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Aim: Mitral valve repair for degenerative disease is widely accepted. Because of low risk and excellent late outcomes, surgical intervention is recommended increasingly early when repair appears possible. The place of repair vis a vis continued medical therapy in the elderly, however, is less well defined as there are scant data on their surgical risk. We reviewed our recent results with mitral valvuloplasty for degenerative disease with attention to the influence of age., Methods: Thirty-day results of mitral valvuloplasty for degenerative disease between January 1996 and April 2000 were examined retrospectively. Patients with ischemic etiology were excluded. Results among those over age 70 years were compared with younger patients., Results: Of 140 patients (78 men and 62 women) aged 27 to 91 (mean 62+/-13) years (44 gs;70 years of age), 61 underwent isolated mitral valvuloplasty, 71 mitral valvuloplasty and coronary artery bypass, and 8 mitral valvuloplasty with other procedures. By multivariate analysis preoperative cardiogenic shock (0.001), but not age, was as a risk factor for death. Among patients stratified by age gs; or <70, there were differences in atrial fibrillation (47.7% vs 29.2%, p=0.03), prolonged ventilation (31.8% vs 15.6%, p=0.03) and hospital stay (median 9.5, range 5-285 vs median 6.5, range 2-36, p=0.001), but not 30-day readmission (15.9% vs 22.9%) or death (5.2% vs 9.1%, p=0.49)., Conclusion: Operative results for mitral valvuloplasty in the elderly are acceptable. Surgery should not be withheld on the basis of age alone.

Background: The purpose of this study was to determine which factors influenced performance on the Thoracic Surgery In-Training Examination (TSITE) and whether the addition of a cardiac-specific didactic study course improved scores., Methods: Between 1989 and 2002, 59 TSITE scores (overall, cardiac [C-TSITE], and thoracic [T-TSITE]) were collected from 33 residents (23 cardiac track, 10 thoracic). Factors assessed with univariate and multivariate analysis included calendar year, year of training (31 year I, 28 year II), standardized test-taking history (average National Board and American Board of Surgery in-training scores), subjective faculty assessment of cardiothoracic knowledge, months on cardiac versus thoracic service, clinical performance, and participation in a cardiac-specific didactic series with faculty lectures and board question reviews (12 residents)., Results: Cardiac-track residents had higher C-TSITE percentile scores (53% +/- 27% versus 38% +/- 27%, p < 0.05), whereas thoracic-track residents had higher T-TSITE scores (70% +/- 24% versus 51% +/- 25%, p < 0.01). Multivariate analysis identified 3 factors associated with higher overall TSITE scores: standardized test-taking history (p < 0.001), subjective faculty assessment of knowledge (p < 0.001), and year of training (p < 0.007). Inclusion in the cardiac-specific didactic series did not affect C-TSITE scores (50% +/- 30% versus 48% +/- 27%, p > 0.82) or overall TSITE scores (p > 0.23)., Conclusions: Standardized test-taking history and subjective faculty assessment of knowledge were associated with higher TSITE scores, but implementation of a cardiac-specific didactic series had no influence. These findings suggest that independent study and reading may be the best way to improve TSITE scores.

Background: It has been well established that complete revascularization with internal mammary artery (IMA) grafting is important in young patients undergoing coronary artery bypass grafting (CABG). Applying these principles to octogenarians remains controversial., Methods: From 1986 to 1999, 358 consecutive patients aged 80 to 94 years underwent CABG. Revascularization was complete in 291 (81%) and incomplete in 67 (19%). The IMA was used in 231 (65%) cases., Results: Operative mortality was 7% +/- 1%, but was not statistically different with or without IMA grafting (IMA 5% +/- 2% versus no IMA 10% +/- 3%, p = 0.11) or complete revascularization (p > 0.41). Midterm survival improved with IMA grafting (70% +/- 3% versus 56% +/- 5% at 4 years, p < 0.03; 36% +/- 4% versus 29% +/- 5% at 8 years, p < 0.08), but was not significant beyond 8 years. Among 138 survivors, those with IMA grafts were more likely to be angina free (82% versus 53%, p < 0.001) and in New York Heart Association class I (60% versus 36%, p < 0.03). Survival, recurrent angina, and functional class were independent of completeness of revascularization (p > 0.21)., Conclusions: IMA grafting improved survival, angina, and functional class of octogenarians, but complete revascularization did not have a similar impact.

Background: The extent of proximal and distal aortic resection that should be performed for acute type A aortic dissections remains controversial., Methods: From 1984 to 1999, 119 patients underwent repair of an acute type A dissection. Distal resection was to the ascending aorta in 78 (66%) and hemiarch in 41 (34%) patients. Proximally, the aortic valve was preserved in 69 (58%) patients, 40 (34%) underwent composite valve grafting, and 10 (8%) underwent separate graft and valve replacement., Results: Operative mortality was higher for separate graft and valve (50%+/-16%) than for valve preservation (16%+/-5%) or composite grafts (20%+/-7%) (p < 0.05). Hemiarch replacement did not increase operative risk compared to distal reconstruction to the ascending aorta (17%+/-6% versus 22%+/-5%, p > 0.71). At 10 years, freedom from reoperation was 81%+/-7% and long-term survival was 60%+/-8%, but neither was related to the proximal or distal surgical technique (p > 0.15). Risk factors for late reoperation included a nonresected primary tear and Marfan syndrome (p < 0.05)., Conclusions: An aggressive surgical approach, including a full root or hemiarch replacement, is not associated with increased operative risk and should be considered when type A dissections extensively involve the valve, sinuses, or arch.

