Poster Presentation & Flash Talk 46th Annual Meeting of the Fetal and Neonatal Physiological Society 2019

Novel gasotransmitter cardio-protection in the developing heart: comparative roles of hydrogen sulphide and carbon monoxide (#119)

Youguo Niu 1 2 , Qiang Lyu 1 3 , Rita M Hess 1 , Sage G Ford 1 , Tess A Garrud 1 , Wen Tong 1 , Kimberley J Botting 1 2 , Dino A Giussani 1 2
  1. Physiology, Development and Neuroscience, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom
  2. Cambridge Cardiovascular Strategic Research Initiative, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom
  3. Aerospace Physiology, The Fourth Military Medical University, Xi'an, Shaanxi Province, China

Background: Hydrogen sulphide (H2S) and carbon monoxide (CO) protect the heart against episodes of ischemia/reperfusion (I/R) in adult individuals.  However, whether H2S or CO protect the fetal heart is unknown, when tissue I/R injury is just as relevant, for instance as a result of birth asphyxia. Using the chicken embryo model, we show preconditioning effects of H2S and CO, conferring significant protection against I/R to the developing heart. The molecular basis underlying fetal cardiac protection by H2S and CO is different. 

Methods: Fertilized Bovans Brown eggs were incubated under normoxia (21% O2). On day 19 of incubation (term is 21 days), the heart was excised following cervical transection and mounted on a Langendorff preparation. Following measurement of basal cardiac function, hearts were randomly treated with a bolus of water vehicle (Control), a H2S donor (NaHS) or a CO donor (CORM-3), with or without the non-selective KATP channel inhibitor Glibenclamide (Glib) or the mitochondrial KATP channel inhibitor 5-hydroxydecanoate (5-HD). An I/R challenge was induced 10 min after treatment for 30 min, followed by 2h of reperfusion. Myocardial infarct size was determined by tetrazolium staining. 

Results: Treatment with either H2S and CO donors improved cardiac function and reduced cardiac infarct size after I/R in the chicken embryo.  However, H2S improved cardiac function earlier while CO did so later after I/R.  While the cardioprotective effects of H2S were blocked by Glib but not 5-HD, the cardioprotectve effects of CO were blocked by both Glib and 5-HD (Fig. 1).    

Conclusions: We introduce new interventional gasotrasmitter therapy against I/R injury in the developing heart.  While H2S confers cardiac protection by opening of myocardial sarcolemmal KATP channels, CO does so via myocardial mitochondrial KATP channels.

 References: 

  1. Papapetropoulos et al. PNAS 106:21972, 2009
  2. Otterbein et al. Circ Res 118:1940, 2016

  Supported by the British Heart Foundation

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