Malignant fibrous histiocytoma of the lung. Report of four cases and review of the literature.

BACKGROUND: Primary malignant fibrous histiocytoma (MFH) of the lung is a rare clinical entity. Only 23 reports of 49 cases have been reported in the literature. Surgery was the primary mode of therapy, with high rates of local and distant recurrence reported. The role of radiation therapy and chemotherapy has never been clearly defined. METHODS: The records of the Mayo Clinic in Scottsdale and Rochester from 1970 to 1990 were reviewed for cases of primary pulmonary MFH. A review of the literature was also undertaken. RESULTS: Four cases from the Mayo records and 49 cases from a review of the literature were identified. Eight patients were alive at 5 years from diagnosis; all had been treated with surgery as the primary modality. No definite relationship between histologic subtype of MFH and survival could be identified and no definite role of radiation therapy or chemotherapy could be defined. CONCLUSIONS: MFH of the lung should be treated by surgical resection if technically feasible. The role of adjuvant therapy remains undefined.

Reoperation after valve repair for mitral regurgitation: early and intermediate results.

To better understand late outcomes of mitral valve repair, we reviewed the cases of 49 consecutive patients who underwent reoperation between January 1974 and May 1992 for recurrent valve dysfunction after previous valvuloplasty for mitral regurgitation. There were 27 men (55%) and 22 women, with a median age of 63 years (range 20 to 84 years). Original procedures included annuloplasty and posterior leaflet repair in 15 patients (31%), annuloplasty and anterior leaflet repair in 15 (31%), commissural plication in 13 (27%), and complex bileaflet repairs in six (12%). Median time between initial mitral repair and reoperation was 2.4 years (range 2 months to 25.3 years). Indications for reoperation included recurrent severe mitral regurgitation in 34 patients (70%), hemolytic anemia from mitral regurgitation in seven (14%), mixed mitral regurgitation and stenosis in seven (14%), and isolated mitral stenosis in one (2%). Before reoperation, 36 patients were in New York Heart Association functional class III and 11 were in class IV. Initial repairs were intact at the second operation in 32 patients (65%), and the etiology of recurrent mitral regurgitation in these patients was fibrosis or calcification of the anulus or leaflets in 22 patients, newly ruptured chordae in seven, and perforated leaflets in three. The causes of mitral regurgitation in the 17 patients whose initial repair had failed included dehiscence of commissural repairs in nine patients, dehiscence of ring annuloplasty in four, and break-down of chordal or leaflet repair in four. Patients with original repairs involving the anterior leaflet had a significantly shorter time between operations (p = 0.006). In eight patients (16%), the mitral valve was repaired again; in the remaining 41 patients (84%), prosthetic replacement was performed. Operative mortality rate was 4% (two patients). All eight patients who underwent mitral valve rerepair had no mitral regurgitation, trivial regurgitation, or mild regurgitation at discharge from the hospital. Follow-up was 100% complete at a mean of 5.1 years (range 1 to 19 years). Forty-one patients (87% were in New York Heart Association functional class I or II, and survival at 5 years was 75.3%. Of the eight patients who underwent a second repair, seven had no regurgitation, trivial regurgitation, or mild regurgitation at a median of 4 years' follow-up. The low mortality associated with reoperation supports an aggressive approach toward mitral regurgitation with initial repair. A second repair can be performed in selected patients with durable results at 4 years.

Radical resection of malignant thymoma with reconstruction of the mediastinal venous confluence.

Thymic tumors are classified as epithelial neoplasm, thymic carcinoids, and thymic carcinoma. Differentiation between benignity and malignancy of thymic epithelial tumors is determined on the basis of local tissue invasion. Surgery is the treatment of choice for locally invasive disease without signs of metastasis. We present a patient who underwent en bloc tumor excision with reconstruction of the mediastinal venous confluence using pericardium.

High risk of thromboemboli early after bioprosthetic cardiac valve replacement.

