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Rivista di Chirurgia Cardiaca, Vascolare e Toracica

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The Journal of Cardiovascular Surgery 2001 February;42(1):43-8

lingua: Inglese

Protective effect of lisinopril against ischemia-reperfusion injury in isolated guinea pig hearts

Dogan R., Farsak B., Isbir S., Sarigül A., Tuncer M. *, Kilinç K. **

From the Department of Thoracic and Cardiovascular Surgery
*Department of Physiology
**Department of Biochemistry Hacettepe University Faculty of Medicine, Ankara, Turkey


Background. In ­order to deter­mine wheth­er angiotensin-converting enzyme inhibitors (ACEI’s) atten­u­ate ische­mia-reper­fu­sion inju­ry, we inves­ti­gat­ed and com­pared the ­effects of lisin­o­pril via dif­fer­ent ­routes of admin­is­tra­tion in an iso­lat­ed guin­ea pig ­heart mod­el of ischae­mia reper­fu­sion.
Methods. The ­effect of lisin­o­pril car­di­o­ple­gia, ­oral pre­treat­ment ­with lisin­o­pril and lisin­o­pril ­enriched reper­fu­sion solu­tion on myo­car­di­um ­after a nor­mo­ther­mic glo­bal ische­mia of 90 min­utes and 30 min­utes of reper­fu­sion in the mod­i­fied Langendorff mod­el was ran­dom­ly stud­ied in 4 ­groups (n=8 in ­each). In all ­groups, car­di­o­pleg­ic ­arrest was ­achieved by admin­is­ter­ing St. Thomas’ Hospital Cardioplegic Solution (­STHCS). The ­first ­group was uti­lized as the con­trol. In the sec­ond ­group, ­hearts ­were arrest­ed ­with lisin­o­pril (1 µmol/L) ­enriched ­STHCS. In the ­third ­group, ani­mals ­were pre­treat­ed ­with ­oral lisin­o­pril (0.2 mg/kg/­twice a day) for ten ­days. In the ­last ­group ­hearts ­were ­again pre­treat­ed ­with ­oral lisin­o­pril (­like in ­Group 3) and the ­heart ­were reper­fused ­with lisin­o­pril ­enriched (1 µmol/L) Krebs-Henseleit solu­tion dur­ing the reper­fu­sion peri­od.
Results. Contractility, ­which was ­expressed as con­trac­tile ­force (g con­trac­til­ity/g ­heart ­weight), was pre­served bet­ter in the ­study ­groups. In the ­last ­group, the ­hearts had the ­best ­left ven­tric­u­lar con­trac­tile func­tion, ­where con­trac­tile ­force was 58.4%±4.82% of the pre­is­chaem­ic val­ues. In Group I, ­Group II and ­Group III ­they ­achieved 29.5%±5.6%, 41.9%±4.9%, and 55.3%±5.8% of ­their pre­is­chaem­ic con­trac­tile ­force val­ues respec­tive­ly. Creatine ­kinase leak­age was sig­nif­i­cant­ly low­er and ­also ­post- ischaem­ic cor­o­nary ­flows ­were sig­nif­i­cant­ly high­er in the 4th ­group. Coronary ­flow ­after reper­fu­sion ­increased ­from 48.0±6.2 to 68.0±4.51 ml/min·g·­heart, in ­Group IV (p<0.05).
Conclusions. Myocardial MDA and GSH con­tents ­showed ­that ­there was a cor­re­la­tion ­between the deple­tion of myo­car­dial GSH con­tent and ­increased lip­id per­ox­i­da­tion. The myo­car­dial GSH con­tent indi­cates ­that the ­best ­results ­were ­obtained in the ­last ­group as com­pared to the oth­er ­groups. These pre­lim­i­nary ­results ­showed ­that ­oral pre­con­di­tion­ing ­improved ­postischaem­ic myo­car­dial func­tion and ­decreased myo­car­dial inju­ry. Because the ­best ­results ­were ­achieved in the ­last ­group, it can be sug­gest­ed ­that lisin­o­pril may ­also ­play a pro­tec­tive ­role ­againts reper­fu­sion inju­ry.

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