title: Preconditioning-induced cardioprotection and release of the second messenger inositol (1,4,5)-trisphosphate are both abolished by neomycin in rabbit heart.
abstract: 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)-triphosphate (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.
authors: Heart Institute/Research, Good Samaritan Hospital, Los Angeles, CA 90017-2395, USA.
authors: B
authors: B
authors: Bauer
authors: B Z
authors: BZ
authors: Simkhovich
authors: R A
authors: RA
authors: Kloner
authors: K
authors: K
authors: Przyklenk
mesh_terms: D000818:Animals; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D009206:Myocardium / Q000378:metabolism*; D009355:Neomycin / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D015290:Second Messenger Systems / Q000187:drug effects* / Q000502:physiology
chemical_list: D011500:Protein Synthesis Inhibitors; D015544:Inositol 1,4,5-Trisphosphate; D009355:Neomycin