Lung vascular injury with protease infusion. Relationship to plasma fibronectin.

Fibronectin exists in a soluble form in plasma and in an insoluble form in tissues. Plasma fibronectin can modulate phagocytic function as well as incorporate into the tissue matrix where it is believed to influence microvascular integrity and tissue repair. The temporal alterations in plasma and lung lymph fibronectin were studied in relation to increased pulmonary vascular permeability induced by protease infusion. The acute sheep lung lymph fistula model was used. A 39% decrease in plasma fibronectin (control = 421 +/- 67 micrograms/ml) was observed 2.5 hours (255 +/- 43 micrograms/ml) after protease infusion. There was an elevation of lymph fibronectin early after protease infusion, followed by a progressive decline. Concomitant with the decrease in plasma fibronectin, an increase in lymph flow (QL) of greater than 200% (from a control of 6.7 +/- 1.0 ml/hr to 13.9 +/- 1.4 ml/hr) was observed within 2.5 hours. Also, there was a sustained elevation in the total protein lymph/plasma concentration (L/P) ratio, which was maximal at 2.5 hours. The transvascular protein clearance (TVPC = QL X L/P) was 4.5 +/- 0.7 ml/hr at the control period and 13.1 +/- 2.0 ml/hr by 2.5 hours. This was indicative of increased flux of protein-rich fluid across the pulmonary endothelial barrier. Lung vascular permeability stabilized after 2.5 hours as manifested by a slowly declining L/P ratio. Thus, plasma fibronectin deficiency may contribute to the etiology of increased lung vascular permeability with protease infusion. Since the progressive decline in plasma fibronectin was not reflected in a proportional increase in lymph fibronectin, plasma fibronectin may have sequestered in tissues such as the lung, or perhaps in reticuloendothelial cells during the injury phase. Whether the progressive decrease in plasma fibronectin reflects its incorporation into the endothelial barrier matrix where it may mediate stabilization of the pulmonary microvascular barrier remains to be determined.     

Effect of OKY 046, a thromboxane synthase inhibitor, on lung vascular permeability after pulmonary embolism in sheep.

OKY 046, a specific thromboxane synthase inhibitor, was used to investigate whether large pulmonary emboli, like microemboli, cause an increase in thromboxane A2 and an associated increase in vascular permeability in sheep. Nineteen sheep were anaesthetised and had cannulas inserted into the afferent lymphatic of the caudal mediastinal lymph node and pulmonary and carotid arteries. Several days later the animals were pretreated with placebo or OKY 046 0.4 mg/kg one hour before being given clotted blood 0.5 g/kg intravenously. After embolisation in the control animals mean pulmonary artery pressure (MPAP) rose from 12 to 34 mm Hg and pulmonary artery wedge pressure (PAWP) fell from 4.4 to 1.5 mm Hg; the cardiac index did not change but the physiological shunt (QS/QT) rose from 17% to 50%. One hour after embolisation the platelet count fell from 76 to 32 x 10(6)/l whereas at 15 minutes thromboxane B2 rose from 116 to 560 pg/ml in plasma and from 324 to 795 pg/ml in lymph (p less than 0.05). By 2 hours the concentration of thromboxane B2 was higher in lymph than in plasma. Lymph flow rose from 8.7 to a maximum of 27.3 ml/h at 15 minutes but despite the increase in flow the lymph:plasma (L:P) protein ratio did not fall, indicating an increased permeability of the blood vessels to protein. Pretreatment with OKY 046 inhibited the rise in plasma and lymph thromboxane B2, and limited the rise of QS/QT. The changes in MPAP, PAWP, cardiac index, platelet count, lymph flow, and L:P protein ratio, however, were no different from those in untreated sheep. These results indicate that a large pulmonary embolus leads to an increase in plasma and lung lymph thromboxane A2, which moderates the rise in QS/QT in part but not the increase in vascular permeability.     

Recurarization after sugammadex reversal in an obese patient

Purpose

We report a case that involved immediate postoperative respiratory failure necessitating tracheal intubation, which was possibly related to recurarization after sugammadex reversal.

Clinical findings

A 54-yr-old woman weighing 115-kg was scheduled for laparoscopic repair of abdominal dehiscence under general anesthesia. Muscle relaxation was induced and maintained with rocuronium (170 mg iv total dose). At the end of the 170-min procedure, two twitches were visualized after supramaximal train-of-four (TOF) stimulation at the adductor pollicis muscle, and the patient’s central core temperature was 35.6°C. Sugammadex 200 mg iv (1.74 mg·kg^?1) was administered. With the patient fully awake, a TOF ratio 0.9 was obtained five minutes later. The tracheal tube was then removed, and the patient was transferred to the postanesthesia care unit. Ten minutes later, the patient presented respiratory failure necessitating tracheal intubation and sedation with propofol. One TOF response only was visualized at the adductor pollicis muscle. Another dose of sugammadex 200 mg iv was administered. Forty-five minutes later, the patient was fully awake and her trachea was extubated after repeated measures of the TOF ratio (≥ 0.9) at the adductor pollicis muscle. The patient fully recovered without sequelae, further complication, or prolonged hospital stay.

