###### Abstract  
Background: Anesthetic preconditioning (AP) is known to mimic ischemic preconditioning. The purpose of this study was to investigate the effects of an interrupted sevoflurane administration protocol on myocardial ischemia/reperfusion (I/R) injury. Methods: Male Wistar rats (\(n=60\)) were ventilated for 30 min with room air (control group, CG) or with a mixture of air and sevoflurane (1 minimum alveolar concentration--MAC) in 5-min cycles, alternating with 5-min wash-out periods (preconditioned groups). Cytokines implicated in the AP response were measured. An (I/R) lesion was produced immediately after the sham intervention (CG) and preconditioning protocol (early AP group, EAPG) or 24 h after the intervention (late AP group, LAPG). The area of fibrosis, the degree of apoptosis and the number of c-kit+ cells was estimated for each group. Results: Cytokine levels were increased post AP. The area of fibrosis decreased in both EAPG and LAPG compared to the CG (\(p<0.000\)). When compared to the CG, the degree of apoptosis was reduced in both LAPG (\(p=0.006\)) and EAPG (\(p=0.007\)) and the number of c-kit+ cells was the greatest for the LAPG (\(p<0.0001\)). Conclusions: Sevoflurane preconditioning, using an interrupted anesthesia protocol, is efficient in myocardial protection and could be beneficial to reduce perioperative or periprocedural ischemia in patients with increased cardiovascular risk.  
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progenitor cells [5,6]. Amongst the population of mesenchymal stromal/stem cells (MSCs), the endothelial progenitor cells (EPC), identified through the specific marker CD34 (also known as flk1), have paracrine activity and play key roles in neovascularization and maintaining endothelial function [7]. IP increases the number of c-kit\({}^{+}\) (receptor for stem cell factor) and flk-1+ progenitor cells in the myocardium subjected to ischemia and reperfusion [6]. Given the similarities between IP and AP, similar mechanisms may underlie cardioprotection conferred by AP as well.  
Patients with cardiovascular disease exhibit low levels of dysfunctional EPC [8,9], which makes them an interesting target for both diagnostic and therapeutic strategies. [PERSON] et al. demonstrated in rat left ventricular samples that sevoflurane, a volatile anesthetic widely used in clinical practice, produces changes in the expression of genes and proteins involved in cardioprotection that persists for 72 h [10]. Sevoflurane has been shown to induce the mobilization of and potentiate the function of EPCs [11,12], possibly through increased cytokine production. After exposure to sevoflurane, human blood monocytes showed overexpression of vascular endothelial growth factor (VEGF) and granulocyte colony stimulating factor (G-CSF) [13]. These factors are known to be involved in the mobilization and recruitment of the MSC [13,14]. In addition, another volatile anesthetic, isoflurane, activates hypoxia induced factor-1 \(\alpha\) (HIF-1 \(\alpha\)), which in turn stimulates the synthesis of VEGF [15,16] and SDF-1 \(\alpha\), cytokines which have been implicated in MSC mobilization and homing [6]. Sevoflurane has also been shown to modulate the expression of integrins and L-selectin, molecules involved in the acute proinflammatory response and which contribute to local injury [13]. Administration of cytokines such as interleukin 1 (IL-1) is associated with resistance to I/R [17,18]. Interleukin-6 (IL-6) deficient mice are resistant to preconditioning, and that preconditioning-mediated activation of STAT1/3, iNOS, and COX-2 is attenuated in these mice [19,20]. Furthermore, AP has been shown to be associated with reduced apoptosis and fibrosis after I/R injury [21, 22, 23, 24, 25].  
We hypothesized that sevoflurane preconditioning may mediate cardioprotection via modulation of paracrine activity and MSCs mobilization, which in turn act to decrease apoptosis and fibrosis after I/R injury.