Role of hypercholesterolemia in accelerated transplant coronary vasculopathy: results of surgical therapy with partial ileal bypass in rabbits undergoing heterotopic heart transplantation.

BACKGROUND: We tested the hypothesis that plasma cholesterol lowering action of partial ileal bypass (PIB) is beneficial in mitigating accelerated transplantation coronary vasculopathy. METHODS: Forty-one New Zealand white rabbits were randomized to receive a normal (n = 21) or 1% cholesterol diet (n = 20). They underwent heterotopic heart transplantation with sham-PIB (n = 19) or PIB (n = 22) and immunosuppression with cyclosporine A (CyA). RESULTS: CyA increased plasma cholesterol of rabbits receiving a normal diet. This effect was mitigated by PIB (101 +/- 50 mg/dl CyA vs baseline 24 +/- 8, p < 0.001; vs 54 +/- 25 mg/dl with PIB, p < 0.05). In cholesterol-fed rabbits, PIB decreased plasma cholesterol levels (520 +/- 236 mg/dl PIB vs baseline 720 +/- 359, p < 0.05; vs 1502 +/- 253 mg/dl with sham PIB, p < 0.00001). Coronary arteries (CA) of 21 5-week survivors were evaluated by light microscopy and digital morphometry. No rejection was noted. Histologic study revealed vasculopathy in 3% of 705 native and 18% of 654 transplant CA (p < 0.05). Graft vasculopathy (GV) was present in 25% of 365 CA of sham-PIB and 10% of 289 CA of PIB rabbits (p = 0.07). In cholesterol-fed rabbits, GV was characterized by fatty proliferative lesions in 75% of 91 pathologic CA of sham and 21% of 28 pathologic CA of PIB rabbits (p < 0.05). Graft intimal hyperplasia was not correlated with cholesterol intake or PIB and was present in 18 of 119 pathologic CA. CONCLUSIONS: GV was characterized by fatty intimal proliferation, fibrous intimal hyperplasia, and a "mixed type." Fibrous intimal hyperplasia developed in native and transplanted hearts, and CyA seemed to promote this state. Hypercholesterolemia promoted fatty proliferative lesions, worsening GV. PIB significantly decreased total cholesterol and retarded fatty proliferation of CA of native and transplanted hearts but did not prevent intimal hyperplastic vasculopathy. Therapy of hypercholesterolemia is recommended to at least mitigate the fatty intimal proliferation of GV.

Prosthetic mitral valve replacement: late complications after native valve preservation.

Preservation of the mitral valve leaflet and tensor apparatus during valve replacement is believed to maintain left ventricular performance. The routine use of this technique may lead to left ventricular outflow or inflow obstruction as illustrated in the present report. We recommend mobilization or excision of the anterior mitral valve leaflet and preservation of the posterior leaflet if replacement of the valve is contemplated for incompetence.

Assessing myocardial perfusion with Albunex during coronary artery bypass surgery: technical considerations and safety of aortic root injections.

OBJECTIVE: To test the safety and report on limiting technical considerations, including optimal dosing of Albunex (Molecular Biosystems, Inc, Mallinckrodt Medical, St. Louis, MO) for myocardial opacification after intra-aortic root injections during cardiac surgery. DESIGN: This was a prospective randomized study with a control group who did not receive Albunex and a group who received intra-aortic root injections of Albunex. SETTING: Multicenter (two) independent university hospitals. PARTICIPANTS: 32 patients scheduled for elective coronary artery bypass surgery were evaluated after individual informed consent was obtained. INTERVENTIONS: 2 to 8 mL of Albunex were injected before and after coronary revascularization. MEASUREMENTS AND MAIN RESULTS: Quality of enhancement in each of four regions of the left ventricle was assessed from a short-axis mid-papillary ultrasound image by three experienced observers blinded to dose. Electrocardiogram (ECG), creatine phosphokinase (CPK) (MB fraction), and hemodynamics were evaluated at baseline and throughout the study period for up to 72 hours. No differences were noted between groups with respect to preoperative and postoperative CPK enzymes (CPK-MB fraction), ECG changes, hemodynamics, requirements for separation from CPB, need for postoperative inotropes, time to extubation, and time to discharge from the intensive care unit. The average total dose of Albunex injected was 19 mL +/- 4 (0.25 mL/kg). A single dose of 4.2 +/- 1.2 mL (0.05 mL/kg) appeared to offer optimal enhancement of contrast effect for myocardial perfusion assessment. CONCLUSION: Albunex is safe and easy to use for myocardial opacification when administered via an antegrade cardioplegia catheter into the aortic root during CPB.

