Altered distribution and density of myocardial beta-adrenoceptors during acute rejection in rats.

BACKGROUND: A better understanding of altered expression of myocardial beta-adrenoceptors can facilitate the diagnosis of early and late acute rejection of heart transplants. METHODS: We submitted rats to heterotopic heart transplantation (iso- and allografts) of which one of each were treated with or without cyclosporin A for 4, 7, and 14 days (n=5, respectively). The cardiac sections were incubated in vitro with [3H]CGP 12177, or the hearts were labeled in vivo by intravenous injection of [3H]CGP 12177. Autoradiographic images of both were analyzed digitally and compared with histologic findings. RESULTS: Beta-adrenoceptor distribution in native hearts and isografts was homogeneous, but highly differential distribution and density in allografts were observed in the left and right ventricular walls and in the interventricular septum despite treatment with cyclosporin A. High-density areas in the progressive course of acute rejection are commonly associated with up-regulation of beta-adrenoceptors in apparently viable myocytes, although histologic findings confirmed many infiltrating mononuclear cells. Low-density areas, which were identified in the right and left ventricular walls as early as 4 days after transplantation, correlated with derangement of myocytes, which was suggestive of early acute rejection. The images obtained by in vivo technique were comparable to in vitro images. CONCLUSIONS: The alteration of beta-adrenoceptor expression in allografts showed a close relationship with the severity of acute rejection, and the techniques employed in this model were useful in our study of the rejection process and in detecting early and late acute rejection in the rat.

Quantitative analysis of cardiac 3-L-nitrotyrosine during acute allograft rejection in an experimental heart transplantation.

BACKGROUND: Recent studies have shown that nitric oxide interacts with superoxide to form peroxynitrite, a potent oxidant that modifies cellular proteins producing 3-L-nitrotyrosine (N-Tyr). This study was designed to evaluate N-Tyr quantitatively with high-performance liquid chromatography (HPLC) during cardiac allograft rejection. METHODS: Rat transplanted hearts (allogeneic or syngeneic grafts) were examined with HPLC analysis, immunohistochemistry for N-Tyr, and histological studies on 0, 1, 3, and 7 days after transplantation. RESULTS: No histological rejection was found in syngeneic grafts, or day 0 or 1 allografts. HPLC demonstrated that N-Tyr in allografts increased on day 1 and continued to increase through day 7, while N-Tyr was not detected in any syngeneic grafts. Immunostaining of the allografts did not show N-Tyr on day 1. CONCLUSION: These results demonstrate that N-Tyr shows a time-dependent accumulation in cardiac allografts during acute rejection. N-Tyr detection using HPLC may be an useful maker for early diagnosis of acute rejection before pathological rejection occurs.

Sound spectral analysis of prosthetic valvular clicks for diagnosis of thrombosed Björk-Shiley tilting standard disc valve prostheses.

To evaluate clinical usefulness of sound spectral analysis in the early detection of prosthetic thrombosis, we analyzed specific patterns of thrombus formation in Björk-Shiley tilting standard disc prostheses in relation to the sound spectral analysis of their click sounds. Among a total of 365 Björk-Shiley tilting standard disc prostheses, nine became thrombotic. These consisted of seven prostheses in the mitral position and two in the aortic position, and the affected valves were replaced in all cases. The sound spectral analysis system includes a wide-frequency microphone and a sound spectral analyzer. To quantify the amplitude of the metallic clicks that are specific to the prosthetic valve sounds, we used a normalized maximal frequency as a diagnostic parameter for valve thrombosis. Thrombus formation was localized at the minor strut in two cases, and these demonstrated abnormally low normalized maximal frequency values only on opening clicks. In four cases thrombus formations were noted at both minor and major struts, and these showed abnormally low normalized maximal frequency values on both opening and closing clicks. In two cases with pannus formation, no abnormalities were found by sound spectral analysis. In one case, which had demonstrated abnormally decreased normalized maximal frequency values of both opening and closing clicks, the normalized maximal frequency values were normalized after thrombolytic therapy, suggesting resolved thrombosis. Reoperation, which was performed for concomitant complication of perivalvular leak, revealed no noticeable thrombus formation. The thrombi were seen on the minor strut during surgical procedures in all cases in which valve thrombosis was indicated by the sound spectral analysis. Therefore, the minor strut is considered to be the prevalent area of thrombus formation, and diagnosis could be made after observation of abnormally low normalized maximal frequency on opening clicks. We found the sound spectral analysis to be an extremely useful diagnostic tool for early detection of thrombosis in the Björk-Shiley tilting standard disc prostheses, especially because the opening clicks of the tilting disc valve were too low in amplitude for auscultation to detect the existence of mild abnormality.

