Evaluation of cystatin C with iohexol clearance in cardiac surgery.

BACKGROUND: Post-operative renal dysfunction after cardiac surgery is not uncommon and can lead to adverse outcome. The ability to accurately monitor renal function is therefore important. Cystatin C is known to be a sensitive marker of the glomerular filtration rate (GFR), but it has not been fully evaluated in cardiac surgery. Iohexol clearance is considered a reliable reference method for the determination of GFR. The aim of this study is to, for the first time, evaluate the diagnostic accuracy of plasma cystatin C compared with iohexol clearance in cardiac surgery. METHODS: Twenty-one patients scheduled for elective coronary artery bypass grafting were prospectively enrolled in the study. Before surgery and on the second post-operative day, an iohexol clearance was performed. Plasma cystatin C, plasma creatinine and plasma C-reactive protein were determined before surgery and on the first, second, third and fifth post-operative day. Estimated creatinine and cystatin C clearances were determined. RESULTS: Post-operative cystatin C and 1/cystatin C correlated strongly to iohexol clearance (r=-0.90 and 0.86) and so did creatinine and 1/creatinine (r=-0.83 and 0.78). Estimated creatinine clearance differed from iohexol clearance (P<0.01), whereas estimated cystatin C clearance did not differ from iohexol clearance (P=0.81). No correlation was found between C-reactive protein and cystatin C. CONCLUSION: This study indicates that clearance estimations based on cystatin C are more accurate compared with estimations based on creatinine in determining GFR in cardiac surgery. Cystatin C has, in this study population, a stronger correlation to iohexol clearance than creatinine.

Clinical experience with a novel endotoxin adsorbtion device in patients undergoing cardiac surgery.

Endotoxaemia is thought to occur in cardiac surgery using extracorporeal circulation (ECC) and a positive correlation has been proposed between the magnitude of endotoxaemia and risk for postoperative complications. We studied the effects of a new endotoxin adsorber device (Alteco LPS adsorber) in patients undergoing cardiac surgery with ECC, with special reference to safety and ease of use. Fifteen patients undergoing coronary artery bypass and/or valvular surgery were studied. In 9 patients, the LPS Adsorber was included in the bypass circuit between the arterial filter and the venous reservoir. Flow through the adsorber was started when the aorta was clamped and stopped at the end of perfusion. Flow rate was kept at 150 ml/min. Six patients served as controls with no adsorber in the circuit. Samples were taken for analysis of endotoxin, TNFalpha, IL-1beta and IL-6 as well as complement factors C3, C4 and C1q. Whole blood coagulation status was evaluated using thromboelastograpy (TEG) and platelet count. No adverse events were encountered when the adsorber was used in the circuit. Blood flow through the device was easily monitored and kept at the desired level. Platelet count decreased in both groups during surgery. TEG data revealed a decrease in whole blood clot strength in the control group while it was preserved in the adsorber group. Endotoxin was detected in only 2 patients and IL-1beta in 4 patients. IL-6 decreased in both groups whereas no change in TNF concentrations was found. C3 fell in both groups, but no changes wer found in C4 and C1q. The Alteco LPS adsorber can be used safely and is easy to handle in the bypass circuit. No complications related to the use of the adsorber were noted. The intended effects of the adsorber, i.e. removal of endotoxin from the blood stream could not be evaluated in this study, presumably due to the small number of patients and the relatively short perfusion times.

A retrospective study on the microbiology in patients with oral complaints and oral mucosal lesions.