Background: The optimal management of aortic valve disease in patients >80 years old depends on functional outcome as well as operative risks and late survival., Methods and Results: We retrospectively identified 133 patients (62 men, 71 women) aged 80 to 91 years (mean 84+/-3 years) who underwent aortic valve replacement alone or in combination with another procedure between January 1, 1993, and April 31, 1998. Demographics included hypertension 68%, diabetes mellitus 17%, and history of stroke 11%. Operative (30 day) mortality rate was 11%. Urgent or emergent surgery, aortic insufficiency, and perioperative stroke or renal dysfunction were risk factors for operative death by multivariable analysis. Intensive care unit and total hospital length of stay were prolonged at 6.2 and 14.7 days, respectively. Late follow-up between July 1, 1998, and November 1, 1999, was 98% complete. Actuarial survival at 1 and 5 years was 80% and 55%, respectively. Predictors of late mortality were preoperative or perioperative stroke, chronic obstructive pulmonary disease, aortic stenosis, and postoperative renal dysfunction. The mean New York Heart Association functional class for 65 long-term survivors improved from 3.1 to 1.7. Quality of life assessed with the Medical Outcomes Study Short Form-36 was comparable to that predicted for the general population >75 years old., Conclusions: Functional outcome after aortic valve replacement in patients >80 years old is excellent, the operative risk is acceptable, and the late survival rate is good. Surgery should not be withheld from the elderly on the basis of age alone.

Background: Intrinsic abnormality of the aortic wall may explain the association of bicuspid aortic valves with ascending aortic aneurysms. Separate valve and graft repair of such lesions, rather than composite valve graft replacement, is more straightforward but leaves potentially abnormal sinuses behind., Methods: Between January 1985 and January 1998, 45 patients underwent separate valve and graft (n = 27) or composite valve graft (n = 18) for an ascending aortic aneurysm and bicuspid aortic valve. Perioperative events and late results were compared., Results: Patients undergoing separate valve and graft were older (mean age, 60 +/- 13 vs 42 +/- 12 years, p < 0.001) and were more likely to have purely stenotic (48% vs 6%, p = 0.003) than purely regurgitant (11% vs 72%, p < 0.001) disease. They were also more likely to require concomitant coronary artery bypass grafting (56% vs 6%, p = 0.001). There were no significant differences in operative risk and no known late complications related to recurrent aneurysms., Conclusions: Root replacement with a composite valve graft can be accomplished with low operative risk and is the first choice for repair of this lesion. Separate valve and graft repair, however, yields satisfactory early and late results and remains an acceptable option, especially when the coronary ostea are not displaced or when concomitant procedures must be performed.

Background: The development of new technologies such as transmyocardial laser revascularization and, more recently, local delivery of angiogenic growth factors has refocused attention on the surgical management of diffuse coronary artery disease. In some cases, coronary endarterectomy is also technically feasible. To facilitate decision-making among these options, we reviewed our experience with coronary endarterectomy to determine the results to be expected with this more traditional approach., Methods: A search of our computerized database identified 7,096 patients undergoing myocardial revascularization between January 1, 1986 and March 30, 1997, of whom 177 (2.3%) underwent endarterectomy of at least one coronary artery. Perioperative events were derived from the database. Follow-up information was obtained from patients at 3 months to 11.5 years (mean = 55.7 +/- 38.8 months) after surgery., Results: Endarterectomy was performed on the right coronary artery (RCA) system in 100 patients, the left anterior descending (LAD) system in 52, the circumflex system in 18, and in multiple distributions in 7. The 30-day mortality was 7% for RCA, 0% for LAD, 17% for circumflex, and 14% for multi-system endarterectomy (p = 0.20). There were no statistically significant differences in perioperative myocardial infarction or ventricular dysrhythmia between these groups. Actuarial survival at 5 years was 76% for patients undergoing RCA endarterectomy and 75% for left sided (LAD or circumflex) endarterectomy (p = 0.91). At late follow-up, 74% (86/117) of survivors were angina-free, 6% (7/117) had undergone subsequent angioplasty, and 3% (4/117) had undergone subsequent surgery., Conclusions: Coronary endarterectomy can be accomplished with acceptable operative risk and good long-term results, even when applied in a highly selective manner. The results of novel therapies for diffuse coronary artery disease should be considered in the context of those achievable with more traditional approaches.

Background: Proximal anastomosis of the radial artery to the side of the internal thoracic artery (ITA) permits complete arterial revascularization in most patients, with the aim of improving long-term results of coronary artery bypass through greater long-term graft patency. The short-term results, however, have yet to be defined. We therefore reviewed our early experience with this grafting strategy., Methods: Between October 1, 1993, and September 1, 1998, 649 patients aged 30 to 85 years (mean, 60+/-10 years) had primary coronary artery bypass using an ITA and radial artery in a T-graft configuration. Left ventricular function was severely depressed (ejection fraction <35%) in 12%, and left main stenosis was present in 14%., Results: A total of 937 distal anastomoses were performed with the left ITA (1.4 per patient) and 1,452 with the radial artery (2.2 per patient). There was one perioperative death (0.2%). There were 32 (5%) q-wave myocardial infarctions, and 14 patients (2%) had transient low output syndrome. There was one episode of hypoperfusion corrected by lengthening the left ITA. Angiography for clinical indications in 27 patients 1 to 35 months postoperatively (mean, 9.5+/-8.3 months) demonstrated a distal anastomotic patency of 100% for ITA and 82% for radial artery grafts., Conclusions: Complete arterial revascularization can be achieved with an ITA and radial artery T-graft with low operative risk and acceptable early patency. These results support the continued investigation of this grafting strategy.