Conclusion

Shortly after tracheal extubation, an obese patient experienced respiratory failure necessitating tracheal intubation and an additional dose of sugammadex. This occurred despite initial reversal of neuromuscular blockade with an appropriate dose of sugammadex 2 mg·kg^?1 iv given at two responses to TOF stimulation.     

Changes in lung vascular permeability after heart-lung transplantation

We have employed multiple indicator dilution techniques (MID) in six patients after heart-lung transplantation to assess changes in the lung vascular permeability-surface area product for urea (PS). Serial PS values for the patients when normalized to the predicted total lung capacity (TLC) in liters, ranged between 1.04 and 6.27 ml/sec/TLC (patient 1), 0 and 2.76 ml/sec/TLC (patient 2), 0.59 and 2.88 ml/sec/TLC (patient 3), 0.13 and 1.23 ml/sec/TLC (patient 4). The elevated values for PS in patient 1 exceed the lethal range described by K.L. Brigham et al. (J. Clin. Invest. 72:339, 1983) for severe ARDS. This strongly suggests a severely increased lung microvascular permeability in this patient possibly secondary to rejection as indicated by endomyocardial biopsy. PS values for surviving patients 2-6 fell well below the corresponding lethal value for ARDS patients. We conclude that PS urea derived from MID provides an indicator of the status of lung microvascular integrity in heart-lung transplant recipients.     

Opsonic fibronectin deficiency in patients with intra-abdominal infection

The reticuloendothelial system provides host defense functions by the intravascular phagocytosis of bacteria and nonbacterial particulates. Fibronectin is opsonic for reticuloendothelial phagocytosis. Plasma fibronectin was measured before and after operation in patients with intra-abdominal infection. Preoperatively opsonic fibronectin was reduced by 39% of normal control levels in 16 patients with intra-abdominal infection. There was an even greater reduction of opsonic fibronectin after operation that was first observed in the recovery room. This deficiency persisted for the first 4 days with a tendency toward recovery of normal circulating levels by the fifth postoperative day. In contrast, patients who underwent elective major abdominal operation without infection manifested a transient opsonic fibronectin deficiency with recovery by the second and third postoperative days. Eight of 16 patients with intra-abdominal infection developed multiple organ failure. The opsonic fibronectin levels in those patients were lower than the levels in eight patients who did not develop multiple organ failure. Furthermore, there was no tendency toward recovery of normal circulating opsonic fibronectin in those patients. On all days when multiple organ failure occurred there was a marked deficiency of circulating opsonic fibronectin. We conclude that transient opsonic fibronectin deficiency occurs after major elective abdominal operation. Patients with intra-abdominal infection manifest opsonic fibronectin deficiency before operation, and further depletion of opsonic fibronectin occurs after operation. Postoperative multiple organ failure occurs only in association with severe opsonic fibronectin deficiency.     

Lung growth after reduced size transplantation in a sheep model

BACKGROUND: The growth of mature allografts is a critical issue in pediatric lung transplantation. This study explores the architectural changes of mature sheep lung when submitted to two different compensatory growth forces: either transplantation into a neonatal host or expansion in an otherwise empty adult hemithorax. METHODS: Right upper lobes (RUL) (mean+/-SEM, 66.7+/-1.9 kg) from 4- to 5-year old (adult sheep) were transplanted into newborn (n=6) lambs (5.4+/-0.3 kg, 5+/-2 days old) that were then allowed to survive for 45 days. Changes in pulmonary volume and architecture were measured before and after transplantation. Allografts were compared with both normal adult RUL (n=10) and adult (65.8+/-2.2 kg and 4 to 5 year old) RUL that remained in situ for 45 days after resection of the corresponding middle and lower lobes (n=6). Statistical differences were analyzed using two-sample and paired t tests. RESULTS: In adult animals, RUL remaining in the otherwise empty hemithorax compensated by an 85% increase in volume (251.5+/-18.7 ml vs. 466+/-32.8 ml) (P<0.0001). Concomitant increases in total internal alveolar surface area (48%) and alveolar size were prominent. The number of alveoli per volume decreased proportionately to the increases in volume (P<0.0001). There was no significant change in the calculated number of alveoli (345.6+/-40.5 x 10(6)) compared with the normal adult RUL (402.4+/-40.7x10(6)) (P=0.37). Transplant recipients received a reduced-size normal adult RUL (49%) in volume (125.3+/-21.5 ml). Allografts 45 days after transplantation showed a 73% increase in volume (216.4+/-21.3 ml) (P<0.0001) with a parallel (83%) increase in total internal alveolar surface area (P=0.008). The number of alveoli per volume remained constant (P=0.21) despite the increase in volume. There was therefore a significant increase in the calculated number of alveoli from before transplantation (172.5+/-35.9x 106) compared with that observed 45 days after transplantation (389.7+/-77.7x10(6)) (P=0.012). CONCLUSIONS: We conclude that mature sheep RUL parenchyma compensates with dilation of the respiratory structures in the adult animal, whereas there is alveolar multiplication when transplanted into newborn recipients.     

