Jefferson M. Lyons

Glucocorticoids reduce cardiac dysfunction after cardiopulmonary bypass and circulatory arrest in neonatal piglets.

Objective The hypotheses were that glucocorticoid administration could improve ventricular recovery by reducing cardiopulmonary bypass (CPB)-induced inflammatory response and that presurgical administration might be more effective than intraoperative dosing. Design Animal case study. Subjects Crossbred piglets (5–7 kg). Interventions Piglets were cooled with CPB, followed by 120 mins of deep hypothermic circulatory arrest (DHCA). Animals were rewarmed to 38°C, removed from CPB, and maintained for 120 mins. Methylprednisolone (60 mg/kg) was administered in the CPB pump prime (intraoperative glucocorticoid [intraop GC]) or 6 hrs before CPB (30 mg/kg) in addition to the intraoperative dose (30 mg/kg; pre- and intraop GC). Controls (no GC) received saline. Measurements and Main Results In no GC, left ventricle (LV) positive change in pressure in time (+dP/dt) (mm Hg/sec) had a mean ± sd of 1555 ± 194 at baseline vs. 958 ± 463 at 120 mins after CPB, p = .01). LV +dP/dt was maintained in glucocorticoid-treated animals (1262 ± 229 at baseline vs. 1212 ± 386 in intraop GC and 1471 ± 118 vs. 1393 ± 374 in pre- and intraop GC). Glucocorticoids reduced myocardial interleukin-6 messenger RNA expression, measured by ribonuclease protection assay, at 120 mins after CPB compared with animals receiving saline (p < .05), although interleukin-6 plasma and LV protein concentrations were not affected. Interleukin-10 myocardial protein concentrations were elevated after CPB-DHCA with higher concentrations in glucocorticoid-treated animals (p < .05). Glucocorticoid treatment maintained myocardial concentrations of the inhibitor of nuclear factor-&kgr;B in the cytosol and decreased nuclear factor-&kgr;B concentrations detected in the nucleus in a DNA/protein interaction array. Conclusions Glucocorticoids improved recovery of LV systolic function in neonatal animals undergoing CPB-DHCA. Animals receiving glucocorticoids before CPB had better postoperative oxygen delivery than those receiving only intraoperative treatment. Maintenance of cardiac function after glucocorticoids might be due, in part, to alterations in the balance of pro- and anti-inflammatory proteins, possibly through nuclear factor-&kgr;B-dependent pathways.

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-&kgr;B) 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 &mgr;g/kg of SN50, a peptide inhibitor of NF-&kgr;B translocation and activation, 1 hour before CPB. The control group received saline. Animals were cooled to 18°C with CPB, the piglets were in DHCA for 120 minutes, and the piglets were then rewarmed on CPB to 38°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-&kgr;B 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−1·cm−5) 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-&kgr;B 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-&kgr;B, 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-&kgr;B 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-&kgr;B activity may reduce ischemia and reperfusion injury after pediatric cardiac surgery.

Prophylactic intravenous immune globulin and polymixin B decrease the incidence of septic episodes and hospital length of stay in severely burned children.

After burn shock resuscitation, serum gamma globulin levels decrease well below normal before slowly recovering over the course of 1 to 2 months. During this period, patients are vulnerable to further insult as a result of this immunocompromise. We hypothesized that intravenous immune globulin and subtherapeutic polymixin B (IVIG-B) could decrease the incidence and/or severity of sepsis after major thermal injury. A retrospective chart review from 1997 through 2003 at two hospitals compared patients who received IVIG-B (Hospital A) with those who did not (Hospital B). Patients with burns 40% or greater TBSA were included, whereas patients with nonsurvivable injuries were excluded from data analysis. A total of 152 patients were included in the study. One hundred two patients received IVIG-B, and 50 did not. Total burn size was 63.4% TBSA at Hospital A and 63.1% TBSA at Hospital B, with full-thickness burns of 54.4 and 61.7% TBSA, respectively (P < .05). Patients treated at Hospital A had a 51.9% incidence of inhalation injury compared with 28% of the patients at Hospital B (P < .05). There was an average of 1.2 and 1.9 septic episodes for patients treated at Hospital A and Hospital B, respectively (P < .05). Length of hospital stay was 77.1 days at Hospital A compared with 103.8 days at Hospital B (P < .05). Mortality was 17.6% and 18% at Hospitals A and B, respectively, and was not significantly different. Our data suggest that prophylactic IVIG-B is associated with a reduction in the incidence of septic episodes and decreased hospital length of stay following major thermal injury.

Compression of an Extracardiac Fontan Following Classic Fontan Revision

Abstract  Background: The extracardiac Fontan arose as an alternative in order to prevent the classical procedures sequelea. Complications of the extracardiac Fontan have been described, but this case report aims to highlight the devastating and infrequent complication of external conduit compression. Methods and Results: A 25‐year‐old male underwent Fontan conversion to extracardiac Fontan for atrial arrhythmias and giant right atrium. He developed postoperative respiratory distress, renal failure, and hemorrhagic pancreatitis, which prompted CT scans of his chest and abdomen that demonstrated external compression of the conduit by mediastinal hematoma. Endovascular stenting restored flow through the conduit, but the patient ultimately expired. Conclusions: External Fontan compression, which can be caused by numerous sources, may lead to significant organ dysfunction and can be difficult to recognize despite invasive monitoring. We report this complication and suggest ringed conduits to be considered to avoid the possibility of external compression. (J Card Surg 2004;19:254‐257)