Validation of cardiac output estimation using the fourth-generation FloTrac/EV1000™ system in patients undergoing robotic-assisted off-pump coronary artery bypass surgery.

The pulmonary artery catheter (PAC)-despite its invasiveness-remains the gold standard for cardiac output (CO) monitoring. The FloTrac system, a less invasive hemodynamic monitor has been developed, which estimates CO using arterial pressure waveform analysis without external calibration. Recently, an upgraded version of FloTrac system with improved algorithm to follow changes in vascular resistance was introduced into the market. The aim of this study was to assess the reliability of the CO estimated from the fourth-generation FloTrac/EV1000 system (COFT) compared to that measured with PAC using the thermodilution method (COPAC) during robotic-assisted off-pump coronary artery bypass (OPCAB) surgery. COFT and COPAC were obtained simultaneously at 4 predefined time points during robotic-assisted OPCAB: 5 min after the induction of general anesthesia (T1), after starting one-lung ventilation (T2), after capnothorax (T3), and after mini-thoracotomy was performed (T4). The agreement of data was investigated by Bland-Altman analysis. Thirty-four patients were initially enrolled. After exclusion, 32 patients and a total of 128 paired CO measurements were obtained. The overall bias was 1.46 L/min, the 95% limits of agreements were - 3.40 to 6.33 L/min, and the percentage error was 72.98%. Regression analysis of the systemic vascular resistance index (SVRI) and the bias between COPAC and COFT showed that the bias was moderately correlated with the SVRI (r2 = 0.43; p < 0.0001). Despite a software upgrade, the reliability of the fourth-generation FloTrac/EV1000™ system during robotic-assisted OPCAB to estimate CO was not acceptable, especially in patients with low SVRI.

Correction to: 4-Phenylbutyric acid protects against vasculitic peripheral neuropathy induced by ischaemia-reperfusion through attenuating endoplasmic reticulum stress.

Unfortunately, Fig. 5 was incorrectly published in the original publication. The complete corrected Fig. 5 is given below.

4-Phenylbutyric acid protects against vasculitic peripheral neuropathy induced by ischaemia-reperfusion through attenuating endoplasmic reticulum stress.

Vasculitic peripheral neuropathy (VPN) is characterized by acute-to-subacute onset of painful sensory and motor disturbances that result from inflammatory obliteration of nerve blood vessels and subsequent ischaemic injury. Endoplasmic reticulum (ER) stress has been implicated in the pathogenesis of various peripheral neuropathies, and 4-phenylbutyric acid (4-PBA) is a chemical chaperone that inhibits ER stress signaling. We investigated the effects of 4-PBA on neuropathic pain associated with VPN induced by ischaemia-reperfusion (IR) and its underlying mechanisms. Male Sprague-Dawley rats were allocated to one of the following groups: sham, sham + 4-PBA, IR, and IR + 4-PBA. IR was achieved by occluding the femoral artery for 4 h followed by reperfusion. The behavioral parameters were assessed, and the expression of ER stress markers and nuclear factor (NF)-κB in sciatic nerves was measured. The behavioral data confirmed that VPN induced by IR leads to hindpaw mechano-allodynia and heat hyperalgesia as well as impaired hindpaw grip strength, indicating the development of neuropathic pain and debilitating symptoms of VPN. The molecular data revealed that VPN induced by IR activated ER stress sensors and effector molecules as well as NF-κB in the sciatic nerves, indicating the involvement of ER stress and NF-κB-mediated neuroinflammation. Notably, 4-PBA significantly reduced the expression of all these markers and improved all behavioral changes induced by IR. This study demonstrated that ER stress and NF-κB-mediated neuroinflammation contribute to VPN induced by IR and that 4-PBA has protective potential against neuropathic pain associated with VPN.

A turn-like structure "KKPE" segment mediates the specific binding of viral protein A27 to heparin and heparan sulfate on cell surfaces.

