Abstract 465: Short Term Hypoxia Can Induce Adult Feline Cardiomyocytes to Re-enter the Cell Cycle and Divide

Rationale: The mammalian adult heart has a very limited capacity to regenerate cardiomyocytes that die from pathological damage. Most recent studies suggest that those few new myocytes found after injury are derived from pre-existing cardiomyocytes. A recent study in mice suggest that systemic hypoxemia in adult animals can induce cardiac myocyte cell cycle reentry and myocyte proliferation. In the present experiments we evaluate the ability of adult feline cardiomyocytes to reenter the cell cycle and proliferate in hypoxic environments. Hypothesis: To determine if hypoxia induces adult feline cardiomyocytes to regenerate. Methods and results: Adult ventricular cardiomyocytes were isolated from adult felines and maintained in culture. For acute hypoxia, cultures were placed in a hypoxic chamber on day 1, 3, 5, 7, 10, or 14 following isolation and subjected to 1% O 2 , 5% CO 2 , and the balance was N 2 for 24 hours. For chronic hypoxia, adult cardiomyocytes were subjected to 1% O 2 , 5% CO 2 with the balance of N 2 at day 1 after isolation and kept at continuous hypoxia for 3, 5, 7, 10, or 14 days. Prior to hypoxia, cells were treated with 10uM EdU to identify new DNA in cardiomyocytes. Acute hypoxia was shown to promote cell division in cardiac myocytes at all time points except at day 1 post isolation when compared to control cultures. However, chronic hypoxia caused cardiomyocyte damage and increased cell death in all time points as compared to control and acute hypoxia cultures. Conclusion: Short term hypoxia can induce adult feline cardiomyocytes to proliferate, while long term exposure leads to injury and apoptosis.