Cerebral Ischemia Elicits Aberration in Myocardium Contractile Function and Intracellular Calcium Handling.

The mechanisms of myocardial dysfunction and calcium handling disturbance underlying cerebral ischemia remain obscure. Here we for the first time report that acute cerebral ischemia significantly increased left ventricular end diastolic pressure (LVEDP), but decreased +dP/dt, -dP/dt, and left ventricular systolic pressure (LVSP). Significant increase in either the resting or KCl-induced [Ca²⁺]_iin ventricular myocytes was also detected by scanning confocal microscopy at 2 and 24 hours after cerebral ischemia. Verapamil as a blocker of I_Ca,L, ryanodine as a specific inhibitor of RyR, thapsigargin as a highly specific inhibitor of sarco(endo)plasmic reticulum Ca²⁺-ATPase 2a (SERCA2a) and SEA0400 as a selective NCX inhibitor changed the area under the curve of averaged ratio of fluorescence (FI/F₀I) induced by KCl. Cardiac expression of Ca_v1.2 was significantly up-regulated at 2 and 24 hours after cerebral ischemia, whereas cardiac expression of SERCA2a and Na⁺-Ca²⁺ exchanger (NCX) was significantly down-regulated at the same time period after cerebral ischemia. Cardiac expression of phospholamban (PLB) was significantly elevated at 2 hours after cerebral ischemia but was restored to about normal level at 24 hours after injury. These data suggest that acute cerebral ischemia may specifically disturb cardiac function and calcium homeostasis, which are related to increase of Ca_v1.2 and decrease of through up-regulating Ca_v1.2 and PLB, down-regulating SERCA2a and NCX, subsequently leading to Ca²⁺ overload by the enhancement of Ca²⁺ influx and inhibition of intracellular Ca²⁺ extrusion and cerebral ischemia-induced myocardial dysfunction. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]