Vaccinia viral envelope protein A27 (110 amino acids) specifically interacts with heparin (HP) or heparan sulfate (HS) proteoglycans for cell surface attachment. To examine the binding mechanism, a truncated soluble form of A27 (sA27-aa; residues 21-84 of A27) with Cys(71) and Cys(72) mutated to Ala was used as the parent molecule. sA27-aa consists of two structurally distinct domains, a flexible Arg/Lys-rich heparin-binding site (HBS) (residues 21-32; (21)STKAAKKPEAKR(32)) and a rigid coiled-coil domain (residues 43-84), both essential for the specific binding. As shown by surface plasmon resonance (SPR), the binding affinity of sA27-aa for HP (K(A) = 1.25 x 10(8) m(-1)) was approximately 3 orders of magnitude stronger than that for nonspecific binding, such as to chondroitin sulfate (K(A) = 1.65 x 10(5) m(-1)). Using site-directed mutagenesis of HBS and solution NMR, we identified a "KKPE" segment with a turn-like conformation that mediates specific HP binding. In addition, a double mutant T22K/A25K in which the KKPE segment remained intact showed an extremely high affinity for HP (K(A) = 1.9 x 10(11) m(-1)). Importantly, T22K/A25K retained the binding specificity for HP and HS but not chondroitin sulfate, as shown by in vitro SPR and in vivo cell adhesion and competitive binding assays. Molecular modeling of the HBS was performed by dynamics simulations and provides an explanation of the specific binding mechanism in good agreement with the site-directed mutagenesis and SPR results. We conclude that a turn-like structure introduced by the KKPE segment in vaccinia viral envelope protein A27 is responsible for its specific binding to HP and to HS on cell surfaces.

Adverse effects of bilateral lower limb ischemia-reperfusion on inducing kidney injuries in rats could be ameliorated by platonin.

OBJECTIVES: Bilateral lower limb ischemia-reperfusion (I/R) could cause significant oxidative stress, elicit inflammatory response, and subsequently induce kidney injury in animals. We tested the effects of platonin, a potent antioxidant, on mitigating the kidney injury induced by lower limb I/R in rats. METHODS: Adult male rats were allocated to receive I/R or I/R plus platonin (100 µg/kg intravenous injection immediately after reperfusion), and denoted as the I/R or the I/R-P group, respectively (n = 10 in each group). Sham groups were run simultaneously. Bilateral lower limb I/R was achieved by applying rubber-band tourniquets high around each thigh for 3 hours, followed by reperfusion for 6 hours. After sacrifice, the level of kidney injury was assayed. RESULTS: I/R significantly increased the plasma concentrations of blood urea nitrogen (BUN) and creatinine (Cr). However, this effect could be mitigated by platonin, as the plasma concentrations of BUN and Cr of the I/R-P group were significantly lower than those of the I/R group. Moreover, histological findings revealed moderate injury in kidney tissues of the I/R group and mild injury in those of the I/R-P group. In addition, the leukocyte infiltration and myeloperoxidase activity in kidney tissues as well as the renal concentrations of inflammatory molecules (i.e., cyclooxygenase-2/prostaglandin E(2), interleukin-6, and macrophage inflammatory protein-2) and malondialdehyde (i.e., the index of lipid peroxidation) of the I/R group were significantly higher than those of the I/R-P group. CONCLUSION: Platonin attenuates kidney injury induced by bilateral lower limb I/R in rats.

Conformational analysis of steroid hormone molecules in the lipid environment--a solid-state NMR approach.

Solid-state (1)H/(13)C cross-polarization/magic angle spinning (CP/MAS) NMR spectroscopy has been applied to two steroid compounds: dehydroepiandrosterone (DHEA) and spironolactone (SPI), to analyze their conformations at the atomic level. In the absence of lipid, the high-resolution (13)C CP/MAS NMR signals of DHEA and SPI in a powder form reveal multiple patterns, with splittings of 30-160 Hz, indicating the existence of multiple conformations. In the mimic lipid environment formed by mixing 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-diheptanoyl-sn-glycero-3-phosphocholine (DHPC) in a molar ratio 3:1, the resulting DHEA and SPI spectra revealed mostly singlet patterns, suggesting that these steroids undergo a conformational change leading to a specific conformation in the lipid environment. Evidence from chemical shift isotropy and anisotropy analysis indicates that DHEA might adopt conformations subtly different from that seen in solution and in the powder form. In conclusion, we demonstrate by solid-state NMR that the structures of DHEA and SPI may adopt slightly different conformations in different chemical environments.