Intracerebral Hemorrhage Elicits Aberration in Cardiomyocyte Contractile Function and Intracellular Ca 2+ Transients

Abstract

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 Ca2+ handling, Ca2+ cycling proteins, I kappa B beta protein (IkappaB) phosphorylation, hypoxia-inducible factor 1alpha (HIF-1alpha), and nitrosative damage within 48 hours of injury. Mechanical and intracellular Ca2+ 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 Ca2+ decay. Myocytes from intracerebral hemorrhage rats exhibited depressed PS, +/-dL/dt, prolonged TPS and TR90, as well as declined baseline FFI and slowed intracellular Ca2+ 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 Ca2+-ATPase 2a and phospholamban was enhanced, whereas that of Na+-Ca2+ exchanger and voltage-dependent K+ channel was decreased. IkappaB phosphorylation, HIF-1alpha, inducible NO synthase, and 3-nitrotyrosine were enhanced 12 hours after injury. These data demonstrated that intracerebral hemorrhage initiates cardiomyocyte contractile and intracellular Ca2+ dysregulation possibly related to altered expression of Ca2+ cycling proteins, nitrosative damage, and myocardial phosphorylation of IkappaB.