title: Cerebral ischemia elicits aberration in myocardium contractile function and intracellular calcium handling.
abstract: 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+](i)in 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 Ca(2+)-ATPase 2a (SERCA2a) and SEA0400 as a selective NCX inhibitor changed the area under the curve of averaged ratio of fluorescence (FI/F(0)I) induced by KCl. Cardiac expression of Ca(v)1.2 was significantly up-regulated at 2 and 24 hours after cerebral ischemia, whereas cardiac expression of SERCA2a and Na(+)-Ca(2+) 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(v)1.2 and decrease of through up-regulating Ca(v)1.2 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.
authors.affiliation: Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Sun
authors.forename: Jing
authors.initials: J
authors.lastname: Ai
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Li
authors.forename: Tianzhu
authors.initials: T
authors.lastname: Zhang
authors.forename: Wanchen
authors.initials: W
authors.lastname: Wu
authors.forename: Pengzhou
authors.initials: P
authors.lastname: Hang
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Lu
authors.forename: Baofeng
authors.initials: B
authors.lastname: Yang
mesh_terms: D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006352:Heart Ventricles / Q000166:cytology; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D010647:Phenyl Ethers / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology
chemical_list: D000814:Aniline Compounds; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004791:Enzyme Inhibitors; C419385:L-type calcium channel alpha(1C); D010647:Phenyl Ethers; D019837:Ryanodine Receptor Calcium Release Channel; C430918:SEA 0400; D019831:Sodium-Calcium Exchanger; D012433:Ryanodine; D011189:Potassium Chloride; D019284:Thapsigargin; D014700:Verapamil; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium