Trimetazidine does not alter metabolic substrate oxidation in cardiac mitochondria of target patient population.

BACKGROUND AND PURPOSE: Trimetazidine, known as a metabolic modulator, is an anti-anginal drug used for treatment of stable coronary artery disease (CAD). It is proposed to act via modulation of cardiac metabolism, shifting the mitochondrial substrate utilization towards carbohydrates, thus increasing the efficiency of ATP production. This mechanism was recently challenged; however, these studies used indirect approaches and animal models, which made their conclusions questionable. The goal of the current study was to assess the effect of trimetazidine on mitochondrial substrate oxidation directly in left ventricular myocardium from CAD patients. EXPERIMENTAL APPROACH: Mitochondrial fatty acid (palmitoylcarnitine) and carbohydrate (pyruvate) oxidation were measured in permeabilized left ventricular fibres obtained during coronary artery bypass grafting surgery from CAD patients, which either had trimetazidine included in their therapy (TMZ group) or not (Control). KEY RESULTS: There was no difference between the two groups in the oxidation of either palmitoylcarnitine or pyruvate, and in the ratio of carbohydrate to fatty acid oxidation. Activity and expression of pyruvate dehydrogenase, the key regulator of carbohydrate metabolism, were also not different. Lastly, acute in vitro exposure of myocardial tissue to different concentrations of trimetazidine did not affect myocardial oxidation of fatty acid. CONCLUSION AND IMPLICATIONS: Using myocardial tissue from CAD patients, we found that trimetazidine (applied chronically in vivo or acutely in vitro) had no effect on cardiac fatty acid and carbohydrate oxidation, suggesting that the clinical effects of trimetazidine are unlikely to be due to its metabolic effects, but rather to an as yet unidentified intracardiac mechanism.

Exercise training promotes cardioprotection through oxygen-sparing action in high fat-fed mice.

Although exercise training has been demonstrated to have beneficial cardiovascular effects in diabetes, the effect of exercise training on hearts from obese/diabetic models is unclear. In the present study, mice were fed a high-fat diet, which led to obesity, reduced aerobic capacity, development of mild diastolic dysfunction, and impaired glucose tolerance. Following 8 wk on high-fat diet, mice were assigned to 5 weekly high-intensity interval training (HIT) sessions (10 × 4 min at 85-90% of maximum oxygen uptake) or remained sedentary for the next 10 constitutive weeks. HIT increased maximum oxygen uptake by 13%, reduced body weight by 16%, and improved systemic glucose homeostasis. Exercise training was found to normalize diastolic function, attenuate diet-induced changes in myocardial substrate utilization, and dampen cardiac reactive oxygen species content and fibrosis. These changes were accompanied by normalization of obesity-related impairment of mechanical efficiency due to a decrease in work-independent myocardial oxygen consumption. Finally, we found HIT to reduce infarct size by 47% in ex vivo hearts subjected to ischemia-reperfusion. This study therefore demonstrated for the first time that exercise training mediates cardioprotection following ischemia in diet-induced obese mice and that this was associated with oxygen-sparing effects. These findings highlight the importance of optimal myocardial energetics during ischemic stress.

Reduced aerobic capacity causes leaky ryanodine receptors that trigger arrhythmia in a rat strain artificially selected and bred for low aerobic running capacity.