Changes in myocardial beta-adrenergic receptors during acute rejection of heterotopically transplanted rat hearts.

To evaluate changes of the myocardial beta-adrenergic receptors in acute cardiac graft rejection, the density and binding affinity value of the myocardial beta-adrenergic receptors in heterotopically transplanted rat isografts and allografts were analyzed. Hearts from Fisher rat donors were transplanted either to the Fisher rats (isografts) or to Lewis rats (allografts). Histologic examination of the allografts showed mild to moderate rejection on the seventh and fourteenth days and showed severe rejection on the twenty-first day after transplantation. The density values in the allografts and isografts similarly increased significantly (p < 0.05) above the normal level on the seventh and fourteenth days after transplantation. The density in allografts on the twenty-first day decreased significantly (p < 0.05) below the normal level, while that in isografts remained at the normal level. In contrast, the binding affinity value of myocardial beta-adrenergic receptors in both isografts and allografts did not change after transplantation. These results demonstrated that myocardial beta-adrenergic receptors presented upregulation in mild to moderate rejection, whereas these receptors presented downregulation in severe rejection. The data suggested that downregulation of myocardial beta-adrenergic receptors plays a major role in decreased cardiac contractility during severe rejection, but not during mild and moderate rejection.

Surgical treatment for hypoplastic left heart syndrome: case reports.

A 58-day-old girl with hypoplastic left heart syndrome underwent bypass grafting from the pulmonary artery to the descending aorta, ligation of the ductus arteriosus, and banding of the main pulmonary artery distal to the graft. Anastomoses of the graft were performed by partial clamping of the arteries under moderate surface hypothermia. The patient tolerated the procedure well and was discharged from the intensive care unit on the eleventh postoperative day, but she died on the twentieth day of metabolic derangement. Our total experience with this anomaly includes three other infants, and a summary of these patients and applied surgical procedures are presented. Surgical and diagnostic considerations for this anomaly based on our experiences are discussed.

Effects of cyclosporine and 15-deoxyspergualin on coronary arteriosclerosis after heart transplantation in the rat.

The development of graft coronary arteriosclerosis remains a serious consequence after heart transplantation and may limit long-term survival. The purpose of this study was to evaluate the effects of 15-Deoxyspergualin on graft coronary arteriosclerosis after heterotopic heart transplantation in a rat model and compare the effects to those of cyclosporine treatment. Two groups of Lewis rats (n = 7 each group) underwent heterotopic heart transplantation from Fischer 344 donors and were treated with either cyclosporine (10 mg/kg/day) or 15-Deoxyspergualin (3 mg/kg/day). Histologic evaluations of rejection (scale: 0 = none, 3 = severe) and graft coronary arteriosclerosis (scale: 0 = normal, 4 = occluded) were made 60 days after transplantation. No significant difference was found between the two groups with respect to the degree of rejection (2.0 +/- 0.7 in the cyclosporine-treated group versus 2.0 +/- 0.5 in the 15-Deoxyspergualin-treated group). However, the extent of graft coronary arteriosclerosis in the 15-Deoxyspergualin-treated group was significantly less than that seen in the cyclosporine-treated group (1.11 +/- 0.34 versus 1.71 +/- 0.24, p < 0.01). Furthermore, the incidence of diseased vessels among all observed vessels was significantly lower in the 15-Deoxyspergualin-treated group compared with the cyclosporine-treated group (63% +/- 12% versus 76% +/- 7%, p < 0.05). Although the protective mechanism of 15-Deoxyspergualin is unknown, it most likely possesses a different immunosuppressive mechanism of action from cyclosporine. We concluded that 15-Deoxyspergualin is superior to cyclosporine in preventing graft coronary arteriosclerosis after heart transplantation.

Proposal of a working left heart model with a heterotopic transplantation technique in rats.

