Halogenated anesthetics reduce interleukin-1beta-induced cytokine secretion by rat alveolar type II cells in primary culture

BACKGROUND: Alveolar epithelial type II (AT II ) cells participate in the intraalveolar cytokine network by secreting cytokines and are widely exposed to volatile anesthetics during general anesthesia. The aim of the current study was to evaluate the effects of halothane, enflurane, and isoflurane on rat AT II cell cytokine secretions in AT II primary cell cultures. METHODS: Alveolar epithelial type II primary cell cultures were obtained from adult rat lungs. AT II cells were stimulated by recombinant murine interleukin-1beta (rmIL-1beta) to mimic an inflammatory response, and immediately exposed for various duration to different concentration of halothane, enflurane, or isoflurane. Interleukin-6, macrophage inflammatory protein-2 (MIP-2), and monocyte chemoattractant protein-1 (MCP-1) protein concentrations were then measured in cell culture supernatants. Recombinant mIL-1beta-stimulated AT II cells exposed to air served as control. RESULTS: Halothane, isoflurane, and enflurane (1 minimum alveolar concentration [MAC], 4 h) decreased rmIL-1beta-stimulated AT II cell secretions of interleukin-6, MIP-2, and MCP-1, but did not modify total protein secretion. Halothane exposure decreased rmIL-1beta-stimulated AT II cell secretions of interleukin-6, MIP-2, and MCP-1 in a dose- and time-dependent manner. Total protein concentrations remained unchanged except AT II 1.5 MAC of halothane, and no cytotoxic effect could be evidenced by lactate dehydrogenase release. These effects were transient as rmIL-1beta-stimulated AT II cell secretions of interleukin-6 and MIP-2 progressively reached control values between 4 and 24 h after the end of halothane exposure. However, MCP-1 inhibition persisted until 24 h. rmIL-1beta-induced MIP-2 and tumor necrosis factor-alpha mRNA expression were decreased by 36 and 24%, respectively, after halothane exposure. CONCLUSIONS: The current study shows that exposure of rmIL-1beta-stimulated AT II cells to volatile anesthetics reversibly alters their cytokine secretion. Therefore, volatile anesthesia, by modulating pulmonary epithelial cell secretion of inflammatory cytokines, might affect the lung inflammatory response.     

Serum and hepatic vitamin E assessment in cirrhotics before transplantation

BACKGROUND: Hepatic vitamin E may have a protective effect against hepatocyte injury; therefore, vitamin E replacement or supplementation may be beneficial in patients with cirrhosis. However, serum vitamin E may not correlate with hepatic vitamin E stores, making decisions regarding treatment difficult based on serum levels alone. The specific aims of this study were to determine hepatic concentrations of vitamin E and to determine whether serum levels of vitamin E correlate with hepatic vitamin E stores in cirrhotics. METHODS: A prospective study of cirrhotics undergoing orthotopic liver transplantation (OLT) was completed. Serum and hepatic levels of vitamin E were measured by high-performance liquid chromatography. Statistical analysis was performed using rank sum tests and Spearman's rank correlation coefficient. RESULTS: Fifty cirrhotics (33 males, 17 females; mean age of 53 years) were studied. The control group (25 males, 25 females; mean age of 47 years) consisted of the liver donors. The median serum levels of vitamin E in controls and cirrhotics were 5.95 and 7.8 mg/L, respectively (p = .009). The median hepatic levels (0.10 mg/g) in the control and cirrhotic groups were similar (p = .037). There was a significant correlation between serum and hepatic vitamin E levels in cirrhotics (R = 0.335; p = .017). CONCLUSIONS: A positive correlation exists between serum and hepatic concentrations of vitamin E in cirrhotics, therefore making serum vitamin E levels a useful reference for treatment using exogenous vitamin E.     

Pressure-flow loops and instantaneous input impedance in the thoracic aorta: another way to assess the effect of aortic bypass graft implantation on myocardial,brain, and subdiaphragmatic perfusion

BACKGROUND: The serious disturbances in ventriculoarterial coupling after thoracic aorta bypass grafting are addressed through aortic entry impedance in the frequency domain from flow-pressure waves. We designed a method for synthesizing pressure and flow waves to evaluate opposal to aortic flow along the cardiac cycle, addressing myocardial, brain, and visceral tissue perfusions from pressure-flow hysteresis loops and forward-backward aortic entry impedance in the ascending aorta, transverse aortic arch, and distal descending aorta, respectively, before and after extra-anatomic grafting of the descending aorta in the swine. METHODS: Twelve pigs underwent extra-anatomic grafting (woven double-velour prosthesis, 18-mm diameter), bypassing the descending aorta. Periarterial flow and endovascular pressure signals were mathematically synthesized (error minimization) to yield continuous functions of flow, pressure along the cardiac cycle before treatment for mean hemodynamics, pressure-flow hysteresis loops, and aortic entry impedance. RESULTS: Grafting of the descending aorta overshadowed pressure-flow hysteresis loops in the ascending aorta by shortening maximum pressure delay on maximum flow and diastolic flow reversal. Clamping of the descending aorta substantially restored hemodynamics in the ascending aorta, although the diastolic flow decrease was accelerated. Identical processes developed in the transverse aorta. Subdiaphragmatic descending aortic flow was flattened after grafting and restored, although thickened, after clamping of the descending aorta. Flow wave peak was framed by a diastolic aortic entry impedance peak, which was damped along the transverse aortic arch (aortic entry impedance peak in the ascending aorta, 1700 +/- 102 kN x s x m(-5); aortic entry impedance peak in the descending aorta, 292 +/- 45 kN x s x m(-5); P <.05). After grafting, the aortic entry impedance peak was transferred to early systole (aortic entry impedance peak in the transverse aortic arch, 2104 +/- 94 kN x s x m(-5); aortic entry impedance peak in the descending aorta, 450 +/- 75 kN x s x m(-5); P <.05). Clamping of the descending aorta attenuated the early systolic aortic entry impedance peak (aortic entry impedance peak in the transverse aortic arch, 1269 +/- 104 kN x s x m(-5); aortic entry impedance peak in the descending aorta, 491 +/- 75 kN x s x m(-5); P <.05), although aortic entry impedance in the descending aorta remained higher than before grafting (P <.05). Specifically, the backward flow ascending aorta to coronary trunks generated a backward aortic entry impedance peak (2234 +/- 350 kN x s x m(-5)) superimposed onto the forward aortic entry impedance peak with asymptotic boundaries that diminished after grafting and further enlarged after clamping of the descending aorta. CONCLUSIONS: Hemodynamic opposition of grafting of the descending aorta are specific to the aortic site and cardiac cycle and are dependent on clamping of the descending aorta. Our approach to thoracic aorta hemodynamics could enable optimization of bypass grafting.