AIM: Rats selectively bred for inborn low capacity of running (LCR) display a series of poor health indices, whereas rats selected for high capacity of running (HCR) display a healthy profile. We hypothesized that selection of low aerobic capacity over generations leads to a phenotype with increased diastolic Ca(2+) leak that trigger arrhythmia. METHODS: We used rats selected for HCR (N = 10) or LCR (N = 10) to determine the effect of inborn aerobic capacity on Ca(2+) leak and susceptibility of ventricular arrhythmia. We studied isolated Fura-2/AM-loaded cardiomyocytes to detect Ca(2+) handling and function on an inverted epifluorescence microscope. To determine arrhythmogenicity, we did a final experiment with electrical burst pacing in Langendorff-perfused hearts. RESULTS: Ca(2+) handling was impaired by reduced Ca(2+) amplitude, prolonged time to 50% Ca(2+) decay and reduced sarcoplasmic reticulum (SR) Ca(2+) content. Impaired Ca(2+) removal was influenced by reduced SR Ca(2+) ATP-ase 2a (SERCA2a) function and increased sodium/Ca(2+) exchanger (NCX) in LCR rats. Diastolic Ca(2) leak was 87% higher in LCR rats. The leak was reduced by CaMKII inhibition. Expression levels of phosphorylated threonine 286 CaMKII levels and increased RyR2 phosphorylation at the serine 2814 site mechanistically support our findings of increased leak in LCR. LCR rats had significantly higher incidence of ventricular fibrillation. CONCLUSION: Selection of inborn low aerobic capacity over generations leads to a phenotype with increased risk of ventricular fibrillation. Increased phosphorylation of CaMKII at serine 2814 at the cardiac ryanodine receptor appears as an important mechanism of impaired Ca(2+) handling and diastolic Ca(2+) leak that results in increased susceptibility to ventricular fibrillation.

High inborn aerobic capacity does not protect the heart following myocardial infarction.

Maximal oxygen uptake (Vo2max) is a strong prognostic marker for morbidity and mortality, but the cardio-protective effect of high inborn Vo2max remains unresolved. We aimed to investigate whether rats with high inborn Vo2max yield cardio-protection after myocardial infarction (MI) compared with rats with low inborn Vo2max. Rats breed for high capacity of running (HCR) or low capacity of running (LCR) were randomized into HCR-SH (sham), HCR-MI, LCR-SH, and LCR-MI. Vo2max was lower in HCR-MI and LCR-MI compared with respective sham (P < 0.01), supported by a loss in global cardiac function, assessed by echocardiography. Fura 2-AM loaded cardiomyocyte experiments revealed that HCR-MI and LCR-MI decreased cardiomyocyte shortening (39%, and 34% reduction, respectively, both P < 0.01), lowered Ca(2+) transient amplitude (37%, P < 0.01, and 20% reduction, respectively), and reduced sarcoplasmic reticulum (SR) Ca(2+) content (both; 20%, P < 0.01) compared with respective sham. Diastolic Ca(2+) cycling was impaired in HCR-MI and LCR-MI evidenced by prolonged time to 50% Ca(2+) decay that was partly explained by the 47% (P < 0.01) and 44% (P < 0.05) decrease in SR Ca(2+)-ATPase Ca(2+) removal, respectively. SR Ca(2+) leak increased by 177% in HCR-MI (P < 0.01) and 67% in LCR-MI (P < 0.01), which was abolished by inhibition of Ca(2+)/calmodulin-dependent protein kinase II. This study demonstrates that the effect of MI in HCR rats was similar or even more pronounced on cardiac- and cardiomyocyte contractile function, as well as on Ca(2+) handling properties compared with observations in LCR. Thus our data do not support a cardio-protective effect of higher inborn aerobic capacity.

Recovery after an intermittent test.

The purpose of this study was to analyse the impact of an intermittent test reproducing the soccer running activity profile on physical performance, subjective ratings and biochemical parameters throughout 72 h recovery. 8 professional soccer players performed the intermittent test on a non-motorised treadmill and data was collected before, immediately after, 24, 48 and 72 h after the test. Squat jump (SJ), countermovement jump (CMJ), peak isometric force (IFpeak), 6-s sprint, repeated sprints test (RS), perceptual ratings (fatigue, muscle soreness, stress), creatine kinase ([CK]) and uric acid ([UA]) were analyzed. After the test, a mean reduction in countermovement jump performance of -8.2% (CI: -12.9 to -3.4, p<0.01) was observed, while perceived fatigue (+2.1±1.7 a.u.; p<0.05), perceived muscle soreness (+1.8±1.5 a.u.; p<0.05), perceived stress (+1.6±1.5 a.u.; p<0.05), creatine kinase (+171±77 IU x l(-1); p<0.01) and uric acid (+168±89 Umol x l(-1); p<0.01) concentrations were significantly increased relative to baseline. No significant effect was found for SJ, IFpeak, 6-s sprint, RS immediately after and throughout the 72 h following the test. In conclusion, soccer running performance does not appear to be the main cause of post soccer match-induced fatigue. Physical data provided by video match analysis systems is insufficient to accurately estimate the level of match fatigue.