OBJECTIVE: The aim of this study was to microbiologically analyze oral mucosal samples collected during 2 years from patients with oral mucosal complaints. MATERIALS AND METHODS: Mucosal scraping samples were taken from 297 patients and semiquantified by culture for detection of opportunistic microorganisms e.g. Staphylococcus aureus, enterococci, aerobic Gram-negative bacilli (AGNB) and yeasts. Antibiotic susceptibility test was performed. RESULTS: Altogether 297 patients were sampled (mean age 56.8 +/- 20.7). Among the 110 patients with known medical condition, 48 were systemically immunocompromised, 35 had systemic diseases, and 27 had only local oral complaints. Opportunists in moderate growth or more were present commonly in all three groups and most frequent in the immunocompromised patients (66.7%). Candida species were the most frequent opportunist (68.8%), however, their level was low and combinations with bacterial opportunists were common (39.6%). All bacterial opportunists tested were antibiotic multiresistant. Follow-up samples were collected in 23 cases out of which seven showed still presence of opportunists in heavy growth despite repeated treatment with ciprofloxacin. CONCLUSIONS: This study showed a frequent presence of bacterial and fungal opportunists in patients with oral mucosal complaints, which were most common in immunocompromised individuals, however, also frequent in patients with local oral complaints only. Systematic evaluation of different treatment strategies is needed.

S100B as a predictor of size and outcome of stroke after cardiac surgery.

BACKGROUND: Stroke after cardiac surgery is a clinical problem with often fatal or disabling outcome. To assess severity and probable outcome in affected patients only from clinical and radiological examinations is difficult. The glial-derived protein S100B has been suggested to be a marker of cerebral ischemia, and increased blood concentrations of S100B have been shown to correlate with size of lesion and prognosis after stroke. We studied the validity of S100B as a predictor of size of brain lesion and median term outcome in a consecutive group of patients suffering from stroke after cardiac surgery. METHODS: During a period of 17 months, 20 patients with clinical signs of postoperative stroke were investigated with S100B measurement, sampled at 5, 15 and 48 hours after surgery. All patients were examined with computed tomography or magnetic resonance imaging to confirm the diagnosis, and the size of cerebral infarction was estimated from the radiological examinations. The patients were followed up for survival 24 to 39 months after surgery. RESULTS: S100B concentration in blood 48 hours after surgery correlated with the size of infarcted brain tissue (r = 0.68, p < 0.001). Nine patients had S100B levels exceeding 0.5 microg/L and a 2-year mortality of 78%, whereas the 11 patients with S100B below 0.5 microg/L had a mortality of 18%. CONCLUSIONS: Increased S100B in patients with a stroke following cardiac surgery correlate with the size of infarcted brain tissue. High S100B levels 48 hours after surgery have a negative predictive value for median term survival.

Elastic properties of the lung and the chest wall in young and adult healthy pigs.

Understanding of the elastic pressure/volume (Pel/V) curve is still limited in health and disease. The aim of the present study was to elucidate the Pel/V curve and elastance of the respiratory system (ERS) lung (EL) and chest wall (ECW) in healthy pigs. Six young (20.8 kg) and seven adult (58.9 kg), anaesthetized, paralysed and ventilated pigs were studied. Pel/V curves were recorded at zero end-expiratory pressure (ZEEP) and at positive end-expiratory pressure (PEEP) up to 40 cmH2O with a computer controlled ventilator during an insufflation at a low, constant flow. Pel/V curves of the respiratory system showed a complex pattern in both young and adult pigs. During the insufflation, ERS decreased, increased, fell, and increased again. A second Pel/V curve recorded immediately after the first one showed lower elastance and only one early fall in ERS. ECW fell over the initial segment and was then nearly stable. Difference between 1st and 2nd curves reflected changes in EL caused by recruitment during the 1st insufflation. At PEEP, such signs of collapse and recruitment were reduced. A strong tendency to lung collapse contributes to a complex pattern of elastic pressure/volume curves. At low volumes and distending pressures the chest wall contributes significantly to changes in respiratory system elastance.

Effects of NO inhalation on pulmonary leukocyte sequestration and blood volume in porcine endotoxaemia.

