TY - JOUR
T1 - Preconditioning-induced cardioprotection and release of the second messenger inositol (1,4,5)-trisphosphate are both abolished by neomycin in rabbit heart
AU - Bauer, B.
AU - Simkhovich, B. Z.
AU - Kloner, R. A.
AU - Przyklenk, K.
PY - 1999/2
Y1 - 1999/2
N2 - The mechanisms responsible for infarct size reduction with preconditioning remain controversial. Our aim was to determine whether release of the second messenger inositol (1,4,5)-trisphosphate (Ins(1,4,5)P3) during the preconditioning stimulus may play a role. To test this concept, Langendorff-perfused rabbit hearts underwent sham perfusion, 5 min of coronary artery occlusion (CO), or 5 min of CO + infusion of neomycin, an agent which inhibits formation of Ins(1,4,5)P3. Direct quantitation (by competitive binding assay) revealed a 2-fold increase in Ins(1,4,5)P3 content with brief ischemia vs shams (0.69 ± 0.14 vs 0.34 ± 0.05 pmol/mg tissue; p < .05) that was blocked by neomycin (0.15 ± 0.04 pmol/mg). Infarct size (by tetrazolium staining) was assessed in additional hearts that underwent 30 min of sustained CO and 2 h of reperfusion. As expected, two 5-min episodes of preconditioning ischemia reduced infarct size versus controls (30 + 6% versus 63 ± 3% of the myocardium at risk; p < .01). In contrast, infarct size was comparable (54-56% of the risk region) in neomycin-treated control and preconditioned hearts. These results demonstrate that myocardial Ins(1,4,5)P3 content is increased in response to brief preconditioning ischemia and are consistent with the concept that Ins(1,4,5)P3 may be a potential mediator of infarct size reduction with preconditioning in isolated rabbit heart.
AB - The mechanisms responsible for infarct size reduction with preconditioning remain controversial. Our aim was to determine whether release of the second messenger inositol (1,4,5)-trisphosphate (Ins(1,4,5)P3) during the preconditioning stimulus may play a role. To test this concept, Langendorff-perfused rabbit hearts underwent sham perfusion, 5 min of coronary artery occlusion (CO), or 5 min of CO + infusion of neomycin, an agent which inhibits formation of Ins(1,4,5)P3. Direct quantitation (by competitive binding assay) revealed a 2-fold increase in Ins(1,4,5)P3 content with brief ischemia vs shams (0.69 ± 0.14 vs 0.34 ± 0.05 pmol/mg tissue; p < .05) that was blocked by neomycin (0.15 ± 0.04 pmol/mg). Infarct size (by tetrazolium staining) was assessed in additional hearts that underwent 30 min of sustained CO and 2 h of reperfusion. As expected, two 5-min episodes of preconditioning ischemia reduced infarct size versus controls (30 + 6% versus 63 ± 3% of the myocardium at risk; p < .01). In contrast, infarct size was comparable (54-56% of the risk region) in neomycin-treated control and preconditioned hearts. These results demonstrate that myocardial Ins(1,4,5)P3 content is increased in response to brief preconditioning ischemia and are consistent with the concept that Ins(1,4,5)P3 may be a potential mediator of infarct size reduction with preconditioning in isolated rabbit heart.
KW - Calcium
KW - Myocardial infarction
KW - Myocardial ischemia
KW - Second messengers
KW - Signal transduction
UR - http://www.scopus.com/inward/record.url?scp=0032940260&partnerID=8YFLogxK
U2 - 10.1007/s003950050124
DO - 10.1007/s003950050124
M3 - Article
C2 - 10097828
AN - SCOPUS:0032940260
VL - 94
SP - 31
EP - 40
JO - Basic Research in Cardiology
JF - Basic Research in Cardiology
SN - 0300-8428
IS - 1
ER -