Spontaneous acquisition of discontinuous pulmonary arteries.

BACKGROUND: Discontinuous pulmonary arteries have been considered a rare complication of systemic-to-pulmonary shunt operations. We report a series of children who spontaneously acquired pulmonary artery discontinuity. METHODS: All children from 1989 through 1995 with congenital pulmonary atresia were reviewed. RESULTS: Pulmonary artery discontinuity developed in 29% (15 patients), none related to shunt operation. In 6 of 15 patients, the neonatal angiogram showed a pattern that seemed to predict subsequent discontinuity; in 9 of 15, pulmonary arteriography was normal at birth. Two clinical patterns were identified: an early rapid acquisition of discontinuity within hours to days, and a delayed, more subtle development that occurred over months. Eight of 15 have died. Pathologic studies in 6 children showed ductal tissue extending along and into the pulmonary artery wall as well as intimal hypertrophic reaction and maladaptive remodeling. CONCLUSIONS: Children with congenital pulmonary atresia may experience spontaneous acquisition of pulmonary artery discontinuity. Ductal tissue is responsible for local pulmonary artery distortion and discontinuity; this may be exacerbated by previous prostaglandin E1 administration. Clinical algorithms are suggested for patients with pulmonary atresia.

University surgical group.

The medical marketplace and various forms of contracted care place academic medical centers at a potential disadvantage. Recruitment of patients and maintenance of the academic mission may at times have disparate agendas. The university surgeon traditionally has embraced patient care, education, research, and administration with relative ease. Major price constraints and new forms of market competition now threaten the centralization of technology, the creativity, and the educational mission of university surgical practices. The university must deal with this new order by being proactive and flexible in negotiation. Faculty should conduct their business among themselves and with outside entities under a practice plan. Business management and physicians must try vigorously to understand each other. Finally, universities should use their expertise to lead in clinical outcomes research. The ideal university practice must show leadership in technological advances, retain the scientific method, and produce useful precise outcomes analysis. The academic surgeon must help solve problems involving excessive costs, assaults on creativity, and the business-medical interface. Time management will be essential.

Tricuspid valve closure in pulmonary atresia and important RV-to-coronary artery connections.

Mortality is high for children with pulmonary atresia, intact ventricular septum, and important connections between the right ventricle and the coronary arteries because of myocardial ischemia: in systole, suprasystemic right ventricular pressure delivers deoxygenated blood to the coronary artery (or arteries) and in diastole, the right ventricle provides a lower resistance alternative to coronary perfusion of the myocardium. Tricuspid valve closure was performed in 10 such children. None had stenosis of native coronary arteries. A trial of tricuspid valve closure (by balloon) was performed in the cardiac catheterization laboratory in 5 of 10 patients. Seven of 10 children survived surgical closure of the tricuspid valve plus concurrent procedures; none had heart block. Two of the 3 nonsurvivors were probably in inoperable condition due to preoperative myocardial ischemia. Before operation, 4 patients had ischemic changes on electrocardiograms; these changes were abolished after operation. Three of 10 patients have had a Fontan operation with 2 survivors. We conclude that children with pulmonary atresia, intact ventricular septum, important connections between the right ventricle and the coronary arteries, and normal native coronary arteries should have surgical closure of the tricuspid valve within the first year of life and treated thereafter as patients with "tricuspid atresia."

Aprotinin for coronary artery bypass grafting: effect on postoperative renal function.

Two hundred sixteen patients undergoing coronary artery bypass graft procedures were randomized to receive either high-dose aprotinin or placebo. Clinically important postoperative renal insufficiency was infrequent, with a single patient (0.9%) from each group requiring dialysis. Although increases in the serum creatinine level occurred postoperatively in more patients who received aprotinin (20/108) than in those given placebo (13/108), the difference between the two groups was not statistically significant (p = 0.186), and the increases were generally small and transient. Likewise, there was no difference between the groups in terms of the incidence of abnormal serum electrolyte levels, blood urea nitrogen levels, or urinalysis findings, or in the frequency of abnormal creatinine clearance rates. Under the conditions described, aprotinin use does not appear to be associated with a significant risk of serious renal toxicity.

