Improved ventilation-perfusion matching by abdominal insufflation (pneumoperitoneum) with CO2 but not with air.

BACKGROUND: Pneumoperitoneum (PP) by CO2-insufflation causes atelectasis however with maintained or even improved oxygenation. We studied the effect of abdominal insufflation by carbon dioxide (CO2) and air on gas exchange during PP. METHODS: Twenty-seven anesthetized pigs were studied during PP with insufflations to 12 mmHg by either 1/CO2, 2/ air or 3/CO2 during intravenous nitroprusside infusion (SNP) (N.=9 in each group). In 3 pigs in each group, gamma camera technique (SPECT) was used to study ventilation and perfusion distributions, in another 6 pigs an inert-gas technique (MIGET) was used for assessing ventilation-perfusion matching (VA/Q). Measurements were made during anesthesia before and after 60 minutes of PP. RESULTS: CO2-PP caused a shift of blood flow away from dependent, non-ventilated (atelectatic) to ventilated regions. Air-PP caused smaller, and SNP-PP even less shift of lung blood flow. Shunt decreased during CO2-PP (6 ± 1% compared to baseline 9 ± 2%, P<0.05), did not change during Air-PP (10 ± 2%) and increased during SNP-PP (16 ± 2%, P<0.05). PaO2 increased from baseline 35 ± 2 to 41 ± 3 kPa during CO2-PP and decreased to 32 ± 3 kPa during Air-PP and to 27 ± 3 kPa during SNP-PP (P<0.05 for all three comparisons). PaCO2 increased during CO2- and SNP-PP. CONCLUSION: CO2-PP enhanced the shift of blood flow towards better ventilated areas of the lung compared to Air-PP and SNP blunted the effects seen with CO2-PP. SNP may thus have blunted and CO2 potentiated vasoconstriction, by hypoxic pulmonary vasoconstriction or another mechanism.

Improved ventilation-perfusion matching with increasing abdominal pressure during CO(2) -pneumoperitoneum in pigs.

BACKGROUND: CO(2) -pneumoperitoneum (PP) is performed at varying abdominal pressures. We studied in an animal preparation the effect of increasing abdominal pressures on gas exchange during PP. METHODS: Eighteen anaesthetized pigs were studied. Three abdominal pressures (8, 12 and 16 mmHg) were randomly selected in each animal. In six pigs, single-photon emission computed tomography (SPECT) was used for the analysis of V/Q distributions; in another six pigs, multiple inert gas elimination technique (MIGET) was used for assessing V/Q matching. In further six pigs, computed tomography (CT) was performed for the analysis of regional aeration. MIGET, CT and central haemodynamics and pulmonary gas exchange were recorded during anaesthesia and after 60 min on each of the three abdominal pressures. SPECT was performed three times, corresponding to each PP level. RESULTS: Atelectasis, as assessed by CT, increased during PP and in proportion to abdominal pressure [from 9 ± 2% (mean ± standard deviation) at 8 mmHg to 15 ± 2% at 16 mmHg, P<0.05]. SPECT during increasing abdominal CO(2) pressures showed a shift of blood flow towards better ventilated areas. V/Q analysis by MIGET showed no change in shunt during 8 mmHg PP (9 ± 1.9% compared with baseline 9 ± 1.2%) but a decrease during 12 mmHg PP (7 ± 0.9%, P<0.05) and 16 mmHg PP (5 ± 1%, P<0.01). PaO(2) increased from 39 ± 10 to 52 ± 9 kPa (baseline to 16 mmHg PP, P<0.01). Arterial carbon dioxide (PCO(2) ) increased during PP and increased further with increasing abdominal pressures. CONCLUSION: With increasing abdominal pressure during PP perfusion was redistributed more than ventilation away from dorsal, collapsed lung regions. This resulted in a better V/Q match. A possible mechanism is enhanced hypoxic pulmonary vasoconstriction mediated by increasing PCO(2) .

