First Canadian experience with donation after cardiac death simultaneous pancreas and kidney transplants.

BACKGROUND: Compared with neurologic determination of death (NDD) donor organs, donation after cardiac death (DCD) donor organs have traditionally been considered of inferior quality owing to warm ischemia experienced during procurement. We present, to our knowledge, the first analysis of simultaneous pancreas and kidney (SPK) transplants using DCD donor organs in Canada. METHODS: We carried out a retrospective cohort study of SPK transplants from 13 DCD and 68 NDD donors performed between October 2008 and July 2016. In all patients immunosuppression was induced with thymoglobulin and continued with tacrolimus, mycophenolate mofetil and prednisone maintenance therapy. RESULTS: Donor and recipient characteristics of DCD and NDD groups were similar with respect to age, sex, body mass index, kidney and pancreas cold ischemia times, and donor terminal creatinine. Mean DCD graft warm ischemia time was 0.5 (range 0.4-0.7) hours. Median follow-up was 2.2 (range 0.1-6.7) years and 2.7 (range 0.3-6.3) years for the DCD and NDD groups, respectively. The DCD and NDD groups were similar with regards to recipient percent panel reactive antibody and presence of human leukocyte antigen antibodies. The groups also received similar total doses of thymoglobulin. In total 38% of patients in the DCD group experienced renal delayed graft function (DGF) compared with 10% in the NDD group (p = 0.027). There were 7 cases of pancreas graft thrombosis requiring relaparotomy in the NDD group compared with none in the DCD group. No patients from either group required insulin at any time after transplant. Although the estimated glomerular filtration rate (eGFR) was lower in the DCD than the NDD group on postoperative days 7 and 14 (p = 0.025), no difference was noted on day 30 or through 4 years after transplant. No differences were seen between the groups with respect to amylase, lipase, or glycosated hemoglobin (HbA1c) up to 4 years after transplant, or in kidney, pancreas, or patient survival at any time after transplant. CONCLUSION: Our results show that, apart from a higher renal DGF rate, SPK transplants with DCD donor organs have comparable outcomes to standard transplants with NDD donor organs.

CONTEXTE: Comparativement aux organes prélevés après détermination de la mort cérébrale (ou détermination du décès neurologique [DDN]), les organes prélevés après détermination du décès cardiocirculatoire (DDC) sont en général considérés de moindre qualité en raison du phénomène d'ischémie chaude inhérent à ce type de prélèvement. Nous présentons, à notre connaissance, la première analyse sur la double greffe rein-pancréas effectuée avec des organes prélevés après DDC au Canada. MÉTHODES: Nous avons procédé à une étude de cohorte rétrospective sur les doubles greffes rein-pancréas effectuées entre octobre 2008 et juillet 2016, soit 13 après DDC et 68 après DDN. Chez tous les patients, l'immunosuppression a été induite par la thymoglobuline et a été maintenue au moyen d'un traitement d'entretien par le tacrolimus, le mycophénolate mofétil et la prednisone. RÉSULTATS: Les caractéristiques des donneurs et des receveurs des 2 groupes (DDC et DDN) étaient semblables sur les plans de l'âge, du sexe, de l'indice de masse corporelle, de la durée de l'ischémie froide du rein et du pancréas, et de la créatinine terminale (donneur). La durée moyenne de l'ischémie chaude des greffons prélevés après DDC a été de 0,5 (étendue : 0,4-0,7) heure. Le suivi médian a été d'une durée de 2,2 (étendue : 0,1-6,7) ans et de 2,7 (étendue : 0,3-6,3) ans, respectivement, pour les groupes DDC et DDN. Les 2 groupes étaient similaires pour ce qui est des pourcentages d'anticorps réactifs et de la présence d'anticorps anti-HLA (human leukocyte antigen) chez les receveurs. Les 2 groupes avaient aussi reçu des doses totales semblables de thymoglobuline. En tout, 38 % des patients du groupe DDC ont manifesté un retard de fonctionnement du greffon rénal, contre 10 % dans le groupe DDN (p = 0,027). On a dénombré 7 cas de thrombose du greffon pancréatique ayant nécessité une réintervention dans le groupe DDN, contre aucun dans le groupe DDC. Aucun des patients n'a eu besoin d'insuline après la transplantation. Le débit de filtration glomérulaire estimé (DFGe) était moins élevé dans le groupe DDC que dans le groupe DDN aux jours 7 et 14 (p = 0,025), mais on n'a plus noté de différence à ce chapitre au jour 30 ni au cours des 4 années suivant la greffe. On n'a observé aucune différence entre les groupes pour ce qui est de l'amylase, de la lipase ou de l'HbA1c jusqu'à 4 ans suivant la greffe, ni pour ce qui est de la survie des greffons rénaux ou pancréatiques ou celle des patients, peu importe le temps écoulé depuis la greffe. CONCLUSION: Selon nos résultats, si ce n'est un taux plus élevé de retard de fonctionnement du greffon rénal, les receveurs d'une double greffe rein-pancréas après DDC obtiennent des résultats semblables à ceux qui subissent une greffe standard d'organes prélevés après DDN.

