Successful retrieval and function of lungs from non-heart-beating donors.

BACKGROUND: Lung transplantation has been used effectively as a therapeutic tool in end-stage pulmonary diseases, but organ shortages have restricted its use. There is growing interest in alternative organ sources such as organs from circulation-arrested cadavers, so called non-heart-beating donors. METHODS: We examined the effects of postmortem rapid in situ cadaver lung cooling by bilateral chest cavity flushing (group 2) and by pulmonary artery flush through right heart catheterization followed by pleural cavity flushing (group 3) on pulmonary function and morphology in a rabbit non-heart-beating donor model. The results were compared with those in a control group of heart-beating donors (group 1). RESULTS: At the end of a 2-hour reperfusion period, there were no significant differences in mean pulmonary artery pressure, pulmonary vascular resistance, pulmonary compliance, arteriovenous oxygen, pulmonary wet to dry weight ratio, and lung morphology between the three groups. CONCLUSIONS: Our study demonstrates that using bilateral chest cavity flushing with or without pulmonary flush protects the function and morphology of cadaver lungs and renders them suitable for lung transplantation.

Angiogenic response induced by mechanical transmyocardial revascularization.

BACKGROUND: Angiogenesis is the proposed mechanism of transmyocardial revascularization. We evaluated mechanical transmyocardial revascularization in a chronically ischemic porcine model by measuring myocardial angiogenic response. METHODS: Ameroid constrictors were implanted 6 weeks before mechanical transmyocardial revascularization. Group I (n = 5) and group II (n = 3) animals received 30 punctures with an 18-gauge needle and samples were harvested at 1 and 4 weeks, respectively, after the operation. Group III (n = 5) had sternotomy only and served as the control group. Myocardial samples were immunohistochemically stained for vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and transforming growth factor beta (TGF-beta) using specific antibodies. Growth factor expression was quantified by means of computer-assisted morphometry. Vascular density was assessed by immunohistochemical stain for VEGF and factor VIII. RESULTS: Compared with group III, increased angiogenic factor levels were found in group I (VEGF 0.47 +/- 0.03 mm(2) vs 0.05 +/- 0.05 mm(2), P =.000; bFGF 0.67 +/- 0.14 mm(2) vs 0.03 +/- 0.03 mm(2), P =. 000; TGF-beta 1.40 +/- 0.18 mm(2) vs 0.09 +/- 0.06 mm(2), P = 0.000), and in group II (VEGF 0.34 +/- 0.06 mm(2) vs 0.05 +/- 0.05 mm(2), P =.003; bFGF 0.06 +/- 0.02 mm(2) vs 0.03 +/- 0.03 mm(2), P =.135; TGF-beta 0.28 +/- 0.09 mm(2) vs 0.09 +/- 0.06 mm(2), P =.042). Vascular densities after mechanical transmyocardial revascularization were also increased (group I, VEGF stain 8.1 +/- 0. 6 vs 1.1 +/- 0.5, P =.000; factor VIII stain 5.1 +/- 2.7 vs 0.4 +/- 0.3, P =.018; group II, VEGF stain 1.9 +/- 0.5 vs 1.1 +/- 0.5, P = 0. 107; factor VIII stain 2.3 +/- 0.4 vs 0.4 +/- 0.3, P =.004). CONCLUSIONS: Mechanical transmyocardial revascularization is associated with increased angiogenic factor expression and concomitant neovascularization at up to 4 weeks. These changes are indistinguishable from those of laser transmyocardial revascularization. Myocardial perfusion studies are needed to establish the functional significance of these angiogenic changes.

Thoracic Surgery Directors Association Award. Angiogenesis in transmyocardial revascularization: comparison of laser versus mechanical punctures.

