A reconstructive algorithm for plastic surgery following extensive chest wall resection.

Chest wall reconstruction following extensive resection is greatly facilitated by the use of vascularised flaps and prosthetic material. Plastic surgeons are often asked to assist with coverage of large chest wall defects. However, in addition to soft tissue coverage, we need to address other important issues such as the status of the pleural cavity, and the requirement for skeletal support. The purpose of this report is to analyse our experience, provide a reconstructive algorithm following the ablative procedure and review the literature. Two hundred chest wall resections were performed from 1975 to 2000. Defect location was divided into anterior (n = 73) lateral (n = 36) anterior-lateral (n = 36) posterior-lateral (n = 19) posterior (n = 22) and forequarter (n = 14) Average number of ribs resected was four. One hundred and fifty-eight patients (79%) required chest wall reconstruction with either prosthetic material and/or flap closure. Mesh closure was required in 85 cases (43%), being highest for lateral defects (61%), and lowest for anterior defects (31%). Vascularised flaps were needed in 112 patients (56%), more common in anterior defects (79%), and less common for the posterior-lateral defects (26%). Inpatient complication rate was 27% (43/158) following reconstruction, with a mortality of 6% (10/158). Chest wall reconstruction is common following extensive resection. This includes management of the pleural cavity, skeletal support and soft tissue coverage. A better understanding of the respiratory mechanics and local thoracoabdominal anatomy is crucial for managing these complex defects. The need for skeletal support was more prevalent in lateral and posterior-lateral defects. Flap reconstruction was required more often to cover large anterior defects, with regional flaps predominating.

Active perfusion of coronary grafts facilitates complex off-pump coronary artery bypass surgery.

BACKGROUND: Hemodynamic stability during cardiac manipulation for complex, multivessel off-pump coronary artery bypass grafting (OPCAB) remains problematic. METHODS: A servo-controlled pump has been utilized to deliver warm whole blood to coronary grafts prior to construction of proximal anastomoses. RESULTS: This technique may avoid detrimental hemodynamic decompensation, which may accompany regional coronary ischemia during cardiac displacement. It may also allow precise infusion of supplemental additives leading to coronary vasodilatation, myocardial resuscitation, and enhancement of myocardial contractility. CONCLUSION: In this report, three complex OPCAB cases are described which were successfully performed with active graft perfusion and which might not otherwise have been technically feasible by conventional OPCAB techniques.

Clinical outcomes, angiographic patency, and resource utilization in 200 consecutive off-pump coronary bypass patients.

BACKGROUND: This retrospective study compared clinical outcomes and resource utilization in patients having off-pump coronary artery bypass grafting (OPCAB) versus conventional coronary artery bypass grafting (CABG). Angiographic patency was documented in the OPCAB group. METHODS: From April 1997 through November 1999, OPCAB was performed in 200 consecutive patients, and the results were compared with those in a contemporaneous matched control group of 1,000 patients undergoing CABG. Patients were matched according to age, sex, preexisting disease (renal failure, diabetes, pulmonary disease, stroke, hypertension, peripheral vascular disease, previous myocardial infarction, and primary or redo status. Follow-up in the OPCAB patients was 93% and averaged 13.4 months. RESULTS: Hospital death (1.0%), postoperative stroke (1.5%), myocardial infarction (1.0%), and re-entry for bleeding (1.5%) occurred infrequently in the OPCAB group. There were reductions in the rates of transfusion (33.0% versus 70.0%; p < 0.001) and deep sternal wound infection (0% versus 2.2%; p = 0.067) in the OPCAB group compared with the CABG group. Angiographic assessment of 421 grafted arteries was performed in 167 OPCAB patients (83.5%) prior to hospital discharge. All but five were patent (98.8%) (93.3% FitzGibbon A, 5.5% FitzGibbon B, 1.2% FitzGibbon O). All 163 internal mammary artery grafts were patent. Off-pump coronary artery bypass grafting reduced postoperative hospital stay from 5.7 +/- 5.3 days in the CABG group to 3.9 +/- 2.6 days (p < 0.001), with a decrease in hospital cost of 15.0% (p < 0.001). CONCLUSIONS: Off-pump coronary artery bypass grafting reduces hospital cost, postoperative length of stay, and morbidity compared with CABG on cardiopulmonary bypass. Off-pump coronary bypass grafting is safe, cost effective, and associated with excellent graft patency and clinical outcomes.

The surgical spectrum of pulmonary neuroendocrine neoplasms.

