Protection by the NO-donor SNAP and BNP against hypoxia/reoxygenation in rat engineered heart tissue

A. Görbe, A. Eder, Z. V. Varga, J. Pálóczi, A. Hansen, P. Ferdinándy, T. Eschenhagen

Research output: Contribution to journalArticle

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Abstract

In vitro assays could replace animal experiments in drug screening and disease modeling, but have shortcomings in terms of functional readout. Force-generating engineered heart tissues (EHT) provide simple automated measurements of contractile function. Here we evaluated the response of EHTs to hypoxia/reoxygenation (H/R) and the effect of known cardiocytoprotective molecules. EHTs from neonatal rat heart cells were incubated for 24 h in EHT medium. Then they were subjected to 180 min hypoxia (93% N2, 7%CO2) and 120 min reoxygenation (40% O2, 53%N2, 7%CO2), change of medium and additional follow-up of 48 h. Time-matched controls (40% O2, 53%N2, 7%CO2) were run for comparison. The following conditions were applied during H/R: fresh EHT medium (positive control), the NO-donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP, 10-7, 10-6, 10-5 M) or the guanylate cyclase activator brain type natriuretic peptide (BNP, 10-9, 10-8, 10-7 M). Frequency and force of contraction were repeatedly monitored over the entire experiment, pH, troponin I (cTnI), lactate dehydrogenase (LDH) and glucose concentrations measured in EHT medium. Beating activity of EHTs in 24 h-medium ceased during hypoxia, partially recovered during reoxygenation and reached time-control values during follow-up. H/R was accompanied by a small increase in LDH and non-significant increase in cTnI. In fresh medium, some EHTs continued beating during hypoxia and all EHTs recovered faster during reoxygenation. SNAP and BNP showed small but significant protective effects during reoxygenation. EHTs are applicable to test potential cardioprotective compounds in vitro, monitoring functional and biochemical endpoints, which otherwise could be only measured by using in vivo or ex vivo heart preparations. The sensitivity of the model needs improvement.

Original languageEnglish
Article numbere0132186
JournalPLoS One
Volume10
Issue number7
DOIs
Publication statusPublished - Jul 6 2015

Fingerprint

S-Nitroso-N-Acetylpenicillamine
Rats
hypoxia
heart
Tissue
rats
lactate dehydrogenase
L-Lactate Dehydrogenase
penicillamine
natriuretic peptides
guanylate cyclase
Preclinical Drug Evaluations
Penicillamine
Troponin I
animal experimentation
Guanylate Cyclase
Brain Natriuretic Peptide
endpoints
protective effect
tissues

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Protection by the NO-donor SNAP and BNP against hypoxia/reoxygenation in rat engineered heart tissue. / Görbe, A.; Eder, A.; Varga, Z. V.; Pálóczi, J.; Hansen, A.; Ferdinándy, P.; Eschenhagen, T.

In: PLoS One, Vol. 10, No. 7, e0132186, 06.07.2015.

Research output: Contribution to journalArticle

Görbe, A. ; Eder, A. ; Varga, Z. V. ; Pálóczi, J. ; Hansen, A. ; Ferdinándy, P. ; Eschenhagen, T. / Protection by the NO-donor SNAP and BNP against hypoxia/reoxygenation in rat engineered heart tissue. In: PLoS One. 2015 ; Vol. 10, No. 7.
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