OBJECTIVES: We studied the rate of thromboembolism in patients undergoing bioprosthetic replacement of the aortic or mitral valve, or both, at serial intervals after operation and the effects of anticoagulant or antiplatelet treatment and risk factors. BACKGROUND: Thromboembolism appears to occur early after operation, but the incidence, timing and risk factors for thromboembolism and the role, timing, adequacy, effectiveness, duration and risk of anticoagulation and antiplatelet agents are uncertain. METHODS: The rate of thromboembolism was studied at three time intervals after operation (1 to 10, 11 to 90 and > 90 days) in 816 patients who underwent bioprosthetic replacement of the aortic or mitral valve, or both, at the Mayo Clinic from January 1975 to December 1982. The effect of antithrombotic therapy (warfarin, aspirin or dipyridamole, alone or in combination) was evaluated. RESULTS: Median follow-up of surviving patients was 8.6 years. The rate of thromboembolism (%/year) decreased significantly (p < 0.01) at each time interval after operation (1 to 10, 11 to 90 and > 90 days) for mitral valve replacement (55%, 10% and 2.4%/year, respectively) and over the first time interval for aortic valve replacement (41%, 3.6% and 1.9%/year, respectively). During the first 10 days, 52% to 70% of prothrombin time ratios were low (< 1.5 x control). Patients with mitral valve replacement who received anticoagulation had a lower rate of thromboembolism for the entire follow-up period (2.5%/year with vs. 3.9%/year without anticoagulation, p = 0.05). Of 112 patients with a first thromboembolic episode, permanent disability occurred in 38% and death in 4%. Risk factors for emboli were lack of anticoagulation, mitral valve location, history of thromboembolism and increasing age. Only 10% of aortic, 44% of mitral and 17% of double valve recipients had anticoagulation at the time of an event. Patients with bleeding episodes (2.3%/year) were older and usually underwent anticoagulation. Blood transfusions were required in 60 of 111 patients (1.2%/year), and 13 patients (0.3%/year) died. CONCLUSIONS: Thromboembolic risk was especially high for aortic and mitral valve replacement for 90 days after operation, and overall was increased with lack of anticoagulation, mitral valve location, previous thromboembolism and increasing age. Anticoagulation reduced thromboemboli and appears to be indicated in all patients as early as possible for 3 months and thereafter in those with risk factors, but needs prospective testing.

Reoperation on prosthetic heart values. Patient-specific estimates of in-hospital events.

Reoperation on prosthetic heart valves is increasingly under consideration for both clinical and prophylactic indications. To determine the correlates of hospital events, including in-hospital mortality, new persisting neurologic deficit, and length of postoperative stay, a three-institution study of 2246 consecutive prosthetic valve reoperations performed on 1984 patients between 1963 and 1992 was undertaken. The combined experience ranged from high-risk patients coming moribund to the operating room to an important number of well individuals undergoing prophylactic reoperations on potentially failing valves. The risk-unadjusted hospital mortality was 10.8%, neurologic deficit at hospital discharge 1.1%, and length of stay 10 days (median). Multivariably determined correlates of outcome included age at reoperation, degree, severity, and acuity of impairment of cardiac function, extensiveness of valvular heart disease, coexisting morbid conditions, number of previous heart operations, and concomitant procedures. The risk-adjusted hospital mortality for the first elective reoperation in a good-risk patient was 1.3% (90% confidence limits 0.3% to 4.4%), neurologic deficit 0.3% (90% confidence limits 0.02% to 1.8%), and length of postoperative stay 7 days (90% confidence limits 4 to 13), emphasizing the wide variance in outcome events. Equations were developed to permit wide application of the results of the study for quantitatively estimating the risk of outcome events based on individual preoperative patient characteristics. These estimates should be useful for informed patient consent, considerations of prophylactic valve replacement, and cost and resource use.

The risk of stroke in the early postoperative period following mitral valve replacement.

All patients (285) undergoing mitral valve replacement (MVR) with a Carpentier-Edwards (C-E) bioprosthesis +/- coronary bypass grafts (CABG) were reviewed (109 men and 176 women with a median age of 70 years). Overall, the 5-year survival rate was 58.9%, 62.7% for MVR (199 patients) and 50.1% for MVR+CABG (86 patients). Late survival was adversely affected by the operative time variables of NYHA class IV, older (> or = 70 years) age, low (> or = 56%) ejection fraction (EF), and the additional performance of associated procedures+CABG with MVR (P < or = 0.001). The 5-year freedom from stroke rate was 89.2%, 89.1% for MVR and 90.2% for MVR +/- CABG. Advanced heart class was the only significant variable associated with a greater risk of late stroke (P < or = 0.01). Neither chronic preoperative atrial fibrillation nor operative obliteration of the left atrial appendage increased or decreased the late risk of stroke in patients following MVR. Hazard function for stroke occurring in the first postoperative year (first 48 h excluded to discount intraoperative events) demonstrated the highest rate within the first month (40%), rapidly diminishing thereafter. This pattern was reproduced in the 12-year hazard function in that the rate of stroke occurrence was greatest in the first year (6.7%) following implantation. The mean stroke rate over 12 years was 2.5%. Strokes following MVR +/- CABG are more likely to occur in older and more compromised patients, and the higher early rate is not reflected in the mean rate. A more aggressive approach to early anticoagulation with IV heparin, Coumadin, and possibly antiplatelet therapy is advocated to reduce this complication rate.

Liposarcoma of the pleura.

Pleural liposarcomas are extremely rare; only eight cases have been reported in the literature. Herein we describe a 38-year-old man who had dyspnea on exertion and chest pain. Computed tomography of the chest revealed a large mass in the right pleural cavity. Thoracotomy was performed, and the patient recovered with no complications. Postoperative adjuvant irradiation was successful. In addition to the current case, we review the previously reported cases of pleural liposarcomas and discuss the treatment outcomes.

Thoracoscopic excision of a peripheral corticotropin-secreting pulmonary carcinoid tumor.

Bronchial carcinoid tumors are rare neuroendocrine neoplasms that arise from the Kulchitsky cells of the bronchial epithelium. These tumors can manifest as central carcinoid tumors, pulmonary carcinoid tumorlets, or peripheral carcinoid tumors. Occasionally, the peripheral carcinoid tumors produce corticotropin and result in Cushing's syndrome. Herein we report the first case of Cushing's syndrome associated with a peripheral pulmonary carcinoid tumor that was excised by video-assisted thoracoscopy. After excision, the patient had complete remission. Video-assisted thoracoscopy may be ideal for resecting a peripheral pulmonary carcinoid, especially in patients with debilitation but no evidence of metastasis.

Late results of valve replacement with the Björk-Shiley valve (1973 to 1982)

Cardiac valve replacement with use of only the Björk-Shiley prosthesis was performed in 1253 patients between January 1973 and December 1982. There were 828 patients having aortic valve replacement, 280 patients having mitral valve replacement, and 145 patients having double valve replacement with aortic and mitral valve prostheses. Patient outcome was stratified according to multiple variables, including valve position and valve model (spherical versus convexo-concave discs). No valve failure due to strut fracture was identified in 26 high-risk patients (mitral valve replacement with greater than or equal to 29 mm implanted in patients less than or equal to 50 years of age) followed up for a mean of 10 years postoperatively. Fifteen patients had late thrombosis of their Björk-Shiley prosthesis (0.28 per 100 patient-years), but there was no significant difference in risk of valve thrombosis comparing the spherical and convexo-concave discs (0.27 per 100 patient-years versus 0.27 per 100 patient-years). One hundred two patients had 128 thromboembolic episodes; rates of thromboembolism after aortic valve replacement, mitral valve replacement, and double valve replacement were 2.1, 4.3, and 4.6 per 100 patient-years, respectively. Percentages of patients free from thromboemboli after aortic valve replacement, mitral valve replacement, and double valve replacement were 93% +/- 1%, 86% +/- 2%, and 89% +/- 3% at 5 years postoperatively and 87% +/- 2%, 79% +/- 5%, and 77% +/- 8% 10 years postoperatively. There was no significant difference in the rates of thromboemboli for spherical and convexo-concave discs for all patients and for each of the subgroups. Ten-year actuarial survival estimates for patients dismissed alive from the hospital after aortic valve replacement, mitral valve replacement, and double valve replacement with the Björk-Shiley valve were 65% +/- 4%, 63% +/- 5%, and 55% +/- 8%, respectively. Overall event-free survival (freedom from death, thromboembolism, anticoagulant-related bleeding, endocarditis, and reoperation) was similar for the three patient groups. Performance of the Björk-Shiley valve as judged by late patient follow-up is similar to other mechanical valves, and modifications in disc design do not appear to have reduced the threat of late valve thrombosis and thromboemboli. Evidence does not support elective explantation of this prosthesis.

Early and late results after isolated coronary artery bypass surgery in 159 patients aged 80 years and older.

