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K R Chien

Publications and source records attributed to K R Chien.

167 records · Page 10Linked to original sources

Prevention by chlorpromazine of ischemic liver cell death.

Ischemic liver tissue was produced by clamping the portal venous and hepatic arterial blood supply to the left lateral and median lobes of rat liver. If, after 2 to 3 hours of ischemia, reflow to the liver was established by removing the clamp, two-thirds or more of the liver cells were histologically dead 24 hours later. Pretreatment with chlorpromazine (20 mg/kg) 30 minutes before inducing ischemia for up to 3 hours virtually completely prevented this ischemic cell death. If the animals were kept alive for an additional 24 hours with no further treatment, the extent of liver cell necrosis at 48 hours was still markedly less than that seen in the untreated ischemic controls. Administration of chlorpromazine after induction of ischemia and immediately prior to the onset of reflow reduced but did not completely prevent ischemic cell death as determined at 24 hours. This protective action of chlorpromazine was confirmed by the ability of the treated animals to regenerate cellular ATP levels after 3 hours of ischemia. In addition, chlorpromazine was shown to significantly reduce the increases in total liver cell and mitochondrial calcium ion contents that accompany the return of blood flow to irreversibly injured liver cells. The protective effect of chlorpromazine could not be attributed to any effect either on the rate or extent to which the liver cells became ischemic or on the perfusion patterns following release of the obstruction, and it is concluded that the action of chlorpromazine must be on some component(s) of the reaction of the cells to the ischemia itself. The possible basis of this action is discussed.

Adenosine Triphosphate↗

Expression of cardiac muscle markers in rat myocyte cell lines.

Recently developed rat heart myocyte cell lines have afforded us the opportunity to evaluate the expression of several transcription factors associated with early cardiac development. These factors include, but are not limited to, Nkx-2.5/Csx, MEF-2C and MLP (Muscle LIM Protein). These factors have been shown to be temporally expressed in pre-cardiac mesenchyme coincident with the earliest stages of heart development. Using the BWEM and CLEM myocyte cell lines as models of the embryonic, committed cardiomyocyte, we have evaluated the basal expression levels of these three genes over multiple passages. Both cell lines express these genes, with MEF-2C being the most abundant based on Northern blot hybridization analyses. Interestingly, as these cells increased their passage number, there was a corresponding increase in their basal expression levels. To evaluate potential 'downstream' effectors of these genes, we examined the basal expression levels of two cardiac-specific genes cTNC and MLC-2v. Transcript levels for both of these contractile filament genes were elevated with passage, suggestive of a inductive process mediated by one or all these three transcription factors. Promoter analysis of MLC-2v expression in the CLEM line shows that this increase is transcriptionally-mediated and the lines retain the necessary regulatory factors to maintain and control the transcription of this gene. Analysis of the dynamics of the regulatory role(s) that these three transcription factors play in cardiac development can now be evaluated in a homogeneous, cell culture system.

Animals↗