Course of plasma fibronectin in burn patients. Its variations during septic episodes

The time course of plasma fibronectin (FNp) was evaluated following burn injury in 62 patients during 30 days. Those patients were divided into three groups: A: 36 non septic survivors, B: 7 septic survivors, C: 19 dead patients. Those groups were statistically different if either age or total body surface area burnt (TBSA), or unit burnt standard (UBS) or the percentage or third degree burnt area were considered. The relationship between FNp, UBS or sepsis was studied. No correlation was found between FNp levels and TBSA or UBS for the first three days. After acute depletion on day 2, the FNp level returned to initial values on day 3. That depletion was probably a consequence of resuscitation since both falls in plasma FNp and haematocrit were parallel from day 1 to day 2. When the patients became septic, there was always a drop in FNp level. The depleted level of FNp remained low in the patients who finally died, whereas in those who survived that level had returned to normal. The observation of FNp level could therefore be useful in determining how serious a sepsis is.     

In vitro reversal of cardiac deterioration in septic shock with tetraethylammonium chloride

Overwhelming sepsis associated with cardiac failure continues to be a major clinical problem. This is commonly associated with a failure to respond to conventional pharmacologic therapy. This study was undertaken to see if manipulations of the electrophysiologic defects previously described by treatment with tetraethylammonium chloride (TEA) would be advantageous. Septic shock was induced in rabbits by a lethal dose of Escherichia coli. Peak tension and velocities of contraction and relaxation were measured in papillary muscle with and without 5mM TEA. Exposure to this compound improved peak tension and velocities of contraction and relaxation to normal values. The action of TEA is not specific to septic tissue as values in normal muscles are similarly improved. Tetraethylammonium chloride or other drugs that decrease outward potassium current and prolong the action potential duration may be helpful in treating cardiac dysfunction that accompanies sepsis.     

Expression of vascular permeability factor in craniopharyngioma.

OBJECT: The expression of vascular endothelial growth/permeability factor (VEG/PF) has recently been correlated with the presence of tumor-associated cysts in some intracranial tumors. The purpose of this study was to evaluate a possible relationship between the presence of VEG/PF and the formation of cysts in craniopharyngiomas. METHODS: The expression of VEG/PF was studied in histological specimens from a series of 12 craniopharyngiomas. In this series, the tumors were classified as presenting a mainly solid pattern with small macroscopic cysts (four patients) or a mainly cystic pattern (eight patients). The mainly solid tumors containing small macroscopic cysts showed little or no VEG/PF positivity, which was mainly present in tumor cells surrounding cysts. Nevertheless, mainly cystic craniopharyngiomas showed a moderate or high degree of VEG/PF positivity in tumor cells. CONCLUSIONS: These findings indicate that the predominance of a cystic or solid macroscopic appearance of craniopharyngiomas may be influenced by the degree of VEG/PF expression within the tumor cells.     

Lung transplantation in a patient with arteriovenous malformations.

Multiple arteriovenous fistulas (AVF) is an infrequent pathology, in which lung transplant is controversial. We report a patient with hereditary hemorrhagic telangiectasia who underwent a single lung transplant with excellent evolution, and three years later (that is, at the time of this paper), she is still alive.     

Lung lymph response to overinfusion with hydroxyethyl starch in sheep. Comparative studies of high and low molecular weight compounds

BACKGROUND: Several hydroxyethyl starch (HES) solutions are available clinically. We performed comparative studies of low and high molecular weight HES to evaluate the effects on lung lymph flow in sheep, to see the difference in the types of HES. METHODS: We prepared awake sheep with vascular monitorings and lung lymph fistulas. We measured systemic artery pressure (Psa), pulmonary artery pressure (Ppa), and left atrial pressure (Pla) continuously. Cardiac output (CO) was measured every 30 min. Lung lymph flow (Qlym) was collected every 15 min. After baseline measurements, two HES solutions were infused over 2 h, respectively. Experiment 1 (n=6): low molecular weight HES (MW 70 000, substitution ratio 0.5-0.55), Experiment 2 (n=5): high molecular weight HES (MW 450 000, substitution ratio 0.7). RESULTS: Both low and high molecular HES behaved similarly as a volume expander, increasing Psa, CO, Pla and Ppa, and decreasing hematocrit. In addition, the actual oncotic pressure gradient (plasma - lymph) was widened after the start of either low or high molecular HES, but the value for high molecular HES was significantly higher than that for low molecular HES. Qlym of low molecular HES rose significantly from the baseline and the percent increase in Qlym for low molecular HES was significantly higher than that for high molecular HES. CONCLUSION: These data suggest that low molecular HES is as useful a plasma substitute as high molecular HES, but may increase lung fluid filtration in the overinfused state.     