There has been only one previous report of an intracardiac gastrinoma causing Zollinger-Ellison syndrome. In this communication we describe the successful surgical resection of a gastrinoma located in the interventricular septum using cardiopulmonary bypass, blood cardioplegia, and mild hypothermia. Preoperative evaluation and histologic examination of the resected tumor strongly suggest that this was a primary intracardiac gastrinoma.

Background: Retrograde perfusion preserves ischemic myocardium when initiated shortly after coronary artery occlusion. However, benefits diminish as the delay increases. In this study, we used this technique to deliver agents known to reduce the injury associated with the reperfusion of ischemic myocardium. We proposed that the local delivery of lidocaine or L-arginine before reperfusion would reduce the damage caused during reperfusion, even after a delay between onset of ischemia and intervention designed to approximate clinical reality., Methods: In a porcine model of myocardial ischemia, the left anterior descending coronary artery was snared immediately distal to its second diagonal branch. After 1 hour of occlusion, 34 animals were randomized into six groups: no intervention (control) (n = 6); administration of normal saline solution into the great cardiac vein (Retro-NS) (n = 6); administration of lidocaine either intravenously (i.v.-LID) (n = 6) or retrograde (Retro-LID) (n = 6); and administration of L-arginine either intravenously (i.v.-L-ARG) (n = 5) or retrograde (Retro-L-ARG) (n = 5). After 90 minutes of ischemia, the snare was released, and the myocardium was reperfused for 3 hours. Two-dimensional echocardiograms were made prior to occlusion and 60, 150, 210, and 270 minutes after occlusion. The infarct size and the area at risk were determined by lissamine green and triphenyltetrazolium chloride staining with computer planimetric quantification. Regional wall motion was assessed by a wall motion score: normal = 1; mild hypokinesia = 2.0; severe hypokinesia = 2.5; and akinesia = 3., Results: The area of the left ventricle at risk for infarction was similar in all groups and represented 25.4% (5.2% [standard deviation]) of the left ventricular mass (p = 0.63). The percent area of infarction in the area at risk after 3 hours of reperfusion was 76.7% (7.1% for the control group, 73.9% (5.7%) for the Retro-NS group, 72.1% (8.7%) for the i.v.-LID group, 54.5% (10.2%) for the Retro-LID group, 58.8% (4.0%) for the i.v.-L-ARG group, and 54.3% (4.0%) for the Retro-L-ARG group p < 0.005, Retro-LID and Retro-L-ARG versus Control, Retro-NS, and i.v.-LID; p < 0.03, i.v.-L-ARG versus control and Retro-NS). No significant difference in wall motion scores between groups was detected by echocardiography (p = 0.578)., Conclusions: Retrograde delivery of lidocaine or L-arginine before reperfusion reduces infarct size without acutely affecting wall motion after 90 minutes of ischemia and 3 hours of reperfusion. Lidocaine must be present before reperfusion to have an effect, whereas L-arginine is beneficial if it is delivered at the time of reperfusion.

Background: The risk of aortic valve replacement (AVR) after previous coronary artery bypass grafting (CABG) is controversial. Its magnitude influences the threshold for recommending this procedure and has been cited in arguments regarding the optimal management of mild aortic stenosis at primary CABG. We therefore reviewed our experience with reoperative AVR +/- CABG and the primary combined procedure., Methods: Between January 1, 1985, and June 30, 1996, 427 patients underwent primary AVR+CABG, and 52 underwent AVR +/- CABG after prior CABG. Demographics, operative characteristics, and operative results were compared between groups. Data for all patients were pooled and analyzed collectively for risk factors influencing mortality., Results: The extent of native coronary artery disease and the incidence of prior myocardial infarction and stroke were greater in the reoperative group. Aortic cross-clamp and cardiopulmonary bypass times were slightly shorter, and fewer distal anastomoses were performed in the reoperative group. Operative mortality (primary group, 6.3% versus reoperative group, 7.4%) and morbidity were similar. Stepwise multivariate logistic regression analysis identified age, perioperative myocardial infarction, intraaortic balloon support, ventricular arrhythmia, perioperative stroke, and development of renal failure or acute respiratory distress syndrome, but not reoperative status, as predictors of mortality., Conclusions: The risk of AVR after previous CABG is similar to that for primary AVR+CABG. Valve replacement should, therefore, be pursued despite prior CABG when hemodynamically significant aortic stenosis develops. Furthermore, a circumspect approach to "prophylactic" AVR for mild aortic stenosis at primary CABG seems warranted.

