Resistance exercise training is the most effective and accepted strategy for increasing skeletal muscle mass and strength. There is tremendous individual variability in the adaptive response to exercise and the source(s) contributing to this variability are largely unknown. Recent evidence in the literature supports the notion that capillaries may be a potential target for improving outcomes to chronic resistance exercise. Aerobic exercise training is a proven stimulus for eliciting angiogenesis and increasing capillary content. Therefore, we hypothesize that completing a period of aerobic training prior to resistance training will result in a greater increase in fibre cross sectional area (CSA) compared to resistance training alone. Fourteen participants (8M, 6F) completed 6 weeks of unilateral single leg aerobic training prior to undergoing 10 weeks of bilateral lower body resistance exercise training. Performance and anthropometric measures were completed at baseline, post aerobic training and post resistance training. Skeletal muscle biopsies were obtained from the vastus lateralis and immunofluorescent staining of muscle cross sections was completed to determine fibre CSA and satellite cell content. Following unilateral aerobic training, single leg VO2 work peak (Watts) (p<0.001), and oxygen consumption (O2 mL  min-1) (p=.0033) was significantly higher in the aerobically trained limb (EX) versus the control (CTL) limb. Capillary to perimeter fibre exchange index (CFPE) (p<0.05), a measure of microvascular perfusion, was significantly higher in the EX versus CTL limb following unilateral aerobic training. Resistance training resulted in increases in 1-repetition maximum of both squat (p<0.0001) and leg press (p<0.0001). A main effect of time was observed for limb fat free mass (p<0.0001) as determined via DEXA. Type-II fibre CSA of the EX limb was greater (p<0.05) versus CTL limb following resistance exercise training. Type-II fibre associated satellite cell content of the CTL limb was elevated (p<0.01) following resistance training. Results suggest that a period of unilateral aerobic training elevates the aerobic capacity and relative microvascular perfusion of the trained leg significantly in comparison to the non-aerobically conditioned limb. Subsequent resistance training, bilateral leg strength increased post resistance training while type II CSA increased in the aerobically pre-conditioned limb following resistance training. Collectively, these results suggest that a period of aerobic preconditioning may augment the muscle’s ability to respond to a hypertrophic stimulus. / Thesis / Master of Science (MSc) / Resistance exercise training is the most effective and accepted strategy for increasing skeletal muscle mass and strength. Yet, there is tremendous individual variability in the adaptive response to exercise and the source(s) contributing to this variability are largely unknown. Recently, evidence has emerged suggesting that capillaries may be a potential target for enhancing the adaptive response to chronic resistance exercise training. Research has only begun to characterize the extent to which microvascular perfusion (capillarization and blood flow to the muscle) plays a role in muscle health and resistance training outcomes. Currently, it is unknown if elevating microvascular perfusion is enough to facilitate greater accretion (hypertrophy) of muscle mass and strength following resistance training. Therefore, the current study hypothesized that increased microvascular perfusion induced by a pre-conditioning period of aerobic training, lasting 6-weeks, would be sufficient to enhance muscle accretion (hypertrophy) and elevate muscle stem cell content following resistance exercise training. To examine this, a cohort of young men and women performed 6 weeks of unilateral (single-leg) cycling following by 10 weeks of bilateral (both legs) resistance exercise training. Results demonstrated an increased oxidative capacity and capillary perfusion in the aerobically-trained limb following single-leg cycling, as expected. Consistent with our initial hypothesis, we observed superior muscle hypertrophy of type-II muscle fibres (increased fibre cross-sectional area), in the aerobically-conditioned limb following resistance training. The results suggest that muscle capillarization may be a determinant and facilitator of adaptation to resistance training and its outcomes.

