TY - JOUR
T1 - Inhibition of p38 MAPK α/β reduces ischemic injury and does not block protective effects of preconditioning
AU - Schneider, Sharron
AU - Chen, Weina
AU - Hou, Janet
AU - Steenbergen, Charles
AU - Murphy, Elizabeth
PY - 2001/2
Y1 - 2001/2
N2 - We examined the effect of inhibition of p38 mitogen-activated protein kinase (MAPK) α/β during ischemia and preconditioning by using the inhibitor SB-202190. Isolated rat hearts were perfused with Krebs-Henseleit buffer, while left ventricular developed pressure (LVDP) and 31P nuclear magnetic resonance spectra were acquired continuously. After 20 min of ischemia and 25 min of reperfusion, recovery of LVDP in untreated hearts was 32 ± 4%, whereas hearts treated with SB-202190 5 min before ischemia recovered 59 ± 7% of their pretreatment LVDP. Preconditioning improved functional recovery to 65 ± 5%, which was unaffected by SB-202190 treatment, added either throughout the preconditioning protocol (56 ± 5% recovery) or during the final reperfusion period of preconditioning (71 ± 11% recovery). Necrosis was assessed after 40 min of ischemia and 2 h of reperfusion using 2,3,5-triphenyltetrazolium chloride (TTC) staining and creatine kinase release. The untreated group had 54 ± 8% necrotic myocardium, whereas the SB-202190-treated group had 32 ± 7% and the preconditioned group had 21 ± 4% necrotic tissue by TTC staining.
AB - We examined the effect of inhibition of p38 mitogen-activated protein kinase (MAPK) α/β during ischemia and preconditioning by using the inhibitor SB-202190. Isolated rat hearts were perfused with Krebs-Henseleit buffer, while left ventricular developed pressure (LVDP) and 31P nuclear magnetic resonance spectra were acquired continuously. After 20 min of ischemia and 25 min of reperfusion, recovery of LVDP in untreated hearts was 32 ± 4%, whereas hearts treated with SB-202190 5 min before ischemia recovered 59 ± 7% of their pretreatment LVDP. Preconditioning improved functional recovery to 65 ± 5%, which was unaffected by SB-202190 treatment, added either throughout the preconditioning protocol (56 ± 5% recovery) or during the final reperfusion period of preconditioning (71 ± 11% recovery). Necrosis was assessed after 40 min of ischemia and 2 h of reperfusion using 2,3,5-triphenyltetrazolium chloride (TTC) staining and creatine kinase release. The untreated group had 54 ± 8% necrotic myocardium, whereas the SB-202190-treated group had 32 ± 7% and the preconditioned group had 21 ± 4% necrotic tissue by TTC staining.
KW - Intracellular pH
KW - Left ventricular developed pressure
KW - Necrosis
KW - P nuclear magnetic resonance
KW - SB-202190
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UR - http://www.scopus.com/inward/citedby.url?scp=0035008371&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.2001.280.2.h499
DO - 10.1152/ajpheart.2001.280.2.h499
M3 - Article
C2 - 11158945
AN - SCOPUS:0035008371
SN - 0363-6135
VL - 280
SP - H499-H508
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 2 49-2
ER -