Exercise experience influences affective and motivational outcomes of prescribed and self-selected intensity exercise.

The purpose of the study was to compare affective and motivational responses to exercise performed at self-selected and prescribed intensity [close to ventilatory threshold (VT)] between physically active and sedentary women. Following a graded exercise test, the women completed two 30 min bouts of treadmill exercise (on separate days, order counterbalanced). Intensity was prescribed in one session and self-selected in the other. Exercise intensity, exercise-efficacy, perceived competence, autonomy and affective responses were assessed. Results showed that the active women self-selected to exercise at a significantly higher %HR(peak) than their sedentary counterparts but, importantly, both groups exercised close to their VT. The order of conditions influenced affective and motivational responses. The active women experienced more positive affect during exercise and greater competence than sedentary women when the self-selected condition was completed first. Autonomy was higher for the self-selected condition. Self-efficacy and competence were higher in the active women. Differences in self-efficacy perceptions before the exercise depended on which condition was completed first. In conclusion, sedentary women felt relatively positive in the self-selected condition but would benefit from familiarization and experience with exercise to enhance their self-efficacy and competence.

Indirect recognition of donor HLA-DR peptides in organ allograft rejection.

To determine whether indirect allorecognition is involved in heart allograft rejection T cells obtained from peripheral blood and graft biopsy tissues were expanded in the presence of IL-2 and tested in limiting dilution analysis (LDA) for reactivity to synthetic peptides corresponding to the hypervariable regions of the mismatched HLA-DR antigen(s) of the donor. Serial studies of 32 patients showed that T cell reactivity to donor allopeptides was strongly associated with episodes of acute rejection. The frequency of allopeptide reactive T cells was 10-50-fold higher in the graft than in the periphery indicating that T cells activated via the indirect allorecognition pathway participate actively in acute allograft rejection. In recipients carrying a graft differing by two HLA-DR alleles the response appeared to target only one of the mismatched antigens of the donor. Indirect allorecognition was restricted by a single HLA-DR antigen of the host and directed against one immunodominant peptide of donor HLA-DR protein. However, intermolecular spreading was demonstrated in patients with multiple rejection episodes by showing that they develop allopeptide reactivity against the second HLA-DR antigen. These data imply that early treatment to suppress T cell responses through the indirect pathway of allorecognition, such as tolerance induction to the dominant donor determinant, may be required to prevent amplification and perpetuation of the rejection process.

Persistent allopeptide reactivity and epitope spreading in chronic rejection of organ allografts.

The role of the indirect allorecognition pathway in acute allograft rejection has been documented both in organ recipients and in experimental models. However, it is unknown whether self-restricted recognition of donor alloantigens also contributes to chronic allograft rejection. The aim of this study was to determine the relationship between allopeptide reactivity, epitope spreading, and chronic rejection. Using synthetic peptides corresponding to the hypervariable region of 32 HLA-DR alleles, we have followed the specificity of self-restricted T cell alloresponses to the donor in a population of 34 heart allograft recipients. T cells from sequential samples of blood collected from the patients up to 36 mo after transplantation were studied in limiting dilution analysis for allopeptide reactivity. The incidence of coronary artery vasculopathy (CAV) was significantly higher in patients who displayed persistent alloreactivity late after transplantation than in patients who showed no alloreactivity after the first 6 mo after transplantation. Both intra- and intermolecular spreading of epitopes was observed with an increased frequency in patients developing CAV in less than 2 yr, compared with patients without CAV; this suggests that diversification of the immune response against the graft contributes to chronic rejection. These data provide a strategy for identifying patients at risk of developing CAV and a rationale for therapeutic intervention aimed to prevent the progression of the rejection process.

Malignant ventricular arrhythmias are well tolerated in patients receiving long-term left ventricular assist devices.

