Effects of perfluorohexan vapor on gas exchange, respiratory mechanics, and lung histology in pigs with lung injury after endotoxin infusion

BACKGROUND: Inhaled perfluorohexan vapor has been shown to improve gas exchange and pulmonary mechanics in oleic acid- and ventilator-induced lung injury. However, in the clinical setting, lung injury frequently occurs in the context of systemic inflammation and consecutive lung injury, which may be induced experimentally by intravenous administration of endotoxin. The authors studied whether vaporized perfluorohexan is efficacious during endotoxin-induced lung injury in domestic pigs. METHODS: Twenty-two pigs (29 [23, 31] kg body weight [first, third interquartile]; tracheostomy) were anesthetized and mechanically ventilated. In the endotoxin (n = 8) and perfluorohexan groups (n = 7), we administered endotoxin of Escherichia coli 111:B4, 1 mg.kg . h for 1 h and 10 microg.kg.h for 5 h in consecutive order. In the perfluorohexan group, inhalation of the test drug was started 2 h 30 min after the start of the intravenous endotoxin and terminated after 30 min. In a control group (n=7), animals were instrumented and observed over time without further intervention. Oxygenation function was assessed from oxygen partial pressures (Po2, blood gases) and calculated shunt fraction. Respiratory compliance was calculated from airway pressure and tidal volume. Measurements were performed before and every hour during endotoxin infusion. RESULTS: After 6 h of endotoxin, gas exchange and pulmonary compliance were deteriorated in the endotoxin group (Pao2: 184 [114, 289] vs. 638 [615, 658] mmHg, pulmonary shunt fraction: 30 [23, 38] vs. 4 [3, 6]%, respiratory compliance: 12 [11, 14] vs. 22 [19, 23] ml/mbar; P < 0.05, endotoxin vs. control). Inhalation of vaporized perfluorohexan did not improve Pao 2 (107 [60, 221] mmHg), pulmonary shunt fraction (32 [26, 58]%), or respiratory compliance (14 [10, 17] ml/mbar) when compared with intravenous endotoxin (not significant, perfluorohexan vs. endotoxin). CONCLUSIONS: Inhalation of vaporized perfluorohexan does not improve pulmonary gas exchange or respiratory compliance in endotoxin-induced porcine lung injury.     

Fluid resuscitation from severe hemorrhagic shock using diaspirin cross-linked hemoglobin fails to improve pancreatic and renal perfusion

BACKGROUND: Fluid resuscitation from hemorrhagic shock is intended to abolish microcirculatory disorders and to restore adequate tissue oxygenation. Diaspirin cross-linked hemoglobin (DCLHb) is a hemoglobin-based oxygen carrier (HBOC) with vasoconstrictive properties. Therefore, fluid resuscitation from severe hemorrhagic shock using DCLHb was expected to improve perfusion pressure and tissue perfusion of kidneys and pancreas. METHODS: In 20 anesthetized domestic pigs with an experimentally induced coronary stenosis, shock (mean arterial pressure 45 mmHg) was induced by controlled withdrawal of blood and maintained for 60 min. Fluid resuscitation (replacement of the plasma volume withdrawn during hemorrhage) was performed with either 10% DCLHb (DCLHb group, n = 10) or 8% human serum albumin (HSA) oncotically matched to DCLHb (HSA group, n = 10). Completion of resuscitation was followed by a 60-min observation period. Regional blood flow to the kidneys and the pancreas was measured by use of the radioactive microspheres method at baseline, after shock and 60 min after fluid resuscitation. RESULTS: All animals (10/10) resuscitated with DCLHb survived the 60-min observation period, while 5/10 control animals died within 20 min due to persisting subendocardial ischemia. In contrast to HSA survivors, pancreas and kidneys of DCLHb-treated animals revealed lower total and regional organ perfusion and regional oxygen delivery. Renal and pancreatic blood flow heterogeneity was higher in the DCLHb group. CONCLUSION: DCLHb-induced vasoconstriction afforded superior myocardial perfusion, but impaired regional perfusion of the kidneys and the pancreas.     

Polyclonal anti-thymocyte globulins influence apoptosis in reperfused tissues after ischaemia in a non-human primate model

Reperfusion triggers the expression of inflammatory cytokines and adhesion molecules that increase the rate of apoptosis in the reperfused tissues after ischaemia, thus worsening the outcome of the grafts. Polyclonal anti-thymocyte globulins (pATGs) are able to reduce the number of lymphocytes as well as block adhesion molecules and induce apoptosis in T-lymphocytes through Fas-ligand. The aims of this study were to investigate the influence of pATGs on the prevention of apoptosis of reperfused tissues after ischaemia and to monitor their capability to enhance lymphocyte apoptosis thus decreasing the deleterious effects of ischaemia/reperfusion injury (IRI). Extremities of cynomolgus monkeys (n=8) were flushed via either the femoral or the brachial artery. After 60 min of ischaemia the limbs were reperfused with human blood. ATG was added to the blood in a therapeutic dose 20 min prior to reperfusion of the extremities. Surgically available limbs (n=20) were assigned to the following groups: ATG group (n=10) and control group (without ATG; n=10). DNA fragmentation analysis was performed in situ to detect apoptosis at the single-cell level. Our study shows an increased rate of muscle and connective tissue apoptosis in the control group compared with the ATG-treated group. Cells found in the vascular areas present different rates of apoptosis, with enhanced cellular death of endothelium and connective perivascular areas being observed in the control group. The group treated with ATG shows an increased rate of white blood cell (WBC) apoptosis in vascular and perivascular areas. Previous studies have shown that pATGs are able to induce apoptosis as well as complement-mediated cell death in peripheral T-lymphocytes in vitro. Our results confirm that pATGs not only increase the rate of apoptosis of WBCs in vivo but also have a protective effect on the reperfused tissue. This may alleviate the damage after reperfusion of solid-organ transplantation.     