OBJECTIVES: The purpose of this study is to review our experience with the spectrum of neuroendocrine neoplasms of the lung with emphasis on the histopathologic classification and surgical therapy of each class of neoplasm. DESIGN: This retrospective review covers the entire spectrum of neuroendocrine neoplasms of the lung over an 11-year period (January 1985 to December 1995) in a university hospital setting. Only patients who underwent surgical resection were included in this review. PATIENTS: During this period, a total of 77 patients underwent lung resection for the following neuroendocrine neoplasms: typical carcinoid (TC), 50 patients; atypical carcinoid (AC), 5 patients; large cell neuroendocrine carcinoma (LCNEC), 9 patients; mixed large-small cell neuroendocrine carcinoma (LSNEC), 4 patients; or small cell neuroendocrine carcinoma (SCC), 9 patients. There were 37 men (48.1%) and 40 women (51.9%) among the patients, with a mean age of 57.9 years (range, 14 to 87 years). INTERVENTIONS: Primary surgical resection consisted of the following procedures: 52 lobectomies (67.5%); 10 pneumonectomies (13%); 13 limited resections (16.9%); 1 left main bronchus sleeve resection; and 1 carinal resection. Six patients had the following concomitant procedures: pericardiectomy, 2 patients; mediastinoscopy, 1 patient; chest wall resection, 1 patient; stapling blebs, 1 patient; and transdiaphragmatic liver biopsy, 1 patient. Four patients underwent bilobectomies, and two patients underwent multiple wedge resections. RESULTS: The hospital mortality rate was 2.6% (2 of 77 patients), and both patients died of pulmonary failure. Follow-up was obtained in 62 of 77 patients (80.9%) for an average of 38.1 months (range, 2 to 132 months). There were a total of 13 deaths, and 8 were disease-related (LCNEC, 4 deaths; SCC, 2 deaths; LSNEC, 1 death; and AC tumor, 1 death. The mean disease-free intervals for patients with these neoplasms were the following: TC tumor, 41.3 months; AC tumor, 20 months; LCNEC, 20.4 months; LSNEC, 25 months; and SCC, 48 months. The overall 3-year survival rate was 45.2% (28 of 62 patients). CONCLUSION: This report will emphasize the classification, surgical management, and treatment considerations of pulmonary neuroendocrine neoplasms. Despite the poor overall prognosis in high-grade neuroendocrine tumors of the lung, surgery remains a viable adjunct in the early stages of this disease.

Glutathione reverses endothelial damage from peroxynitrite, the byproduct of nitric oxide degradation, in crystalloid cardioplegia.

BACKGROUND: NO has been advocated as an adjunct to cardioplegia solutions. However, NO undergoes a rapid biradical reaction with superoxide anions to produce peroxynitrite (ONOO(-)). ONOO(-) in crystalloid cardioplegia solution induces injury to coronary endothelium and to systolic function after cardioplegia and reperfusion. However, ONOO(-) may be degraded to less lethal or cardioprotective intermediates with glutathione (GSH) in reactions separate from its well known antioxidant effects. We hypothesized that GSH detoxifies ONOO(-) and reverses defects in endothelial function and systolic function when present in crystalloid cardioplegia. METHODS AND RESULTS: In anesthetized dogs on cardiopulmonary bypass, a 45-minute period of global normothermic ischemia was followed by 60 minutes of intermittent cold crystalloid cardioplegia (Plegisol) and 2 hours of reperfusion. The cardioplegia solution contained 5 micromol/L authentic ONOO(-); catalase was included to attenuate the potential antioxidant effects of GSH and to unmask the effects on ONOO(-). In 1 group (CP+GSH, n=5), the cardioplegia contained 500 micromol/L GSH, whereas 1 group received crystalloid cardioplegia without GSH (CCP, n=6). There were no group differences in postcardioplegia left ventricular systolic function (end-systolic pressure-volume relation, impedance catheter: CCP 10.0+/-2.4 versus CP+GSH 10.6+/-1.3 mm Hg/mL) or diastolic chamber stiffness (ss-coefficient: CCP 0.35+/-0.2 versus CP+GSH 0.31+/-0.18). Myocardial neutrophil accumulation (myeloperoxidase activity) was attenuated in CP+GSH versus CCP (2.2+/-0.7 versus 5.4+/-1.2, P:<0.05). In postexperimental coronary arteries, maximal endothelium-dependent relaxation was greater in CP+GSH than in CCP (118+/-6% versus 92+/-5%, P:<0.05), with a smaller EC(50) value (-7. 10+/-0.05 versus -6.98+/-0.03, respectively, P:<0.05). Smooth muscle relaxation was complete in both groups. The adherence of neutrophils to postexperimental coronary arteries as a measure of endothelial function was less in CP+GSH than in CCP (98+/-18 versus 234+/-36 neutrophils/mm(2), P:<0.05). Nitrosoglutathione, a byproduct of the reaction between ONOO(-) and GSH, was greater in CP+GSH than in CCP (4.1+/-2.3 versus 0.4+/-0.2 microg/mL, P:<0.05). CONCLUSIONS: GSH in crystalloid cardioplegia detoxifies ONOO(-) and forms cardioprotective nitrosoglutathione, resulting in attenuated neutrophil adherence and selective endothelial protection through the inhibition of neutrophil-mediated damage.

