Role of IL-13Rα2 in modulating IL-13-induced MUC5AC and ciliary changes in healthy and CRSwNP mucosa.

BACKGROUND: The IL-13 receptor α2 (IL-13Rα2) is a receptor for IL-13 which has conflicting roles in mediating IL-13 responses in the lower airway, with little known about its impact on upper airway diseases. We sought to investigate the expression of IL-13 receptors, IL-13Rα1 and IL-13Rα2, in chronically inflamed nasal epithelium, and explore IL-13-induced signaling pathways in an in vitro model of human nasal epithelial cells (hNECs). METHODS: The protein and mRNA expression levels of IL-13 and its receptors in nasal biopsies of patients with nasal polyps (NP) and healthy controls were evaluated. We investigated goblet cell stimulation with mucus hypersecretion induced by IL-13 (10 ng/mL, 72 hours) treatment in hNECs using a pseudostratified epithelium in air-liquid interface (ALI) culture. RESULTS: There were significant increases in IL-13, IL-13Rα1, and IL-13Rα2 mRNA and protein levels in NP epithelium with healthy controls as baseline. MUC5AC mRNA positively correlated with IL-13Rα2 (r = .5886, P = .002) but not with IL-13Rα1 in primary hNECs. IL-13 treatment resulted in a significant increase in mRNA and protein levels of IL-13Rα2 only in hNECs. IL-13 treatment induced an activation of extracellular signal-regulated kinases (ERK)1/2 and an upregulation of C-JUN, where the IL-13-induced effects on hNECs could be attenuated by ERK1/2 inhibitor (50 µmol/L) or dexamethasone (10-4 -10-7  mol/L) treatment. CONCLUSIONS: IL-13Rα2 has a potential role in IL-13-induced MUC5AC and ciliary changes through ERK1/2 signal pathway in the nasal epithelium. IL-13Rα2 may contribute to airway inflammation and aberrant remodeling which are the main pathological features of CRSwNP.

A comparison of ON-PUMP vs OFF-PUMP coronary artery bypass surgery among low, intermediate, and high-risk patients: the Hartford Hospital experience.

BACKGROUND: Off-pump coronary artery bypass (OP-CAB) graft surgery is being used with increasing frequency. This study was designed to compare OP-CAB outcomes with conventional surgical revascularization using cardiopulmonary bypass (CPB) in patients with varying risk categories at a high-volume center. METHODS AND RESULTS: Between 1/1/1999 and 1/31/2001, bypass surgery was performed on 1,312 patients, including 348 OP-CAB cases and 964 CPB cases. Compared to CPB cases, OP-CAB patients were more likely to be female and had a lower incidence of three vessel coronary artery disease, prior percutaneous intervention, and prior bypass surgery. Postoperatively, OP-CAB patients had a lower incidence of renal failure and prolonged ventilatory support, as well as a lower composite endpoint of inhospital mortality, perioperative myocardial infarction, cerebrovascular accident, and/or renal failure. In addition, OP-CAB patients required fewer transfusions and had a shorter total length of hospital stay. In general, morbidity and mortality increased in both OP-CAB and CPB groups with increasing Parsonnet score. CONCLUSIONS: OP-CAB surgery is a safe and effective alternative to conventional coronary artery bypass graft (CABG) surgery, with a lower incidence of major in-hospital adverse clinical events and a decreased requirement for medical resources. Adverse OP-CAB outcomes correlate well with pre-operative Parsonnet Score.

Long-term survivors of heart transplantation: the Hartford Hospital experience.

Heart transplantation has been a clinical program at Hartford Hospital for the past 15 years, resulting in 206 transplants. The five-year survival rate is 69% and is 43% at 10 years. The first recipient is surviving and has had full rehabilitation. Thirteen patients have survived 10 years or more. Advances in immunosuppression are ongoing and will result in further long-term survivors. Graft vasculopathy and lack of organ donation are current problems.

A better long-term outcome in cardiac transplant recipient with a history of previous open heart operations.

