Cellular and Molecular Biology


Isoflurane post-conditioning stimulates the proliferative phase of myocardial recovery in an ischemia-reperfusion model of heart injury in rats

Ivan Agnić1, Katarina Vukojević2, Mirna Saraga-Babić2, Natalija Filipović2 and Ivica Grković2

1Department of Anesthesiology, University Hospital Split, Split and 2Department of Anatomy, Histology and Embryology, University of Split School of Medicine, Split, Croatia

Offprint requests to: Professor Ivica Grković, Department of Anatomy, Histology and Embryology, University of Split School of Medicine, Soltanska 2, 21000 Split, e-mail: ivica.grkovic@mefst.hr

Summary. The application of isoflurane in a post-conditioning manner, during early reperfusion following a period of coronary occlusion, has numerous beneficial effects on the ischemic myocardium, including reduction of infarct size. It does so by stimulating a sequence of well studied anti-apoptotic pro-survival mechanisms in a similar manner to various ‘ischemic’ pre-/post-conditioning approaches which achieve their cardio protective effects in both laboratory and clinical situations. Proliferation of newly formed blood vessels, resulting in formation of highly vascularized granulation tissue, is an essential stage of infarct healing. It can be evaluated by detecting various angiogenic factors, including vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) or by quantification of expression of vascular smooth muscle progenitors, such as Nestin. Expression of these three markers was used to evaluate the effect of early isoflurane post-conditioning in ischemia-reperfusion type cardiac injury. A large reduction in infarct size (59.3% of control), and marked increase of expression of VEGF (43.4%), PECAM-1/CD31 (136%) and Nestin (77.9%) was found in experimental animals when compared to control animals that did not receive isoflurane treatment. Hence, based on our results, we can emphasize two morphologically detectable benefits of isoflurane post-conditioning: a marked reduction in infarct size and much better organization/vascularization of necrotic tissue
. Histol Histopathol 29, 89-99 (2014)

Key words: Myocardial infarction, Ischemia-reperfusion model, VEGF, PECAM/CD31, Nestin

DOI: 10.14670/HH-29.89