ROLE OF TITIN ISOFORMS IN DIASTOLIC DYSFUNCTION OF CIRRHOTIC CARDIOMYOPATHY
TK Glenn, H Honar, H Liu, SS Lee
Liver Unit, GI Research Group, University of Calgary, Calgary, Alberta
BACKGROUND: Significance of diastolic dysfunction in cirrhotic cardiomyopathy has been brought to the forefront with several reports of unexpected deaths from heart failure following liver transplantation and transjugular intrahepatic portosystemic stent-shunt (TIPS). Titin, the third myofilament of striated muscle, is responsible for developing passive force and is an important determinant of diastolic stiffness.
AIM: To determine the pathological role of diastolic dysfunction in cirrhotic cardiomyopathy, and the possible role of titin in the pathogenesis of this condition. Hypothesis: Increase in titin N2B isoform expression in cirrhotic rats leads to altered diastolic function in cardiomyocytes.
METHODS: Four weeks after bile duct ligation, diastolic function was examined in vitro in isolated functioning cardiomyocytes and trabeculae muscle to determine any change in force, muscle length and sarcomere length. Gel electrophoresis was examined for N2B and N2BA expression.
RESULTS: There was no significant difference in N2B isoform levels between shams and BDL (Figure 1A, B). In the BDL isolated cardiomyocytes, the time taken to return to baseline is shown to be shorter than the sham groups at all frequencies (Figure 2).
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