OBJECTIVES: We sought to quantitate the incidence of malignant ventricular arrhythmias and to identify subsequent hemodynamic changes and untoward events in patients who have received an implantable left ventricular circulatory assist device as an extended bridge to heart transplantation. BACKGROUND: Implantable long-term mechanical circulatory assist devices have been used clinically with increasing frequency and success for the past 4 years. Previous investigators have suggested that patients with malignant ventricular arrhythmias receiving a left ventricular assist device will require both left and right ventricular assistance to maintain vital organ perfusion. METHODS: We reviewed our 4-year experience with 21 patients who underwent implantation of a left ventricular assist device. Device flows and mean arterial pressure were used to assess systemic perfusion; central venous pressure provided a gauge of right ventricular function. Charts were screened for evidence of end-organ injury resulting from malignant ventricular arrhythmias. RESULTS: Malignant ventricular arrhythmias occurred in 4 patients (19%) before device placement and in 9 patients (43%) during device support. The latter nine patients formed the final study group; their arrhythmias occurred 0 to 186 days after device implantation and had a duration of 10 min to 12 days. The patients reported weakness or palpitation; however, none reported syncope or dyspnea. Mean arterial pressure and central venous pressure were insignificantly changed by the arrhythmias. Device flow decreased by 1.4 +/- 0.6 liters/min (p < 0.05) at the onset of the arrhythmias but returned to normal after cardioversion. No thromboembolic events or significant end-organ dysfunction occurred. CONCLUSION: Absence of right ventricular contraction during malignant ventricular arrhythmias is well tolerated in recipients of a left ventricular assist device. The diagnosis of malignant arrhythmia should be suspected if an unexplained decrease in left ventricular assist device flow occurs. Early electrical cardioversion is warranted to avoid both thrombus formation in the native heart and right ventricular myocardial injury from prolonged fibrillation.

Heart transplantation in children with congenital heart disease.

OBJECTIVES: The aim of this study was to describe heart transplantation in children with congenital heart disease and to compare the results with those in children undergoing transplantation for other cardiac diseases. BACKGROUND: Reports describe decreased survival after heart transplantation in children with congenital heart disease compared with those with cardiomyopathy. However, transplantation is increasingly being considered in the surgical management of children with complex congenital heart disease. Present-day results from this group require reassessment. METHODS: The diagnoses, previous operations and indications for transplantation were characterized in children with congenital heart disease. Pretransplant course, graft ischemia time, post-transplant survival and outcome (rejection frequency, infection rate, length of hospital stay) were compared with those in children undergoing transplantation for other reasons (n = 47). RESULTS: Thirty-seven children (mean [+/- SD] age 9 +/- 6 years) with congenital heart disease underwent transplantation; 86% had undergone one or more previous operations. Repair of extracardiac defects at transplantation was necessary in 23 patients. Causes of death after transplantation were donor failure in two patients, surgical bleeding in two, pulmonary hemorrhage in one, infection in four, rejection in three and graft atherosclerosis in one. No difference in 1- and 5-year survival rates (70% vs. 77% and 64% vs. 65%, respectively), rejection frequency or length of hospital stay was seen between children with and without congenital heart disease. Cardiopulmonary bypass and donor ischemia time were significantly longer in patients with congenital heart disease. Serious infections were more common in children with than without congenital heart disease (13 of 37 vs. 6 of 47, respectively, p = 0.01). CONCLUSIONS: Despite the more complex cardiac surgery required at implantation and longer donor ischemic time, heart transplantation can be performed in children with complex congenital heart disease with success similar to that in patients with other cardiac diseases.

Imaging of cardiac allograft rejection in dogs using indium-111 monoclonal antimyosin Fab.

The acute rejection of cardiac allografts is currently diagnosed by the presence of myocyte necrosis on endomyocardial biopsy. We evaluated the efficacy of noninvasive scintigraphic imaging with indium-111-labeled anticardiac myosin Fab fragments (indium-111 antimyosin) to detect and quantify cardiac allograft rejection. Six dogs that had intrathoracic heterotopic cardiac allograft transplantation were injected with indium-111 antimyosin and planar and single photon emission computed tomographic (SPECT) images were obtained in various stages of acute and subacute rejection. Four dogs had an allograft older than 8 months and had been on long-term immunosuppressive therapy; two dogs had an allograft less than 2 weeks old and were not on immunosuppressive therapy. Count ratios comparing heterotopic with native hearts were calculated from both SPECT images and in vitro scans of excised and sectioned hearts and were compared with the degree of rejection scored by an independent histopathologic review. Indium-111 antimyosin uptake was not visible in planar or SPECT images of native hearts. Faint diffuse uptake was apparent in cardiac allografts during long-term immunosuppression and intense radioactivity was present in hearts with electrocardiographic evidence of rejection. The heterotopic to native heart count ratios in SPECT images correlated significantly with the count ratios in the excised hearts (r = 0.93) and with the histopathologic rejection score (r = 0.97). The distribution of indium-111 antimyosin activity in right and left ventricles corresponded to areas of histopathologic abnormalities. Immunoperoxidase studies showed deposition of indium-111 antimyosin only in areas of myocyte necrosis. The results demonstrate that indium-111 antimyosin imaging can noninvasively detect the presence, location and severity of canine cardiac allograft rejection.

