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 (PO(2)) 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" PO(2) 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.

Microscopic imaging of extended tissue volumes.

1. Detailed information about three-dimensional structure is key to understanding biological function. 2. Confocal laser microscopy has made it possible to reconstruct three-dimensional organization with exquisite resolution at cellular and subcellular levels. 3. There have been few attempts to acquire large image volumes using the confocal laser scanning microscope. 4. Previously, we have used manual techniques to construct extended volumes (several mm in extent, at 1.5 microm voxel size) of myocardial tissue. 5. We are now developing equipment and efficient automated methods for acquiring extended morphometric databases using confocal laser scanning microscopy.

Cardiac electrical activity--from heart to body surface and back again.

We report here on our latest developments in the forward and inverse problems of electrocardiology. In the forward problem, a coupled cellular model of cardiac excitation-contraction is embedded within an anatomically realistic model of the cardiac ventricles, which is itself embedded within a torso model. This continuum modelling framework allows the effects of cellular-level activity on the surface electrocardiogram (ECG) to be carefully examined. Furthermore, the contributions of contraction and local ischemia on body surface recordings can also be elucidated. Such information can provide theoretical limits to the sensitivity and ultimately the detection capability of body surface ECG recordings. Despite being very useful, such detailed forward modelling is not directly applicable when seeking to use densely sampled ECG information to assess a patient in a clinical environment (the inverse problem). In such a situation patient specific models must be constructed and, due to the nature of the inverse problem, the level of detail that can be reliably reproduced is limited. Extensive simulation studies have shown that the accuracy with which the heart is localised within the torso is the primary limiting factor. To further identify the practical performance capabilities of the current inverse algorithms, high quality experimental data is urgently needed. We have been working towards such an objective with a number of groups, including our local hospital in Auckland. At that hospital, in patients undergoing catheter ablation surgery, up to 256 simultaneous body surface signals were recorded by using various catheter pacing protocols. The geometric information required to customize the heart and torso model was obtained using a combination of ultrasound and laser scanning technologies. Our initial results indicate that such geometric imaging modalities are sufficient to produce promising inversely-constructed activation profiles.