Michael F Carey’s research while affiliated with Victoria University and other places

The Angiotensin Converting Enzyme (ACE) gene may influence the risk of heart disease and the response to various forms of exercise training may be at least partly dependent on the ACE genotype. We aimed to determine the effect of ACE genotype on the response to moderate intensity circuit resistance training in chronic heart failure (CHF) patients. The relationship between ACE genotype and the response to 11weeks of resistance exercise training was determined in 37 CHF patients (New York Heart Association Functional Class=2.3±0.5; left ventricular ejection fraction 28±7%; age 64±12years; 32:5 male:female) who were randomised to either resistance exercise (n=19) or inactive control group (n=18). Outcome measures included V˙O(2peak), peak power output and muscle strength and endurance. ACE genotype was determined using standard methods. At baseline, patients who were homozygous for the I allele had higher V˙O(2peak) (p=0.02) and peak power (p=0.003) compared to patients who were homozygous for the D allele. Patients with the D allele, who were randomised to resistance training, compared to non-exercising controls, had greater peak power increases (ID p<0.001; DD p<0.001) when compared with patients homozygous for the I allele, who did not improve. No significant genotype-dependent changes were observed in V˙O(2peak), muscle strength, muscle endurance or lactate threshold. ACE genotype may have a role in exercise tolerance in CHF and could also influence the effectiveness of resistance training in this condition.

We aimed to determine the role of skeletal muscle mitochondrial ATP production rate (MAPR) in relation to exercise tolerance after resistance training (RT) in chronic heart failure (CHF). Thirteen CHF patients (New York Heart Association functional class 2.3 +/- 0.5; Left ventricular ejection fraction 26 +/- 8%; age 70 +/- 8 years) underwent testing for peak total body oxygen consumption (VO(2peak)), and resting vastus lateralis muscle biopsy. Patients were then randomly allocated to 11 weeks of RT (n = 7), or continuance of usual care (C; n = 6), after which testing was repeated. Muscle samples were analyzed for MAPR, metabolic enzyme activity, and capillary density. VO(2peak) and MAPR in the presence of the pyruvate and malate (P+M) substrate combination, representing carbohydrate metabolism, increased in RT (P < .05) and decreased in C (P < .05), with a significant difference between groups (VO(2peak), P = .005; MAPR, P = .03). There was a strong correlation between the change in MAPR and the change in peak total body oxygen consumption (VO(2peak)) over the study (r = 0.875; P < .0001), the change in MAPR accounting for 70% of the change in VO(2peak). These findings suggest that mitochondrial ATP production is a major determinant of aerobic capacity in CHF patients and can be favorably altered by muscle strengthening exercise.

Studies that have attributed gains in lean body mass to dietary supplementation during resistance exercise (RE) training have not reported these changes alongside adaptations at the cellular and subcellular levels. Therefore, the purpose of this study was to examine the effects of two popular supplements--whey protein (WP) and creatine monohydrate (CrM) (both separately and in combination)--on body composition, muscle strength, fiber-specific hypertrophy (i.e., type I, IIa, IIx), and contractile protein accrual during RE training. In a double-blind randomized protocol, resistance-trained males were matched for strength and placed into one of four groups: creatine/carbohydrate (CrCHO), creatine/whey protein (CrWP), WP only, or carbohydrate only (CHO) (1.5 g x kg(-1) body weight per day). All assessments were completed the week before and after an 11-wk structured, supervised RE program. Assessments included strength (1RM, three exercises), body composition (DEXA), and vastus lateralis muscle biopsies for determination of muscle fiber type (I, IIa, IIx), cross-sectional area (CSA), contractile protein, and creatine (Cr) content. Supplementation with CrCHO, WP, and CrWP resulted in significantly greater (P < 0.05) 1RM strength improvements (three of three assessments) and muscle hypertrophy compared with CHO. Up to 76% of the strength improvements in the squat could be attributed to hypertrophy of muscle involved in this exercise. However, the hypertrophy responses within these groups varied at the three levels assessed (i.e., changes in lean mass, fiber-specific hypertrophy, and contractile protein content). Although WP and/or CrM seem to promote greater strength gains and muscle morphology during RE training, the hypertrophy responses within the groups varied. These differences in skeletal muscle morphology may have important implications for various populations and, therefore, warrant further investigation.

The influence of sprint training on endogenous urinary purine loss was examined in 7 active male subjects (age, 23.1 1.8y; body mass, 76.1 3.1kg; VO2 peak, 56.3 4.0mLkg¹min¹). Each subject performed a 30 s sprint performance test (PT), before and after 7d of sprint training. Training consisted of 15 sprints, each lasting 10 s, on an air-braked cycle ergometer performed twice each day. A rest period of 50 s separated each sprint during training. Sprint training resulted in a 20% higher muscle ATP immediately after PT, a lower IMP (57% and 89%, immediately after and 10min after PT, respectively), and inosine accumulation (53% and 56%, immediately after and 10min after the PT, respectively). Sprint training also attenuated the exercise-induced increases in plasma inosine, hypoxanthine (Hx), and uric acid during the first 120min of recovery and reduced the total urinary excretion of purines (inosine+ Hx+ uric acid) in the 24h recovery period following intense exercise. These results show that intermittent sprint training reduces the total urinary purine excretion after a 30 s sprint bout.

Different dietary proteins affect whole body protein anabolism and accretion and therefore, have the potential to influence results obtained from resistance training. This study examined the effects of supplementation with two proteins, hydrolyzed whey isolate (WI) and casein (C), on strength, body composition, and plasma glutamine levels during a 10 wk, supervised resistance training program. In a double-blind protocol, 13 male, recreational bodybuilders supplemented their normal diet with either WI or C (1.5 gm/kg body wt/d) for the duration of the program. Strength was assessed by 1-RM in three exercises (barbell bench press, squat, and cable pull-down). Body composition was assessed by dual energy X-ray absorptiometry. Plasma glutamine levels were determined by the enzymatic method with spectrophotometric detection. All assessments occurred in the week before and the week following 10 wk of training. Plasma glutamine levels did not change in either supplement group following the intervention. The WI group achieved a significantly greater gain (P < 0.01) in lean mass than the C group (5.0 +/- 0.3 vs. 0.8 +/- 0.4 kg for WI and C, respectively) and a significant (P < 0.05) change in fat mass (-1.5 +/- 0.5 kg) compared to the C group (+0.2 +/- 0.3 kg). The WI group also achieved significantly greater (P < 0.05) improvements in strength compared to the C group in each assessment of strength. When the strength changes were expressed relative to body weight, the WI group still achieved significantly greater (P < 0.05) improvements in strength compared to the C group.

Different dietary proteins affect whole body protein anabolism and accretion and therefore, have the potential to influence results obtained from resistance training. This study examined the effects of supplementation with two proteins, hydrolyzed whey isolate (WI) and casein (C), on strength, body composition, and plasma glutamine levels during a 10 wk, supervised resistance training program. In a double-blind protocol, 13 male, recreational bodybuilders supplemented their normal diet with either WI or C (1.5 gm/kg body wt/d) for the duration of the program. Strength was assessed by 1-RM in three exercises (barbell bench press, squat, and cable pull-down). Body composition was assessed by dual energy X-ray absorptiometry. Plasma glutamine levels were determined by the enzymatic method with spectrophotometric detection. All assessments occurred in the week before and the week following 10 wk of training. Plasma glutamine levels did not change in either supplement group following the intervention. The WI group achieved a significantly greater gain (P < 0.01) in lean mass than the C group (5.0 +/- 0.3 vs. 0.8 +/- 0.4 kg for WI and C, respectively) and a significant (P < 0.05) change in fat mass (-1.5 +/- 0.5 kg) compared to the C group (+0.2 +/- 0.3 kg). The WI group also achieved significantly greater (P < 0.05) improvements in strength compared to the C group in each assessment of strength. When the strength changes were expressed relative to body weight, the WI group still achieved significantly greater (P < 0.05) improvements in strength compared to the C group.

The influence of allopurinol on urinary purine loss was examined in 7 active male subjects (age 24.9 +/- 3.0 years, weight 82.8 +/- 8.3 kg, V O2peak 48.1 +/- 6.9 mL.kg(-1).min(-1)). These subjects performed, in random order, a trial with 5 days of prior ingestion of a placebo or allopurinol. Each trial consisted of eight 10-second sprints on an air-braked cycle ergometer and was separated by at least a week. A rest period of 50 seconds separated each repeated sprint. Forearm venous plasma inosine, hypoxanthine (Hx) and uric acid concentrations were measured at rest and during 120 minutes of recovery from exercise. Urinary inosine, Hx, xanthine, and uric acid excretion were also measured before and for 24 hours after exercise. During the first 120 minutes of recovery, plasma Hx concentrations, as well as the urinary Hx and xanthine excretion rates, were higher (P < .05) with allopurinol compared with the placebo trial. In contrast, plasma uric acid concentration and urinary uric acid excretion rates were lower (P < .05) with allopurinol. The total urinary excretion of purines (inosine + Hx + xanthine + uric acid) above basal levels was higher in the allopurinol trial compared with placebo. These results indicate that the total urinary purine excretion after intermittent sprint exercise was enhanced with allopurinol treatment. Furthermore, the composition of urinary purines was markedly affected by this drug.

