Soyeon Goo

Trabeculae carneae as models of the ventricular walls: implications for the delivery of oxygen

Trabeculae carneae are the smallest naturally arising collections of linearly arranged myocytes in the heart. They are the preparation of choice for studies of function of intact myocardium in vitro. In vivo, trabeculae are unique in receiving oxygen from two independent sources: the coronary circulation and the surrounding ventricular blood. Because oxygen partial pressure (PO2) in the coronary arterioles is identical in specimens from both ventricles, whereas that of ventricular blood is 2.5-fold higher in the left ventricle than in the right ventricle, trabeculae represent a “natural laboratory” in which to examine the influence of “extravascular” PO2 on the extent of capillarization of myocardial tissue. We exploit this advantage to test four hypotheses. (1) In trabeculae from either ventricle, a peripheral annulus of cells is devoid of capillaries. (2) Hence, sufficiently small trabeculae from either ventricle are totally devoid of capillaries. (3) The capillary-to-myocyte ratios in specimens from either ventricle are identical to those of their respective walls. (4) Capillary-to-myocyte ratios are comparable in specimens from either ventricle, reflecting equivalent energy demands in vivo, driven by identical contractile frequencies and comparable wall stresses. We applied confocal fluorescent imaging to trabeculae in cross section, subsequently using semi-automated segmentation techniques to distinguish capillaries from myocytes. We quantified the capillary-to-myocyte ratios of trabeculae from both ventricles and compared them to those determined for the ventricular free walls and septum. Quantitative interpretation was furthered by mathematical modeling, using both the classical solution to the diffusion equation for elliptical cross sections, and a novel approach applicable to cross sections of arbitrary shape containing arbitrary disposition of capillaries and non-respiring collagen cords.

Dietary pre‐exposure of rats to fish oil does not enhance myocardial efficiency of isolated working hearts or their left ventricular trabeculae

Dietary fish oil has been found to have protective effects against cardiovascular disease, particularly in its role as an anti‐arrhythmic agent. An additional mechanism proposed for the putative cardio‐protective effect is enhanced efficiency of metabolic energy usage by the heart. We tested whether dietary supplementation of fish oil enhances cardiac efficiency or otherwise improves mechano‐energetic performance. Experiments were performed at two distinct physiological levels (whole organ and isolated tissues) employing two independent metabolic indices (oxygen consumption and heat production), respectively. Feeding rats with either a fish oil‐enriched or a saturated fatty acid‐enriched diet did not alter the efficiency of either the isolated whole heart or its left ventricular trabeculae.

Comparison of the Gibbs and Suga formulations of cardiac energetics: the demise of "isoefficiency".

Two very different sorts of experiments have characterized the field of cardiac energetics over the past three decades. In one of these, Gibbs and colleagues measured the heat production of isolated papillary muscles undergoing isometric contractions and afterloaded isotonic contractions. The former generated roughly linear heat vs. force relationships. The latter generated enthalpy-load relationships, the peak values of which occurred at or near peak isometric force, i.e., at a relative load of unity. Contractile efficiency showed a pronounced dependence on afterload. By contrast, Suga and coworkers measured the oxygen consumption (Vo(2)) while recording the pressure-volume-time work loops of blood-perfused isolated dog hearts. From the associated (linear) end-systolic pressure-volume relations they derived a quantity labeled pressure-volume area (PVA), consisting of the sum of pressure-volume work and unspent elastic energy and showed that this was linearly correlated with Vo(2) over a wide range of conditions. This linear dependence imposed isoefficiency: constant contractile efficiency independent of afterload. Neither these data nor those of Gibbs and colleagues are in dispute. Nevertheless, despite numerous attempts over the years, no demonstration of either compatibility or incompatibility of these disparate characterizations of cardiac energetics has been forthcoming. We demonstrate that compatibility between the two formulations is thwarted by the concept of isoefficiency, the thermodynamic basis of which we show to be untenable.

The collagenous microstructure of cardiac ventricular trabeculae carneae

Cardiac ventricular trabeculae are widely used in the study of cardiac muscle function, primarily because their myocytes are axially-aligned. However, their collagen content has not been rigorously determined. In particular, it is unknown whether the content of collagen differs between specimens originating from the left (LV) and right (RV) ventricles and whether, indeed, either corresponds to the collagen content of the ventricular walls themselves. In order to redress this deficit of knowledge, we have used the techniques of fluorescence confocal microscopy and environmental scanning electron microscopy to quantify the proportion of perimysial collagen comprising the cross-sectional area of trabeculae carneae. In trabeculae from both the RV and LV of adult rat hearts, collagen may occupy as little as 1% or as much as 100% of the cross-section. For specimens of dimensions typically used experimentally, there was no difference in average collagen content (6.03 ± 5.14%, n = 33) of preparations from the two ventricles.

Dietary supplementation with either saturated or unsaturated fatty acids does not affect the mechanoenergetics of the isolated rat heart

It is generally recognized that increased consumption of polyunsaturated fatty acids, fish oil (FO) in particular, is beneficial to cardiac and cardiovascular health, whereas equivalent consumption of saturated fats is deleterious. In this study, we explore this divergence, adopting a limited purview: The effect of dietary fatty acids on the mechanoenergetics of the isolated heart per se. Mechanical indices of interest include left‐ventricular (LV) developed pressure, stroke work, cardiac output, coronary perfusion, and LV power. The principal energetic index is whole‐heart oxygen consumption, which we subdivide into its active and basal moieties. The primary mechanoenergetic index of interest is cardiac efficiency, the ratio of work performance to metabolic energy expenditure. Wistar rats were divided into three Diet groups and fed, ad libitum, reference (REF), fish oil‐supplemented (FO), or saturated fatty acid‐supplemented (SFA) food for 6 weeks. At the end of the dietary period, hearts were excised, mounted in a working‐heart rig, and their mechanoenergetic performance quantified over a range of preloads and afterloads. Analyses of Variance revealed no difference in any of the individual mechanoenergetic indices among the three Diet groups. In particular, we found no effect of prior dietary supplementation with either saturated or unsaturated fatty acids on the global efficiency of the heart.

Assessing the Efficiency of the Diabetic Heart at Subcellular, Tissue and Organ Level

In this review, we focus on the diabetic heart rather than the vascular complications of diabetes. Focus is further narrowed to a specific, but widely used, animal model: the diabetic rat heart in which diabetes has been induced by a single injection of streptozotocin. Our experimental approach is primarily biophysical and ranges from measurements made in isolated working whole-hearts, to those made from isolated left-ventricular tissues and mitochondria. Our interest is on the effect of severe diabetes on cardiac energetics, in terms of efficiency of cardiac work performance, ATP synthesis and oxygen consumption. By designing experiments to test the energetic performance of the heart and its trabeculae across a wide range of protocols, we have revealed the dependence of efficiency on afterload. This has allowed us to clarify a long-standing uncertainty in the literature; whereas the diabetic heart is unable to work against high afterloads, it nevertheless retains normal peak efficiency. But a further anomaly has been revealed. Whereas there is no evidence that the diabetic myocardium loses peak mechanical efficiency, its mitochondria demonstrate a decreased P:O ratio - i.e., a decreased bioenergetic efficiency. This decrease is consistent with an increase in the rate of production of reactive oxygen species, together with elevated proton leakage across the inner mitochondrial membrane at near maximal phosphorylating respiration states.