Pre-hospital discharge car safety seat testing in infants following congenital heart surgery.

The purpose of this study was to expand the American Academy of Pediatrics' (AAP) car safety seat testing recommendation to include high-risk infants following cardiac surgery. Car safety seat testing (< or =4 days prior to discharge) was retrospectively reviewed for 66 postoperative infants. Car safety seat testing was performed according to AAP guidelines. Failure of the test was defined as the occurrence of apnea, bradycardia, or oxygen desaturation. Average birth weight was 3.1 +/- 0.5 kg. Two patients were born <37 weeks of gestation. Surgical procedures included modified Blalock-Taussig shunt (15), arterial switch operation (12), Norwood-Sano modification (11), coarctation repair (8), repair of tetralogy of Fallot (6), repair of truncus arteriosus (4), repair of total anomalous pulmonary venous return (3), pacemaker (2), repair of interrupted aortic arch and ventricular septal defect (VSD) (1), repair of coarctation/VSD (1), orthotopic heart transplant (1), repair of VSD (1), and patent ductus arteriosus ligation (1). Average age at discharge was 28 +/- 21 days. Four patients (6%) failed car safety seat testing secondary to a decrease in oxygen saturation. One of four passed on retesting after parental education; three of 4 (75%) were discharged home in a supine car safety seat. There was no relationship between the type of surgery and car safety seat test failure. It may be beneficial to extend the AAP recommendations for car safety seat testing to include this high-risk patient population.

Prehospital discharge car safety seat testing of infants after congenital heart surgery.

BACKGROUND: This study aimed to expand the American Academy of Pediatrics (AAP) car safety seat testing recommendation to include high-risk infants after cardiac surgery. METHODS: Car safety seat testing (< or =4 days before discharge), performed according to AAP guidelines, was retrospectively reviewed for 66 postoperative infants. Failure was defined as apnea, bradycardia, or oxygen desaturation. RESULTS: The average birth weight of the study infants was 3.1 +/- 0.5 kg. Two patients were born at less than 37 weeks gestation. Surgical procedures included modified Blalock-Taussig shunt technique (n = 15), arterial switch operation (n = 12), Norwood Sano modification (n = 11), coarctation repair (n = 8), repair of tetralogy of Fallot (n = 6), repair of truncus arteriosus (n = 4), repair of total anomalous pulmonary venous return (n = 3), pacemaker placement (n = 2), repair of interrupted aortic arch and ventriculoseptal defect (VSD) (n = 1), repair of coarctation and VSD (n = 1), orthotopic heart transplant (n = 1), repair of VSD (n = 1), and patent ductus arteriosus ligation (n = 1). The average age at discharge was 28 +/- 21 days. Four patients (6%) failed car safety seat testing because of a fall in oxygen saturation. One of the four patients passed on retesting after parental education, whereas three of the four (75%) were discharged home in a supine car safety seat. There was no relationship between the type of surgery and car safety seat test failure. CONCLUSION: It may be beneficial to extend the AAP recommendations for car safety seat testing to include high-risk infants after cardiac surgery.

Risk factors for interstage death after the Norwood procedure.

Operative survival after the Norwood procedure has significantly improved during the past 10 years. However, there remains attrition among Norwood survivors before reaching planned second-stage palliation. The purpose of this study was to evaluate potential risk factors for interstage mortality among Norwood survivors. All patients undergoing the Norwood procedure at the Medical University of South Carolina from January 1996 through January 2001 were retrospectively reviewed. Patient and procedural variables were examined as potential risk factors for interstage mortality. Among 50 Norwood survivors, 8 (16%) died prior to second-stage palliation. The mean age at death was 102 +/- 72 days (median, 61; range, 35-208). By multivariate analysis, the presence of an arrhythmia in the postoperative period (p = 0.02) and decreased ventricular function at hospital discharge (p = 0.05) were identified as risk factors for interstage mortality. There remains a significant risk for interstage mortality among Norwood survivors. Patients with postoperative arrhythmias and/or decreased ventricular function at discharge are at increased risk for interstage death after Norwood procedure. More frequent follow-up and aggressive medical management of arrhythmia or decreased function may be warranted for these high-risk patients.