Comparison of high-dose thrombin time with activated clotting time for monitoring of anticoagulant effects of heparin in cardiac surgical patients.

The activated clotting time (ACT) is routinely used for monitoring of heparin effects during cardiopulmonary bypass (CPB). However, ACT is not a specific assay for heparin and may be influenced by several other factors, which may be misleading with regard to the proper administration of heparin and protamine. In this pilot study, we compared a new test, the high-dose thrombin time (HiTT), with the conventional ACT test for both in vitro and in vivo heparin-induced anticoagulation. Our in vitro results showed that there were heparin dose-dependent increases in ACT and HiTT. Data on 30 adult cardiac patients indicated that HiTT correlated well with heparin concentration both after initial heparin administration and during CPB (r = 0.645 and 0.515). Hypothermia and hemodilution occurring during CPB did not alter HiTT results. ACT also correlated well with both heparin concentration and HiTT before CPB, but the linear relationship was lost during CPB. Our results suggest that HiTT is a useful assay for monitoring heparin effects during cardiac surgery, even during hypothermia and hemodilution.

Rigid internal fixation of the sternum in postoperative mediastinitis.

OBJECTIVE: The current standard treatment of mediastinitis following median sternotomy is radical sternal débridement and obliteration of anterior mediastinal dead space with muscle or omental flaps. This report describes and reviews our experiences with a new technique of sternal salvage based on osseous quantitative bacteriologic assessment and rigid fixation in patients with postoperative mediastinitis. DESIGN: A retrospective review of 29 patients treated with sternal rigid internal fixation. SETTING: Two tertiary care academic medical centers in Chicago, Ill, and Ann Arbor, Mich. PATIENTS: Patients with postoperative mediastinitis following median sternotomy who underwent rigid internal fixation of retained sternum. INTERVENTION: Following débridement, quantitative bacteriologic assessment and sternal vascularity were assessed. Sternal segments with good vascularity and in bacteriologic balance were anatomically reduced and rigidly fixed to each other with titanium miniplates in 24 patients with postoperative mediastinitis. Five of the 29 patients, at high risk for mediastinitis, underwent rigid internal fixation immediately after their cardiac procedure. MAIN OUTCOME MEASURES: Resolution of infection, wounds remaining closed, and stable sternums. RESULTS: Bony union was obtained in 27 (93%) of 29 patients. The postoperative hospital stay ranged from 5 to 84 days, with a mean stay of 17 days and a median stay of 7 days. Length of stay was directly related to pulmonary function, which correlated with preoperative intubation status. CONCLUSIONS: Radical sternal débridement may not be necessary in all patients with postoperative mediastinitis following median sternotomy. Sternal salvage can safely and reliably be performed with a combination of clinical assessment of vascularity and osseous quantitative bacteriologic assessment. Anatomic reduction of the viable sternal segments is possible even in severely osteoporotic bone.

Aprotinin for coronary bypass operations: efficacy, safety, and influence on early saphenous vein graft patency. A multicenter, randomized, double-blind, placebo-controlled study.

The purpose of this study was to evaluate the efficacy and safety of aprotinin in a U.S. population of patients undergoing coronary artery bypass grafting. Early vein graft patency rates were assessed by ultrafast computed tomography. A total of 216 patients at five centers were randomized to receive either high-dose aprotinin or placebo during the operation; 151 patients underwent primary operation, and 65 underwent repeat procedures. Total blood product exposures in the primary group were 2.2 per patient receiving aprotinin as compared with 5.7 per patient receiving placebo (p = 0.010). The repeat group had 0.3 exposures per patient receiving aprotinin as compared with 10.7 per patient receiving placebo (p = < 0.001). Consistent reductions in the percent of patients requiring donor red blood cells and in the number of units of platelets, fresh frozen plasma, and cryoprecipitate required were associated with the use of aprotinin in both primary and repeat groups. Mortality was 5.6% in the aprotinin group and 3.7% in the placebo group (p = 0.517). In the primary group, clinical diagnoses of myocardial infarction were made in 8.9% of patients receiving aprotinin as compared with 5.6% of the patients receiving placebo (p = 0.435). In the repeat group, infarctions occurred in 10.3% of patients receiving aprotinin and 8.3% of patients receiving placebo (p = 1.000). Secondary analysis of electrocardiograms and available enzyme data showed no significant difference in infarction rates between the treatment groups. There was no difference in clinically significant renal dysfunction. The early vein graft patency rates were 92.0% in the aprotinin group and 95.1% in the placebo group (p = 0.248). In this study, aprotinin was effective in reducing bleeding and blood product transfusion rates, and its use was not associated with an increase in complications. An adverse effect on early vein graft patency rates was not demonstrated, but the number of grafts assessed was insufficient for absolute conclusions in this regard.