Implantable left ventricular assist devices provide an excellent outpatient bridge to transplantation and recovery.

OBJECTIVES: Our recent experience with outpatient left ventricular assist device (LVAD) support is presented to demonstrate the possibilities and limitations of long-term outpatient mechanical circulatory assistance. BACKGROUND: The experience with inpatient LVAD support as a bridge to transplantation has proved the efficacy of such therapy in improving circulatory hemodynamic status, restoring normal end-organ function and facilitating patient rehabilitation. With miniaturization of the power supplies and controllers, such mechanical circulatory support can now be accomplished in an outpatient setting. METHODS: Between March 1993 and February 1997, 32 patients (26 male, 6 female, mean [+/-SEM] age 49 +/- 15 years) underwent implantation of the ThermoCardiosystems (TCI) Heartmate vented electric (VE) LVAD. The VE LVAD is powered by batteries worn on shoulder holsters and is operated by a belt-mounted system controller, allowing unrestricted patient ambulation and hospital discharge. RESULTS: Mean duration of support was 122 +/- 26 days (range 3 to 605), with a survival rate to transplantation or explantation of 78%. Nineteen patients were discharged from the hospital on mean postoperative day 41 +/- 4 (range 17 to 68), for an outpatient support time of 108 +/- 30 days (range 2 to 466). Four patients underwent early transplantation and could not participate in the discharge program, and three patients currently await discharge. The complication rate was not statistically different from that encountered in our previous 52 patients with a pneumatic LVAD. CONCLUSIONS: Outpatient LVAD support is safe and provides improved quality of life for patients awaiting transplantation. Wearable and totally implantable LVADs should be studied as permanent treatment options for patients who are not candidates for heart transplantation.

Factors affecting long-term survival (>10 years) after cardiac transplantation in the cyclosporine era.

OBJECTIVES: The aim of this study was to determine long-term survival (>10 years) after cardiac transplantation in the cyclosporine era and identify risk factors influencing long-term survival. BACKGROUND: Despite the availability of newer modalities for heart failure, cardiac transplantation remains the treatment of choice for end-stage heart disease. METHODS: Between 1983 and 1988, 195 patients underwent heart transplantation at a single center for the treatment of end-stage heart disease. Multivariable logistic regression analysis of pretransplant risk factors affecting long-term survival after cardiac transplantation included various recipient and donor demographic, immunologic and peritransplant variables. RESULTS: Among the group of 195 cardiac transplant recipients, actuarial survival was 72%, 58% and 39% at 1, 5 and 10 years respectively. In the 65 patients who survived >10 years, mean cardiac index was 2.91/m2 and mean ejection fraction was 58%. Transplant-related coronary artery disease (TRCAD) was detected in only 14 of the 65 patients (22%). By multivariable analysis, the only risk factor found to adversely affect long-term survival was a pretransplant diagnosis of ischemic cardiomyopathy (p = 0.04). CONCLUSIONS: Long-term survivors maintain normal hemodynamic function of their allografts with a low prevalence of TRCAD. It is possible that similar risk factors that lead to coronary artery disease in native vessels continue to operate in the post-transplant period, thereby contributing to adverse outcomes after cardiac transplantation. Aggressive preventive and therapeutic measures are essential to limit the risk factors for development of coronary atherosclerosis and enable long-term survival after cardiac transplantation.

Cytomegalovirus pneumonitis after cardiac transplantation.

