Mechanisms of vortices termination in the cardiac muscle

We propose a solution to a long standing problem: how to terminate multiple vortices in the heart, when the locations of their cores and their critical time windows are unknown. We scan the phases of all pinned vortices in parallel with electric field pulses (E-pulses). We specify a condition on pacing parameters that guarantees termination of one vortex. For more than one vortex with significantly different frequencies, the success of scanning depends on chance, and all vortices are terminated with a success rate of less than one. We found that a similar mechanism terminates also a free (not pinned) vortex. A series of about 500 experiments with termination of ventricular fibrillation by E-pulses in pig isolated hearts is evidence that pinned vortices, hidden from direct observation, are significant in fibrillation. These results form a physical basis needed for the creation of new effective low energy defibrillation methods based on the termination of vortices underlying fibrillation.The research leading to the results has received funding from Max Planck Gesellschaft, the European Community Seventh Framework Pro- gramme FP7/2007-2013 under Grant Agreement 17 No. HEALTH-F2-2009-241526, EUTrigTreat (DH, TB, SB, VIK, SL), and from EPSRC (UK) grant EP/I029664 (VNB).We also acknowledge support from the German Federal Ministry of Education and Research (BMBF) (project FKZ 031A147, GO-Bio), the German Research Foundation (DFG) (Collaborative Research Centres SFB 1002 Project C3 and SFB 937 Project A18), the Ger- man Center for Cardiovascular Research (DZHK e.V.) (DH, TB, SB, VIK, SL), Science & Engineering Research Board of Department of Science & Technology, Govern- ment of India (TKS), EPSRC (UK) grant EP/N014391 (VNB) and U.S. NIH Grant No. R01HL089271 (NFO)

Mechanisms of vortices termination in the cardiac muscle

We propose a solution to a long standing problem: how to terminate multiple vortices in the heart, when the locations of their cores and their critical time windows are unknown. We scan the phases of all pinned vortices in parallel with electric field pulses (E-pulses). We specify a condition on pacing parameters that guarantees termination of one vortex. For more than one vortex with significantly different frequencies, the success of scanning depends on chance, and all vortices are terminated with a success rate of less than one. We found that a similar mechanism terminates also a free (not pinned) vortex. A series of about 500 experiments with termination of ventricular fibrillation by E-pulses in pig isolated hearts is evidence that pinned vortices, hidden from direct observation, are significant in fibrillation. These results form a physical basis needed for the creation of new effective low energy defibrillation methods based on the termination of vortices underlying fibrillation.The research leading to the results has received funding from Max Planck Gesellschaft, the European Community Seventh Framework Pro- gramme FP7/2007-2013 under Grant Agreement 17 No. HEALTH-F2-2009-241526, EUTrigTreat (DH, TB, SB, VIK, SL), and from EPSRC (UK) grant EP/I029664 (VNB).We also acknowledge support from the German Federal Ministry of Education and Research (BMBF) (project FKZ 031A147, GO-Bio), the German Research Foundation (DFG) (Collaborative Research Centres SFB 1002 Project C3 and SFB 937 Project A18), the Ger- man Center for Cardiovascular Research (DZHK e.V.) (DH, TB, SB, VIK, SL), Science & Engineering Research Board of Department of Science & Technology, Govern- ment of India (TKS), EPSRC (UK) grant EP/N014391 (VNB) and U.S. NIH Grant No. R01HL089271 (NFO)

Uncovering the Dynamics of Cardiac Systems Using Stochastic Pacing and Frequency Domain Analyses

Alternans of cardiac action potential duration (APD) is a well-known arrhythmogenic mechanism which results from dynamical instabilities. The propensity to alternans is classically investigated by examining APD restitution and by deriving APD restitution slopes as predictive markers. However, experiments have shown that such markers are not always accurate for the prediction of alternans. Using a mathematical ventricular cell model known to exhibit unstable dynamics of both membrane potential and Ca2+ cycling, we demonstrate that an accurate marker can be obtained by pacing at cycle lengths (CLs) varying randomly around a basic CL (BCL) and by evaluating the transfer function between the time series of CLs and APDs using an autoregressive-moving-average (ARMA) model. The first pole of this transfer function corresponds to the eigenvalue (λalt) of the dominant eigenmode of the cardiac system, which predicts that alternans occurs when λalt≤−1. For different BCLs, control values of λalt were obtained using eigenmode analysis and compared to the first pole of the transfer function estimated using ARMA model fitting in simulations of random pacing protocols. In all versions of the cell model, this pole provided an accurate estimation of λalt. Furthermore, during slow ramp decreases of BCL or simulated drug application, this approach predicted the onset of alternans by extrapolating the time course of the estimated λalt. In conclusion, stochastic pacing and ARMA model identification represents a novel approach to predict alternans without making any assumptions about its ionic mechanisms. It should therefore be applicable experimentally for any type of myocardial cell

Use of Ultrasound Imaging to Map Propagating Action Potential Waves in the

Presently, the nature of action potential propagation deep within myocardial tissue is unclear. As a result, a complete understanding of cardiac dynamics remains elusive. Here we present a technique using ultrasound and electromechanical modeling that has the potential to unlock this mystery. We also present information suggesting tension in the heart behaves as a long-range force incapable of being captured through only local observation of myocardial tissue deformation. 1

Glomerular CD34 Expression in Short- and Long-term Diabetes

Aging and diabetes are associated with exacerbated expression of adhesion molecules. Given their importance in endothelial dysfunction and their possible involvement in the alteration of glomerular permeability occurring in diabetes, we have evaluated expression of the sialomucin-type adhesion molecule CD34 in renal glomerular cells of normal and diabetic animals at two different ages by colloidal gold immunocytochemistry and immunoblotting. CD34 labeling was mostly assigned to the plasma membranes of glomerular endothelium and mesangial processes. Podocyte membranes were also labeled, but to a lesser degree. Short- and long-term diabetes triggers a substantial increase in immunogold labeling for CD34 in renal tissues compared with young normoglycemic animals. However, the level of labeling in old diabetic and healthy control rats is similar, suggesting that the effect of diabetes and aging on CD34 expression is similar but not synergistic. Western blotting of isolated glomerular fractions corroborated immunocytochemical results. Increased expression of CD34 may reflect its involvement in the pathogenesis of glomerular alterations related to age and diabetes. Alterations present in early diabetes, resembling those occurring with age, strengthen the concept that diabetes is an accelerated form of aging.(J Histochem Cytochem 56:605–614, 2008