Pharmacokinetics and safety of intravenously administered citrulline in children undergoing congenital heart surgery: potential therapy for postoperative pulmonary hypertension.

OBJECTIVE: Pulmonary hypertension may complicate surgical correction of congenital heart defects, resulting in increased morbidity and mortality. We have previously shown that plasma levels of the nitric oxide precursors citrulline and arginine drop precipitously after congenital cardiac surgery and that oral citrulline supplementation may be protective against the development of pulmonary hypertension. In this study, we assessed the safety and pharmacokinetic profile of intravenous citrulline as a potential therapy for postoperative pulmonary hypertension. METHODS: The initial phase of this investigation was a dose-escalation study of intravenously administered citrulline in infants and children undergoing one of five congenital cardiac surgical procedures (phase 1). The primary safety outcome was a 20% drop in mean arterial blood pressure from the baseline pressure recorded after admission to the intensive care unit. Based on our previous work, the target circulating plasma citrulline trough was 80 to 100 micromol/L. Each patient was given two separate doses of citrulline: the first in the operating room immediately after initiation of cardiopulmonary bypass and the second 4 hours later in the pediatric intensive care unit. Stepwise dose escalations included 50 mg/kg, 100 mg/kg, and 150 mg/kg. After model-dependent pharmacokinetic analysis, we enrolled an additional 9 patients (phase 2) in an optimized dosing protocol that replaced the postoperative dose with a continuous infusion of citrulline at 9 mg/(kg.h) for 48 hours postoperatively. RESULTS: The initial stepwise escalation protocol (phase 1) revealed that an intravenous citrulline dose of 150 mg/kg given after initiation of cardiopulmonary bypass yielded a trough level of in the target range of approximately 80 to 100 micromol/L 4 hours later. The postoperative dose revealed that the clearance of intravenously administered citrulline was 0.6 L/(h.kg), with a volume of distribution of 0.9 L/kg and estimated half-life of 60 minutes. Because of the short half-life, we altered the protocol to replace the postoperative dose with a continuous infusion of 9 mg/(kg.h). An additional 9 patients were studied with this continuous infusion protocol (phase 2). Mean plasma citrulline levels were maintained at approximately 125 mumol/L, with a calculated clearance of 0.52 L/(h.kg). None of the 17 patients studied had a 20% drop in mean arterial blood pressure from baseline. CONCLUSIONS: In this first report of the use of intravenous citrulline in humans, we found citrulline to be both safe and well tolerated in infants and young children undergoing congenital cardiac surgery. Because of the rapid clearance, the optimal dosing regimen was identified as an initial bolus of 150 mg/kg given at the initiation of cardiopulmonary bypass, followed 4 hours later by a postoperative infusion of 9 mg/(kg.h) continued up to 48 hours. Using this regimen, plasma arginine, citrulline, and nitric oxide metabolite levels were well maintained. Intravenous citrulline needs to be studied further as a potential therapy for postoperative pulmonary hypertension.

Recombinant factor seven therapy for postoperative bleeding in neonatal and pediatric cardiac surgery.

BACKGROUND: Severe bleeding is a major complication in the postoperative pediatric cardiac surgery patients. We evaluated the efficacy and safety of recombinant factor seven (rFVIIa) therapy in this patient population. METHODS: A retrospective unmatched case-control study for the previous five years in a single institution was undertaken. Patients with severe bleeding treated with rFVIIa therapy (study group) were compared with patients treated with blood products only (control group) using analysis of variance. Mediastinal bleeding, blood products transfusion, and coagulation studies before and six hours after the first dose of rFVIIa therapy were analyzed using the Student paired t test. The dose, frequency, and side-effects of rFVIIa therapy were studied. RESULTS: Forty-six patients with severe bleeding were studied. Twenty-three of 24 patients in the study group, including 12 patients placed on extracorporeal membrane oxygenation (ECMO), responded to rFVIIa therapy (mean dose 43 +/- 22.9 microg/kg/dose). There was significant reduction in chest tube drainage (from 52.3 +/- 36.1 mL/kg/hour to 18.8 +/- 20.9 mL/kg/hour, p = 0.0003) along with significant reduction of blood products transfusion (p < 0.001) in the study group patients as compared with control group patients. One patient who failed to respond had surgical bleeding. Two patients developed major thrombotic complications that included clots in the ECMO circuit and thrombosis at bleeding arterial line site resulting in limb ischemia. Four additional patients in the study group developed mediastinal clots. Overall, 25% of patients developed thrombosis after rFVIIa therapy. CONCLUSIONS: The rFVIIa therapy seems to be an effective treatment for severe bleeding in postoperative pediatric cardiac surgery patients in the absence of surgical bleeding. It must be judiciously used in patients bleeding from multiple sites or having preexistent clots in the ECMO circuit to prevent major thrombotic complications.

Retrospective analysis of local sensorimotor deficits after radial artery harvesting for coronary artery bypass grafting.

OBJECTIVES: The radial artery (RA) has gained widespread acceptance as a conduit for coronary artery bypass. We analyze patient-based data to determine risk factors for long-term upper limb morbidities associated with RA harvest for coronary artery bypass grafting. STUDY DESIGN/METHODS: Between April 1997 and March 2004, a total of 1030 patients underwent RA harvesting for coronary artery bypass grafting for a total of 1704 harvest sites. Patients were contacted by telephone and asked to report any ongoing severe sensory and functional motor deficits for each harvest site since surgery. Retrospective chart review was performed and preoperative risk factors were evaluated. Patient-based risk factors were evaluated for development of significant long-term local sensorimotor deficits including gender, elderly age (>70 y), diabetes, smoking, and whether the RA was harvested from the dominant hand. RESULTS: Successful evaluation of 629 patients for a total of 1048 RA harvest sites was completed. The mean follow-up time was 48.3 mo (range, 2 to 86 mo). The mean age of the patients analyzed was 62.2 y. On statistical analysis, diabetics and elderly did not report significantly greater functional or sensory deficits than nondiabetics and nonelderly, respectively. There was a significantly higher incidence of sensory deficits in smokers compared with nonsmoker patients (4.2% versus 1.4%; P = 0.005) but no difference in their functional impairment was noted. Harvesting from the dominant hand did not influence the occurrence of sensory or motor functional deficits. CONCLUSIONS: RA harvesting for coronary artery bypass grafting can be done with minimal serious long-term upper limb morbidity in higher risk patients. Based on our findings, harvesting of the RA from the dominant hand is not contraindicated in these patients.

Genetic variation in the mitochondrial enzyme carbamyl-phosphate synthetase I predisposes children to increased pulmonary artery pressure following surgical repair of congenital heart defects: a validated genetic association study.

Increased pulmonary artery pressure (PAP) can complicate the postoperative care of children undergoing surgical repair of congenital heart defects. Endogenous NO regulates PAP and is derived from arginine supplied by the urea cycle. The rate-limiting step in the urea cycle is catalyzed by a mitochondrial enzyme, carbamoyl-phosphate synthetase I (CPSI). A well-characterized polymorphism in the gene encoding CPSI (T1405N) has previously been implicated in neonatal pulmonary hypertension. A consecutive modeling cohort of children (N=131) with congenital heart defects requiring surgery was prospectively evaluated to determine key factors associated with increased postoperative PAP, defined as a mean PAP>20 mmHg for at least 1h during the 48h following surgery measured by an indwelling pulmonary artery catheter. Multiple dimensionality reduction (MDR) was used to both internally validate observations and develop optimal two-variable through five-variable models that were tested prospectively in a validation cohort (N=41). Unconditional logistic regression analysis of the modeling cohort revealed that age (OR=0.92, p=0.01), CPSI T1405N genotype (AC vs. AA: OR=4.08, p=0.04, CC vs. AA: OR=5.96, p=0.01), and Down syndrome (OR=5.25, p=0.04) were independent predictors of this complex phenotype. MDR predicted that the best two-variable model consisted of age and CPSI T1405N genotype (p<0.001). This two-variable model correctly predicted 73% of the outcomes from the validation cohort. A five-variable model that added race, gender and Down's syndrome was not significantly better than the two-variable model. In conclusion, the CPSI T1405N genotype appears to be an important new factor in predicting susceptibility to increased PAP following surgical repair of congenital cardiac defects in children.

Rapid diagnosis of cannula migration by cerebral oximetry in neonatal arch repair.

Although it has gained much interest in other surgical specialties, the application of near-infrared spectroscopy to assess cerebral perfusion during cardiac surgery is relatively new. Regional cerebral oxygen saturation (rSO2) is a function of cerebral oxygen supply and demand. Continuous monitoring of the rSO2 permits early detection of cerebral ischemia allowing for prompt intervention. The following is a description of a repair of truncus arteriosus with type A interrupted aortic arch during which continuous cerebral oximetry assisted with the positioning of the arterial cannula avoiding a prolonged episode of cerebral ischemia.

Nitric oxide precursors and congenital heart surgery: a randomized controlled trial of oral citrulline.

OBJECTIVE: The study sought to determine whether citrulline supplementation, a precursor to nitric oxide synthesis, is safe and efficacious in increasing plasma citrulline concentrations and decreasing the risk of postoperative pulmonary hypertension. STUDY DESIGN: Forty children, undergoing cardiopulmonary bypass and at risk for pulmonary hypertension, were randomized to receive 5 perioperative doses (1.9 g/m2 per dose) of either oral citrulline or placebo. Plasma citrulline and arginine concentrations were measured at 5 time points. Measurements of systemic blood pressure and presence of pulmonary hypertension were collected. RESULTS: Median citrulline concentrations were significantly higher in the citrulline group versus the placebo group immediately postoperatively (36 micromol/L vs 26 micromol/L, P = .012) and at 12 hours postoperatively (37 micromol/L vs 20 micromol/L, P = .015). Mean plasma arginine concentrations were significantly higher in the citrulline group versus the placebo group by 12 hours postoperatively (36 micromol/L vs 23 micromol/L, P = .037). Mean systemic blood pressure did not differ between groups (P = .53). Postoperative pulmonary hypertension developed in 9 patients, 6 of 20 (30%) in the placebo group and 3 of 20 (15%) in the citrulline group (P = .451), all of whom had plasma citrulline concentrations less than age-specific norms. Postoperative pulmonary hypertension did not develop in patients who demonstrated plasma citrulline concentrations in excess of 37 mumol/L (P = .036). CONCLUSIONS: Oral citrulline supplementation safely increased plasma citrulline and arginine concentrations compared with placebo after cardiopulmonary bypass. Postoperative pulmonary hypertension did not occur in children with naturally elevated citrulline levels or elevations through supplementation. Oral citrulline supplementation may be effective in reducing postoperative pulmonary hypertension.

Plastic bronchitis: is thoracic duct ligation a real surgical option?

Plastic bronchitis is an unusual clinical scenario of unknown cause and occurs in multiple clinical settings. The disease is characterized by the development of arborizing, thick, tenacious casts of the tracheobronchial tree that results in airway obstruction. Patients with congenital heart disease who have undergone a Fontan operation are at high risk for having this problem develop. Management of this distressing situation is difficult with only palliative options being available, such as repeated bronchoscopies, inhaled heparin, tissue plasminogen activator, inhaled bronchodilators, or azithromycin. The patients with Fontan circuits have a myriad of unique complications develop, such as atrial arrhythmias, recurrent pleural effusions, chylothoraces, protein-losing enteropathy, and plastic bronchitis. High intrathoracic lymphatic pressures with nondemonstrable lympho-bronchial fistulas were believed to be the cause for the development of these recurrent bronchial casts in plastic bronchitis. Faced with recurrent plastic bronchitis resistant to medical management in 2 Fontan patients with normal Fontan pressures on cardiac catheterization, we decided to explore a surgical solution by performing a thoracic duct ligation. This resulted in complete resolution of the formation of casts in both patients, who were discharged home and remain asymptomatic on continued follow-up. Thoracic duct ligation provides a surgical cure for plastic bronchitis by decreasing intrathoracic lymphatic pressure and flow.

Inhaled nitric oxide use in bidirectional Glenn anastomosis for elevated Glenn pressures.

BACKGROUND: Children frequently undergo bidirectional Glenn anastomosis in the staged surgical management of single ventricle physiology. The purpose of our study was to investigate the role of inhaled nitric oxide therapy in children with marked elevations in Glenn pressures after this surgery. METHODS: A retrospective study over a 30-month period was performed. The effect of inhaled nitric oxide therapy was analyzed in children with marked elevations of Glenn pressures resulting in decreased systemic perfusion. Effects on Glenn pressures, respiratory indices, and systemic perfusion were evaluated after initiation of nitric oxide therapy and compared with baseline parameters. RESULTS: Sixteen patients were placed on nitric oxide therapy for marked elevations of Glenn pressures (22.4 +/- 3.9 mm Hg). In the 11 responsive patients, there were significant reductions in Glenn pressures (from 22.4 mm Hg to 17.1 mm Hg, p < 0.001) and significant improvement in partial pressure of oxygen to fraction of inspired oxygen ratio (from 49 to 74.3, p = 0.001) and oxygenation index (from 17 to 12, p = 0.005). There was simultaneous significant reduction in inotrope score (from 14.9 to 11.4, p < 0.001) and fluid volume support (from 11.4 mL/kg to 2.3 mL/kg, p < 0.001) in the responsive patients. Five patients that failed to show any response were found, subsequently, to have an anatomic lesion. CONCLUSIONS: Inhaled nitric oxide produces significant reduction in Glenn pressures and improvement in systemic perfusion and pulmonary gas exchange in patients with marked elevations of Glenn pressures after bidirectional Glenn anastomosis. Patients who fail to respond should be investigated for an anatomic lesion.

Clinical outcomes of 84 children with congenital heart disease managed with extracorporeal membrane oxygenation after cardiac surgery.

The purpose of our research was to study the clinical outcomes of children with congenital heart disease (CHD) requiring extracorporeal membrane oxygenation (ECMO) support after cardiac surgery at a tertiary care children's hospital. Retrospective review of all patients with CHD who required postcardiotomy ECMO between January 2001 and September 2004 (45 months) was undertaken. Various outcome predictors were tested for any association with survival to hospital discharge using univariate analysis. A total of 84 children were placed on ECMO after CHD surgery; 39 (46.4%) were placed on ECMO in the operating room. Median age of the patients was 128 days (1 day to 5 years) and median weight was 4.53 kg (2-18 kg). Active cardiopulmonary resuscitation was ongoing at the time of cannulation in 27 children (32%). Fifty-two children (61.9) survived > 24 hours after decannulation and 31 (36.9%) survived to discharge. High arterial serum lactate levels at the time of ECMO initiation were strongly correlated with nonsurvival (p = 0.004). Nonsurvivors had longer duration on ECMO than survivors (p = 0.003). The odds of survival dropped significantly after 144 hours (day 6) of ECMO. ECMO support results in improved outcomes in patients who suffered hemodynamic collapse post cardiac surgery. Underlying cardiac lesion, age, weight, gender, initial arterial pH, location of ECMO initiation, need for hemofiltration and placement of ECMO after active ongoing cardiopulmonary resuscitation did not increase the mortality risk. Initial arterial serum lactate level and inability to wean off by 6 days were strongly correlated with nonsurvival.

Expression of multiple KCNE genes in human heart may enable variable modulation of I(Ks).

Voltage-gated potassium (K(V)) channels are modulated by at least three distinct classes of proteins including the KCNE family of single transmembrane accessory subunits. In the human genome, KCNE proteins are encoded by five genes designated KCNE1 through KCNE5. KCNE1 associates with KCNQ1 in vitro to generate a potassium current closely resembling the slowly activating delayed rectifier (I(Ks)). Other KCNE proteins also affect the activity of heterologously expressed KCNQ1. To investigate the potential physiological relevance of this gene family in human heart, we examined the relative expression of KCNQ1 and all five KCNE genes in samples derived from normal tissues representing major regions of human heart by real-time, quantitative RT-PCR. KCNE genes are expressed in human heart with a relative abundance ranking of KCNE1 > KCNE4 > KCNE5 approximately KCNE3 >> KCNE2. In situ hybridization revealed prominent expression of KCNE1 and KCNE3-5 in human atrial myocytes. In cardiomyopathic hearts, expression of KCNE1, KCNE3, KCNE4, and KCNQ1 was significantly increased, while KCNE2 and KCNE5 exhibited reduced expression. In a cell line stably expressing KCNQ1 and KCNE1, transient expression of KCNE3, KCNE4, or KCNE5 significantly altered I(Ks) current profiles. Even in the presence of additional KCNE1, KCNE4 and KCNE5 exert dominant effects on I(Ks). Although KCNE1 is the predominant KCNE family member expressed in human heart, the abundance of other KCNE transcripts including potential KCNQ1 suppressors (KCNE4 and KCNE5) and their altered expression patterns in disease lead us to speculate that a balance of KCNE accessory subunits may be important for cardiac K(V) channel function.

Cerebral activation of mitogen-activated protein kinases after circulatory arrest and low flow cardiopulmonary bypass.

OBJECTIVES: Mitogen-activated protein kinases (MAPK) are important intermediates in the signal transduction pathways involved in neuronal dysfunction following cerebral ischemia-reperfusion injury. One subfamily, extracellular regulated kinase 1/2, has been heavily implicated in the pathogenesis of post-ischemic neuronal damage. However, the contribution of extracellular regulated kinase 1/2 to neuronal damage following deep hypothermic circulatory arrest and low flow cardiopulmonary bypass is unknown. We attempted to correlate the extent of neuronal damage present following deep hypothermic circulatory arrest and low flow cardiopulmonary bypass with phosphorylated extracellular regulated kinase 1/2 expression in the cerebral vascular endothelium. METHODS: Piglets underwent normal flow cardiopulmonary bypass (n=4) deep hypothermic circulatory arrest (n=6) and low flow cardiopulmonary bypass (n=5). Brains were harvested following 24 h of post-cardiopulmonary bypass recovery. Cerebral cortical watershed zones, hippocampus, basal ganglia, thalamus, cerebellum, mesencephalon, pons and medulla were evaluated using hematoxylin and eosin staining. A section of ischemic cortex was evaluated by immunohistochemistry with rabbit polyclonal antibodies against phosphorylated extracellular regulated kinase 1/2. RESULTS: Compared to cardiopulmonary bypass controls, the deep hypothermic circulatory arrest and low flow cardiopulmonary bypass piglets exhibited diffuse ischemic changes with overlapping severity and distribution. Significant neuronal damage occurred in the frontal watershed zones and basal ganglia of the deep hypothermic circulatory arrest group (P<0.05). No detectable phosphorylated extracellular regulated kinase 1/2 immunoreactivity was found in the cardiopulmonary bypass controls; however, ERK 1/2 immunoreactivity was present in the cerebral vascular endothelium of the deep hypothermic circulatory arrest and low flow cardiopulmonary bypass groups. CONCLUSIONS: Our results indicate that phosphorylated extracellular regulated kinase 1/2 may play a prominent role in early cerebral ischemia-reperfusion injury and endothelial dysfunction. The pharmacologic inhibition of extracellular regulated kinase 1/2 represents a new and exciting opportunity for the modulation of cerebral tolerance to low flow cardiopulmonary bypass and deep hypothermic circulatory arrest.

Blockade of the extracellular signal-regulated kinase pathway by U0126 attenuates neuronal damage following circulatory arrest.

OBJECTIVES: The extracellular signal-regulated kinase pathway of the mitogen-activated protein kinase signal transduction cascade has been implicated in the neuronal and endothelial dysfunction witnessed following cerebral ischemia-reperfusion injury. Extracellular signal-regulated kinase is activated by mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2. We evaluated the ability of a mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2-specific inhibitor (U0126) to block extracellular signal-regulated kinase activation and mitigate ischemic neuronal damage in a model of deep hypothermic circulatory arrest. METHODS: Piglets underwent normal flow cardiopulmonary bypass (control, n = 4), deep hypothermic circulatory arrest (n = 6), and deep hypothermic circulatory arrest with U0126 (n = 5) at 20 degrees C for 60 minutes. The deep hypothermic circulatory arrest with U0126 group was given 200 microg/kg of U0126 45 minutes prior to initiation of bypass followed by 100 microg/kg at reperfusion. Following 24 hours of post-cardiopulmonary bypass recovery, brains were harvested. Eleven distinct cortical regions were evaluated for neuronal damage using hematoxylin and eosin staining. A section of ischemic cortex was further evaluated by immunohistochemistry with rabbit polyclonal antibody against phosphorylated extracellular signal-regulated kinase 1/2. RESULTS: The deep hypothermic circulatory arrest and deep hypothermic circulatory arrest with U0126 groups displayed diffuse ischemic changes. However, the deep hypothermic circulatory arrest with U0126 group possessed significantly lower neuronal damage scores in the right frontal watershed zone of cerebral cortex, basal ganglia, and thalamus (P < or =.05) and an overall trend toward neuroprotection versus the deep hypothermic circulatory arrest group. This neuroprotection was accompanied by nearly complete blockade of phosphorylated extracellular signal-regulated kinase in the cerebral vascular endothelium. CONCLUSIONS: In this experimental model of deep hypothermic circulatory arrest, U0126 blocked extracellular signal-regulated kinase activation and provided a significant neuroprotective effect. These results support targeting of the extracellular signal-regulated kinase pathway for inhibition as a novel therapeutic approach to mitigate neuronal damage following deep hypothermic circulatory arrest.

Modeling the effects of functional performance and post-transplant comorbidities on health-related quality of life after heart transplantation.

BACKGROUND: Health-related quality of life and functional performance are important outcome measures following heart transplantation. This study investigates the impact of pre-transplant functional performance and post-transplant rejection episodes, obesity and osteopenia on post-transplant health-related quality of life and functional performance. METHODS: Functional performance and health-related quality of life were measured in 70 adult heart transplant recipients. A composite health-related quality of life outcome measure was computed via principal component analysis. Iterative, multiple regression-based path analysis was used to develop an integrated model of variables that affect post-transplant functional performance and health-related quality of life. RESULTS: Functional performance, as measured by the Karnofsky scale, improved markedly during the first 6 months post-transplant and was then sustained for up to 3 years. Rejection Grade > or =2 was negatively associated with health-related quality of life, measured by Short Form-36 and reversed Psychosocial Adjustment to Illness Scale scores. Patients with osteopenia had lower Short Form-36 physical scores and obese patients had lower functional performance. Path analysis demonstrated a negative direct effect of obesity (beta = - 0.28, p < 0.05) on post-transplant functional performance. Post-transplant functional performance had a positive direct effect on the health-related quality of life composite score (beta = 0.48, p < 0.001), and prior rejection episodes grade > or =2 had a negative direct effect on this measure (beta = -0.29, p < 0.05). Either directly or through effects mediated by functional performance, moderate-to-severe rejection, obesity and osteopenia negatively impact health-related quality of life. These findings indicate that efforts should be made to devise immunosuppressive regimens that reduce the incidence of acute rejection, weight gain and osteopenia after heart transplantation.

Bilateral pectoral myocutaneous advancement flaps and anatomic sternal wound reconstruction in cyanotic infants with mediastinitis.

OBJECTIVE: The purpose of this study was to assess the results and applicability of a modified chest closure technique employing bilateral pectoral myocutaneous advancement flaps after sternal re-approximation for postoperative mediastinitis in cyanotic infants. METHODS: The study population is of a single surgeon's pediatric cardiac experience (n = 253) over a 2-year period. With retrospective hospital chart review six cases with deep sternal wound complications were identified (five mediastinitis and one hypoxemic wound necrosis). Sternal wound reconstruction was done with the above technique in all cases. Follow up was completed by outpatient record review and with telephone interviews. RESULTS: All six cases presented in this paper were neonates or infants with complex cyanotic cardiac malformations. Following chest wall reconstruction all had complete resolution of their mediastinitis with no mortality and no wound healing complications. Three of them have since undergone elective staged repair, with no evidence of residual wound infection. Two babies died during follow-up as a result of progressive respiratory compromise. CONCLUSION: For postcardiotomy mediastinitis in cyanotic infants we recommend limited debridement and anatomic sternal reconstruction supported by bilateral pectoral myocutaneous advancement flap closure.

Factor V Leiden protects against blood loss and transfusion after cardiac surgery.

BACKGROUND: The outcome of cardiac surgery is influenced by several factors, but the impact of specific genetic variants has not been systematically explored. Because blood conservation is a pressing issue in cardiac surgery, we tested the hypothesis that factor V Leiden (FVL), a common coagulation factor polymorphism, may protect against blood loss and transfusion in patients undergoing cardiac surgery. METHODS AND RESULTS: We enrolled 517 patients undergoing cardiac surgery, including 26 heterozygous FVL carriers, and evaluated the impact of FVL on chest tube output and transfusion by using univariate and multivariate techniques. For patients with FVL, blood loss at 6 (238+/-131 mL) and 24 hours (522+/-302 mL) was significantly lower than that for noncarriers (358+/-259 mL and 730+/-452 mL; P<0.001 and P=0.001, respectively). In a multivariate regression analysis, controlling for ethnicity and factors known to affect blood loss, FVL was a significant independent contributor at both time points. Using a similar regression approach, FVL did not have a significant effect on the number of units transfused. However, logistic regression of the risk of receiving any transfusion during hospitalization demonstrated a significant independent protective effect of FVL on overall transfusion risk. CONCLUSIONS: FVL represents a common genetic trait that may protect against blood loss and transfusion in this population. This study demonstrates that genetic variability can affect the outcome of cardiac surgery.

Morbidity after procurement of radial arteries in diabetic patients and the elderly undergoing coronary revascularization.

BACKGROUND: The use of radial arteries for coronary revascularization is increasing. There remain concerns regarding alteration of upper extremity function after radial artery procurement. This study evaluates the functional morbidity in higher risk patients. METHODS: Between April 1997 and September 1999, 374 patients underwent unilateral or bilateral radial artery procurement. A questionnaire was used to evaluate symptoms related to motor and sensory function and changes in appearance after radial artery harvest. RESULTS: Two hundred eighty-nine patients were successfully interviewed. The average age was 63 years. Median follow-up was 9.5 months (range, 2 to 23 months). No patient suffered limb loss. Altered gross and fine motor function, residual pain, paresthesias, numbness, pallor, swelling, and altered temperature sensation were compared among diabetic patients, patients older than 70 years, and patients without these characteristics. CONCLUSIONS: Radial artery procurement for elective coronary revascularization can be done with minimal serious morbidity in higher risk patients. The most common symptoms were numbness and paresthesia. Despite the finding of greater residual pain in diabetic patients, we do not believe the use of radial artery conduits is contraindicated in these patients.

Left ventricular assist device implantation via left thoracotomy: alternative to repeat sternotomy.

Repeat sternotomy for left ventricular assist device insertion may result in injury to the right heart or patent coronary grafts, complicating intraoperative and postoperative management. In 4 critically ill patients, left thoracotomy was used as an alternative to repeat sternotomy. Anastomosis of the outflow conduit to the descending thoracic aorta provided satisfactory hemodynamic support.