Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Pfeiffer, S.
Contractile dysfunction of cardiomyocytes in a rat model with compensated renal failure and diastolic dysfunction
Humanmedizin; [ Diplomarbeit ] Medical University of Graz; 2015. pp.
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Heinzel Frank
- Primessnig Uwe
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- Abstract:
- Background: Cardio renal syndrome type IV describes the interaction between chronic renal failure and heart failure. Heart failure with preserved ejection fraction (HFpEF) becomes more and more important in the last years and till now there is no specific therapeutic strategy to treat patients with signs and symptoms of HFpEF, mainly because of poor understanding of the underlying mechanisms. To explore the cellular pathomechanism of cardiomyocytes dysfunction in HFpEF we used a rat model with compensated renal failure and diastolic dysfunction. Methods: Young male Wistar rats (250 – 275 grams) were used and underwent subtotal nephrectomy (NXT) and sham operation (Sham). After 8 and 24 weeks the hearts were removed and left ventricular (LV) cardiomyocytes were enzymatically isolated with a Langendorff perfusion system. For the cell shortening (CS%) measurements an inverted microscope equipped with a CCD camera was used to record edge detection during stimulation in an electrical field at 1, 2 3, 5, 6, 8 Hz and 1 Hz recovery after a short stimulation break. In a subset of animals after 24 weeks LV cardiomyocytes were treated with a Na+/Ca2+ exchanger (NCX) inhibitor (SEA0400 300 nm, 5 minutes). Results: Cell shortening (CS) and contraction amplitude (time to peak, TTP) at 1 Hz after 8 and 24 weeks was unchanged. Early relaxation (RT50) was significantly prolonged (P< 0.05) in NXT after 8 and 24 weeks. Additionally early relaxation (RT50) was significant prolongation in NXT after 24 weeks vs. 8 weeks. Late relaxation (RT90) of 24 weeks group was significantly prolonged in NXT against Sham. There were no changes in Sham cardiomyocytes relaxation with blocked NCX. In contrast NCX inhibited NXT cardiomyocytes showed a significantly prolongation in early relaxation (RT50) at 1 Hz, but late relaxation (RT90) remained constant. During increasing frequencies NXT cells showed a significant prolongation of early and late relaxation. Also CS% was increased in higher frequencies (5 and 6 Hz) in contrast to sham cells. Conclusion: Isolated cardiomyocytes from NXT show signs of contractile dysfunction. Relaxation was slowed at all frequencies. The positive shortening-frequency relationship was absent in NXT at 24 weeks.