Faculty Bibliography

BACKGROUND: We tested the hypothesis that sodium-hydrogen exchange inhibition attenuates ventricular dysfunction after ischemia-reperfusion injury in the intact porcine heart. METHODS: Twelve pigs (weight, 30-45 kg) were evenly divided into 2 groups. Baseline ventricular function studies were based on echocardiography, conductance, aortic flow, and left ventricular pressure. Animals were given vehicle (control) or benzamide-N-(aminoiminomethl)-4-(4-[2-furanylcarbonyl]-1-piperazinyl)-3-(m ethylsulfonyl)methanesulfonate (BIIB 513; 3 mg/kg administered intravenously). Ten minutes later, hearts were subjected to 75 seconds of ventricular fibrillation. After reperfusion for 40 minutes, function studies were repeated. Hearts were arrested and excised. Postmortem data included passive pressure-volume curves and myocardial water content. RESULTS: Preload recruitable stroke work was significantly decreased from baseline after ischemia and reperfusion in the control group (27.7 +/- 2.5 vs 48.0 +/- 5.6 mm Hg [+/- SEM], P =.001) but not in the BIIB 513 group (43.0 +/- 5.8 vs 45.5 +/- 4.1 mm Hg, P = not significant). In vivo diastolic and postmortem passive left ventricular compliance were reduced after ischemia and reperfusion for control animals but remained unchanged for animals receiving BIIB 513. Time required to recover baseline blood pressure after ventricular fibrillation was significantly longer for control animals (159 +/- 15 vs 88 +/- 14 seconds [+/- SEM], P =.008). Myocardial water content (78.97% +/- 0.94% vs 77.86% +/- 0.46% [+/- SEM]) and normalized left ventricular mass (137.24 +/- 6.17 vs 128.41 +/- 1.96 g [+/- SEM]) were insignificantly increased in control animals. CONCLUSIONS: Sodium-hydrogen exchange inhibition attenuates ventricular dysfunction after 75 seconds of ventricular fibrillation and 40 minutes of reperfusion. This family of agents might prove useful in patients with severe left ventricular dysfunction undergoing ventricular fibrillation for implantable cardioverter defibrillator testing

BACKGROUND: Extracorporeal life support (ECLS) has been used for post-cardiotomy rescue, but its use as a bridge to heart transplantation (OHT) in patients with post-surgical or end-stage ventricular failure remains controversial. METHODS: Records were reviewed for patients receiving ECLS for ventricular failure from January 1991 to August 2001. Patients listed for OHT were analyzed separately. Listing for OHT requirements were improbable myocardial recovery, absence of contraindications (central nervous system damage, high pulmonary resistance, ongoing infection, etc.), and parental consent. Outcome variables included patient demographics, diagnosis, days from ECLS initiation to United Network for Organ Sharing (UNOS) listing (latency), list time, renal function, and survival to discharge. RESULTS: Of 145 patients with ventricular failure who received ECLS, 21 pediatric patients were UNOS listed. Of 124 non-listed patients, 57 (46%) survived to discharge. All but 3 survivors were separated from ECLS in </=7 days. Twelve underwent OHT and 10 survived to discharge (list time, 6 days; median ECLS time, 14 days). Five had ECLS discontinued without undergoing OHT (1 later underwent OHT, 2 survived to discharge). Five experienced complications while receiving ECLS and died without undergoing OHT. Six of 9 patients who required dialysis for renal failure died. Of 11 infants listed, 4 were weaned from ECLS without undergoing OHT (2 survived to discharge), 5 had OHT (ECLS support, 4 days; 4 survived to discharge) and 2 died (ECLS support, 16 and 47 days). CONCLUSIONS: (1) Extracorporeal life support can be used as a bridge to OHT (even among the infant population) for at least 2 weeks with acceptable survival and hospital discharge rates, and (2) renal insufficiency with the concomitant requirement for dialysis decreases the likelihood of survival before and after OHT

Background. Tetralogy of Fallot with subarterial ventricular septal defect is frequently seen among Asians. Compared with infracristal ventricular septal defect, postoperative right ventricular outflow obstruction is more likely because of subpulmonary extension of the defect. Moreover the incidence of aortic regurgitation is a concern because of the absence of a supporting infundibulum. Methods. Four hundred cases of classic tetralogy were reviewed, 61 of which had subarterial ventricular septal defect. Results. Aortic regurgitation (of more than mild degree) was identified in 7 cases with subarterial and 7 with infracristal ventricular septal defects. The mechanism of infracristal defect was predominantly an annular dilation before surgery. In contrast 5 cases with subarterial defect had progression of aortic regurgitation after operation yielding an actuarial incidence of 29.7% at 20 years. In 2 patients the cause seemed to be fixation or plication of the aortic valve annulus by the ventricular septal patch. Compared with infracristal defect, subarterial defect was associated with increased incidence of reoperation (12.0% versus 1.9% at 10 years, p = 0.01), frequent use of transannular patch (70.5% versus 45.7%, p = 0.0004), and worse New York Heart Association (NYHA) functional class (p = 0.007). Right ventricular outflow obstruction was the reason for reoperation in 3 patients with subarterial defect and was associated with worse NYHA classification in the long-term, on multivariate analysis (p = 0.0002). Conclusions. Tetralogy with subarterial ventricular septal defect was associated with worse functional outcome. To prevent adverse outcomes, precise suturing of the distal ventricular septal patch, extensive infundibulectomy, lower threshold for transannular incision, and smaller-sized ventricular septal patch placement are warranted

OBJECTIVE: To determine the effects of adding 5% albumin to the cardiopulmonary bypass prime on perioperative fluid status and fluid management in young children. DESIGN: Prospective randomized study. SETTING: Single university hospital. PATIENTS: Pediatric patients of <14 kg undergoing cardiac surgery requiring cardiopulmonary bypass. INTERVENTIONS: Patients received a 5% albumin prime or a crystalloid prime. Perioperative fluid intake, output, and daily weights were recorded. Serial hematocrits, colloid osmotic pressures, and serum albumins were measured. Outcomes and complications were documented. MEASUREMENTS AND MAIN RESULTS: There were 86 patients aged 3 days to 4 yrs; 44 patients had an albumin prime and 42 had a crystalloid prime. Patients in the albumin group had a net negative fluid balance at the end of cardiopulmonary bypass compared with a net positive fluid balance in the crystalloid group. Patients in the albumin group had significantly higher serum albumins and colloid osmotic pressures and gained less weight postoperatively. However, their hematocrits were lower, and more patients in the albumin group received packed red blood cells. By 24 hrs postoperatively, there were no differences in colloid osmotic pressures and hematocrits between groups, and by the fourth postoperative day, there was no difference in weight gain. No differences were found in length of mechanical ventilation, intensive care unit or hospital stay, complications, or mortality. CONCLUSIONS: Albumin in the prime may attenuate the extravasation of fluid out of the vascular space, but it may be associated with an increased transfusion rate. The risk/benefit ratio for this intervention warrants further study

This report presents a case of pulmonary atresia/intact ventricular septum with right ventricular-dependent coronary circulation. At 7 months of age, the infant underwent coil embolization of the connection between the right ventricle and the coronary circulation. The child is currently well following surgical decompression of the right ventricle