Age-predicted maximal heart rate in healthy subjects: The HUNT fitness study.

Maximal heart rate (HRmax ) declines substantially with age, but the magnitude and possible modifying effect of gender, body composition, and physical activity are not fully established. The present study examined the relationship between HRmax and age in 3320 healthy men and women within a wide age range using data from the HUNT Fitness Study (2007-2008). Subjects were included if a maximal effort could be verified during a maximal exercise test. General linear modeling was used to determine the effect of age on HRmax . Subsequently, the effects of gender, body mass index (BMI), physical activity status, and maximal oxygen uptake were examined. Mean predicted HRmax by three former prediction formulas were compared with measured HRmax within 10-year age groups. HRmax was univariately explained by the formula 211 - 0.64·age (SEE, 10.8), and we found no evidence of interaction with gender, physical activity, VO2max level, or BMI groups. There were only minor age-adjusted differences in HRmax between these groups. Previously suggested prediction equations underestimated measured HRmax in subjects older than 30 years. HRmax predicted by age alone may be practically convenient for various groups, although a standard error of 10.8 beats/min must be taken into account. HRmax in healthy, older subjects and women were higher than previously reported.

Individual patient meta-analysis of exercise training effects on systemic brain natriuretic peptide expression in heart failure.

BACKGROUND: Brain natriuretic peptide (BNP) predicts exercise performance and exercise training may modulate BNP and its N-terminal portion (NT-pro-BNP), we therefore conducted an individual patient analysis of exercise training effects on BNP and NT-pro-BNP. AIMS: To use an individual patient meta-analysis to relate changes in BNP, NT-pro-BNP, and peak VO(2); to link these changes to volume parameters of exercise training programmes (intensity etc.); and to identify patient characteristics likely to lead to greater improvements in BNP, NT-pro-BNP, and peak VO(2). DESIGN: Individual patient meta-analysis. METHODS: A systematic search was conducted of Medline (Ovid), Embase.com, Cochrane Central Register of Controlled Trials, and CINAHL (until July 2008) to identify randomized controlled trials of aerobic and/or resistance exercise training in systolic heart failure patients measuring BNP and/or NT-pro-BNP. Primary outcome measures were change in BNP, NT-pro-BNP, and peak VO2. Subanalyses were conducted to identify (1) patient groups that benefit most and (2) exercise programme parameters enhancing favourable changes in primary outcome measures. RESULTS: Ten randomized controlled studies measuring BNP or NT-pro-BNP met eligibility criteria, authors provided individual patient data for 565 patients (313 exercise and 252 controls). Exercise training had favourable effects on BNP (-28.3%, p < 0.0001), NT-pro-BNP (-37.4%, p = < 0.0001), and peak VO(2) (17.8%, p < 0.0001). The analysis showed a significant change in primary outcome measures; moreover, change in BNP (r = -0.31, p < 0.0001) and NT-pro-BNP (r = -0.22, p < 0.0001) were correlated with peak VO(2) change. CONCLUSION: Exercise training has favourable effects on BNP, NT-pro-BNP, and peak VO(2) in heart failure patients and BNP/NT-pro-BNP changes were correlated with peak VO(2) changes.

Venous gas embolism as a predictive tool for improving CNS decompression safety.

A key process in the pathophysiological steps leading to decompression sickness (DCS) is the formation of inert gas bubbles. The adverse effects of decompression are still not fully understood, but it seems reasonable to suggest that the formation of venous gas emboli (VGE) and their effects on the endothelium may be the central mechanism leading to central nervous system (CNS) damage. Hence, VGE might also have impact on the long-term health effects of diving. In the present review, we highlight the findings from our laboratory related to the hypothesis that VGE formation is the main mechanism behind serious decompression injuries. In recent studies, we have determined the impact of VGE on endothelial function in both laboratory animals and in humans. We observed that the damage to the endothelium due to VGE was dose dependent, and that the amount of VGE can be affected both by aerobic exercise and exogenous nitric oxide (NO) intervention prior to a dive. We observed that NO reduced VGE during decompression, and pharmacological blocking of NO production increased VGE formation following a dive. The importance of micro-nuclei for the formation of VGE and how it can be possible to manipulate the formation of VGE are discussed together with the effects of VGE on the organism. In the last part of the review we introduce our thoughts for the future, and how the enigma of DCS should be approached.

Expression of perilipins in human skeletal muscle in vitro and in vivo in relation to diet, exercise and energy balance.

The perilipin proteins enclose intracellular lipid droplets. We describe the mRNA expression of the five perilipins in human skeletal muscle in relation to fatty acid supply, exercise and energy balance. We observed that all perilipins were expressed in skeletal muscle biopsies with the highest mRNA levels of perilipin 2, 4 and 5. Cultured myotubes predominantly expressed perilipin 2 and 3. In vitro, incubation of myotubes with fatty acids enhanced mRNA expression of perilipin 1, 2 and 4. In vivo, low fat diet increased mRNA levels of perilipin 3 and 4. Endurance training, but not strength training, enhanced the expression of perilipin 2 and 3. Perilipin 1 mRNA correlated positively with body fat mass, whereas none of the perilipins were associated with insulin sensitivity. In conclusion, all perilipins mRNAs were expressed in human skeletal muscle. Diet as well as endurance exercise modulated the expression of perilipins.

High intensity interval training alters substrate utilization and reduces oxygen consumption in the heart.

AIMS: although exercise training induces hypertrophy with improved contractile function, the effect of exercise on myocardial substrate metabolism and cardiac efficiency is less clear. High intensity training has been shown to produce more profound effects on cardiovascular function and aerobic capacity than isocaloric low and moderate intensity training. The aim of the present study was to explore metabolic and mechanoenergetic changes in the heart following endurance exercise training of both high and moderate intensity. METHODS AND RESULTS: C57BL/6J mice were subjected to 10 wk treadmill running, either high intensity interval training (HIT) or distance-matched moderate intensity training (MIT), where HIT led to a pronounced increase in maximal oxygen uptake. Although both modes of exercise were associated with a 10% increase in heart weight-to-body weight ratio, only HIT altered cardiac substrate utilization, as revealed by a 36% increase in glucose oxidation and a concomitant reduction in fatty acid oxidation. HIT also improved cardiac efficiency by decreasing work-independent myocardial oxygen consumption. In addition, it increased cardiac maximal mitochondrial respiratory capacity. CONCLUSION: This study shows that high intensity training is required for induction of changes in cardiac substrate utilization and energetics, which may contribute to the superior effects of high compared with moderate intensity training in terms of increasing aerobic capacity.

Maximal lactate steady state is altered in the heat.

The aim of this study was to compare the maximal lactate steady state (MLSS) and ventilatory threshold (VT) under different environments (TEMP: 22°C; and HOT: 40°C; 50% RH). 8 male subjects (age 23.9±2.4 years, body mass 75.9±7.3 kg and VO2(max) 47.8±4.9 mL·kg(-1)·min(-1)) performed a series of tests to determine the peak workload (W(peak)), VT and MLSS on a cycle ergometer. W(peak) was higher in the TEMP as compared to the HOT condition (225±9 W vs. 195±8 W, respectively; p<0.05). The workload at MLSS was higher at 22°C (180±11 W) than 40°C (148±11 W; p<0.05), as well as VT at 22°C (156±9 W) was higher than 40°C (128±6 W). Likewise, the blood lactate concentration at MLSS was higher at 22°C (5.60±0.26 mM) than 40°C (4.22±0.48 mM; p<0.05). The mean of heart rate (HR) was not statistically different between TEMP (168±3 bpm) and HOT (173±3 bpm) at MLSS, despite being different at trials between the 25(th) and the 30(th) min of exercise. The HR at VT was significantly higher in HOT (153±4 bpm) as compared to the TEMP (145±2 bpm). Our results suggest that environmental conditions may influence the determination of MLSS and VT. Moreover, VT was appropriate for estimation of the workload at MLSS in the HOT.