Ketamine anaesthesia in a patient with septic shock

A 71-year-old male patient was operated on in a septic state (tachycardia, hypotonia, fever peaks, disorientation) because of an occluding tumour of the biliary tract. Ketamine was used as the main anaesthetic. Mean arterial pressure increased markedly and diuresis started during the anaesthesia. The inotropic support (dopamine, dobutamine, noradrenaline) could be reduced. Ketamine anaesthesia seemed to have a beneficial haemodynamic effect in septic shock.     

Extrapulmonary tuberculosis in a patient with septic shock

A 61-year-old woman who was negative for type 1 human immunodeficiency virus developed vertebral osteomyelitis and skin lesions due to sepsis by Staphylococcus aureus. Microscopic examination of the skin showed alcohol-resistant acid-fast bacilli. A polymerase chain reaction (PCR) assay for Mycobacterium tuberculosis was positive for skin and spinal samples, although the cultures were negative. The diagnosis of M. tuberculosis infection is difficult, particularly when the disease is extrapulmonary. Rapid diagnostic tests that use PCR identify the DNA of the bacillus with greater sensitivity than microscopic examination and can give results within 24 hours of receipt of a sample. We analyze the utility of PCR for diagnosing extrapulmonary tuberculosis.     

Complete reversal of tumoral calcinosis after subtotal parathyroidectomy in a hemodialysis patient

IntroductionTumoral calcinosis is a rare complication of chronic hemodialysis whose mechanism is incompletely understood. The treatment is challenging and should target the main precipitating factors, most notably secondary hyperparathyroidism and calcium–phosphate (Ca×P) product elevation.Case reportIn this 41-year-old patient, tumoral calcinosis developed in the right hip and subacromial bursa of the right shoulder after 3 years of chronic hemodialysis. Laboratory tests showed hyperparathyroidism with Ca×P elevation. Subtotal parathyroidectomy was performed. Eight months later, there was no evidence of tumoral calcinosis at either of the previously affected sites.ConclusionThe effectiveness of parathyroidectomy in our patient underlies the key role played by secondary hyperparathyroidism in the pathogenesis of tumoral calcinosis complicating hemodialysis.     

Reversal of fibronectin and opsonic deficiency in patients. A controlled study

Plasma fibronectin is an opsonic glycoprotein which augments reticuloendothelial phagocytic clearance of nonbacterial particulates. We evaluated the influence of intravenous infusion of plasma cryoprecipitate on circulating immunoreactive fibronectin and associated opsonic activity at 0.5, 2.0, 4.0, 10, and 21 hr postinfusion in septic (n = 8) and nonseptic (n = 6) surgical and/or trauma patients with documented plasma fibronectin deficiency. The study was a randomized, double-blind, crossover clinical protocol in which fibronectin-poor (0.116 +/- 0.025 mg/ml) cryoprecipitate extracted plasma (placebo) was compared to fibronectin-rich (2.139 +/- 0.161 mg/ml) plasma cryoprecipitate. Septic injured patients (149.37 +/- 17.11 micrograms/ml) had lower (p less than 0.05) plasma fibronectin levels than nonseptic injured patients (212.17 +/- 7.14 micrograms/ml) and both were less (p less than 0.05) than normal (330 +/- 30 micrograms/ml). As tested in vitro with a peritoneal macrophage monolayer assay, cryoprecipitate manifested opsonic activity related to its fibronectin concentration. Intravenous infusion of fibronectin rich cryoprecipitate reversed both the immunoreactive fibronectin and opsonic deficiency, while infusion of the placebo at a comparable total protein load did not reverse either deficient parameter. Reversal of fibronectin deficiency was more sustained in nonseptic injured patients as compared to septic injured patients. Thus, reversal of opsonic deficiency in septic and nonseptic injured patients is observed after infusion of plasma cryoprecipitate and not with infusion of fibronectin deficient plasma at comparable protein loads. Also, cryoprecipitate extracted plasma may serve as an appropriate control solution for randomized studies evaluating the therapeutic value of fibronectin-rich plasma cryoprecipitate.