[The influence of cardiopulmonary bypass operation on the biodistribution of 99mTc-HMPAO-labelled granulocytes - Evaluation in pigs by planar scintigraphy and section-analyses]. / Einfluss der extrakorporalen Perfusion auf die Biodistribution 99mTc-HMPAO-markierter Granulozyten. Evaluierung im Schwein mittels planarer Szintigraphie und Sektionsanalytik.

AIM: of the study was to evaluate the influence of an extra corporal perfusion (cardiopulmonary bypass operation - cpb) on activation and biodistribution of (99m)Tc labelled granulocytes in pigs with and without inhibition of the granulocytes by a leukocyte inhibition module (LIM). The cpb is often related to an activation of granulocytes resulting in an inflammatory answer. The biological mechanisms are unsolved yet. First trials of our group showed that LIM may inhibit the activation of neutrophils and therefore antagonize a cpb-caused impairment of cardiac function. This study is the continuation of these experiments with a higher number of animals and the focus on scintigraphic imaging. ANIMALS, MATERIAL, METHODS: 39 German landrace pigs were subdivided into three groups: group A (control) median sternotomy without cpb, group B with cpb, group C with LIM in addition to cpb. After labelling with (99m)Tc-HMPAO autologues granulocytes were reinjected. Subsequently to cpb, the animals underwent scintigraphic imaging. Quantification was performed with ROI evaluation and with tissue samples (section analysis) examined in a well counter. RESULTS: A high uptake of (99m)Tc-HMPAO was found in the liver. The count rates in brain, heart, lung, spleen and kidneys were far below. The amount of 99mTc-activity in the organ related to the half life corrected administered activity [%] was for the tissue samples (group A/B/C): brain 0.01/0.02/0.03; lung 12.1/8.3/11.5; heart 0.35/0.54/0.42; kidney 1.24/0.87/1.02; spleen 4.0/4.0/4.5, liver 16.8/20.9/19.6. The count rates determined by ROI-evaluation of the scintigraphic images related to the total count rate in the image [%] were (group A/B/C): brain 1.1/0.9/1.0; lung 15.6/10.4/12.2; heart 4.0/3.5/3.4; kidney 4.0/2.9/3.2; spleen 7.6/7.7/9.5, liver 23.1/36.7/31.4. A significant difference in the tracer uptake between the groups could neither be detected by scintigraphic imaging nor evaluation of tissue samples. CONCLUSION: Scintigraphic imaging as well as section analysis showed a comparable biodistribution of the tracer. Therefore, the initial results of our group were not confirmed with a considerably higher number of animals. Neither cpb nor the use of the LIM influenced distribution of 99mTc-labelled granulocytes in pigs significantly.

Serious complications that require surgical interventions after endoluminal stent-graft placement for the treatment of infrarenal aortic aneurysms.

BACKGROUND: Endoluminal stent-graft placement for the treatment of infrarenal abdominal aortic aneurysms has gained widespread acceptance because it is associated with lower peri-interventional morbidity than conventional transabdominal surgery. In this study the long-term morbidity of the procedure was evaluated. METHODS AND RESULTS: Between September 1994 and December 1998, 150 patients (age, 69.6 +/- 8.49 years; 142 men, 8 women) with abdominal aortic aneurysms were treated with the placement of an intravascular nitinol stent-graft (Stentor [55] and Vanguard-System [95]); there were eight tubular grafts and 142 bifurcated grafts. Initial placement of the stent-graft was successful in 144 patients. Mean follow-up was 49 +/- 25 months. In 13.3% of stent-graft placements we encountered the following complications: 4 cases of migration or dislocation of the prosthesis (30.5 +/- 7.4 months after placement); 2 ruptures of the aorta (26.7 and 15.0 months after placement); 3 recurrent thromboses of the stent-graft (25.5 +/- 5.3 months after placement); 3 endoleaks (27.5 +/- 15.7 months after placement); and 5 infections of the prosthesis (26.6 +/- 16.5 months after placement). There was no correlation between the complications and the type of stent used. All of these patients were treated by surgical replacement of the prosthesis with a Dacron graft. CONCLUSIONS: (1) The results suggest that most complications are due to a continuation of the disease process leading to loosening of the prosthesis. (2) Explantation of the prosthesis and surgical repair is feasible but bears additional risks. (3) Because the onset of reperfusion of the excluded aneurysm cannot be predicted, all patients with infrarenal aortic stent-grafts require frequent computer tomographic follow-up. (4) Finally, the results call for further improvements in the design of the stent-graft.

Investigations on the new free radical scavenger polynitroxyl-albumin to prevent ischemia and reperfusion injury after orthotopic heart transplantation in the pig model.

