Comparison of Isoflurane-, Sevoflurane-, and Desflurane-Induced Pre- and Postconditioning Against Myocardial Infarction in Mice In Vivo

Abstract

The murine in vivo model of acute myocardial infarction is increasingly used to investigate anesthetic-induced preconditioning (APC) and postconditioning (APOST). However, in mice the potency of different volatile anesthetics to reduce myocardial infarct size (IS) has never been investigated systematically nor in a head to head comparison with regard to ischemic preconditioning (IPC) and postconditioning (IPOST). Male C57BL/6 mice were subjected to 45 min of coronary artery occlusion (CAO) and 180 min of reperfusion. To induce APC, 1.0 MAC isoflurane (ISO), sevoflurane (SEVO) or desflurane (DES) was administered 30 min prior to CAO for 15 min. In an additional group, ISO was administered 45 min prior to CAO for 30 min. To induce APOST, 1.0 MAC ISO, SEVO or DES was administered for 18 min starting 3 min prior to the end of CAO. IPC was induced by 3 or 6 cycles of 5 min ischemia/reperfusion, 40 or 60 min prior to CAO, respectively. IPOST was induced by 3 cycles of 30 sec reperfusion/ischemia at the beginning of reperfusion. Area at risk (AAR) and IS were determined with Evans Blue and TTC staining, respectively. IS (IS/AAR) was 50 +/- 4% (mean +/- SEM) in the control group and was significantly (*P < 0.05) reduced by 3x5 IPC (26 +/- 3%*), 6 x 5 IPC (26 +/- 4%*), IPOST (20 +/- 2%*), ISO APOST (19 +/- 1%*), SEVO APOST (15 +/- 1%*), DES APOST (14 +/- 2%*) and SEVO APC (27 +/- 6%*). ISO APC significantly reduced IS compared to control when administered 30 min (33 +/- 4%*), but not when administered 15 min (48 +/- 6%). DES APC significantly reduced IS compared to control and to SEVO APC (7 +/- 1%*). Within the paradigm of preconditioning, the potency of volatile anesthetics to reduce myocardial infarct size in mice significantly increases from ISO over SEVO to DES, whereas within the paradigm of postconditioning the potency of these volatile anesthetics to reduce myocardial infarct size in mice is similar.

Desflurane‐induced and ischaemic postconditioning against myocardial infarction are mediated by Pim‐1 kinase

“…Both 15-min administration of 1 MAC DES during early reperfusion and three cycles of each 10-s reperfusion/ischaemia immediately after prolonged myocardial ischaemia exerted remarkable cardioprotective effects, represented by a pronounced reduction in myocardial IS. These results are in line with findings from various other investigations regarding either APOST 5,11,29 or Data are mean Ϯ SEM. Data were analysed during baseline period (BL), before (PreCAO) and during (CAO) CAO, during early reperfusion period (POST) and 60, 120 and 180 min after the onset of reperfusion, as indicated by triangles in Figure 1.…”

“…IPOST, [5][6][7]29 and provide further evidence that APOST and IPOST are promising strategies to alleviate cardiac ischaemia/reperfusion injury. In this study, DES and IPOST reduced myocardial IS to a similar extent.…”

“…3 IPOST has been demonstrated to reduce myocardial IS among others in dogs, 3 rabbits 4 and mice. [5][6][7] In humans, IPOST has been shown to reduce myocardial IS as assessed 6 months after acute myocardial infarction and to improve left ventricular ejection fraction after 1 year. 8 Cardioprotective properties of volatile anaesthetics during early reperfusion are known for more than a decade since the first description of Schlack's group.…”

“…9 Later, this phenomenon was termed anaesthetic-induced postconditioning (APOST). 10 APOST reduces myocardial IS, 5,10,11 improves left ventricular function after myocardial ischaemia 12 and has been demonstrated to occur in humans. 13 Isoflurane, sevoflurane and desflurane (DES) are equally effective to reduce myocardial IS in mice in vivo.…”

“…13 Isoflurane, sevoflurane and desflurane (DES) are equally effective to reduce myocardial IS in mice in vivo. 5 Both IPOST and APOST afford their cardioprotective properties via reduction of reperfusion injury and are mediated via phosphatidylinositol-3-kinase (PI3K)/Akt 10,14,15 as a part of the reperfusion injury salvage kinase (RISK) pathway. 16 The serine/threonine kinase Pim-1 belongs to the family of calcium/calmodulin-dependent protein kinases (CaMK).…”