Temperature affects lung fluid and recoil during high tidal ventilation at low resting volume

Effects of tidal volume (VT), end-expiratory pressure (EEP), and environmental temperature (Tenv) on elastic recoil force (Pel) and edema formation were examined in open-chest anesthetized rabbits. Sixty-two rabbits in four groups were ventilated for 3 h with VT of either 10 or 25 ml/kg body wt, EEP of 0 or 2 cmH2O, and Tenv of 18 or 35 degrees C. After ventilation, Pel at 80% of total lung capacity (P80) was significantly increased when ventilation was performed with the combination of large VT, 0 EEP, and low Tenv. This change was prevented by altering any one of the three conditions, e.g., small VT, positive EEP, or high Tenv. Similarly, elevation of minimum surface tension and reduction of surface activity index of lavages from excised lungs after ventilation were observed only when increased P80 was noted. Additionally, the increase of P80 was well correlated with increment of wet weight-to-dry weight ratio and degree of perivascular cuffing and alveolar edema formation of excised lungs. These results indicate that elevation of Pel after high tidal ventilation in open-chest animals in vivo was influenced by level of EEP and Tenv and that the degree of edema formation was closely related to the increase of Pel. The increased Pel is presumably primary and causes fluid accumulation.     

Effect of mechanical load on tidal volume during high-frequency jet ventilation

High-frequency jet ventilation (HFJV) was studied in twelve deeply anesthetized, paralyzed dogs. Entrained volume and total expired volume were directly measured by integration of flow. Jet volume was computed from these measurements. Seven dogs were ventilated with a driving pressure of 10 psi at rates of 2 and 5 Hz for each of three mechanical loads: control, thoracoabdominal wrap, and histamine infusion. Both load conditions reduced total expired volume and entrained volume but had no effect on jet volume. Wrap reduced entrainment more at 2 Hz while the effect of histamine infusion was frequency independent. Control arterial blood gases demonstrated that PO2 was higher and PCO2 was lower during 2 Hz ventilation than during 5 Hz ventilation despite equivalent minute volumes. Five additional dogs were studied using control and wrap loads and an additional ventilator setting of 15 psi at 5 Hz. This group demonstrated that wrap reduces entrainment more at lower frequencies for ventilatory settings providing equivalent gas exchange. We conclude that increasing mechanical load reduces entrainment during HFJV and that this reduction is frequency dependent for restrictive loads.     

High tidal volume ventilation induces lung injury after hepatic ischemia-reperfusion

Ischemia-reperfusion not only damages the affected organ but also leads to remote organ injuries. Hepatic inflow interruption usually occurs during hepatic surgery. To investigate the influence of liver ischemia-reperfusion on lung injury and to determine the contribution of tidal volume settings on liver ischemia-reperfusion-induced lung injury, we studied anesthetized and mechanically ventilated rats in which the hepatic inflow was transiently interrupted twice for 15 min. Two tidal volumes, 6 ml/kg as a low tidal volume (IR-LT) and 24 ml/kg as a high tidal volume (IR-HT), were assessed after liver ischemia-reperfusion, as well as after a sham operation, 6 ml/kg (NC-LT) and 24 ml/kg (NC-HT). Both the IR-HT and IR-LT groups had a gradual decline in the systemic blood pressure and a significant increase in plasma TNF-alpha concentrations. Of the four groups, only the IR-HT group developed lung injury, as assessed by an increase in the lung wet-to-dry weight ratio, the presence of significant histopathological changes, such as perivascular edema and intravascular leukocyte aggregation, and an increase in the bronchoalveolar lavage fluid TNF-alpha concentration. Furthermore, only in the IR-HT group was airway pressure increased significantly during the 6-h reperfusion period. These findings suggest that liver ischemia-reperfusion caused systemic inflammation and that lung injury is triggered when high tidal volume ventilation follows liver ischemia-reperfusion.     

Oxidative stress responses during cassava post-harvest physiological deterioration

A major constraint to the development of cassava (Manihot esculenta Crantz) as a crop to both farmers and processors is its starchy storage roots' rapid post-harvest deterioration, which can render it unpalatable and unmarketable within 24–72 h. An oxidative burst occurs within 15 min of the root being injured, that is followed by the altered regulation of genes, notably for catalase and peroxidase, related to the modulation of reactive oxygen species, and the accumulation of secondary metabolites, some of which show antioxidant properties. The interactions between these enzymes and compounds, in particular peroxidase and the coumarin, scopoletin, are largely confined to the vascular tissues where the visible symptoms of deterioration are observed. These, together with other data, are used to develop a tentative model of some of the principal events involved in the deterioration process. Abbreviations: ACMV, African cassava mosaic virus; AFLP, amplified fragment length polymorphism; CAT, catalase; cDNA, complementary deoxyribonucleic acid; CIAT, International Centre for Tropical Agriculture; Cu/ZnSOD, copper/zinc superoxide dismutase; DAB, 3,3-diaminobenzidine tetrahydrochloride; DPPH, 1,1-diphenyl-2-picrylhydrazyl; FeSOD, iron superoxide dismutase; FW, fresh weight; GUS, -glucuronidase; HPTLC, high-performance thin-layer chromatography; HR, hypersensitive response; IEF-PAGE, isoelectric focusing polyacrylamide gel electrophoresis; MAS, marker-assisted selection; MeJa, methyl jasmonate; MnSOD, manganese superoxide dismutase; NADPH, nicotinamide adenine dinucleotide phosphate (reduced form); NBT, nitroblue tetrazolium; PAL, phenylalanine ammonia-lyase; PCD, programmed cell death; PCR, polymerase chain reaction; POX, peroxidase; PPD, post-harvest physiological deterioration; QTL, quantitative trait loci; ROS, reactive oxygen species; RT, room temperature; SAR, systemic acquired resistance; SDS, sodium dodecyl sulfate; SOD, superoxide dismutase     