Management of isolated Adrenal Lesions in Cancer Patients.

BACKGROUND: Adrenal lesions are commonly identified in patients with extra-adrenal cancer. When lesions are present, it is important to identify if the lesion is a metastasis of the primary cancer or a primary adrenal neoplasm. If primary, the adrenal lesion must be evaluated for hypersecretion and its malignant potential determined for appropriate treatment planning. METHODS: Recent literature was reviewed that focused on the normal investigation of adrenal lesions including radiographic imaging and hormonal evaluations as well as specific focused therapeutic options available for isolated metastatic adrenal lesions. RESULTS: This review presents a pathway approach in investigating these lesions and also discusses various potential treatment options. CONCLUSIONS: A proper investigative workup of an adrenal lesion in a cancer patient is critical for proper management. Isolated adrenal metastatic lesions in the cancer patient should be surgically removed when possible, but other options can be considered. In patients who do not have metastasis from extra-adrenal cancer, the decision for surgical resection is dependent on functionality of the tumor and it's potential for malignancy. Observation plays a key role in those tumors that are nonfunctioning and have a low risk of malignancy.

Glucocorticoids improve calcium cycling in cardiac myocytes after cardiopulmonary bypass.

BACKGROUND: Glucocorticoids can reduce myocardial dysfunction associated with ischemia and reperfusion injury following cardiopulmonary bypass (CPB) and circulatory arrest. The hypothesis was that maintenance of cardiac function after CPB with methylprednisolone therapy results, in part, from preservation of myocyte calcium cycling. METHODS: Piglets (5-7 kg) underwent CPB and 120 min of hypothermic circulatory arrest with (CPB-GC) or without (CPB) methylprednisolone (30 mgkg(-1)) administered 6h before and at CPB. Controls (No-CPB) did not undergo CPB or receive glucocorticoids (n=6 per treatment). Myocardial function was monitored in vivo for 120 min after CPB. Calcium cycling was analyzed using rapid line-scan confocal microscopy in isolated, fluo-3-AM-loaded cardiac myocytes. Phospholamban phosphorylation and sarco(endo)plasmic reticulum calcium-ATPase (SERCA2a) protein levels were determined by immunoblotting of myocardium collected 120 min after CPB. Calpain activation in myocardium was measured by fluorometric assay. RESULTS: Preload recruitable stroke work in vivo 120 min after reperfusion decreased from baseline in CPB (47.4±12 versus 26.4±8.3 slope of the regression line, P<0.05), but was not different in CPB-GC (41±8.1 versus 37.6±2.2, P=0.7). In myocytes isolated from piglets, total calcium transient time remained unaltered in CPB-GC (368±52.5 ms) compared with controls (434.5±35.3 ms; P=0.07), but was prolonged in CPB myocytes (632±83.4 ms; P<0.01). Calcium transient amplitude was blunted in myocytes from CPB (757±168 nM) compared with controls (1127±126 nM, P<0.05) but was maintained in CPB-GC (1021±155 nM, P>0.05). Activation of calpain after CPB was reduced with glucocorticoids. Phospholamban phosphorylation and SERCA2a protein levels in myocardium were decreased in CPB compared with No-CPB and CPB-GC (P<0.05). CONCLUSIONS: The glucocorticoid-mediated improvement in myocardial function after CPB might be due, in part, to prevention of calpain activation and maintenance of cardiac myocyte calcium cycling.