OBJECTIVE: Sequestration and migration of activated neutrophils plays a major role in the pulmonary injury typical of septic shock and the adult respiratory distress syndrome. Inhaled NO may counteract alveolar-capillary damage attributed to activated neutrophils. The present study describes a method to directly demonstrate the effects of NO inhalation on endotoxin-induced sequestration of 99mTc-labelled leukocytes [As(t)] in the lungs of pigs. DESIGN: Prospective controlled study. SETTING: Laboratory for experimental surgery at a university medical centre. SUBJECTS: Anaesthetised and ventilated pigs. INTERVENTIONS: To induce inflammatory shock 26 animals received a continuous endotoxin infusion. Thirteen animals inhaled NO from the start of the experiments, while 13 served as controls. In 13 animals from both groups, leukocytes were labelled in vitro and reinjected, while in the 13 others erythrocytes were labelled in vivo to provide corrections for changes in blood volume. MEASUREMENTS AND RESULTS: The pulmonary distribution of 99mTc-labelled leukocytes or erythrocytes was studied dynamically for 180 min. After correction for changes in pulmonary and heart blood volume (PBV, HBV), leukocyte sequestration curves were generated. Endotoxin induced pulmonary vasoconstriction, reduced PBV, impaired oxygenation, and caused a maximum increase in As(t) of 30% in the lungs. NO inhalation attenuated pulmonary vasoconstriction and the reduction in PBV. The maximum increase in As(t) was reduced to 15% of baseline. CONCLUSIONS: Inhaled NO exerts its main vascular effects in the pulmonary microvasculature, the primary site of physiological neutrophil margination and pathological adhesion of activated leukocytes. Early use of NO inhalation may offer protection against the development of more lasting pulmonary failure in septic shock by reducing leukocyte sequestration in the lungs.

Neuron-specific enolase increases in plasma during and immediately after extracorporeal circulation.

BACKGROUND: Minor cerebral complications are common after cardiac surgery. Several biochemical markers for brain injury are under research; one of these is neuron-specific enolase (NSE). The purpose of this study was to investigate the release of this enzyme into the blood during and immediately after extracorporeal circulation and to evaluate the effect of hemolysis on this release. METHODS: Sixteen patients scheduled for elective heart surgery were included in the study. Blood samples for analysis of NSE and free hemoglobin in plasma were drawn before, during, and up to 48 hours after the end of extracorporeal circulation. The release of NSE from erythrocytes and its correlation to the release of free hemoglobin was studied by serial dilution and hemolysis in vitro. RESULTS: The peri- and postoperative course was uneventful in all patients. Extracorporeal circulation initiated a release of NSE that reached a maximum 6 hours after the end of perfusion. Thereafter, the levels declined with an estimated t1/2 of 30 hours. The concentration of free hemoglobin increased during the perfusion, with maximum levels at the end of perfusion, after which they fell rapidly to normal values. The in vitro study showed a strong linearity between the release of NSE and free hemoglobin after induced hemolysis. CONCLUSIONS: The increased levels of enolase at the end of cardiopulmonary bypass can, to a major part, be explained by the release from hemolysed erythrocytes. The value of NSE as a marker for brain injury in these situations is therefore doubtful.

Elimination of S100B and renal function after cardiac surgery.

OBJECTIVES: To determine the biologic half-life of the S100B protein and to investigate if the elimination of S100B depends on glomerular filtration rate (GFR). DESIGN: Prospective human study. SETTING: University hospital. PARTICIPANTS: Sixteen patients who underwent cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Shed mediastinal blood (autotransfusion) was returned to the patients postoperatively and used to study the kinetics of S100B. Iohexol was infused simultaneously to estimate GFR. S100B was measured at 0, 20, 40, 60, and 180 minutes after infusion. Iohexol was measured at 180 and 240 minutes after infusion. MEASUREMENTS AND MAIN RESULTS: S100B followed first-order kinetics, and the biologic half-life for S100B was determined to be 25.3 +/- 5.1 minutes. GFR was determined to be 63.8 +/- 34.4 mL/min. No correlation was found between GFR and S100B half-life. CONCLUSIONS: The elimination of S100B after cardiac surgery is faster than reported earlier and not affected by a moderate decrease in GFR. This finding is important when evaluating S100B levels after cardiac surgery.