OBJECTIVE: To investigate the effect of previous open heart operations (POHO) on the outcome of heart transplantation (HTX). METHODS: Between November 1984 and May 1996, HTX was performed on 151 patients at Hartford Hospital. Among them, 61 patients had previous open heart operations (POHO) (group A), and 90 did not (group B). The average follow-up period was 1615 +/- 1185 days for group A and 1330 +/- 1125 days for group B. The recipient age was 55 +/- 10 years for group A and 48 +/- 12 years for group B (P < 0.01). There were 17 patients (26%) in group A and 14 (50%) in group B who were over 60 years of age. There was more coronary artery disease (74% versus 37%, P < 0.001) as etiology, and more diabetics in group A (P < 0.02). RESULTS: The time for cardiopulmonary bypass (133 +/- 20 min versus 106 +/- 18 min, P < 0.01) and aortic clamp time (73 +/- 16 min versus 61 +/- 13 min, P < 0.01) were longer in group A. The operative mortality (within 30 days) was 0 and 2.2%, and the cumulative deaths were 16 (26%) and 43 (48%) respectively for group A and group B (P < 0.01). The causes of death were (group A vs group B): infection (31% vs 26%), rejection (13% vs 28%, P < 0.05), malignancy (25% vs 16%), cardiac event (6% vs 14%) and others (25% vs 16%). In patients over 60, there were 4 deaths (24%) in group A and 7 (50%) in group B. The difference was not significant. No patients died of rejection in this subgroup. The actuarial survival rates in group A versus group B were: 1 year, 93% versus 83%; 2 years, 85% versus 74%; 3 years, 81% versus 71%; 5 years, 76% versus 58%; and 10 years, 57% versus 24% (P < 0.01). CONCLUSION: The survival rate in patients who had POHO is much higher than that in patients who had HTX as their primary operation.

Retrograde flush and cold storage for twenty-two to twenty-five hours lung preservation with and without prostaglandin E1.

BACKGROUND: Our previous study showed that retrograde flush through the left atrium is better than antegrade flush in 6-hour lung preservation. Whether it is feasible in long-term lung preservation is not clear. Several studies suggested that prostaglandin E1 may not be necessary in retrograde flush because of the low vascular resistance on the venous side. This study evaluates the effects of retrograde flush and prostaglandin E1 in 24-hour lung preservation. METHODS: Canine donor lungs were retrograde flushed with University of Wisconsin solution. Group A (n = 7) was pretreated with prostaglandin E1. No prostaglandin E1 was used in group B (n = 7). After flush and cold storage at 4 degrees C for 22 to 25 hours, left lung allotransplantation was performed. Measurements were taken before transplantation (baseline), and at 10, 30, 60, and 120 minutes after transplantation while the right pulmonary artery was occluded. RESULTS: After 120 minutes of reperfusion, the oxygen tension and carbon dioxide tension were 643 +/- 24 and 37 +/- 3 mm Hg in group A and 600 +/- 29 and 37 +/- 3 mm Hg in group B, respectively (p = NS). Pulmonary artery pressure (group A vs group B) was 20 +/- 1 versus 28 +/- 2 mm Hg (p < 0.01); right atrium pressure: 4 +/- 1 versus 8 +/- 1 mm Hg (p < 0.01); left pulmonary vascular resistance: 1109 +/- 51 versus 1525 +/- 133 dyne.sec.cm-5 (p < 0.05); airway resistance: 22 +/- 1 versus 24 +/- 1 cm H2O/L/sec (p = NS); lung dynamic compliance: 30 +/- 1 versus 26 +/- 1 cc/cm (p < 0.05) respectively. As compared with the baseline (19 +/- 1), airway resistance was significantly increased after 2 hours of reperfusion in group B (p < 0.05). Electron microscopy revealed that type I pneumocytes, capillary endothelial cells, and epithelial cells of bronchi were well preserved and the contents of lamellar bodies of type II pneumocyte were reduced. CONCLUSIONS: Canine lung was well preserved by retrograde flush and cold storage with University of Wisconsin solution after 24 hours preservation. Pretreatment of prostaglandin E1 is helpful in reducing pulmonary vascular resistance and airway resistance and improving lung dynamic compliance.

Organ transplantation at the Hartford Transplant Center.

Over 1,243 organ transplants have been performed at the Hartford Transplant Center over the past two decades. Survival in kidney, heart, liver, and pancreas patients is at or above the national average. Hartford was one of the first centers to use triple immunosuppression, which significantly improved survival in kidney transplantation. For recipients of kidneys from living related donors and cadaveric kidneys, two-year actuarial graft survival has been 98% and 83%, respectively, over the last five years. For heart and liver transplants, two-year survival has been 79% and 67%, respectively. Despite high success rates at most transplant centers, donor organs remain scarce. This problem needs to be addressed through increased cooperative efforts in the health-care community and the general public.

Retrograde versus antegrade flush in canine left lung preservation for six hours.