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ABSTRACT There is substantial evidence to suggest that independent of conventional BP, LV mass (LVM) is higher in African-Americans than in European-Americans a difference that may translate into a higher prevalence of cardiovascular diseases. In the present thesis I assessed whether LVM is similarly elevated in groups of African descent living in Africa, and subsequently whether 24-hour, day or night BP or indices of arterial stiffness could explain the variability in LVM beyond conventional BP in this population group. As there is considerable controversy as to whether 24-hour BP measurements are better predictors of the regression of LVH than conventional BP and whether antihypertensive agents that target the renin-angiotensin system (RAS) regress LV hypertrophy (LVH) independent of BP in groups of African descent, in the present thesis I therefore also assessed these questions. In 141 healthy adult participants obtained from a random sample of nuclear families (n=399) of African ancestry living in Soweto, I determined that LVM adjusted for body surface area to the first power was an appropriate allometric signal to account for growth effects on LVM. The allometric signals established in other populations considerably over-adjusted for LVM in the group that I studied with marked negative relations noted. After adjusting for body surface area I noted upper thresholds of LVM index (LVMI) of 134 g/m2 for men and 112 g/m2 for women. As compared to thresholds described for other population samples these thresholds were noted to be modestly higher. In 187 women from randomly recruited nuclear families of African ancestry, after appropriate adjustments, conventional BP was as closely associated with LVMI as 24- hour BP, and daytime BP was as closely associated with LVMI as night-time BP in women. However, in 110 men from randomly recruited nuclear families of African ancestry, after appropriate adjustments, only night-time BP was associated with LVMI, an effect that was independent of conventional BP (r=0.21, p<0.05). Indices of nocturnal decreases in BP were not associated with LVMI in either gender group. Furthermore, in randomly recruited nuclear families of African ancestry, after appropriate adjustments, including systolic BP or pulse pressure, pulse wave velocity (an index of arterial stiffness assessed using applanation tonometry) was independently associated with LVMI in women (n=204, r=0.25, p<0.0005), but not in men (n=123, r=-0.07). In 173 hypertensive patients of African descent of whom 64 were previously untreated and 109 were previously treated, I assessed whether ambulatory BP is a better predictor of on-treatment decreases in LVMI over a 4 month treatment period. In the previously untreated patients, the regression in LVMI correlated to a similar degree (p<0.09) with decreases in conventional (r=0.34; p<0.005) and 24-hour (r=0.26; p<0.04) systolic BP. In this same study sample followed prospectively for 25 months, accounting for effects on ambulatory BP at each time point, the use of the angiotensin-converting enzyme inhibitor, enalapril, was not associated with LVMI, whereas, on-treatment conventional systolic BP (p=0.01) and night-time systolic BP (p=0.01) were associated with LVMI. In a further study conducted in 87 patients of African ancestry with hypertension and LVH, I showed that changes in systolic ambulatory BP (daytime, r=0.46, p=0.006) were predictive of changes in LVMI after 2 months of treatment with an angiotensin II receptor blocker (candesartan), ACE-I (ramipril) and the diuretic agent, hydrochlorothiazide. Moreover, in a final study I showed that in hypertensive patients of African ancestry, initiating therapy with the diuretic, indapamide SR and then adding the ACE-I, perindopril 4 mg (n=42), was equally as effective as amlodipine (calcium channel blocker) (n=44) therapy at reducing ambulatory BP and LVMI. Thus, in conclusion, groups of African descent living in Africa have only marginally higher thresholds for LVM than other population groups. Moreover, in this population group, nocturnal BP has a conventional BP-independent effect on LVMI in men, but not in women, whereas arterial stiffness has a conventional BP-independent effect on LVMI in women, but not in men. Further, in this population, reductions in LVM produced by antihypertensive therapy appear to be equally as closely related to conventional as ambulatory BP and in contrast to findings in groups of European ancestry, where RAS blockers produce unique benefits on LVM beyond conventional BP reductions, in groups of African ancestry in Africa, RAS blockers produce no BPindependent reductions in LVM. Moreover, in this population, decreases in LVM in patients with LVH produced by RAS blockers are related to ambulatory BP changes and despite the ineffectiveness of RAS blockers on BP when used as monotherapy in this population, RAS blockers together with diuretics are equally as effective in decreasing BP and LVM as compared to a class of antihypertensive agents with established efficacy (calcium channel blockers). Hence when compelling indications for RAS blockade exist, RAS blocker-diuretic combinations are effective therapy in patients of African descent living in Africa.

Abstract not available

The newborn heart possesses a higher tolerance to ischemia in comparison to adult hearts. Post-ischemic interventions that increase energy production are beneficial for recovery. These data suggest that the newborn heart holds on a very tight energetic plasticity and may not be capable to effectively respond to increases in energetic demand. Congenital heart defects can lead to the development of cardiac hypertrophy and often require surgical intervention. Using an animal model of newborn hypertrophy and biventricular isolated working heart we confirm the metabolic profile of the newborn rabbit heart, in which fatty acid oxidation provides the vast majority of energy to the heart. Our findings show that when right ventricle load is added, the increasing energy requirements are met by increasing glucose oxidation rates. Our data generated by the isolated biventricular working heart model further supports the concept of the newborn heart in a state of deficient energy reserve.