Prolonged exhaustive submaximal exercise in humans induces marked metabolic changes, but little is known about effects on muscle Na+-K+-ATPase activity and sarcoplasmic reticulum Ca2+ regulation. We therefore investigated whether these processes were impaired during cycling exercise at 74.3 +/- 1.2% maximal O2 uptake (mean +/- SE) continued until fatigue in eight healthy subjects (maximal O2 uptake of 3.93 +/- 0.69 l/min). A vastus lateralis muscle biopsy was taken at rest, at 10 and 45 min of exercise, and at fatigue. Muscle was analyzed for in vitro Na+-K+-ATPase activity [maximal K+-stimulated 3-O-methylfluorescein phosphatase (3-O-MFPase) activity], Na+-K+-ATPase content ([3H]ouabain binding sites), sarcoplasmic reticulum Ca2+ release rate induced by 4 chloro-m-cresol, and Ca2+ uptake rate. Cycling time to fatigue was 72.18 +/- 6.46 min. Muscle 3-O-MFPase activity (nmol.min(-1).g protein(-1)) fell from rest by 6.6 +/- 2.1% at 10 min (P <0.05), by 10.7 +/- 2.3% at 45 min (P <0.01), and by 12.6 +/- 1.6% at fatigue (P <0.01), whereas 3[H]ouabain binding site content was unchanged. Ca2+ release (mmol.min(-1).g protein(-1)) declined from rest by 10.0 +/- 3.8% at 45 min (P <0.05) and by 17.9 +/- 4.1% at fatigue (P < 0.01), whereas Ca2+ uptake rate fell from rest by 23.8 +/- 12.2% at fatigue (P=0.05). However, the decline in muscle 3-O-MFPase activity, Ca2+ uptake, and Ca2+ release were variable and not significantly correlated with time to fatigue. Thus prolonged exhaustive exercise impaired each of the maximal in vitro Na+-K+-ATPase activity, Ca2+ release, and Ca2+ uptake rates. This suggests that acutely downregulated muscle Na+, K+, and Ca2+ transport processes may be important factors in fatigue during prolonged exercise in humans.

Background: We sought to determine whether skeletal muscle oxidative capacity, fiber type proportions, and fiber size, capillary density or muscle mass might explain the impaired exercise tolerance in chronic heart failure (CHF). Previous studies are equivocal regarding the maladaptations that occur in the skeletal muscle of patients with CHF and their role in the observed exercise intolerance. Methods and results Total body O(2) uptake (VO(2peak)) was determined in 14 CHF patients and 8 healthy sedentary similar-age controls. Muscle samples were analyzed for mitochondrial adenosine triphosphate (ATP) production rate (MAPR), oxidative and glycolytic enzyme activity, fiber size and type, and capillary density. CHF patients demonstrated a lower VO(2peak) (15.1+/-1.1 versus 28.1+/-2.3 mL.kg(-1).min(-1), P<.001) and capillary to fiber ratio (1.09+/-0.05 versus 1.40+/-0.04; P<.001) when compared with controls. However, there was no difference in capillary density (capillaries per square millimeter) across any of the fiber types. Measurements of MAPR and oxidative enzyme activity suggested no difference in muscle oxidative capacity between the groups. Conclusions: Neither reductions in muscle oxidative capacity nor capillary density appear to be the cause of exercise limitation in this cohort of patients. Therefore, we hypothesize that the low VO(2peak) observed in CHF patients may be the result of fiber atrophy and possibly impaired activation of oxidative phosphorylation.

This study tested the hypothesis that active recovery between bouts of intense aerobic exercise would lead to better maintenance of exercise performance in the second bout of exercise. Seven trained men on 2 separate occasions (VO(2peak) = 58.3+/- 9.4 ml x kg(-1) x min(-1)) performed as much work as possible during two 20-min cycling exercise bouts, separated by a 15-min recovery period. During passive recovery (PR), subjects rested supine, while during active recovery (AR) subjects continued to cycle at 40% VO(2peak). Muscle biopsies and blood samples were obtained. Neither muscle glycogen or lactate was different when comparing AR with PR at any point. In contrast, plasma lactate concentration was higher (p<.05) in PR versus AR during the recovery period, such that subjects commenced the second bout of intense exercise with a lower (p <.05) plasma lactate concentration in AR (4.4 +/- 0.7 vs. 7.7 +/- 1.4 mmol. L(-1) following AR and PR, respectively). Work performed in Bout 2 was less than that performed in Bout 1 in both trials (p<.01), with no difference in work performed between trials. These data do not support the benefit of AR when compared to PR in the maintenance of subsequent intense aerobic exercise performance.