Elastic pressure-volume curves of the respiratory system reveal a high tendency to lung collapse in young pigs.

OBJECTIVE: To study pressure-volume (P/V) curves over a wide pressure and volume range in pigs. DESIGN: Dynamic and static P/V curves (P(dyn)/V and P(st)/V) and compliance of the respiratory system were studied. The effects of recruitment, positive end-expiratory pressure (PEEP) and body position were analysed. SETTING: Research animal laboratory. MATERIALS: Seven anaesthetised, paralysed and ventilated healthy pigs of 21 kg. MEASUREMENTS: P/V curves up to a pressure of about 40 cmH(2)O were recorded with a computer-controlled ventilator. P(st)/V curves were obtained with the static occlusion method and P(dyn)/V curves during an insufflation at a low, constant flow rate. RESULTS: P(dyn)/V recording showed a complex pattern. During the insufflation compliance increased, fell, increased and fell again. A 2nd P(dyn)/V recording immediately following the 1st one was displaced towards higher volumes and showed only one maximum of compliance. The difference between the two curves reflected: (1) lung collapse during a period of 5 min of ventilation at zero end-expiratory pressure (ZEEP) following a recruitment manoeuvre, (2) recruitment during the measurement of the 1st P(dyn)/V curve. These observations were similar in the supine and in the left lateral position. After ventilation at PEEP, 4 cmH(2)O, the signs of collapse and recruitment were reduced. It was confirmed that PEEP offers a partial protection against collapse. P(st)/V curves showed higher volumes and higher compliance values compared to P(dyn)/V curves. This reflects the influence of viscoelastance on P(dyn)/V curves. CONCLUSION: The study demonstrates a particularly strong tendency to lung collapse in pigs.

Substance P relaxes rat bronchial smooth muscle via epithelial prostanoid synthesis.

BACKGROUND: Substance P is present in bronchial nerve fibres. The physiological actions of substance P are mediated via tachykinin NK(1) receptors. Immunochemical studies have demonstrated tachykinin NK(1) receptors in the rat airway epithelium. OBJECTIVE: To elucidate how epithelial tachykinin NK(1) receptors affect smooth muscle response to substance P. METHODS: Contractile response of isolated rat bronchial trunk with or without epithelium was recorded. RESULTS: In intact segments precontracted by 5-hydroxytryptamine, relaxation was induced by substance P and the nitric oxide donor, sodium nitroprusside. Removal of the epithelium abolished relaxation induced by substance P but did not affect relaxation induced by sodium nitroprusside. The cyclo-oxygenase inhibitor, indomethacin, but not the nitric oxide synthase inhibitor, L-N(G)-monomethylarginine, reduced the relaxation in response to substance P. CONCLUSIONS: Epithelial tachykinin NK(1) receptors mediate substance-P-induced relaxation of rat bronchial smooth muscle via release of prostanoids but not nitric oxide.

Intestinal and hepatic perfusion and metabolism in hypodynamic endotoxic shock. Effects of nitric oxide synthase inhibition.

