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/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.

Keywords: capillary; heart; mitochondria; myofibril; work.

Fig. 1.

Electron micrographs of left ventricular tissue showing the hierarchy of magnifications used for stereological analysis. A: low magnification (×1,700) used to determine the densities of cardiomyocytes, collagen, capillaries, fibroblast cells, pericytes, and other larger noncapillary vessels in the left ventricular tissue. B: high magnification (×11,500) used to determine the densities of myofibrils, mitochondria, sarcoplasmic reticuli, t-tubules, nuclei, and other components (cytosol, lipid, sarcolemma, intercalated disc) within the cardiomyocytes. C: capillary micrographs (×4,200) used for luminal diameter measurements. D: mitochondrion micrographs (×60,000) used for inner membrane surface density measurements. Images in A–C are from goats, and image in D is from a sheep.

Fig. 2.

Output of the oxygen transport model that we applied to the left ventricular tissue of sheep and goats during simulated heavy exercise. A: blood entering the capillary has a Po₂ of 16.6 kPa, whereas blood exiting has a Po₂ of 0.6 kPa. Tissue regions operating at Po₂ levels <0.05 kPa (light grey) and <0.01 kPa (dark grey) are shown. Mean capillary path length (L) is 0.060 cm, capillary radius (R_c) is 0.00036 cm, and tissue cylinder radius (R_t) is 0.0012 cm. This is for the standard case assuming an oxygen demand rate of 670 nmol O₂·s⁻¹·cm⁻³ of tissue and an external mechanical efficiency of 20%. B: predicted effect of varying the oxygen demand rate (nmol O₂·s⁻¹·cm⁻³ of tissue) on the proportion of cardiac tissue operating at Po₂ levels <0.05 and <0.01 kPa. C: predicted effect of varying the external mechanical efficiency (%) on the proportion of cardiac tissue operating at <0.05 and <0.01 kPa.

Fig. 3.

Output of the oxygen transport model that we applied to the left ventricular tissue of sheep and goats showing the relationship between oxygen supply, demand, and consumption. Predicted oxygen consumption rate (nmol O₂·s⁻¹·cm⁻³ of tissue) keeps pace with an increasing oxygen demand rate (nmol O₂·s⁻¹·cm⁻³), except at very high levels of demand, where consumption is limited by the oxygen supply rate (nmol O₂·s⁻¹·cm⁻³). This is for the standard case assuming an external mechanical efficiency of 20%. Inset: same model as applied to skeletal muscle (47).

Fig. 4.

Interspecific scaling of mitochondrial and myofibril volume density in the left ventricle of mammals. A: mitochondrial volume density (% of cardiomyocyte) in sheep and goats from the present study (●) and in other mammals sourced from the literature, including shrew, bat, wood mouse, house mouse, rat, guinea pig, ferret, rabbit, cat, fox, coyote, wolf, dog, goat, human, pig, horse, and cow (○) (5, 25, 36). B: myofibril volume density (% of cardiomyocyte) in sheep and goats from the present study and in the other mammals sourced from the literature. Myofibril volume densities in the other mammals are either published values or calculated by subtraction of the volume density of the mitochondria and of the other cardiomyocyte components (assumed to represent 12.7% of cardiomyocyte volume as determined in the present study). M_body is body mass (kg). Exponents are presented with ±95% CI.