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Protein kinase C epsilon (PKC ε‐) peptide inhibitor exerts cardioprotective effects in ischemia/reperfusion injury when given at reperfusion
Author(s) -
Kay Helen Young,
Teng Jane,
Adams Jovan,
Grilli Christopher,
Guglielmello Giuseppe,
Bell Adrian,
Young Lindon Howard
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a318-b
Subject(s) - protein kinase c , reperfusion injury , peptide , ischemia , pharmacology , chemistry , medicine , kinase , cardiology , biochemistry
Ischemia followed by reperfusion (I/R) in the presence of polymorphonuclear leuokocytes (PMNs) results in a marked cardiac contractile dysfunction. Isolated rat hearts following ischemia (20 min) and reperfusion (45 min) were studied in the presence of activated PMNs. In hearts subjected to I/R and reperfused with PMNs in the presence of 5μM N‐myristoylated PKC ε‐ (I/R + PMN + ε ‐, n=6), cardiac function was significantly restored within 15 min post‐reperfusion when given at the beginning of reperfusion. Left ventricular developed pressure (LVDP) and maximal rate of LVDP (+dP/dt max ) recovered to 99% ± 6% and 87% ± 5% of baseline values, respectively. This protection was sustained throughout the 45 min reperfusion protocol.I/R hearts receiving PMNs alone (I/R + PMN, n=6) recovered to 55% ± 9% and 47% ± 8% for LVDP and +dP/dt max of baseline values, respectively (p<0.01). These cardiac function indices correlated with significantly better restoration of heart rate in I/R + PMN + ε ‐ (5μM) hearts compared to control (p<0.05). Significantly lower post‐reperfusion end diastolic pressure correlated with significantly better coronary flow, where I/R+ PMN hearts recovered to 34% ± 7% while IR + PMN + ε ‐ (5μM) hearts recovered to 62% ± 4% (p<0.01) of pre‐ischemic coronary flow. Function recovered dose‐dependently on all courses. Collectively, these data suggest that PKC ε ‐ significantly attenuates PMN‐mediated cardiac contractile dysfunction. This study was supported by NHLBI Grant 1R15HL‐76235‐01.