Animal models in the study of exercise-induced cardiac hypertrophy.

Exercise training-induced cardiac hypertrophy occurs following a program of aerobic endurance exercise training and it is considered as a physiologically beneficial adaptation. To investigate the underlying biology of physiological hypertrophy, we rely on robust experimental models of exercise training in laboratory animals that mimic the training response in humans. A number of experimental strategies have been established, such as treadmill and voluntary wheel running and swim training models that all associate with cardiac growth. These approaches have been applied to numerous animal models with various backgrounds. However, important differences exist between these experimental approaches, which may affect the interpretation of the results. Here, we review the various approaches that have been used to experimentally study exercise training-induced cardiac hypertrophy; including the advantages and disadvantages of the various models.

Mechanisms of exercise-induced improvements in the contractile apparatus of the mammalian myocardium.

One of the main outcomes of aerobic endurance exercise training is the improved maximal oxygen uptake, and this is pivotal to the improved work capacity that follows the exercise training. Improved maximal oxygen uptake in turn is at least partly achieved because exercise training increases the ability of the myocardium to produce a greater cardiac output. In healthy subjects, this has been demonstrated repeatedly over many decades. It has recently emerged that this scenario may also be true under conditions of an initial myocardial dysfunction. For instance, myocardial improvements may still be observed after exercise training in post-myocardial infarction heart failure. In both health and disease, it is the changes that occur in the individual cardiomyocytes with respect to their ability to contract that by and large drive the exercise training-induced adaptation to the heart. Here, we review the evidence and the mechanisms by which exercise training induces beneficial changes in the mammalian myocardium, as obtained by means of experimental and clinical studies, and argue that these changes ultimately alter the function of the whole heart and contribute to the changes in whole-body function.

Combined effect of resting heart rate and physical activity on ischaemic heart disease: mortality follow-up in a population study (the HUNT study, Norway).

BACKGROUND: The combined effect of resting heart rate (RHR) and physical activity (PA) on ischaemic heart disease (IHD) has never been assessed. The objective of this study was to assess the association of RHR with IHD mortality, and to evaluate the potentially modifying effect of PA on this association. METHODS: In a prospective cohort study of 24 999 men and 25 089 women free from cardiovascular disease at baseline, Cox proportional hazard models were used to estimate adjusted hazard ratios of death from IHD related to RHR measured at baseline. The combined effect of RHR and self-reported PA on the risk of death from IHD was also assessed. RESULTS: During a mean of 18.2 (SD 4) years of follow-up, 2566 men and 1814 women died from cardiovascular causes. For each increment of 10 heart beats per minute, risk of death from IHD was 18% higher in women <70 years of age (p<0.001); no such association was observed among women > or =70 years. Among men, there was a corresponding 10% higher risk in the younger (p = 0.004), and 11% higher risk in the older age group (p = 0.01). Among women, the risk associated with high RHR was substantially attenuated in those who reported a high level of PA, whereas in men, there was no clear indication that PA could modify the positive effect of RHR. CONCLUSION: RHR is positively associated with the risk of death from IHD, and among women, the results suggest that by engaging in PA, the risk associated with a high RHR may be substantially reduced.

Validity of a repeated-sprint test for football.

Three studies involving 108 football players were conducted to examine the reliability of a repeated-shuttle-sprint ability (RSSA) test and its ability to differentiate between players of various competitive levels and playing positions. Study 1: Short-term reliability was determined in 22 professional players completing the RSSA test (6 x 40-m sprints with 20 s of recovery between sprints) on two separate occasions. Study 2: Long-term reliability (seasonal changes) was examined in 31 professional players completing the RSSA test four times (during the preseason period, at the start, middle and end of the competitive season). Study 3: 108 players were divided and compared according to competitive level or playing position. Standard error of measurement values expressed as coefficient of variation for RSSA mean time and best time were 0.8 and 1.3 % (short-term reliability) and 0.9 and 1.2 % (long-term reliability), respectively. The smallest worthwhile changes were 0.5 % for both mean and best time. Professional players showed better RSSA performance than amateur players, and defenders displayed the lowest RSSA performance. In conclusion, the RSSA test showed adequate construct validity but only RSSA mean time showed sufficient reliability to detect large training-induced changes but not small important differences.

