Key result
Ischemic preconditioning and the PKC activator PMA significantly reduced myocardial infarct size from 38% to 10-20% in isolated rabbit hearts, an effect that was blocked by the PKC inhibitor calphostin C.
Why the study?
Does ischemic preconditioning or PKC activation reduce infarct size and improve functional recovery in isolated rabbit hearts subjected to ischemia-reperfusion?
Does ischemic preconditioning or PKC activation reduce infarct size and improve functional recovery in isolated rabbit hearts subjected to ischemia-reperfusion?
p-value: p=<0.05
Ischemic preconditioning protects isolated rabbit hearts from ischemia-reperfusion injury, likely through the selective activation and translocation of the PKC-ε isozyme.
Does not inform clinical practice; leaves open whether PKC activation translates to human cardioprotection.
Background:We tested recent evidences that IP triggers selective activation of protein kinase C (PKC isozymes using isolated Langendorff-perfused rabbit heart with PKC activator, phorbol ester (PMA, 0.01 nM or inhibitor (calphostin C, 200 nM. Methods:After stabilization of baseline hemodynamics, the hearts were subjected to 45 min global ischemia (Ⅰ followed by 120 min reperfusion (R with IP (IP group, n=18 or without IP (ischemic control group, n=16. IP was induced by single episode of 5 min Ⅰ and 10 min R. In the PMA-treated group (n=19 and calphostin C-treated preconditioned group (n=15, PMA and calphostin C was given for 5 and 15 min before 45 min Ⅰ, respectively. Myocardial cytosolic and membrane PKC activities were measured by 32P-γ-ATP incorporation into PKC-specific pepetide;PKC isozymes were analyzed by Western blot with monoclonal antibodies. Results:IP significantly increased the recovery of the LV function including LVDP and coronary flow (p<0.05; however, enhancement of the functional recovery disappeared by calphostin C or PMA treatment. Cytosolic PKC activity decreased to 82-76% in the IP and PMA-treated group (p<0.05; membrane PKC activity increased to 218-272% (p<0.01. However, both fraction of PKC activity was not changed in the calphostin C-treated preconditioned group. In addition, Western blot revealed that PKC-α and e, especially e, were selectively translocated during subsequent sustained ischemia after IP or PMA administration. IP and PMA also reduced infarct size (frim 38 to 10-20%, p<0.05. However, calphostin C blocked infarct reduction effect of IP. Conclusion:These results indicate that in isolated rabbit heart model, cardioprotective effect of IP may be related, at least in part, to trigger selective translocation of PKC, especially e isotype. (Korean Circulation J 1999;29(6 :602-611
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Kim et al. (1999) studied Myocardial Ischemia (n=68). Ischemic preconditioning and PMA (PKC activator) vs. Ischemic control was evaluated on Infarct size (p=<0.05). Ischemic preconditioning and the PKC activator PMA significantly reduced myocardial infarct size from 38% to 10-20% in isolated rabbit hearts, an effect that was blocked by the PKC inhibitor calphostin C.
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