To evaluate the incidence and clinical features of cytomegalovirus (CMV) pneumonitis after cardiac transplantation, we identified 27 (16%) of 171 consecutive recipients in whom CMV pneumonitis was confirmed by strict diagnostic criteria. Cytomegalovirus pneumonitis occurred in 6 (30%) of 20 patients treated with azathioprine and prednisone, and 8 (25%) of 32 patients treated with azathioprine, cyclosporine, and prednisone, but only 13 (11%) of 119 patients treated with cyclosporine and prednisone. The incidence of CMV pneumonitis was not related to recipient preoperative CMV titers or to postoperative cardiac rejection, but there was a trend toward increased CMV pneumonitis in patients who received organs from CMV-positive donors. Mean onset of CMV pneumonitis was 2.9 +/- 1.6 (SD) months after transplantation. In the azathioprine-prednisone group, CMV was always associated with at least one other respiratory pathogen (Aspergillus, n = 5; Pneumocystis carinii, n = 2). In the two cyclosporine groups, CMV was either the sole respiratory pathogen (n = 9), or associated with P carinii (n = 11). Roentgenographically, diffuse bilateral hazy pulmonary opacities were present in 19 (70%) of 27 patients, but focal subsegmental opacity (26%), small pleural effusion (26%), and lobar consolidation (7%) were also observed. When bronchoscopy was performed, bronchoalveolar lavage was the most sensitive technique for detecting CMV (72%), whereas transbronchial biopsy (39%) and combined washings and brushings (33%) were relatively insensitive techniques. Respiratory failure and death occurred in 52% and 44%, respectively, of patients with CMV pneumonitis. In this population of immunocompromised hosts: (1) CMV pneumonitis, alone or with other respiratory pathogens, was a major cause of morbidity and mortality; (2) localized roentgenographic opacity did not exclude CMV pneumonitis; (3) bronchoalveolar lavage was the most sensitive bronchoscopic technique for detecting CMV pneumonitis.

Anti-idiotypic antibodies specific for HLA in heart and kidney allograft recipients.

Chronic rejection is the major threat to both heart and renal allograft survival. We have explored the possibility that some patients with anti-donor HLA antibodies (Ab1) develop specific anti-idiotypic antibodies (Ab2) which suppress the production of Ab1, and subsequently, the progression of chronic rejection. Analysis of Ab2 in sera obtained from Ab1 producers showed that 22% of heart and 18% of kidney recipients produced Ab2. The 4- and 5-year actuarial graft survivals in Ab2 producers were 100% and 83%, respectively, compared to 57% in patients who formed Ab1 but not Ab2 (p < 0.004). Patients carrying the DR2 alleles, DRB1*1501, *1502 or *1601 were at a lower risk of producing anti-donor HLA antibodies.

Immunologic monitoring in lung allograft recipients.

To identify patients with increased risk of chronic lung allograft rejection, we assessed the utility of an in vitro biopsy-derived lymphocyte growth assay and serum anti-HLA antibody screening as a complement to currently available methods of monitoring lung allograft recipients. Lymphocyte growth assay was performed on bronchoscopic fragments of tissue cultured in medium with rIL-2. Seventy-nine biopsies from 31 lung transplant recipients were tested by lymphocyte growth assay, and results were correlated with histopathology findings. Positive lymphocyte growth was found in 12/26 (46%) episodes of acute rejection, 5/44 biopsies without rejection (11%), and 0/9 episodes of bronchitis. Positive lymphocyte growth was seen in 7/16 (44%) grade A1 rejections and in 5/10 (50%) grade A2 rejections, as opposed to only 5/44 (11%) grade A0 (no rejection) biopsies (P < 0.01 for both A1 and A2 with respect to A0). Actuarial probability of remaining free from obliterative bronchiolitis (OB)* tended to be higher in patients who did not exhibit lymphocyte growth in biopsies. Sequential samples of sera obtained at the time of the biopsy were screened for lymphocytotoxic anti-HLA antibodies. Twenty-two of 44 recipients (50%) developed anti-HLA antibodies during the first postoperative year, exhibiting greater than 10% reactivity to an HLA reference panel of lymphocytes in four or more consecutive serum samples. Actuarial survival of lung allograft recipients with anti-HLA antibodies (n = 22) was lower than in those without anti-HLA antibodies (n = 22; P = 0.03). Of the 22 antibody producers, 7/12 died as a consequence of OB. Of the 22 non-antibody-producers, 1/2 deaths occurred as a consequence of OB. Anti-HLA antibodies were present in 9/11 instances of OB (82% sensitivity) and in 13/33 patients without OB (61% specificity; P = 0.03). These data indicate that lung transplant recipients with positive lymphocyte growth and anti-HLA antibodies are at an increased risk of chronic allograft rejection.

Prolongation of primate cardiac xenograft survival with cyclosporine.

