Application of high-dose propofol during ischemia improves postischemic function of rat hearts: effects on tissue antioxidant capacity.

Centre for Anesthesia and Analgesia, Department of Pharmacology and Therapeutics, University of British Columbia, Vancouver, Canada.
Canadian Journal of Physiology and Pharmacology (Impact Factor: 1.56). 11/2004; 82(10):919-26. DOI: 10.1139/y04-097
Source: PubMed

ABSTRACT Previous studies have shown that reactive oxygen species mediated lipid peroxidation in patients undergoing cardiac surgery occurs primarily during cardiopulmonary bypass. We examined whether application of a high concentration of propofol during ischemia could effectively enhance postischemic myocardial functional recovery in the setting of global ischemia and reperfusion in an isolated heart preparation. Hearts were subjected to 40 min of global ischemia followed by 90 min of reperfusion. During ischemia, propofol (12 microg/mL in saline) was perfused through the aorta at 60 microL/min. We found that application of high-concentration propofol during ischemia combined with low-concentration propofol (1.2 microg/mL) administered before ischemia and during reperfusion significantly improved postischemic myocardial functional recovery without depressing cardiac mechanics before ischemia, as is seen when high-concentration propofol was applied prior to ischemia and during reperfusion. The functional enhancement is associated with increased heart tissue antioxidant capacity and reduced lipid peroxidation. We conclude that high-concentration propofol application during ischemia could be a potential therapeutic and anesthetic strategy for patients with preexisting myocardial dysfunction.

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    ABSTRACT: OBJECTIVES: In a variety of experimental models, propofol has been shown to protect the brain. It was hypothesized that a clinically achievable high dose of propofol would induce cerebral protective effects in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). The authors investigated the effects of different target plasma concentrations of propofol on cerebral injury by measuring serum S-100β protein and neuron-specific enolase (NSE) levels in patients undergoing single-valve replacement with CPB. DESIGN: A prospective, randomized study. SETTING: A university hospital. PARTICIPANTS: Forty-two patients undergoing single-valve replacement with CPB. INTERVENTIONS: Patients were randomly divided into 3 groups (n = 14 each). Each group received a target-controlled infusion of propofol with plasma concentrations of 1.8μg/mL (low dose, Group-L), 2.4μg/mL (medium dose, Group-M), or 3.2μg/mL (high dose, Group-H). The propofol target concentrations were unchanged throughout the surgery. MEASUREMENTS AND MAIN RESULTS: In all 3 groups of patients, at all time points after CPB, the plasma S-100β protein and NSE levels, which served as biochemical markers of brain damage, were significantly higher than the preoperative levels (p<0.05). Group-H showed significant decreases in S-100β protein and NSE compared with Group-L (p< 0.05). CONCLUSION: In the range of commonly used clinical concentrations, administration of a high dose of propofol during CPB attenuated the biochemical markers of brain damage as compared with low-dose propofol anesthesia.
    Journal of cardiothoracic and vascular anesthesia 04/2013; · 1.06 Impact Factor
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    ABSTRACT: To determine whether or not the antioxidants N-acetylcysteine (NAC) and allopurinol (ALP) confer synergistic cardioprotection against myocardial ischemia/reperfusion (MI/R) injury by stabilizing hypoxia inducible factor 1α (HIF-1α)/heme oxygenase 1 (HO-1) signaling in diabetic myocardium. Control or diabetic [streptozotocin (STZ)-induced] Sprague Dawley rats received vehicle or NAC, ALP or their combination for four weeks starting one week after STZ injection. The animals were then subjected to thirty minutes of coronary artery occlusion followed by two hours reperfusion in the absence or presence of the selective HO-1 inhibitor, tin protoporphyrin-IX (SnPP-IX) or the HIF-1α inhibitor 2-Methoxyestradiol (2ME2). Cardiomyocytes exposed to high glucose were subjected to hypoxia/re-oxygenation in the presence or absence of HIF-1α and HO-1 achieved by gene knock-down with related siRNAs. Myocardial and plasma levels of 15-F2t-isoprostane, an index of oxidative stress, were significantly increased in diabetic rats while cardiac HO-1 protein and activity were reduced; this was accompanied with reduced cardiac protein levels of HIF-1α, and increased post-ischemic myocardial infarct size and cellular injury. NAC and ALP given alone and in particular their combination normalized cardiac levels of HO-1 and HIF-1α protein expression and prevented the increase in 15-F2t-isoprostane, resulting in significantly attenuated post-ischemic myocardial infarction. NAC and ALP also attenuated high glucose-induced post-hypoxic cardiomyocyte death in vitro. However, all the above protective effects of NAC and ALP were cancelled either by inhibition of HO-1 or HIF-1α with SnPP-IX and 2ME2 in vivo or by HO-1 or HIF-1α gene knock-down in vitro. NAC and ALP confer synergistic cardioprotection in diabetes via restoration of cardiac HIF-1α and HO-1 signaling.
    PLoS ONE 01/2013; 8(7):e68949. · 3.73 Impact Factor

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