BACKGROUND: Transmyocardial laser revascularization (TMLR), which has been shown to reduce angina in clinical trials, was originally based on the belief that laser channels are unique and can remain patent. An increasing body of evidence indicates otherwise, and transmyocardial revascularization (TMR) angiogenesis is currently thought to be induced by nonspecific inflammatory response to tissue injuries. We tested the hypothesis that mechanical transmyocardial revascularization (TMMR) may induce angiogenic responses similar to that seen with lasers. METHODS: Ameroid constrictors were implanted around proximal circumflex arteries of porcine hearts. Six weeks later, they were randomly assigned (n = 5 each) to receive 10 transmural channels in the ischemic zone by a carbon dioxide laser (group I) or by a needle (group II). A third group (group III) had 30 needle channels in the same area, while a control group (group IV) received no TMR. The hearts were harvested 1 week later, and, using immunohistochemistry, vascular endothelial growth factor (VEGF) expression was studied and quantified by computerized morphometric analysis. Densities of vascular structures positively stained for VEGF per high-power field (HPF) were also compared. RESULTS: Virtually no TMR channels remained patent histologically. Group III had a significant higher level of total VEGF expression (14.18+/-0.78 mm2) compared with group I (7.07+/-2.06 mm2, p < 0.001) and group II (4.74+/-3.35 mm2, p < 0.001). Vascular density was significantly elevated in all treatment groups compared with the control (group I, 7.7+/-0.8/HPF vs group II, 4.5+/-2.3/HPF vs group III, 8.1+/-0.6/HPF vs group IV, 1.1+/-0.5/HPF). CONCLUSIONS: In view of the significant cost implications, our findings that needle punctures may also induce angiogenic response comparable with that with laser suggest that it is justifiable and desirable to include a TMMR arm for comparison with TMLR in future clinical trials.

Endothelin receptor antagonist improves pulmonary hemodynamics during lung ischemia/reperfusion injury.

BACKGROUND: We have previously shown that elevated release of endothelin-1 is associated with increased pulmonary vascular resistance (PVR) immediately after reperfusion of the transplanted lung. In the present study, we investigated the effect of ET receptor blockage on pulmonary hemodynamics and function in an ex vivo lung reperfusion model after 6 hr of cold ischemia. METHODS: Eighteen rabbits were divided into three groups: no ischemia followed by 3 hr of reperfusion (group I) and 6 hr of cold ischemia followed by 3 hr of reperfusion with either blood (group II) or blood + SB209670 (mixed ETA/ETB receptor antagonist) (group III). RESULTS: Shortly after reperfusion, mean pulmonary artery pressure, PVR, and pulmonary edema were increased, and pulmonary compliance and PO2 were decreased in group II compared with group I. Treatment with SB209670 resulted in a significant decrease in mean pulmonary artery pressure, PVR, and pulmonary edema, and improvement in pulmonary compliance and PO2. CONCLUSION: The data suggest an important role for ET-1 in lung ischemia/reperfusion injury and that the use of ET receptor antagonist immediately after transplantation may provide a new therapeutic tool in the management of early graft dysfunction.

Efficacy of administering an endothelin-receptor antagonist (SB209670) in ameliorating ischemia-reperfusion injury in lung allografts.

The purpose of this study was to determine whether treatment with an endothelin-1 (ET-1)-receptor antagonist could prevent ET-1-mediated ischemia-reperfusion injury and early allograft dysfunction. Eleven dogs were subjected to left lung allotransplantation. Donor lungs were preserved with modified Eurocollins solution and stored at 4 degrees C for 18 to 20 h. Animals received an intravenous infusion of either the ET-receptor antagonist SB209670 (n = 6) (15 microg/kg/min) or saline (control, n = 5), in a blinded fashion. The infusion started 30 min before transplantation and continued for up to 6 h after transplantation. Hemodynamic measurements, blood gas tensions, and plasma samples were obtained with animals functioning solely on the transplanted lung. Open-lung biopsies were obtained for wet-to-dry-weight ratios and histologic and immunohistochemical analyses. Survival at 6 h after transplantation was 40% in the control group and 100% in the treatment group. Pulmonary vascular resistance and lung tissue wet-to-dry-weight ratio were significantly lower in treated animals at 3 and 6 h after transplantation. Histology of the transplanted lungs revealed more intense airway and interstitial inflammatory infiltration and edema in the control group. Arterial and venous plasma ET-1 concentrations increased after transplantation; however, they were significantly higher in the treatment group. Immunohistochemical analysis revealed more intense ET-1 immunostaining in the airways and parenchyma of the treatment group. We conclude that treatment of lung allografts with the mixed endothelin A/endothelin B (ETA/ETB) receptor antagonist SB209670 can ameliorate ischemia-reperfusion injury, resulting in improved graft function and survival after lung transplantation.

