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Post-conditioning with cyclosporine A fails to reduce the infarct size in an in vivo porcine model.

Abstract：

BACKGROUND:Cyclosporine A has generated intense interest in the field of cardioprotection due to its ability to protect the mitochondria at reperfusion by blocking the opening of the mitochondrial permeability transition pore. The aim of our study was to examine the cardioprotective effect of Sandimmun, a clinically available formulation of cyclosporine A, in an in vivo large mammal model. METHODS:Forty-eight pigs were randomly allocated to one of three groups: (i) Control group (Con, n=19), (ii) Cyclosporine group, (Cyclo, n=19) Sandimmun 10 mg/kg i.v. bolus 5 min before reperfusion and (iii) Pre-conditioning group (Precon, n=10) two cycles of 10 min ischemia interspersed with 30-min reperfusion. The study was further sub-divided into a metabolic protocol, evaluating myocardial metabolism by measuring changes in the interstitial lactate concentration, and a coronary flow protocol. All animals were subjected to 40 min of left anterior descending coronary artery occlusion, followed by 180 min of reperfusion before histochemical staining and assessment of infarct size by planimetry. RESULTS:Infarct sizes were measured as: Con 51.4 +/- 16.5%, Cyclo 47.3 +/- 15.7% and Precon 2.4 +/- 3.6%, with no significant difference between the Con and Cyclo groups but a highly significant difference between the Precon and Cyclo and Con groups (P<0.0001 for both comparisons). In the Cyclo group, the interstitial lactate concentration was significantly increased compared with the Con group at 6-min reperfusion, although significantly lower at 14 min presumably due to accelerated washout. CONCLUSION:In this large animal model, a 10 mg/kg bolus administration of Sandimmun 5 min before reperfusion did not reduce the infarct size.

journal_name

Acta Anaesthesiol Scand

journal_title

Acta anaesthesiologica Scandinavica

authors

Lie RH,Stoettrup N,Sloth E,Hasenkam JM,Kroyer R,Nielsen TT

doi

10.1111/j.1399-6576.2010.02241.x

subject

Has Abstract

pub_date

2010-08-01 00:00:00

pages

804-13

issue

7

eissn

0001-5172

issn

1399-6576

pii

AAS2241

journal_volume

54

pub_type

杂志文章

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