A.Marc Gillinov

Valve replacement in patients with endocarditis and acute neurologic deficit

BACKGROUND Acute neurologic deficits occur in up to 40% of patients with left heart endocarditis. Appropriate evaluation and management of patients with acute neurologic dysfunction who require valve operations for endocarditis remain controversial. This retrospective review was undertaken to develop recommendations for the evaluation and treatment of these challenging patients. METHODS From 1983 to 1995, 247 patients underwent operations for left heart native valve endocarditis at the Johns Hopkins Hospital. From a review of medical and pathology records, 34 patients (14%) with preoperative neurologic deficits were identified. Data on these 34 patients were recorded and analyzed. RESULTS Causes of neurologic dysfunction included embolic cerebrovascular accident (n = 23, 68%), embolic cerebrovascular accident with hemorrhage (n = 4, 12%), ruptured mycotic aneurysm (n = 3, 9%), transient ischemic attack (n = 2, 6%), and meningitis (n = 2, 6%). Preoperative diagnostic studies included computed tomography (32 patients), magnetic resonance imaging (11 patients), cerebral angiogram (14 patients), and lumbar puncture (2 patients). Computed tomography demonstrated structural lesions in 29 of 32 patients; in only 1 patient did magnetic resonance imaging reveal a lesion not already seen on computed tomography. Of 14 patients having cerebral angiograms, 7 had a mycotic aneurysm. Three mycotic aneurysms had ruptured, and these were clipped before cardiac operations. The mean interval from onset of neurologic deficit to cardiac operation was 22.2 +/- 2.8 days for all patients and 22.1 +/- 3.0 days for those with embolic cerebrovascular accident. The hospital mortality rate was 6%. New or worse neurologic deficits occurred in 2 patients (6%). CONCLUSIONS Neurologic deficits are common in patients with endocarditis referred for cardiac operations. Despite substantial preoperative morbidity, most of these patients do well if the operation can be delayed for 2 to 3 weeks. Computed tomography scan is the preoperative imaging technique of choice, as routine magnetic resonance imaging and cerebral angiogram are unrewarding. Cerebral angiogram is indicated only if computed tomography reveals hemorrhage.

Neutrophil adhesion molecule expression during cardiopulmonary bypass with bubble and membrane oxygenators

The neutrophil-mediated tissue injury associated with cardiopulmonary bypass (CPB) is thought to require the interaction of specific neutrophil and endothelial adhesion molecules. In this study, the effects of CPB on the expression of neutrophil CD11b and CD18 (the components of the Mac-1 adhesion molecule) were examined; the effects of membrane versus bubble oxygenators on the expression of neutrophil CD11b and CD18 were compared; and the plasma levels of the intercellular adhesion molecule-1 (cICAM-1), an inducible endothelial adhesion molecule, were measured. In addition, the time courses of complement activation and neutrophil granule release were measured to determine their temporal relationship to the expression of the neutrophil adhesion molecule. Fifteen adult patients underwent procedures requiring cardiopulmonary bypass; hollow-fiber membrane oxygenators were used in 8 (group M) and bubble oxygenators were used in 7 (group B). Blood samples were drawn before, during, and after CPB for determination of the expression of neutrophil CD11b and CD18 (immunofluorescent flow cytometry), and the plasma cICAM-1, elastase, lactoferrin (enzyme-linked immunoabsorbent assay), and plasma C3a (radioimmunoassay) levels. CPB caused an immediate and sustained increase in the neutrophil CD11b and CD18 expression in both groups; after 60 minutes of CPB, CD11b expression had increased by 116.9% +/- 19.1% in group B and by 79.3% +/- 8.5% in group M (p = 0.78). Over the same period, CD18 expression increased by 97.2% +/- 17.9% in group B and by 72.4% +/- 16.8% in group M (p = 0.67).(ABSTRACT TRUNCATED AT 250 WORDS)

