No abstract

Background-Recent investigations at our institution have studied a variety of vasodilatory shock states that are characterized by vasopressin deficiency and pressor hypersensitivity to the exogenous hormone. Our experience in adults prompted the use of arginine-vasopressin (AVP) in a similar group of critically ill children. Methods and Results-This report describes our early experience (from February 1997 through April 1998) in 11 profoundly ill infants and children (5 male, 6 female) ages 3 days to 15 years (median, 35 days) treated with AVP for hypotension after cardiac surgery which was refractory to standard cardiopressors. Although underlying heart disease was present (congenital heart defects in 10 and dilated cardiomyopathy in 1), only 2 patients had severely depressed cardiac function as demonstrated by 2D echocardiogram before administration of AVP. All patients were intubated and receiving multiple catecholamine pressors and inotropes, including dobutamine (nϭ10), epinephrine (nϭ8), milrinone (nϭ7), and dopamine (nϭ4) before receiving AVP. Five patients received AVP intraoperatively immediately after cardiopulmonary bypass, 5 in the intensive care unit within 12 hours of surgery, and 1 on postoperative day 2 for hypotension associated with sepsis. The dose of AVP was adjusted for patient size and ranged from 0.0003 to 0.002 U ⅐ kg Ϫ1 ⅐ min Ϫ1. During the first hour of treatment with AVP, systolic blood pressure rose from 65Ϯ14 to 87Ϯ17 mm Hg (PϽ0.0001; nϭ11), and epinephrine administration was decreased in 5 of 8 patients and increased in 1. Plasma AVP levels before treatment were available in 3 patients and demonstrated AVP depletion (median, 4.4 pg/mL; nϭ3). All 9 children with vasodilatory shock survived their intensive care unit stay. The 2 patients who received AVP in the setting of poor cardiac function died, despite transient improvement in blood pressure. Conclusions-Infants and children with low blood pressure and adequate cardiac function after cardiac surgery respond to the pressor action of exogenous AVP. AVP deficiency may contribute to this hypotensive condition. (Circulation. 1999;100[suppl II]:II-182-II-186.

We developed a tissue-engineered vascular graft (TEVG) for use in children and present results of a U.S. Food and Drug Administration (FDA)–approved clinical trial evaluating this graft in patients with single-ventricle cardiac anomalies. The TEVG was used as a Fontan conduit to connect the inferior vena cava and pulmonary artery, but a high incidence of graft narrowing manifested within the first 6 months, which was treated successfully with angioplasty. To elucidate mechanisms underlying this early stenosis, we used a data-informed, computational model to perform in silico parametric studies of TEVG development. The simulations predicted early stenosis as observed in our clinical trial but suggested further that such narrowing could reverse spontaneously through an inflammation-driven, mechano-mediated mechanism. We tested this unexpected, model-generated hypothesis by implanting TEVGs in an ovine inferior vena cava interposition graft model, which confirmed the prediction that TEVG stenosis resolved spontaneously and was typically well tolerated. These findings have important implications for our translational research because they suggest that angioplasty may be safely avoided in patients with asymptomatic early stenosis, although there will remain a need for appropriate medical monitoring. The simulations further predicted that the degree of reversible narrowing can be mitigated by altering the scaffold design to attenuate early inflammation and increase mechano-sensing by the synthetic cells, thus suggesting a new paradigm for optimizing next-generation TEVGs. We submit that there is considerable translational advantage to combined computational-experimental studies when designing cutting-edge technologies and their clinical management.

Hybrid procedures are becoming increasingly important, especially in the management of congenital heart lesions for which there are no ideal surgical or interventional options. This report describes a multicenter experience with perventricular muscular venticular septal defect (VSD) device closure. Three groups of patients (n = 12) were identified: infants with isolated muscular VSDs (n = 2), neonates with aortic coarctation and muscular VSDs (n = 3) or patients with muscular VSDs and other complex cardiac lesions (n = 2), and patients with muscular VSDs and pulmonary artery bands (n = 5). Via a sternotomy or a subxyphoid approach, the right ventricle (RV) free wall was punctured under transesophageal echocardiography guidance. A guidewire was introduced across the largest defect. A short delivery sheath was positioned in the left ventricle cavity. An Amplatzer muscular VSD occluding device was deployed across the VSD. Cardiopulmonary bypass was needed only for repair of concomitant lesions, such as double-outlet right ventricle, aortic coarctation, or pulmonary artery band removal. No complications were encountered using this technique. Discharge echocardiograms showed either mild or no significant shunting across the ventricular septum. At a median follow-up of 12 months, all patients were asymptomatic and 2 patients had mild residual ventricular level shunts. Perventricular closure of muscular VSDs is safe and effective for a variety of patients with muscular VSDs.