Key result
In canine hearts, ischemic preconditioning reduced infarct size (11-16% vs 49%, P<0.01), an effect that was not blunted by the tyrosine kinase inhibitors genistein or lavendustin A.
Why the study?
Does tyrosine kinase activation contribute to the infarct size-limiting effect of ischemic preconditioning in canine hearts?
Does tyrosine kinase activation contribute to the infarct size-limiting effect of ischemic preconditioning in canine hearts?
Tyrosine kinase does not activate ecto-5'-nucleotidase or trigger the infarct size-limiting effect of the early phase of ischemic preconditioning in canine hearts.
Tyrosine kinase inhibition does not blunt preconditioning protection in canines; leaves open its role in other species or preconditioning phases.
Protein kinase C (PKC) plays an important role in ischemic preconditioning (IP). Because (1) tyrosine kinase is located at the downstream of PKC for IP in the rabbit hearts and (2) we have reported that ecto-5'-nucleotidase is the substrate for PKC and plays a crucial role for the infarct size-limiting effect, we tested whether tyrosine kinase activation contributes to either activation of ecto-5'-nucleotidase or the infarct size-limiting effect of the early phase of IP in the canine heart. In dogs, the IP procedure (4 cycles of 5-minute occlusion of coronary artery) and exposure to 12, 13-phorbol myristate acetate (PMA) each activated myocardial ecto-5'-nucleotidase and Lck tyrosine kinase. Genistein (10, 30, and 100 microg. kg(-)(1). min(-)(1) IC), an inhibitor of tyrosine kinase, attenuated the activation of Lck tyrosine kinase but did not attenuate the activation of ecto-5'-nucleotidase due to either IP or PMA. In the other canine hearts, IP attenuated infarct size (49+/-5 versus 11+/-3 or 16+/-3%, P<0.01) due to 90 minutes of coronary occlusion followed by 6 hours of reperfusion, which was not blunted by 3 or 2 (30 and 100 microg. kg(-)(1). min(-)(1)) doses of genistein (infarct sizes, 15+/-4, 13+/-4, and 13+/-3%, respectively, and 17+/-3 and 15+/-4%, respectively) or lavendustin A. Tyrosine kinase does not activate ecto-5'-nucleotidase or trigger the infarct size-limiting effect of the early phase of IP in canine hearts.
No takes yet. Share an insight, caveat, or question.
Kitakaze et al. (2000) studied Myocardial infarction and ischemic preconditioning. Genistein or lavendustin A (tyrosine kinase inhibitors) vs. Ischemic preconditioning without inhibitor, and control without preconditioning was evaluated on Infarct size (p=<0.01). In canine hearts, ischemic preconditioning reduced infarct size (11-16% vs 49%, P<0.01), an effect that was not blunted by the tyrosine kinase inhibitors genistein or lavendustin A.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: