Computer modeling has shown that conduction velocity (CV), upstroke rate, and action potential amplitude are all increased relative to the straight-fiber case when fibers curve toward the wavefront (i.e., the wavefront propagates toward the concave side). also present when pacing was slowed from 350 ms to 500 ms (n=6). In a control group (n=8) with uncurved fibers, CV was the same in both directions (p=NS). We conclude that fiber curvature is a factor in modulating cardiac propagation. Keywords:Arrhythmia, Anisotropy, Cardiomyocytes, Optical mapping, Electrophysiology == Introduction == Cardiac myocytes are elongated and align axially along cardiac fibers [1,2]. Intercellular connectivity is anisotropic: gap junctions (the primary pathway for intercellular ionic currents) are found predominantly at the ends of the myocytes (the longitudinal direction), with comparatively few gap junctions between the sides of adjacent cells (the transverse direction) [2,3]. Electrical anisotropy results from this structure. Transverse intercellular resistance is higher than longitudinal intercellular resistance, resulting in slower conduction velocity in the transverse direction [46]. Propagation transverse to the fibers is asymmetric when the fibers are curved. In two dimensions, the wavefront can cross the curved fibers either from their convex or their concave side. Computer modeling has shown that conduction velocity (CV), upstroke rate, and action potential amplitude are all Diphenhydramine hcl increased relative to the straight-fiber case when fibers curve toward the wavefront (i.e., the wavefront propagates toward the Diphenhydramine hcl concave side). These effects are all reversed when waves propagate in the opposite direction relative to the fibers. The effects are due to directional differences in the electrical load on the wavefront [7,8]. Fiber curvature is clearly present in the heart. The spatial orientation of cardiac fibers has been measured in dog [9], rabbit [10], and pig [11] hearts. Regions are present in which fibers are curved in planes parallel to the epicardium [911]. More pronounced fiber curvature is present where the right and left ventricles join at the septum [11] and is also very likely to occur where endocardial structures such as trabeculae and papillary muscles join the bulk myocardium. In computer models, fiber curvature has been shown to affect the dynamics of reentrant waves by causing nominally stationary reentry to drift [7]. Other models have shown that fiber curvature may be important in defibrillation [12]. Computer modeling of the effect of surface curvature, which modulates wavefront loading in a similar manner to fiber curvature, has shown that even very small loading effects (CV changes on the order of 2%) can convert a stable reentrant activation pattern to a complex VF-like state [13]. It has been proposed that Diphenhydramine hcl the insertion points of ventricular trabeculae and papillary muscles are involved in wavebreak and reentry [14,15]. Although the mechanism of this involvement is not well understood, fiber curvature may play a role. Despite the potential importance of the effects of fiber curvature on cardiac propagation, it has not yet been demonstrated Mouse monoclonal to CD45.4AA9 reacts with CD45, a 180-220 kDa leukocyte common antigen (LCA). CD45 antigen is expressed at high levels on all hematopoietic cells including T and B lymphocytes, monocytes, granulocytes, NK cells and dendritic cells, but is not expressed on non-hematopoietic cells. CD45 has also been reported to react weakly with mature blood erythrocytes and platelets. CD45 is a protein tyrosine phosphatase receptor that is critically important for T and B cell antigen receptor-mediated activation experimentally. Native tissue preparations are not well suited for such studies because it is difficult to isolate fiber curvature’s role from that of other heterogeneities. In the present study, we test for the effects of fiber Diphenhydramine hcl curvature on transverse CV using anisotropic monolayers of cultured cardiac myocytes with controlled fiber orientation. We find that as predicted, propagation is faster when fibers curve toward the wavefront than when they curve in the opposite direction. == Materials and Methods == All protocols involving animals were approved by the Institutional Animal Care and Use Committee at the University of Alabama at Birmingham. == Cell Culture Substrate Preparation == Polyvinyl chloride (PVC) coverslips (Fisher Scientific) were scratched using a razor blade with a finely serrated edge. Controlled serrations were made in the edge of the razor blade using a fly-cutter on a tabletop milling machine (Sherline Products, Vista, CA). Serrations were produced with 18m spacing, consistent with the width of scratches previously shown to maximize anisotropy [5]. The serrated blade was then fixed in place and PVC.