Optimal positive end-expiratory pressure during robot-assisted laparoscopic radical prostatectomy.

BACKGROUND: Increased intra-abdominal pressure during laparoscopic surgery causes cephalad displacement of the diaphragm, resulting in the formation of atelectasis, which can be overcome by positive end-expiratory pressure (PEEP). The aim of this prospective study was to investigate the level of optimal PEEP to maintain adequate arterial oxygenation and hemodynamics during robot-assisted laparoscopic radical prostatectomy (RLRP). METHODS: One hundred patients undergoing RLRP were randomly allocated to one of five groups (n = 20) (0, 3, 5, 7 and 10 cmH2O of PEEP). Hemodynamic variables and respiratory parameters were measured at baseline with the patient in the supine position; at 30 min, 1, 2, 3 and 4 h during CO2 insufflation with the patient in the post-Trendelenburg position; and after deflation in the supine position with increasing PEEP. RESULTS: The PaO2 levels and alveolar-arterial difference in oxygen tension (AaDO2) were improved in patients with PEEPs compared with patients in whom PEEP was not used. The application of PEEP (10 cmH2O) resulted in higher PaO2 levels compared to those with lower PEEP levels, but excessive peak airway pressure (PAP) was sometimes observed. The application of a PEEP of 7 cmH2O resulted in similar PaO2 levels without causing excessive PAP. There was a significant difference in central venous pressure between the groups, but there were no significant differences in heart rate, mean arterial pressure or minute ventilation between the groups. CONCLUSIONS: A PEEP of 7 cmH2O is associated with the greater improvement of PaO2 and AaDO2 without causing excessive PAP during RLRP.

Antioxidant effect of muscle relaxants (vecuronium, rocuronium) on the rabbit abdominal aortic endothelial damage induced by reactive oxygen species.

BACKGROUND: Muscle relaxants induce vascular smooth muscle relaxation by inducing synthesis of the prostaglandins that influence vasomotor tone. However, the effects of muscle relaxants on endothelial cells and tissues following injury by reactive oxygen species (ROS) are unclear. We tested the effects of the muscle relaxants vecuronium and rocuronium on impaired acetylcholine (ACh)-induced relaxation following induction of ROS in rabbit aorta in vitro. METHODS: Isolated rabbit abdominal aortic ring segments were pretreated with vecuronium or rocuronium at 10(-4), 3 × 10(-4), 10(-3) or 3 × 10(-3) M, with or without inhibitors of Cu/Zn superoxide dismutase (diethyldithiocarbamate; DETCA, 0.8 mM) or catalase (3-amino-1,2,4-triazole; 3AT, 50 mM). All groups of aortic rings were then exposed to ROS generated by electrolysis in the organ bath medium (Krebs-Henseleit solution). The effects of vecuronium and rocuronium on ROS-induced impairment of relaxation induced by ACh (10(-6) M) were assessed. RESULTS: Aortic rings treated with vecuronium or rocuronium at 10(-4), 3 × 10(-4), 10(-3) or 3 × 10(-3) M preserved the capacity for ACh-induced endothelial relaxation following ROS exposure in a dose-dependent manner. Pretreatment with DETCA partially inhibited the protective effects of vecuronium and rocuronium on ACh-induced relaxation (P < 0.001), but pretreatment with 3AT had no effect. CONCLUSIONS: Muscle relaxants protected the endothelium in isolated rabbit abdominal aorta from free-radical injury in a dose-dependent manner. These results suggest that vecuronium and rocuronium may act as superoxide anion scavengers.

Cocoa procyanidins attenuate 4-hydroxynonenal-induced apoptosis of PC12 cells by directly inhibiting mitogen-activated protein kinase kinase 4 activity.

Neurodegenerative disorders such as Alzheimer's disease (AD) are associated with oxidative stress, and it has been suggested that apoptosis is a crucial pathway in neuronal cell death in AD patients. 4-Hydroxynonenal (HNE), one of the aldehydic products of membrane lipid peroxidation, is reported to be elevated in the brains of AD patients and mediates the induction of neuronal apoptosis in the presence of oxidative stress. In this study, we investigated the HNE-induced apoptosis mechanism and the protective effects of the cocoa procyanidin fraction (CPF) and its major antioxidant procyanidin B2 against the apoptosis induced by HNE in rat pheochromocytoma (PC12) cells. HNE-induced nuclear condensation and increased sub-G1 fraction, both of which are markers of apoptotic cell death, were inhibited by CPF and procyanidin B2. Intracellular reactive oxygen species (ROS) accumulation was attenuated by pretreatment with CPF and procyanidin B2. CPF and procyanidin B2 also prevented HNE-induced poly(ADP-ribose) polymerase cleavage, antiapoptotic protein (Bcl-2 and Bcl-X(L)) down-regulation, and caspase-3 activation. Activation of c-Jun N-terminal protein kinase (JNK) and mitogen-activated protein kinase kinase 4 (MKK4) was attenuated by CPF and procyanidin B2. Moreover, CPF and procyanidin B2 bound directly to MKK4 and inhibited its activity. Data obtained with SP600125, a selective inhibitor of JNK, revealed that JNK is involved in HNE-induced apoptosis through the inhibition of PARP cleavage and caspase-3 activation in PC12 cells. Collectively, these results indicate that CPF and procyanidin B2 protect PC12 cells against HNE-induced apoptosis by blocking MKK4 activity as well as ROS accumulation.

Attenuation of oxidative neuronal cell death by coffee phenolic phytochemicals.

Neurodegenerative disorders such as Alzheimer's disease (AD) are strongly associated with oxidative stress, which is induced by reactive oxygen species (ROS) including hydrogen peroxide (H(2)O(2)). Recent studies suggest that moderate coffee consumption may reduce the risk of neurodegenerative diseases such as AD, but the molecular mechanisms underlying this effect remain to be clarified. In this study, we investigated the protective effects of chlorogenic acid (5-O-caffeoylquinic acid; CGA), a major phenolic phytochemical found in instant decaffeinated coffee (IDC), and IDC against oxidative PC12 neuronal cell death. IDC (1 and 5 microg/ml) or CGA (1 and 5 microM) attenuated H(2)O(2)-induced PC12 cell death. H(2)O(2)-induced nuclear condensation and DNA fragmentation were strongly inhibited by pretreatment with IDC or CGA. Pretreatment with IDC or CGA also inhibited the H(2)O(2)-induced cleavage of poly(ADP-ribose) polymerase (PARP), and downregulation of Bcl-X(L) and caspase-3. The accumulation of intracellular ROS in H(2)O(2)-treated PC12 cells was dose-dependently diminished by IDC or CGA. The activation of c-Jun N-terminal protein kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) by H(2)O(2) in PC12 cells was also inhibited by IDC or CGA. Collectively, these results indicate that IDC and CGA protect PC12 cells from H(2)O(2)-induced apoptosis by blocking the accumulation of intracellular ROS and the activation of MAPKs.

Cocoa procyanidins protect PC12 cells from hydrogen-peroxide-induced apoptosis by inhibiting activation of p38 MAPK and JNK.

Oxidative stress induced by reactive oxygen species has been strongly associated with the pathogenesis of neurodegenerative disorders, including Alzheimer's disease. In this study, we investigated the possible protective effects of a cocoa procyanidin fraction (CPF) and procyanidin B2 (epicatechin-(4beta-8)-epicatechin) - a major polyphenol in cocoa - against apoptosis of PC12 rat pheochromocytoma (PC12) cells induced by hydrogen peroxide (H(2)O(2)). CPF (1 and 5 microg/ml) and procyanidin B2 (1 and 5 microM) reduced PC12 cell death caused by H(2)O(2), as determined by MTT and trypan blue exclusion assays. CPF and procyanidin B2 attenuated the H(2)O(2)-induced fragmentation of nucleus and DNA in PC12 cells. Western blot data demonstrated that H(2)O(2) induced cleavage of poly(ADP-ribose)polymerase (PARP), downregulated Bcl-X(L) and Bcl-2 in PC12 cells. Pretreatment with CPF or procyanidin B2 before H(2)O(2) treatment diminished PARP cleavage and increased Bcl-X(L) and Bcl-2 expression compared with those only treated with H(2)O(2). Activation of caspase-3 by H(2)O(2) was inhibited by pretreatment with CPF or procyanidin B2. Furthermore, H(2)O(2)-induced rapid and significant phosphorylation of c-Jun N-terminal protein kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), and both of these effects were attenuated by CPF or procyanidin B2 treatment. These results suggest that the protective effects of CPF and procyanidin B2 against H(2)O(2)-induced apoptosis involve inhibiting the downregulation of Bcl-X(L) and Bcl-2 expression through blocking the activation of JNK and p38 MAPK.