Background: Short-term studies suggest that cardiac transplant immunosuppression without maintenance corticosteroids is feasible in selected patients. However, concern exists as to the long-term effects, specifically the possibility of increased morbidity and mortality because of late allograft rejection and allograft coronary artery disease., Methods: We retrospectively reviewed the records from 441 consecutive heart transplantation procedures done in 416 patients with use of an immunosuppressive protocol that attempted corticosteroid withdrawal within 2 months of transplantation. forty-two patients died or underwent retransplantation during the first 3 months and were excluded from further analysis. Analysis focused on demographic and long-term outcome variables (including death, rejection, retransplantation, and infection)., Results: Thirty percent (111) of eligible patients (374) met the definition of successful early steroid withdrawal. Only male gender independently predicted successful withdrawal. Mortality, both short and long term, was significantly lower in patients in whom successful early withdrawal from corticosteroids was achieved than in patients in whom the early attempts failed (1.7% per year versus 4.7% per year; p < 0.0001). The prevalence of late acute allograft rejection (more than 1 year after transplantation) was lower in patients successfully withdrawn from steroid therapy early after transplantation (0.07 pt-yr of follow-up versus 0.15 pt-yr; p = 0.002). Multivariate analysis of the entire group identified incidence of infection (p = 0.001), older age (p = 0.001), failed early steroid withdrawal (p = 0.006), and female gender (p = 0.016) as independent predictors of mortality., Conclusions: Successful early corticosteroid withdrawal identifies a subgroup of "immunologically privileged" patients with a low risk for long-term mortality and is not associated with an increased prevalence of late rejection or clinically significant coronary artery disease.

In summary, the National Database Committee's Audit and Validation Subcommittee is working to maximize the data completeness and quality of the STS National Database. Toward this end, we welcome your suggestions for improvement.

In spite of study findings that incriminated hyperkalemia as the toxic factor of cardioplegic solutions, the results of later experiments documented the safety and effectiveness of osmotically balanced hyperkalemic solutions in patients undergoing cardiac surgical procedures. The concepts of hyperkalemic cardioplegia and the early animal and clinical studies leading to its reintroduction as a useful adjunct in cardiac surgical procedures are referenced in this report.

Prenatal correction of certain cardiac lesions with a poor prognosis may have advantages over postnatal repair. For this to be done, safe and effective support of the fetal circulation must be devised. Studies involving fetal cardiac bypass have demonstrated progressive fetal hypoxemia, hypercapnia, and acidosis, indicating placental dysfunction. We performed fetal cardiac bypass in 18 fetal lambs (126 to 140 days' gestation) to assess the effect of flow rate on fetal oxygenation and metabolism and function of the placenta as an in vivo oxygenator. Fetal cardiac bypass was done for a 30-minute study period at normothermia in all fetuses. During the study period the fetal aorta was cross-clamped and cold cardioplegia was administered to the heart so there was no fetal cardiac contribution to systemic output. Nine fetuses underwent studies at low flow rates (109 +/- 20 mL.kg-1.min-1) and 9 at higher flow rates (324 +/- 93 mL.kg-1.min-1). At the lower flow rate, mean aortic pressure, arterial pH, and oxygen tension decreased whereas carbon dioxide tension and lactate levels increased when compared with prebypass levels. At the higher flow rate mean aortic pressure, pH, oxygen tension, carbon dioxide tension, and lactate levels remained similar to prebypass levels during the 30-minute study period. When the animals were weaned from the bypass circuit after studies at high flow rates, arterial oxygen tension and pH decreased whereas carbon dioxide tension increased to levels similar to those in the low-flow group.(ABSTRACT TRUNCATED AT 250 WORDS)

To summarize this rather wide-ranging study, let us review the high points. The future practice of thoracic surgery will be increasingly affected by governmental factors and will have even greater technological dimensions. To do this work, we must continue to attract high-caliber individuals, and this is best accomplished by the early and continuing involvement in the educational process of strong role models from our field. These future surgeons must be motivated to do good work and should have high ethical standards as well as maturity and high intelligence. Experienced, involved faculty leading the residents through a broad program that offers graduated assumption of clinical and leadership responsibilities will facilitate the development of mature clinical judgment. Residents must be taught the clinical skills necessary to do all thoracic operations, leaving subspecialization to postresidency fellowships. The educational program should be humane in its demands and collegial in its application. It should incorporate experiences beyond the operating room, including the opportunity to read, think, and interact with local mentors and colleagues from around the country. The requirements of certification should not be so rigid as to preclude the development of different pathways to the same end. Likewise, although the accreditation process must protect the resident from exploitation, it must not be so restrictive that it does not allow for educational innovation and justifiable differences among programs. These are the thoughtful opinions of our colleagues. They deserve serious consideration.

Between March 1985 and December 1991, mediastinitis developed in 12 of 420 cardiac transplantation patients (2.8%). The mortality rate in this group of patients was 8.3% (1/12). Actuarial survival (1 year, 75%; and 5 years, 65%) was not significantly different from that of the group without mediastinitis (1 year, 88%; and 5 years, 75%). A higher percentage of the patients in the group with mediastinitis were listed as UNOS status 1 (50% versus 35%) and had a history of previous sternotomies (58% versus 44%). The presentation of mediastinitis was typical. Computed tomographic scanning with or without aspiration was a valuable adjunct in the diagnosis of mediastinitis. Induction immunotherapy with minimal steroids in the perioperative period was used in all patients. This may contribute to the patients' ability to mount an appropriate and effective response to infection, permitting earlier diagnosis. The debridement irrigation technique used in 8 of 12 patients had a low success rate of 33%, whereas the debridement muscle flap technique used in 4 of 12 was 100% successful in eliminating infection.