BACKGROUND: Optimal antimicrobial prophylaxis for the pediatric cardiac surgical patient is unknown. We have reviewed our experience with more than 4,000 pediatric cardiac surgical patients at the University of Michigan to evaluate antibiotic prophylaxis regimens. METHODS: Three antibiotic prophylaxis protocols were serially used during a 6-year period: Protocol 1 (n = 786): cefazolin was administered before operation and continued as long as thoracostomy tubes or central venous catheters were present; Protocol 2 (n = 1095): cefazolin was discontinued 48 hours postoperatively, regardless of the presence of tubes or catheters; Protocol 3 (n = 2039): cefazolin was continued as long as thoracostomy tubes were present, but not for central venous catheters. Patients with an open chest postoperatively received vancomycin and gentamicin until chest closure. This was identical during all three protocols. We retrospectively determined the rate of surgical site infections and unrelated bloodstream infections (the latter for both cardiac medical and surgical patients) for the three protocols. RESULTS: Surgical site infections per 100 operations for protocols 1, 2, and 3 was 2.04, 6.58, and 1.67, respectively (p < 0.05 for protocol 2 versus protocols 1 and 3). The mean age of patients with a surgical site infection ranged from 12 to 15.4 months. Patients with an open chest had a higher rate of surgical site infection (18.8% for protocol 2 and 9.3% for protocol 3). Bloodstream infections per 1,000 patient days for protocols 1, 2, and 3 were 2.18, 6.51, and 5.02, respectively (p < 0.05 protocol 1 versus protocols 2 and 3). CONCLUSIONS: These data suggest that pediatric cardiac surgical patients may benefit from prophylactic antibiotics as long as thoracostomy tubes are in place

BACKGROUND: Apoptosis contributes to ventricular remodeling in heart failure (HF). Nitric oxide (NO) inhibits caspase 3, a key effector apoptotic enzyme. We hypothesized that reduced endogenous NO in HF disinhibits cardiac caspase 3 to promote apoptosis. METHODS: Caspase 3 activity was measured colorimetrically in myocardial cell lysates from endothelial NO synthase (eNOS)-deficient mice (eNOS -/-; n = 18), cardiomyopathic (CMP) hamsters (n = 8), and explanted failing human hearts (n = 10). We stimulated myocardial caspase 3 activity by adding upstream caspase 8 or 9. Cell lysates were incubated with 10(-4) mol/liter NO donor, S-nitroso-N-acetyl penicillamine; NOS inhibitor, nitro-L-arginine-methyl ester (L-NAME); or angiotensin-converting enzyme (ACE) inhibitor, enalaprilat. Hamsters underwent echocardiography so we could study the progression of ventricular dysfunction. RESULTS: Stimulated caspase 3 activity was lower in myocardium of eNOS +/+ compared with eNOS -/- mouse hearts (5.1 +/- 0.5 vs 7.6 +/- 1.0 pmol/10 microg/min, p < 0.05). L-NAME increased enzyme activity only in eNOS +/+ mice, indicating that endogenous NO inhibits caspase 3. Stimulated caspase 3 activity was lower in control hamsters, 3.3 +/- 0.3 pmol/10 microg/min, compared with CMP hamsters, 9.6 +/- 0.7 and 6.9 +/- 0.4 pmol/10 microg/min at 4 and 9 months, respectively. This was associated with progressive ventricular dysfunction, thinning, and dilatation. L-NAME increased enzyme activity in normal but not in CMP hamsters. In failing human myocardium, L-NAME failed to alter caspase activity, indicating reduced NO availability. Enalaprilat inhibited caspase 3, which was reversed by L-NAME. S-nitroso-N-acetyl penicillamine reversed caspase 3 activation in all groups. CONCLUSIONS: Nitric oxide reversibly inhibits myocardial caspase 3 independent of the apoptotic signaling pathway. Reduced NO in HF increases myocardial caspase 3 activity. Agents that promote NO synthesis, including ACE inhibitors, may prevent caspase activation in HF

Aortic atresia is the most severe variant of hypoplastic left heart syndrome (HLHS), and has been associated with significant mortality after stage I palliation. Coronary artery abnormalities are more prominent in this group of patients, especially in the presence of a patent mitral valve. Herein, we describe a case of isolated left ventricular ischemia after the Norwood procedure in a neonate with hypoplastic left heart syndrome, left ventricular hypertrophy, mitral stenosis, aortic atresia, and anomalous left coronary artery