Oxidative stress responses during cassava post-harvest physiological deterioration

A major constraint to the development of cassava (Manihot esculenta Crantz) as a crop to both farmers and processors is its starchy storage roots’ rapid post-harvest deterioration, which can render it unpalatable and unmarketable within 24–72 h. An oxidative burst occurs within 15 min of the root being injured, that is followed by the altered regulation of genes, notably for catalase and peroxidase, related to the modulation of reactive oxygen species, and the accumulation of secondary metabolites, some of which show antioxidant properties. The interactions between these enzymes and compounds, in particular peroxidase and the coumarin, scopoletin, are largely confined to the vascular tissues where the visible symptoms of deterioration are observed. These, together with other data, are used to develop a tentative model of some of the principal events involved in the deterioration process.     

Alterations of lymphocyte count and platelet volume precede cerebrovascular lesions in stroke-prone spontaneously hypertensive rats

Abstract

Background: Cerebral small vessel disease (CSVD) is associated with future stroke. Although pathological alteration in small vessels of patients with CSVD can be detected by neuroimaging, diagnosis of CSVD is delayed because it is an asymptomatic disease. The stroke-prone spontaneously hypertensive rat (SHRSP) show similar pathological features to human CSVD and develop stroke-related symptoms with advancing age.

Objective: We investigated the time course of haematological parameters in Wistar rats and SHRSP.

Material and Methods: Blood cells were analysed using an automated haematological analyser.

Results: SHRSP develop stroke-related symptoms including onset of neurological symptoms, decreased body weight and blood brain barrier leakage between 12 and 14?weeks of age. Lymphocyte counts were gradually decreased at 3?weeks before development of stoke-related symptoms and then were further decreased after the development of stroke-related symptoms. The both mean platelet volume and large platelet ratio gradually increased at 3?weeks before the development of stoke-related symptoms. However, although SHRSP showed more microcytic red cells than Wistar rats, the trajectories of change in erythrocyte-related parameters were similar between Wistar rats and SHRSP.

Conclusion: Our pilot study suggests that alterations of lymphocyte count and platelet volume predictive indicators for asymptomatic CSVD and symptomatic stroke in SHRSP.     

High tidal volume mechanical ventilation with hyperoxia alters alveolar type II cell adhesion

Patients with acute respiratory distress syndrome undergoing mechanical ventilation may be exposed to both high levels of stretch and high levels of oxygen. We hypothesized that the combination of high stretch and hyperoxia promotes loss of epithelial adhesion and impairs epithelial repair mechanisms necessary for restoration of barrier function. We utilized a model of high tidal volume mechanical ventilation (25 ml/kg) with hyperoxia (50% O(2)) in rats to investigate alveolar type II (AT2) cell adhesion and focal adhesion signaling. AT2 cells isolated from rats exposed to hyperoxia and high tidal volume mechanical ventilation (MVHO) exhibited significantly decreased cell adhesion and reduction in phosphotyrosyl levels of focal adhesion kinase (FAK) and paxillin compared with control rats, rats exposed to hyperoxia without ventilation (HO), or rats ventilated with normoxia (MV). MV alone increased phosphorylation of p130(Cas). RhoA activation was increased by MV, HO, and the combination of MV and HO. Treatment of MVHO cells with keratinocyte growth factor (KGF) for 1 h upon isolation reduced RhoA activity and restored attachment to control levels. Attachment and migration of control AT2 cells was significantly decreased by constitutively active RhoA or a kinase inactive form of FAK (FRNK), whereas expression of dominant negative RhoA in cells from MVHO-treated rats restored cell adhesion. Mechanical ventilation with hyperoxia promotes changes in focal adhesion proteins and RhoA in AT2 cells that may be deleterious for cell adhesion and migration.     