Ventilation-perfusion distributions and gas exchange during carbon dioxide-pneumoperitoneum in a porcine model.

BACKGROUND: Carbon dioxide (CO2)-pneumoperitoneum (PP) of 12 mm Hg increases arterial oxygenation, but it also promotes collapse of dependent lung regions. This seeming paradox prompted the present animal study on the effects of PP on ventilation-perfusion distribution (V/Q) and gas exchange. METHODS: Fourteen anaesthetized pigs were studied. In seven pigs, single photon emission computed tomography (SPECT) was used for spatial analysis of ventilation and perfusion distributions, and in another seven pigs, multiple inert gas elimination technique (MIGET) was used for detailed analysis of V/Q matching. SPECT/MIGET and central haemodynamics and pulmonary gas exchange were recorded during anaesthesia before and 60 min after induction of PP. RESULTS: SPECT during PP showed no or only poorly ventilated regions in the dependent lung compared with the ventilation distribution during anaesthesia before PP. PP was accompanied by redistribution of blood flow away from the non- or poorly ventilated regions. V/Q analysis by MIGET showed decreased shunt from 9 (sd 2) to 7 (2)% after induction of PP (P<0.05). No regions of low V/Q were seen either before or during PP. Almost no regions of high V/Q developed during PP (1% of total ventilation). Pa(o2) increased from 33 (1.2) to 35.7 (3.2) kPa (P<0.01) and arterial to end-tidal Pco2 gradient (Pae'(co2) increased from 0.3 (0.1) to 0.6 (0.2) kPa (P<0.05). CONCLUSIONS: Perfusion was redistributed away from dorsal, collapsed lung regions when PP was established. This resulted in a better V/Q match. A possible mechanism is enhanced hypoxic pulmonary vasoconstriction.

One-lung ventilation induces hyperperfusion and alveolar damage in the ventilated lung: an experimental study.

BACKGROUND: One-lung ventilation (OLV) increases mechanical stress in the lung and affects ventilation and perfusion (V, Q). There are no data on the effects of OLV on postoperative V/Q matching. Thus, this controlled study evaluates the influence of OLV on V/Q distribution in a pig model using a gamma camera technique [single-photon emission computed tomography (SPECT)] and relates these findings to lung histopathology after OLV. METHODS: Eleven anaesthetized and ventilated pigs (V(T)=10 ml kg(-1), Fio2=0.40, PEEP=5 cm H2O) were studied. After lung separation, OLV and thoracotomy were performed in seven pigs (OLV group). During OLV and in a two-lung ventilation (TLV), control group (n=4) ventilation settings remained unchanged. SPECT with (81m)Kr (ventilation) and (99m)Tc-labelled macro-aggregated albumin (perfusion) was performed before, during, and 90 min after OLV/TLV. Finally, lung tissue samples were harvested and examined for alveolar damage. RESULTS: OLV affected ventilation and haemodynamic variables, but there were no differences between the OLV group and the control group before and after OLV/TLV. SPECT revealed an increase of perfusion in the dependent lung compared with baseline (49-56%), and a corresponding reduction of perfusion (51-44%) in non-dependent lungs after OLV. No perfusion changes were observed in the control group. This resulted in increased low V/Q regions and a shift of V/Q areas to 0.3-0.5 (10(-0.5)-10(-0.3)) in dependent lungs of OLV pigs and was associated with an increased diffuse alveolar damage score. CONCLUSIONS: OLV in pigs results in a substantial V/Q mismatch, hyperperfusion, and alveolar damage in the dependent lung and may thus contribute to gas exchange impairment after thoracic surgery.

Segmental colonic transit studies: comparison of a radiological and a scintigraphic method.

