Bryan M. Steinberg

Impact of heparin bonding on pediatric cardiopulmonary bypass: a prospective randomized study

BACKGROUND Heparin-coated circuits reduce the inflammatory response to cardiopulmonary bypass in adult patients; however, little is known about its effects in the pediatric population. Two studies were performed to assess this technologys impact on inflammation and clinical outcomes. METHODS In a pilot study, complement and interleukins were measured in 19 patients who had either uncoated cardiopulmonary bypass circuits or heparin-bonded circuits. Subsequently, 23 additional patients were studied in a randomized fashion. Respiratory function and blood product utilization were recorded. RESULTS In the pilot study, heparin-bonded circuit patients had less complement 3a (p < 0.001) and interleukin-8 (p < 0.05) compared with uncoated cardiopulmonary bypass circuit patients. The randomized study revealed that the heparin-bonded circuit was associated with reduced complement 3a (p = 0.02). Multiple variable analysis revealed that the following postoperative variables were increased with bypass time (p = 0.01) and diminished with heparin-bonded circuits: interleukins (p = 0.01), peak airway pressures (p = 0.05), and prothrombin time (p = 0.03). CONCLUSIONS Heparin-bonded circuits significantly reduce cytokines and complement during cardiopulmonary bypass and lower interleukin levels postbypass; they were also associated with improved pulmonary and coagulation function. Heparin-bonded circuits ameliorate the systemic inflammatory response in pediatric patients from cardiopulmonary bypass.

Mechanical endothelial damage results in basic fibroblast growth factor–mediated activation of extracellular signal-regulated kinases

BACKGROUND Endothelial damage, such as that associated with balloon angioplasty or preparation of veins for bypass grafts, results in intimal hyperplasia. Growth factors and cytokines that modulate endothelial cell functions through various intracellular signaling pathways mediate rapid endothelial repair, which may prevent or reduce restenosis. Here we investigated the effect of mechanical injury of endothelial cells on the mitogen-activated kinase signaling pathways, extracellular-signal-regulated kinases (ERKs), C-Jun N-terminal kinase (JNK/SAPK), and p38. METHODS Confluent human umbilical vein endothelial cells or bovine aortic endothelial cells were wounded with a razor blade; mitogen-activated kinase activation was monitored by immunoblotting with antibodies to active ERK, JNK/SAPK, or p38. RESULTS Wounding of human umbilical vein endothelial cell or bovine aortic endothelial cell monolayers resulted in rapid (5-minute) activation of ERK-1 and -2, which was abolished by monoclonal antibody to basic fibroblast growth factor (FGF-2). This antibody or an inhibitor of ERK activation, PD98059, also blocked endothelial cell migration after the wounding. Thus FGF-2-induced ERK activation mediates the endothelial response to wounding. CONCLUSIONS ERK-1 and -2 are activated by FGF-2 released from endothelial cells in response to injury. Therapeutic strategies aimed at reducing FGF-2-induced intimal hyperplasia should preserve ERK activation in endothelial cells while abolishing it in smooth muscle cells.

Anterior leaflet procedures during mitral valve repair do not adversely influence long-term outcome

OBJECTIVES This study was done to assess the impact of anterior mitral leaflet reconstructive procedures on initial and long-term results of mitral valve repair. BACKGROUND It has been suggested that involvement of the anterior leaflet in mitral valve disease adversely affects the long-term outcome of mitral valve repair. Our policy has been to aggressively repair such anterior leaflets with procedures that include triangular resections in some cases. METHODS From June 1979 through June 1993, 558 consecutive Carpentier-type mitral valve repairs were performed. The anterior mitral leaflet and chordae tendineae were repaired in 156 patients (mean age 58 years). The procedures included anterior chordal shortening in 78 patients (50%), anterior leaflet resections in 44 (28%), resuspension of the anterior leaflet to secondary chordae in 42 (27%) and anterior chordal transposition in 27 (17%). Concomitant cardiac surgical procedures were performed in 75 patients (48%). RESULTS The operative mortality rate was 2.5% (2 of 81) for isolated mitral valve anterior leaflet repair and 3.8% (6 of 156) for all mitral valve anterior leaflet repair. Freedom from reoperation at 5 and 10 years was, respectively, 89.7% (n = 160) and 83.4% (n = 24) for the entire series of 558 patients, 91.9% (n = 51) and 81.2% (n = 10) for patients with anterior leaflet procedures, 88.8% (n = 109) and 84.4% (n = 14) for patients without anterior leaflet procedures and 91.7% (n = 118) and 88.9% (n = 18) for patients without rheumatic disease. Logistic regression showed that rheumatic origin of disease (odds ratio 2.99), but not anterior leaflet repair, increased the risk for reoperation. CONCLUSIONS These results demonstrate that expansion of mitral valve techniques to include anterior leaflet disease yields immediate and long-term results equal to those seen in patients with posterior leaflet disease.

Severe calcification does not affect long-term outcome of mitral valve repair

Some surgeons have suggested that the presence of severe calcification in the mitral valve annulus or leaflets precludes successful repair. Our institution has attempted to repair these calcified valves when good annular and leaflet mobility could be achieved by annular debridement and leaflet resection. From June 1979 through June 1993 558 mitral valve repairs were performed using Carpentiers techniques. When calcified valves were encountered, these techniques were modified to include annular debridement and mechanical leaflet decalcification. Calcification was identified preoperatively in 49 patients (8.8%) by either left ventricular fluoroscopy or echocardiography and was debrided in 64 patients (11.5%). This included 24 annular debridements, 28 leaflet debridements, and 12 annular and leaflet debridements. Patient ages ranged from 13 to 83 years (mean age, 62.3 years), and 25 patients (39.1%, 25/64) had concomitant cardiac procedures. Operative mortality was 6.2% (4/64) overall and 2.6% (1/39) for isolated mitral valve repairs. Calcium debridement was performed in 19.3% (23/119) of patients with a rheumatic cause compared with 9.3% (41/439) of the nonrheumatic patients (p < 0.01). Long-term follow-up revealed the necessity for reoperation in 7.8% (5/64) in patients with calcium debridement as compared with 7.7% (38/494) with no debridement (p = not significant). Cumulative freedom from reoperation at 10 years was 83.3% for all patients, 88.1% for debrided patients, and 82.6% for nondebrided patients (p = not significant). Cox proportional hazards analysis revealed that the presence of rheumatic disease significantly increased the risk of reoperation (odds ratio = 3.28; p < 0.001), whereas calcium debridement had no significant effect. These results demonstrate that when good annulus and leaflet motion can be achieved in calcified mitral valves, calcium debridement allows durable repairs.

Mammary Artery Versus Saphenous Vein Grafts: Assessment of Basic Fibroblast Growth Factor Receptors

Neointimal hyperplasia limits the long-term patency of saphenous vein grafts (SVGs), but is notably absent from most internal mammary artery (IMA) grafts. Basic fibroblast growth factor (bFGF) is a local endothelial and vascular smooth muscle mitogen known to be involved in the pathogenesis of neointimal hyperplasia. This study used an animal model to compare the number of available high-affinity (HAR) and low-affinity (LAR) bFGF receptors in SVGs and IMA grafts and to determine whether distention injury causes an increase in receptor availability. The IMA and SVG specimens were harvested from 12 dogs and distended at 25 or 200 mm Hg for 15 minutes, and then the bFGF receptor uptake was measured in them using iodine 125-labeled bFGF. In the IMA conduits distended at low pressure, there were 2.54 +/- 0.10 (mean +/- standard error of the mean) HARs per mm2 of intimal surface area available and 5.19 +/- 0.40 LARs per mm2. High-pressure distention significantly (p < 0.001) increased the number of available HARs to 5.06 +/- 0.27 per mm2 and of LARs to 7.27 +/- 0.042 per mm2. At low pressure, the SVGs had significantly (p < 0.001) more HARs (9.14 +/- 0.84 per mm2) and LARs (18.2 +/- 0.57 per mm2) available than did the IMA conduits, and high pressure significantly (p < 0.001) increased the number of HARs available in SVGs to 24.1 +/- 2.43 per mm2 and the number of LARs to 44.7 +/- 2.34 per mm2.(ABSTRACT TRUNCATED AT 250 WORDS)