We have studied 159 patients 80 years of age or older who have had isolated coronary artery bypass grafting (CABG) since 1977. Eighty-seven percent have had surgery since 1984. Two thirds of the patients were male, and the mean age was 82 years. Most patients (97%) were in New York Heart Association (NYHA) functional class III or IV, 89% had unstable/postinfarction angina pectoris, and 67% had rest pain. Almost half (47%) required preoperative admission to the coronary care unit, 6% required preoperative use of an intra-aortic balloon pump, and 20% were operated on emergently. Significant left main coronary artery disease (greater than or equal to 50% stenosis) was present in 41%. Ten patients (6.3%) died within 30 days of surgery, with seven more patients dying during the same hospital admission or soon after transfer to another institution. This resulted in an overall hospital mortality of 10.7%. The median hospital stay was 10 days. On univariate analysis, the significant predictors of hospital mortality were NYHA IV, angina at rest, preoperative admission to the coronary care unit, emergency operation, ejection fraction less than 0.50, and the presence of mitral regurgitation. On multivariate analysis, ejection fraction less than 0.50 was the only significant risk factor (p less than 0.01). Of hospital survivors, 98% have been followed for a mean of 29 months. The estimated 5-year survival (+/- SEM) of all patients was 71 +/- 4.5%, and for hospital survivors, 80 +/- 4.5%. The most important predictor of adverse survival was an ejection fraction less than 0.50. Seventy-nine percent are angina-free, and 89% are in NYHA classes I and II. The majority of patients felt that they were improved by surgery. We conclude that CABG in patients 80 years or older, although associated with increased operative risk, gives excellent relief of symptoms and good 5-year survival. Patients should not be denied CABG because of age alone.

Thrombotic obstruction of disc valves: clinical recognition and surgical management.

Twenty-seven patients underwent reoperation because of thrombotic obstruction of a disc-type cardiac valve prosthesis. Preoperative clinical features included effort dyspnea in 81%, new-onset angina in 44%, a new murmur in 89%, and an abnormal opening or closing sound associated with the prosthetic valve in 56%. Symptoms were present for 1 week or more before reoperation in 86%, although many patients were referred only after acute exacerbation of heart failure and development of pulmonary edema. Noninvasive studies confirmed prosthetic valve malfunction in only 33%, but cardiac catheterization documented thrombotic obstruction in all 15 patients in whom it was performed. In 14 of the 27 patients, prothrombin time was in the therapeutic range at the time of admission. Prompt reoperation for valve replacement or thrombectomy was performed with an operative mortality of 11%, and long-term outcome was satisfactory in all but 1 hospital survivor. These findings emphasize the importance of considering the diagnosis of thrombosed heart valves in patients with mechanical heart valves who are seen with nonspecific symptoms.

The outcome of surgical treatment of hypertrophic obstructive cardiomyopathy. Experience over 15 years.

From 1972 through 1987, 115 patients between the ages of 1 and 83 years (mean, 44.5 years) underwent operation for hypertrophic obstructive cardiomyopathy. Methods of relief of left ventricular outflow obstruction were septal myectomy/myotomy (n = 109), mitral valve replacement (n = 4), and myectomy/myotomy plus mitral valve replacement (n = 2); concomitant procedures included coronary artery bypass (n = 19) and aortic valve replacement (n = 9). Systolic gradient (peak-to-peak) from the left ventricle to the aorta decreased from 70 +/- 38 mm Hg (mean +/- standard deviation) to 9 +/- 11 mm Hg. There were six hospital deaths, for an overall operative risk of 5.2%; one death occurred among 83 patients less than age 65 years (operative risk, 1.2%), and five deaths occurred in 32 older patients (operative risk, 15.6%; p = 0.008 for difference between age groups). Four (22.2%) of 18 patients with a residual gradient greater than 15 mm Hg died, compared with two (2.1%) of 97 patients with a lower gradient (p = 0.003). Follow-up ranged from 0.5 to 16 years (mean, 5.1 years), and 5-year actuarial survival rate, including hospital deaths, was 84% +/- 4%. The 5-year survival rate was decreased in patients who had operative procedures other than myectomy/myotomy (69% versus 91%, p less than 0.005) and in patients aged 65 years or older (54% versus 93%, p less than 0.005). No correlation was found between preoperative symptoms, functional class, left ventricle-aorta pressure gradient, or mitral valve insufficiency and operative or late mortality. Preoperative symptoms were relieved in 57 (76%) of 75 patients with dyspnea, 49 (83%) of 59 patients with angina, and 22 (96%) of 23 patients with syncope. This experience confirms the effectiveness of operation for relief of symptoms in patients with the obstructive form of hypertrophic cardiomyopathy. The current operative mortality rate is low, especially in patients less than 65 years of age (1.2%). Our experience suggests that incomplete relief of left ventricular outflow obstruction may increase the risk of early postoperative death.

