Ex vivo study shows polyamine pathway activation triggers pro-apoptotic signaling in post-ischemic rat hearts, indicating that ornithine decarboxylase inhibition protects reperfused cardiac tissue.
Polyamines play a role in ischemia-reperfusion injury of brain, kidney and probably heart. Primary data on car- diac myoblasts suggested that the induction of polyamine metabolism induces a hypertrophy like effect in normoxic hearts but apoptosis in reperfused hearts. The aim of this study was to investigate the relevance of these findings for post- ischemic hearts. Rat hearts were exposed to 45 min global normothermic flow arrest followed by 120 min of reperfusion. Controls were constitutively perfused for 165 min under normoxic conditions. Ornithine decarboxylase (ODC) activity was inhibited by administration of difluoromethylornithine (DFMO, 100 � M) starting 30 min after the onset of reperfu- sion and lasting for 10 min. Calcium receptor activation was induced by administration of putrescine (100 � M) and its in- hibition by administration of NPS (10 � M).Left ventricular mRNA expression of bcl-2, bax, and BNP were determined by real time RT-PCR. Results: BNP was induced by putrescine via activation of calcium receptors in normoxic and post- ischemic hearts. Inhibition of ODC had a strong effect on bcl-2 expression whereby putrescine induced bax in post- ischemic but not normoxic hearts. Inhibition of ODC increased the bcl-2/bax ratio but putrescine worsened it. In conclu- sion, induction of polyamine metabolism induced a pro-apoptotic profile in left ventricles via calcium receptor activation in post-ischemic hearts but not in normoxic hearts and induced BNP expression under both conditions.
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Mörlein et al. (2010) studied this question.
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