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.

Closure of symptomatic ventricular septal defects: how early is too early?

With improvements in technology and surgical technique, pediatric cardiologists are challenging surgeons to close symptomatic ventricular septal defects (VSDs) in ever smaller patients. Although delaying surgery may facilitate operative repair, early intervention decreases the period of time these patients require therapy to prevent heart failure, maintains growth, and minimizes exposure to increased pulmonary pressures. To evaluate early intervention, we compare the outcomes of VSD closure in different-sized children. From December 2002 to July 2005, 225 patients underwent closure of a VSD. These patients were divided into four weight-based groups: <4 kg (group 1, n = 28), 4 to 6 kg (group 2, n = 93), 6 to 10 kg (group 3, n = 47), and >10 kg (group 4, n = 57). We reviewed operative and postoperative data, and comparisons were made between the groups. Median weights and ages at the time of surgery were 3.5 kg and 77 days (group 1), 4.9 kg and 128 days (group 2), 7.1 kg and 309 days (group 3), and 18.2 kg and 190 days (group 4). Operative data included cardiopulmonary bypass (CPB), aortic cross-clamp, and procedure times. CPB (p = 0.064), cross-clamp (p = 0.665), and procedure (p = 0.187) times were not significantly affected by decreasing weight. Postoperative continuous data included duration of ventilation and length of intensive care unit (ICU) and hospital stay. Ventilation (p = 0.667) and ICU (p = 0.976) times and length of hospital stay (p = 0.905) were also unaffected by decreasing weight. Postoperative catagoric data included complications and presence of a residual VSD. There was no significant difference in complications (p = 0.763) or residual VSD (p = 0.696) between groups. There was no mortality and no persistent heart block requiring placement of a permanent pacemaker. With improvements in technology and surgical technique, safe and effective VSD closure can be performed in increasingly smaller children. Earlier repair decreases the period of time these patients require aggressive medical therapy to prevent heart failure and maintain growth. It also decreases the period of time for which they are exposed to increased pulmonary pressures and are at risk for infectious respiratory complications. It does not appear to affect operative or postoperative outcomes.

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.

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.

Mechanical environment, donor age, and presence of endothelium interact to modulate porcine artery viability ex vivo.

Though ex vivo culture of arteries is a widely used model of native arteries and is closely aligned with efforts to generate tissue-engineered arteries, the effects of culture conditions on artery viability are poorly characterized. To investigate factors regulating long-term viability of cultured arteries, carotid arteries from neonatal and adolescent pigs were perfused for up to 27 days with steady laminar flow ranging from approximately 2% to approximately 200% of physiological flow rates. Arteries from neonatal animals (2 weeks old, approximately 5 kg) were susceptible to spontaneous progressive endothelial denudation followed by deterioration of the vessel wall that spread from luminal to abluminal regions. Subphysiological levels of flow and pressure abrogated this deterioration. Arteries harvested from adolescent (6 months old, approximately 100 kg) animals maintained viability and retained structure for at least 9 days as assessed by normal histology, presence of intact endothelium, normal mitochondrial activity, and low levels of cell death and proliferation, unless the vessels were subjected to superphysiological levels of flow or the endothelium was intentionally denuded. Adolescent arteries perfused at subphysiological, but not physiological, flow rates maintained viability and normal structure for at least 27 days. These data indicate that under the appropriate conditions, arteries may be cultured long term but careful attention to the viability is merited.

Gastrointestinal carcinoids: characterization by site of origin and hormone production.

OBJECTIVE: To describe a large series of patients with carcinoid tumors in terms of presenting symptoms, hormonal data, stage at diagnosis, pathologic features, and survival. SUMMARY BACKGROUND DATA: Published series have described significant prognostic features of carcinoid tumors as site of origin, age, sex, stage at diagnosis, presence of high hormone levels, and increased T stage. Of these, stage at diagnosis and T stage seem to emerge most often as independent predictors of survival in multivariate analyses. Of carcinoid tumors, those arising from a midgut location have higher levels of serotonin and serotonin breakdown products, as well as more frequent metastatic disease at presentation, than those arising from either foregut or hindgut locations. METHODS: A prospective database of carcinoid patients seen at Duke University Medical Center was kept from 1970 to the present. Retrospective medical record review was performed on this database to record presenting symptoms, hormonal data, pathologic features, and survival. Statistical methods included analysis of variance, Kaplan-Meier analysis, and Mantel-Cox proportional hazard survival analysis, with P <.05 considered significant for all tests. RESULTS: Carcinoids arising in different locations had different presentations: rectal carcinoids presented significantly more often with gastrointestinal bleeding, and midgut carcinoids presented significantly more often with flushing, diarrhea, and the carcinoid syndrome. Patients with midgut tumors had significantly higher levels of serotonin and serotonin breakdown products, corresponding to higher metastatic tumor burdens. Although age, stage, region of origin, and urinary level of 5-hydroxyindoleacetic acid predicted survival by univariate analysis, only the latter three were independent predictors of survival by multivariate analysis. Of the patients with metastatic disease at diagnosis, those with midgut tumors had better survival than those with foregut or hindgut tumors. CONCLUSIONS: Although region of origin is certainly an important factor in determination of prognosis, stage of disease at presentation is more predictive of survival. Pancreatic and midgut carcinoids are metastatic at diagnosis more often than those arising in other locations, leading to a worse overall prognosis. Among patients with distant metastases, patients with midgut primary tumors have improved survival despite increased hormone production compared with patients with tumors arising in other primary sites.

Extracorporeal membrane oxygenation for infant postcardiotomy support: significance of shunt management.

BACKGROUND: After repair of complex congenital heart defects in infants and children, postcardiotomy cardiac failure requiring temporary circulatory support can occur. This is usually accomplished with the use of extracorporeal membrane oxygenation (ECMO). ECMO management of patients with single-ventricle physiology and aorto-pulmonary shunts can be particularly challenging. We retrospectively reviewed our experience with postcardiotomy support with particular attention to those children with single-ventricle palliation. METHODS: Thirty-five consecutive children (age 1 to 820 days, median 19 days) out of 1,020 patients (3.4%) required mechanical support (ECMO) after repair of congenital cardiac lesions from February 1994 to April 1999. Twenty-five patients underwent two ventricle repairs and 10 patients had single-ventricle palliation. Various parameters analyzed included strategies of shunt management, presence of presupport cardiac arrest, and timing of support initiation. RESULTS: Overall hospital survival for these 35 patients was 61%. There were four additional late deaths. Hospital survival was the same for those patients in whom support was initiated for failure to wean from cardiopulmonary bypass in the operating room versus those patients in whom support was initiated after successful separation from cardiopulmonary bypass (6 of 10 vs 15 of 25 or 60% survival). In those patients with shunt-dependent pulmonary circulation, survival was significantly improved in those patients in which the aorto-pulmonary shunt was left open (4 of 5 with open shunt vs 0 of 4 with occluded shunt (p = 0.048). CONCLUSIONS: The ability to readily implement postcardiotomy support is vital to the management of children with complex congenital cardiac disease. Overall survival can be quite satisfactory if support is employed in a rational and expedient manner. In patients with single-ventricle physiology and aorto-pulmonary shunts, leaving the shunt open during the period of support can result in markedly improved outcomes.

Foregut carcinoids: a clinical and biochemical analysis.

BACKGROUND: Gastrointestinal foregut carcinoids make up a small percentage (3% to 6%) of all reported carcinoids. Because these tumors are so uncommon, comparisons between the subtypes have been difficult. The goal of this study was to compare the hormonal and clinical characteristics of gastric, duodenal, and pancreatic carcinoids. METHODS: A prospective database of approximately 750 carcinoid patients seen by one author over 25 years was reviewed, and the 104 patients with gastric (33), duodenal (17), or pancreatic (54) carcinoids were selected as the subgroup for analysis. These patients were compared with regard to hormone levels, clinical course, treatment, and survival. RESULTS: Duodenal carcinoids exhibited significantly lower serotoninergic hormone levels than did the gastric and pancreatic carcinoids (urine 5-hydroxyindoleacetic acid [mg/24 h], 5 +/- 1 vs 16 +/- 5 and 47 +/- 12, respectively, P = .03). Pancreatic carcinoids presented with more advanced stage (distant metastases 87% vs 42% and 20% for gastric and duodenal, respectively) and had worse outcomes than patients with gastric and duodenal tumors with 10-year survivals of 10%, 59%, and 58%, respectively (P = .003). CONCLUSIONS: Pancreatic carcinoids produce higher levels of serotoninergic hormones and have a significantly higher stage and worse outcome than other foregut carcinoids. This study demonstrates that the organ of origin is an important determinant of hormonal activity and clinical course for patients with foregut carcinoids.

Carcinoids of unknown origin: comparative analysis with foregut, midgut, and hindgut carcinoids.

BACKGROUND: Carcinoids are rare neuroendocrine tumors typically arising in the gastrointestinal tract. A significant percentage of these tumors present as metastatic disease of unknown primary site. The aim of this study was to better define the functional and clinical characteristics of carcinoids of unknown primary (CUP) site. METHODS: This study examines the hormonal activity, clinical characteristics, and survival of 434 patients with carcinoids originating in the foregut, midgut, hindgut, or unknown location. The 143 patients with CUP were compared with the other groups with regard to presenting characteristics, diagnostic tests and therapeutic modalities used, hormonal activity, and survival. RESULTS: The hormone levels (urinary 5-hydroxyindoleacetic acid and serotonin, serum and platelet serotonin) of CUP were not significantly different from midgut carcinoids with metastatic disease. Although survival with CUP was shorter than with carcinoids with identified primaries (10-year survivals of 22% vs 62%, 50%, and 48% for foregut, midgut, and hindgut, respectively), the survival curve for CUP was quite similar to that of patients with midgut carcinoids with distant disease (10-year survival of 22% vs 28%). CONCLUSIONS: CUP are similar to midgut carcinoids presenting with metastatic disease with regard to hormone production and survival. Like other carcinoids, CUP can be an indolent disease process with gradual progression over decades.

Acute functional consequences of left ventriculotomy.

BACKGROUND: Left ventriculotomies are sometimes used during intracardiac congenital defect repair. Acute changes in left ventricular function after longitudinal or apical ventriculotomy were assessed using dynamic pressure-dimensional data. METHODS: Ultrasonic dimension transducers along the major, minor, and septal free wall axes and micromanometers were placed in 24 piglets. Pressure-volume data were collected during caval occlusions at baseline and 60 minutes after warm cardiopulmonary bypass alone or with longitudinal ventriculotomy or apical left ventriculotomy. Hemodynamics, contractility, and contraction geometry were analyzed. RESULTS: Cardipulmonary bypass caused decreased compliance in all groups, with equally decreased preload and cardiac output. Heart rate increased, but ventriculotomy led to a significantly greater increase. Longitudinal ventriculotomy produced a greater loss of stroke volume and ejection fraction than apical ventriculotomy. Contractility assessed by the preload recruitable stroke work relationship showed no difference between groups; however, all groups showed a slight increase in unit myocardial power at 60 minutes. Axis fractional shortening revealed that the septal freewall is responsible for 50% of stroke volume and that this axis is significantly impaired after longitudinal ventriculotomy. CONCLUSION: Apical left ventriculotomy impairs the less important major axis only and is predicted to be better tolerated.

Measurement of cerebral blood flow during cardiopulmonary bypass with near-infrared spectroscopy.

OBJECTIVE: A novel noninvasive method for repeatedly measuring cerebral blood flow during cardiopulmonary bypass by near-infrared spectroscopy is described. The reproducibility of the method is investigated and a comparison is made with an established technique. METHODS AND RESULTS: The method is derived from the Fick principle and uses indocyanine green dye, injected into the bypass circuit, as an intravascular tracer. Cerebral blood flow was measured in nine children undergoing cardiopulmonary bypass on a total of 49 occasions. Results from this study suggest that an integrating period of 4 seconds provided a consistent measurement of global cerebral blood flow. The values obtained ranged from 3.2 to 32.4 (median 15.9) ml.100 gm-1.min-1. In an additional 10 children in whom repeated measurements were made, the coefficient of variation was 11% +/- 7% (mean +/- standard deviation). In a further study, the method was compared with microsphere injection in five piglets undergoing cardiopulmonary bypass. The comparison within each animal with the linear least squares method gave values for R2 in the range 0.91 to 0.99. The gradients of the fits ranged from 0.5 to 1.8 (median 1.0). The mean difference between the two techniques was 5.7 ml.100 gm-1.min-1 or 7%. The coefficient of variation for the piglets was 14% +/- 9% (mean +/- standard deviation). CONCLUSIONS: Indocyanine green and near-infrared spectroscopy allow frequent and repeated measurements of cerebral blood flow during cardiopulmonary bypass. The measurements are reproducible and accurately reflect changes in cerebral blood flow. It may be widely applicable both in research and clinical practice.

Thromboxane A2-receptor blockade improves cerebral protection for deep hypothermic circulatory arrest.

OBJECTIVE: Following the use of deep hypothermic circulatory arrest in cardiac surgery, cerebral blood flow and cerebral oxygen metabolism are impaired. These may result from abnormal cerebral vasospasm. Powerful vasoconstrictors including endothelins and thromboxane A2 could mediate these processes. We investigated possible involvement of these two factors by assessing the effects of (a) phosphoramidon-an inhibitor of endothelin converting enzyme, and (b) vapiprost (GR32191B)-a specific thromboxane A2-receptor antagonist, on the recovery of cerebral blood flow and cerebral oxygen metabolism following deep hypothermic circulatory arrest. METHODS: A total of 18 1-week-old piglets were randomised into three groups (n = 6 per group). At induction, the control group received saline; group PHOS received phosphoramidon 30 mg kg-1 intravenously. Group VAP received vapiprost 2 mg kg-1 at induction and at 30 min intervals thereafter. All groups underwent cardiopulmonary bypass cooling to 18 degrees C, exposed to 60 min of deep hypothermic circulatory arrest, rewarmed and reperfused for 1 h. Cerebral blood flow was measured with radio-labeled microspheres: cerebral oxygen metabolism was calculated at baseline before deep hypothermic circulatory arrest and at 1 h of reperfusion and rewarming. RESULTS: In the control group, cerebral blood flow decreased to 40.2 +/- 2.0% of baseline after deep hypothermic circulatory arrest and cerebral oxygen metabolism decreased to 50.0 +/- 5.5% (P < 0.0005). The responses in group PHOS were similar. In group VAP, cerebral blood flow and cerebral oxygen metabolism were 64.3 +/- 10.6 and 80.1 +/- 9.8% of baseline, respectively, after deep hypothermic circulatory arrest. Thus, treatment with vapiprost significantly improved recovery of cerebral blood flow (P = 0.046) and cerebral oxygen metabolism (P = 0.020) following deep hypothermic circulatory arrest. No such improvement was seen after treatment with phosphoramidon. CONCLUSIONS: Thromboxane A2 mediates impairments in cerebral perfusion and metabolism following deep hypothermic circulatory arrest. These changes were attenuated by blockade of thromboxane A2-receptors using vapiprost. Endothelins are not shown to be involved. Better knowledge of injury mechanisms will enable development of more effective cerebral protection strategies and allow safer application of deep hypothermic circulatory arrest.

Cardiopulmonary bypass and circulatory arrest increase endothelin-1 production and receptor expression in the lung.

BACKGROUND: Endothelin-1 has been shown to be a mediator of pulmonary hypertension after cardiopulmonary bypass and deep hypothermic circulatory arrest. It is not known whether the mechanism is increased production of endothelin-1 or alterations in expression of endothelin-1 receptors in the lung. This study was designed to test the hypothesis that circulatory arrest increases endothelin-1 mRNA levels and endothelin-1 receptor expression in the lung. METHODS AND RESULTS: Twenty-four piglets (7 to 30 days old) were studied randomly either at baseline (controls, n = 12) or after cardiopulmonary bypass with 30 minutes of circulatory arrest (deep hypothermic circulatory arrest, n = 12). Lungs and pulmonary arteries were harvested immediately after hemodynamic data collection. Deep hypothermic circulatory arrest significantly increased pulmonary vascular resistance (p < 0.01). Deep hypothermic circulatory arrest also produced a significant increase in endothelin-1 mRNA levels in the pulmonary arteries (149 +/- 55 pg vs 547 +/- 111 pg, p = 0.007). There was no significant change in the pulmonary parenchymal endothelin-1 mRNA levels (4102 +/- 379 pg vs 4623 +/- 308 pg, p = 0.32). Ligand binding studies of the lung parenchyma revealed a single specific endothelin-1 binding site with an EC50 value (effective concentration causing 50% of the maximum response) of about 1 x 10(-8) mol/L, consistent with the endothelin B subtype. Deep hypothermic circulatory arrest resulted in a significant increase in the number of endothelin-1 receptors in the lung (109 +/- 6 fmol/mg total protein to 135 +/- 9 fmol/mg total protein, p = 0.02). CONCLUSIONS: Deep hypothermic circulatory arrest increases production of endothelin-1 by the pulmonary vascular endothelium. Endothelin-1 production in the pulmonary parenchyma does not change. Expression of endothelin B receptors in the pulmonary parenchyma also increases after cardiopulmonary bypass with deep hypothermic circulatory arrest. This study supports the hypothesis that deep hypothermic circulatory arrest results in pulmonary vascular endothelial activation with increased endothelin-1 mRNA production.

Low-flow cardiopulmonary bypass produces greater pulmonary dysfunction than circulatory arrest.

BACKGROUND: Deep hypothermic circulatory arrest (DHCA) is used during the repair of congenital heart disease in neonates. However, because of concern about neurologic injury after DHCA, there is increasing use of continuous deep hypothermic low-flow cardiopulmonary bypass (DHCPB). This study examines the effects of DHCPB versus DHCA on pulmonary dynamics in 1-week-old piglets (weight range, 2.5 to 3.5 kg). METHODS: Animals were placed on CPB (37 degrees C) at 100 mL.kg-1.min-1, cooled to 18 degrees C, and then assigned to one of two groups: DHCPB (n = 7), 25 to 50 mL.kg-1.min-1 DHCPB for 90 minutes; or DHCA (n = 8), DHCA for 90 minutes. Animals were rewarmed to 37 degrees C, weaned from CPB, and observed for 30 minutes. Static pulmonary compliance and pulmonary vascular resistance index were assessed before CPB, 5 minutes after CPB, and 30 minutes after CPB. RESULTS: There was greater impairment of static pulmonary compliance after DHCPB compared with 90 minutes of DHCA. There was a trend toward higher pulmonary vascular resistance index in the DHCPB group; however, significance was not reached. CONCLUSIONS: Deep hypothermic low flow cardiopulmonary bypass produces greater pulmonary dysfunction than DHCA, manifested by decreased static pulmonary compliance. If DHCPB is used in place of DHCA in congenital heart operations, close attention to ventilatory and fluid management is mandatory in the postoperative period to prevent further worsening of pulmonary dysfunction.

Nitric oxide production affects cerebral perfusion and metabolism after deep hypothermic circulatory arrest.

BACKGROUND: Use of deep hypothermic circulatory arrest (DHCA) in infant cardiac surgery is associated with reduced cerebral perfusion and metabolism during the recovery period. We investigated the impairment of nitric oxide production as a possible cause. METHODS: A group of 1-week-old piglets underwent normothermic cardiopulmonary bypass (group A); three other groups (B, C, and D; n = 6 per group) underwent 60 minutes of DHCA at 18 degrees C and 60 minutes of rewarming. The animals were then treated as follows: Groups A and B received L-omega-nitro-arginine-methyl-ester (L-NAME, 50 mg.kg-1); group C, saline solution; and group D, L-arginine (600 mg.kg-1). RESULTS: In group A, global cerebral blood flow decreased to 37.3% +/- 4.2% of baseline after L-NAME administration (p < 0.005). In group B, global cerebral blood flow decreased to 44.6% +/- 4.4% of baseline after DHCA and 28.9% +/- 3.4% after L-NAME administration (p < 0.001). Following L-arginine treatment after DHCA (group D), global cerebral blood flow increased from 43.8% +/- 3.0% of baseline to 61.6% +/- 9.1% (p < 0.05); cerebral oxygen metabolism increased from 1.93 +/- 0.16 mL.min-1.100 g-1 after DHCA to 2.42 +/- 0.25 mL.min-1.100 g-1 (p < 0.05). CONCLUSIONS: Tonal production of nitric oxide is impaired in the brain after DHCA and is partly responsible for the circulatory and metabolic changes observed. Stimulation of nitric oxide production (L-arginine) significantly improved recovery of cerebral blood flow and cerebral oxygen metabolism after DHCA.

Effects of cardiopulmonary bypass and circulatory arrest on endothelium-dependent vasodilation in the lung.

Endothelial injury with failure of pulmonary endothelium-dependent vasodilatation has been proposed as a possible cause for the increased pulmonary vascular resistance observed after cardiopulmonary bypass, but the mechanisms underlying this response are not understood. An in vivo piglet model was used to investigate the role of endothelium-dependent vasodilatation in postbypass pulmonary hypertension. The pulmonary vascular responses to acetylcholine, a receptor-mediated endothelium-dependent vasodilator, and nitric oxide, an endothelium-independent vasodilator, were studied in one group of animals after preconstriction with the thromboxane A2 analog U46619 (n = 6); a second group was studied after bypass with 30 minutes of deep hypothermic circulatory arrest (n = 6). After preconstriction with U46619, both acetylcholine and nitric oxide caused significant decreases in pulmonary vascular resistance (34% +/- 6% decrease, p = 0.007, and 39% +/- 4% decrease, p = 0.001). After cardiopulmonary bypass with circulatory arrest, acetylcholine did not significantly change pulmonary vascular resistance (0% +/- 8% decrease, p = 1.0), whereas nitric oxide produced a 32% +/- 4% decrease in pulmonary vascular resistance (p = 0.007). These results demonstrate a loss of receptor-mediated endothelium-dependent vasodilatation with normal vascular smooth muscle function after circulatory arrest. Administration of the nitric oxide synthase blocker Ngamma-nitro-L-arginine-methyl-ester after circulatory arrest significantly increased pulmonary vascular resistance; thus, although endothelial cell production of nitric oxide may be diminished, it continues to be a major contributor to pulmonary vasomotor tone after cardiopulmonary bypass with deep hypothermic circulatory arrest. In summary, cardiopulmonary bypass with deep hypothermic circulatory arrest results in selective pulmonary endothelial cell dysfunction with loss of receptor-mediated endothelium-dependent vasodilatation despite preserved ability of the endothelium to produce nitric oxide and intact vascular smooth muscle function.

Delayed right heart failure following lung transplantation.

Dynamic right ventricular outflow tract obstruction (RVOTO) has been reported following lung transplantation for pulmonary hypertension, usually in association with the use of inotropic agents. This report describes delayed severe right-sided heart failure associated with right ventricular outflow tract obstruction following sequential bilateral lung transplantation and closure of a ventricular septal defect. The patient had no evidence of outflow tract obstruction in the early posttransplant period but developed progressive right heart failure more than 2 months later. Catheterization revealed dynamic RVOTO and an elevated right ventricular end-diastolic pressure. The patient was treated with metoprolol tartrate and diltiazem hydrochloride with resolution of the outflow tract obstruction and heart failure. This case demonstrates that RVOTO can occur in the late posttransplant period and must be included in the differential diagnosis for patients who develop right-sided heart failure.

pH-stat cooling improves cerebral metabolic recovery after circulatory arrest in a piglet model of aortopulmonary collaterals.

Cardiopulmonary bypass with deep hypothermic circulatory arrest increases the risk of neurologic injury in patients with aortopulmonary collaterals. Experimental studies have demonstrated that such collaterals decrease the rate of cerebral cooling before arrest and cerebral metabolic recovery after circulatory arrest. Use of pH-stat blood gas management has been shown to increase cerebral blood flow during cooling. The current study was designed to test whether cooling with pH-stat blood gas management can decrease the cerebral metabolic impact of aortopulmonary collaterals. Twenty 4- to 6-week-old piglets underwent placement of a shunt between the left subclavian artery and main pulmonary artery. In control animals (n = 10) the shunts were immediately ligated, whereas in the shunt animals (n = 10) the shunts were left patent. All animals were supported with cardiopulmonary bypass, cooled to 18 degrees C by means of either alpha-stat (five control and five shunt animals) or pH-stat (five control and five shunt animals) blood gas management, subjected to circulatory arrest for 90 minutes, and rewarmed to 37 degrees C. The cerebral metabolic rate of oxygen consumption (a marker for neurologic function) was significantly lower after circulatory arrest in the shunt animals cooled with alpha-stat blood gas management than in the control animals subjected to alpha-stat management (1.2 +/- 0.2 vs 2.3 +/- 0.2 ml oxygen per 100 gm/min, p < 0.05). By contrast, there was no difference between the pH-stat shunt animals and either control group (2.1 +/- 0.2 vs 2.3 +/- 0.2 [alpha-stat] and 2.0 +/- 0.3 [pH-stat] ml oxygen per 100 gm/min, p = not significant). pH-Stat cooling protected the brain from shunt-related injury. When circulatory arrest is used in the presence of aortopulmonary collaterals, the use of pH-stat blood gas management during cooling results in better cerebral protection than alpha-stat blood gas management.

Effects of aortopulmonary collaterals on cerebral cooling and cerebral metabolic recovery after circulatory arrest.

BACKGROUND: Aortopulmonary collaterals (APC) have been associated with an increased risk of choreoathetosis after deep hypothermic circulatory arrest (DHCA). To study the effects of APC on cerebral hemodynamics and metabolism before and after DHCA, a piglet model was developed. METHODS AND RESULTS: Protocol 1: Eight 4- to 6-week-old piglets underwent placement of a left subclavian-to-main pulmonary artery shunt. Control shunts (n = 4) were ligated, APC shunts (n = 4) were left patent. All animals were placed on cardiopulmonary bypass (CPB) and cooled in identical fashion for 20 minutes. Temperature probes were placed in the nasopharynx, cortex, and deep brain. Control animals achieved significantly lower temperatures in all three areas by the end of cooling (17.5 degrees C versus 20.1 degrees C, 19.0 degrees C versus 22.3 degrees C, and 17.5 degrees C versus 21.0 degrees C, respectively, P < .005). Protocol 2: Six control and six APC animals were instrumented as described. All were placed on CPB, cooled to 18 degrees C, arrested for 90 minutes, and rewarmed to 37 degrees C. Cerebral blood flow (CBF) was measured with radioactive microspheres while warm on CPB, after cooling, and after rewarming. Arterial and sagittal sinus blood gases and CBF were used to calculate the cerebral metabolic rate of oxygen consumption (CMRO2). Both CBF and CMRO2 were significantly higher after rewarming to 37 degrees C in control versus APC animals (28 +/- 3 versus 14 +/- 2 mL/100 g per minute and 1.72 +/- 0.21 versus 1.04 +/- 0.14 mL O2/100 g per minute, respectively, P < .05). CONCLUSIONS: APC decrease the rate of cerebral cooling on CPB and even if temperature is controlled result in increased cerebral metabolic derangement after DHCA. Patients with such collaterals may need additional measures to optimize cerebral protection.