Dose-dependent protection of cardiac function by propofol during ischemia and early reperfusion in rats: effects on 15-F_2t-isoprostane formation

Abstract

We examined the effects of propofol (2,6-diisopropylphenol) on functional recovery and 15-F2t-isoprostane generation during ischemia-reperfusion in Langendorff-perfused rat hearts. Before the induction of 40 min of global ischemia, hearts were perfused (10 min) with propofol at 5 (lo-P) or 12 microg/mL (hi-P) in saline or with saline only (control). During ischemia, saline, lo-P, or hi-P was perfused through the aorta at 60 microL/min. During the first 15 min of reperfusion, propofol (5 or 12 microg/mL) was continued, followed by perfusion with 5 microg/mL propofol for 75 min in both propofol-treated groups. After 90 min of reperfusion (Rep-90), heart tissues were harvested for assessment of antioxidant status. In hi-P, we observed increased latency to and greater reduction of ischemic contracture relative to the lo-P or control groups. 15-F2t-Isoprostane concentrations increased during ischemia and were significantly lower in hi-P and lo-P than in control (P < 0.01). At Rep-90, myocardial functional recovery was greater in both propofol-treated groups relative to control, and it correlated positively with tissue antioxidant capacity preservation. Tissue antioxidant capacity was better preserved in hi-P than in lo-P treatment (P < 0.05). We conclude that oxidant injury occurs during ischemia and reperfusion, and propofol provides dose-dependent protection primarily by enhancing tissue antioxidant capacity and reducing lipid peroxidation.

Propofol protects against hydrogen peroxide-induced injury in cardiac H9c2 cells via Akt activation and Bcl-2 up-regulation

“…Propofol (2,6-diisopropylphenol), an intravenous anesthetic, has been found to attenuate oxidative stress induced mechanical and metabolic derangements in the isolated rat heart and prevent ischemia/reperfusion injury [1][2][3]. The antioxidant mechanism mainly relates to its phenolic chemical structure.…”

Propofol cardioprotection for on-pump aortocoronary bypass surgery in patients with type 2 diabetes mellitus (PRO-TECT II): a phase 2 randomized-controlled trial

“…Our study intervention was derived from prior in vitro and in vivo studies of the concentration and time-dependent effects of propofol which define a therapeutic window that we correlate with cyto-and cardioprotection (4.2-8.4 lgÁmL ). 16,17,23 These concentrations were achieved in the systemic circulation at reperfusion in 87% of participants where aortic cross-clamp intervals exceeded 60 min. Our technique enriches blood cardioplegia.…”

“…25 A prior in vitro study from our laboratory determined that the normothermic heart was a major source of 15-F 2t -isoprostane. 17,18,26 Mean (SD) arterial 15-F 2t -isoprostane measurements were lower than concurrent CS measurements [30.1 (18.9) vs 94.0 (32.1) pg.mL -1 , respectively] in samples from the first ten participants that were analyzed without unmasking the allocation. Based on these results, the primary endpoint was modified with subsequent analyses based on only CS 15-F 2t -isoprostane levels.…”

“…16 Applying propofol just before, during, and briefly following ischemia-reperfusion in rat heart models decreases release of plasma free 15-F 2t -isoprostane, 17,18 a biomarker of oxidative stress. It exacerbates myocardial IRI, producing left ventricular dysfunction directly via receptor-induced coronary artery vasoconstriction.…”

“…23 Accordingly, in this study, we investigated the concentration and time-dependent effects of propofol (whole blood concentration 4-12 lgÁmL -1 ) compared with isoflurane on cyto-and cardioprotective measures of oxidative injury. 16,17 We hypothesized that propofol would decrease 15-F 2t -isoprostane release and, as a result, reduce the incidence of LCOS. We further explored concomitant myocardial Bcl-2 expression as it may affect or be affected by 15-F 2t -isoprostane release.…”