Modulation of nuclear factor-kappaB improves cardiac dysfunction associated with cardiopulmonary bypass and deep hypothermic circulatory arrest.

OBJECTIVE: The hypothesis is that partial nuclear factor-kappaB (NF-kappaB) inhibition can alleviate cardiopulmonary dysfunction associated with ischemia and reperfusion injury following cardiopulmonary bypass and deep hypothermic circulatory arrest (CPB/DHCA) in a pediatric model. DESIGN: Animal case study. SUBJECTS: Two-week-old piglets (5-7 kg). INTERVENTIONS: Piglets received 100 microg/kg of SN50, a peptide inhibitor of NF-kappaB translocation and activation, 1 hour before CPB. The control group received saline. Animals were cooled to 18 degrees C with CPB, the piglets were in DHCA for 120 minutes, and the piglets were then rewarmed on CPB to 38 degrees C and maintained for 120 minutes after CPB/DHCA. MEASUREMENTS: Sonomicrometry and pressure catheters collected hemodynamic data. Transmural left and right ventricular tissues were obtained at the terminal time point for determination of NF-kappaB activity by enzyme-linked immunosorbent assay. Data are expressed as mean +/- sd. MAIN POINTS: Oxygen delivery was maintained at 76 +/- 13 mL/min at baseline and 75 +/- 5 mL/min at 120 minutes after CPB/DHCA (p = 0.75) in SN50-treated animals vs. 99 +/- 26 mL/min at baseline and 63 +/- 20 mL/min at 120 minutes in the untreated group (p = 0.0001). Pulmonary vascular resistance (dynes.sec.cm) increased from 124 +/- 59 at baseline to 369 +/- 104 at 120 minutes in the untreated piglets (p = 0.001) compared with SN50-treated animals (100 +/- 24 at baseline and 169 +/- 88 at 120 minutes, p = 0.1). NF-kappaB activity was reduced by 74% in left ventricles of SN50-treated compared with SN50-untreated animals (p < 0.001). Plasma endothelin-1 (pg/mL), an important vasoconstrictor regulated by NF-kappaB, increased from 2.1 +/- 0.4 to 14.2 +/- 5.7 in untreated animals (p = 0.004) but was elevated to only 4.5 +/- 2 with SN50 treatment (p = 0.005). CONCLUSIONS: Improvement of cardiopulmonary function after ischemia/reperfusion was associated with the reduction of NF-kappaB activity in piglet hearts. Maintenance of systemic oxygen delivery and alleviation of pulmonary hypertension after CPB/DHCA in piglets administered SN50, possibly through a reduction of circulating endothelin-1, suggest that selective inhibition of NF-kappaB activity may reduce ischemia and reperfusion injury after pediatric cardiac surgery.

Acute beta-blockade prevents myocardial beta-adrenergic receptor desensitization and preserves early ventricular function after brain death.

OBJECTIVE: Beta-adrenergic receptor desensitization through activation of the G protein-coupled receptor kinase 2 is an important mechanism of early cardiac dysfunction after brain death. We hypothesized that acute beta-blockade can prevent myocardial beta-adrenergic receptor desensitization after brain death through attenuation of G protein-coupled receptor kinase 2 activity, resulting in improved cardiac function. METHODS: Adult pigs underwent either sham operation, induction of brain death, or treatment with esmolol (beta-blockade) for 30 minutes before and 45 minutes after brain death (n = 8 per group). Cardiac function was assessed at baseline and for 6 hours after the operation. Myocardial beta-adrenergic receptor signaling was assessed 6 hours after operation by measuring sarcolemmal membrane adenylate cyclase activity, beta-adrenergic receptor density, and G protein-coupled receptor kinase 2 expression and activity. RESULTS: Baseline left ventricular preload recruitable stroke work was similar among sham, brain death, and beta-blockade groups. Preload recruitable stroke work was significantly decreased 6 hours after brain death versus sham, and beta-blockade resulted in maintenance of baseline preload recruitable stroke work relative to brain death and not different from sham. Basal and isoproterenol-stimulated adenylate cyclase activities were preserved in the beta-blockade group relative to the brain death group and were not different from the sham group. Left ventricular G protein-coupled receptor kinase 2 expression and activity in the beta-blockade group were markedly decreased relative to the brain death group and similar to the sham group. Beta-adrenergic receptor density was not different among groups. CONCLUSION: Acute beta-blockade before brain death attenuates beta-adrenergic receptor desensitization mediated by G protein-coupled receptor kinase 2 and preserves early cardiac function after brain death. These data support the hypothesis that acute beta-adrenergic receptor desensitization is an important mechanism in early ventricular dysfunction after brain death. Future studies with beta-blocker therapy immediately after brain death appear warranted.

Beta-adrenergic receptor antagonism preserves myocardial function after brain death in a porcine model.

BACKGROUND: Cardiac dysfunction after brain death decreases the already limited number of potential donors for cardiac transplantation. Acute beta-adrenergic receptor (betaAR) desensitization after the brain death-associated catecholamine surge is an important mechanism. We hypothesized that acute betaAR antagonism could improve myocardial function after brain death by preserving betaAR signaling. METHODS: Pigs were randomly assigned to three study groups (n = 5): sham; brain death; and brain death with betaAR antagonist (200 microg/kg/min esmolol), 30 minutes before brain death until 45 minutes after brain death. Functional data were collected for 6 hours after brain death and tissues procured. RESULTS: Compared with baseline, pre-load recruitable stroke work (PRSW), a pre-load-independent measure of systolic function (21.4 +/- 7.5 vs 43.3 +/- 6.8, slope of regression line during vena caval occlusion, p < 0.001), diastolic function (Tau, 101 +/- 54.7 vs 36.4 +/- 5.4 ms, p = 0.03) and systemic oxygen delivery (151 +/- 79.7 vs 298 +/- 78.7 ml/min, p < 0.001) deteriorated in untreated animals at 6 hours after brain death. In contrast, betaAR antagonist maintained baseline systolic function (PRSW, 37.8 +/- 5.6 vs 38.2 +/- 4.7, slope of regression line during vena caval occlusion, p = 0.92), diastolic function (Tau, 32.6 +/- 5.1 vs 48.5 +/- 28.3 ms, p = 0.57) and oxygen delivery (427 +/- 116 vs 397 +/- 98.8 ml/min, p = 0.36) at 6 hours after brain death. betaAR antagonist preserved betaAR signaling, as demonstrated by similar left ventricular (LV) basal (55.4 +/- 32.8 vs 58.8 +/- 10.9 pmol/mg/min, p = 0.40) and isoproterenol-stimulated (125 +/- 70.5 vs 124 +/- 52.0 pmol/mg/min, p = 0.49) adenylate cyclase activity at 6 hours after brain death, upon comparing betaAR antagonist and sham treatment groups. Both LV basal and isoproterenol-stimulated adenyl cyclase activity were higher with betaAR antagonist (25.9 +/- 4.8 pmol/mg/min, p = 0.03) than with untreated brain death (55.6 +/- 17.3 pmol/mg/min, p = 0.02). CONCLUSIONS: Beta-adrenergic receptor antagonism before brain death preserves cardiac function by preventing betaAR desensitization. This therapy in potential donors might increase the number of organs available for transplantation.

Glucocorticoids alter the balance between pro- and anti-inflammatory mediators in the myocardium in a porcine model of brain death.

