Inhibition of inducible nitric oxide synthase ameliorates rat lung allograft rejection

AbstractRecently, the inducible isoform of nitric oxide synthase has been shown to be an important immunomodulation molecule in allograft rejection. We have observed the production of nitric oxide during rejection and the effect of nitric oxide synthase inhibition on allograft rejection in a rat lung transplant model. Rat left lung allotransplants were performed in two strain combinations: brown Norway–to–F344 (major histocompatibility complex incompatible); and Lewis-to-F344 (minor loci incompatible) as severe and mild rejection models respectively. Syngeneic F344-to-F344 transplants were performed as a negative control. Nitric oxide production during rejection was determined by measuring the recipient's serum nitrite/nitrate levels as a stable end product of nitric oxide. The progression of rejection was evaluated radiographically and the grade of rejection was determined histologically. After operation, recipients of allotransplantation were randomly divided into two groups and received either aminoguanidine (200 mg/kg, intraperitoneal every 6 hours), a potent inducible nitric oxide synthase inhibitor, or normal saline treatment. The levels of serum nitrite and nitrate in recipients increased in the early phase of rejection in both allotransplant combinations. However, in the terminal phase of rejection, the serum nitrite/nitrate level decreased significantly compared with the peak level in the brown Norway–to–F344 recipients. The serum nitrite/nitrate levels in the syngeneic transplant recipients were normal during the entire observation period. In aminoguanidine-treated animals, serum nitrite/nitrate levels remained normal in both allograft combinations. Significant suppression of rejection in aminoguanidine-treated recipients was observed histologically and radiographically in comparison with untreated recipients in the brown Norway–to–F344 combination. In the Lewis-to-F344 combination, aminoguanidine treatment significantly ameliorated histologic rejection but did not affect radiologic appearance. We therefore conclude nitric oxide is produced during early allograft rejection and may prove to be a marker and mediator of early rejection. The inhibition of inducible nitric oxide synthase results in significant reduction in rat lung allograft rejection. (J THORAC CARDIOVASC SURG 1995;110:1449-60

Modelling the impact of vector control interventions on Anopheles gambiae population dynamics

<p>Abstract</p> <p>Background</p> <p>Intensive anti-malaria campaigns targeting the <it>Anopheles </it>population have demonstrated substantial reductions in adult mosquito density. Understanding the population dynamics of <it>Anopheles </it>mosquitoes throughout their whole lifecycle is important to assess the likely impact of vector control interventions alone and in combination as well as to aid the design of novel interventions.</p> <p>Methods</p> <p>An ecological model of <it>Anopheles gambiae sensu lato </it>populations incorporating a rainfall-dependent carrying capacity and density-dependent regulation of mosquito larvae in breeding sites is developed. The model is fitted to adult mosquito catch and rainfall data from 8 villages in the Garki District of Nigeria (the 'Garki Project') using Bayesian Markov Chain Monte Carlo methods and prior estimates of parameters derived from the literature. The model is used to compare the impact of vector control interventions directed against adult mosquito stages - long-lasting insecticide treated nets (LLIN), indoor residual spraying (IRS) - and directed against aquatic mosquito stages, alone and in combination on adult mosquito density.</p> <p>Results</p> <p>A model in which density-dependent regulation occurs in the larval stages via a linear association between larval density and larval death rates provided a good fit to seasonal adult mosquito catches. The effective mosquito reproduction number in the presence of density-dependent regulation is dependent on seasonal rainfall patterns and peaks at the start of the rainy season. In addition to killing adult mosquitoes during the extrinsic incubation period, LLINs and IRS also result in less eggs being oviposited in breeding sites leading to further reductions in adult mosquito density. Combining interventions such as the application of larvicidal or pupacidal agents that target the aquatic stages of the mosquito lifecycle with LLINs or IRS can lead to substantial reductions in adult mosquito density.</p> <p>Conclusions</p> <p>Density-dependent regulation of anopheline larvae in breeding sites ensures robust, stable mosquito populations that can persist in the face of intensive vector control interventions. Selecting combinations of interventions that target different stages in the vector's lifecycle will result in maximum reductions in mosquito density.</p

Congenital Ventricular Diverticulum or Aneurysm: A Difficult Diagnosis to Make

A pouch protruding from the free wall of the left ventricle may be either a congenital ventricular diverticulum (CVD) or aneurysm (CVA). Being aware of these rare congenital anomalies is critical in making the diagnosis. Differentiating the two is important for treatment decisions. We describe a patient with dextrocardia, Tetralogy of Fallot, and a congenital left ventricular apical diverticulum diagnosed following the induction of anesthesia. CVD and CVA may present in the antenatal period through late adulthood with differing morphology, location, and symptoms. Echocardiography is paramount in the diagnosis and characterization of these lesions. If this anomaly is encountered after the induction of anesthesia or during intraoperative echocardiography, the cardiothoracic anesthesiologist should make the surgical team aware so it can be further characterized and a treatment plan made prior to incision

A Versatile Extracorporeal Circuit for Use During Repair of Descending and Thoracoabdominal Aortic Aneurysms in High-Risk Patients with Cardiac and/or Pulmonary Dysfunction: A Novel Approach to a Significant Perfusion Management Dilemma

The incidence of ischemic complications associated with repair of descending and thoracoabdominal aortic aneurysms has been significantly reduced by the use of distal aortic perfusion with moderate hypothermia, cerebral spinal fluid drainage, and segmental sequential clamping techniques. However, because the maintenance of proximal perfusion, the adequacy of left heart bypass (LHB), and the ability to ventilate patients on only one lung are all dependent on ventricular and pulmonary function, high- risk patients with descending and/or thoracoabdominal aortic aneurysms in the presence of cardiopulmonary insufficiency or instability present a difficult challenge for the surgical team. Traditional closed LHB circuits become nonfunctional in the event of cardiac arrest or refractory arrhythmias that create hemodynamic instability and are unable to provide necessary pulmonary support if the patient fails to ventilate adequately on one lung during thoracotomy. Furthermore, converting a patient from closed LHB to traditional venoarterial cardiopulmonary bypass (CPB) is frequently difficult, especially when the perfusionist works without the benefit of extra personnel to assist during such crises. Consequently, a modified extracorporeal circuit was designed to provide closed LHB with desired therapeutic adjuncts while also satisfying the additional need for a rapid infusion device, a source of supplemental ventilation/oxygenation, and, if necessary, the ability to convert the patient to venoarterial CPB conveniently in the event of cardiac and/or pulmonary failure during surgery to repair descending and/or thoracoabdominal aortic aneurysms