Protective effect of lisinopril against ischemia-reperfusion injury in isolated guinea pig hearts.
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 micromol/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 micromol/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 against reperfusion injury.
Doğan
R
R
Department of Thoracic and Cardiovascular Surgery, Hacettepe University, Faculty of Medicine, Ankara, Turkey. Carvas@gen.hun.edu.tr
Farsak
B
B
Isbir
S
S
Sarigül
A
A
Tuncer
M
M
Kilinç
K
K
D000284:Administration, Oral; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000818:Animals; D001639:Bicarbonates; D002122:Calcium Chloride; D002314:Cardioplegic Solutions; D005978:Glutathione / Q000378:metabolism; D006168:Guinea Pigs; D006324:Heart Arrest, Induced; D015227:Lipid Peroxidation; D017706:Lisinopril / Q000008:administration & dosage*; D008274:Magnesium; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D011189:Potassium Chloride; D012965:Sodium Chloride
D000806:Angiotensin-Converting Enzyme Inhibitors; D001639:Bicarbonates; D002314:Cardioplegic Solutions; C041711:St. Thomas' Hospital cardioplegic solution; D012965:Sodium Chloride; D008315:Malondialdehyde; D011189:Potassium Chloride; D017706:Lisinopril; D005978:Glutathione; D008274:Magnesium; D002122:Calcium Chloride