High in comparison with low tidal volume ventilation aggravates oxidative stress-induced lung injury

Ventilator settings influence the development and outcome of acute lung injury. This study investigates the influence of low versus high tidal volume (V(t)) on oxidative stress-induced lung injury.Isolated rabbit lungs were subjected to one of three ventilation patterns (V(t)-positive end-expiratory pressure, PEEP): LVZP (6 ml/kg-0 cm H(2)O), HVZP (12 ml/kg-0 cm H(2)O), LV5P (6 ml/kg-5 cm H(2)O). These ventilation patterns allowed a comparison between low and high V(t) without dependence on peak inspiratory pressure (PIP). Infusion of hypochlorite (1000 nmol/min) or buffer (control) was started at t=0 min. Pulmonary artery pressure (PAP), PIP and weight were continuously recorded. Capillary filtration coefficient [K(f,c) (10(-4) ml s(-1) cm H(2)O(-1) g(-1))] was gravimetrically determined (-15/30/60/90/120 min).PIP averaged 5.8+/-0.6/13.9+/-0.6/13.9+/-0.4 cm H(2)O in the LVZP, HVZP and LV5P groups. PIP, K(f,c) or PAP did not change in control groups, indicating that none of the ventilation patterns caused lung injury by themselves. Hypochlorite-induced increase in K(f,c) but not hypochlorite-induced increase in PAP, was significantly attenuated in the LVZP-/LV5P- versus the HVZP-group (K(f,c,max.) 1.0+/-0.23/1.4+/-0.40 versus 3.2+/-1.0*). Experiments with hypochlorite were terminated due to excessive edema (>50 g) at 97+/-2.2/94.5+/-4.5 min in the LVZP-/LV5P-group versus 82+/-3.8* min in the HVZP-group (*: P<0.05).Low V(t) attenuated oxidative stress-induced increase in vascular permeability independently from PIP and PEEP.     

Lung injury caused by high tidal volume mechanical ventilation and hyperoxia is dependent on oxidant-mediated c-Jun NH2-terminal kinase activation

Both prolonged exposure to hyperoxia and large tidal volume mechanical ventilation can each independently cause lung injury. However, the combined impact of these insults is poorly understood. We recently reported that preexposure to hyperoxia for 12 h, followed by ventilation with large tidal volumes, induced significant lung injury and epithelial cell apoptosis compared with either stimulus alone (Makena et al. Am J Physiol Lung Cell Mol Physiol 299: L711-L719, 2010). The upstream mechanisms of this lung injury and apoptosis have not been clearly elucidated. We hypothesized that lung injury in this model was dependent on oxidative signaling via the c-Jun NH(2)-terminal kinases (JNK). We, therefore, evaluated lung injury and apoptosis in the presence of N-acetyl-cysteine (NAC) in both mouse and cell culture models, and we provide evidence that NAC significantly inhibited lung injury and apoptosis by reducing the production of ROS, activation of JNK, and apoptosis. To confirm JNK involvement in apoptosis, cells treated with a specific JNK inhibitor, SP600125, and subjected to preexposure to hyperoxia, followed by mechanical stretch, exhibited significantly reduced evidence of apoptosis. In conclusion, lung injury and apoptosis caused by preexposure to hyperoxia, followed by high tidal volume mechanical ventilation, induces ROS-mediated activation of JNK and mitochondrial-mediated apoptosis. NAC protects lung injury and apoptosis by inhibiting ROS-mediated activation of JNK and downstream proapoptotic signaling.     

Influence of tidal volume on pulmonary NO release,tissue lipid peroxidation and surfactant phospholipids

Mechanical stress during ventilation may cause or aggravate acute lung injury. This study investigates the influence of low vs. high tidal volume (V(t)) on factors known to play key roles in acute lung injury: nitric oxide release, eNOS and iNOS gene expression, lipid peroxidation (LPO), and surfactant phospholipids (PL). Isolated rabbit lungs were subjected to one of three ventilation patterns for 135 min (V(t)-PEEP): 6 ml/kg-0 cm H(2)O. 12 ml/kg-0 cm H(2)O 6 ml/kg-5 cm H(2)O, 12 ml/kg-0 cm H(2)O, and 6 ml/kg-5 cm H(2)O resulted in comparable peak inspiratory pressure (PIP). This allowed comparing low and high V(t) without dependence on PIP. Ventilatory patterns did not induce changes in pulmonary artery pressure, vascular permeability (K(f,c)), PIP or pulmonary compliance. High V(t) in comparison with both of the low V(t) groups caused an increase in BALF-nitrite (30.6+/-3.0* vs. 21.4+/-2.2 and 16.2+/-3.3 microM), BALF-PL (1110+/-19* vs. 750+/-68 and 634+/-82 microg/ml), and tissue LPO product accumulation (0.62+/-0.051* vs. 0.48+/-0.052 and 0.43+/-0.031 nmol/mg), *P<0.05 each. Perfusate nitrite and BALF-PL composition (assessed by use of 31P-NMR spectroscopy and MALDI-TOF mass spectrometry) did not differ among the groups. High V(t) ventilation reduced eNOS gene expression but did not affect iNOS expression. The increased release of NO and the accumulation of LPO products may represent early lung injury while elevated BALF-PL may reflect distension-induced surfactant secretion.