BACKGROUND: Inhibition of nitric oxide synthase (NOS) has been claimed to be beneficial in septic shock. We investigated the overall and regional effects of a NOS-inhibitor on perfusion and metabolism during severe endotoxic shock. METHODS: Nineteen anaesthetised pigs were catheterised and ultrasonic flow-probes were placed around the portal vein, the hepatic artery, and the superior mesenteric artery. Thirteen animals were given a 3-h infusion of endotoxin; in 6 of these an infusion of NG-nitro-L-arginine-methyl-ester (L-NAME) was started an hour after the start of endotoxin while 7 animals served as controls and received endotoxin only. Six animals were sham operated with no further intervention. RESULTS: Endotoxin produced a hypodynamic shock with pulmonary hypertension. L-NAME did not increase arterial blood pressure, but deepened the fall in cardiac output and enhanced the increase in systemic and pulmonary vascular resistance. The infusion of endotoxin caused a decrease in flows in all regions. The addition of L-NAME induced a further decrease in the mesenteric artery flow only. L-NAME had no additional effect on hepatic artery flow ratio, while a transient decrease was seen in mesenteric flow ratio. Portal flow ratio decreased in the control group only. Global as well as regional oxygen extraction increased in both groups, more so in the L-NAME group. Lactate levels increased with no differences between the groups. CONCLUSION: In hypodynamic endotoxic shock, L-NAME infusion enhanced pulmonary vasoconstriction and increased left ventricular afterload. The resulting hypoperfusion caused an increase in mortality. The effects of L-NAME on global and mesenteric blood flow and metabolism were similar, while L-NAME had no additional effects on hepatic hypoperfusion or oxygen extraction. Thus, nitric oxide does not seem to be a major factor in the preservation of hepatic perfusion during unresuscitated endotoxic shock.

S100beta after coronary artery surgery: release pattern, source of contamination, and relation to neuropsychological outcome.

BACKGROUND: S100beta has been suggested as a marker of brain damage after cardiac operation. The aim of this study was to characterize the early S100beta release in detail and relate it to neuropsychological outcome. METHODS: Three groups of patients were investigated. All patients underwent coronary artery bypass surgery (CABG) with extracorporeal circulation. In group A, 110 patients had sampling of S100beta for the first 10 postoperative hours and also underwent neuropsychological testing. In group B, 14 patients were examined for the effect of autotransfusion on S100beta levels. Eight patients in group C had their intraoperative bleeding processed with a cell-saving device. RESULTS: Group A had a heterogeneous release pattern with several rapid elevations in S100beta concentration. In group B, high concentrations of S100beta were found in the autotransfusion blood (range 0.2 to 210 microg/L) with a concurrent elevation of serum S100beta levels after transfusion of shed blood. In group C, high levels of S100beta were found in the blood from the surgical field (12.0+/-6.0 microg/L) and decreased (1.1+/-0.64 microg/L) after wash. Group C had significantly lower S100beta values at the end of cardiopulmonary bypass compared to group A (0.53+/-0.35 microg/L versus 2.40+/-1.5 microg/L). S100beta values were corrected for extracerebral contamination with a kinetic model. With this correction, an association was found between adverse neuropsychological outcome and S100beta release in group A (r = 0.39, p < 0.02). CONCLUSIONS: A significant amount of S100beta is found both in the blood from the surgical field and in the shed mediastinal blood postoperatively. Infusion of this blood will result in infusion of S100beta into the blood and interfere in the interpretation of early systemic S100beta values.

Significance of serum S100 release after coronary artery bypass grafting.

BACKGROUND: S100 protein has been suggested to be a serum marker for cerebral complications after cardiac operation and extracorporeal circulation. The aim of this study was to characterize the S100 release pattern after extracorporeal circulation in 515 consecutive patients undergoing coronary artery bypass grafting. METHODS: Clinical variables and outcome were prospectively registered. The cerebral outcome was determined by clinical examination. S100 was measured at the end of extracorporeal circulation, and after 5, 15, and 48 hours. RESULTS: After operation, 13 patients had stroke, 12 had delayed awakening, and 17 had encephalopathy. Early S100 release, immediately after extracorporeal circulation, was associated with age and perfusion time, but not with cerebral outcome. However, S100 release after 5 to 48 hours was associated with cerebral complications and risk factors for such outcome. Patients with stroke had higher S100 levels after 15 to 48 hours. A subset of patients with renal failure had overall higher S100 levels at 5 hours. CONCLUSIONS: Early and late S100 release indicate different mechanisms for release and emphasizes the potential power of this new biochemical marker for cerebral damage.

The effects of nitric oxide inhalation on respiratory mechanics and gas exchange during endotoxaemia in the pig.