Influence of concomitant CABG and urgent/emergent status on mitral valve replacement surgery.

BACKGROUND: Outcomes and resource utilization of patients undergoing mitral valve replacement (MVR) with or without concomitant coronary artery bypass grafting (CABG) were reviewed. METHODS: Data for 1,844 patients undergoing isolated primary MVR at Emory University Hospitals between 1980 and 1997 were recorded prospectively in a computerized database. RESULTS: The four groups included patients undergoing elective MVR with (n = 360) or without CABG (n = 1332) and urgent/emergent MVR with (n = 66) or without CABG (n = 86). Length of stay was significantly higher in patients undergoing elective MVR with CABG (15 days) than in those without CABG (11 days) but was not significantly different in patients undergoing urgent/emergent MVR with CABG (17 days) than in those without CABG (19 days). In-hospital mortality was significantly higher for patients undergoing elective (14%) or urgent/emergent (41%) MVR with CABG than in those undergoing MVR without CABG (elective:6%; urgent/emergent:20%). The 19-year survival rate was 32% for patients undergoing elective MVR with CABG compared with 51% for those without CABG and 28% for patients undergoing urgent/emergent MVR with CABG compared with 46% for those without CABG. Multivariate correlates of long-term mortality included older age, concomitant CABG, and urgent/emergent status. Hospital costs were significantly higher for patients undergoing elective MVR with ($33,216) than for those without ($23,890) CABG. No significant difference in cost were noted between patients undergoing urgent/emergent MVR with ($40,535) and without ($31,981) CABG. CONCLUSIONS: The addition of CABG or urgent/emergent status to patients undergoing MVR significantly increases morbidity, mortality, and costs. Careful scrutiny of the benefits versus resource utilization is required for patients undergoing high risk MVR.

Ten-year trends in heart valve replacement operations.

BACKGROUND: There has been increasing concern in recent years about the quality and cost of heart valvular replacement procedures. The purpose of this study is to examine the profile of patients undergoing valvular operations during the past decade, and to look at trends in outcome and resource utilization over that period. METHODS: Clinical and procedural data of 2,972 patients undergoing heart valve replacement at Emory University Hospitals between 1988 and 1997 were recorded prospectively on standardized forms by trained medical personnel and entered into a computerized database. RESULTS: There were 1,802 patients undergoing aortic valve replacement (AVR), 966 undergoing mitral valve replacement (MVR), and 204 undergoing combined aortic and mitral valve procedures (AVR + MVR). No patients were excluded. There was a statistically significant trend for patients undergoing AVR, MVR, or AVR + MVR over time to be older and sicker by multiple criteria. Nonetheless, procedural outcome and inhospital mortality for patients undergoing AVR remained unchanged. Cost and length of stay increased from 1988 to 1992 when a concerted effort to decrease resource utilization began. Between 1992 and 1997 for AVR, length of stay decreased from 13.4 to 8.0 days and cost from $37,047 to $21,856. Similarly, between 1992 and 1997 for MVR, length of stay decreased from 15.6 to 8.1 days and cost from $45,072 to $21,747. The net result over the time period from 1988 to 1997 was an average decline in the cost of operation of $785 a year, adjusted for other factors. CONCLUSIONS: This study reveals that outcome of valvular replacement during the period from 1988 to 1997 has remained constant despite the patients becoming older and sicker during the same period. This constant outcome has been accomplished, but length of stay has decreased significantly. Hospital costs increased during the first years of the study period, but then decreased to levels in 1997 that were equal to or significantly less than 1988 levels.

Recombinant human complement C5a receptor antagonist reduces infarct size after surgical revascularization.