BACKGROUND: Cardiac dysfunction after brain death (BD) limits donors for cardiac transplantation. Glucocorticoids ameliorate brain death-induced donor heart dysfunction. We hypothesized that glucocorticoid therapy alleviates myocardial depression through altering the balance between pro- and anti-inflammatory mediators via the nuclear factor-kappaB (NF-kappaB)/inhibitor of kappaB-alpha (IkappaBalpha) pathway and/or by preserving beta-adrenergic receptor (betaAR) signaling in the heart. METHODS: Crossbred pigs (25 to 35 kg) were randomly assigned to the following groups (n = 5/treatment): sham (Group 1); BD (Group 2); and BD with glucocorticoids (30 mg/kg methylprednisolone), either 2 hours before (Group 3) or 1 hour after BD (Group 4). Tumor necrosis factor-alpha (TNF-alpha) levels were measured in plasma at baseline and 1 hour and 6 hours after BD. Protein levels were measured in left ventricular homogenates procured 6 hours after BD. RESULTS: Pro-inflammatory proteins (TNF-alpha) and interleukin-6 were lower in Group 3 and Group 4 compared with Group 2 at 6 hours after BD (p < 0.01). Intracellular adhesion molecule-1 was also lower in Group 4 compared with Group 2 (p = 0.001). Interleukin-10, an anti-inflammatory mediator, was lower in Group 4 than in Group 2 (p < 0.001), but not different between Groups 2 and 3. At 6 hours after BD, neither NF-kappaB activity nor basal adenylate cyclase activity differed between Groups 3 and 4 compared with Group 2. CONCLUSIONS: Glucocorticoids maintained myocardial function and shifted the balance of pro- and anti-inflammatory mediators after BD. The mechanisms by which glucocorticoids preserve myocardial function, however, do not appear to involve the NF-kappaB pathway or betaAR signaling.

Pulmonary atresia with intact ventricular septum: initial management.

BACKGROUND: Outcomes for pulmonary atresia with intact ventricular septum are suboptimal, while initial management remains controversial. This study was undertaken to determine the effect of catheter-based therapy on the need for early surgical intervention. METHODS: A single-institution retrospective chart review was made of all 25 neonates with pulmonary atresia with intact ventricular septum from 1999 to 2005. RESULTS: Mean age at first intervention was 3.1 +/- 2.2 days, mean weight 3.3 +/- 0.5 kg. Right ventricular hypoplasia varied: 20% normal, 16% mild, 28% moderate, 28% moderately severe or severe, 8% not classified. Median tricuspid valve z-score was -2.3 +/- 2.6. First intervention was catheter-based therapy in 56% (14 of 25), operative in 36% (9 of 25), and no therapy in 2. Technically adequate valvotomy was achieved in 79% (11 of 14). Serious catheter-related complications occurred in 3 of 14 (21%). Only 5 of 14 (36%) with catheter-based therapy weaned from prostaglandins without surgery. Of these, 2 required surgery for cyanosis at 1 and 3 months. Surgery after catheter-based therapy consisted of right ventricular outflow patch in 36% (4 of 11), systemic to pulmonary shunt in 64% (7 of 11). Median time between catheter-based therapy and surgery was 8.5 days (range, 1 to 89). Only 3 of the 23 treated patients avoided operation during infancy. There was 1 early and 1 late death after operation after initial catheter-based therapy, and 1 late death after primary surgery alone during a mean follow-up of 33 months (range, 1.5 to 79). CONCLUSIONS: Balloon valvotomy alone for pulmonary atresia with intact ventricular septum rarely obviates the need for an additional source of pulmonary blood flow--either shunt or ductal stenting.

Current treatments for congenital aortic stenosis.

PURPOSE OF REVIEW: Congenital valvar aortic stenosis is a challenging disease that often requires repeated palliative procedures. Stenosis can range from mild and asymptomatic, not requiring intervention, to severe, as seen in hypoplastic left heart syndrome. New advances such as fetal balloon valvuloplasty, improvements in the Ross technique, and long-term studies of trans-catheter balloon valvuloplasty and surgical valvotomy warrant a review of the outcomes and optimal timing of the various interventions. RECENT FINDINGS: Fetal balloon valvuloplasty has shown promise. Despite some mortality and morbidity, some fetuses are showing significant growth in left ventricular structures, allowing biventricular repair. In neonates and infants with congenital aortic stenosis, excellent initial results are obtained with trans-catheter balloon valvuloplasty, although stenosis resistant to further balloon dilation or regurgitation may develop, necessitating surgical intervention. Midterm results from the Ross procedure are encouraging, demonstrating low rates of mortality, aortic insufficiency and re-intervention. Stenosis of the pulmonary allograft may be inevitable, and recent long-term follow-up suggests an increase in aortic insufficiency. SUMMARY: While availability of fetal balloon valvuloplasty is limited, it has promise for promoting in-utero left ventricle growth and improving function. The optimal procedure for infants and neonates is trans-catheter balloon valvuloplasty. For older patients, the Ross procedure is the repair of choice, although more long-term studies are needed to assess the natural course of the autograft. Outcomes should improve with advances in pulmonary allografts.

Glucocorticoid administration reduces cardiac dysfunction after brain death in pigs.

BACKGROUND: Traumatic brain injury and subsequent brain death (BD) account for nearly half of all organ donors, yet only 33% of available hearts are transplanted. Alterations in multiple physiologic pathways after BD can lead to cardiac dysfunction and exclusion from transplantation. Triple hormone resuscitation with methylprednisolone, thyroid hormone and vasopressin has had inconsistent results in the effort to reduce cardiac dysfunction associated with BD, but individual analysis of these agents is limited. The hypothesis was that glucocorticoid administration alone could reduce BD-associated cardiac dysfunction. METHODS: Crossbred pigs (25 to 35 kg) had BD induced by sub-dural balloon inflation. Hemodynamics were measured for 360 minutes after BD. Negative cerebral perfusion pressures and decreased laser Doppler cerebral blood flow confirmed BD. Animals (n = 5/treatment group) received: saline (Group 1); 30 mg/kg methylprednisolone 2 hours before BD (Group 2); or 30 mg/kg methylprednisolone 1 hour after BD (Group 3). Repeated measures analysis of variance and unpaired t-tests were used for appropriate comparisons. RESULTS: Left ventricular (LV) pre-load recruitable stroke work (PRSW) decreased in untreated Group 1 over time (p < 0.001), whereas PRSW in animals treated with glucocorticoids, Groups 2 and 3, was not different from baseline at 360 minutes after BD. Diastolic function measured as LV -dP/dt (minimum derivative of the change in pressure over time) and tau (time constant of isovolumic relaxation) was also preserved 360 minutes after brain death by glucocorticoids in Groups 2 and 3 (p > 0.05). Oxygen delivery 360 minutes after BD was higher in Group 2 compared with Group 1 (p = 0.02) and Group 3 (p = 0.006). CONCLUSIONS: Glucocorticoid therapy before or after BD preserved LV systolic and diastolic function. Glucocorticoids administered after brain death might increase the number of hearts available for transplant by reducing brain death-associated cardiac dysfunction.

Role of the beta-adrenergic receptor kinase in myocardial dysfunction after brain death.

OBJECTIVE: Significant cardiac dysfunction after brain death leading to exclusion from procurement for cardiac transplantation is seen in up to 25% of potential organ donors in the absence of structural heart disease. The cause includes uncoupling of the myocardial beta-adrenergic receptor signaling system. The mechanism, however, has not yet been described. This study investigates our hypothesis that brain death causes acute activation of the betaAR kinase and leads to desensitization of myocardial beta-adrenergic receptors and impaired ventricular function. METHODS: Adult pigs underwent a sham operation or induction of brain death by means of subdural balloon inflation (n = 8 in each group). Cardiac function was assessed by using sonomicrometry at baseline and for 6 hours after the operation. beta-Adrenergic receptor signaling was assessed at 6 hours after the operation by measuring myocardial sarcolemmal membrane adenylate cyclase activity, beta-adrenergic receptor density, beta-adrenergic receptor kinase expression, and activity. RESULTS: Induction of brain death led to significantly decreased left ventricular systolic and diastolic function. Basal and isoproterenol-stimulated adenylate cyclase activity was blunted in the brain dead group compared with the sham-operated group (28.3 +/- 4.3 vs 48.3 +/- 7.6 pmol of cyclic adenosine monophosphate.mg(-1) x min(-1) [P = .01] and 54.8 +/- 9.6 vs 114.5 +/- 18 pmol of cyclic adenosine monophosphate x mg(-1) x min(-1) [P < .02]). There was no difference in beta-adrenergic receptor density between the brain dead and sham-operated groups. Myocardial beta-adrenergic receptor kinase expression was 3-fold greater in the brain dead versus sham-operated groups, and membrane beta-adrenergic receptor kinase activity was 2.5-fold greater in the brain dead group compared with that seen in the sham-operated group. CONCLUSION: Induction of brain death leads to significant left ventricular dysfunction in this porcine model. Cardiac beta-adrenergic receptors are clearly uncoupled after brain death, and our data suggest that the mechanism is acute increase of myocardial beta-adrenergic receptor kinase activity, leading to beta-adrenergic receptor desensitization and ventricular dysfunction.