BACKGROUND: A heterotopically transplanted rat heart model described by Ono and Lindsey in 1969 has been widely used as a fundamental animal model of heart transplantation. However this "nonworking" model is greatly different from the orthotopic heart in view of left ventricular work, in which the experimental results obtained may not always reflect the clinical setting with an orthotopic transplanted "working" heart. We herein propose a new "working" left heart model in rats using a heterotopic abdominal transplantation technique by modifying the method of Ono and Lindsey. METHODS: First, a donor heart graft and a recipient were prepared in the conventional fashion. Second, the donor heart was tailored by the ligation of main pulmonary artery and the removal of tricuspid valve and interatrial septum. Third, the ascending aorta and right atrium of the donor heart were anastomosed to the infrarenal abdominal aorta and to the inferior vena cava of the recipient, respectively. Consequently, the left atrium and ventricle of heart graft were loaded with the blood from the right atrium through the interatrial communication. RESULTS: This surgical procedure required an average of 58 minutes and had negligible operative risk. The donor left ventricle produced a systolic blood pressure almost equal to the recipient's aortic pressure and maintained vigorous beat. CONCLUSIONS: This model is easily reproducible and would be useful for various studies on heart transplantation.

Hemodynamic performance in a heterotopically transplanted dog heart: proposal of techniques for working left heart model of heterotopic (abdominal) heart transplantation.

To study hemodynamics together with various aspects of rejection after experimental heart transplantation, we developed a technique to produce a working left heart model of heterotopic (abdominal) heart transplantation. The interatrial septum and tricuspid valve of the donor heart are removed. The pulmonary arterial trunk, pulmonary veins, and inferior vena cava are ligated, and the stumps of the donor aorta and superior vena cava are anastomosed in an end-to-side fashion to the recipient abdominal aorta and inferior vena cava, respectively. Arterial blood from the recipient abdominal aorta thus perfuses the donor myocardium through the coronary artery, and the donor left ventricle receives venous blood from the recipient inferior vena cava as preload. In this model, the donor left ventricle does not pump out enough venous blood to desaturate the recipient femoral arterial blood but does generate approximately the same pressure as the recipient's heart. This model is reproducible, easy to manage, and can be applied to heterotopic heart transplantation in various experimental animals including rats.

Egocentric perception through interaction among many sensory systems.

We perceive the egocentric position and velocity of ourselves by many senses, such as vision, proprioception and vestibular sense. Normally the information by these senses is in harmony. However, there are situations in which the information is inharmonious. When we watch a wide-screen monitor or we ride in an accelerating or turning vehicle, visual information conflicts with proprioceptive and vestibular information. Since human egocentric perception has been studied for each separate sense in the previous research, it is not clear how the integration among these senses contributes to perception of human orientation. In Experiment 1, we investigated the contribution of visual, proprioceptive and vestibular information in isolation and in combination to perception of direction of forward self-motion. An observer rode in small vehicle (vestibular information) or walked (proprioceptive information) through a narrow corridor. Many vertical bars were hung from a ceiling of the corridor. When the observer moved forward, she/he viewed expanding optic flow of the bars (visual information) through video cameras and a helmet-mounted stereoscopic display. By fastening the observer and/or the cameras at different angles, consistent or conflicting information about forward direction was given through each sense. It was found that when there was conflicting information about the direction of forward motion (a) vestibular information was more dominant than visual cute, (b) visual and proprioceptive information was linearly added with weighting, and (c) visual information was dominant for backward motion. In Experiment 2, we investigated sensory integration when we moved forward with linear acceleration. Direction of the acceleration was either forward or sideways, namely corresponding to a ride in an accelerating or turning vehicle. We developed a new method to measure sensation or self-motion more objectively by using the three-dimensional position-sensor system. Positions of observer's head, shoulder, waist and ankle were measured to find body tilt accompanied by sensation of self-motion. It was found that the body tilted towards the opposite direction of the self-acceleration and the angle of body tilt was in good agreement with the subjective amount of the accelerating sensation. The body tilt was even induced by solely visual information. This implied that visual information contributed to perception of self-acceleration as well as self-motion.

A single pericardial patch technique for repair of partial anomalous pulmonary venous drainage associated with sinus venosus atrial septal defect.

A technique is described for repair of partial anomalous pulmonary venous drainage associated with sinus venosus atrial septal defect. The procedure, using a single autologous pericardial patch, is able to facilitate both reconstruction of the pulmonary venous channel and enlargement of the superior vena cava. This technique also reduces the incidence of arrhythmias.

Recurrent thymoma in patients with myasthenia gravis.