Sprint vs. interval training in football.

The aim of this study was to compare the effects of high-intensity aerobic interval and repeated-sprint ability (RSA) training on aerobic and anaerobic physiological variables in male football players. Forty-two participants were randomly assigned to either the interval training group (ITG, 4 x 4 min running at 90 - 95 % of HRmax; n = 21) or repeated-sprint training group (RSG, 3 x 6 maximal shuttle sprints of 40 m; n = 21). The following outcomes were measured at baseline and after 7 weeks of training: maximum oxygen uptake, respiratory compensation point, football-specific endurance (Yo-Yo Intermittent Recovery Test, YYIRT), 10-m sprint time, jump height and power, and RSA. Significant group x time interaction was found for YYIRT (p = 0.003) with RSG showing greater improvement (from 1917 +/- 439 to 2455 +/- 488 m) than ITG (from 1846 +/- 329 to 2077 +/- 300 m). Similarly, a significant interaction was found in RSA mean time (p = 0.006) with only the RSG group showing an improvement after training (from 7.53 +/- 0.21 to 7.37 +/- 0.17 s). No other group x time interactions were found. Significant pre-post changes were found for absolute and relative maximum oxygen uptake and respiratory compensation point (p < 0.05). These findings suggest that the RSA training protocol used in this study can be an effective training strategy for inducing aerobic and football-specific training adaptations.

Effect of plyometric training on sand versus grass on muscle soreness and jumping and sprinting ability in soccer players.

OBJECTIVE: The lower impact on the musculoskeletal system induced by plyometric exercise on sand compared to a firm surface might be useful to reduce the stress of intensified training periods or during rehabilitation from injury. The aim of this study was to compare the effects of plyometric training on sand versus a grass surface on muscle soreness, vertical jump height and sprinting ability. DESIGN: Parallel two-group, randomised, longitudinal (pretest-post-test) study. METHODS: After random allocation, 18 soccer players completed 4 weeks of plyometric training on grass (grass group) and 19 players on sand (sand group). Before and after plyometric training, 10 m and 20 m sprint time, squat jump (SJ), countermovement jump (CMJ), and eccentric utilization ratio (CMJ/SJ) were determined. Muscle soreness was measured using a Likert scale. RESULTS: No training surface x time interactions were found for sprint time (p>0.87), whereas a trend was found for SJ (p = 0.08), with both groups showing similar improvements (p<0.001). On the other hand, the grass group improved their CMJ (p = 0.033) and CMJ/SJ (p = 0.005) significantly (p<0.001) more than players in the sand group. In contrast, players in the sand group experienced less muscle soreness than those in the grass group (p<0.001). CONCLUSIONS: Plyometric training on sand improved both jumping and sprinting ability and induced less muscle soreness. A grass surface seems to be superior in enhancing CMJ performance while the sand surface showed a greater improvement in SJ. Therefore, plyometric training on different surfaces may be associated with different training-induced effects on some neuromuscular factors related to the efficiency of the stretch-shortening cycle.

Reduced pH and contractility in failing rat cardiomyocytes.