Lung injury following thoracic aortic occlusion: comparison of sevoflurane and propofol anaesthesia

Background: Halogenated anaesthetics have been shown to reduce ischaemia–reperfusion injuries in various organs due to pre- and post-conditioning mechanisms. We compared volatile and total intravenous anaesthesia with regard to their effect on remote pulmonary injury after thoracic aortic occlusion and reperfusion.
Methods: Eighteen pigs were randomized after sternotomy and laparotomy (fentanyl–midazolam anaesthesia) to receive either sevoflurane or propofol in an investigator-blinded fashion. Ninety minutes of thoracic aortic occlusion was induced by a balloon catheter. During reperfusion, a goal-directed resuscitation protocol was performed. After 120 min of reperfusion, the anaesthetic regimen was changed to fentanyl–midazolam again for another 180 min. The oxygenation index and intra-pulmonary shunt fractions were calculated. After 5 h of reperfusion, a bronchoalveolar lavage was performed. The total protein content and lactate dehydrogenase activity were measured in epithelial lining fluid (ELF). Alveolar macrophage oxidative burst was analysed. The wet to dry ratio was calculated and tissue injury was graded using a semi-quantitative score. Ten animals ( n =5 for each anaesthetic) without aortic occlusion served as time controls.
Results: The oxygenation index decreased and the intra-pulmonary shunt fraction increased significantly in both occlusion groups. There were no significant differences between sevoflurane and propofol with respect to the oxygenation index, ELF composition, morphologic lung damage, wet to dry ratio and alveolar macrophage burst activity. Differences were, however, seen in terms of systemic haemodynamic stability, where catecholamine requirements were less pronounced with sevoflurane.
Conclusion: We conclude that the severity of remote lung injury was not different between sevoflurane and propofol anaesthesia in this porcine model of severe lower-body ischaemia and reperfusion injury.     

Validation of pulse contour derived stroke volume variation during modifications of cardiac afterload

Background: Left ventricular stroke volume variation (SVV) or its surrogatesare useful tools to assess fluid responsiveness in mechanicallyventilated patients. So far it is unknown, how changes in cardiacafterload affect SVV. Therefore, this study compared left ventricularSVV derived by pulse contour analysis with SVV measured usingan ultrasonic flow probe and investigated the influence of cardiacafterload on left ventricular SVV. Methods: In 13 anaesthetized, mechanically ventilated pigs [31(SD 6)kg], we compared cardiac output (CO), stroke volume (SV), andSVV determined by pulse contour analysis and by an ultrasonicaortic flow signal (Bland–Altman analysis). After obtainingbaseline measurements, cardiac afterload was increased usingphenylephrine and decreased using adenosine (both continuouslyadministered). Measurements were performed with a constant tidalvolume (12 ml kg^–1) without PEEP. Results: Neither increasing mean arterial pressure (MAP) [from 59 (7)to 116 (19)] nor decreasing MAP [from 63 (7) to 39 (4)] affectedCO, SV, and SVV (both methods). Method comparison revealed abias for SVV of 0.1% [standard error of the mean (SE) 0.8] atbaseline, –1.2% (SE 0.8) during decreased and 4.0% (SE0.7) during increased afterload, the latter being significantlydifferent from the others (P < 0.05). Thereby, pulse contouranalysis tended to underestimate SVV during decreased afterloadand to overestimate SVV during increased afterload. Limits ofagreement were approximately 6% for all points of measurement. Conclusions: Left ventricular SVV is not affected by changes in cardiac afterload.There is a good agreement of pulse contour with flow derivedSVV. The agreement decreases, if afterload is extensively augmented.     

Regional blood flow during hyperoxic haemodilution

BACKGROUND: Ventilation with pure oxygen (hyperoxic ventilation, HV) increases arterial oxygen content (CaO(2)). However HV induces arteriolar constriction and thus potentially affects O(2) supply. We therefore investigated the effects of HV on regional blood flow (RBF) and O(2) supply of different vital organs during moderate normovolaemic anaemia. METHODS: Twenty-two anaesthetized dogs were haemodiluted under normoxia (i.e. FiO(2) = 0.21) to a target haemoglobin concentration (Hb) of 7 g dl(-1) and were subsequently ventilated with pure O(2). RBF was determined by use of the radioactive microspheres method in the myocardium, kidney, skeletal muscle, liver, intestine, stomach, and pancreas at Hb = 7 g dl(-1) and after subsequent initiation of HV. RBF in proportion to cardiac output (RBF(relative)), the variation coefficient of RBF (VC) and regional O(2) supply (rDO(2)) were calculated. RESULTS: Initiation of HV at Hb = 7.0 +/- 0.3 g dl(-1) reduced cardiac index (-17%) as well as RBF within the myocardium (-21%), pancreas (-25%), and skeletal muscle (-25%), whereas renal, hepatic, and intestinal RBF remained unchanged. Consequently RBF(relative) of the latter organs increased. Heterogeneity of RBF was marginally affected by HV. CONCLUSION: The initiation of HV during moderate normovolaemic anaemia (Hb =7 g dl(-1)) was accompanied by RBF redistribution with preference for renal, hepatic and intestinal O(2) supply. Cardiac, pancreatic and muscular O(2) supply decreased, however without any critical restriction of organ function.