当前位置： SCI文献检索 > BASIC RESEARCH IN CARDIOLOGY期刊下所有文献 > Postconditioning's protection is not dependent on circulating blood factors or cells but involves adenosine receptors and requires PI3-kinase and guanylyl cyclase activation.

Postconditioning's protection is not dependent on circulating blood factors or cells but involves adenosine receptors and requires PI3-kinase and guanylyl cyclase activation.

Abstract：

:Protection from postconditioning has been documented in in situ animal models and it has been proposed that it is targeting circulating leukocytes. We therefore tested whether postconditioning can protect leukocyte-free, buffer-perfused rabbit hearts. Infarct size was measured with triphenyltetrazolium staining. In control hearts undergoing 30 min of regional ischemia and 2 h of reperfusion, 33.3 +/- 2.2% of the risk zone infarcted. The protocol previously used in open-chest animals of four postconditioning cycles of 30 s reperfusion/30 s ischemia starting at the beginning of reperfusion decreased infarction to only 24.8 +/- 2.5% of the risk zone in these isolated hearts. Because of the meager protection induced by four 30 s postconditioning cycles, we evaluated the effect of postconditioning with 6 cycles of 10 s reperfusion/10 s ischemia starting at the beginning of reperfusion. Robust salvage was seen with only 10.4 +/- 3.4% of the risk zone infarcting (p < 0.001 vs control and p < 0.003 vs 4 cycles of 30 s ischemia). The 10s protocol was used in all studies of signal transduction. Wortmannin (100 nM), a phosphatidylinositol 3- (PI3-) kinase antagonist, infused for 20 min starting 5 min before reperfusion, blocked postconditioning's, protection (31.2 +/- 4.2% infarction) as did 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ) (2 microM) a guanylyl cyclase inhibitor (36.9 +/- 5.3%) and 8-p-(sulfophenyl) theophylline (SPT) (100 microM), a non-specific adenosine receptor blocker (34.2 +/- 2.8%). Thus, postconditioning's protection is not dependent on circulating blood factors or cells, and its anti-infarct effect appears to require PI3-kinase activation, stimulation of guanylyl cyclase and occupancy of adenosine receptors. These signaling steps have also been identified in preconditioning and during pharmacologic cardioprotection and suggest commonality of a protective mechanism.

journal_name

Basic Res Cardiol

journal_title

Basic research in cardiology

authors

Yang XM,Philipp S,Downey JM,Cohen MV

doi

10.1007/s00395-004-0498-4

keywords:

subject

Has Abstract

pub_date

2005-01-01 00:00:00

pages

57-63

issue

eissn

0300-8428

issn

1435-1803

journal_volume

100

pub_type

杂志文章

在线工具

Postconditioning's protection is not dependent on circulating blood factors or cells but involves adenosine receptors and requires PI3-kinase and guanylyl cyclase activation.