Chronic pulmonary thromboembolism in dogs treated with tranexamic acid.

BACKGROUND: Many questions remain regarding the pathogenesis, natural history, diagnosis, and treatment of chronic thromboembolic pulmonary hypertension in patients. To answer such questions, we developed an animal model of this disorder. The brisk thrombolytic response of canines to acute embolism has, previously, prevented the establishment of such a model. METHODS AND RESULTS: The fibrinolytic inhibitor tranexamic acid was given orally to canines before, and for intervals after, pulmonary emboli were released from venous thrombi formed in vivo in femoral veins or the inferior vena cava. Preliminary studies disclosed that embolic residuals from femoral vein thrombi were not sufficient to cause significant, persistent pulmonary hypertension. With repetitive, larger thrombi embolized from the inferior vena cava, however, persistent pulmonary hypertension was achieved in most animals. CONCLUSIONS: Resolution of emboli in the canine can be inhibited by tranexamic acid. As in humans, a spectrum of embolic residuals is encountered, and the perfusion lung scan consistently underestimates the extent of embolic residuals. Studies of this animal model continue.

Treatment of end-stage chronic obstructive pulmonary disease with double lung transplantation.

Six patients with end-stage emphysema (age 44 +/- 2 years) underwent double lung transplantation (Tx) from June 1988 through May 1990. All suffered from severe inanition and required oxygen therapy. The ischemic time was 193 +/- 28 minutes. Post-Tx immune suppression was OKT3 (14 days), cyclosporine (trough levels of 150 +/- 25 ng/ml), azathioprine to keep WBC at 3,000 to 5,000/cu mm (1 to 3.0 mg/kg/day) and following OKT3, a tapering prednisone regimen. Two rejection episodes that occurred in two patients on post-Tx day 5 and 10 were treated with bolus doses of methylprednisolone. The mean hospital stay was 32 +/- 7 days (range, 20 to 69 days). Four patients required treatment of cytomegalovirus (CMV) infection: gastritis (+donor, +recipient) in one and CMV pneumonia in two (+donor, -recipient). A fourth (+donor, -recipient) had right-sided Candida empyema six weeks post-Tx, developed CMV and staphylococcal sepsis, and died 64 days post-Tx. One patient required pyloroplasty eight weeks post-Tx and one patient underwent tracheal suture line repair at eight weeks. During a follow-up of 81 patients months (range, 8 to 24 months), one patient had developed Epstein-Barr viral (EBV) induced lymphoproliferative disease in the lung and one patient had developed EBV lymphoma. Three patients are at work, one is continuing rehabilitation, and one is at home. Double lung Tx offers a definitive benefit to patients with emphysema; however, a prolonged postoperative course can be expected. Viral infections remain serious but treatable problems.

Comparative effects of transdermal clonidine and oral atenolol on acute exercise performance and response to aerobic conditioning in subjects with hypertension.

We compared the effects of transdermal clonidine and oral atenolol on acute exercise performance and on conditioning response to an 8-week program of regular aerobic exercise in young, otherwise healthy subjects with mild hypertension. The study was a double-blind, randomized, parallel-group study with placebo control. Twenty-seven subjects (11 receiving transdermal clonidine, 8 receiving oral atenolol, and 8 receiving placebo) completed the study. Atenolol controlled blood pressure in all 8 subjects, vs 6 of 11 in the transdermal clonidine group and 0 of 8 in the placebo group. Both active drugs lowered systolic blood pressure during exercise. With clonidine treatment, the antihypertensive effect during exercise was smaller and was observed only at low and moderate workloads. Acute exercise performance (subjects receiving drug but still unconditioned) was assessed by endurance time at a constant workload equal to the highest workload completed on a previous 2-minute incremental exercise test. Endurance time was reduced 35% by atenolol but not by transdermal clonidine or placebo. Neither active drug interfered with the progress of the conditioning program, as measured by gradual lengthening of exercise time. However, as assessed by change in oxygen uptake standardized to a heart rate of 170 beats per minute, the improvement in conditioning was twice as great in subjects receiving transdermal clonidine and placebo (+20%, +18%) as it was in those receiving atenolol (+8%). Subjects receiving placebo and transdermal clonidine lost weight; subjects receiving oral atenolol gained weight. The changes in weight were small.