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The external work (EW) efficiency of individual arrhythmic beats of the left ventricle (LV) cannot directly be obtained since LV O(2) consumption (VO(2)) of each beat cannot directly be measured under beat-to-beat varying contractile and loading conditions. We, however, have recently reported that VO(2) of each arrhythmic beat can reasonably be estimated by VO(2) = aPVA + bE(max) + c even under varying PVA and E(max). Here, PVA is the LV pressure-volume (P-V) area as a measure of the LV total mechanical energy, E(max) is the LV end-systolic elastance as an index of the LV contractility, a is a constant O(2) cost of PVA, b is a constant O(2) cost of E(max), and c is the basal metabolic VO(2) of the beat, all on a per-beat basis. Using the above formula in this study, we calculated VO(2) of the individual arrhythmic beats from their measured PVA and E(max) during electrically induced atrial fibrillation (AF) in normal canine hearts. We then calculated their LV EW efficiency by dividing their measured EW with the estimated VO(2). We found that the thus calculated EW efficiency of the arrhythmic beats had a rightward skewed distribution with a mode of 15% and a maximum of 18% around a mean of 13% on average in six hearts. This mode remained comparable to the efficiency (15%) at regular tachycardia though 22% lower than mean arrhythmic tachycardia.

The goal of our study was to evaluate the origin of the increased O(2) consumption in electrically stimulated left ventricular slices of isoproterenol-induced hypertrophied rat hearts with normal left ventricular pressure. O(2) consumption per minute (mVO(2)) of mechanically unloaded left ventricular slices was measured in the absence and presence of 1-Hz field stimulation. Basal metabolic mVO(2), i.e., mVO(2) without electrical stimulation, was significantly smaller, but mVO(2) for the total Ca(2+) handling in excitation-contraction coupling (E-C coupling mVO(2)), i.e., delta mVO(2) (=mVO(2) with stimulation - mVO(2) without stimulation), was significantly larger in the hypertrophied heart. Furthermore, the fraction of E-C coupling mVO(2) was markedly altered in the hypertrophied heart. Namely, mVO(2) consumed by sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2) was depressed by 40%; mVO(2) consumed by the Na(+)/K(+)-ATPase (NKA)-Na(+)/Ca(2+) exchange (NCX) coupling was increased by 100%. The depressed mVO(2) consumption by SERCA2 was supported by lower protein expressions of phosphorylated-Ser(16) phospholamban and SERCA2. The increase in NKA-NCX coupling mVO(2) was supported by marked augmentation of NCX current. However, the increase in NCX current was not due to the increase in NCX1 protein expression, but was attributable to attenuation of the intrinsic inactivation mechanisms. The present results demonstrated that the altered origin of the increased E-C coupling mVO(2) in hypertrophy was derived from decreased SERCA2 activity (1ATP: 2Ca(2+)) and increased NCX activity coupled to NKA activity (1ATP: Ca(2+)). Taken together, we conclude that the energetically less efficient Ca(2+) extrusion pathway evenly contributes to Ca(2+) handling in E-C coupling in the present hypertrophy model.

We examined the sarcomere length-dependence of the spacing of the hexagonal lattice of the myofilaments and the mass transfer of myosin cross-bridges during contraction of right ventricular papillary muscle of the rat. The lattice spacing and mass transfer were measured by using X-ray diffraction, and the sarcomere length was monitored by laser diffraction at the same time. Although the lattice spacing and the sarcomere length were inversely related, their relationship was not exactly isovolumic. The cell volume decreased by about 15% when the sarcomere length was shortened from 2.3 micro m to 1.8 micro m. Twitch tension increased with sarcomere length (the Frank-Starling law). At the peak tension, the ratio of the intensity of the (1,0) equatorial reflection to that of the (1,1) reflection was smaller when the tension was greater, showing that the larger tension at a longer sarcomere length accompanies a larger amount of mass transfer of cross-bridges from the thick to the thin filament. The result suggests that the Frank-Starling law is due to an increase in the number of myosin heads attached to actin, not in the average force produced by each head.

The purpose of this study was to evaluate the feasibility of the conductance catheter (CC) method in measuring cross-sectional area (CSA) of small vessels like human coronary arteries. Lumen CSA (A) of phantom tubes (2–10 mm in diameter) and excised canine arteries (n = 10, 2.3–4.5 mm in diameter) were measured with 3-F CC (A cc) and intravascular ultrasound (A us). To investigate the influence of parallel conductance in accuracy of A cc, solution with various resistivities was applied to the surrounding of the arteries (n = 4). A cc showed an excellent agreement with phantom model CSA. In the excised arteries, A cc and A us highly correlated (R 2 = 0.906) with each other. When the resistivities of the solution surrounding the vessels was changed, A cc–Aus regression lines were similar regardless of different resistivities. The conductance method is feasible to measure CSA of small vessels like human coronary arteries.

Daniel Burkhoff MD PhD , Itzik Shemer , Bella Felzen , Juichiro Shimizu , Yuval Mika , Marc Dickstein , David Prutchi , Nissim Darvish 3 and Shlomo A. Ben-Haim 2,5 Divisions of Circulatory Physiology and Cardiology, Cardiac Physiology Laboratory, Department of Medicine, Columbia University, N.Y., Impulse Dynamics, Tirat HaCarmel 39120, Israel, Department of Physiology and Biophysics, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, P.O.B. 9649, Haifa 31096, Israel, Department of Anesthesiology, Columbia University, N.Y., Harvard-Thorndike Arrhythmia Institute, Beth-Israel Hospital, 330 Brookline Ave, Boston, Massachusetts 02215, USA

We have reported that the postextrasystolic potentiation (PESP) decays in alternans or monotonically, respectively, depending on whether the first postextrasystolic beat interval has a compensatory pause or not, in the canine left ventricle. To get better mechanistic insight into the alternans PESP decay, we hypothesized that the myocardial mechanical restitution and potentiation could partly account for both types of PESP decay. To test this hypothesis, we simulated PESP decay on a computer using a documented equation combining myocardial mechanical restitution and potentiation. We changed the first postextrasystolic beat interval after a fixed extrasystolic beat interval without changing regular and other postextrasystolic beat intervals. The simulated PESP decayed in alternans or monotonically as a function only of the first postextrasystolic beat interval. Thus, the myocardial mechanical restitution and potentiation could partly account for both alternans and monotonic decay of PESP. We conclude that myocardial mechanical restitution and potentiation may partly underlie the initial two alternating beats, the first beat being the most potentiated and the second beat being the most depressed, of alternans PESP decay in the canine heart.