Cardiac xenotransplantation in nonprimates using traditional immunosuppression (azathioprine and prednisone) or cyclosporine has been unsuccessful or has required doses of immunosuppressants not tolerated by man. This study sought to determine if primate hearts could be transplanted successfully across genus boundaries using a dose of cyclosporine applicable to human transplantation. The hearts of outbred cynomolgus monkeys (Macaca fascicularis) were heterotopically transplanted into the necks of outbred baboons (Papio anubis). Hyperacute rejection did not occur and there were no cyclosporine-induced malignancies or nephrotoxicity. A 12-fold prolongation of mean cardiac xenograft survival to 77 days was accomplished using parenteral cyclosporine and steroids. The histology of rejection was notable for the appearance of reversible rejection on the 30-day biopsies. The histopathologic and immunologic data support the role of both cell-mediated and humoral mechanisms in primate cardiac xenograft rejection. Neither mixed lymphocyte cultures or cytotoxic antibody assays were predictive of graft loss, but there was a significant increase in their respective levels at the time of cessation of graft function. Thus, significant prolongation of primate cardiac graft survival across a genus boundary was accomplished using a dose of cyclosporine similar to that used in human transplantation.

Beta-adrenergic receptor sensitivity and guanine nucleotide regulatory proteins in transplanted human hearts and autotransplanted baboons.

This study was conducted in human subjects and in baboons to assess elements of the beta-adrenergic receptor complex in vivo and in vitro following cardiac transplantation. In human subjects, the concentration at which administered isoproterenol increased heart rate by 25 beats per min was within the normal range (mean, 3.2 +/- 0.4 micrograms). Myocardial biopsies and lymphocytes were obtained from 14 transplant recipients undergoing routine right heart catheterization. The stimulatory guanine nucleotide regulatory protein, Gs, was significantly greater in the lymphocyte than in right ventricular myocardium (5.8 +/- 1.7 vs. 2.0 +/- 0.5 relative to standard rat heart membrane preparation, P less than 0.05). In contrast, Gi was significantly greater in the myocardium than in the lymphocyte (4.2 +/- 1.3 vs. 1.1 +/- 0.3, P less than 0.025). There was no correlation between lymphocyte and cardiac G protein determinations. In the autotransplanted baboon heart, beta-receptors were increased (73 +/- 4 vs. 36 +/- 10 fmol/mg, P less than 0.05). Gs was not significantly different in denervated myocardial tissue vs. control cardiac tissue (1.1 +/- 0.2 vs. 0.8 +/- 0.2, P greater than 0.05). However, the inhibitory G protein, Gi, was significantly greater in transplanted animals (0.4 +/- 0.1 vs. 0.2 +/- 0.04, P less than 0.05). Relative enrichment of a Gi-like protein in the autotransplanted baboon heart was associated with a non-statistically significant trend towards a uniform reduction in basal and Gs-mediated adrenergic effects on adenylate cyclase activity. Despite the lack of biochemical evidence of enhanced beta-adrenergic receptor-mediated adenylate cyclase coupling, denervation in the autotransplanted baboon was associated with in vitro evidence of chronotropic and inotropic supersensitivity to isoproterenol. The results call into question the notion of adrenergic hypersensitivity in human subjects following cardiac transplantation, indicate the potential role for guanine nucleotide regulatory proteins in mediating responses of the denervated heart, and distinguish between several characteristics of the chronically denervated, transplanted human heart compared with the acutely auto-denervated of the baboon heart.

New strategies for early diagnosis of heart allograft rejection.

BACKGROUND: Allograft rejection is mediated by T cells that recognize allogeneic major histocompatibility complex (MHC) molecules via the direct and indirect pathway. The direct pathway involves T cells that react against MHC/peptide complexes expressed on the surface of donor antigen-presenting cells (APCs). In contrast, T cells involved in the indirect pathway recognize peptides derived from processing and presentation of allogeneic MHC molecules by self (recipient) APCs. To explore the relative contribution of these two pathways to rejection, we have evaluated the response of peripheral blood T cells from 50 heart transplant recipients against donor APCs (direct recognition) and against self APCs pulsed with synthetic peptides corresponding to the hypervariable region of the mismatched HLA-DR antigens of the donor (indirect recognition). METHODS: T cell reactivity against donor APCs was quantitated by measuring the expression of CD69 on allostimulated CD3+ LDA1+ cells. Reactivity to synthetic allopeptides was determined in limited dilution assays. RESULTS: Serial studies of the kinetics of direct and indirect recognition showed that both pathways contribute to early acute rejection episodes. Primary rejection was accompanied invariably by indirect recognition of a dominant allopeptide. Intermolecular spreading of T cell epitopes was observed during recurrent rejections. Enhanced recognition of donor alloantigens via the direct pathway was found predominantly during early rejection episodes. A single form of allorecognition was shown to occur in some rejection episodes. CONCLUSIONS: Monitoring of the direct and indirect pathway of allorecognition provides a reliable method for prediction and differential diagnosis of acute rejection of heart allografts.