AIM: To determine whether reduced cardiomyocyte contractility in heart failure is associated with reduced intracellular pH (pH(i)). Involvement of the Na(+)/H(+) exchanger and the H(+)/K(+) ATPase were investigated with specific blockers. METHODS: Myocardial infarction and subsequent heart failure in Sprague-Dawley rats were induced by chronic occlusion of the left coronary artery. 6 weeks post-ligation, contractility (cell shortening) and pH(i) (BCECF fluorescence) were recorded in freshly dissociated cardiomyocytes during 2-10 Hz electrical stimulation, with or without either Na(+)/H(+) exchanger or H(+)/K(+) ATPase inhibition. RESULTS: Elevated end-diastolic and reduced peak systolic pressures confirmed heart failure. Increased heart weights (20-30%; P < or = 0.01) and cardiomyocyte lengths and widths (22-25%; P < or = 0.01) confirmed substantial cardiac hypertrophy. In myocytes isolated from sham operated rats, a positive staircase response occurred with stimulation rates from 2 to 7 Hz; further increases in stimulation rate up to 10 Hz reduced contractility. In contrast, pH(i) fell progressively over the entire stimulation range. In failing myocytes, pH(i) was consistently 0.07 pH units lower and contractility 40% lower (P < or = 0.01) than sham control values; the shape of the contractility staircase remained similar to controls. At all stimulation frequencies, Na(+)/H(+) exchanger inhibition reduced pH(i) by 0.05 pH units (P < or = 0.01) and contractility by 22% (P < or = 0.05) in cardiomyocytes from the heart failure group. A significantly smaller decrease of pH(i) and reduction in contractility was observed after inhibition of Na(+)/H(+) exchanger (10 micro m HOE694) in sham myocytes. H(+)/K(+) ATPase inhibition (100 micro m SCH28080) had no effect on pH(i). CONCLUSION: Reduced pH(i) is accompanied by reduced cardiomyocyte contractility in isolated myocytes from post-MI heart failure. The data suggest compensatory Na(+)/H(+) exchanger activation in heart failure, whereas H(+)/K(+) ATPase does not appear to contribute significantly to pH(i) maintenance.

The effect of endurance training on the rate of nitrogen elimination in women.

INTRODUCTION: The rate of nitrogen elimination may be an important factor in evaluating the risk of DCS following dives. The present study determined the reproducibility of a method for evaluating nitrogen elimination (series I), and the effect of chronic training on the nitrogen elimination in healthy young women (series II). METHODS: Nitrogen elimination was determined with subjects wearing an AGA full-face mask breathing pure oxygen. To evaluate the reproducibility of the method for nitrogen elimination, three tests were performed in six subjects in series I. Nitrogen elimination in series II was measured before and after the training period. The training protocol (series II) consisted of interval training, three times per week for eight weeks. Four repeated intervals alternated between four minutes at 90-95% of maximum heart rate and three minutes at 50-60%. RESULTS: There was no significant difference between the three repeated tests. Interval training for eight weeks increased maximum oxygen uptake by 22.1%. Endurance training did not influence the total nitrogen elimination at rest. CONCLUSION: The method for evaluating nitrogen elimination at rest was found to be reproducible. Improved aerobic capacity does not increase the rate of nitrogen elimination at rest.

Effect of a short-acting NO donor on bubble formation from a saturation dive in pigs.

It has previously been reported that a nitric oxide (NO) donor reduces bubble formation from an air dive and that blocking NO production increases bubble formation. The present study was initiated to see whether a short-acting NO donor (glycerol trinitrate, 5 mg/ml; Nycomed Pharma) given immediately before start of decompression would affect the amount of vascular bubbles during and after decompression from a saturation dive in pigs. A total of 14 pigs (Sus scrofa domestica of the strain Norsk landsvin) were randomly divided into an experimental (n = 7) and a control group (n = 7). The pigs were anesthetized with ketamine and alpha-chloralose and compressed in a hyperbaric chamber to 500 kPa (40 m of seawater) in 2 min, and they had 3-h bottom time while breathing nitrox (35 kPa O(2)). The pigs were all decompressed to the surface (100 kPa) at a rate of 200 kPa/h. During decompression, the inspired Po(2) of the breathing gas was kept at 100 kPa. Thirty minutes before decompression, the experimental group received a short-acting NO donor intravenously, while the control group were given equal amounts of saline. The average number of bubbles seen during the observation period decreased from 0.2 to 0.02 bubbles/cm(2) (P < 0.0001) in the experimental group compared with the controls. The present study gives further support to the role of NO in preventing vascular bubble formation after decompression.