BACKGROUND: Retrograde flush through the left atrium is now used by some investigators in clinical lung preservation. However, to date there are no studies which compare its result with that of routine antegrade flush. METHODS: Mongrel dogs were divided into two groups: antegrade group (n = 7) and retrograde group (n = 8). After flush and 6 hours of cold storage in Euro-Collins solution, the left lung was transplanted in weight matched recipients, and their right pulmonary artery was then clamped at 10-, 30-, 60-, and 120-minute intervals for 10 minutes to test the lung function. The ultrastructure of lungs in both groups were also studied. RESULTS: Results showed the following (antegrade group versus retrograde group): the wet/dry ratio of the transplanted lung was 7.14 +/- 0.15 versus 6.33 +/- 0.20 (p < 0.01); the arterial oxygen tension (mm Hg) was 389 +/- 42 versus 534 +/- 23 (p < 0.05) and 370 +/- 51 versus 580 +/- 37 (p < 0.01) at 60 and 120 minutes, respectively. The peak airway pressure (cm H2O) was 23.4 +/- 0.8 versus 20.6 +/- 0.6 (p < 0.05) and 23.7 +/- 0.6 versus 21.3 +/- 0.8 (p < 0.05) at 10 and 60 minutes, respectively. Electron microscopic studies showed that at the end of preservation, type I and type II pneumocytes and capillaries were normal in both groups. Occluded capillaries with red blood cells were found in the antegrade group. After reperfusion, damaged epithelium and thicker air-blood barrier were found in the antegrade group. CONCLUSIONS: Retrograde flush offers a better lung preservation with less edema, decreased airway resistance, and improved oxygenation as compared with the antegrade group in 6 hours lung preservation.

A comparison of 10% pentastarch and 5% albumin in patients undergoing open-heart surgery.

Colloids are useful in cardiac surgery to increase preload and improve cardiac output without the risks associated with blood transfusions. Pentastarch is a new low-molecular weight hydroxyethyl starch compound under investigation for this purpose. The authors compared, in a randomized fashion, 12 patients who received pentastarch and 17 patients who received albumin for volume expansion after open-heart surgery. During the 24-hour study period there was no significant difference between the two groups with respect to systemic blood pressure, mean arterial pressure, cardiac index, right atrial pressure, and pulmonary capillary wedge pressure, with the exception of a higher mean arterial pressure and systolic blood pressure at 4 hours in the albumin group and higher heart rate at 12 hours in the pentastarch group. In addition, postoperative prothrombin time, partial thromboplastin time, fibrinogen, platelets, and factor VIII levels were not significantly different between the two groups. There were no complications attributed to colloid administration. The hemodynamic parameters were further evaluated in a subset of 6 pentastarch and 9 albumin patients who received the first 500 mL of colloid in a similar time frame and under similar clinical conditions. The patients who received pentastarch showed a significantly greater increase in cardiac index than did the patients who received albumin. No significant change in other parameters were noted between the two groups. The authors conclude that pentastarch is as safe as albumin and may be a more effective volume expander than albumin when used in open-heart surgery patients.

Traumatic intramyocardial dissection secondary to significant blunt chest trauma: a case report.

The case of a patient with delayed mitral regurgitation and right coronary artery traumatic injury in association with intramyocardial dissection without rupture or pseudoaneurysm is presented. These findings evolved secondary to blunt chest trauma and were confirmed by cardiac ultrasound scanning, magnetic resonance imaging, and cardiac catheterization. Successful surgical correction was facilitated with this combination of diagnostic testing.

Single-pump techniques for assisted circulation in cardiogenic shock: experimental evaluation and case report.

Acute cardiogenic shock or bridging to transplantation often involves the need for circulatory and cardiac support systems that are more effective than the intraaortic balloon pump. Biventricular failure, which is present in many cases, is generally treated with total cardiac replacement or with a complex of pumps and oxygenator that makes application difficult. With the goal of developing a universally applicable method of cardiac and circulatory support, we undertook a series of canine experiments designed to evaluate the effect of various treatment methods on survival, hemodynamics, and metabolic function. The series involved 123 dogs, in which cardiogenic shock was induced by means of multiple coronary artery ligations. The individual animals were then subjected to bypass, treated medically, or left untreated, depending on random selection. Each treatment lasted for 4 hours and was followed by a 2-hour period of observation. The following single-pump methods were tested: 1) left ventricular (LV) bypass, 2) left atrial (LA) bypass, 3) left ventricular and right atrial (LV + RA) bypass, 4) left atrial and right atrial (LA + RA) bypass, 5) LV + RA bypass, plus treatment with substrates (cysteine and ribose), and 6) LV + RA bypass, plus treatment with fluosol. Each bypass system incorporated a single reservoir and a centrifugal pump, and blood was returned to a femoral artery. Medical therapy consisted of either 1) treatment with sodium nitroprusside alone or 2) treatment with substrates alone. With respect to survival and hemodynamic effects (as reflected by oxygen consumption), LV + RA bypass and LA + RA bypass proved superior. During the posttreatment period, LV + RA bypass was associated with the highest survival rates and, therefore, with the most satisfactory recovery of myocardial or cardiac function. Despite the limited desaturation produced during venous shunting from the right atrium, perfusion of the entire body and consumption of oxygen were least in the LV + RA bypass group. The addition of substrates, or even of fluosol, caused a reduction in oxygen consumption. Our experience also includes one clinical case in which LA + RA bypass was used to support a 57-year-old man for 32 hours, after left atrial bypass alone proved inadequate. The dual-chamber technique brought about an improvement not only in hemodynamics but also in blood-gas values and pH. On the basis of this case and the canine experiments, we conclude that LV + RA and LA + RA bypass techniques offer safe, effective means of long-term temporary support for patients in severe cardiogenic shock.