OBJECTIVE: Nitroxides have strong antioxidant capacity but their effectiveness is limited by their rapid intracellular inactivation. Polynitroxyl-Albumin (PNA) is capable of regenerating inactivated nitroxide. We tested the effect of PNA against reperfusion injury in heart transplantation. METHODS: Pig hearts were transplanted orthotopically. In the control group (n=9) reperfusion was performed without reperfusion modifications. In the experimental group (n=10) 1 ml/kg PNA was given before cross-clamp release. RESULTS: Hemodynamic performance was impaired after transplantation in both groups without significant intergroup differences. Plasma malonedialdehyde levels were significantly diminished in the PNA group as compared to the controls. CK-MB levels in both groups were increased within the first 2 h of reperfusion without significant intergroup differences. In contrast, there were found significant higher values of myocardial specific lactate dehydrogenase (LD1) in the controls versus PNA group. CONCLUSIONS: PNA was able to reduce lipid peroxidation and attenuate free radical activity. Contractile dysfunction could no be improved, indicating that (a) the radical scavenging effect was to weak or (b) other mechanisms than free oxygen radicals are responsible for myocardial damage in this experimental model.

Pathomorphological and histological analysis of the indirect revascularization method.

OBJECTIVE: This experimental study was initiated to determine whether TMLR may prevent porcine myocardium from ischemia and necrosis after acute myocardial infarction. In addition, the influence of TMLR on healthy myocardium was analyzed. METHODS: The short-term effectiveness of TMLR was evaluated in 38 open-chest anesthetized pigs with (n = 18) or without (n = 20) acute LAD occlusion (observation period 6 hours): Six pigs served as controls (thoracotomy only). An additional six pigs had LAD occlusion only (ischemic group). A subsequent 12 pigs were treated by TMLR (CO2) prior to LAD occlusion: Six pigs received one laser channel/cm2 (group 1) and in six pigs two channels/cm2 in the LAD territory (group 2) were performed. In addition, 14 pigs underwent TMLR without ischemia: Seven pigs received 1 channel/cm2 (group 3) and seven pigs 2 channels/cm2 (group 4). Pathomorphological assessment and histology were performed. RESULTS: TMLR limits the expansion of the myocardial infarction zone: laser group 2 demonstrated a significantly smaller area of necrosis in the area at risk (ischemic group (32%) vs. laser group 1 (18%, p = ns) and 2 (8%, p = 0.0076); laser group 1 vs. 2, p = 0.0056). The amount of the area of necrosis of laser groups 3 (0.4%) and 4 (0.04%) compared to control (0%) did not differ significantly (p = ns). Furthermore, in the lased territories of laser groups 3 and 4 microscopic analysis revealed signs of ischemia in 10 +/- 30.9% of all examined histological samples (p = ns vs. control). During a short coronary occlusion the laser-induced tracks were partially filled with blue dye in 94.8 +/- 27.0/85.9 +/- 34.3/94.85 +/- 22.0%/70.21 +/- 47.0% (laser groups 1 - 4 respectively p = ns) The myocardial water content-measurements (MWC) of the ischemia and laser group 1 were not different at the end of the experiment (p = ns). In contrast, laser groups 2, 3 and 4 revealed significantly higher MWC values compared to control (p = 0.036, p < 0.001, p < 0.001; respectively). CONCLUSIONS: This prolonged acute study demonstrates that preventive CO2-laser revascularization significantly reduces the amount of necrosis in the area at risk. Histological examination supported the idea that some pigment gained access to the ischemic tissue via patent channels. In healthy myocardium, TMLR significantly increases myocardial water content and induces non-significant small ischemic and very small necrotic areas surrounding open laser channels.

Controlled limb reperfusion with a simplified perfusion system.

UNLABELLED: The goal of revascularisation of an acutely ischemic limb is to prevent the loss of the extremity and to enable return of normal function. Although reperfusion of an ischemic limb is a prerequisite for the preservation or reestablishment of function, it may, in itself, cause further injury. Controlled reperfusion after revascularisation may reduce this injury and may facilitate return of normal function. Thus far, the technique of controlled limb reperfusion required the use of cardiosurgical equipment and has therefore been reserved for cardiac surgery centers. However, the majority of patients with acute limb ischemia are referred to hospitals, where the technical equipment for controlled reperfusion is not available. We modified the technique of controlled limb reperfusion using a simplified perfusion system with a pressure-cuffed bag, which allows controlled reperfusion without the use of a roller pump. The modified reperfusion technique was applied to 9 patients with acute and persistent ischemia of the limbs (mean ischemic period: 21 +/- 21 hours). Controlled reperfusion consisted of a 30 min infusion of a normothermic reperfusate solution, which was mixed with the patient's blood (6:1, blood/reperfusate ratio) distally to the proximal obstruction. RESULTS: Five patients (56%) recovered with normal function of the limb. Two patients (22%) lost the ischemic limb (ischemic periods: 77 h and 9h; creatine kinase before operation: 6230 U/I and 1045 U/I): another two patients (22%) died, who were in profound cardiogenic shock. CONCLUSION: The simplified perfusion system allows to put controlled limb reperfusion into practice in any operating room. The results support the notion that controlled limb reperfusion should be applied in any patient with acute ischemia of an extremity.