Myocyte hypertrophy is the major compensatory response of the heart to chronic stress. It is induced by the activation of a network of interdependent, intracellular signaling pathways.1 An important pathway activated during the hypertrophic response is the calcineurin Abeta-NFATc transcription factor pathway.2 Our laboratory has recently discovered that calcineurin Abeta and NFATc transcription factors can associate with the scaffold protein mAKAPbeta.3 mAKAPbeta is a scaffold protein that forms a multimolecular signalosome located to the nuclear envelope of cardiac myocytes. Preliminary data demonstrate that calcineurin Abeta binds to a specific site on mAKAPbeta that lacks any of the consensus calcineurin binding sequences previously described. In this report, it is shown that a peptide, which contains the mAKAPbeta -calcineurin Abeta binding domain, associates with calcineurin Abeta in a calcium/calmodulin dependent manner. In addition, the binding of this mAKAPbeta peptide to calcineurin Abeta has no effect on calcineurin?s phosphatase activity. In fact, calcineurin Abeta bound to this mAKAPbeta peptide is catalytically active and capable of dephosphorylating NFAT. This is novel since other scaffold proteins that associate with calcineurin Abeta have been reported to inhibit its phosphatase activity. Furthermore, in our laboratory it has been shown that mAKAPbeta is required for both the nuclear translocation of NFATc and the induction of myocyte hypertrophy in vitro.4 In this report it is demonstrated that inhibition of calcineurin Abeta association to mAKAPbeta affects NFATc phosphorylation state and attenuates the norepinephrine induced hypertrophic response in primary neonatal cardiac myocytes. This study supports the hypothesis that the formation of multimolecular signaling complexes, like the mAKAPbeta signalosome, is necessary for the integration and fidelity of signal transduction involved in physiological processes like hypertrophy. Although hypertrophy is an adaptive response; it is often accompanied by maladaptive remodeling of the heart that can result in heart failure, a leading cause of death in the United States. Research in the signaling complexes involved in myocyte hypertrophy, like the mAKAPbeta signalosome, may lead to the development of novel treatments for pathologic hypertrophy and heart failure.

It is now generally accepted that strength training in pubertal children will increase strength, but it is unlikely to induce morphological changes. However research in this area is limited as most studies fail to control for the confounding effects of normal growth, or employ appropriate training programs. To overcome these limitations it is suggested that researchers should use a within-subject design employing an exercise regime of sufficient intensity. In adults, eccentric training has been shown to have the greatest effect on hypertrophy and strength. The purpose of the study was to examine the effects of eccentric training on muscle strength and development in children, using a one arm training model. Seventeen boys in grades 6, 7, and 8 participated in an eight week eccentric elbow flexion training program; three training sessions per week. The program consisted of 2 5 sets of 6 10 reps using progressive resistance. Pre and post test strength (Eccentric and concentric elbow flexion maximal strength by a Biodex System 3 Dynamometer and 1 RM with dumbbells) and bicep thickness measurements were performed. The change in biceps thickness was significantly greater in the training arm versus the non-training arm (7.3 +/- 8.3% vs. 0.7 +/- 7.5%) (p<0.05). No significant difference was found for isokinetic concentric strength gain between arms (p>0.05), but isokinetic eccentric strength gain in the training arm was significantly greater than the non-training arm (25.4 +/- 16.6% vs. 2.4% +/- 15.6%) (p<0.05). Training arm 1 RM isotonic strength significantly increased when compared to the non-training arm, both concentrically (35.0 +/- 15.8% vs. 14.8 +/- 13.1%) and eccentrically (45.0 +/- 16.1% vs. 21.8 +/- 8.0%) (p<0.05). Results from this study indicate eccentric strength training can increase muscle strength and hypertrophy in pubertal boys.

It is now generally accepted that strength training in pubertal children will increase strength, but it is unlikely to induce morphological changes. However research in this area is limited as most studies fail to control for the confounding effects of normal growth, or employ appropriate training programs. To overcome these limitations it is suggested that researchers should use a within-subject design employing an exercise regime of sufficient intensity. In adults, eccentric training has been shown to have the greatest effect on hypertrophy and strength. The purpose of the study was to examine the effects of eccentric training on muscle strength and development in children, using a one arm training model. Seventeen boys in grades 6, 7, and 8 participated in an eight week eccentric elbow flexion training program; three training sessions per week. The program consisted of 2 5 sets of 6 10 reps using progressive resistance. Pre and post test strength (Eccentric and concentric elbow flexion maximal strength by a Biodex System 3 Dynamometer and 1 RM with dumbbells) and bicep thickness measurements were performed. The change in biceps thickness was significantly greater in the training arm versus the non-training arm (7.3 +/- 8.3% vs. 0.7 +/- 7.5%) (p<0.05). No significant difference was found for isokinetic concentric strength gain between arms (p>0.05), but isokinetic eccentric strength gain in the training arm was significantly greater than the non-training arm (25.4 +/- 16.6% vs. 2.4% +/- 15.6%) (p<0.05). Training arm 1 RM isotonic strength significantly increased when compared to the non-training arm, both concentrically (35.0 +/- 15.8% vs. 14.8 +/- 13.1%) and eccentrically (45.0 +/- 16.1% vs. 21.8 +/- 8.0%) (p<0.05). Results from this study indicate eccentric strength training can increase muscle strength and hypertrophy in pubertal boys.