BACKGROUND: In the adult respiratory distress syndrome, nitric oxide (NO) inhalation improves oxygenation through reducing ventilation-perfusion mismatching, but detailed information on the pulmonary effects of NO inhalation in septic shock is scarce. The present study investigated the effects of inhaled NO on alveolar dead space (Vdalv) and venous admixture as well as on respiratory system compliance (Crs) and respiratory system resistance (Rrs) in a porcine model of septic shock. Protective effects of NO are discussed. METHODS: Thirteen anaesthetised and ventilated pigs were given an infusion of endotoxin for an observation time of 220 min to induce acute lung injury (ALI). In the NO-early group (n=6), an inhalation of 60 ppm NO was started simultaneously with the endotoxin infusion and continued for 190 min. In 7 control/NO-late animals, 60 ppm NO was administered for 30 min following 190 min of endotoxin infusion. Haemodynamics, single-breath CO2-, pressure-, and flow signals were recorded. RESULTS: Endotoxin induced haemoconcentration, pulmonary vasoconstriction, and a decrease in Crs, while venous admixture, Vdalv, and Rrs increased. In the NO-early group, the pulmonary vasoconstriction was attenuated, no increase in pulmonary venous admixture or in Vdalv was seen before cessation of NO, and the improvements in oxygenation outlasted the NO inhalation. In the control/NO-late group, the NO inhalation reversed the changes in dead space and venous admixture. NO had no effect on the changes in respiratory mechanics. CONCLUSION: In porcine ALI, 60 ppm NO diminishes pulmonary vasoconstriction and improves gas exchange by reducing pulmonary venous admixture and alveolar dead space, but does not prevent a fall in Crs. NO inhalation may help prevent long-lasting pulmonary failure.

The appearance of S-100 protein in serum during and immediately after cardiopulmonary bypass surgery: a possible marker for cerebral injury.

OBJECTIVE: To investigate the appearance and elimination of brain-specific S-100 protein in serum during and immediately after cardiopulmonary bypass. DESIGN: Prospective study. PARTICIPANTS: Twenty-nine patients undergoing elective cardiac surgery. INTERVENTIONS: Twenty-seven patients were operated on for coronary artery disease; two patients had valve replacement. Serial measurements of S-100 in arterial blood during and up to 48 hours after cardiopulmonary bypass were made. MEASUREMENTS AND MAIN RESULTS: The perioperative and postoperative course was uneventful in 25 patients, with no clinical signs of neurologic complications. S-100 was not detected before extracorporeal circulation was started. Detectable concentrations (detection limit, 0.2 microgram/L) appeared in serum after 10 minutes of perfusion and reached maximum levels, 2.43 +/- 0.3 micrograms/L, at the end of bypass. The levels then declined with elimination t1/2 of 2.2 hours. Only two patients had detectable concentrations of S-100 48 hours after the end of bypass. In four patients who developed clinical signs of cerebral injury, levels of S-100 were significantly higher at the end of bypass and 24 hours after the end of bypass. CONCLUSIONS: Cardiopulmonary bypass initiates a release of brain-specific S-100 to the systemic circulation. The release and elimination of S-100 seem to follow a reproducible pattern in patients with no signs of cerebral injury. In patients who developed cerebral injury, the concentrations of S-100 in blood were increased, thus suggesting that S-100 may be a usable marker for cerebral injury after extracorporeal circulation.

Differential effects of nitric oxide synthase modulation on porcine systemic and pulmonary circulation in vivo.