Double-chambered left ventricle: submitral accessory valvular tissue causing inlet and outlet obstruction.

We report a patient with a large submitral ridge of muscular and fibrous tissue that divides the left ventricle into two distinct chambers causing inlet and outlet obstruction. Doppler echocardiography revealed obstruction to both filling and ejection. Echocardiography demonstrated that the obstruction was in series with the mitral apparatus. Surgery was done with resection of much of this ring of tissue. Subsequent studies revealed morphologic and hemodynamic improvement.

Myocardial distribution of cardioplegic solution after retrograde delivery in patients undergoing cardiac surgical procedures.

The myocardial distribution of both antegrade and retrograde cardioplegia for cardiac surgical intervention, after induction of cardioplegia via the aortic root, was directly assessed and compared in 19 patients by means of contrast echocardiography. Two-dimensional transesophageal echocardiographic images of the short axis of the left ventricle at the level of the papillary muscles were obtained after sonicated Renografin-76 microbubbles were injected into an aortic root and/or transatrial coronary sinus catheter during delivery of cardioplegic solution. Segmental distribution of cardioplegic solution was immediately noted in the myocardium at the time of contrast injections. In 11 of 18 patients (61%) cardioplegic solution was dispersed to all left ventricular myocardial segments after antegrade delivery. In 17 of 19 patients (90%) retrogradely delivered cardioplegic solution (after antegrade induction of cardioplegia in 18 of the 19 patients) was dispersed to all the left ventricular myocardial segments, including the septum. In 2 of the patients, initial lack of retrograde distribution of cardioplegic solution was remedied when the coronary sinus catheter was repositioned and contrast cardioplegic solution was reinjected. Imaging of the right ventricle was possible in only 4 of the 19 patients and revealed that after retrograde delivery, cardioplegic solution had been at least partially distributed to the right ventricle as well. We performed off-line videodensitometric analysis in 9 patients after retrograde delivery of cardioplegic solution. Mean peak pixel-intensity ratio of flow from the endocardium to the epicardium in the left ventricular free wall was 1.46 +/- 0.27, and mean peak pixel-intensity ratio of flow from the left to the right intraventricular septal endocardium was 1.39 +/- 0.33 (p < or = 0.05).

Mechanical prostheses: old and new.

The four mechanical valve prostheses currently available on the U.S. market have evolved from a field of more than 50 valves produced for human implantation since the early 1950s (Tables 11-1 to 11-4). This literature establishes that good results can be achieved with a number of cardiac prostheses if properly used and monitored after implant. The current generation of valves have demonstrated ease of implantation, improved durability, good hemodynamic performance, and reduced thromboembolism and thrombosis with proper anticoagulation. The cost and complexity of completing PMA by the FDA, concern over product liability, and patent rights on design and raw materials have narrowed the choice of devices for surgeons in the United States and slowed the pace of new market entries. The evolution of mechanical valves has been reviewed and modes of valve failure reviewed when pertinent. Clinical expectations for earlier generation devices and present valves also are reviewed. Prostheses under evaluation are discussed along with considerations for valve implantation, surveillance, and anticoagulation. We have employed the SJM valve since about 1985. The proven good hemodynamic performance in small sizes and low profile have made its application well suited to the pediatric population and for smaller aortic roots. The well-guarded hinge mechanism and low probability for disc entrapment have facilitated its use in chordal sparing mitral replacements in our experience. Application in the tricuspid position also has been successful but requires close attention to anticoagulation.