To evaluate cardiac retransplantation as an appropriate utilization of scarce donor organs we analyzed data from the registry of the International Society for Heart and Lung Transplantation (ISHLT) (n = 449) and the Utah Cardiac Transplant Program (n = 20). Actuarial survival among retransplants was lower than in patients who received only one transplant in both the ISHLT registry patients (1 year survival, 48% versus 78%; p = 0.001) and the Utah series (1 year survival, 74% versus 88%; p = 0.06). Uncontrolled rejection, short interval (< 6 months) between transplantations, and the need for mechanical circulatory support were identified as risk factors for retransplantation. The incidence of rejection and infection was similar in first and second transplant recipients. Second transplant recipients had a higher level of sensitization, a greater incidence of donor-specific positive crossmatches, and an increased early mortality. Repetition in the second donor of mismatched HLA antigens present in the first donor did not adversely affect survival. If patients who underwent retransplantation within 6 months of their initial transplantation, those receiving transplants for uncontrolled rejection, and those requiring mechanical assistance were eliminated from the study, the short-term and long-term survival after cardiac retransplantation does not differ from that in patients having a single transplant.

The technical details of orthotopic cardiac transplantation in a 17-year-old man with a single ventricle and transposition of the great vessels are described. Special considerations in the evaluation and management of patients with complex congenital heart disease who are to undergo cardiac transplantation are delineated.

The development of orthotopically positioned cardiac replacement devices requires a knowledge of the space available to guide the design of the blood pumping system. Pericardial dimensions from in vivo and cadaver studies of normal subjects have been reported, but little information is available on in vivo pericardial dimensions in patients with dilated cardiomyopathies. The critical pericardial dimensions were determined in 13 men who were cardiac transplant recipients (age, 42 +/- 13 years; body mass, 72 +/- 11 kg; three with ischemic and 10 with idiopathic cardiomyopathy) by comparison of corresponding pericardial axes on chest radiographs to measurements obtained during orthotopic cardiac transplant in the context of a total artificial heart fit trial. The main pericardial dimensions measured intraoperatively were found to be the T10 midline anteroposterior (AP) axis (12.3 +/- 1.4 cm), the aortic root to diaphragm length (9.7 +/- 1.5 cm), the T10 total cardiac lateral axis (18.1 +/- 2.3 cm), and the tricuspid annulus to left ventricular apex (12.1 +/- 1.7 cm). All patients had cardiomegaly as indicated by a greater than normal cardiothoracic ratio. These data described the limited dimensions of the pericardial space available for orthotopic cardiac replacement devices. Chest film dimensions can be corrected using 0.92 and 0.88 as reduction factors for the (AP) and lateral axis dimensions, respectively. In this patient sample, there was little or no correlation between pericardial dimension and patient body mass or diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

The poor prognosis of certain cardiac abnormalities detected prenatally by echocardiography has led some investigators to consider intrauterine cardiac surgery. Investigation into the efficacy of open cardiac procedures in-utero will require techniques for safe and effective fetal extracorporeal circulation and myocardial protection. We performed cardiopulmonary bypass in 8 fetal lambs to assess the feasibility of fetal cardiopulmonary bypass. Four fetuses underwent studies at 37 degrees C (Group I) and 4 at 25 degrees C (Group II). The aorta was clamped and cold crystalloid cardioplegia administered. Perfusion was carried out for 10 minutes each at high (95 +/- 18 cc/kg/min), moderate (67 +/- 10 cc/kg/min), and low (49 +/- 8 cc/kg/min) flow rates while hemodynamic and blood gas measurements were made. Total time on bypass averaged 57 min in Group I and 75 min in Group II. Four fetuses were successfully weaned from bypass following the study period. Fetal pO2 and oxygen saturation was very low at all flow rates in Group II and at low flow rates in Group I, indicating poor function of the placenta as an oxygenator at 25 degrees C and at low flow rates during normothermia. Lambs undergoing bypass at 37 degrees C had a progressive rise in pCO2 levels as flow decreased, while pCO2 was relatively normal at all flow rates at 25 degrees C. These studies serve as a starting point for the development of techniques to allow intrauterine correction of experimentally produced fetal cardiac lesions.

Because administration of murine monoclonal anti-CD3 antibody (OKT3) may result in the formation of human antimouse antibody, which complexes with OKT3, we conducted this study to assess the incidence and effect of human antimouse antibody formation during prophylactic administration of OKT3 in heart transplantation. Human antimouse antibody developed in eight of 55 (14%) cardiac allograft recipients receiving OKT3 prophylaxis as measured by enzyme-linked immunosorbent assay. Additionally, two recipients had an inexplicable rise in CD3+ lymphocytes during therapy without detectable antibody. The outcome of these 10 sensitized recipients was compared with that of 45 nonsensitized recipients. Age, preoperative diagnosis, hemodynamics, and the need for intravenous inotropes or mechanical assistance before transplantation were similar in both groups. No female patients were in the sensitized group, whereas 33% of the nonsensitized group were female patients. A trend toward greater sensitization when prophylaxis was extended to 21 days (28%) compared with the more conventional 14-day administration (10%) was not statistically significant. Retransplantation because of rejection was required in a single patient in each group. Allograft survival was significantly lower by 3 months in the sensitized group, and allograft loss caused by rejection selectively accounted for that difference. In survivors, rejection frequency and infectious complications were similar. These findings suggest that sensitization to OKT3 occurs at low frequency after prophylactic administration in heart transplantation but is associated with an increased frequency of graft loss because of rejection.

Potent prophylactic immunosuppressive protocols promote the safe withdrawal of corticosteroid maintenance. The benefits of corticosteroid-free maintenance immunosuppression include the absence of the cushingoid habitus, fewer infections, less obesity, and lower serum cholesterol. The incidence of allograft coronary artery disease is not increased by corticosteroid-free maintenance. To assess the long-term effects of corticosteroid-free immunosuppression on allograft function, we compared results of hemodynamic study and noninvasive evaluation over the 2-year follow-up of 57 patients on corticosteroid-free maintenance to 40 patients who required corticosteroid. Age and pretransplantation diagnoses were similar, but a greater percentage of those who required corticosteroid maintenance were female (28% versus 2%, p less than 0.001). Indexes of allograft function were similar in both groups and these indexes included ejection fraction, right atrial pressure, pulmonary artery pressure, pulmonary capillary wedge pressure, cardiac index, left ventricular end-diastolic dimension, and posterior wall thickness. Patient survival was identical in the two groups (98%). These data indicate that corticosteroids can be safely withdrawn with the subsequent early benefits and without compromising long-term allograft function.

Although the etiology of allograft coronary artery disease, a major limiting factor in long-term survival after cardiac transplantation, is poorly understood, it is undoubtedly in part immune mediated and not detected by routine endomyocardial biopsy. Therefore it is possible that withdrawal of maintenance corticosteroids, although providing other short- and long-term benefits, could increase the prevalence of allograft coronary artery disease by permitting undetected immune-mediated vascular injury to occur. To assess whether corticosteroid-free maintenance immunosuppression increased the prevalence of allograft coronary artery disease, we reviewed serial angiograms of 102 patients (49% not receiving corticosteroid maintenance therapy) who underwent heart transplantation after March 7, 1985. Multiple variables including serum cholesterol, recipient and donor age, sex, blood pressure, rejection frequency and severity, early rejection prophylaxis protocol (polyclonal versus monoclonal T-cell agents), and corticosteroid use were examined in relation to allograft coronary artery disease by univariate and multivariate analyses. Allograft coronary artery disease was identified in 21 patients (seven severe, four moderate, and 10 mild). The prevalence by Kaplan-Meier life-table analysis was 17% at 1 year and 25% at 2 years. No further allograft coronary artery disease was detected among patients undergoing angiography at three years. Increased allograft coronary artery disease was not noted in patients withdrawn from maintenance corticosteroids when compared with their corticosteroid-requiring counterparts. In fact, with each 1 gm increment in cumulative corticosteroid use, a slightly increased risk (1.04, p less than 0.05) of allograft coronary artery disease was noted (Cox regression model). None of the other variables correlated with the prevalence of allograft coronary artery disease. Thus withdrawal of maintenance corticosteroids is not associated with an increased risk of early allograft coronary artery disease and minimization of corticosteroids may lead to a decreased long-term incidence of coronary artery disease in cardiac transplant recipients.

The relative effectivenss of hypothermic potassium (K) cardioplegia in conjunction with either continuous or intermittent aortic cross-clamping was evaluated in 20 mongrel dogs. Isovolumetric left ventricular (LV) contractions and myocardial biopsies were obtained before and after a total of 90 minutes of aortic cross-clamping. The dogs were randomly divided into four groups of five dogs each as follows: Group I, continuous 90 minute cross-clamping and multidose K at 4 degrees C (40 mEq/L); Group II, intermittent cross-clamping consisting of six 15 minute periods of cross-clamping separated by 5 minute reperfusion periods and K cardioplegia at 4 degrees C given at the start of each cross-clamping period; Group III, continuous 90 minute cross-clamping and multidose buffered saline at 4 degrees C; Group IV, intermittent cross-clamping, consisting of six 15 minute periods of cross-clamping separated by 5 minute reperfusion periods and buffered saline at 4 degrees C given at the initiation of each cross-clamp period. Group I dogs had the best myocardial performance, with no difference between control values of peak LV pressure and dP/dtmax and those recordings obtained 60 minutes after release of the aortic cross-clamp. Significant depression of LV function was noted in all other groups. Examination of force-velocity and length-tension relationships confirmed better myocardial performance in Groups I and II (multidose K at 4 degrees C) than in Groups III and IV (buffered saline at 4 degrees C). Groups I and III (continuous cross-clamping) had no de-rease in diastolic LV compliance after cross-clamping, whereas compliance was decreased in both Groups II and IV (intermittent cross-clamping) at higher preloads (p less than 0.05 and p less than 0.025, respectively). The wet weight/dry weight myocardial ratios were lower in Groups I and III (continuous cross-clamping) than in Groups II and IV (intermittent cross-clamping). Although creatine phosphate (CP) concentrations were rapidly restored by reperfusion in all groups, adenosine triphosphate (ATP) and glycogen myocardial stores were better preserved at the end of cross-clamping in Groups I and II (multidose K at 4 degrees C). Although LV diastolic compliance was decreased and myocardial water content was increased in Groups II and IV (intermittent cross-clamping), no differences in the minimal extent of subendocardial hemorrhage, edema, and contraction-band necrosis were observed among any of the groups examined electron microscopically. The present study identifies continuous aortic cross-clamping with multidose K at 4 degrees C as a superior method of myocardial protection.

Postoperative fever and pericardial-pleural reaction, designated postpericardiotomy syndrome (PPS), is a common complication of cardiac surgery involving entry into the pericardium. To determine whether the etiology of PPS is viral or immunologic, we undertook a prospective, triple-blind study of consecutive long-term survivors of intrapericardial surgery in the pediatric age group. We evaluated clinical evidence of syndrome and concurrent appearance of antiheart antibody (AHA) by indirect immunofluorescence and antiviral antibody (AVA) by complement fixation in sera preoperatively and serially postoperatively. Incidence of PPS was 27% overall in 400 subjects, but only 3.5% in infants younger than 2 years of age. AHA in high titer appeared in all patients with PPS. A fourfold or greater rise in titer to AVA was found in 70% of these but in only 5% of those with negative AHA and no PPS. AVA rise, tested in 280 consecutive patients, was to no single one of the eight viruses studied (adenovirus, cytomegalovirus, and coxsackievirus B 1-6). Instead, the rise and fall, consistent with antiviral response to a recent infection, was exhibited usually to one but occasionally to two or more viruses, and the viral prevalence changed from year to year, as did that in the community. The study suggests that concurrent fresh or reactivated viral illness plays a role in triggering the immunologic response that characterizes the PPS.

Repeat cardiac surgery is significantly more difficult than the original surgery. Pericardial closure to limit adhesion formation between the heart and mediastinal structures and thus reduce the increased difficulty of reoperation has been considered. To investigate the feasibility of effecting loose pericardial closure with homologous pericardial grafts, glutaraldehyde-preserved pericardial allografts were implanted in 10 mongrel dogs. After a mean period of 6.7 months (range 6 to 8 months) the grafts were studied grossly and histologically. Adhesion formation was minimal and the adhesions were easily dissectible. The allografts evoked no significant inflammatory response. No infections resulted from graft placement. It is concluded that glutaraldehyde-preserved pericardial allografts may be useful to effect pericardial closure and deserve further investigation in this regard.

Histamine is known to enhance the contractility of the human myocardium in vitro. We have observed that when the H2-receptor antagonist cimetidine (or ranitidine) blocks the positive inotropic effect of histamine in spontaneously beating pectinate muscles isolated from human right atrial appendage, a negative inotropic effect is unmasked. This decrease in contractility is independent of changes in rate, as it occurs in preparations paced at constant rate, is mimicked by the H1-receptor agonist 2-(2-thiazolyl)-ethylamine (ThEA) and is abolished by the H1-antagonist pyrilamine. Thus, the negative inotropic effect of histamine appears to be mediated by H1-receptors. Our data indicate that the inotropic response of the human myocardium to histamine consists of two opposing components: an increase in contraction, mediated by H2-receptors, and a decrease in contraction, mediated by H1-receptors. Given the widespread use of H2-blockers and the multitude of clinical conditions in which histamine is released, there may well be circumstances in which an H1-response predominates. This could result in a decrease in myocardial contractility.

The influence of age on cardiac allograft rejection was studied in 57 consecutive recipients. Twenty-one subjects were 54 years of age or older (mean, 57.7 +/- 0.6 years [+/- SEM]; range, 54 to 63 years) and 36 subjects were 52 years of age or younger (mean, 39.9 +/- 1.8 years; range, 16 to 52 years; p less than 0.001). The older recipients had fewer rejection episodes during the first four months following cardiac transplantation (0.24 +/- 0.05 episodes per month versus 0.72 +/- 0.09 episodes per month; p less than 0.001) and during the total duration of follow-up (0.20 +/- 0.03 episodes per month versus 0.40 +/- 0.07 episodes per month; p = 0.045), and experienced their first rejection episode later (50.4 +/- 4.0 days versus 27.7 +/- 8.5 days; p = 0.008). Younger age was found to add significantly as a predictor of rejection in a multivariate analysis that controlled for sex, immunosuppressive agents, cause of heart failure, and pretransplantation lymphocyte cross-match status (r = 0.64, p less than 0.05). Decreased rejection frequency occurred without a concomitant increase in the serious infection rate (67 percent in both groups). The 12-month actuarial survival was 100 percent in the older group and 94 percent in the younger group (p = NS). Decreased rejection in the older recipients is likely a manifestation of an age-associated decline in immune function and might represent an advantage in transplantation for carefully selected older patients.

The autoperfusing heart-lung preparation holds promise as a method for extended organ preservation. Further understanding of the hemodynamics, metabolism, and quality of tissue preservation of this preparation may increase the number of available organs for heart-lung transplantation. We describe the materials and operative technique for a small animal model of the autoperfusing heart-lung preparation. The method is easy to learn, the materials and animal subjects are inexpensive, and the preparation is fully monitored to provide consistent and reproducible data. The rabbit autoperfusing heart-lung preparation is an excellent vehicle for the investigator studying warm organ preservation.

In the absence of thiamine deficiency, the specific effects of protein-calorie malnutrition on left ventricular (L.V.) function are unknown. Mature beagle dogs of both sexes were subjected to a hypocaloric, nitrogen-poor diet which resulted in a weight loss of approximately 40% after seven weeks. Following preparation of this nutritional model, myocardial contractility was assessed acutely by obtaining isovolumetric L.V. contractions on cardiopulmonary bypass at constant heart rate, mean aortic pressure, and at a wide range of end-diastolic volumes. These changes were compared to a matched group of animals which were normally fed. There were consistent decreases in L.V. compliance in malnourished animals compared with normals; indices of ventricular contractility per se (L.V. dp/dt, force-velocity relations, peak developed L.V. pressure) were also diminished in the experimental animals. Myocardial concentration of glycogen was diminished in malnourished compared to control animals. Light and electron microscopic examination confirmed the presence of myofibrillar atrophy in the presence of interstitial edema. These results suggest that protein-calorie malnutrition seriously interferes with normal L.V. function in the experimental animal by reducing compliance as a result of "starvation edema," and by reducing myocardial contractility associated with atrophy of the myofibers.

To assess differences between male and female recipients after heart transplantation, we retrospectively reviewed 140 consecutive heart transplant recipients (119 males and 21 females) with regard to sex and characteristics before and after transplantation. Before transplantation, fewer female recipients had heart failure on the basis of coronary artery disease (14% versus 56%, p = 0.001), and more females required inotropic agents (71% versus 38%, p = 0.007). Although average follow-up (for females 430 +/- 73 days, range 12 to 1097 days; for males 412 +/- 27 days, range 1 day to 1103 days, mean +/- standard error of the mean), mortality (one female and nine males), and proportion of recipients with infectious complications (48% females and 52% males) did not differ between the groups, female recipients manifested a higher incidence of rejection during the first 4 months (2.39 +/- 0.27 episodes versus 1.67 +/- 0.11 episodes, p = 0.010) and during follow-up (3.24 +/- 0.44 episodes versus 2.20 +/- 0.21 episodes, p = 0.012). Although it was possible to discontinue maintenance dosages of corticosteroids in 65% of males, corticosteroid discontinuation was possible in only 17% of females (p less than 0.001). Furthermore, in a stepwise logistic regression analysis that included age, crossmatch (no female recipients with positive results, three males with positive results), cause of heart failure, and hemodynamic status before transplantation, females were more likely to experience a rejection episode than males (p less than 0.001). Although female recipients experience rejection episodes more than their male counterparts after heart transplantation and are more likely to require maintenance corticosteroid therapy, survival and the incidence of infectious complications are not different.

In an 18-month period, 50 orthotopic cardiac transplantations were done in Utah in 48 patients with end-stage heart failure. The 12-month actuarial survival was 98%, indicating that successful cardiac transplantation can be done in a newly established program and that the intermountain West has an adequate supply of potential recipients and donors for a moderate- to high-volume program. Furthermore, the administration of cardiac transplantation in a setting of other treatment modalities of heart failure in a multi-institutional program that crosses private practice-academic barriers is feasible. Results such as these need to be considered by the federal government as it establishes eligibility criteria for centers to be approved for Medicare-funded cardiac transplantation.

Myocardial function with ultrastructure and high energy phosphate levels in dogs was correlated after 24 hours of sepsis using live Klebsiella aerogenes. All animals developed progressive hemodynamic deterioration over a 24 hour period. Mean arterial pressure decreased from 148 +/- 7 mmHg to 85 (P less than 0.01) and cardiac output decreased from 3.43 +/- .31 to 1.6 +/- 0.5 L/min. Left ventricular stroke work decreased from 48.2 +/- 5 to 18.1 +/- 6 gm-meters (P less than 0.001). Systemic and pulmonary vascular resistances were increased at 24 hours (3,538 +/- 27 to 7,404 +/- 1,400 dyne/sec/cm-5 (P less than 0.01), and 185 +/- 20 and 619 +/- 90 dyne/sec/cm-5 (P less than 0.001), respectively. Left ventricular function curves at 24 hours showed a fixed low output. However, myocardial ultrastructure was preserved and high energy phosphate levels remained normal. These observations correlate well with the changes seen clinically in early gram negative sepsis in hypovolemic patients. Thus, this appears to be a suitable model for further investigation of the effects of gram negative sepsis on myocardial performance, ultrastructure, and maintenance of energy stores.

The accessibility and success of cardiac transplantation promotes transplantation for a broad range of recipients, including those requiring intravenous inotropes or mechanical-assist devices. To determine if survival is dependent on preoperative requirements for hemodynamic support, we studied 230 patients who underwent transplant at the Loyola, Stanford, and UTAH programs from December 1, 1984 through November 30, 1986, and who were followed up for 34 months postoperatively. Group 1 (n = 132 of 230, 57%) patients required only oral medical therapy to maintain hemodynamic compensation; Group 2 (n = 69 of 230, 30%) patients were dependent on intravenous inotropic support; and Group 3 (n = 29 of 230, 13%) patients required mechanical assistance. Pretransplant characteristics showed that dilated cardiomyopathy was more common in Group 2 patients, and lower cardiac index and ejection fraction were more prevalent in Group 3 patients as expected. Although survival was lower in Group 3 only at 1 month (Group 1, 98.5%; Group 2, 92.8%; and Group 3, 86.2%; p less than 0.01), the survival advantage in Groups 1 and 2 was lost by 3 months, with 1-year survival rates of 88.6% in Group 1, 81.2% in Group 2, and 82.8% in Group 3. Allograft survival and cause of death were not different among the three groups. Acute rejection occurred at a lower monthly frequency in the first 4 months in Group 3 (Group 1, 0.47 +/- 0.03; Group 2, 0.47 +/- 0.05; and Group 3, 0.29 +/- 0.06; p less than 0.01), whereas infectious complications occurred at similar frequencies.(ABSTRACT TRUNCATED AT 250 WORDS)