Calculation of viable and infarcted myocardial mass from thallium-201 tomograms.

The feasibility of determining the mass of both viable and infarcted myocardium from tomographic images of thallium-201 distribution in the heart was studied in two normal dogs and ten dogs with acute infarction. Twenty-four hours after occlusion, thallium-201 was injected and 10 min later the hearts were removed and transaxial emission computed tomograms were obtained. Using the computer, an operator defined the epi- and endocardial surfaces of the left ventricle and the area of infarction in each tomogram. The computer then calculated values for total left-ventricular mass (TLVM) infarcted mass (IM) and the percentage of the left ventricle infarcted (% LVI). The calculated values were compared with measured weights, and good correlation was found between them: for TLVM, r = 0.87; for IM, r = 0.90; and for %LVI, r = 0.87. Good interobserver and intra-observer correlations were also found. Thallium-201 emission computed tomography offers a potential means to measure both myocardial mass and acute myocardial injury.

Imaging of cardiac transplantation rejection in primates using two new antimyosin agents.

Indium-111-labeled monoclonal antimyosin Fab has been used to image myocardial infarction, myocarditis and cardiac transplant rejection with localization in myocytes that have suffered irreversible loss of cell membrane integrity. Technical factors potentially limiting clinical usefulness of 111In antimyosin include dosimetry (72 hr half-life of 111In), slow blood clearance of antibody proteins delaying optimal imaging to 24 to 48 hr postinjection and nontarget organ uptake. Therefore, two new antimyosin imaging agents experimentally shown to potentially improve dosimetry, shorten time from injection to imaging or decrease nonspecific cell binding were evaluated in a primate cardiac transplant model. The two agents evaluated were polylysine 111In-antimyosin (0.023 mg Fab modified with a 3.3 kd polymer of polylysine and labeled with 111In) and 99mTc-antimyosin (0.5 mg Fab' antimyosin labeled using the RP-1 ligand technique). A total of eight baboons were studied: three with heterotopic (cervical) xenographs, three with orthotopic allographs and two control animals. Each animal was injected first with 12-23 mCi of 99mTc-RP-1 antimyosin and 5-16 hr after completion of imaging, was injected with 0.72-1.88 mCi of 111In-polylysine antimyosin (PIs) and reimaged 12-48 hr later. The imaging results were compared to the histology of the animals. Biexponential curves were fit to the blood sample data and rate constants were determined and expressed as T1/2 values. There were no significant differences between the two agents in either the early fast components or the late slow components. On planar imaging, there was blood-pool activity at 10-12 hr postinjection of both agents, but by 16-24 hr postinjection, blood pool was negligible on the 111In-PIs scans. Both agents were concentrated in the rejected cardiac tissue. The slow blood-pool clearance combined with the 6 hr half-life of 99mTc-RP-1 AMA make this agent less promising for detection of diffuse myocardial uptake than 111In Fab modified with polylysine.

Tomographic thyroid scintigraphy: comparison with standard pinhole imaging: concise communication.

Coded-aperture imaging (CAI) and multiple-view pinhole imaging (PI) of the thyroid were compared in a prospective study in 136 consecutive patients. Following 10 mCi of pertechnetate, 200K-count pinhole images were obtained in the anterior, RAO, and LAO projections, and CAI data were obtained in the anterior position. Four coronal tomographic sections were reconstructed by computer. Five observers read the studies separately, and ROC curves were constructed. Based on 109 pairs of studies, the ROC curves revealed similar performance for all observers for both techniques. When four observers compared the studies subjectively they rated the CAI more useful in 36% of cases, the PI in 6%, and the two equal in 58%. The advantages offered by the tomograms included improved contrast, accurate size representation of the gland at all depths, freedom frm pinhole-type distortion, and faster data acquisition. The major disadvantage to tomography was the 2-hr computer-processing time required. It this can be reduced, CAI offers sufficient advantages over conventional pinhole imaging to warrant its routine use.

Immunologic assessment of patients treated with bovine fibrin as a hemostatic agent.

