiovascular disease events (The Framingham Heart Study)

A delayed heart rate (HR) recovery after graded exercise testing has been associated with increased all-cause mortality in clinic-based samples. No prior study has examined the association of HR recovery after exercise with the incidence of coronary heart disease (CHD) and cardiovascular disease (CVD) events. We evaluated 2,967 Framingham study subjects (1,400 men, mean age 43 years) who were free of CVD and underwent a treadmill exercise test (Bruce protocol) at a routine examination. We examined the relations of HR recovery indexes (decrease in HR from peak exercise) to the incidence of a first CHD or CVD event and all-cause mortality, adjusting for established CVD risk factors. During follow-up (mean 15 years), 214 subjects experienced a CHD event (156 men), 312 developed a CVD event (207 men), and 167 died (105 men). In multivariable models, continuous HR recovery indexes were not associated with the incidence of CHD or CVD events, or with all-cause mortality. However, in models evaluating quintile-based cut points, the top quintile of HR recovery (greatest decline in HR) at 1-minute after exercise was associated with a lower risk of CHD (hazards ratio vs bottom 4 quintiles 0.54, 95% confidence interval [CI], 0.32 to 0.93) and CVD (hazards ratio 0.61, 95% CI 0.41 to 0.93), but not all-cause mortality (hazards ratio 0.99, 95% CI 0.60 to 1.62). In our community-based sample, HR recovery indexes were not associated with all-cause mortality. A very rapid HR recovery immediately after exercise was associated with lower risk of CHD and CVD events. These findings should be confirmed in other settings.

Usefulness of isometric handgrip during treadmill exercise stress echocardiography

Usefulness of isometric handgrip during treadmill exercise stress echocardiography

The cardioprotection of rutaecarpine is mediated by endogenous calcitonin related-gene peptide through activation of vanilloid receptors in guinea-pig hearts.

Previous investigations have shown that calcitonin gene-related peptide (CGRP) protects against myocardial ischemia-reperfusion injury and that rutaecarpine activates vanilloid receptors to evoke CGRP release. In the present study, we examined whether rutaecarpine enhances preservation with cardioplegia in guinea-pig hearts, and whether the protective effects of rutaecarpine are related to stimulation of endogenous CGRP release via activating vanilloid receptors. The isolated guinea-pig heart was arrested using St. Thomas Hospital solution, and then reperfused with normothermic Krebs-Henseleit solution for 30 min after a 4-h hypothermic ischemic period. Hypothermic ischemia caused a decline in cardiac function (left ventricular pressure, +/-dp/dt(max), heart rate and coronary flow) and an increased release of creatine kinase during reperfusion. Rutaecarpine at the concentration of 1.0 microM significantly improved the recovery of cardiac function and reduced the release of creatine kinase during reperfusion after hypothermic ischemia. Rutaecarpine at the concentration of 3.0 microM significantly reduced the release of creatine kinase and increased the coronary flow, but only caused a slight improvement of left ventricular pressure, +/-dp/dt(max), heart rate during reperfusion. The cardioprotective effects of rutaecarpine were abolished by capsazepine, a competitive vanilloid receptor antagonist, or by CGRP (8-37), a selective CGRP receptor antagonist. Rutaecarpine at the concentration of 1.0 or 3.0 microM significantly increased the release of CGRP, which was also abolished by capsazepine. These results suggest that rutaecarpine enhances preservation with cardioplegia in guinea-pig hearts and that the protective effects of rutaecarpine are due to stimulation of endogenous CGRP release via activating vanilloid receptors.

Tolerance of acute hypercapnic acidosis by the European eel ( Anguilla anguilla).