OBJECTIVE: Colonic transit studies are used to diagnose slow transit constipation (STC) and to evaluate segmental colonic transit before segmental or subtotal colectomy. The aim of the study was to compare a single X-ray radio-opaque marker method with a scintigraphic technique to assess total and segmental colonic transit in patients with STC. METHOD: Thirty-one female patients (median age 46 years) with severe constipation and a prolonged or borderline prolonged colonic transit time on radio-opaque marker study were included in the study. They were subsequently investigated with (111)Indium-DTPA colonic transit scintigraphy, with a median time between the investigations of 4(range 1-27) months. Normal values of healthy female controls were used for comparison. RESULTS: There was no difference between the two methods in terms of prolonged or normal total colonic transit time. Twenty-nine of 31 female patients had a prolonged transit time only in one or two segments on the marker study. On scintigraphy, the transit time was prolonged for patients in the left (P < 0.05 to P < 0.001), but not in the right colon. With respect to prolonged or normal segmental transit time, there was a significant difference between the two methods only in the descending colon (P = 0.02). However, the results varied considerably for individual patients. CONCLUSION: Segmental colonic delay was a common finding. The two methods gave similar results for groups of patients, except in the descending colon. The variation of the results for individuals suggests that a repeated transit test may improve the assessment of total and segmental transit.

Day-to-day variability in glomerular filtration rate in normal dogs by scintigraphic technique.

The sources of variability in variability of scintigraphic measurements of glomerular filtration rate (GFR) have not been determined. The day to day variability of GFR was studied in 18 healthy beagle dogs. The renal uptake of 99mTc-diethylenetriaminepentaacetic acid (DTPA) of each dog was measured using a scintigraphic technique three times at intervals of 5-26 days. GFR was calculated from a regression equation relating uptake to plasma clearance, derived in our laboratory. The mean GFR was 3.97 +/- 0.72 (SD) ml/min/kg with values from 2.66 to 5.67 ml/min/kg. Analysis of variance (ANOVA) using a linear mixed model showed that most variability is a result of the dogs, less because of day to day variability and very little to the measurement variability. The repeatability coefficients for the day to day variability and measurement variability were 1.06 and 0.21 ml/min/kg respectively. The day to day variability can be caused by physiological homeostatic adjustments by the kidneys needed because of fluctuations in food and fluid intake, each dog's individual capacity to adjust, and to intrinsic errors in the measurement method. These results should be considered when using the scintigraphic method for clinical evaluation and research.

Thallium-201 myocardial imaging at rest in male orienteers and other endurance athletes.

During the period 1979 to 1992, 16 sudden unexpected cardiac deaths were known to have occurred in young Swedish orienteers. Autopsy indicated myocarditis to be the most frequent finding, most often combined with extensive myocardial fibrosis. The aim of the present investigation was to explore whether young male orienteers show a higher frequency than other young elite endurance athletes (controls) in the occurrence of Thallium-201 myocardial perfusion defects at rest, suggestive of fibrosis evoked by myocarditis. Thallium-201 perfusion abnormalities at rest were more frequently found in the controls than in the orienteers (26% vs. 12%, p=0.03). Uneven Tl-201 perfusion was associated with left ventricular mass (r=0.32, r=0.24, p<0.01, p=0.02) and body weight (r=0.30, r=0.31, p<0.01, p=0.03) in orienteers and controls, respectively. Echocardiographic left ventricular wall motion abnormalities were found in 11 athletes (9 orienteers and 2 controls) but only two displayed an abnormal Thallium-201 perfusion scan at rest. Perfusion abnormalities at rest did not occur more frequently in the orienteers but were commonly found in both groups of apparently healthy athletes making it futile to discern abnormals from normals. Thallium-201 perfusion aberrations were not associated with left ventricular wall motion abnormalities obtained by echocardiography.

Radioimmunolocalization of human colonic cancer xenografts; aspects of extensive purification of monoclonal anti-CEA-antibodies.