OBJECTIVE: To study and compare the effects of inhibiting endothelial nitric oxide synthase on systemic and pulmonary circulation in an in vivo model. DESIGN: Prospective, randomized, controlled study. SETTING: Laboratory for experimental surgery at a university medical center. SUBJECTS: Seventeen anesthetized, mechanically ventilated pigs. INTERVENTIONS: To produce a stable and continuous stimulation of endothelial nitric oxide synthase, an infusion of acetylcholine was given to one group of animals (n = 5) in a dose that decreased mean arterial pressure by 15%. After 45 mins, N(G)-monomethyl-L-arginine (L-NMMA) was given in a dose of 3 mg/kg for 5 mins in order to inhibit the enzyme. A second dose of 10 mg/kg was given 30 mins later. L-arginine was then given in a dose of 100 mg/kg to reverse the inhibition. One group of animals (n = 6) received a single dose of indomethacin (2.5 mg/kg) 15 mins after the start of acetylcholine infusion. L-NMMA and L-arginine were then given. In a control group (n = 5), the effects of L-NMMA and L-arginine were studied without acetylcholine. Circulatory parameters were monitored and resistance indices were calculated via arterial, central venous, and pulmonary artery catheters. MEASUREMENTS AND MAIN RESULTS: In control animals, 3 and 10 mg/kg of L-NMMA induced an increase in mean arterial pressure of 14% and 25%, respectively, with similar increases in systemic vascular resistance. Mean pulmonary arterial pressure increased by 22% and 48%, respectively. Acetylcholine lowered mean arterial pressure by 15% and did not affect the relative changes induced by L-NMMA. Acetylcholine had no effect on pulmonary resting tone but enhanced the pulmonary hypertension and increase in resistance induced by L-NMMA. This enhancement was abolished by indomethacin, which produced systemic hypertension while no effect on pulmonary pressure was seen. CONCLUSIONS: A basal release of nitric oxide contributes to the maintenance of normal vascular tone in the anesthetized pig. Stimulation of endothelial nitric oxide synthase by acetylcholine did not result in any further pulmonary vasodilation as was seen in the systemic circulation. Inhibition of nitric oxide synthase had a greater effect on pulmonary pressure than on systemic pressure. However, this difference was abolished by the administration of indomethacin. Increased nitric oxide release or acetylcholine itself seems to stimulate the production of a vasoconstricting prostanoid in the pulmonary circulation.

Nitric oxide inhalation decreases pulmonary platelet and neutrophil sequestration during extracorporeal circulation in the pig.

OBJECTIVE: The inhibiting effect of nitric oxide on the aggregation and adhesion of neutrophils and platelets has been well documented in vitro. In vivo evidence, however, is more scant. In this study, we studied the effects of inhaled nitric oxide on pulmonary cellular sequestration in our sham hemodialysis model. Accumulation of neutrophils and platelets in the lungs has been shown to be an early event in this model. DESIGN: Prospective, randomized, controlled study. SETTING: Animal laboratory at a university medical center. SUBJECTS: Twenty-six anesthetized, mechanically ventilated pigs. INTERVENTIONS: 111Indium-oxine was used to selectively label neutrophils or platelets and the activity over the lungs was followed dynamically with a gamma camera. Sham hemodialysis, using a cuprophan hollow-fiber dialyzer, was instituted via catheters in the femoral vessels. The animals were divided into two main groups: a) the nitric oxide recipient group (n = 12, with platelets labeled in seven animals and neutrophils labeled in five animals); and b) the control group (n = 14, with platelets labeled in seven animals and neutrophils labeled in seven animals). The animals in the former group were given 50 parts per million of nitric oxide in the inspiratory gas from the beginning of dialysis and for 30 mins onward. MEASUREMENTS AND MAIN RESULTS: Inhalation of nitric oxide attenuated the increase in activity over the lungs in both the neutrophil and platelet groups during sham hemodialysis. In addition, an inhibiting effect on the increase in pulmonary pressure was noted. CONCLUSION: Apart from the effects of nitric oxide on central hemodynamics in this model, the scintigraphic findings indicate an in vivo effect of nitric oxide on the accumulation of platelets and neutrophils in the lungs, probably due to inhibition of the adhesion and/or aggregation of these cells.

Circulatory and ventilatory effects of intermittent nitric oxide inhalation during porcine endotoxemia.