Inhibition of p38 reduces myocardial infarction injury in the mouse but not pig after ischemia-reperfusion.

The MAPK family member p38 is activated in the heart after ischemia-reperfusion (I/R) injury. However, the cardioprotective vs. proapoptotic effects associated with p38 activation in the heart after I/R injury remain unresolved. Another issue to consider is that the majority of past studies have employed the rodent as a model for assessing p38's role in cardiac injury vs. protection, while the potential regulatory role in a large animal model is even more uncertain. Here we performed a parallel study in the mouse and pig to directly compare the extent of cardiac injury after I/R at baseline or with the selective p38 inhibitor SB-239063. Infusion of SB-239063 5 min before ischemia in the mouse prevented ischemia-induced p38 activation, resulting in a 25% reduction of infarct size compared with vehicle-treated animals (27.9 +/- 2.9% vs. 37.5 +/- 2.7%). In the pig, SB-239063 similarly inhibited myocardial p38 activation, but there was no corresponding effect on the degree of infarction injury (43.6 +/- 4.0% vs. 41.4 +/- 4.3%). These data suggest a difference in myocardial responsiveness to I/R between the small animal mouse model and the large animal pig model, such that p38 activation in the mouse contributes to acute cellular injury and death, while the same activation in pig has no causative effect on these parameters.

A comparison of laparoscopic and open pyloromyotomy at a teaching hospital.

BACKGROUND/PURPOSE: An increasing number of pediatric surgeons are using the laparoscopic approach to treat pyloric stenosis. The advantage of laparoscopic pyloromyotomy is uncertain and has not been evaluated in the setting of a pediatric surgery fellowship program. METHODS: The authors retrospectively reviewed the medical records of all patients who underwent pyloromyotomy for congenital hypertrophic pyloric stenosis at their institution from January 1, 1997 through December 31, 2000 (n = 117). Information obtained included age, sex, weight, admission laboratory values, attending surgeon, resident surgeon and their level of training, operating time, intraoperative and postoperative complications, time to full feedings, incidence of postoperative emesis, duration of postoperative emesis, length of stay, and total hospital charges. These variables then were compared between the open (OPEN) and laparoscopic (LAP) groups. RESULTS: From January 1, 1997 through December 31, 2000, 65 LAP and 52 OPEN pyloromyotomies were performed. Characteristics of patients in the OPEN and LAP groups were similar. The mean operating time was 33 +/- 2 minutes for OPEN versus 38 +/- 2 minutes for LAP (P =.07). The incidence of postoperative emesis (LAP, 68%, OPEN, 65%), duration of postoperative emesis (LAP, 7.3 +/- 1.2 hours; OPEN, 8.1 +/- 1.8 hours), and time to full feedings (LAP, 19.5 +/- 1.6 hours; OPEN, 19.5 +/- 1.3 hours) did not differ significantly between groups (P >.05). Mean postoperative length of stay in both groups was similar (LAP, 31 +/- 5; OPEN, 28 +/- 2 hours; P =.64). Mucosal perforation occurred in 5 patients (8%) in the Lap and 2 patients (4%) in the OPEN group (P =.39). Postoperative complications occurred in 12 LAP (18%) and 6 OPEN patients (12%, P =.31). Five LAP cases were converted to OPEN. In the LAP group there was one unrecognized mucosal perforation and one incomplete pyloromyotomy both of which required reoperation. As the laparoscopic approach was adopted, general surgery resident participation as operating surgeon in these cases decreased from 81% in 1997 to 19% in 2000. Hospital charges were higher in the LAP group, but not significantly (LAP, $6,676 +/- 1,005; OPEN, $5,292 +/- 306; P = 27). CONCLUSIONS: Laparoscopic pyloromyotomy has progressively become the dominant surgical approach to pyloromyotomy at our institution. The LAP and OPEN approaches have similar outcomes. However, the Lap approach may be associated with increased complication rates, a reduction in general surgery resident operative experience, and higher hospital charges.