Tumour-to-normal tissue ratios of i.p. injected 125I-labelled monoclonal antibodies (MAbs), reacting with CEA were determined in nude rats xenografted with human colonic cancer cells (LS 174 T). Two MAbs, I-38S1 and II-16, reactive with the GOLD 1-epitope on CEA were tested. MAb I-38S1 was also tested after additional purification using anion exchange chromatography (thereafter named AEC 38). In the external activity measurements, MAb AEC 38 showed significantly better tumour-to-liver ratios than did MAb II-16 on all 4 days after injection. MAb I-38S1 gave intermediate ratios but was significantly better than II-16 only on day 3. The mean tumour-to-blood ratios were 3.0, 2.6 and 1.5 and the mean tumour-to-liver ratios were 6.6, 4.8 and 3.5 for MAbs AEC 38, I-38S1 and II-16 respectively. Gamma camera registrations in 3 animals on 4 days showed good imaging properties for all three MAbs and the patterns of tissue uptake were consistent with those seen in the external measurements. Furthermore, histopathological and immunohistochemical determinations were performed, showing that MAb II-16 gave about the same spatial binding as the previously analysed MAb I-38S1. The results indicate that additional purification of MAbs using anion exchange chromatography may potentiate tumour uptake in this model.

Radioimaging of human malignant gliomas using indium-labelled monoclonal antibodies.

A monoclonal antibody (MUC 2-63) was raised against a neuroectodermal antigen expressed on human malignant gliomas, neuroblastomas and melanomas. The mouse monoclonal antibody MUC 2-63 was of IgG1 isotype, it binds the antigenic determinants with the molecular weight of 32,000 Dalton present on the cell surface of native glioma cells. Seven patients with brain tumours, five with biopsy proven malignant gliomas, received an intravenous injection of the 111In-DTPA coupled monoclonal antibody MUC 2-63. Six patients had an uptake of 0.01-0.04% of the injected dose at the site of the tumour, which correlated to the computerized tomography (CT) images. The half-lives in the tumours of 111In were 38-259 h. The maximal uptake in the tumours were noticed between 40 and 67 h. One patient failed to demonstrate any intracranial uptake of the radioactivity. This patient had been treated with surgery and radiotherapy for a stage 2 testicular seminoma four years ago. He recently developed clinical signs of a primary brain tumour and the CT diagnosis was malignant glioma. All patients had nonspecific uptake in the liver, half-lives were between 60 and 84 h, the corresponding maximal uptake was detected between 22 and 45 h. No side effects were observed by administration of the mouse monoclonal antibody MUC 2-63.

In vivo imaging and treatment of human brain tumours utilizing the radiolabelled monoclonal antibody MUC 2-63.

The monoclonal antibody MUC 2-63 identifies a glycoprotein antigen with a molecular weight of 32,000 Dalton present on human malignant gliomas but not detected on normal nerve and brain tissues. This was the prerequisite for these clinical studies with 111In-MUC 2-63 for imaging and 90Y-MC 2-63 for treatment. Seven patients with malignant gliomas, 6 with astrocytomas grade III-IV and 1 with a relapsing astrocytoma grade I-11 received the 111In labelled monoclonal antibody MUC 2-63 for in vivo diagnosis. Six patients had an uptake in the tumour of 0.01 to 0.05% of the MUC 2-63- 111In monoclonal antibody. The patient with the relapsing astrocytoma grade I-II had a negative scan due to a radical operation before the diagnostic dose. All patients received treatment with 90Y-MUC 2-63 intravenously in doses ranging from 146 to 830 MBq. Two patients with relapsing grade III-IV astrocytomas demonstrated clinical improvements and CT changes interpreted as necroses. No serious side-effects were observed in the 5 patients who only received one dose. The two patients who received up to 4 doses experienced grade 3 to 4 leukocyte and thrombocyte toxicity, most likely related to the bone-marrow toxicity by 90Yttrium. These data indicate the potential usefulness of the MUC 2-63 monoclonal antibody for in vivo image on humans with brain tumours and for adjunct treatment after operation and external radiotherapy.

Radioimmunodetection of prostatic cancer with 125I-labelled antibody against prostatic specific antigen.

A murine monoclonal antibody directed against human prostatic specific antigen was labelled with 125I and used in immunoscintigraphy studies of nude mice bearing xenografts of a human prostatic carcinoma cell line (DU-145). The antibody was injected intraperitoneally and the distribution was followed daily with the use of a gamma scintillation camera. Specific uptake was seen in the tumor, with optimal imaging 7-9 days after the injection of the radio-labelled antibody. Fab fragments of the radio labelled antibody were also investigated. These exhibited a strikingly shorter bio-distribution time, with optimal visualization of the tumor after 14-28 hours. Normal murine IgG and Fab fragments used in control experiments exhibited radioactivity that was comparable to that of normal tissue.

Variance measurements with two semiconductor dose detectors.

Variance measurements were performed with pairs of semiconductor detectors of different ionization volumes in continuous and pulsed radiation fields. By a statistical analysis the relative variance of the detector was separated from that of the accelerator. The relative variance of the detector signal was shown to be correlated to the detector volume and to the dose per pulse. From the measurements the number of events per pulse within the detector volume was estimated and the number of pulses needed to have a reading with a given precision was estimated.

Thromboembolism after total hip replacement: role of epidural and general anesthesia.

The effects of continuous epidural anesthesia and of general anesthesia on the incidence of thromboembolism following total hip replacement were studied. Sixty patients were randomly allotted to one of two groups receiving either epidural or general anesthesia. Epidural anesthesia (N = 30) consisted of 0.5% bupivacaine with epinephrine intraoperatively; for pain relief in the postoperative period (24 h), 0.25% bupivacaine with epinephrine was given every 3 h. General anesthesia (N = 30) consisted of controlled ventilation with N2O-O2 and intravenous fentanyl and pancuronium bromide; postoperatively, narcotic analgesics were given intramuscularly on demand for pain relief. Significantly lower frequencies were found following epidural anesthesia than after general anesthesia in deep venous thrombosis involving the popliteal and femoral veins (13% and 67%, respectively), deep venous thrombosis involving both calf and thigh veins (40% and 77%), and pulmonary embolism (10% and 33%). Possible explanations for these differences include increased circulation in the lower extremities, less tendency for intravascular clotting to occur, and more efficient fibrinolysis in association with continuous epidural anesthesia. The decrease in blood loss associated with epidural anesthesia with lower transfusion requirements also might play a role. Epidural analgesia prolonged into the postoperative period, in addition to other appropriate thromboprophylactic measures, should be of value in patients undergoing operations associated with a high risk of thromboembolic complications.

Comparative influences of epidural and general anaesthesia on deep venous thrombosis and pulmonary embolism after total hip replacement.

In an investigation on deep venous thrombosis and pulmonary embolism, where neither dextran nor antithrombotic drug prophylaxis were employed, 30 patients undergoing total hip replacement were randomly allotted to one of two groups receiving either epidural or general anaesthesia. The epidural group (n = 15) was given 0.5% bupivacaine with epinephrine (5 micrograms/ml) and this was prolonged into the postoperative period for pain relief. The general anaesthesia group (n = 15) was operated on under artificial ventilation with nitrous oxide/oxygen via an endotracheal tube and intravenously administered fentanyl and pancuronium bromide. In this group of patients narcotic analgesics (ketobemidone) were given intramuscularly on demand for pain relief postoperatively. The frequency of deep venous thrombosis involving the femoral veins, as observed at phlebography, was significantly lower in patients receiving continuous epidural block (3 of 15; 20%), than in those receiving general anaesthesia and parenteral analgesics postoperatively (11 of 15; 73%). Further, the frequency of pulmonary embolism, as determined by pulmonary perfusion lung scanning, was lower in patients receiving continuous epidural block (2 of 15) than in the general anaesthesia group (7 of 15). Possible explanations for these findings are discussed, including a hyperkinetic lower limb blood flow and lower fibrinolysis inhibition activity in patients given epidural block. Lower blood transfusion requirements in patients given epidural block might also play a role, as well as a "stabilizing" effect of local anaesthetics on platelets, leukocytes and endothelial cells.