当前位置： SCI文献检索 > CARDIOVASCULAR RESEARCH期刊下所有文献 > Preischaemic as well as postischaemic application of a Na+/H+ exchange inhibitor reduces infarct size in pigs.

Preischaemic as well as postischaemic application of a Na+/H+ exchange inhibitor reduces infarct size in pigs.

Abstract：

BACKGROUND:During reperfusion of ischaemic myocardium, Na+/H+ exchange promotes recovery from acidosis resulting in an accumulation of intracellular Na+. This leads to calcium overload via Na+/Ca2+ exchange and might result in cell necrosis contributing to reperfusion injury. METHODS AND RESULTS:We assessed whether HOE 694, a specific inhibitor of Na+/H+ exchange, is able to reduce infarct size in swine myocardium. Experiments were performed in pentobarbitone-anaesthetized, open-chest pigs which were subjected to a 60 min occlusion of the left anterior descending coronary artery (LADCA) followed by 2 h of reperfusion. Three groups of animals were studied. In the pre-reperfusion group (pre-REP, n = 7) HOE 694 infusion (7 mg/kg/15 min) was started at 45 min of occlusion of the LADCA and continued until the end of occlusion, while in pre-occlusion group (pre-TCO, n = 7) HOE 694 infusion was started 15 min before occlusion and stopped at the onset of ischaemia. In the control group (n = 7) animals received vehicle alone. At the end of the protocol, infarct size (as d% of the left ventricular risk region) was determined by the p-nitroblue tetrazolium method. Treatment with HOE 694 prior to the ischaemic insult or upon reperfusion significantly reduced infarct size [4.1%(1.4%), P < 0.01 and 38.2%(5.8%), P < 0.05, respectively], compared with 77.7%(4.0%) in the control group. However, infarct size was significantly more reduced in the pre-TCO group than in the pre-REP group (P < 0.05). CONCLUSION:Treatment with HOE 694 leads to a significant reduction in infarct size, even when administered after the onset of ischaemia. Thus, inhibition of Na+/H+ exchange was able to limit cell necrosis. This implicates an important role for Na+/H+ exchange in the pathogenesis of infarct expansion and provides evidence that reperfusion injury exists. However, HOE 694 was even more effective when given before ischaemia, indicating an additional protective effect during ischaemia which might be due to slowing down of a vicious cycle that consumes ATP and generates H+.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Rohmann S,Weygandt H,Minck KO

subject

Has Abstract

pub_date

1995-12-01 00:00:00

pages

945-51

issue

eissn

0008-6363

issn

1755-3245

pii

0008636395001549

journal_volume

pub_type

杂志文章

在线工具

Preischaemic as well as postischaemic application of a Na+/H+ exchange inhibitor reduces infarct size in pigs.