OBJECTIVES: This study tested the hypothesis that a recombinant human C5a antagonist, CGS 32359, attenuates neutrophil activation and reduces infarct size in a porcine model of surgical revascularization. METHODS: CGS 32359 (0.16-16 micromol/L) dose-dependently inhibited superoxide production by human C5a-activated porcine neutrophils (18 +/- 3.7 vs 1.6 +/- 0.5 nmol/5 min/5 x 10(6) neutrophils; P <.05) and reduced neutrophil adherence to coronary endothelium from 194 +/- 9 to 43 +/- 6 neutrophils/mm(2) (P <.05). The left anterior descending coronary artery was occluded for 50 minutes, after which saline solution (n = 8), mannitol-buffer vehicle (n = 9, 102 mg/kg bolus, 102 mg. kg(-1). h(-1)), or CGS 32359 (CGS, n = 7, 60 mg/kg bolus, 60 mg. kg(-1). h(-1)) was infused. After ischemia, 1-hour arrest was achieved by means of multidose hypothermic (4 degrees C) blood cardioplegia, followed by 2.5 hours of off-bypass reperfusion. The ligature on the left anterior descending artery was released before the second infusion of cardioplegic solution. RESULTS: Area at risk was similar in all groups (saline solution, 27% +/- 2%; mannitol-buffer vehicle, 26% +/- 2%; CGS, 26% +/- 2% left ventricular mass). Infarct size (area necrosis/area at risk) was significantly reduced by CGS (18% +/- 6%, P <.05) versus saline solution (52% +/- 3%) and mannitol-buffer vehicle (60% +/- 4%). Postischemic systolic shortening (sonomicrometry) in the area at risk was significantly improved with CGS (0.8% +/- 0.9%) compared with saline solution (-3.7% +/- 1.1%) and mannitol-buffer vehicle (-6.4% +/- 1.0%). Myeloperoxidase activity from accumulated neutrophils was less in the ischemic zone of CGS (0.014 +/- 0.002 U/100 mg tissue; P <.05) than mannitol-buffer vehicle (0.133 +/- 0.012 U/100 mg tissue). CONCLUSIONS: We conclude that the recombinant human C5a receptor antagonist CGS 32359 inhibits surgical ischemia-reperfusion injury after coronary occlusion.

Myocardial protection: an overview.

The goals of myocardial protection during cardiac surgery are not only to facilitate the operation by providing a quiet bloodless field, thereby facilitating the precision of the operation, but also to avoid iatrogenic injury induced by cardiopulmonary bypass itself or by surgically imposed ischemia. In addition, myocardial protective strategies are geared to preventing reperfusion injury upon resolution of the coronary occlusion and the ultimate release of the aortic cross clamp. Cardioplegia plays a very important role in myocardial protection strategies. Acting as a selective perfusion agent, cardioplegia solutions can alter or inhibit ischemic injury by virtue of hypothermia and asystole. In addition, cardioplegia can be used to avoid reperfusion injury by altering the conditions of its delivery and the composition of the solution using various adjunctive agents and pharmacologic therapies for which cardioplegia solutions serve as a vector. Future strategies, particularly for off-pump surgical procedures, may incorporate systemic delivery of therapeutic agents to the heart directly either in conjunction with or without cardioplegia.

Nonanticoagulant heparin inhibits NF-kappaB activation and attenuates myocardial reperfusion injury.

Heparin reduces ischemia-reperfusion injury to myocardium. This effect has been attributed to complement inhibition, but heparin also has other activities that might diminish ischemia-reperfusion. To further probe these mechanisms, we compared heparin or an o-desulfated nonanticoagulant heparin with greatly reduced anticomplement activity. When given at the time of coronary artery reperfusion in a canine model of myocardial infarction, heparin or o-desulfated heparin equally reduced neutrophil adherence to ischemic-reperfused coronary artery endothelium, influx of neutrophils into ischemic-reperfused myocardium, myocardial necrosis, and release of creatine kinase into plasma. Heparin or o-desulfated heparin also prevented dysfunction of endothelial-dependent coronary relaxation following ischemic injury. In addition, heparin and o-desulfated heparin inhibited translocation of the transcription nuclear factor-kappaB (NF-kappaB) from the cytoplasm to the nucleus in human endothelial cells and decreased NF-kappaB DNA binding in human endothelium and ischemic-reperfused rat myocardium. Thus heparin and nonanticoagulant heparin decrease ischemia-reperfusion injury by disrupting multiple levels of the inflammatory cascade, including the novel observation that heparins inhibit activation of the proinflammatory transcription factor NF-kappaB.

Hypothermic circulatory arrest causes multisystem vascular endothelial dysfunction and apoptosis.

BACKGROUND: Multiple organ failure after deep hypothermic circulatory arrest (DHCA) may occur secondary to endothelial dysfunction and apoptosis. We sought to determine if DHCA causes endothelial dysfunction and apoptosis in brain, kidney, lungs, and other tissues. METHODS: Anesthetized pigs on cardiopulmonary bypass were: (1) cooled to 18 degrees C, and had their circulation arrested (60 minutes) and reperfused at 37 degrees C for 90 minutes (DHCA, n = 8); or (2) time-matched normothermic controls on bypass (CPB, n = 6). Endothelial function in cerebral, pulmonary, and renal vessels was assessed by vasorelaxation responses to endothelial-specific bradykinin (BK) or acetylcholine (ACh), and smooth muscle-specific nitroprusside. RESULTS: In vivo transcranial vasorelaxation responses to ACh were similar between the two groups. In small-caliber cerebral arteries, endothelial relaxation (BK) was impaired in CPB vs DHCA (maximal 55% +/- 2% [p < 0.05] vs 100% +/- 6%). Pulmonary artery ACh responses were comparable between CPB (110% +/- 10%) and DHCA (83% +/- 6%), but responses in pulmonary vein were impaired in DHCA (109% +/- 3%, p < 0.05) relative to CPB (137% +/- 6%). In renal arteries, endothelial (ACh) responses were impaired in DHCA (71% +/- 13%) relative to CPB (129% +/- 14%). Apoptosis (DNA laddering) occurred primarily in duodenal tissue, with a greater frequency in DHCA (56%, p < 0.05) compared with normothermic CPB (17%) and nonbypass controls (0%). CONCLUSIONS: DHCA is associated with endothelial dysfunction in cerebral microvessels but not in the in vivo transcranial vasculature; in addition, endothelial dysfunction was noted in large-caliber renal arteries and pulmonary veins. DHCA is also associated with duodenal apoptosis. Vascular endothelial dysfunction and apoptosis may be involved in the pathophysiology of multisystem organ failure after DHCA.

Perfusion-assisted direct coronary artery bypass: selective graft perfusion in off-pump cases.

BACKGROUND: Hemodynamic instability during multivessel off-pump coronary artery bypass grafting can lead to hypotension, progressive myocardial ischemia, further hypotension, and the need for urgent cardiopulmonary bypass. METHODS: In 10 patients undergoing off-pump coronary artery bypass grafting, a novel technique of pressure-controlled blood delivery has been used that allows the immediate restoration of arterial blood to distal coronary beds after distal coronary anastomosis. This technique utilizes a servo-controlled pump to allow delivery of blood at systemic or suprasystemic pressures, and provides the option for infusion of supplemental additives for myocardial resuscitation, myocardial vasodilation, and enhancement of myocardial performance. RESULTS: Myocardial perfusion was successfully enhanced via one or two grafts in all 10 patients with an average graft flow of 98+/-8 mL/min. In 3 patients, a 27% increase in perfusion pressure led to a 59% increase in perfusate flow. All patients were hemodynamically stable after initiation of selective graft perfusion. CONCLUSIONS: Based on this preliminary patient series, the selective perfusion of grafted vessels seems to facilitate multivessel off-pump coronary artery bypass grafting by promoting rapid recovery of grafted segments, by enhanced hemodynamic stability during subsequent anastomoses, and by providing increased flexibility in the sequence of grafting.

Broad-spectrum cardioprotection with adenosine.

Ischemia-reperfusion results in contractile dysfunction, necrosis, and vascular injury. This postischemic injury is mediated in part by superoxide radical production, neutrophils, dysfunction to ionic pumps, and edema formation. Adenosine is an autacoid released tonically by myocytes, endothelium, and neutrophils; the release of adenosine from the myocyte compartment into the interstitium is increased during ischemia. The major effects of adenosine are mediated by specific receptors identified as A1, A2a, A2b, and A3. Each receptor subtype contributes to physiological responses that influence ischemia-reperfusion injury. Adenosine has potent cardioprotective properties exerted during three major windows of opportunity: pretreatment, ischemia, and reperfusion. The cardioprotective effects exerted during pretreatment and ischemia may involve metabolic changes and hyperpolarization via K(ATP)-channel activation, mediated through A1 receptor mechanisms. The cardioprotective mechanisms exerted during reperfusion involve inhibition of neutrophils directly (superoxide anion generation, expression of adhesion molecules), and by inhibiting activation of the endothelium through A2 receptor-mediated mechanisms, thereby preventing neutrophil-endothelial cell interactions, which initiate the inflammatory-like component of reperfusion injury. Activation of the newly identified A3 receptor has been shown to be cardioprotective partially by inhibition of neutrophil adherence to endothelium and by neutrophil-independent mechanisms. These mechanisms of cardioprotection have been suggested to play major roles in the reduction of infarction and apoptosis after myocardial ischemia, cardioplegic arrest, and subsequent reperfusion. Adenosine has been used as an adjunct to both crystalloid and blood cardioplegia, but its potential as a cardioprotective agent has not been fully explored.

Adenosine-supplemented blood cardioplegia attenuates postischemic dysfunction after severe regional ischemia.

BACKGROUND: Various studies have reported that the administration of adenosine (ADO) in cardioplegia reduces myocardial ischemic injury, but this timing may not utilize ADO's potential against myocardial reperfusion injury. This study tested the hypothesis that ADO-supplemented blood cardioplegia (BCP) or ADO administered during reperfusion reduces postischemic dysfunction after severe regional ischemia. METHODS AND RESULTS: After 75 minutes of left anterior descending coronary artery occlusion, total cardiopulmonary bypass was initiated; cold (4 degrees C) antegrade BCP (8:1 blood:crystalloid) was delivered every 20 minutes for the first 3 doses, and 27 degrees C BCP was delivered for the terminal infusion. Dogs (n=6 per group) received unsupplemented BCP, ADO (100 micromol/L/L) supplemented in all infusions of BCP (ADO-CP), or ADO (100 micromol x L(-1) x L(-1)) supplemented only in the terminal infusion of BCP followed by intravenous ADO (140 microg x kg(-1) x min(-1)) infusion for the first 30 minutes of reperfusion (ADO-R). Postischemic regional systolic shortening was significantly greater in the ADO-R group (5+/-2.0%) than in the BCP group (-3+/-1.0%), but not in the ADO-CP group (2+/-0.2%). Postischemic regional diastolic stiffness in the area at risk during end reperfusion was lower with ADO-R (1.8+/-0.3%) than with ADO-CP (2.7+/-0.3%) or BCP (4.4+/-0.5%). Infarct size was reduced in the ADO-CP (29+/-2%) and ADO-R (21+/-2%) groups compared with the BCP group (42+/-4%). Edema in the myocardial area at risk was decreased in the ADO-CP (82+/-0.2%) and ADO-R (80+/-0.4%) groups compared with the BCP group (86+/-0.7%). Adherence of fluorescently labeled neutrophils (PMNs) to postischemic coronary artery endothelium was attenuated by ADO-R (55+/-2 PMNs/mm(2)), but not by ADO-CP (114+/-5 PMNs/mm(2)), compared with BCP (118+/-3 PMNs/mm(2)). CONCLUSIONS: The results show that BCP supplemented with ADO reduces infarct size, preserves postischemic systolic and diastolic regional function but does not attenuate coronary artery endothelial dysfunction unless administered during reperfusion.

Peroxynitrite, the breakdown product of nitric oxide, is beneficial in blood cardioplegia but injurious in crystalloid cardioplegia.

BACKGROUND: Peroxynitrite (ONOO(-)) has been implicated as a primary mediator in the deleterious effects of nitric oxide (NO) in crystalloid solutions, possibly due to a lack of detoxification mechanisms, leading to the formation of.OH. In contrast, ONOO(-) may exert cardioprotective effects in blood environments secondary to detoxification and the subsequent formation of NO-donating nitrosothiols. This dichotomy in physiological effects of ONOO(-) may exist between crystalloid and blood cardioplegia (BCP) environments. In the present study, we tested the hypothesis that ONOO(-) is cardiotoxic in crystalloid cardioplegia but cardioprotective in BCP in ischemically injured hearts. METHODS AND RESULTS: In anesthetized dogs on cardiopulmonary bypass, global 37 degrees C ischemia was imposed for 30 minutes, followed by 60 minutes of intermittent 4 degrees C hyperkalemic crystalloid (Plegisol) or BCP with (+) or without (-) 5 micromol/L authentic ONOO(-). After 2 hours of reperfusion, left ventricular (LV) function (end-systolic pressure-volume relations, in percent of baseline) was 56+/-3% in Plegisol-, which was further reduced in Plegisol+ to 40+/-4%.* In contrast, postischemic systolic function was better in BCP+ groups than in BCP- groups (96+/-2%* versus 82+/-2%, respectively). Differences in functional recovery could not be attributed to differences in hemodynamics. LV end-diastolic stiffness was significantly increased with the addition of ONOO(-) in both Plegisol (298+/-26% versus 466+/-30%*) and BCP (201+/-22% versus 267+/-13%*) groups. Consistent with increased LV chamber stiffness, myocardial edema was increased in BCP+ compared with BCP- (78.9+/-0.3% versus 76.4+/-0.3%*) and in Plegisol+ compared with Plegisol- (81.1+/-0.3% versus 79.6+/-0.4%*). Creatine kinase activity was significantly increased in Plegisol+ (48+/-6) compared with that in Plegisol- (31+/-6) but was unchanged in BCP- (14+/-2) relative to BCP+ (18+/-1). Nitrotyrosine (ng/mg protein) accumulation in LV myocardial biopsy samples confirmed myocardial exposure to ONOO(-) or its metabolites (Plegisol- 1.2+/-0.1, Plegisol+ 3.31+/-0.3*, BCP- 1.4+/-0.2, BCP+ 2.9+/-0.2*). CONCLUSIONS: We conclude that (1) the postcardioplegic cardiodynamic effects of ONOO(-) depend on its environment and (2) ONOO(-) in crystalloid solution impairs postcardioplegia systolic and diastolic functional recovery, whereas (3) ONOO(-) in BCP increases functional recovery. This environment-dependent dichotomy in the effect of ONOO(-) may affect the benefits of NO-related adjuncts to crystalloid or BCP solutions (*P<0.05 versus group without ONOO(-)). :II-384-II-391.)