Use of nesiritide (human B-type natriuretic peptide) in infants following cardiac surgery.

We report the use of nesiritide in two infants following cardiac surgery. Both infants had increased intracardiac filling pressures postoperatively, despite traditional afterload reduction and diuretics. Both infants demonstrated clinical improvement with nesiritide therapy. There is currently limited data available describing the use of nesiritide in infants.

Hemodynamic effects of inspired carbon dioxide after the Norwood procedure.

BACKGROUND: Mortality in the early postoperative period after the Norwood procedure remains substantial. Inspired carbon dioxide (CO2) has been suggested to improve hemodynamic status in this setting. Inspired CO2 can be delivered by one of two strategies, ie, with or without an accompanying increase in minute ventilation. The hemodynamic effects of these two strategies have not previously been studied in a controlled fashion. METHODS: Seventeen infants (median age, 9 days; range, 4 to 49 days) undergoing Norwood procedures were prospectively enrolled in this crossover study. Patients were studied while sedated, paralyzed, and mechanically ventilated 1 day to 6 days after operation. The inspired oxygen fraction was kept constant (mean value, 0.24 +/- 0.01). Measurements were made at five time points: 1 = baseline; 2 = inspired CO2 with increased ventilation; 3 = baseline; 4 = inspired CO2 alone; and 5 = baseline. Mixed venous oxygen saturation was monitored using indwelling lines in the superior vena cava. RESULTS: Inspired CO2 with increased ventilation produced a rise in mean airway pressure with no change in arterial CO2 tension or pH. This strategy had no effect on hemodynamic status or oxygen delivery. Inspired CO2 alone produced a rise in arterial CO2 tension and a fall in arterial pH (respiratory acidosis). This strategy resulted in significant improvement in both variables of systemic oxygen delivery: mixed venous oxygen saturation increased from 48% +/- 2% to 56% +/- 2% (p < 0.05), and arteriovenous oxygen saturation difference decreased from 3% +/- 2% to 26% +/- 2% (p < 0.05). CONCLUSIONS: Inspired CO2 after the Norwood procedure can improve oxygen delivery. This improvement occurs only if minute ventilation is kept constant. There is no improvement if minute ventilation is increased. Clinical use of inspired CO2 may be limited by the accompanying fall in pH. Differentiation of cerebral from total-body effects of inspired CO2 will require further study.

Effects of gene deletion of the tissue inhibitor of the matrix metalloproteinase-type 1 (TIMP-1) on left ventricular geometry and function in mice.

Alterations in the expression and activity of the matrix metalloproteinases (MMPs) and the tissue inhibitors of the MMPs (TIMPs) have been implicated in tissue remodeling in a number of disease states. One of the better characterized TIMPs, TIMP-1, has been shown to bind to active MMPs and to regulate the MMP activational process. The goal of this study was to determine whether deletion of the TIMP-1 gene in mice, which in turn would remove TIMP-1 expression in LV myocardium, would produce time-dependent effects on LV geometry and function. Age-matched sibling mice (129Sv) deficient in the TIMP-1 gene (TIMP-1 knock-out (TIMP-1 KO), n=10) and wild-type mice (n=10) underwent comparative echocardiographic studies at 1 and 4 months of age. LV catheterization studies were performed at 4 months and the LV harvested for histomorphometric studies. LV end-diastolic volume and mass increased (18+/-4 and 38+/-3%, respectively, P<0.05) at 4 months in the TIMP-1 KO group; a significant increase compared to wild-type controls (P<0.05). At 4 months, LV and end-diastolic wall stress was increased by over two-fold in the TIMP-1 KO compared to wild type (P<0.05). However, LV systolic pressure and ejection performance were unchanged in the two groups of mice. LV myocyte cross-sectional area was unchanged in the TIMP-1 KO mice compared to controls, but myocardial fibrillar collagen content was reduced. Changes in LV geometry occurred in TIMP-1 deficient mice and these results suggest that constitutive TIMP-1 expression participates in the maintenance of normal LV myocardial structure.

Diastolic heart failure: diagnosis and treatment.

The most frequent hospital diagnosis-related group is congestive heart failure (CHF). CHF increases dramatically with age, making it an important problem in our aging population. CHF is caused by a primary abnormality in diastolic function (diastolic heart failure [DHF]) in 50% of patients with CHF who are > 70 years of age. Mortality rates in patients with DHF are comparable to those of patients with systolic heart failure, approaching 50% over 5 years. Successful therapy of DHF requires making a correct diagnosis, identifying the underlying cause, and applying specific and individualized treatment.

Hyperventilation impairs oxygenation after bidirectional superior cavopulmonary connection.

BACKGROUND: Bidirectional superior cavopulmonary connection (BSCC) may be complicated by systemic hypoxemia. Hyperventilation, which is standard therapy for postoperative hypoxemia, has opposing effects on the pulmonary and cerebral vascular beds, which are connected after BSCC. It is unknown which of these effects predominates and, therefore, whether hyperventilation improves or impairs systemic oxygenation after BSCC. METHODS AND RESULTS: Twelve consecutive patients (median age, 6.4 months; age range, 6.0 to 32.0, months) undergoing BSCC were studied prospectively. Patients were studied in the intensive care unit within 6 hours of surgery and while sedated, paralyzed, and mechanically ventilated. Inotropes were not altered, and no transfusions were given. FIO2 was set at 100%, and peak end-expiratory pressure was set at 0. Each patient was studied first during normal ventilation, then during hyperventilation, and finally again during normal ventilation. Hyperventilation resulted in significant decreases in arterial PO2, systemic oxygen saturation, and transpulmonary gradient. Cerebral blood flow velocity was measured in 6 patients through transcranial Doppler sonography of the middle cerebral artery. Mean cerebral flow velocity decreased significantly during hyperventilation. CONCLUSIONS: Hyperventilation significantly impairs systemic oxygenation after BSCC. This fall in oxygenation occurs despite a decrease in transpulmonary gradient. A possible mechanism for this effect is that hyperventilation lowers arterial PCO2, raising cerebral vascular resistance, and lowering cerebral, superior vena caval, and pulmonary blood flows. Supportive evidence for this mechanism is the decrease in cerebral flow velocity that occurs during hyperventilation. After BSCC, normal ventilation rather than hyperventilation should be used to improve systemic oxygen levels.

Analysis of retroviral protease cleavage sites reveals two types of cleavage sites and the structural requirements of the P1 amino acid.

Retroviruses encode a protease which cleaves the viral Gag and Gag/Pol protein precursors into mature products. To understand the target sequence specificity of the viral protease, the amino acid sequences from 46 known processing sites from 10 diverse retroviruses were compared. Sequence preference was evident in positions P4 through P3' when compared to flanking sequences. Approximately 80% of all cleavage site sequences could be grouped into two classes based on the sequence composition flanking the scissile bond. The sequences at the amino-terminal cleavage site of the major capsid protein of Gag is always a member of one of the two classes while the carboxyl-terminal cleavage site is of the other class, suggesting a biological role for the two classes. Known processing site sequences proved useful in a motif searching strategy to identify processing sites in retroviral protein sequences, particularly in Gag. In all known cleavage sites, the P1 amino acid is hydrophobic and unbranched at the beta-carbon. The sequence requirements of the P1 position were tested by site-directed mutagenesis of the P1 Phe codon in an HIV-1 Pol cleavage site. Mutations were tested for protease-mediated cleavage of the Pol precursor expressed in Escherichia coli.