Immature (14 days old) rat heart is more resistant to cardiac ischaemia and reperfusion than adult heart (Modi & Suleiman 2004). The reason for this difference is not known although developmental changes including intracellular calcium mobilisation and metabolism have been implicated. We have shown that the intermediary metabolite pyruvate attenuates ischaemia/reperfusion injury in rat adult heart (Kerr et al. 1999). Whether pyruvate is also cardioprotective in the more resistant immature rat heart is not currently known. Male Wistar rats (14 days old) were humanely killed, and the hearts were quickly removed, cannulated in the Langendorff mode and perfused with Krebs buffer at 37oC as described previously (Modi & Suleiman 2004). After 20 min equilibration, control hearts (n=4) were exposed to normothermic global ischaemia for 60 minutes. Hearts were then reperfused for 50 min and functional recovery determined. In the experimental group (n=8), 10 mmol/l pyruvate was present 10 min before and during ischaemia, but was washed out after 20 min reperfusion. Left ventricular developed pressure (and computed heart rate) was measured using a balloon inserted in the left ventricle. All results are expressed means ± S.E.M. and analysed using ANOVA with Fischer’s PLSD post hoc test. Pyruvate had no effect on heart rate but slightly increased LVDP (39.7 ± 5 to 44.0 ±5 mmHg). Time to induce contractile arrest was similar for both groups (5.2 ± 0.8 vs. 4.4 ± 0.5min for pyruvate and control, respectively). Pyruvate significantly increased the time to onset of ischaemic contracture (17.4 ± 0.8 vs. 7.8 ± 1.1min, p<0.05). Figure 1 shows that pyruvate significantly (p<0.05) improved % recovery in rate pressure product (mmHg. beats min-1) as measured at the end of reperfusion. Our data demonstrate that pyruvate is cardioprotective in the immature heart just as it is in the adult heart. The delay in the onset of ischaemic contracture may underlie its cardioprotective action. However, whether the mechanism is similar to adult heart remains to be investigated.
University of Bristol (2005) J Physiol 567P, PC20
Poster Communications: Pyruvate is cardioprotective in a model of Langendorff perfused immature rat heart
Khan, Irfan H; King, Nicola; Halestrap, Andrew P; Angelini, Gianni D; Suleiman, M. Saadeh;
1. Bristol Heart Institute, University of Bristol, Bristol, United Kingdom. 2. Department of Biochemistry, University of Bristol, Bristol, United Kingdom.
View other abstracts by:
Where applicable, experiments conform with Society ethical requirements.