Heparin-coated bypass circuits reduce pulmonary injury☆☆☆

Heparin coating of the extracorporeal circuit not only reduces heparin requirements during cardiac operations but also may reduce organ injury associated with cardiopulmonary bypass (CPB). To examine this possibility, pulmonary injury and neutrophil adhesion molecule expression after CPB were studied in pigs undergoing CPB with a standard extracorporeal circuit (group S, n = 6) or a heparin-coated CPB circuit (Carmeda BioActive Surface) (group HC, n = 6). Pigs received heparin sodium (300 U/kg intravenously) and then underwent 90 minutes of hypothermic (28 degrees C) CPB using membrane oxygenators, followed by 2 hours of observation. Blood samples were obtained for determination of neutrophil number and expression of the neutrophil adhesion molecule subunit CD18 (by immunofluorescence flow cytometry). The CPB-associated injury was less in group HC. Two hours after CPB, the arterial oxygen tension group was higher in group HC (597.2 +/- 31.2 versus 220.5 +/- 42.3 mm Hg; p < 0.0001), the pulmonary vascular resistance was lower in these animals (408.6 +/- 69.4 versus 1,159.8 +/- 202.4 dyne.s.cm-5; p = 0.02), and the static compliance was higher in group HC (66.4 +/- 5.4 versus 39.8 +/- 5.8 mL/mm Hg; p = 0.004). After 60 minutes of CPB, both groups had similar increases in expression of the neutrophil adhesion molecule subunit CD18 (29.4% +/- 19.5% versus 26.0% +/- 24.4%, group S and group HC, respectively) and similar decreases in neutrophil counts (6,056 +/- 1,285 to 2,453 +/- 979 cells/microL versus 6,010 +/- 1,748 to 3,197 +/- 1,225 cells/microL, group S and group HC, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of neutrophil adhesion during cardiopulmonary bypass

Blood contact with synthetic surfaces during cardiopulmonary bypass (CPB) causes a diffuse inflammatory reaction that includes neutrophil activation. The purpose of this study was to determine if inhibition of neutrophil adhesion with a new antiinflammatory agent NPC 15669 (N-(9H-(2,7-dimethylfluorenyl-9-methoxy)-carbonyl)-L-leucine) could reduce pulmonary injury in a porcine model of CPB. NPC 15669 blocks adherence of activated neutrophils by inhibiting upregulation of the Mac-1 (CD11b/CD18) adhesion molecule. Sixteen piglets underwent 2 hours of hypothermic CPB followed by 2 hours of observation; 8 received NPC 15669 (10 mg/kg intravenous bolus followed by 6 mg.kg-1.h-1 intravenous infusion) and 8 received equal volumes of vehicle. After 90 minutes of CPB, expression of neutrophil adhesion molecule subunit CD18 increased 118% in control piglets but only 36% in piglets treated with NPC 15669 (p < 0.01). Although neutropenia developed in all animals during CPB, lung tissue myeloperoxidase content was significantly lower in treated than in control animals 2 hours after CPB (94.9 +/- 10.4 versus 46.9 +/- 5.5 mumol.10 mg-1.min-1; p < 0.002). Free radical-mediated lipid peroxidation (quantitated by spectrophotometric assay of plasma conjugated dienes) was significantly reduced by treatment with NPC 15669 during and after CPB. Pulmonary function was better in NPC 15669-treated animals: 2 hours after CPB, pulmonary vascular resistance increased 477% in control piglets but only 140% in piglets receiving NPC 15669 (p < 0.03); arterial oxygen tension was significantly greater in piglets receiving NPC 15669 (428 +/- 33 mm Hg) than in controls (141 +/- 46; p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Repair of Coarctation of the Aorta in Neonates and Infants: A Thirty-Year Experience

Between January 1962 and December 1991, 179 children less than 1 year of age underwent repair of coarctation of the aorta. Group I (1962 to 1971) consisted of 19 patients, group II (1972 to 1981) of 57 patients, group III (1982 to 1991) of 103 patients. Neonates (< 30 days old) made up 60% of group I, 57% of group II, and 70% of group III. The proportion of infants with associated complex cardiac abnormalities was 7% in group I, 25% in group II, and 39% in group III. Techniques of repair included resection with end-to-end anastomosis (n = 65), subclavian flap repair (n = 85), patch aortoplasty (n = 18), and other procedures (n = 11). The early mortality (< 30 days) was lowest in group III (group I, 21%; group II, 21%; and group III, 7%; p < 0.05), but the late mortality was similar in all groups (group I, 11%; group II, 13%; and group III, 15%). The overall actuarial survival was 57.7% +/- 0.15% at 27.1 years in group I, 65.7% +/- 0.07% at 19.7 years in group II, and 77.5% +/- 0.04% at 9.3 years in group III (p = not significant). Twenty-five restenoses requiring intervention occurred in 23 patients, for an overall restenosis rate of 16.4%. The incidence of restenosis was 23% for the patients who underwent end-to-end anastomosis, 11% for those who underwent subclavian flap repair (p < 0.1), and 27% for those who underwent patch aortoplasty (p < 0.01). Balloon angioplasty was successful in relieving 11 of the 12 restenoses in groups II and III.(ABSTRACT TRUNCATED AT 250 WORDS)

