A structure-function analysis of the left ventricle

Abstract

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/cm of tissue at rest and was estimated to increase to ∼0.060 W/cm 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 O·s·cm of tissue at rest to ∼600 nmol O·s·cm 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 O·s·cm of mitochondria at rest and ∼3,600 nmol O·s·cm 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.

Scaling of morphology and ultrastructure of hearts among wild African antelope

“…Nonetheless, if the scaling of heart mass is associated with stroke work (≈stroke volume×mean arterial blood pressure), then stroke work would be predicted to scale with an exponent of 0.88, and if maximum heart rate scales with an exponent of −0.16, as it does across broader interspecific analyses of mammals (Bishop, 1997), then assuming the heart's metabolic to mechanical energy conversion efficiency is independent of body mass, we would expect the antelope heart's maximum oxygen-consumption rate to scale with an exponent of 0.88-0.16=0.72, not far off the scaling of 0.74-0.78 obtained for the structures that support this cardiac work. Further evidence for symmorphosis at the cellular level of cardiac design for the oxygen cascade is provided by mathematical modelling that shows perfusion and cardiac capillary investment are sufficient to satisfy approximately 90% of the heart's maximum oxygen requirements, and that cardiac mitochondria operate within 80% of their capacity when the heart is working near its functional limits during simulated heavy exercise (Snelling et al, 2016). Adequate perfusion and a proportionate investment of cardiac capillaries is further implied by evidence that shows lactate release from the myocardium is relatively modest during exercise (Gertz et al, 1981(Gertz et al, , 1988van Hall, 2010).…”

“…; Kyron Laboratories, Johannesburg, South Africa). We then fixed their hearts chemically using solutions that we had established for sheep and goat hearts (Snelling et al, 2016). We made no attempt to fix the heart in a particular state of contraction.…”

“…While some uncertainty remains regarding a universal scaling law for heart size in mammals, there is greater uncertainty about the scaling of the ultrastructural components of the heart that relate to myocardial oxygen supply and oxygen consumption. In particular, analysis of the scaling of the heart's capillary and mitochondrial components would be valuable because these structures are responsible for the delivery and consumption of oxygen in an organ that remains predominantly aerobic even during periods of maximum mechanical work (Snelling et al, 2016;Stanley et al, 2005). The only ultrastructure scaling analysis carried out to date showed that across 11 species of mammal, the heart's mitochondrial volume density scales with body mass according to a power equation with an exponent of −0.04±0.02, a value significantly less than zero (independent of body mass), and representing an appreciable decrease in mitochondrial volume density from 36.1% in a 2.4 g shrew to 21.1% in a 920 kg cow (Hoppeler et al, 1984).…”

Two-dimensional speckle tracking echocardiography in goats: repeatability, variability, and validation of the technique using an exercise test and an experimentally induced acute ischemic cardiomyopathy.

“…As echocardiographic measurements were shown to vary strongly with HR and with exercise intensity, standardized exercise tests were developed in horses [30,31] and humans [32]. This is not the case in goats, although different exercise tests have already been performed in this species for other reasons than stress echocardiography [13,33]. Moreover, unlike in humans, echocardiography could not be achieved during an exercise test in animals, thus stress echocardiography in animals was performed just after the end of exercise [29,31].…”

Two-dimensional speckle tracking echocardiography in goats: repeatability, variability, and validation of the technique using an exercise test and an experimentally induced acute ischemic cardiomyopathy.

“…As echocardiographic measurements were shown to vary strongly with HR and with exercise intensity, standardized exercise tests were developed in horses [30,31] and humans [32]. This is not the case in goats, although different exercise tests have already been performed in this species for other reasons than stress echocardiography [13,33]. Moreover, unlike in humans, echocardiography could not be achieved during an exercise test in animals, thus stress echocardiography in animals was performed just after the end of exercise [29,31].…”