Influence of different routes of flush perfusion on the distribution of lung preservation solutions in parenchyma and airways.

OBJECTIVE: The present study was performed to investigate the influence of different routes of perfusion on the distribution of the preservation solutions in the lung parenchyma and upper airways. METHODS: Pigs were divided into four groups: control (n = 6), pulmonary artery (PA) (n = 6), simultaneous PA + bronchial artery (BA) (n = 8), and retrograde delivery (n = 6). After preparation and cannulation, cardioplegia solution and Euro-Collins solution (ECS) for lung preservation were given simultaneously. After removal of the heart, the double lung bloc was harvested. Following parameters were assessed: total and regional perfusion (dye-labeled microspheres), tissue water content, PA, aorta, left atrial and left ventricular pressures, cardiac output and lung temperature. RESULTS: Our data show that flow of the ECS in lung parenchyma did not reach control values (9.4+/-1.0 ml/min per g lung wet weight) regardless of the route of delivery (PA 6.3+/-1.5, PA + BA 4.8+/-0.9, retrograde 2.7+/-0.9 ml/min per g lung wet weight). However, flow in the proximal and distal trachea were significantly increased by PA + BA delivery (0.970+/-0.4, respectively, 0.380+/-0.2 ml/min per g) in comparison with PA (0.023+/-0.007, respectively, 0.024+/-0.070 ml/min per g), retrograde (0.009+/-0.003, respectively, 0.021+/-0.006 ml/min per g) and control experiments (0.125+/-0.0018, respectively, 0.105+/-0.012 ml/g per min). Similarly the highest flow rates in the right main bronchus were achieved by PA + BA delivery (1.04+/-0.4 ml/min per g) in comparison with 0.11+/-0.03 in control, 0.033+/-0.008 in PA, and 0.019+/-0.005 ml/min per g in retrograde group. Flows in the left main bronchus were 0.09+/-0.02 ml/min per g in control, 0.045+/-0.012 ml/min per g in PA, and 0.027+/-0.006 ml/min per g in retrograde group. The flow rates were significantly (P = 0.001) increased by PA + BA delivery of the storage solution (0.97+/-0.3 ml/min per g). CONCLUSIONS: Our data show that the distribution of ECS for lung preservation is significantly improved in airway tissues (trachea and bronchi) if a simultaneous PA + BA delivery is used.

Distribution of lung preservation solutions in parenchyma and airways: influence of atelectasis and route of delivery.

BACKGROUND: Bronchial healing remains one of the dominant issues in lung transplantation. Among other factors the quality of airway protection during lung procurement may contribute to improve bronchial healing. METHODS: Thirty-three pigs were divided into four groups: controls (n = 6), those receiving antegrade delivery of Euro-Collins solution with (n = 4) and without prostacyclin (n = 9), and those receiving retrograde delivery of Euro-Collins solution (n = 14). In addition, the atelectatic and nonatelectatic regions of the lungs from all groups were compared. After preparation and cannulation, cardioplegic solution and Euro-Collins solution for lung preservation were given simultaneously. After removal of the heart the double-lung bloc was harvested. During each experiment lungs were assessed by the following methods: dye-labeled microspheres for total and regional lung perfusion, tissue water content, pulmonary artery, left atrial and left ventricular pressures, cardiac output, lung temperature, and microscopic examination. Data were expressed as mean +/- standard error of the mean. RESULTS AND CONCLUSIONS: Our data show that (1) injection of modified dye-labeled microspheres is a useful method to determine absolute flow in lung parenchyma and airways, (2) determination of tissue water content is a simple and reproducible method to investigate the distribution of hyperosmolar lung preservation solutions, (3) atelectasis leads to a significant maldistribution of lung preservation solutions regardless of the route of delivery (0.7 +/- 0.2 versus 6.5 +/- 1.0 ml/min/gm lung wet weight, p = 0.0001) and a severe increase in water content (80.6% +/- 0.4% versus 79.0% +/- 0.5%, p = 0.024), (4) prostacyclin added to the pulmonary artery flush solution results in only a slight improvement in the distribution, and (5) retrograde delivery of Euro-Collins solution through the left atrium is technically feasible and seems to improve flow to the airways even without the addition of prostacyclin.