One hundred sixty-six patients underwent operation for myasthenia gravis between 1977 and 1989. Thirty-eight patients had associated thymoma, registering stages I (n = 17), II (n = 9), III (n = 11), and IVa (n = 1) according to the classification of Masaoka and colleagues. Extended thymectomy was performed on 128 patients without thymoma; thymothymectomy, with resection of the anterior mediastinal fat and tissues adherent to the tumor, was performed in all patients with thymoma. There were no instances of early or late death. Neuromuscular function improved, and clinical myasthenic symptoms stabilized in almost all patients except 2 patients in stage III and 1 patient in stage IVa, who had an exacerbation of the myasthenic symptoms associated with recurrence of thymoma. All the recurrent tumors were on the pleura and could be resected. The suspected cause of recurrence is either dissemination of tumor cells as a result of operative manipulation or undetected disseminated foci that existed at the time of the first operation. The resections of the recurrent invasive thymomas localized on the pleura were easily performed and improved the myasthenic symptoms.

Pulmonary vascular changes induced by congenital obstruction of pulmonary venous return.

BACKGROUND: Pulmonary venous obstruction (PVO) induces pulmonary arterial hypertension, as well as pulmonary venous hypertension, and jeopardizes the repair of cardiac lesions. METHODS: Four cases of congenital mitral stenosis and 4 cases of cor triatriatum (Lucas type A), ages ranging from 2 months to 16 years, were histologically examined on pulmonary vasculature. Histometrical analysis was performed on medial thickness and intimal changes of both pulmonary arteries and veins. For comparison, the examination of pulmonary vasculature in ventricular septal defect (VSD) cases was also performed. RESULTS: Medial thickening and intimal fibrosis, in both pulmonary arteries and veins with widespread lymphangiectasia, were characteristic vascular changes of PVO cases. Medial thickness of pulmonary arteries was correlated with preoperative pulmonary arterial pressure (PAP) (r = 0.77, p = 0.03 for systolic PAP), and greater than that of VSD cases. Medial thickness of pulmonary veins was also greater in PVO cases. Intimal fibrosis of pulmonary arteries and veins was seen extensively at the advanced ages, whereas no plexiform lesions or more advanced stages of pulmonary vascular disease were present. CONCLUSIONS: Congenital PVO induced progressive medial thickening and intimal fibrosis in pulmonary arteries and veins accompanied by lymphangiectasia. However, no plexiform lesions or more advanced stages of pulmonary vascular disease were present, which may explain the reversibility of pulmonary hypertension due to congenital PVO.

Extracardiac conduit composed of gutter-shaped prosthesis and pedicled pericardial valved patch for pulmonary trunk reconstruction.

A conduit for reconstruction of the pulmonary trunk is presented. A Gelseal vascular prosthesis (Vascutek Ltd, Inchinnan, Scotland) was split longitudinally in two halves, and one half was used as a posterior wall of the conduit like a gutter. The anterior wall was constructed by a pedicled pericardial valved patch. Finally, the proximal anastomosis of the conduit was completed with a gusset cut from the Gelseal prosthesis. This conduit can be applied to patients who require the Rastelli procedure, and growth potential of the pedicled pericardial patch may be expected.

Cleft on tricuspid anterior leaflet.

We report a case of isolated congenital tricuspid regurgitation caused by a cleft in the anterior tricuspid leaflet associated with a patent foramen ovale. Preoperative echocardiography revealed severe tricuspid regurgitation resulting from anterior tricuspid leaflet prolapse. The patient underwent successful tricuspid valve repair with simple cleft suture and annuloplasty and direct closure of the patent foramen ovale.

Spontaneous rupture of the thoracic aorta.

BACKGROUND: Spontaneous rupture of the thoracic aorta without trauma, aneurysm, or dissection is an extremely rare but catastrophic disorder. Two cases of spontaneous aortic rupture are presented, both treated surgically with satisfactory results. METHODS: A review of the English literature found 16 patients with the diagnosis of spontaneous rupture of the thoracic aorta from 1961 through 1998. Eighteen reported cases, including the 2 cases presented herein, are reviewed. RESULTS: The representative clinical picture is one of a middle-aged hypertensive patient with acute chest pain and collapse, with imaging modalities demonstrating hemopericardium, hemomediastinum, or hemothorax. According to the reported experiences, aortography was accurate for identifying the rupture site although the findings were sometimes subtle. Misdiagnosis or nonsurgical management resulted in the patient's death. All 8 patients who did not undergo aortic repair died within 3 weeks after the onset, whereas 9 of 10 patients who underwent surgical aortic repair survived. CONCLUSIONS: For patients with a definitive or possible diagnosis of spontaneous rupture of the thoracic aorta, prompt operation is imperative through an optimal surgical approach to identify and repair the rupture site with appropriate circulatory support.