Complement and neutrophil activation during cardiopulmonary bypass: A study in the complement-deficient dog

Cardiopulmonary bypass (CPB) is known to cause complement and neutrophil activation, but the relative importance and interaction of these components in CPB-induced inflammation is unknown. In this study, a strain of dogs genetically deficient in the third component of complement (C3) was used to determine the contribution of C3 to neutrophil activation and pulmonary injury after CPB. Eleven dogs (5 C3-deficient and 6 controls) underwent 150 minutes of hypothermic CPB (28 degrees C) followed by 2 hours of observation. Before CPB, C3 levels were normal in controls and less than 1% of normal in C3-deficient dogs. In control dogs, functional activity of C3 decreased to 53.2% of baseline after 1 hour of CPB and there was immunohistochemical evidence of C3 deposition in lung after CPB; C3-deficient dogs had no C3 deposition in lung. Although similar degrees of neutropenia occurred during CPB in the two groups, expression of neutrophil adhesion molecule subunit CD18 was significantly lower in C3-deficient dogs than controls after 1 hour of CPB (45.9 +/- 3.7 versus 82.9 +/- 10.0 mean fluorescence units; p < 0.02). Postbypass lung tissue myeloperoxidase content was also less in C3-deficient dogs (43.8 +/- 4.6 versus 71.1 +/- 8.6 mumol x 10 mg-1 x min-1; p < 0.03). Cardiopulmonary bypass-associated lung injury (assessed by alveolar-arterial oxygen gradient, pulmonary vascular resistance, percent lung water, and light and electron microscopic appearance) was similar between groups. These results demonstrate that (1) C3 is deposited on pulmonary vascular endothelium during CPB and (2) C3 mediates increased expression of neutrophil CD18 and neutrophil sequestration in lung after CPB.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Operations in Children With Marfan’s Syndrome: Indications and Results

BACKGROUND The development of new screening techniques for the early detection of Marfans syndrome has prompted evaluation of the results of cardiac operations in children with this syndrome. The purpose of this study was to determine the surgical indications, operative results, and need for reoperation in children with Marfans syndrome. METHODS From 1980 to 1996, 245 patients underwent cardiac operations for complications of Marfans syndrome; 26 (11%) were less than 18 years of age. The mean age at the time of operation was 10.3 +/- 1 years (range, 8 months to 17 years); 18 of the patients were male. Indications for operation were aortic root dilatation (15 patients), mitral regurgitation (4 patients), aortic root dilatation and mitral regurgitation (6 patients), and aortic arch aneurysm (1 patient). Operations included aortic root replacement (15 patients), aortic root replacement and mitral repair (5 patients), aortic root replacement and mitral replacement (1 patient), mitral repair (3 patients), mitral replacement (1 patient), and arch aneurysm repair (1 patient). The mean aortic root diameter in patients undergoing aortic root replacement was 6.2 +/- 0.2 cm. Only 1 patient underwent ascending aortic dissection. RESULTS. There were no operative deaths. At a mean follow-up of 67.1 +/- 10.2 months, 8 patients required a second cardiac procedure (41% +/- 17% 10-year freedom from reoperation). Indications for further operations were distal aortic pathology (3 patients), aortic root dilatation after initial mitral operation (3 patients), failed mitral repair (1 patient), and homograft degeneration (1 patient). Risk factors for a second cardiac procedure were age less than 10 years at the time of the first operation (p < 0.003) and mitral regurgitation (p < 0.04). Overall, 25 (96%) of 26 patients have undergone aortic root replacement and 11 (42%) patients have undergone a mitral procedure. There have been 4 late deaths, all of presumed cardiac origin. The 10-year survival rate is 79% +/- 10%. All surviving patients are in New York Heart Association functional class I or II. CONCLUSIONS We conclude that (1) aortic root dilatation is the most common surgical indication in children with Marfans syndrome, (2) mitral regurgitation is the second most common indication, (3) aortic dissection is unusual in children with Marfans syndrome, and (4) careful follow-up is necessary, particularly in younger children, because more than half of all children with Marfans syndrome require repeated cardiac operations within 10 years.

Hypothermic circulatory arrest as a surgical adjunct: A 5-year experience with 60 adult patients

As a surgical adjunct, the technique of hypothermic circulatory arrest (HCA) is well established in pediatric cardiac surgery but is used less frequently in adults. This study was undertaken to review the application, utility, and safety of HCA in adult surgery at a single institution. Between January 1985 and October 1990, 60 adult patients (greater than 18 years old) underwent surgical procedures that included HCA. There were 30 men and 30 women; mean patient age was 56.4 years (range, 20 to 81 years). Operative procedures were thoracic aortic aneurysm repair (35 patients, 58%), resection of intraabdominal malignancy (15 patients, 25%), coronary artery bypass (4 patients, 7%), and other miscellaneous procedures (6 patients, 10%). Eighty-two percent of the procedures were elective, whereas 18% were emergencies. Mean circulatory arrest time was 28.5 minutes (range, 2 to 64 minutes). Operative mortality was 15%; by multivariate analysis, risk factors for death included prolonged cardiopulmonary bypass time (p less than 0.05), higher post-HCA rectal temperature (p less than 0.05), and intraoperative hypotension (p less than 0.001). Patient age, sex, emergency status, duration of HCA, and perfusion variables on cardiopulmonary bypass did not predict operative mortality. The incidence of perioperative neurologic injury was 15%. The only risk factor for neurologic injury was intraoperative hypotension (p less than 0.05). One- and 3-year actuarial survival for patients undergoing operation on the heart or great vessels was 75.9% and 70%, respectively, whereas patients with intraabdominal malignancy had 75% and 23.4% 1- and 3-year survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary embolism in the cardiac surgical patient

Pulmonary embolism (PE) is thought to occur infrequently after cardiac operations, possibly because systemic heparinization during cardiopulmonary bypass prevents deep vein thrombosis. This retrospective study was undertaken to determine the actual incidence of PE after cardiac operations and to identify risk factors. Between January 1, 1985, and December 31, 1989, 5,694 adult patients (greater than 18 years old) had open heart operations at the Johns Hopkins Hospital. Thirty-two patients (20 men and 12 women) had PE within 60 days of operation, an overall PE incidence of 0.56%. The diagnosis of PE was established by ventilation/perfusion scan, pulmonary angiogram, or autopsy. Mortality among patients with PE was 34%. Using a case-control method, preoperative and postoperative risk factors for PE were identified by multivariate and multiple logistic regression analyses. Preoperative risk factors included bed rest (p less than 0.003), prolonged hospitalization before operation (p less than 0.004), and cardiac catheterization performed through the groin within 15 days before operation (p less than 0.01). Post-operative risk factors were congestive heart failure (p less than 0.008), prolonged bed rest (p less than 0.05), and deep vein thrombosis (p less than 0.03). This study demonstrates that PE is an unusual complication after cardiac operations, has a high mortality rate, and is often related to perioperative immobility and recent groin catheterization. These results also suggest that minimizing preoperative hospital stay may be important in PE prophylaxis.

Platelet activating factor inhibition reduces lung injury after cardiopulmonary bypass

Because cardiopulmonary bypass (CPB) produces a diffuse inflammatory reaction that may injure multiple organs and complicate cardiac surgical procedures, we examined the use of a competitive inhibitor of platelet activating factor (SDZ HUL-412) in a porcine model of CPB as a means to ameliorate pulmonary injury after CPB. Thirteen pigs (35 to 40 kg) underwent CPB at 28 degrees C for 2 hours, followed by 2 hours of observation. Group I (n = 6) received SDZ HUL-412 (a quinolinium compound) intravenously (3 mg/kg loading dose and 2 mg.kg-1.h-1 continuous infusion) starting before sternotomy. Group II (n = 7) received a saline vehicle. Peak airway pressure, pulmonary arterial pressure, left atrial pressure, and arterial blood gases were measured and flow cytometry evaluated surface expression of adhesion molecule subunit CD18 on circulating neutrophils. Pulmonary function was significantly improved in group I. Fifteen minutes after CPB, dynamic lung compliance in group I was 91% +/- 12% of baseline versus 49% +/- 5.2% in group II (p = 0.06 by analysis of variance). After CPB, the arterial oxygen pressure was also significantly better in group I than in group II (425 +/- 61 versus 234 +/- 76 mm Hg) (p < 0.05). The rise in pulmonary vascular resistance after CPB was less in group I (p < 0.05) (323 +/- 55 to 553 +/- 106 dynes.s.cm-5) than in group II (531 +/- 177 to 884 +/- 419 dynes.s.cm-5) at the end of the observation period. CD18 up-regulation increased similarly in the two groups during CPB.(ABSTRACT TRUNCATED AT 250 WORDS)