Effects of 6-mercaptopurine in pressure overload induced right heart failure

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Julie Birkmose Axelsen
  • Stine Andersen
  • Xiao-Qing Sun, Department of Pulmonology, VU University Medical Center, Amsterdam, The Netherlands.
  • ,
  • Steffen Ringgaard
  • Janus Adler Hyldebrandt
  • Kondababu Kurakula, Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands.
  • ,
  • Marie-José Goumans, Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands.
  • ,
  • Frances S de Man, Department of Pulmonology, VU University Medical Center, Amsterdam, The Netherlands.
  • ,
  • Jens Erik Nielsen-Kudsk
  • Harm-Jan Bogaard, Department of Pulmonology, VU University Medical Center, Amsterdam, The Netherlands.
  • ,
  • Asger Andersen

BACKGROUND: Several antineoplastic drugs have been proposed as new compounds for pulmonary arterial hypertension treatment but many have cardiotoxic side effects. The chemotherapeutic agent 6-mercaptopurine may have an effect in treatment of pulmonary arterial hypertension but at the same time, its effects on the afterload adaption of the right ventricle is unpredictable due to interaction with multiple downstream signalling pathways in the cardiomyocytes. We investigated the direct cardiac effects of 6-mercaptopurine in rats with isolated right heart failure caused by pulmonary trunk banding (PTB).

METHODS: Male Wistar rat weanlings (112±2 g) were randomized to sham operation (sham, n = 10) or PTB. The PTB animals were randomized to placebo (PTB-control, n = 10) and 6-mercaptopurine (7.5 mg/kg/day) groups with treatment start before the PTB procedure (PTB-prevention, n = 10) or two weeks after (PTB-reversal, n = 10). Right ventricular effects were evaluated by echocardiography, cardiac MRI, invasive pressure-volume measurements, and histological and molecular analyses.

RESULTS: PTB increased right ventricular afterload and caused right ventricular hypertrophy and failure. 6-mercaptopurine did not improve right ventricular function nor reduce right ventricular remodelling in both prevention and reversal studies compared with placebo-treated rats.

CONCLUSION: Treatment with 6-mercaptopurine did not have any beneficial or detrimental effects on right ventricular function or remodelling. Our data suggest that treatment of pulmonary arterial hypertension with 6-mercaptopurine is not harmful to the failing right ventricle.

Original languageEnglish
Article numbere0225122
JournalPLOS ONE
Volume14
Issue11
ISSN1932-6203
DOIs
Publication statusPublished - 2019

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