Replacement of the transverse aortic arch for type A acute aortic dissection.

Surgical treatment of acute aortic dissection involving the segment of transverse aortic arch is difficult and often associated with a high mortality and morbidity. The high mortality and morbidity are primarily related to anatomic features and techniques of cerebral protection employed during the period of aortic branch occlusion needed for reconstruction. This study reports our experience of 20 consecutive cases of acute type A aortic dissection treated by repair or replacement of the transverse aortic arch during emergency operation. Ages of the patients ranged from 56 to 76 years. All patients were referred to us within 2 weeks of onset (mean time, 58 hours). Selective cerebral perfusion or deep hypothermia with complete circulatory arrest was employed during the period of aortic branch occlusion. Duration of cerebral perfusion, circulatory arrest, myocardial ischemia, and cardiopulmonary bypass averaged 106 minutes, 32 minutes, 127 minutes, and 248 minutes, respectively. There were three operative deaths. All three dissections were ruptured ones, and the patients died of hemorrhage, deep coma, or multiple organ failure. One patient died of infection 3 months after operation. The remaining patients are alive and well without any detectable neurological deficit 1 month to 4 years postoperatively. This experience emphasizes that repair or replacement of acute type A aortic dissection involving the aortic arch can be performed safely by adequate selection of patients, supportive measures, and operative methods.

Protection of the brain during hypothermic perfusion.

The adequacy of the circuits for brain perfusion has been explored by hemodynamic assessment using the ability of the brain to autoregulate blood flow as an indicator, and by morphologic observation using carbon black or Evans blue infusion into the brain perfused antegradely or retrogradely. It is concluded that the safe pressure of cerebral perfusion needed to maintain cerebral integrity is between 40 and 50 mm Hg in both normothermic and hypothermic perfusions, a pressure that can be generated by nonpulsatile pump flows through the pump greater than 40 mL.kg-1 x min-1. Morphologic studies revealed development of focal infarctions in the brain and destruction of the blood-brain barrier by retrograde cerebral perfusion. The retrograde approach, therefore, is definitely inferior to the antegrade method. Antegrade perfusion for 90 minutes, however, produced minimal cerebral edema, suggesting the need for further improvement even in techniques of antegrade perfusion.

Thoracic aortic operations in patients aged 70 years or older.

Thirty-one patients over the age of 70 years (group A) and 72 patients less than 69 years (group B) underwent a variety of thoracic aortic surgical procedures. Early and long-term results and cerebral function were compared between the two groups. Preoperative and postoperative cerebral function was evaluated using mini mental state-Himeji and Wechsler adult intelligence scale tests. The operative mortality of groups A and B was 12.9% and 11.1%, respectively (not significant). There were no significant differences in postoperative complications between the two groups. The late mortality rates of groups A and B were 11.1% and 9.3%, respectively (not significant). There were no significant differences between the two groups in the mini mental state-Himeji test, digit symbol, vocabulary, and total Wechsler adult intelligence scale scores before and after operation. We conclude that thoracic aortic surgical procedures in patients over 70 years of age can be performed with acceptable mortality and morbidity risks. Most patients showed symptomatic improvement.

Permanent pacemaker implantation in premature infants less than 2,000 grams of body weight.

Pacemaker implantation in premature infants presents technical problems because of the relatively larger size of the pulse generator compared with their bodies. A new technique with which successful generator implantation was performed in 2 premature infants less than 2,000 g of body weight is described. The generator is wrapped in a Gore-Tex surgical membrane. A piece of membrane overlying the electrical contact surface of the generator is removed, and the generator is fixed to the abdominal wall in the peritoneal cavity. The technique is simple to perform and would give relative ease in generator exchange.

Tricuspid valve closure for neonatal Ebstein's anomaly.

A respirator-dependent 11-day-old boy with Ebstein's anomaly is presented. His cardiac anomaly with progressive cardiomegaly was first noticed at 24 weeks' gestation on fetal echocardiography. After birth, he required mechanical ventilation because of massive tricuspid regurgitation and restricted pulmonary blood flow. The operation of tricuspid valve patch closure, resection of right atrial wall, and central shunt successfully weaned him from the respirator on postoperative day 13. Cavopulmonary anastomosis was performed without problem when the patient was 8 months of age.