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S Keshavjee

Publications and source records attributed to S Keshavjee.

64 records · Page 4Linked to original sources

Optimal inflation volume for hypothermic preservation of rat lungs.

BACKGROUND: Recent studies have suggested that preservation of donor lungs with inflation provides better pulmonary function after transplantation, but hyperinflation of pulmonary grafts during storage increases reperfusion pulmonary edema. To elucidate the optimal inflation volume during the preservation period, and the possible role of barotrauma in lung injury after atelectatic storage, we examined the effects of inflation volume and reinflation protocols in hypothermically preserved rat lungs. METHODS: Adult rat lung blocks were preserved at 4 degrees C for 18 hours at various levels of inflation. Static pulmonary compliance was measured and compared before and after preservation. The hemodynamics and gas exchange function of optimally inflated lungs were then compared with lungs preserved atelectatically in a rat paracorporeal reperfusion model. RESULTS: We found that the optimal level of inflation for preservation is 50% of total lung capacity (TLC). Lungs stored atelectatically or inflated to 25% of TLC showed deterioration of postpreservation lung compliance, whereas air leaks were observed in most of the lungs preserved with inflation to 75% or 100% of TLC. The hemodynamics and gas exchange function in lungs preserved with inflation at 50% of TLC were significantly better than that of atelectatically preserved lungs. A gentle reexpansion of atelectatically stored lungs did not prevent the deterioration of pulmonary function. CONCLUSION: Donor lungs should be preserved at an optimal inflation volume, and mechanisms other than barotrauma after atelectatic storage may be responsible for postpreservation and postreperfusion lung injury.

Animals↗

Prevention of rapid reperfusion-induced lung injury with prostaglandin E1 during the initial period of reperfusion.

We have found that the instantaneous restoration of blood flow causes acute dysfunction and massive edema in rat lungs after 4 hours of room temperature ischemia. This is associated with an early increase in pulmonary artery pressure (Ppa) and can be prevented by a stepwise increase in flow rate during the first 10 minutes of reperfusion. The objectives of this study were to determine whether rapid reperfusion causes lung injury after hypothermic preservation, and whether this injury can be attenuated by a short-course of prostaglandin E1 (PGE1). Rat lungs were flushed preserved with low-potassium dextran solution for 12 hours at 4 degrees C and randomly divided into three groups: (1) control (no PGE1); (2) PGE1 only in the flush solution; and (3) PGE1 in both flush solution and blood perfusate during the first 10 minutes of reperfusion. Postpreservation pulmonary function was assessed in an isolated rat lung reperfusion model developed previously. We found that rapid initiation of reperfusion led to significant pulmonary dysfunction, which was attenuated by a short-course of PGE1 in the blood perfusate. The addition of PGE1 to the flush solution alone did not have such an effect. Administration of PGE1 to the blood perfusate during the first 10 minutes resulted in significant lower Ppa and airway pressure and better gas exchange. There was a positive correlation between the peak Ppa during the first 10 minutes of reperfusion and the final shunt fraction. The physical forces generated by the rapid initiation of blood reperfusion appear to induce severe injury. The first 10 minutes of reperfusion seem to be a transition phase in which mechanical factors play an important role relating to ultimate post reperfusion lung function. A short course of PGE1 may be a useful maneuver to prevent rapid reperfusion-induced lung injury.

Airway Resistance↗

Lymphocytic airway infiltration as a precursor to fibrous obliteration in a rat model of bronchiolitis obliterans.

BACKGROUND: Bronchiolitis obliterans is the most significant complication adversely affecting prolonged survival of lung allograft recipients. The evolution from the initial insult to the final pathologic entity is largely unknown. The aim of this study was to characterize the evolution of transplant-induced fibrous airway obliteration in a rat tracheal transplant model of bronchiolitis obliterans. METHODS: Tracheal segments were transplanted from Brown Norway rats to Brown Norway rats (isografts) or to Lewis rats (allografts). Grafts were implanted into a subcutaneous pouch and an abdominal omental wrap. They were harvested at 14 different time points (from 1 day to 1 year after transplantation) and assessed histologically. RESULTS: The fibrous airway obliteration developed only in allografts showing a triphasic time course: an initial ischemic phase (observed in both isografts and allografts) was followed by a marked lymphocytic infiltrative phase with complete epithelial loss (observed only in allografts, P<0.01), and finally by an obliterative phase with fibrous obliteration of the allograft airway lumen (P<0.01). CONCLUSIONS: This animal model shows a distinct and reproducible triphasic time course in the development of obliterative airway lesions in allografts. It confirms that the mechanism leading to airway obliteration is immune mediated as only allografts showed this lesion and that lymphocytic infiltration is a precursor of the lesion in this model. The insights into the different phases demonstrated may lead to novel approaches regarding the type and timing of therapeutic interventions.

Animals↗

Mediastinal parathyroid cysts.

BACKGROUND: Mediastinal parathyroid cysts are a relatively rare clinical entity. The clinical presentation can be quite varied, although most are found incidentally during investigations for esophageal or respiratory symptoms. METHODS: We present a review of the literature and describe two instructive cases showing specific clinical findings. The clinical presentation, radiologic and pathologic findings, and treatment of mediastinal parathyroid cysts are discussed. RESULTS: In the first patient, the presenting symptom was increasing hoarseness resulting from paresis of the right recurrent laryngeal nerve. This case illustrates the rare association of a benign mediastinal parathyroid cyst with unilateral vocal cord palsy. The second patient presented with the more classic findings of progressive dyspnea and stridor related to tracheal compression. CONCLUSIONS: Although mediastinal parathyroid cysts are rare and can have varied presentations, thorough investigation can reveal the underlying cyst. Surgical excision is the treatment of choice and can be expected to produce excellent results.

Aged↗

Status of lung transplant recipients surviving beyond five years.

BACKGROUND: Prolonged survival after lung transplantation is now commonplace as a result of advances in surgical techniques and postoperative management protocols. Although 1- and 5-year functional and survival data after lung transplantation are well known, sparse information is available regarding functional status of recipients surviving beyond 5 years. METHODS: The medical records and pulmonary function study results of lung transplant recipients who had survived at least 5 years as of September 1995 were retrospectively reviewed. RESULTS: Of the 76 transplantations performed between November 1983 and September 1990, 30 (39.5%) were double lung transplantations, and 46 (60.5%) were single lung transplantations. Thirty-one recipients were alive 5 years after transplantation (12 double lung transplantations, 19 single lung transplantations). The 5-, 6-, and 7-year survival rates were 44%, 34%, and 29%, respectively. There was no association or difference in cytomegalovirus status, sex, and blood group between those who died within 5 years and those who survived beyond 5 years. The median percent predicted FEVs for single and double lung transplant recipients were as follows: 5 yrs-75%, 75%; 6 years-73%, 75%; 7 years-68%, 73%. The proportion of recipients with bronchiolitis obliterans syndrome according to published criteria was as follows: stage 0, 32%; stage I, 19%; stage II, 16%; and stage III, 19%. The functional status (i.e., active, working, disabled) 5 years after transplantation was as follows: active/working, 74%; active but not working, 13%; some limitation/independent, 10%; and disabled, 3%. CONCLUSION: Bronchiolitis obliterans syndrome is a frequent occurrence in long-term survivors. Nevertheless, in spite of this condition, most recipients have acceptable lung function, are active, and are generally working.

Activities of Daily Living↗

Management of Tracheal Neoplasms.

Patients with tracheal involvement from primary or secondary neoplasms usually present with relatively nonspecific symptoms of cough, wheeze, and shortness of breath. Prompt diagnosis often requires a high index of suspicion. Tomography or computed tomography of the chest will often confirm the presence of a tracheal lesion. A detailed rigid bronchoscopic assessment by an experienced thoracic surgeon is essential for establishing the extent of tracheal involvement. Although advanced tumor stage often precludes surgical resection, the application of current operative techniques allows a significant number of tracheal tumors to be completely excised and primarily reconstructed. Adjuvant radiotherapy is often employed with surgical resection to improve local control and enhance the potential for cure.

Journal Article↗

A reevaluation of heparin requirements for cardiopulmonary bypass.

We wished to determine if reduction in the standard heparin administration for cardiopulmonary bypass could be accomplished safely with the use of membrane oxygenators. An experimental study was designed to evaluate two different heparin administration protocols for cardiopulmonary bypass with hollow-fiber membrane oxygenators. Two groups of six pigs were submitted to hypothermic cardiopulmonary bypass (28 degrees C) for 3 hours, then rewarmed, decannulated, and reassessed after 1 hour. In group I (control) heparin was administered to maintain the activated clotting time in excess of 450 seconds; in group II activated clotting time was maintained between 250 and 300 seconds. The mean total heparin administered was 41,000 units in group I and 25,000 units in group II. Concentration of coagulation factors II, V, and VIII, fibrinogen, and platelet count were determined before, during, and 1 hour after bypass. No significant difference in any of these coagulation parameters was observed between the groups. The performance of the oxygenators was similar in both groups, with no evidence of thrombosis. Thus reduced heparin administration, enough to keep activated clotting time between 250 and 300 seconds, was not related either to major coagulation factors and platelet consumption or to derangements in the oxygenator's performance.

Animals↗

The effect and optimal time of administration of verapamil on lung preservation.

Calcium channel blockers have recently been shown to improve pulmonary and myocardial preservation. The effect of verapamil on hypothermic lung preservation was investigated using an isolated ventilated rabbit lung perfusion model. In phase 1, preserved lungs were not flushed prior to extraction. Four groups of five animals were studied: group 1 (no verapamil), group 2 (verapamil administration prior to extraction), group 3 (verapamil at reperfusion only), group 4 (verapamil both prior to extraction and at reperfusion). In phase 2, two groups of five animals received pulmonary artery flush with low potassium (4 mmol/L), 2% low-potassium dextran (LPD) solution; group 1 (without verapamil), group 2 (flush and reperfusion with verapamil). As in phase 1, lungs were stored for 30 hr at 10 degrees C prior to reperfusion. In phase 3, the protocol was identical to phase 2, except that the storage time was extended to 48 hr. PO2 (mean +/- SE) of effluent blood in lungs treated with verapamil prior to extraction (122.8 +/- 5.0 mmHg) was significantly increased in comparison with lungs not receiving verapamil (69.0 +/- 3.3 mmHg) or only receiving verapamil at the time of reperfusion (87.1 +/- 11.9 mmHg). Gas exchange after 30 hr storage was equivalent in lungs flushed with LPD with or without verapamil. However verapamil did provide an advantage when preservation times were extended to 48 hr (62.3 +/- 8.5 mmHg, 46.9 +/- 2.3 mmHg). Verapamil administered prior to lung extraction provides better lung function following preservation, but has benefit over LPD flush only with extended periods of preservation (48 hr).

Animals↗