Aging augments IL-17 T-cell alloimmune responses.

As increasing numbers of elderly patients require solid organ transplantation, the need to better understand how aging modifies alloimmune responses increases. Here, we examined whether aged mice exhibit augmented, donor-specific memory responses prior to transplantation. We found that elevated donor-specific IL-17, but not IFN-gamma, responses were observed in aged mice compared to young mice prior to transplantation. Further characterization of the heightened IL-17 alloimmune response with aging demonstrated that memory CD4(+) T cells were required. Reduced IL-2 alloimmune responses with age contributed to the elevated IL-17 phenotype in vitro, and treatment with an anti-IL-17 antibody delayed the onset of acute allograft rejection. In conclusion, aging leads to augmented, donor-specific IL-17 immune responses that are important for the timing of acute allograft rejection in aged recipients. IL-17 targeting therapies may be useful for averting transplant rejection responses in older transplant recipients.

Relation between component parts of fibrocystic disease complex and breast cancer.

Specimens of benign breast disease obtained from biopsies performed at Vanderbilt Hospital (Nashville, Tenn.) between 1952 and 1959 were histologically reviewed and characterized as to individual component types of fibrocystic disease. Follow-up for information regarding breast cancer development was 94% successful. Carcinoma developed more often when epithelial proliferative lesions were present. Atypical lobular hyperplasia had a greater predictive value than other epithelial lesions and was associated with an elevated risk six times that expected prior to the age of 45 years and a tripling of risk after the age of 45 years. Various ductal hyperplastic lesions are associated with approximately a doubly increased risk that is present only if the lesions are identified at biopsy after the age of 45 years. Women with cysts, sclerosing adenosis, fibrosis, and other nonhyperplastic changes were at no greater risk for subsequent carcinoma than women in the general population.

Successful aortocoronary bypass in osteogenesis imperfecta.

Cardiovascular abnormalities are infrequently documented in osteogenesis imperfecta, one of a group of hereditary, generalized connective tissue disorders. A patient with osteogenesis imperfecta is described with mitral valve prolapse, significant coronary artery disease and a coronary artery aneurysm. The latter two cardiac defects are apparently rare in this disease. The option of surgery was carefully considered with regard to technical feasibility and potential deterioration of the graft anastomoses. Although successful aortocoronary bypass surgery had not been previously reported in osteogenesis imperfecta, this patient received such surgery with therapeutic benefit. Therefore, coronary artery vascularization should be considered as a safe and effective treatment modality for patients with osteogenesis imperfecta and coexisting coronary atherosclerosis.

Factors affecting outcome of coronary reperfusion with intracoronary streptokinase in acute myocardial infarction.

Aggressive interventional therapy in acute myocardial infarction (AMI) is expensive, time-consuming and not without significant risk. To determine which patients are most likely to benefit from such therapy, the effects of patient age, reperfusion success, admission left ventricular (LV) function, infarct location, admission clinical class, time from onset of pain to reperfusion and admission electrocardiographic findings on the outcome of coronary reperfusion in AMI were assessed in 292 prospectively studied, sequential patients from August 1980 to January 1984. Two hundred ten patients received intracoronary streptokinase (SK) therapy on admission and 82 patients, who either refused the protocol or met exclusion criteria, served as control subjects. Patients older than 65 years showed little improvement in 1-year mortality risk and no significant improvement in LV function during hospitalization after treatment with intracoronary SK. The remaining patients, 178 treated with SK and 48 control, were well matched and served as the basis for further comparisons. In this subgroup of patients, reperfusion success was associated with improved survival and LV function (mortality rate 3%, vs 17% in control subjects; increase in ejection fraction [EF] 18% vs 4%). Patients with an EF of less than 45% on admission showed a 21 +/- 30% increase in EF, compared with an increase in control subjects of 8 +/- 19%, and a lower 1-year mortality rate than controls (6% vs 21%, p = 0.01). Patients with anterior AMI had a significant increase in EF in the SK group (22 +/- 31%) and lower mortality compared with control subjects (5% vs 25%, p = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

Improved recovery of cardiac function after hypothermic ischemic storage with ouabain.

We investigated the hypothesis that ouabain would reduce energy expenditure in the hypothermic, ischemic heart by inhibiting membrane-bound sodium/potassium-activated adenosine triphosphatase and lead to improved function on reperfusion. Additionally, we compared ouabain with another potential adjunct, the calcium channel blocker verapamil. The isolated rabbit heart was used as a model, and three experimental groups were studied after 1, 6, 12, and 24 hours of 4 degrees C ischemia. Hearts in group I were stored in a standard high potassium solution; hearts in groups II and III were stored in the same solution supplemented with verapamil (2 mg/L) and ouabain (3 mg/L), respectively. After ischemia, all hearts were reperfused for 45 minutes on a modified Langendorff apparatus, and left ventricular function was measured before freeze-clamping the heart for metabolite determination. At 1 and 6 hours, hearts in all groups functioned well, but the group III hearts had higher levels of adenosine triphosphate, phosphocreatine, total adenine nucleotides, and glycogen. After 12 hours of ischemia, function was significantly better in group III hearts (p less than 0.01) compared with that of hearts in groups I and II. Group III hearts also exhibited higher levels of high energy phosphates and glycogen. After 24 hours of storage, all hearts functioned poorly, and there was a marked decline in measured metabolites. Although we could show no improvement with the addition of verapamil, ventricular function was improved after storage in a high potassium hypothermic solution containing ouabain. Because ouabain inhibits the hydrolysis of adenosine triphosphate by sodium/potassium-activated adenosine triphosphatase, this result suggests that the glycoside maintains energy-rich phosphates necessary for optimal resumption of cardiac function.

Early experience with the ionescu-shiley pericardial xenograft valve. Accelerated calcification in children.

Recognizing the problems of thromboembolism and anticoagulation in children and the high incidence of calcification in porcine valves in children, we hoped that the Ionescu-Shiley valve might be a good choice in the younger age group. We implanted 2,372 Ionescu-Shiley valves in 2,167 patients between 1978 and 1982, of which 30 were in children 16 years of age and younger. Although there have been no known instances of thromboembolism, valve infection, or valve disruption in this group of children, seven (23%) have already required reoperation for calcific stenosis. Although calcification appears maximal in postpubertal children less than 17 years of age, we consider it unwise currently to place these valves in any child and have returned to mechanical valves for this purpose.

Early bypass grafting following intracoronary thrombolysis with streptokinase.

Early bypass grafting following intracoronary thrombolysis with streptokinase may be indicated in patients with acute coronary artery thrombosis and severe coronary disease. To evaluate this approach, we prospectively studied 41 patients (32 men and nine women, mean age 53 years) with acute infarction. Emergency cardiac catheterization was performed within 18 hours after onset of chest pain and intracoronary streptokinase was given. All patients underwent bypass 3 to 10 days later (mean 7 days). Serial gated radionuclide left ventricular angiograms to determine ejection fraction were obtained on hospital admission, preoperatively, and 3 to 6 months later. Thirty-four patients had complete occlusion of the artery supplying the infarcted segment. In 30 patients (88%) reperfusion was not successful. In seven patients the artery was not totally thrombosed. Thirty-two patients (78%) had multivessel disease. An average of 2.8 grafts per patient were placed with an operative mortality of 2% (one patient). Serial measurements of ejection fraction were obtained in 23 patients in whom the admission ejection fraction was less than 50%. There was a significant increase in ejection fraction from admission (33% +/- 11%) to the preoperative measurement (41% +/- 9%, p less than 0.001), and this improvement persisted at follow-up (40% +/- 14%). Intracoronary streptokinase has been shown to restore blood flow to infarcting myocardium and to improve left ventricular performance. In patients with significant organic stenosis, the risk of bypass grafting 3 to 10 days after intracoronary streptokinase infusion appears to be no different from the risk of elective operation performed at a time remote from an acute infarction.

Techniques and results of ventricular aneurysmectomy with emphasis on anteroseptal repair.

We have reviewed an 8 year experience with ventricular aneurysmectomy in 170 patients. Ninety percent had anterior aneurysms and underwent "anteroseptal repair" with exclusion of nonfunctioning septal myocardium. Preoperative left ventriculograms and coronary arteriograms were studied and "scored," and the hospital mortality and long-term survival rates for various subsets of the group were correlated with their radiographic data. A postoperative score for the coronary arteries was developed according to the preoperative anatomy and the vessels bypassed. Both the ventriculogram score and the postoperative coronary score had significant effects on both hospital mortality and long-term survival rates. The severity of preoperative coronary disease had minimal predictive value. Recent myocardial infarction did not preclude a good result. The value of an aggressive surgical approach to patients with ventricular aneurysm was confirmed even for certain subsets with indicators suggestive of poor prognosis. Anteroseptal repair appears to give optimal results for the typical "anterior" aneurysm. All suitable coronary arteries should be bypassed. Attention to the details of preoperative anatomy and function allows the most accurate prediction of prognosis and dictates the optimal therapeutic approach.

Esophageal obstruction caused by mediastinal histoplasmosis: beneficial results of operation.

A patient presented with progressive dysphagia and chest pain. Radiologic investigation showed extrinsic compression of the esophagus by enlarged, calcified, mediastinal lymph nodes. Immunologic studies suggested that this was due to previous histoplasmosis, currently inactive. The nodes were excised at thoracotomy, with complete relief of symptoms. Operative management was most appropriate because of the apparent inactivity of the infection, the severity and progressive nature of the symptoms, and the possible prophylaxis of mediastinal fibrosis, a well-documented complication of histoplasmosis.

Cholangitis with a silver lining.

Acute obstructive cholangitis developed secondary to a common duct stone formed around a silver hemostatic clip, introduced at cholecystectomy two years previously, that had migrated from a long cystic duct remnant. Stone formation around a silk suture is well known, and silver clips in the area of the porta hepatis may constitute a similar hazard.

Peripheral pulmonary artery aneurysm in a patient with limited respiratory reserve: controlled resection using cardiopulmonary bypass.

Pulmonary artery aneurysms are rare lesions for which operative management is not frequently undertaken. When operation is indicated, central lesions involving the pulmonary trunk, right main pulmonary artery, or left main pulmonary artery are repaired using cardiopulmonary bypass. Peripheral aneurysms in segmental intrapulmonary arteries have been managed most frequently by lobectomy, but occasionally by aneurysmectomy and pulmonary arterial repair. We used cardiopulmonary bypass for peripheral pulmonary aneurysmectomy in a patient with limited respiratory reserve because he had undergone prior contralateral bilobectomy; this allowed controlled resection while preserving a maximal amount of pulmonary parenchyma.

Apicoaortic conduits for complex left ventricular outflow obstruction: 10-year experience.

We interposed valved conduits between the left ventricular apex and aorta in 38 patients over a 10-year period. Indications included tunnel subaortic stenosis, aortic annular hypoplasia, tubular supravalvular aortic hypoplasia, and severe calcification of the ascending aorta. Operative mortality was 11%, but 78% of the survivors were alive at 5 years, and 70% had had no major complication. The results were better in adolescents and adults than in young children. Although complications included calcific degeneration of the valve and disruption of the conduit at the site of insertion into the ventricular apex, we continue to believe in the utility of this procedure in a few patients with complex left ventricular outflow tract obstruction.

Atrial rupture in a child from cardiac massage by his parent.

A 4-year-old boy presented with a single seizure following a viral syndrome. He had a pericardial effusion on admission, and this increased suddenly on the third day of hospitalization, producing cardiac tamponade. After blood was aspirated from the child's pericardial cavity, the father revealed that he performed cardiac massage on his son following the seizure. A laceration of the right atrium was repaired at operation, and the boy made a good recovery. Cardiopulmonary resuscitation by lay persons is not without hazard, and patients with such a history should be watched carefully for the possibility of damage to intrathoracic structures.

Comparison of dopamine and dobutamine therapy during intraaortic balloon pumping for the treatment of postcardiotomy low-output syndrome.

Treatment of postcardiotomy low-output syndrome includes intraaortic balloon pumping (IABP), volume loading, pharmacological afterload reduction, and stimulation with an inotropic agent. This study compares the effectiveness of combined nitroprusside and dopamine therapy and nitroprusside and dobutamine therapy in 12 patients requiring IABP postoperatively. Serial hemodynamic measurements were made before and during infusion of nitroprusside and after administration of the combined therapy (N = 6 in each group). Prior to pharmacological therapy, cardiac index was 1.47 +/- 0.31 L/min/m2 and systemic vascular resistance (SVR) was 3,114 +/- 1,350 dynes sec cm-5 in patients subsequently given dopamine, and 1.59 +/- 0.38 L/min/m2 and 2,661 +/- 405 dynes sec cm-5, respectively, in those given dobutamine. With infusion of nitroprusside, both groups showed significant reduction in SVR. Nitroprusside plus either inotropic agent resulted in augmentation of cardiac index and an additional reduction in SVR, both changes being greater in the group given dopamine. Larger doses of dobutamine than dopamine were needed to achieve similar hemodynamic improvement. We conclude that the addition of an inotropic agent to vasodilator therapy during IABP results in a greater increase in cardiac index and a greater decrease in afterload than a vasodilator alone. In addition to its beneficial effect on renal perfusion at the dose required to effect these improvements, dopamine appears a better inotropic agent than dobutamine for postcardiotomy low-output syndrome.

Surgical treatment of aneurysms of the transverse aortic arch: experience with 25 patients using hypothermic techniques.

Surgical treatment of aneurysms of the transverse aortic arch has been a challenge to cardiovascular surgeons. The problems include protection of the brain and spinal cord from ischemic or embolic injury, prevention of hemorrhage and coagulopathy, and prevention of myocardial damage during prolonged extracorporeal circulation. Two methods are described. Group 1 included 20 patients in whom deep hypothermic conditions were induced (12 degree to 16 degree C) followed by circulatory arrest and partial exsanguination. In this group a 50% hospital mortality occurred. Patients in Group 2 underwent moderate induced hypothermia (24 degree to 26 degree C) with continuous cerebral perfusion during the period of peripheral circulatory arrest. Four of 5 patients survived this technique, leading us to believe this method is preferred over the deeper levels of hypothermia. A method of preclotting the Dacron graft with platelet-rich plasma and autoclaving is described. It has eliminated interstitial bleeding through fabric grafts.

Cardiovascular surgery in patients with congenital plasma coagulopathies.

From 1978 to 1986, fifteen cardiovascular operations were performed on 13 patients with known congenital bleeding disorders. The patients (10 men and 3 women) had a mean age of 51.1 +/- 3.4 years. Four were seen with cardiovascular lesions and documented hemophilia A (Factor VIII deficiency); 3 had hemophilia B (Factor IX deficiency); 3 had Factor XI deficiency; 2 had von Willebrand's disease, and 1 had dysfibrinogenemia. All patients had a history of major hemorrhage after dental extractions or general surgical procedures, and had clearly documented coagulation disorders on hematological evaluation. Elective cardiovascular procedures performed in these patients included aortocoronary bypass grafting (eight), cardiac valve replacement or repair (five), aortic graft placement (one), and carotid endarterectomy (one). The mainstay of perioperative management included appropriate replacement therapy with blood components. Coagulation factor levels were measured routinely to guide therapy. There were no deaths. Two hemorrhagic complications necessitated reexploration. We conclude that in patients known to have congenital coagulation disorders, cardiovascular operations using systemic heparinization can be performed with minimal morbidity and mortality when carried out with preoperative and perioperative support from the hematology service, adequate replacement therapy using blood components, and careful monitoring of the coagulation status.

Resection of aortic arch aneurysms: a comparison of hypothermic techniques in 60 patients.

Hypothermic circulatory arrest has been used to facilitate resection of aneurysms of the aortic arch. During a five-year period, two methods of hypothermic arrest were compared in 60 patients. In Group 1, 20 patients underwent deep hypothermia (14 degrees to 18 degrees C) and circulatory arrest to allow repair of the transverse arch under optimal conditions. A hospital mortality of 50% occurred and was attributed to uncontrolled hemorrhage and cerebral or cardiac complications. In Group 2, modified techniques were employed in 40 patients and included moderate levels of hypothermia (22 degrees to 26 degrees C) and simplified operative methods, which reduced the duration of circulatory arrest and shortened the length of perfusion. Pretreatment of plasma-soaked Dacron grafts by autoclaving eliminated serious bleeding problems. A marked improvement in patient survival (90%) and reduction in postoperative complications were observed after adoption of these modifications. The improved results in the present series have reconfirmed our belief that this type of intervention is the preferred approach to aneurysms of the aortic arch.

Surgical treatment of cardiac tumors: a 25-year experience.

From 1964 to 1989, we performed operations on 133 patients with cardiac tumors. There were 58 male and 75 female patients ranging in age from three days to 81 years; 101 were adults, and 32 were children (less than 12 years of age). Primary tumors (102 benign and 12 malignant) were found in 114 patients and metastatic tumors in 19. Symptoms included congestive heart failure, arrhythmias, emboli, and chest pain. Diagnosis was accomplished through angiography, echocardiography, computed tomography, and magnetic resonance imaging. Operative treatment encompassed techniques ranging from biopsy to complete excision (including hypothermic circulatory arrest and cardiac autotransplantation) depending on the site of disease and the extent of involvement. Overall operative survival was 91%. Twelve patients died early (within 30 days of operation), and follow-up was obtained for 110 (90.9%) of the remaining 121 survivors (total patient-years of follow-up, 572.8; mean follow-up, 5.2 years). Of the 20 patients who died late, 15 had malignant disease. Operative survival for patients with primary cardiac malignancies and for those with metastatic disease was 83% and 68.4%, respectively, with 3 and 5 patients, respectively, still living. We advocate an aggressive surgical approach, especially in patients with benign tumors, who can expect an excellent outcome. For patients with malignant or metastatic disease, palliation and cure are also possible if aggressive surgical actions are taken.

Reoperation for aortic coarctation: techniques, results, and indications for various approaches.

To define the safety and efficacy of operation for recurrent thoracic aortic coarctation, we reviewed the hospital records and subsequent courses of 53 patients who underwent such procedures over a 23-year period. Previous operations included end-to-end anastomosis, prosthetic patch or subclavian flap aortoplasty, and prosthetic interposition or bypass grafts, performed in patients ranging from 1 day to 44 years old. Several different reoperative procedures were used, including an ascending-descending aortic bypass graft in 4 patients who had had two previous repairs. There were no hospital or late deaths and only 3 relatively minor complications. Only 2 patients have hypertension requiring drug therapy at follow-up, which now averages 7 years. We conclude that operative management of severe, recurrent coarctation is both safe and effective, and that several techniques of reconstruction may have a place in such therapy.

Durability and low thrombogenicity of the St. Jude Medical valve at 5-year follow-up.

Between November, 1978, and December, 1983, 736 patients had valve replacement with the St. Jude Medical valve prosthesis. There were 478 patients with aortic valve replacement (AVR), 188 with mitral valve replacement (MVR), 63 with double valve replacement, and 7 with tricuspid valve replacement (they were not included in this study). The mean age at the time of operation was 46.7 years for patients having AVR and 48.6 years for those having MVR and AVR + MVR. Follow-up totaled 1,116 patient-years (range, 4 to 82 months). Early (30-day) mortality was lowest for isolated MVR (2.3%) and AVR (3.7%), and increased with reoperation or when associated procedures were combined with valve replacement. Patients undergoing reoperation or having associated procedures made up 49% of the AVR and 54% of the MVR groups. All patients were advised of the need for long-term anticoagulation with warfarin sodium. Nine patients (7 with AVR, 1 with MVR, 1 with AVR + MVR) had suspected or confirmed episodes of systemic thromboembolism, a linearized incidence of 0.99% per patient-year for AVR, 0.36% per patient-year for MVR, and 0.98% per patient-year for AVR + MVR. Eight patients with AVR underwent reoperation for prosthetic valve endocarditis (5 of the 8 patients had endocarditis prior to initial valve replacement). There were no instances of structural valve failure. There were 37 late deaths. Actuarial survival at 5 years (excluding early mortality, 95% confidence limits) was 89.8% for AVR, 84.8% for MVR, and 95.2% for AVR + MVR.(ABSTRACT TRUNCATED AT 250 WORDS)