当前位置： SCI文献检索 > JOURNAL OF CARDIOVASCULAR PHARMACOLOGY期刊下所有文献 > Monophosphoryl lipid A attenuates myocardial stunning in dogs: role of ATP-sensitive potassium channels.

Monophosphoryl lipid A attenuates myocardial stunning in dogs: role of ATP-sensitive potassium channels.

Abstract：

:Results of previous studies indicate that monophosphoryl lipid A (MLA) reduces myocardial infarct size when administered 24 but not 1 h before a prolonged period of regional ischemia in dogs and rabbits. This cardioprotective effect of MLA could be reversed by the administration of the adenosine triphosphate (ATP)-sensitive potassium channel (K(ATP)) blockers, glibenclamide, or 5-hydroxydecanoate. MLA also was shown to attenuate myocardial stunning in dogs; however, its mechanism in this model remains unknown. Therefore the major aim of our study was to determine the dose-related effect of MLA to enhance contractile function in stunned myocardium and to determine the role of the K(ATP) channel in mediating its cardioprotective effect. To produce myocardial stunning, barbital-anesthetized dogs were subjected to five cycles of 5 min of left anterior descending (LAD) coronary artery occlusion interspersed with 10 min of reperfusion and finally followed by 2 h of reperfusion. Regional segment shortening (%SS) was determined by sonomicrometers implanted in the subendocardium of the ischemic region. Single intravenous doses of MLA in the range of 10-35 microg/kg given 24 h before ischemia resulted in an improvement in %SS over a 2-h reperfusion period. Similar to results obtained in the canine and rabbit infarct models, cardioprotection against stunning with MLA appears to require activation of K(ATP) channels during ischemia, because glibenclamide (50 microg/kg, 15 min before ischemia) completely blocked the effect of MLA to improve regional %SS during reperfusion. Cardioprotective doses of MLA were without effect on systemic hemodynamics, blood gases, and pH throughout the experiment. No treatment-related effects on regional myocardial blood flow were observed during ischemia or reperfusion. These results suggest that MLA improves %SS at doses of 10-35 microg/kg by an ATP-sensitive potassium channel-dependent process, and that MLA may mimic the antistunning effects observed during the second window of ischemic preconditioning.

journal_name

J Cardiovasc Pharmacol

journal_title

Journal of cardiovascular pharmacology

authors

Elliott GT,Mei DA,Gross GJ

doi

10.1097/00005344-199807000-00008

subject

Has Abstract

pub_date

1998-07-01 00:00:00

pages

49-56

issue

eissn

0160-2446

issn

1533-4023

journal_volume

pub_type

杂志文章

在线工具

Monophosphoryl lipid A attenuates myocardial stunning in dogs: role of ATP-sensitive potassium channels.