Pulmonary cell death in warm ischemic rabbit lung is related to the alveolar oxygen reserve.

BACKGROUND: If lungs could be retrieved for transplantation from non-heart-beating cadavers, the shortage of donors might be significantly alleviated. METHODS: We studied the effect of different postmortem lung conditions on pulmonary cell death. Lungs from 208 New Zealand white rabbits were flushed with trypan blue vital dye solution at intervals after circulatory arrest, fixed, and mounted for histologic examination. Pulmonary cells were judged to be viable on the basis of their ability to exclude trypan blue dye. In the control group, lungs were excised immediately after death and immersed in cold (4 degrees C) saline solution. In the other groups, cadavers were left at room temperature with lungs deflated, ventilated with room air or 100% oxygen or 100% nitrogen, or inflated with room air or 100% oxygen. RESULTS: There was a gradual increase in percentage (mean +/- SEM) of nonviable cells in the control group from 2.5%+/-0.9% (preischemic value) to 18.1%+/-2.8% at 24 hours after death (p < 0.001). In cadavers with lungs deflated, 79.7%+/-2.1% of cells were nonviable at 24 hours after circulatory arrest (p < 0.001 versus control group). In contrast, room air-ventilated cadavers showed only 21.4%+/-2.7% nonviable cells at this interval (p < 0.001 versus deflated group; not significant versus control group). Values in oxygen-ventilated animals were similar. Nitrogen-ventilated cadavers, however, had significantly more nonviable lung cells (73.8%+/-3.2%; p < 0.001 vs room air and oxygen-ventilated group, not significant vs deflated group). Oxygen-inflated lungs showed a parallel decrease in cell viability up to 4 hours after death when compared with room air-inflated cadaveric lungs, but thereafter more cells became nonviable in the latter group (11.1%+/-0.7% vs 19.6%+/-3.2% at 6 hours and 48.7%+/-7.2% vs 75.5%+/-4.6% at 24 hours, respectively; p < 0.01). CONCLUSIONS: Postmortem room air ventilation is as good as oxygen ventilation in delaying pulmonary cell death, and its effect is comparable to cold storage; nitrogen ventilation, however, is ineffective and not different from deflation; oxygen inflation will preserve ischemic cells for longer intervals as opposed to room air inflation. Therefore the alveolar oxygen reserve seems to be the critical factor to protect-the lung parenchyma from warm ischemic damage.

[Estrogen secretion and cellular source of ovarian epithelial tumors].

This paper studies the estrogen secretion of ovarian epithelial tumors in postmenopausal women by using the radioimmunoassay method to measure the concentration of estradiol (E2) in peripheral and ovarian venous blood, using the immunohistochemical method (ABC) to locate the cell position of E2 in tumor tissue, and observing the clinical symptoms of the patients. The results demonstrated that epithelial ovarian tumors in postmenopausal women can secret E2 and the secretory function of mucinous tumor is most active in epithelial ovarian tumors; the E2 produced by the tumors is not only from the stromal cells of the tumors, but mainly from the epithelial cells of the tumors. The secretory function of E2 is usually manifested in "the subclinical condition", but sometimes it may show clinical symptoms. So, epithelial ovarian tumors should be considered when women have the symptom of postmenopausal uterine bleeding.

[Reversal operation after female sterilization by mucilago phenol].

A reversal operation after occlusion of fallopian tubes by mucilago phenol was carried out in 30 women. A revised method of tubocornual implantation was the operation of choice. The resected portions of the tubes were examined by both light microscope and electron-microscope and no abnormalities were observed in the portion of the tube adjacent to the occluded segment. After reversal, the tubal patency rate was 97%. During a follow-up period of 18-26 months, the pregnancy rate and term-pregnancy rate was 76% and 72% respectively. The results indicate that occlusion by mucilago phenol is a reversible method of tubal sterilization.