Quality care and cost-effectiveness. An organized approach to problem solving.

The reflexive approach to rising hospital costs and decreased revenue is to balance the budget by curtailing expenses. This places budgetary limitations on personnel, supplies, and equipment and ultimately has an impact on the quality of care. An alternative approach is to modify traditional practice patterns so that quality is preserved and costs are reduced. We reviewed elective class I and II coronary artery bypass graft surgery on a cost basis to identify potential problems. High costs in blood and blood-product usage were identified. An in-depth analysis of practice patterns was conducted, and comparisons were made between data from our hospital and other institutions. Modifications that improved quality and reduced costs were designed. Blood and blood-product usage was reduced from an average of 9.2 U to 3.4 U per case, resulting in an estimated cost avoidance of $111,286 per year. No cost advantage was observed with the use of cell savers, membrane oxygenators, or automated coagulation analysis in these routine short pump run surgeries. Though not cost-effective, the cell saver did allow the salvage of 2 U of blood per case. Mediastinal drainage systems (Sorenson) as well as reeducation regarding the safe, albeit low, hematocrit (no transfusions for hematocrits above 25% [0.25]) were effective in eliminating unnecessary use of potentially dangerous and expensive blood products.

Comparative penetration of cefonicid and cefazolin into the atrial appendage and pericardial fluid of patients undergoing open-heart surgery.

The penetration of cefonicid and cefazolin into cardiac tissue was compared after a single 30-mg/kg dose in 30 patients undergoing aortocoronary artery bypass graft surgery. Samples of the right atrial appendage, pericardial fluid, and serum were obtained at various times and assayed for drug content. The concentrations of cefonicid in serum and the atrial appendage were at least twice those observed for cefazolin at a given time after a dose. The mean (+/- standard deviation) atrial appendage-serum ratio was 0.47 +/- 0.14 for cefonicid and 0.34 +/- 0.06 for cefazolin (P less than 0.005). Pericardial fluid concentrations of cefonicid were slightly lower than those observed in patients receiving cefazolin (P greater than 0.05). A single intravenous dose of cefonicid provides high and sustained concentrations in serum and cardiac tissue and thus may be useful in antibiotic prophylaxis of certain surgical procedures; however, further study of the efficacy of this agent in the prevention and treatment of infections associated with Staphylococcus spp. is needed.

Penetration of ceforanide and cefamandole into the right atrial appendage, pericardial fluid, sternum, and intercostal muscle of patients undergoing open heart surgery.

Doses of 30 mg of ceforanide or cefamandole per kg were administered intravenously to 26 patients just before their chests were opened for coronary artery bypass or cardiac valve replacement surgery. Samples of right atrial appendage, pericardial fluid, plasma, aortic wall, intercostal muscle, and sternum were obtained at different times after the antibiotic was injected, and these samples were assayed for cephalosporin concentration. For ceforanide the pre-bypass plasma half-life was 2.5 h, and the atrial appendage half-life was 2.1 h; for cefamandole the pre-bypass plasma half-life was 0.75 h and the atrial appendage half-life was 0.72 h. At 3 h the concentrations of ceforanide and cefamandole in atrial appendages were 28.0 and 5.0 micrograms/g, respectively. Ceforanide achieved higher and more sustained concentrations in other tissues than cefamandole. Considering the minimal inhibitory concentrations of these drugs for staphylococci, cefamandole and ceforanide should provide adequate protection against infection by these organisms for the duration of the surgical procedure.