The role of zofenopril in myocardial protection during cardioplegia arrest: an isolated rat heart model.
BACKGROUND
Zofenopril has beneficial effects in acute myocardial infarction, and improves the functional recovery after ischemia and reperfusion.


OBJECTIVE
The aim of this study was to investigate the cardioprotective effects of zofenopril, when added to a standard cardioplegic solution or when orally administered as pretreatment.


METHODS
A Langendorff model for isolated rat hearts was employed: three groups of eight hearts each were used, respectively, with plain St. Thomas cardioplegia as control (group A and C), and the same solution added with 12.5 mg of zofenopril (group B). The third group (C) was pretreated for 7days with oral administration of zofenopril (6.5 mg/day). The hearts had a baseline perfusion for 30 minutes with Krebs-Henseleit solution at 37 degrees C, cardioplegia administration for 3 minutes, then 30 minutes of ischemia without any perfusion, and finally 30 minutes of reperfusion with Krebs-Henseleit solution at 37 degrees C.


RESULTS
Left ventricle developed pressure was significantly higher in the reperfusion period only in the pretreated group (group C) with respect to groups A and B (p = 0.016). Similar results were obtained regarding dP/dt curves (p = 0.020). No differences were demonstrated between groups for cellular viability expressed as creatine phospho-kinase (p = ns) and lactate dehydrogenase release (p = ns).


CONCLUSIONS
Zofenopril as oral pretreatment showed protective effects in an isolated model of cardioplegic arrest, although improvements in myocardial viability (enzymatic release) could not be demonstrated. Further experimental and clinical evaluations are necessary to assess the direct cardioprotective effect of zofenopril, modifying the length of treatment and the dosage of the drug.
Leva
Cristian
C
Department of Surgical Sciences, Cardiothoracic Division, Varese University Hospital, Varese, Italy.
Mariscalco
Giovanni
G
Ferrarese
Sandro
S
Bruno
Vito Domenico
VD
Orrù
Alessandro
A
Cattaneo
Paolo
P
Sala
Andrea
A
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002216:Captopril / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003402:Creatine Kinase / Q000378:metabolism; D004195:Disease Models, Animal; D006324:Heart Arrest, Induced; D066298:In Vitro Techniques; D007432:Intraoperative Period; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome; D017725:Ventricular Pressure / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; C044958:zofenopril; D002216:Captopril; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase