Isolation and immunocytochemical characterization of human bone marrow stromal macrophages in hemopoietic clusters.

Stromal macrophages (M phi) have been localized in situ and isolated within erythroid clusters from human marrow. Stromal M phi arborize in an extensive network uniformly distributed throughout marrow interstitium, and express the phenotype CD4+, CD11a+, CD11c+, CD13+, CD14+, CD16+, CD18+, CD31+, CD32+, FcRI+, HLA-DR+, and CD35-, transferrin receptor-negative, and CD11b (weak). They express endocytic receptor antigens, but show significant differences in myeloid antigen expression compared with freshly harvested or cultured monocytes. Human stromal M phi are therefore specialized mature marrow M phi that are accessible for further investigations in infectious, storage, or hemopoietic disorders.

Investigation and management of primary cardiac tumors in infants and children.

Seven children with primary cardiac tumors are discussed. The diagnosis was achieved by cardiac catheterization in all seven patients. In four patients, surgical excision was undertaken with one long-term good result. One of the other three surgical patients died of acute heart failure at the discontinuation of cardiopulmonary bypass. One of the other two surgical patients died suddenly late postoperatively, presumably from arrhythmia. The other, affected by fibrosarcoma, also died suddenly while undergoing chemotherapy. The histologic findings on the tumor masses were available in six patients. There were three rhabdomyomas, one fibrosarcoma, one fibroma and one hamartomatous mass. In one patient with tuberous sclerosis, a presumptive diagnosis of rhabdomyoma was made clinically on the basis of multiple masses infiltrating the left ventricle. Two-dimensional echocardiography is the best noninvasive tool to determine the extent and location of the tumor and suitability for surgery. When surgery is indicated, cardiac catheterization for pressure data is also required. Surgery is recommended in symptomatic solitary lesions that most likely are fibromas and have an overall good surgical outcome.

Angiography and complement activation. Evidence for generation of C3a anaphylatoxin by intravascular contrast agents.

The potent anaphylatoxin C3a was measured in the peripheral blood of eleven patients receiving radiocontrast agents whilst undergoing coronary angiography. In seven patients C3a levels were raised during this procedure and in three of these the anaphylatoxin was increased between four and tenfold. In four patients C3a levels remained within the normal range. In vitro tests of five contrast agents revealed marked heterogeneity in their ability to generate C3a from serum.

Macroaggregation of platelets in plasma, as distinct from microaggregation in whole blood (and plasma), as determined using optical aggregometry and platelet counting respectively, is specifically impaired following cardiopulmonary bypass in man.

We determined changes in platelet aggregability following cardiopulmonary bypass, using optical aggregometry to assess macroaggregation in platelet-rich plasma (PRP), and platelet counting to assess microaggregation both in whole blood and PRP. Hirudin was used as the anticoagulant to maintain normocalcaemia. Microaggregation (%, median and interquartile range) in blood stirred with collagen (0.6 micrograms/ml) was only marginally impaired following bypass (91 [88, 93] at 10 min postbypass v 95 (92, 96] prebypass; n = 22), whereas macroaggregation (amplitude of response; cm) in PRP stirred with collagen (1.0 micrograms/ml) was markedly impaired (9.5 [8.0, 10.8], n = 41 v 13.4 [12.7, 14.3], n = 10; p < 0.0001). However, in PRP, despite impairment of macroaggregation (9.1 [8.5, 10.1], n = 12), microaggregation was near-maximal (93 [91, 94]), as in whole blood stirred with collagen. In contrast, in aspirin-treated patients (n = 14), both collagen-induced microaggregation in whole blood (49 [47, 52]) and macroaggregation in PRP (5.1 [3.8, 6.6]) were more markedly impaired, compared with control (both p < 0.001). Similarly, in PRP, macroaggregation with ristocetin (1.5 mg/ml) was also impaired following bypass (9.4 [7.2, 10.7], n = 38 v 12.4 [10.0, 13.4]; p < 0.0002, n = 20), but as found with collagen, despite impairment of macroaggregation (7.2 [3.5, 10.9], n = 12), microaggregation was again near-maximal (96 [93, 97]). The response to ristocetin was more markedly impared after bypass in succinylated gelatin (Gelofusine) treated patients (5.6 [2.8, 8.6], n = 17; p < 0.005 v control), whereas the response to collagen was little different (9.3 v 9.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult human valve dimensions and their surgical significance.

After cardiac valve replacement, some patients may show little improvement in functional status, in part because their prosthesis is restrictive. Guidelines were sought for valve replacement from measurements of valve circumference and calculated circularized orifice area in 160 postmortem hearts from adults with and without congestive cardiac failure. Multivariate analysis was used to relate valve area to age, sex, height, body surface area and cardiac failure. Only sex and cardiac failure were significantly related to valve area. Body surface area and other variables were poorly related to valve area. The mean (+/- standard deviation) circularized orifice area for adult male (M) and female (F) heart valves in the absence of cardiac failure were: Aortic, M 4.81 +/- 1.30, F 3.73 +/- 0.98; pulmonary, M 4.88 +/- 1.25, F 4.32 +/- 1.03; mitral, M 8.70 +/- 2.08, F 6.94 +/- 1.41; and tricuspid, M 11.9 +/- 2.72, F 9.33 +/- 2.02. In cardiac failure, atrioventricular valves enlarge (p less than 0.004). Guided by these dimensions, the surgeon can aim to insert a prosthesis of appropriate size. Comparison of these sizes with the manufacturer's calculated area for current prostheses shows that most mechanical valves and bioprostheses are potentially restrictive at rest. Improved prosthestic design, valve repair whenever possible, and anular enlargement procedures would be required to eliminate this size disparity.

Proximal aortic perfusion for complex arch and descending aortic disease.

OBJECTIVE: Cannulation of the femoral artery is used routinely for hypothermic circulatory arrest operations on the aortic arch. A two-stage approach is advocated for combined arch and descending aortic disease. These methods are associated with important neurologic injury through embolism or malperfusion. We therefore changed to a central cannulation technique through extended left thoracotomy. METHODS: Eighteen patients with arch or combined pathologic conditions underwent one-stage repair with hypothermic circulatory arrest using ascending aortic cannulation and venous drainage from the pulmonary artery. Emergency operations were performed for bleeding or dissection. Cerebral and myocardial perfusion were restored during descending aortic replacement. RESULTS: One elderly patient died of gastrointestinal hemorrhage after initial recovery (overall mortality 5.6%, range 0.14% to 27%, p = 0.05). One possible transient monoparesis occurred but without computed tomographic scan evidence of embolism. No other significant events and no morbidity occurred from the surgical methods. CONCLUSIONS: Extended left thoracotomy with central cannulation allows safe one-stage replacement of the arch and descending aorta using anterograde cerebral perfusion. We believe that this method will reduce cerebral complications in arch and descending aortic operations.

Successful mitral valve replacement and myocardial revascularization in an adult with anomalous origin of the left coronary artery from the pulmonary artery.

A 35-year-old white woman with anomalous origin of the left coronary artery from the pulmonary artery had infective endocarditis and severe mitral regurgitation. She survived mitral valve replacement and occlusion of the anomalous left main stem, but subsequently deterioration of her condition necessitated urgent saphenous vein bypass grafts to the left anterior descending and circumflex coronary arteries. Pulmonary hypertension with raised right ventricular end-diastolic pressure probably compromised collateral flow from the right to the left coronary systems.

Replacement of the thoracic aorta with collagen-impregnated woven Dacron grafts. Early results.

We used the collagen-impregnated woven double-velour Dacron graft in 120 patients undergoing 122 aortic reconstructions. Seventy-nine aortic root, ascending, or arch replacements were performed during cardiopulmonary bypass with or without circulatory arrest; 53 of the 79 were for acute aortic dissection. In addition, three infants and one child underwent repair of truncus arteriosus. There were no deaths caused by hemorrhage or bleeding-related complications. For aortic root replacement, the impervious nature of the collagen-impregnated woven double velour Dacron graft allowed elimination of wrap-around techniques. Eight deaths occurred as a result of multisystem organ failure, which followed late diagnosis of type A dissection. Two patients underwent reoperation for late complications of type A dissection. Thirty-nine patients underwent treatment for disease of the descending aorta; eight of these patients underwent a central cannulation technique with profound hypothermic cardiopulmonary bypass. The other 31 underwent repair with aortic crossclamping without bypass. Four of these patients died: two as a result of multisystem organ failure, one as a result of uncontrolled bleeding from the native dissected aorta, and one as a result of intestinal necrosis. Follow-up studies for 2 months to 5 years revealed three late deaths caused by the rupture of a persistent aneurysmal false lumen after type A dissection. The intraoperative advantages of the collagen-impregnated woven double velour Dacron graft represent an important advance in vascular graft technology. Its handling and suturing characteristics are excellent, and the graft is completely impervious in its originally manufactured state. Needle holes self-seal rapidly. Medium-term follow-up by clinical, angiographic, computed tomographic, and magnetic resonance imaging techniques showed no late graft complications--specifically, no dilatation or thrombus formation.

A bifurcated silicone rubber stent for relief of tracheobronchial obstruction.

Though the techniques for surgical treatment after postintubation tracheal stenoses are well defined, the management of major airway obstruction by tracheal tumor, external compression, or diffuse intrinsic tracheal disease below the thoracic inlet still presents a difficult problem. Existing methods do not provide safe and effective relief at the level of the distal trachea, carina, and main bronchi. This report describes a bifurcated silicone rubber stent initially designed to preserve patency of the airways in a patient after severe and diffuse scalding injury to the trachea and main bronchi. This stent has since been used to provide relief from airway obstruction by tracheal or mediastinal tumors below the thoracic inlet. The method for insertion by tracheostomy with guide bougies passed under direct bronchoscopic vision past the obstructing lesion is described in detail and illustrated by reference to two patients with tracheobronchial obstruction. Once the tube is in place, the patient breathes normally through the mouth and nose and can speak, cough, or clear his own airway by suction if necessary. This method has proved a safe and effective means to restore patency of the major airways and provide relief from asphyxia while further treatment is planned or healing ensues. Our initial experience indicates that the tube may be allowed to remain in position for several months without adverse effects.

Thrombolysis and postinfarction ventricular septal rupture.

We studied all patients with postinfarction ventricular septal rupture referred to the Oxford Heart Centre for operation over a 4 1/2-year period. Twenty one women and 8 men were admitted to the Centre, 13 of whom had received streptokinase and 16 of whom had not. The median interval between symptomatic onset of myocardial infarction and the development of septal rupture was 24 hours for those treated by early thrombolysis (all streptokinase) and six days for those who were not. Of the 26 patients who underwent surgical repair, three were operated on less than 36 hours after streptokinase infusion, in one case within 12 hours of thrombolytic treatment. Macroscopic observation of the disintegrating myocardium showed muscle bundles dissected by blood rendered incoagulable by thrombolytic treatment, together with the histologic features of reperfusion injury. The overall surgical mortality rate for the streptokinase group was 33% and for the others 21%. The patient operated on within 12 hours of thrombolytic treatment recovered uneventfully. Six of seven surgical deaths were caused by left ventricular or biventricular failure and one by gastrointestinal hemorrhage. All survivors were in New York Heart Association classes II or III between 2 weeks and 4 1/2 years after operation. We conclude that thrombolysis leads to early breakdown of the interventricular septum after acute myocardial infarction but does not preclude early repair.

Combined cardiac and abdominal aortic aneurysm operations. The dual operation on cardiopulmonary bypass.

Eight patients underwent both cardiac operation and repair of abdominal aortic aneurysm. All had respiratory impairment and significant impairment of left ventricular function, whereas six patients had severe diffuse distal coronary disease. In all patients the cardiac procedure was performed first, and the patients continued to receive cardiopulmonary bypass. Rewarming was not commenced until the abdominal repair was well under way, to protect the vital organs. There were no problems in weaning the patients from bypass, and six of the patients were extubated within 24 hours; one required ventilation for 36 hours. One patient died of colonic infarction complicated by kidney failure without being extubated. Another patient who was initially extubated in 11 hours required reintubation because of poor lung function and eventually died of multisystem organ failure caused by bilateral lower limb ischemia that persisted despite embolectomies. All survivors are well and in New York Heart Association functional class I or II between 3 and 18 months postoperatively. We conclude that for patients considered unfit for abdominal aortic aneurysm operations because of the nature of the cardiac disease, the combined operation with cardiopulmonary bypass is both safe and effective.

Valve replacement with a stentless bioprosthesis: versatility of the porcine aortic root.

OBJECTIVE: Stentless valves convey important hemodynamic benefits but are used selectively depending on aortic root structure. The Freestyle valve (Medtronic, Inc, Minneapolis, Minn) is a versatile device that can be implanted by different methods depending on operating conditions. We aimed to demonstrate that a stentless valve could be used in every patient without increased risk of morbidity or mortality. We documented the effects of this valve on clinical outcome and left ventricular mechanics. METHODS: The Freestyle valve was implanted by the modified subcoronary method into 200 consecutive unselected patients who received a tissue valve in the aortic position and by root replacement in 2. Forty-three percent were older than 75 years. Forty percent underwent coronary bypass. Detailed clinical and echocardiographic follow-up (Food and Drug Administration protocol) was used out to 3 years. RESULTS: Mean ischemic time was 43+/-6 minutes for isolated aortic valve replacement and 63+/-14 minutes with concomitant procedures. Thirty-day mortality was 6%, none of the deaths being valve related. Hemodynamic function improved progressively with falling valve gradients and increased effective orifice areas. Left ventricular mass fell within normal limits over 2 years, but at 3 years there was a non-valve-related upswing. No instances of valve thrombosis, hemolysis, or paravalvular leak were noted. Less than 5% had mild to moderate aortic regurgitation. CONCLUSIONS: The Freestyle valve can be used in virtually every patient with aortic valve disease and provides superlative hemodynamic outcome. Hospital mortality and morbidity are similar to those reported for stented valves in an elderly population.

Increased production of peroxidation products associated with cardiac operations. Evidence for free radical generation.

We investigated the degree and time course of neutrophil sequestration into human lungs during cardiac operations. At the same time, measurement of the concentration of peroxidation products in the plasma was used as an index of oxidant free radical activity. The study was performed in two groups of patients. Group A (n = 11) had studies extending over the entire operative period and showed a highly significant sequestration of neutrophils into the lung, together with a highly significant (p less than 0.001) rise in peroxidation products from 2.8 +/- 0.12 nmol/ml(mean +/- standard error of the mean)before bypass to a peak of 5.05 +/- 0.13 nmol/ml at the end of bypass. As these changes occurred only during the time after release of the aortic cross-clamp, we investigated this period in more detail in a second group of patients (Group B, n = 7). Results from this group showed that significant release of peroxidation products occurred at the same time as pulmonary neutrophil sequestration. This study has produced evidence of increased oxidant activity in the lung associated with cardiac operations. Nevertheless, it is not known whether the neutrophils sequestered into the lung alone induced the increased activity. Similarly, whether neutrophil-derived oxidant species are the sole cause of lung tissue injury remains unproved.

The Jarvik 2000 Oxford system: increasing the scope of mechanical circulatory support.

METHODS: We developed a system for mechanical circulatory support based on the Jarvik 2000 intraventricular axial flow impeller pump (Jarvik Research, Inc., New York, N.Y.) and percutaneous electric power. The adult pump provides flow at a rate up to 10 L/min with an energy requirement of 7 to 10 watts. The device was implanted into the apex of the left ventricle through a left thoracotomy without cardiopulmonary bypass. A Dacron graft conveyed blood to the descending thoracic aorta. In patients, we will use a skull-mounted carbon pedestal to transmit fine electric wires through the scalp skin. Being highly vascular, the scalp skin is resistant to infection. RESULTS: We tested 16 adult systems and one pediatric system in 17 adult ewes weighing between 60 and 90 kg. Five died of perioperative complications. Twelve survived between 3 and 198 days (mean 44 days) with a functioning device. None of the sheep could receive adequate anticoagulation with warfarin (INR 1.0 to 1.5). Acute thrombotic occlusion occurred after a 3-hour power loss in one device (46 days) but was cleared with streptokinase. In a second animal with endocarditis, the pump inflow became occluded with vegetations. No other device-related problems or important hemolysis developed despite pump speeds between 10,000 and 18,000 rpm. Renal function remained normal in all animals. Autopsy studies showed no pannus ingrowth at the device inflow despite the restrictive left ventricular cavity size. No sign of thromboembolism could be detected in the brains or kidneys. CONCLUSION: Our findings indicate the Jarvik 2000 Oxford System to be a safe and effective circulatory assist device. Potential uses include permanent circulatory support, bridge to transplantation, or bridge to myocardial recovery in acute or chronic left ventricular failure.

Effect of cardiopulmonary bypass on systemic release of neutrophil elastase and tumor necrosis factor.

Leukocyte counts, plasma neutrophil elastase, tumor necrosis factor-alpha and C-reactive protein were determined serially in 19 patients undergoing elective coronary artery surgery with cardiopulmonary bypass. Neutrophil counts (mean +/- standard deviation 3.85 +/- 1.20 x 10(9)/L preoperatively) peaked 4 hours postoperatively at 10.35 +/- 4.24 x 10(9)/L (p < 0.001) and remained significantly elevated 48 hours postoperatively at 7.80 +/- 2.70 x 10(9)/L, p < 0.05. Plasma neutrophil elastase level (187 +/- 74 ng/ml preoperatively) peaked at 698 +/- 323 ng/ml at the end of surgery (p < 0.001) and remained significantly elevated at 424 +/- 146 ng/ml 48 hours postoperatively (p < 0.01). Peak elastase levels correlated significantly with duration of bypass (r = 0.47, n = 19, p < 0.05). Monocyte counts (0.29 +/- 0.19 x 10(9)/L preoperatively) peaked 4 hours postoperatively (0.87 +/- 0.41 x 10(9)/L, p < 0.001) and fell to baseline levels by 48 hours postoperatively. Plasma tumor necrosis factor-alpha, detectable in 10 of the 19 patients preoperatively (median 0.39 U/ml, range up to 10.1 U/ml), did not change significantly during or after bypass. Plasma C-reactive protein level (median 1.67 [range 0.69 to 34.33] micrograms/ml preoperatively) rose significantly to 3.99 (range 1.95 to 12.55) micrograms/ml 4 hours postoperatively (p < 0.01) and rose 48 hours postoperatively at 303 (210 to 410) micrograms/ml, p < 0.001. Oxygenation, determined by the respiratory index, was impaired at the end of operation (2.07 +/- 0.82) and remained impaired 24 hours postoperatively (2.48 +/- 0.83). Impairment of oxygenation was temporally related to elevated elastase levels, but neither peak elastase levels nor the change in elastase levels with lung reperfusion correlated significantly with the area under the respiratory index curve up to 6 hours postoperatively. This study demonstrates neutrophil elastase release during cardiopulmonary bypass but fails to show a definite role for neutrophil activation or tumor necrosis factor-alpha in the etiology of pulmonary dysfunction after cardiopulmonary bypass.

Is there a relationship between serum S-100beta protein and neuropsychologic dysfunction after cardiopulmonary bypass?

OBJECTIVES: Over the past decade, the glial protein S-100beta has been used to detect cerebral injury in a number of clinical settings including cardiac surgery. Previous investigations suggest that S-100beta is capable of identifying patients with cerebral dysfunction after cardiopulmonary bypass. Whether detection of elevated levels S-100beta reflects long-term cognitive impairment remains to be shown. The present study evaluated whether perioperative release of S-100beta after coronary artery operations with cardiopulmonary bypass could predict early or late neuropsychologic impairment. METHODS: A total of 100 patients undergoing elective coronary bypass without a previous history of neurologic events were prospectively studied. To exclude noncerebral sources of S-100beta, we did not use cardiotomy suction or retransfusion of shed mediastinal blood. Serial perioperative measurements of S-100beta were performed with the use of a new sensitive immunoluminometric assay up to 8 hours after the operation. Patients underwent cognitive testing on a battery of 11 tests before the operation, before discharge from the hospital, and 3 months later. RESULTS: No significant correlation was found between S-100beta release and neuropsychologic measures either 5 days or 3 months after the operation. CONCLUSION: Despite using a sensitive immunoluminometric assay of S-100beta, we found no evidence to support the suggestion that early release of S-100beta may reflect long-term neurologic injury capable of producing cognitive impairment.

Complement and the damaging effects of cardiopulmonary bypass.

Postoperative cardiac, pulmonary, renal and coagulation dysfunction, along with C3a levels, were studied prospectively in 116 consecutive patients undergoing open cardiac operations and 12 patients undergoing closed operations in the same time period. The level of C3a 3 hours after open operation was high (median value 882 ng X ml-1 plasma) and was related to the C3a level before cardiopulmonary bypass (CPB) (p = 0.03), the level at the end of CPB (p less than 0.0001), elapsed time of CPB (p = 0.07), and older age at operation (p less than 0.0001). It was inversely related to the cardiac output as reflected by the strength of the pedal pulses (p = 0.006). In contrast, C3a levels did not rise in patients undergoing closed operations. The probability of postoperative cardiac dysfunction after open operations (present in 27 of 116 patients) was predicted by C3a levels 3 hours after operation (p = 0.02), the CPB time (p = 0.02), and younger age (p less than 0.0001). The same risk factors pertained for postoperative pulmonary dysfunction (present in 41 of the 116 patients); renal dysfunction (present in 24 of the 116 patients) except that CPB time was not a risk factor here; abnormal bleeding (present in 21 of the 116 patients); and important overall morbidity (present in 26 of 116 patients). As regards important overall morbidity, the C3a level effect became evident at about 1,900 ng X ml-1 (a level reached by 9% of patients); the effect of increasing time of CPB became evident at about 90 minutes of CPB time; and the effect of young age became evident as age decreased from 10 to 4 years. This study demonstrates the damaging effects of CPB, relates them in part to complement activation by the foreign surfaces encountered by the blood, and supports the hypothesis that the mechanisms of the damaging effects include a whole-body inflammatory reaction.

A simple method for continuous pericardial drainage.

Needle pericardiocentesis is performed routinely for relief of symptoms in patients with pericardial effusion and cardiac tamponade. In many patients however, reaccumulation of fluid requires further aspiration or surgical drainage, occasionally as a matter of urgency. Both procedures carry significant risks which may be avoided by insertion of an indwelling catheter. The Viggo subclavian cannula proves ideal for prolonged drainage of pericardial effusions and for relief of tamponade in an emergency situation. Introduction into the pericardium is simple, safe, and can be performed quickly without specialised equipment. This procedure is described and illustrated in patients with tuberculous and rheumatoid pericarditis.

Monocusp homograft VSD patch in atrioventricular canal with tetralogy of Fallot.

A monocusp aortic homograft was used to compensate for deficient right atrioventricular valve tissue during repair of complete atrioventricular canal defect with tetralogy of Fallot. The homograft was used to produce a comma-shaped ventricular septal defect patch together with the septal leaflet of the right atrioventricular valve, thus committing native leaflet tissue to left atrioventricular valve reconstruction. One year postoperatively the child is in New York Heart Association class I with no tricuspid regurgitation.

Aprotinin in perspective.

Aprotinin is a nonspecific serine protease inhibitor extracted from bovine lung. It was first used during cardiopulmonary bypass to inhibit plasmin-induced complement activation. By chance significant reductions of blood loss and blood requirements were noted in treated patients. Subsequent investigation showed improved hemostasis to result from protection of platelet adhesive receptors (Gp Ib) at the onset of cardiopulmonary bypass. Without aprotinin the contact system of plasma is massively activated on first passage through the cardiopulmonary bypass circuit. Activation of the intrinsic coagulation pathway causes thrombin formation, which impairs platelet adhesive function. Aprotinin blocks contact activation of the kallikrein system during cardiopulmonary bypass and in synergy with heparin prevents thrombin formation through inhibition of the intrinsic clotting cascade. It is likely that neither thrombin nor platelets become involved in the blood-foreign surface contact activation process in aprotinin-treated patients. The fact that the hemostatic process is affected from the very beginning of cardiopulmonary bypass is substantiated by the fact that low-dose aprotinin therapy (2 x 10(6) KIU aprotinin added to the pump prime) leads to the same preservative effect on Gp Ib receptors and blood loss as continuous high-dose infusion (6 x 10(6) KIU) throughout the whole surgical procedure. In the presence of heparin aprotinin prolongs the activated clotting time and the in vitro activated partial thromboplastin time. This has important implications for heparin dosage. An inhibitory effect on the endothelial cell anticoagulant function may also have consequences during hypothermic low flow and circulatory arrest states.(ABSTRACT TRUNCATED AT 250 WORDS)