A structure-function analysis of the left ventricle.

This study presents a structure-function analysis of the mammalian left ventricle and examines the performance of the cardiac capillary network, mitochondria, and myofibrils at rest and during simulated heavy exercise. Left ventricular external mechanical work rate was calculated from cardiac output and systemic mean arterial blood pressure in resting sheep (Ovis aries; n = 4) and goats (Capra hircus; n = 4) under mild sedation, followed by perfusion-fixation of the left ventricle and quantification of the cardiac capillary-tissue geometry and cardiomyocyte ultrastructure. The investigation was then extended to heavy exercise by increasing cardiac work according to published hemodynamics of sheep and goats performing sustained treadmill exercise. Left ventricular work rate averaged 0.017 W/cm3 of tissue at rest and was estimated to increase to ∼0.060 W/cm3 during heavy exercise. According to an oxygen transport model we applied to the left ventricular tissue, we predicted that oxygen consumption increases from 195 nmol O2·s-1·cm-3 of tissue at rest to ∼600 nmol O2·s-1·cm-3 during heavy exercise, which is within 90% of the oxygen demand rate and consistent with work remaining predominantly aerobic. Mitochondria represent 21-22% of cardiomyocyte volume and consume oxygen at a rate of 1,150 nmol O2·s-1·cm-3 of mitochondria at rest and ∼3,600 nmol O2·s-1·cm-3 during heavy exercise, which is within 80% of maximum in vitro rates and consistent with mitochondria operating near their functional limits. Myofibrils represent 65-66% of cardiomyocyte volume, and according to a Laplacian model of the left ventricular chamber, generate peak fiber tensions in the range of 50 to 70 kPa at rest and during heavy exercise, which is less than maximum tension of isolated cardiac tissue (120-140 kPa) and is explained by an apparent reserve capacity for tension development built into the left ventricle.

Bone resorption is suppressed immediately after the third and fourth days of multiday cycling but persistently increased following overnight recovery.

Previous studies suggest that seasoned cyclists may incur a low bone mineral density. This study investigated the effect of multiday cycling on bone turnover. Ten male cyclists completed 4 consecutive days of cycling for 3 h·day(-1). Sweat calcium excretion during exercise and serum calcium, cortisol, bone formation marker (bone alkaline phosphotase (bone-ALP)), bone resorptive marker (C-terminal telopeptide of type I collagen (ß-CTX)), and parathyroid hormone concentration were measured before and immediately postexercise each day. Serum ß-CTX concentration increased from pre- to postcycling on days 1 and 2 (p = 0.01) (day 1: 0.31 ± 0.14 to 0.60 ± 0.4 ng·mL(-1); day 2: 0.58 ± 0.26 to 0.87 ± 0.42 ng·mL(-1)), while serum bone-ALP concentration remained unchanged. Conversely, on days 3 and 4 both serum ß-CTX (day 3: 0.60 ± 0.26 to 0.43 ± 0.26 ng·mL(-1), p < 0.05; day 4: 0.63 ± 0.21 to 0.43 ± 0.22 ng·mL(-1), p < 0.001) and bone-ALP (p < 0.01) response to exercise was suppressed. Interestingly, calcium lost to sweat and postexercise serum cortisol concentration were also significantly lower on days 3 and 4 than on day 1 (p < 0.05). However, both serum ß-CTX (102%-124%) and bone-ALP (25%-29%) remained persistently elevated after 21 h of overnight recovery on all successive days compared with day 1 pre-exercise, where the percentage increase was greater for ß-CTX (p < 0.05). Bone resorption, immediately following prolonged cycling, is acutely reduced by the third and fourth consecutive days and is coincident to reduced sweat calcium excretion and cortisol concentration. However, multiday cycling imposes a persistent increase in bone resorption following overnight recovery.

Rheumatoid arthritis impacts on the independent relationships between circulating adiponectin concentrations and cardiovascular metabolic risk.

Adiponectin and leptin are likely involved in the pathophysiology of rheumatoid arthritis (RA) and therefore potential new therapeutic targets. Adiponectin inhibition could be expected to enhance cardiovascular metabolic risk. However, it is unknown whether RA changes the influence of adipokines on cardiovascular metabolic risk. We determined whether RA impacts on the independent relationships of circulating leptin and adiponectin concentrations with cardiovascular risk factors and carotid intima-media thickness (cIMT) in 277 black African subjects from a developing population; 119 had RA. RA impacted on the relationships of adiponectin concentrations with lipid concentrations and blood pressure, independent of confounders including adiposity (interaction P < 0.05). This translated into an association of adiponectin concentrations with more favorable lipid variables including HDL cholesterol (P = 0.0005), non-HDL cholesterol (P = 0.007), and triglyceride (P = 0.005) concentrations, total cholesterol-HDL cholesterol (P = 0.0002) and triglycerides-HDL cholesterol (P = 0.0003) ratios, and higher systolic (P = 0.0006), diastolic (P = 0.0004), and mean blood pressure (P = 0.0007) in RA but not non-RA subjects. Leptin was not associated with metabolic risk after adjustment for adiposity. The cIMT did not differ by RA status, and adipokine concentrations were unrelated to atherosclerosis. This study suggests that leptin and adiponectin inhibition may not alter overall cardiovascular risk and disease in RA.

Contribution of circulating angiotensinogen concentrations to variations in aldosterone and blood pressure in a group of African ancestry depends on salt intake.

In high-Na(+), low-K(+) diets, which suppress renin release in salt-sensitive groups, the mechanisms maintaining increases in renin-angiotensin-aldosterone system activation downstream from renin and renin-angiotensin-aldosterone system-induced effects on blood pressure (BP) are uncertain. Whether circulating angiotensinogen concentrations (AGT) or its determinants may contribute to maintaining serum aldosterone concentrations (aldosterone) and increases in BP on high-Na(+), low-K(+) diets was evaluated in 579 participants of a community sample of African ancestry. Plasma renin concentrations were inversely related to BP (P<0.0001) and an index of salt intake (24-hour urinary Na(+)/K(+), P<0.0001). An interaction between AGT and urinary Na(+)/K(+) was independently associated with aldosterone (P<0.001) and systolic BP (SBP; P<0.05). Independent of confounders, in participants with urinary Na(+)/K(+) at or more than the median for the sample, AGT was positively associated with aldosterone (P<0.0001) and SBP (P<0.005). No independent AGT-aldosterone or AGT-SBP relationships were noted in participants with urinary Na(+)/K(+) less than the median for the sample. Standardized ß-coefficients (slopes) of AGT-aldosterone and AGT-SBP relationships were greater in participants with urinary Na(+)/K(+) at or more than the median (AGT-aldosterone=0.30±0.06, AGT-SBP=0.16±0.05) compared with those with urinary Na(+)/K(+) less than the median (AGT-aldosterone=-0.04±0.06; AGT-SBP=-0.03±0.05; P<0.01-0.0001 for comparison of slopes). The AGT-SBP relationship in participants with urinary Na(+)/K(+) at or more than the median for the sample was equivalent to the relationship between body mass index and BP. In conclusion, in participants of African ancestry, in the presence of high-Na(+), low-K(+) diets, which suppress renin release, renin-angiotensin-aldosterone system activation and its impact on BP are maintained in part by AGT.