Intracerebral Hemorrhage Elicits Aberration in Cardiomyocyte Contractile Function and Intracellular Ca Transients

Background and Purpose—The sequelae of intracerebral hemorrhage involve multiple organ damage including electrocardiographic alteration, although the mechanism(s) behind myocardial dysfunction is unknown. The aim of this study was to examine the impact of intracerebral hemorrhage on cardiomyocyte contractile function, intracellular Ca handling, Ca cycling proteins, I kappa B beta protein (I B) phosphorylation, hypoxia-inducible factor 1 (HIF-1 ), and nitrosative damage within 48 hours of injury. Methods—Mechanical and intracellular Ca properties were evaluated including peak shortening (PS), maximal velocity of shortening/relengthening ( dL/dt), time-to-PS (TPS), time-to-90% relengthening (TR90), fura-2 fluorescence intensity (FFI), and intracellular Ca decay. Results—Myocytes from intracerebral hemorrhage rats exhibited depressed PS, dL/dt, prolonged TPS and TR90, as well as declined baseline FFI and slowed intracellular Ca decay between 12 and 24 hours after injury. Most of these aberrations returned to normal levels 48 hours after hemorrhage with the exception of dL/dt and TR90. Myocytes from 24-hour posthemorrhage rats exhibited a stepper negative staircase in PS with increased stimulus frequency. Cardiac expression of sarco(endo)plasmic reticulum Ca -ATPase 2a and phospholamban was enhanced, whereas that of Na -Ca exchanger and voltage-dependent K channel was decreased. I B phosphorylation, HIF-1 , inducible NO synthase, and 3-nitrotyrosine were enhanced 12 hours after injury. Conclusions—These data demonstrated that intracerebral hemorrhage initiates cardiomyocyte contractile and intracellular Ca dysregulation possibly related to altered expression of Ca cycling proteins, nitrosative damage, and myocardial phosphorylation of I B. (Stroke. 2006;37:1875-1882.)