European eels ( Anguilla anguilla) were exposed sequentially to partial pressures of CO(2) in the water ( PwCO(2)) of 5, 10, 20, 40, 60 then 80 mm Hg (equivalent to 0.66-10.5 kPa), for 30 min at each level. This caused a profound drop in arterial plasma pH, from 7.9 to below 7.2, an increase in arterial PCO(2) from 3.0 mm Hg to 44 mm Hg, and a progressive decline in arterial blood O(2) content (caO(2)) from 10.0% to 1.97% volume. Gill ventilation rate increased significantly at water PwCO(2)s of 10, 20 and 40 mm Hg, followed by a decline at PwCO(2)s of 60 and 80 mm Hg, due to periodic breathing. Mean opercular pressure amplitude increased steadily throughout hypercapnic exposure and was significantly elevated at a PwCO(2) of 80 mm Hg. Hypercapnia caused a tachycardia between PwCO(2)s of 5 mmHg and 10 mm Hg, followed by a progressive decline in heart rate. Cardiac output (CO) remained unchanged throughout, as a consequence of a significant increase in stroke volume at PwCO(2)s of 40, 60 and 80 mm Hg. The eels maintained O(2) uptake at routine normocapnic levels throughout hypercapnic exposure. A comparison of the rates of blood O(2) delivery (calculated from CO and caO(2)) against O(2) consumption at PwCO(2)s of 60 mm Hg and 80 mm Hg indicated that a portion of O(2) uptake was due to cutaneous respiration. Thus, the European eel's exceptional tolerance of acute hypercapnia is probably a consequence of the tolerance of its heart to acidosis and hypoxia, and a contribution to O(2) uptake from cutaneous respiration.

Effect of Beta-Blockade on Heart Rate and VO2 Kinetics during Recovery in Patients with Coronary Artery Disease

Background: Recently, there has been heightened interest in the functional and prognostic applications of VO₂ and heart rate kinetics during the early recovery phase from exercise in patients with cardiovascular disease. However, the effect of beta-blockade on these responses is unknown. The purpose of this study was to evaluate the effects of beta-blockade on VO₂ and heart rate kinetics during recovery from exercise in patients with coronary artery disease (CAD), and compare these responses to those of normal individuals and patients with chronic heart failure (CHF). Methods: A cardiopulmonary exercise test using a ramp protocol was performed in 18 healthy subjects, 18 patients with CAD not taking a beta-blocker, 19 patients with CAD taking a cardioselective beta-blocker (metoprolol), 19 patients with mild or moderate CHF, and 19 patients with moderately severe CHF. The kinetics of oxygen uptake and heart rate were calculated and expressed as a single exponential relation between heart rate or VO₂ and time during the first 3 min of recovery. Results: No differences in time of recovery of VO₂ were found between normal subjects and CAD patients, whether or not they were taking a beta-blocker; VO₂ in recovery was slowed only among patients with moderately severe CHF. The slope of the decline in heart rate during recovery was steeper in patients with CAD taking a beta-blocker compared with the other groups (p < 0.05). Conclusion: In patients with CAD, cardioselective beta-blockade causes a faster decline in heart rate during the early recovery period without any effect on VO₂ recovery kinetics. The effect of beta-blockade should be accounted for when considering the prognostic utility of heart rate recovery.

Effectiveness of a two-dose regimen of prostaglandin administration in inducing luteolysis without adverse side effects in mares.

Our objectives were to determine whether repeated administration of prostaglandin F2alpha (PGF2alpha) to simulate the endogenous mode of secretion would be more effective than a single injection in inducing luteolysis and enable use of smaller doses less likely to cause adverse side effects. The main study comprised 43 dioestrous mares, who were given im. either a single 10 mg dose of natural PGF2alpha (n = 22) or 2 doses of 0.5 mg PGF2, 24 h apart (n = 21). The intensity of side effects was assessed in 8 dioestrous mares given 5, 1.5, 0.5 or 0 mg PGF2alpha in consecutive cycles. Two doses of 0.5 mg PGF2alpha 24 h apart caused lysis of the corpus luteum in all mares, whether this was determined from a fall in plasma progesterone concentrations or reproductive tract/behavioural changes; and when 10 mg PGF2, was given, the corpus luteum was lysed in 17 of 22 mares i.e. a lower proportion (P = 0.0485). A single dose of 0.5 mg PGF2a was no more effective than saline in inducing luteolysis.The intensity of side effects of PGF2alpha increased with dose. Although the 0.5 mg dose was no more likely than saline to cause sweating or muscle spasms, it raised plasma cortisol concentrations and prevented the decline in heart rate seen after saline. We conclude that a 2 dose regimen of administration increases the luteolytic efficacy of PGF2alpha and thereby provides a way to minimise adverse side effects.