The effects of intermittent inhalation of 57 ppm nitric oxide (NO) were studied in eight anesthetized, ventilated pigs given a continuous infusion of Escherichia coli endotoxin. Seven animals served as controls. By administering NO synchronized with inspiration and close to the orotracheal tube, measurable amounts of the toxic metabolite, NO2, in the inspiratory gas mixture were avoided. No direct systemic effects of NO inhalation were seen, but through counteracting pulmonary vasoconstriction, a fall in cardiac output was delayed. Nitric oxide effectively attenuated the initial peak rise in mean pulmonary artery pressure and resistance, both returning to control levels after cessation of NO. These effects were reproduced during later phases of endotoxemia, giving further proof to the role of gaseous NO as a selective pulmonary vasodilator. Nitric oxide diminished pulmonary shunting, but unimpaired oxygenation was preserved only during the first inhalation period. Leukocyte counts decreased drastically and platelet aggregation was enhanced, but after 1.5 hours of endotoxin infusion, platelet hyperaggregation was maintained in the NO group while it decreased in the control group.

Iloprost attenuates trauma-related pulmonary sequestration of leucocytes and platelets.

The purpose of this study was to investigate the effects of iloprost, a synthetic prostacyclin analogue, on the pulmonary cellular trapping after a standardized soft tissue trauma. In two groups 1 and 2 iloprost was given in doses of 100 ng/kg/min commencing 30 and 20 min respectively prior to trauma and ceasing 10 min after trauma. 111Indium-oxine was used to label neutrophils in 6 animals from each group. Platelets were labelled in 6 and 7 animals respectively. A third group of 11 pigs served as a control and did not receive iloprost. The pulmonary sequestration of platelets and neutrophils was studied dynamically with a gamma camera and directly after trauma was significantly less in group 1 when compared to the control group. A rise in pulmonary vascular resistance and pulmonary arterial pressure was seen in the control group immediately after trauma but this was not evident in the iloprost groups. PaO2 decreased significantly in group 1 and 2 during the iloprost infusion. The results indicate that iloprost attenuates the pulmonary cellular sequestration and changes in central hemodynamics during trauma in this model.

Lung mechanics, gas exchange and central circulation during treatment of intra-abdominal hemorrhage with pneumatic anti-shock garment and intra-aortic balloon occlusion. An experimental study in pigs.

Standardized intra-abdominal hemorrhage was induced in 7 anesthetized pigs. The resulting hypovolemic shock was treated with pneumatic anti-shock garment (PASG) followed by intra-aortic balloon occlusion. The effects of this treatment on circulation, lung mechanics and gas exchange were studied. Hemorrhage was induced by pulling out sutures introduced in the inferior caval vein. We found that the use of PASG partially restored mean arterial blood pressure from 44 +/- 6 to 66 +/- 6 mm Hg. When intraaortic balloon occlusion was added, the arterial pressure returned to basal levels. Cardiac output fell severely due to the hemorrhage from 3.7 +/- 0.2 to 1.3 +/- 0.2 liters/min and could not be restored during the treatment. A severe fall in total lung compliance was recorded after inflation of the PASG from 18.6 +/- 0.9 to 10 +/- 0.7 ml/cm H2O, this was accompanied by a fall in alveolar ventilation. These findings emphasize the severe restriction in lung function that occurred during treatment with PASG. Both parameters returned to near normal values when the PASG was deflated and the intra-aortic balloon was inflated. Pulmonary vascular resistance increased by more than 400% and remained high during the study period. There was no change in arterial PO2, however the fall in mixed venous PO2 caused by hemorrhage was reversed at the end of the treatment. Indirect monitoring of cerebral function by continuous EEG showed a decreased voltage during the hemorrhage, this was reversed by the combined treatment. We conclude that the outlined treatment makes it possible to restore central hemodynamics and preserve cerebral function at least for a short period of time until definite surgical treatment can be performed. However, severe restriction on lung mechanics, especially when PASG was inflated, makes it probable that ventilatory support can be necessary in such cases.