Biomedical subjects

S H Keshavjee

Publications and source records attributed to S H Keshavjee.

25 records · Page 2Linked to original sources

PubMed1991

The effect of low-potassium-dextran versus Euro-Collins solution for preservation of isolated type II pneumocytes.

Limited availability of donor organs is a major factor restricting the clinical application of lung transplantation. Improvements in preservation techniques are essential for prolonging storage time and improving lung function following transplantation. The present investigation used primary cultures of adult rat alveolar type II cells as a model for evaluating lung-preservation solutions. Type II cells were plated onto tissue-culture plastic at a density 5 x 10(5) cells/cm2 and maintained in Dulbecco's modified Eagle's medium containing 10% fetal bovine serum (D10) for 40 hr. Cells were then exposed to Euro-Collins solution or a low-potassium-dextran solution (LPD). At designated time points, measurements of lactate-dehydrogenase (LDH) release, protein content, and incorporation of 3H-thymidine into cellular DNA were made. During 12 hr of "storage" at 37 degrees C, cells maintained in LPD released less LDH (14.3 +/- 1.2% of cellular total, mean +/- SEM, n = 5) than their counterparts stored in EC (20.6 +/- 1.6%, P less than 0.05). During the 36 hr following a 6-hr exposure to preservative solutions, LPD-treated cells incorporated more thymidine per mg of protein (2566 +/- 419.8 cpm/micrograms protein, mean +/- SEM, n = 6) compared with cells maintained continuously in D10 (1431 +/- 351, P less than 0.05). By contrast, cells exposed to EC incorporated less thymidine (82.2 +/- 62.8 cpm/micrograms protein) than either cells maintained in LPD or D10 (P less than 0.01 for each comparison). These results suggest that LPD solution is less cytotoxic than EC and that LPD enables higher levels of metabolic activity in recovering epithelial cells. In vitro cultures of type II epithelial cells are a useful model system for the study of lung preservation and posttransplantation lung injury.

Alkaline Phosphatase↗

PubMed1991

The effect of pulmonary arterial flow and positive end-expiratory pressure on retrograde bronchial mucosal blood flow.

Bronchial viability within the first few days after lung transplantation depends on collateral blood flow from the pulmonary to the bronchial circulation. In the present study the relationship between pulmonary arterial flow and retrograde bronchial blood flow, and the effect of positive end-expiratory pressure on bronchial blood flow were evaluated by laser Doppler velocimetry in an isolated in situ lung perfusion model. Nine adult mongrel dogs were exsanguinated by way of a left atrial cannula. Blood was pumped by a roller pump into the main pulmonary artery. Lungs were perfused at random flow (in 0.5 L/min increments) at rates of 1 to 3 L/min. Steady-state laser Doppler velocimetric measurements at each level of flow were made at the tracheal carina and both bronchial carina. Pump flow was then set at baseline cardiac output and positive end-expiratory pressure was applied. Steady-state laser Doppler velocimetric measurements were obtained at each level of positive end-expiratory pressure (5 cm H2O and 10 cm H2O). Bronchial blood flow correlated well with pulmonary arterial flow (for the tracheal carina; rs = 0.912 and p less than 0.0005; for the right bronchial carina, rs = 0.799, p less than 0.0005; for the left bronchial carina, rs = 0.917, p less than 0.0005; where rs is the common correlation coefficient). The bronchial blood flow at the left bronchial carina and the right bronchial carina were significantly higher than at the tracheal carina (p less than 0.005 and p less than 0.05, respectively). At baseline cardiac output, bronchial blood flow in the in situ model was approximately 50% lower than observed in the intact animals. Positive end-expiratory pressure increased the bronchial blood flow at the tracheal carina and both bronchial carina (p less than 0.05).

Animals↗

PubMed1990

Radiologic correlation with early physiologic function of the transplanted canine lung.

There is no single reliable method for assessment of the transplanted lung. Multiple modes of assessment are therefore used. In a canine model designed to assess lung preservation, the reliability of information gained from chest radiographs performed in the early post-transplant period was examined. The function of 20 left lung allografts, stored for 12 hours after pulmonary artery flush preservation was studied. Radiographs graded according to disease severity were compared with physiologic function of the transplanted lung assessed immediately and at three days post-transplantation. This protocol enables study of acute preservation-related lung injury and the delayed manifestations of ischemic and reperfusion injury after a three day period of recovery, while avoiding confounding rejection and infectious episodes. The chest radiograph did not reliably reflect function of the flush-preserved transplanted lung. Thus, relying only on this modality may lead to erroneous conclusions. In this study, the progression of radiographic changes associated with the "reimplantation response" differed from previous descriptions, possibly reflecting differences in operative technique or improved lung preservation.

Animals↗

PubMed1990

The superiority of an extracellular fluid solution over Euro-Collins' solution for pulmonary preservation.

Limited donor supply is the major factor restricting the application of lung transplantation. A uniformly reliable method of lung preservation would improve donor organ availability. At present, Euro-Collins' solution, an intracellular fluid-type solution, is most widely used in organ preservation. However, we have previously shown that initial pulmonary flush with an extracellular-type solution (low-potassium dextran solution [LPD]) provided better pulmonary preservation than Euro-C. In the present study, we used an in vitro-ventilated, blood-perfused rabbit lung model to examine whether the mechanism for this improvement was related to the effect of LPD during pulmonary flush or its effect during storage. Rabbit lungs were harvested and stored after pulmonary flush with different solutions (group 1: 400 ml of LPD; group 2: 400 ml of Euro-C; group 4: 300 ml of Euro-C followed by 100 ml of LPD; n = 5 in each group). The lungs were then preserved at 10 degrees C for 18 hr and reperfused with fresh venous blood. After 10 min of reperfusion, lungs in group 1 showed the highest PO2 (group 1: 124.4 +/- 7.7 mmHg; group 2: 46.2 +/- 9.4 mmHg P less than 0.01). Lungs in both group 3 and group 4 showed better lung function and lower wet/dry weight ratio than those in group 2. We conclude that LPD provides better lung preservation by its effects both on pulmonary flush and on storage.

Animals↗

PubMed1989

A method for safe twelve-hour pulmonary preservation.

The clinical application of lung transplantation is severely limited by the shortage of suitable donor organs. Current techniques of lung preservation allow a maximum of 4 to 6 hours of safe ischemic time. The function of canine left lung allografts stored for 12 hours after being cooled by pulmonary artery flush was studied. Two types of flush solution were used: group I; Euro-Collins solution; group II, low-potassium-dextran solution. Lung function was studied immediately and 3 days after transplantation. This protocol enables study of acute preservation-related lung injury and the delayed manifestations of ischemic and reperfusion injury after a 3-day period of recovery. Inflatable cuffs were placed around each pulmonary artery at operation and were attached to subcutaneous injection ports. Temporarily occluding either pulmonary artery allowed independent study of the native or transplanted lung. Using this model, we were able to demonstrate reliable and reproducible preservation of lungs for 12 hours. The low-potassium-dextran solution provided significantly better immediate function of the preserved lung than the Euro-Collins solution: arterial oxygen tension 509 +/- 15 mm Hg versus 111 +/- 16 mm Hg (p less than 0.0001). Function on the third day was excellent for both groups. Pulmonary artery pressure, pulmonary vascular resistance, and carbon dioxide tension were not significantly different between the groups immediately or on day 3.

Animals↗

PubMed1989

The effect of ischemic time and temperature on lung preservation in a simple ex vivo rabbit model used for functional assessment.

Despite 25 years of research in lung transplantation, little progress has been made in methods for improving lung preservation. To evaluate many factors that may affect lung function after preservation, we have developed a simple, reliable, and inexpensive animal model. This consists of an isolated rabbit lung preparation perfused with blood and ventilated with a closed-circuit system. Heart-lung blocks were harvested and the left lung was assessed after ligation of the right pulmonary artery and right main-stem bronchus. On completion of a storage period, the left lung was ventilated and perfused with fresh rabbit venous blood at a rate of 40 ml/min for 10 minutes. Assessment of lung function included gas analysis of infused and effluent blood, oxygen uptake, mean pulmonary artery perfusion pressure, and mean airway pressure. A control group and six preservation groups were evaluated, each with different storage temperatures (38 degrees C, 34 degrees C, 23 degrees C, 15 degrees C, 10 degrees C, and 4 degrees C). For each temperature, ischemic periods ranging from 1 to 30 hours were studied. In the control group, the lungs were assessed immediately after being harvested. In the preservation groups, the lungs were kept partially inflated, stored at a predetermined temperature by immersion, and later assessed after variable ischemic periods. Our studies demonstrated the following: (1) The degree of impaired lung function produced by ischemia is reflected by a decrease in oxygen uptake and in oxygen tension of the effluent pulmonary venous blood and an increase in pulmonary artery perfusion pressure; (2) hypothermia improves ischemic tolerance; (3) preservation of lung at 10 degrees C is superior to preservation at 15 degrees C and 4 degrees C. This screening model has allowed evaluation of independent multiple factors and methods pertinent to lung preservation and enables one to assess lung function reliably and rapidly.

Animals↗

PubMed1985

Neuropathology of chronic pancreatitis in humans.

To investigate the pathogenesis of pain in chronic pancreatitis, tissue resected from 50 patients with this condition was examined by light microscopy. An examiner, blinded to clinical and pathological data, graded perineural fibrosis, inflammation and the composition of inflammatory infiltrate in 2132 separate perineural fields. Correlation of perineural fibrosis and inflammation grading with alcohol ingestion and pain severity was insignificant. Pain severity did correlate with the timing of alcohol consumption. Although calcification significantly affected pain severity, the status of duct dilatation was not significant. Eosinophils were observed in disproportionate numbers in the perineural infiltrate. The correlation of percentage eosinophilic infiltrate and pain severity was highly significant. Timing of alcohol consumption also correlated significantly with the percentage eosinophilic infiltration. As eosinophils are known to be cytotoxic and injurious to tissue by liberation of enzymes through degranulation, the findings of this study suggest that the pain of chronic pancreatitis may be mediated by perineural eosinophils, through a chemotactic mechanism involving alcohol.

Alcohol Drinking↗