The Effects of Cold-Water Immersion on Power Output and Heart Rate in Elite Cyclists

The purpose of this study was to examine the effects of cold-water immersion on power output, heart rate, and time to peak power in 10 well-trained cyclists. The Compu-trainer Professional Model 8001 computerized stationary trainer was used to evaluate maximum power, average power, and time to peak power during a simulated cycling sprint. The heart rate was measured using a Polar heart rate monitor. Subjects performed 2 maximum-effort sprints (for approximately 30 seconds) separated by either an experimental condition (15 minutes of cold-water immersion at 12 degrees C up to the level of the iliac crest) or a control condition (15 minutes of quiet sitting). All subjects participated under both control and experimental conditions in a counterbalanced design in which 5 subjects performed the experimental condition first and the other 5 subjects performed the control condition first. Each condition was separated by at least 2 days. The time to peak power was not different between the 2 conditions. Maximum and average powers declined by 13.7 and 9.5% for the experimental condition but only by 4.7 and 2.3% for the control condition, respectively. The results also demonstrated a significantly greater decline in maximum heart rate after cold-water immersion (8.1%) than under the control condition (2.4%). Average heart rate showed a decrease of 4.2% under the experimental condition, as compared with an increase of 1.5% under the control condition. The major findings of this study suggest that a relatively brief period of cold-water immersion can manifest significant physiological effects that can impair cycling performance.

Dynamics of the heart rate response to sinusoidal work in humans: influence of physical activity and age

The purpose of the present study was to define the influence of age and exercise training on the heart rate (HR) dynamic response (i.e. kinetics) to sinusoidal work. A total of 63 healthy subjects (31 men and 32 women; age range 19-69 years) underwent a three-step incremental work test, during which peak oxygen uptake (.V(O)(2peak)) was estimated by the YMCA method. Sinusoidal work varying between 20% and 60% of HR(reserve) was employed for periods of 1, 3, 6, 9 and 12 min. HR was monitored in a beat-by-beat manner with a cardiotachometer. The kinetics of the HR response were analysed by frequency analysis and estimated by a first-order transfer function with time constant (tau) and time delay (TD). Physical training status was estimated as stepping frequency, as measured with a pedometer during the daytime, and averaged over seven consecutive days. The mean response time of HR kinetics (HR(MRT): tau pulse TD) tended to increase gradually with age (0.36 s.year(-1)), and linear regression analysis revealed that the correlation between HR(MRT) and age was significant (r=0.31, P<0.05), although not as highly significant as that between HR(MRT) and physical activity (r=-0.48, P<0.0001). HR(MRT) was not related to the S.D. of HR variation (an indicator of parasympathetic mediation) at rest. In addition, .V(O)(2peak) showed a significantly greater correlation with age (r=-0.60, P<0.0001) than with physical activity (r=-0.14, not significant). In conclusion, these findings suggest that HR dynamics, which may depend on sympathetic nervous activity, are more sensitive to physical activity than to age, but that .V(O)(2peak), as estimated by the age-associated decline in maximum HR, is unrelated to physical training status.

Peripheral vagal control of heart rate is impaired in neuronal NOS knockout mice.

The role of nitric oxide (NO) in the vagal control of heart rate (HR) is controversial. We investigated the cholinergic regulation of HR in isolated atrial preparations with an intact right vagus nerve from wild-type (nNOS+/+, n = 81) and neuronal NO synthase (nNOS) knockout (nNOS-/-, n = 43) mice. nNOS was immunofluorescently colocalized within choline-acetyltransferase-positive neurons in nNOS+/+ atria. The rate of decline in HR during vagal nerve stimulation (VNS, 3 and 5 Hz) was slower in nNOS-/- compared with nNOS+/+ atria in vitro (P < 0.01). There was no difference between the HR responses to carbamylcholine in nNOS+/+ and nNOS-/- atria. Selective nNOS inhibitors, vinyl-L-niohydrochloride or 1-2-trifluoromethylphenyl imidazole, or the guanylyl cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one significantly (P < 0.05) attenuated the decrease in HR with VNS at 3 Hz in nNOS+/+ atria. NOS inhibition had no effect in nNOS-/- atria during VNS. In all atria, the NO donor sodium nitroprusside significantly enhanced the magnitude of the vagal-induced bradycardia, showing the downstream intracellular pathways activated by NO were intact. These results suggest that neuronal NO facilitates vagally induced bradycardia via a presynaptic modulation of neurotransmission.