A(3) adenosine receptor activation attenuates neutrophil function and neutrophil-mediated reperfusion injury.

This study tested the hypothesis that A(3) adenosine receptors inhibit neutrophil (PMN) function and PMN-mediated reperfusion injury. 2-Chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide (Cl-IB-MECA), an A(3) agonist, did not attenuate superoxide production or myeloperoxidase release from stimulated PMNs. However, Cl-IB-MECA reduced platelet-activating factor-stimulated PMN adherence to coronary endothelium at low concentrations: 52 +/- 27, 45 +/- 10, and 87 +/- 23 PMNs/mm(2) at 0.1, 1.0, and 10 nM vs. 422 +/- 64 PMNs/mm(2) with platelet-activating factor alone. This inhibition was not blocked by A(1) (5 microM KW-3902) or A(2a) (5 microM KF-21326) antagonists: 44 +/- 3 and 43 +/- 2 PMNs/mm(2), respectively. Endothelial pretreatment with 1 nM Cl-IB-MECA reduced PMN adherence, which was reversed by the A(3) antagonist MRS-1220 (100 nM). PMN-mediated reperfusion injury was initiated in isolated rabbit hearts by infusion of 28 x 10(6) PMNs/min for 10 min early in reperfusion. PMNs caused a significant decrease in recovery of left ventricular developed pressure and positive and negative time derivatives of pressure (23 +/- 3, 25 +/- 3, and 23 +/- 3% of baseline, respectively) vs. buffer-perfused hearts (43 +/- 7, 44 +/- 7, and 45 +/- 6%, respectively). Cl-IB-MECA (10 nM) given at reperfusion attenuated the PMN-mediated loss of contractile recovery (40 +/- 3, 46 +/- 5, and 42 +/- 4% of baseline). Cl-IB-MECA reduced myeloperoxidase release activity (5.3 +/- 0.6 absorbance units/min) and CD18-positive cells (54 +/- 9 cells/slide) compared with the untreated PMN group (17.9 +/- 1.7 absorbance units/min and 183 +/- 68 cells/slide). We conclude that Cl-IB-MECA attenuates reperfusion injury by decreasing PMN-endothelial cell interactions. These results suggest that the A(3) adenosine receptor may be a novel therapeutic target for treatment of myocardial ischemia and reperfusion.

Risk neutralization in cardiac operations: detection and treatment of associated carotid disease.

BACKGROUND: A screening and treatment protocol was implemented to extend the benefit of prophylactic carotid endarterectomy to patients who had open heart operations. METHODS: Patients aged 65 or older or who at any age had left main coronary disease, transient ischemic attack, or stroke were eligible for preoperative carotid duplex screening. Carotid endarterectomies and open heart operations were planned as a staged (n = 59) or combined procedure (n = 55) for angiographically confirmed carotid stenosis of at least 80%. RESULTS: Duplex scans were obtained in 1,719 of 7,035 open heart surgical patients over 8 years. The overall stroke rate was 1.5% (108 of 7,035). Seven of these were strokes of carotid origin (0.1%). There were 129 patients with at least 80% stenosis. One hundred fourteen had carotid endarterectomy preceding open heart operation, and none had carotid artery stroke. Twelve patients with at least 80% carotid stenosis by duplex scan had open heart operations without prophylactic carotid endarterectomies. There were four carotid strokes in these 12 patients (p = 0.0001; odds ratio, 20.2). Stroke risk remained significantly elevated (16.8%, p = 0.005) in the 50% to 79% group. The changes associated with the reduced risk afforded by this screening and treatment strategy amounted to $346 for each patient in the study. CONCLUSIONS: The risk of carotid stroke at the time of cardiac operation can be defined by duplex screening. Prophylactic carotid endarterectomy neutralizes the risk in those with at least 80% stenosis. Consideration for lowering the threshold for assessment and treatment of carotid stenoses appears warranted. The economic investment is recouped by the savings in system resources that would have been depleted through care for carotid stroke and its sequelae.

Penetrating cardiac trauma at an urban trauma center: a 22-year perspective.