Twenty-one cardiothoracic surgical patients have been treated with fibrin as a topical hemostatic/sealing agent, prepared from bovine fibrinogen clotted with bovine thrombin. Serum samples have been collected before treatment with fibrin and postoperatively between 1 and 9 days, 3 and 12 weeks, and 6 and 8 months. The titers of anti-bovine fibrinogen antibodies, measured by ELISA specific for immunoglobulins IgG or IgM, increased to maximal values after about 8 or 6 weeks, respectively. After 8 months, IgG titers were on average 20-fold lower than the mean maximal value, while IgM titers returned to the normal range. IgG was the predominant anti-bovine fibrinogen immunoglobulin as documented by ELISA, affinity chromatography and electrophoresis. Anti-bovine fibrinogen antibodies present in patients reacted readily with bovine fibrinogen, but did not cross-react with human fibrinogen as measured by ELISA or by immunoelectrophoresis. A significant amount of antibodies against bovine thrombin and factor V has been found, many cross-reacting with the human counterparts. No hemorrhagic or thrombotic complications, or clinically significant allergic reactions, occurred in any patient, in spite of antibody presence against some bovine and human coagulation factors. The treatment of patients with bovine fibrin, without induction of immunologic response against human fibrinogen, appeared to be an effective topical hemostatic/sealing measure.

What is 'minimally invasive' coronary bypass surgery? Experience with a variety of surgical revascularization procedures for single-vessel disease.

BACKGROUND: Although the use of small incisions is theoretically appealing, it has been argued that the true advantage of minimally invasive approaches to myocardial revascularization lies in the avoidance of cardiopulmonary bypass. METHODS: Of 25 patients referred for surgical revascularization of single-vessel coronary disease, 20 elected to undergo a minimally invasive coronary artery bypass grafting (MICABG) procedure, while 5 opted to have conventional surgery with cardiopulmonary bypass (CPB). Patients having MICABG underwent single-vessel revascularization without CPB, via limited anterior thoracotomy, hemisternotomy, or median sternotomy. Intraoperatively, hemodynamics, anastomotic time, and total operative time were recorded. Postoperatively, length of hospital stay, incidence of myocardial infarction, indexes of end-organ function, and morbidity rates were recorded. In addition, patient questionnaires were used to assess subjective end points such as postoperative pain, wound drainage, and quality of life. RESULTS: Fifteen of 20 patients undergoing MICABG underwent revascularization without CPB, while 4 were converted to standard coronary artery bypass grafting with CPB due to technical reasons and 1 for intraoperative ventricular fibrillation. Patients undergoing MICABG had no perioperative myocardial infarctions, while those having CPB had two infarctions (20%). Furthermore, there were no differences in length of stay or postoperative morbidity among the various approaches, while the MICABG procedures, especially via median sternotomy, were associated with shorter operative times. CONCLUSIONS: The advantage of MICABG lies mainly in the avoidance of CPB. Thus, we advocate that surgeons initially utilize the median sternotomy and limited skin incision for MICABG to assure adequate exposure, technical precision, and patient safety. After a reasonable level of technical proficiency and experience are attained, the limited anterior thoracotomy approach can be used.

Heart reduction surgery: an analysis of the impact on cardiac function.

OBJECTIVES: Reports of improved ejection fraction, coupled with decreased filling pressures, have prompted a number of centers to begin evaluating the efficacy of heart reduction surgery to ameliorate symptoms of heart failure. However, the impact of this operation on cardiac mechanics is unknown. We applied a multiple compartment elastance model to simulate the effects of excising cardiac mass on heart function. METHODS: The left ventricle was divided into two functional compartments to simulate excision of part of the wall. At multiple increments of mass reduction, the resulting end-systolic elastance, ejection fraction, stroke volume, end-diastolic pressure and volume, and diastolic stiffness were determined. RESULTS: Changes in systolic function were accompanied by offsetting changes in diastolic function; consequently, overall pump function (the Frank-Starling Relationship) was found to be depressed. The geometric rearrangement associated with this operation leads to a reduction in wall stress for a given level of pressure generation, thus implying an increase in the efficiency with which wall stress is transduced into intraventricular pressure. CONCLUSIONS: Overall pump function is depressed in the short run after heart reduction surgery. However, on the basis of theoretic arguments, heart reduction surgery may have long-term beneficial implications. Importantly, this analysis revealed that changes in parameters of ventricular function have different implications during heart reduction surgery than when such changes are observed with inotropism caused by acute pharmacologic therapy.