Repair of tricuspid valve insufficiency in patients undergoing double (aortic and mitral) valve replacement. Perioperative mortality and long-term (1 to 20 years) follow-up in 109 patients.

Between 1965 and 1984, 109 patients underwent simultaneous aortic and mitral valve replacement and tricuspid valve repair at the Mayo Clinic, with a perioperative mortality of 21%. The only variable predictive of perioperative mortality on multiple regression analysis was New York Heart Association class IV disability. The median follow-up was 5.6 years (range 1 to 20 years). Cumulative 5-, 10-, and 15-year survival rates in patients discharged from the hospital were 70% +/- 5%, 42% +/- 6%, and 33% +/- 7%. Multivariate analysis identified advanced age and class IV disability as significant predictors of poor survival. Five-year survival rates were similar in patients undergoing operation between 1965 and 1974 and after 1975, despite an increase in age and in the severity of preoperative symptoms in the recent group. Late mortality was due to sudden death in 38% of the patients, heart failure in 21%, reoperation in 5%, endocarditis in 2%, and thromboembolism and bleeding in 4%. Late complications included systemic emboli in 22% (embolism rate 4.5 events/100 patient-years), bleeding in 17%, reoperation in 14%, myocardial infarction in 8%, permanent pacemaker implantation in 5%, and infective endocarditis in 3%. Of 43% of the patients still alive, 79% are in class I or II.

The association of unexplained gastrointestinal bleeding with calcific aortic stenosis.

The association of chronic gastrointestinal bleeding and aortic stenosis remains problematical. The cases of 91 patients (age 38 to 80 years) with these disorders who were examined between 1955 and 1975 were reviewed to address this controversy. All patients underwent upper and lower gastrointestinal radiography, small bowel series, and proctoscopy. Other studies were endoscopy in 84 patients, colonoscopy in 61, and visceral angiography in 16. Of the 37 patients who underwent abdominal exploration, 35 (95%) continued to bleed postoperatively, including 8 of 10 patients who had bowel resection for angiodysplasia. Forty patients did not have an abdominal operation, and all have continued to bleed. Sixteen patients (2 of whom had had an abdominal procedure) underwent aortic valve replacement for aortic stenosis. There were 2 intraoperative deaths among these 16 patients. At follow-up, which ranged from 8 to 12 years, only 1 patient who underwent aortic valve replacement had recurrent bleeding secondary to excessive anticoagulation. Thus, overall, gastrointestinal operation was successful in only 5% of patients, but aortic valve replacement was effective in 93%. For unexplained gastrointestinal bleeding associated with aortic stenosis, aortic valve replacement should be considered because of the likelihood of cure.

Coronary artery disease and its management: influence on survival in patients undergoing aortic valve replacement.

Data from 1,156 patients greater than or equal to 30 years of age who underwent aortic valve replacement alone or with coronary artery bypass grafting from 1967 through 1976 (early series) and 227 similar patients operated on during 1982 and 1983 (late series) were reviewed. In the early series, 414 patients (36%) had preoperative coronary arteriography (group 1): group 1A (n = 224) did not have coronary artery disease, group 1B (n = 78) had coronary artery disease but did not undergo bypass grafting and group 1C (n = 112) had coronary artery disease and underwent bypass grafting. The 742 patients in group 2 did not have preoperative arteriography. Operative mortality rates (30 day) in groups 1A, 1B, 1C and 2 were 4.5, 10.3, 6.3 and 6.3%, respectively (p = NS). The 10 year survival in both groups 1 and 2 was 54%; in groups 1A, 1B and 1C it was 63, 36 and 49%, respectively (1A and 1B, p less than 0.01). In the late series, the 227 patients were divided into similar groups (group 1A, n = 73; 1B, n = 32; 1C, n = 99), and 90% had preoperative coronary arteriography. Operative mortality rates (30 day) for groups 1A, 1B and 1C were 1.4, 9.4 and 4.0%, respectively; that for group 2 (no preoperative arteriography, n = 23) was 4.3%. Definition of coronary anatomy by angiography seems important in most patients greater than or equal to 50 years old who are candidates for aortic valve replacement, and bypass grafting is recommended for those with significant coronary artery disease.

Repair of ascending aortic dissection. Influence of associated aortic valve insufficiency on early and late results.

Operative treatment of dissections of the ascending aorta differs from that for the descending aorta, not only because of the need for cardiopulmonary bypass, but also because of the frequent occurrence of aortic valve insufficiency. To determine the early and late results of operative repair, we have reviewed the case histories of 121 consecutive patients who underwent repair of ascending aortic dissections between 1962 and 1985. Ages ranged from 16 to 79 years (mean 56 +/- 14 years); 54 patients had operation within 2 weeks of onset of symptoms (acute), and the remainder had later repair (chronic). Seventy patients (58%) had clinical evidence of aortic insufficiency at the time of admission. During repair of acute dissection, 10 patients (19%) had aortic valve resuspension and 15 patients (28%) had aortic valve replacement. During repair of chronic dissection, eight patients (12%) had resuspension and 43 patients (64%) had replacement. Overall operative mortality was 22%, significantly higher for patients with acute than for those with chronic dissections (39% versus 9%, p less than 0.01). Operative risk was similar for patients who underwent repair of ascending aortic dissections without valve resuspension or replacement (31%) versus those who had repair with aortic valve resuspension (17%) or replacement (17%). During a follow-up period ranging from 1 to 208 months, aortic regurgitation developed in only two patients who did not have aortic insufficiency at the time of repair. Late aortic regurgitation necessitating reoperation developed in one of the 15 survivors who had aortic valve resuspension. Eight patients undergoing aortic valve replacement had complications of their prostheses, including one periprosthetic leak and four mechanical failures. We conclude that resuspension or replacement of the aortic valve does not increase the risk of repair of ascending aortic dissections. Selective management of aortic insufficiency (with valve repair whenever possible) yields satisfactory long-term results.

Temporal changes in the causes of aortic stenosis: a surgical pathologic study of 646 cases.

Among 646 patients with pure aortic stenosis who underwent valve replacement at our institution between 1981 and 1985, the three most frequent causes were calcification of congenitally bicuspid aortic valves (38%), degenerative (senile) calcification of tricuspid aortic valves (33%), and postinflammatory (presumably rheumatic) calcification and fibrosis (24%). Among the 324 patients younger than 70 years of age, calcified bicuspid valves were observed in 50%. In contrast, among 322 patients 70 years of age or older, degenerative calcification accounted for 48% of the stenotic aortic valves. During the 5 years of the study, the relative frequency of postinflammatory disease decreased from 30% to 18%, and that of bicuspid valves decreased from 37% to 33%. In contrast, the relative frequency of degenerative calcification increased from 30% to 46%. Consequently, degenerative (senile) calcification is currently the most common cause of aortic stenosis among patients undergoing valve replacement at our institution. This finding may be related to changes in life expectancy in the general population, alterations in patient referral practices, and an increased willingness of surgeons to operate on older patients. Regardless of cause, the observed temporal changes in etiologic factors for aortic stenosis may indicate a potential source of increasing health-care costs among the elderly population.

Influence of antioxidants (mannitol and allopurinol) on oxygen free radical generation during and after cardiopulmonary bypass.

Oxygen-derived free radicals (O2-, H2O2, OH.) are produced during oxidative metabolism, ischemia and reperfusion, and cardiopulmonary bypass (CPB). When oxygen free radical production exceeds scavenging capacity, peroxidation of structural lipids in cell membranes can occur with potentially injurious consequences. In this prospective study, 45 patients were evaluated to determine the effect of CPB on oxygen free radical generation. Twenty patients in group I were controls. Exogenous oxygen free radical antioxidants were administered before bypass to patients in group II (n = 15, mannitol) and group III (n = 10, allopurinol). In group I, plasma H2O2 increased during extracorporeal circulation from 65 +/- 6.0 to 125 +/- 12 microM/ml (p less than .001). At similar sampling intervals, plasma H2O2 levels were significantly lower in group II (p less than .03) and group III (p less than .05) when compared with those in group I. Red blood cell H2O2 did not change in group I or group II. White blood cell H2O2 levels decreased in group I (p less than .04) and group II during CPB. (Intracellular concentrations of H2O2 were not obtained in group III patients). We conclude that cytotoxic oxygen radicals are generated during CPB and that pretreatment with free radical antioxidants, mannitol or allopurinol, may minimize the free radicals available for lipid peroxidation of biomembranes.