This is a report of a 22-year experience with penetrating cardiac trauma at a single urban Level I trauma center. We conducted a retrospective chart review supplemented by computerized patient log. Comparisons of mortality between Period 1 (1975-1985; 113 patients) and Period 2 (1986-1996; 79 patients) were by chi2 or Fisher's exact tests. Statistical significance was defined as P < or = 0.05. From 1975 to 1996, 192 patients (mean age, 32 years; 88% male) with penetrating cardiac stab wounds (68%) or gunshot wounds (32%) were treated. The most common initial clinical presentation was cardiac tamponade, and most patients (54%) were hypotensive (systolic blood pressure 30-90 mm Hg). The most common initial intervention in the emergency center was tube thoracostomy. The use of pericardiocentesis as a diagnostic and therapeutic modality in the emergency center virtually disappeared in Period 2, as compared with Period 1. Since 1994, surgeon-performed cardiac ultrasound has been performed and has correctly diagnosed hemopericardium in 12 patients (100% survival). The overall mortality for all patients during the 22-year study interval was 25 per cent and was not significantly different between Period 1 (27%) and Period 2 (22%). The mortality associated with gunshot wounds was increased compared with that of stab wounds. Similarly, mortality for patients who arrested in the emergency center was increased compared with those patients who did not arrest. We conclude: 1) cardiac tamponade is the most common presentation in patients with cardiac wounds; 2) pericardiocentesis in the emergency center has essentially disappeared; 3) surgeon-performed ultrasound of the pericardium should improve survival of future patients who are normotensive or mildly hypotensive; 4) over the last 11 years, there has been a substantial decrease in mortality in patients with stab wounds and a statistically significant decrease in arrested patients; and 5) overall mortality for penetrating cardiac trauma has not changed during the 22-year interval.

Nitric oxide and the vascular endothelium in myocardial ischemia-reperfusion injury.

The normal coronary vascular endothelium (VE) tonically releases nitric oxide (NO) by converting L-arginine to citrulline by a constitutive NO synthase. Reperfusion after myocardial ischemia reduces basal and stimulated release of NO. This "vascular reperfusion injury" is mediated largely by neutrophils (PMN) through specific interactions between adhesion molecules on the endothelium and the PMN, an interaction that precedes myocyte injury. NO inhibits the PMN-mediated reperfusion injury by direct effects on both the PMN and the vascular endothelium. Cardioprotective strategies include augmentation of endogenous NO by the precursor L-arginine and the administration of exogenous NO donors at the time of perfusion, which (1) attenuates PMN adherence to the coronary artery and venous endothelium, (2) reduces PMN-mediated endothelial dysfunction, (3) reduces PMN accumulation in the area at risk, and (4) reduces infarct size. Hence, NO represents a powerful therapeutic tool with which to attenuate the consequences of ischemia-reperfusion injury on vascular injury and infarction.

Adenosine A(3)-receptor stimulation attenuates postischemic dysfunction through K(ATP) channels.

We tested the hypothesis that selective adenosine A(3)-receptor stimulation reduces postischemic contractile dysfunction through activation of ATP-sensitive potassium (K(ATP)) channels. Isolated, buffer-perfused rat hearts (n = 8/group) were not drug pretreated (control) or were pretreated with adenosine (20 microM), 2-chloro-N(6)-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (Cl-IB-MECA; A(3) agonist, 100 nM), Cl-IB-MECA + 8-(3-noradamantyl)-1,3-dipropylxanthine (KW-3902; A(1) antagonist, 5 microM), Cl-IB-MECA + glibenclamide (Glib; K(ATP)-channel blocker, 0. 3 microM), or Glib alone for 12 min before 30 min of global normothermic ischemia followed by 2 h of reperfusion. After 2 h of reperfusion, left ventricular developed pressure (LVDP, %baseline) in control hearts was depressed to 34 +/- 2%. In hearts pretreated with Cl-IB-MECA, there was a statistically significant increase in LVDP (50 +/- 6%), which was reversed with coadministration of Glib (37 +/- 1%). Control hearts also showed similar decreases in left ventricular peak positive rate of change in pressure (dP/dt). Therefore, the A(3) agonist significantly attenuated postischemic cardiodynamic injury compared with the control, which was reversed by Glib. Cumulative creatine kinase (CK in U/min) activity was most pronounced in the control group (10.4 +/- 0.6) and was significantly decreased by Cl-IB-MECA (7.5 +/- 0.4), which was reversed by coadministration of Glib (9.4 +/- 0.2). Coronary flow was increased during adenosine infusion (160% of baseline) but not during Cl-IB-MECA infusion. Effects of Cl-IB-MECA were not reversed by the specific A(1) antagonist KW-3902. We conclude that cardioprotection afforded by A(3)-receptor stimulation may be mediated in part by K(ATP) channels. Cl-IB-MECA may be an effective pretreatment agent that attenuates postischemic cardiodynamic dysfunction and CK release without the vasodilator liability of other adenosine agonists.