Engagement of inducible nitric oxide synthase at the rostral ventrolateral medulla during mevinphos intoxication in the rat.

We evaluated the relationship between the toxicity induced by the organophosphate mevinphos (Mev) and inducible nitric oxide synthase (iNOS) in the rostral ventrolateral medulla (RVLM), the medullary origin of sympathetic neurogenic vasomotor tone. Adult Sprague-Dawley rats that were anesthetized and maintained with propofol were used. Laser scanning confocal microscopic analysis revealed colocalization of the M2 subtype of muscarinic receptors (M(2)R) and iNOS immunoreactivity in RVLM neurons. Comicroinjection bilaterally of Mev (10 nmol) and artificial cerebrospinal fluid (aCSF) into the RVLM elicited a progressive decline in systemic arterial pressure (SAP) and heart rate. This was accompanied during phase 1 Mev intoxication by an increase in the power density of the very high-frequency (VHF; 5-9 Hz), high-frequency (HF; 0.8-2.4 Hz), low-frequency (LF; 0.25- 0.8 Hz) and very low-frequency (VLF; 0-0.25 Hz) components of SAP signals. Phase 2 exhibited a reversal of the VHF and VLF power to control levels and a further reduction in the power density of both HF and LF components to below baseline. Hypotension and bradycardia promoted by Mev were significantly blunted on coadministration into the RVLM of the selective iNOS inhibitors S-methylisothiourea (250 pmol) or aminoguanidine (250 pmol). Not only was the augmented power density of HF and LF components during phase 1 Mev intoxication further enhanced, the reduced power of these two spectral components during phase 2 was appreciably antagonized. On the other hand, the temporal changes in VHF and VLF power were essentially the same as with coadministration of Mev and aCSF. We conclude that, as a cholinesterase inhibitor, Mev may induce toxicity via nitric oxide produced by iNOS on activation of the M(2)R by the accumulated acetylcholine in the RVLM.

A 30-Year Follow-Up of the Dallas Bed Rest and Training Study

Cardiovascular capacity declines with aging, as evidenced by declining maximal oxygen uptake (VO(2)max ), with little known about the specific mechanisms of this decline. Our study objective was to assess the effect of a 30-year interval on body composition and cardiovascular response to acute exercise in 5 healthy subjects originally evaluated in 1966. Anthropometric parameters and the cardiovascular response to acute maximal exercise were assessed with noninvasive techniques. On average, body weight increased 25% (77 versus 100 kg) and percent body fat increased 100% (14% versus 28%), with little change in fat-free mass (66 versus 72 kg). On average, VO(2)max decreased 11% (3.30 versus 2.90 L/min). Likewise, VO(2)max decreased when indexed to total body mass (43 versus 31 mL. kg(-1). min(-1)) or fat-free mass (50 versus 43 mL/kg fat-free mass per minute). Maximal heart rate declined 6% (193 versus 181 bpm) and maximal stroke volume increased 16% (104 versus 121 mL), with no difference observed in maximal cardiac output (20.0 versus 21.4 L/min). Maximal AV oxygen difference declined 15% (16.2 versus 13.8 vol%) and accounted for the entire decrease in cardiovascular capacity. Cardiovascular capacity declined over the 30-year study interval in these 5 middle-aged men primarily because of an impaired efficiency of maximal peripheral oxygen extraction. Maximal cardiac output was maintained with a decline in maximal heart rate compensated for by an increased maximal stroke volume. Most notably, 3 weeks of bedrest in these same men at 20 years of age (1966) had a more profound impact on physical work capacity than did 3 decades of aging.