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Biomedical subjects

Jeffrey M Pearl

Publications and source records attributed to Jeffrey M Pearl.

At least 19 recordsLinked to original sources
PubMed2006

Pulmonary atresia with intact ventricular septum: initial management.

BACKGROUND: Outcomes for pulmonary atresia with intact ventricular septum are suboptimal, while initial management remains controversial. This study was undertaken to determine the effect of catheter-based therapy on the need for early surgical intervention. METHODS: A single-institution retrospective chart review was made of all 25 neonates with pulmonary atresia with intact ventricular septum from 1999 to 2005. RESULTS: Mean age at first intervention was 3.1 +/- 2.2 days, mean weight 3.3 +/- 0.5 kg. Right ventricular hypoplasia varied: 20% normal, 16% mild, 28% moderate, 28% moderately severe or severe, 8% not classified. Median tricuspid valve z-score was -2.3 +/- 2.6. First intervention was catheter-based therapy in 56% (14 of 25), operative in 36% (9 of 25), and no therapy in 2. Technically adequate valvotomy was achieved in 79% (11 of 14). Serious catheter-related complications occurred in 3 of 14 (21%). Only 5 of 14 (36%) with catheter-based therapy weaned from prostaglandins without surgery. Of these, 2 required surgery for cyanosis at 1 and 3 months. Surgery after catheter-based therapy consisted of right ventricular outflow patch in 36% (4 of 11), systemic to pulmonary shunt in 64% (7 of 11). Median time between catheter-based therapy and surgery was 8.5 days (range, 1 to 89). Only 3 of the 23 treated patients avoided operation during infancy. There was 1 early and 1 late death after operation after initial catheter-based therapy, and 1 late death after primary surgery alone during a mean follow-up of 33 months (range, 1.5 to 79). CONCLUSIONS: Balloon valvotomy alone for pulmonary atresia with intact ventricular septum rarely obviates the need for an additional source of pulmonary blood flow--either shunt or ductal stenting.

Cardiac Surgical Procedures↗
PubMed2006

Brain magnetic resonance imaging abnormalities after the Norwood procedure using regional cerebral perfusion.

OBJECTIVES: Neurologic deficits are common after the Norwood procedure for hypoplastic left heart syndrome. Because of the association of deep hypothermic circulatory arrest with adverse neurologic outcome, regional low-flow cerebral perfusion has been used to limit the period of intraoperative brain ischemia. To evaluate the impact of this technique on brain ischemia, we performed serial brain magnetic resonance imaging in a cohort of infants before and after the Norwood operation using regional cerebral perfusion. METHODS: Twenty-two term neonates with hypoplastic left heart syndrome were studied with brain magnetic resonance imaging before and at a median of 9.5 days after the Norwood operation. Results were compared with preoperative, intraoperative, and postoperative risk factors to identify predictors of neurologic injury. RESULTS: Preoperative magnetic resonance imaging (n = 22) demonstrated ischemic lesions in 23% of patients. Postoperative magnetic resonance imaging (n = 15) demonstrated new or worsened ischemic lesions in 73% of patients, with periventricular leukomalacia and focal ischemic lesions occurring most commonly. Prolonged low postoperative cerebral oximetry (<45% for >180 minutes) was associated with the development of new or worsened ischemia on postoperative magnetic resonance imaging (P = .029). CONCLUSIONS: Ischemic lesions occur commonly in neonates with hypoplastic left heart syndrome before surgery. Despite the adoption of regional cerebral perfusion, postoperative cerebral ischemic lesions are frequent, occurring in the majority of infants after the Norwood operation. Long-term follow-up is necessary to assess the functional impact of these lesions.

Brain Ischemia↗
PubMed2006

Current treatments for congenital aortic stenosis.

PURPOSE OF REVIEW: Congenital valvar aortic stenosis is a challenging disease that often requires repeated palliative procedures. Stenosis can range from mild and asymptomatic, not requiring intervention, to severe, as seen in hypoplastic left heart syndrome. New advances such as fetal balloon valvuloplasty, improvements in the Ross technique, and long-term studies of trans-catheter balloon valvuloplasty and surgical valvotomy warrant a review of the outcomes and optimal timing of the various interventions. RECENT FINDINGS: Fetal balloon valvuloplasty has shown promise. Despite some mortality and morbidity, some fetuses are showing significant growth in left ventricular structures, allowing biventricular repair. In neonates and infants with congenital aortic stenosis, excellent initial results are obtained with trans-catheter balloon valvuloplasty, although stenosis resistant to further balloon dilation or regurgitation may develop, necessitating surgical intervention. Midterm results from the Ross procedure are encouraging, demonstrating low rates of mortality, aortic insufficiency and re-intervention. Stenosis of the pulmonary allograft may be inevitable, and recent long-term follow-up suggests an increase in aortic insufficiency. SUMMARY: While availability of fetal balloon valvuloplasty is limited, it has promise for promoting in-utero left ventricle growth and improving function. The optimal procedure for infants and neonates is trans-catheter balloon valvuloplasty. For older patients, the Ross procedure is the repair of choice, although more long-term studies are needed to assess the natural course of the autograft. Outcomes should improve with advances in pulmonary allografts.

Aortic Valve Stenosis↗
PubMed2006

Bilateral semilunar valve disease in a child with partial deletion of the Williams-Beuren syndrome region is associated with elastin haploinsufficiency.

Elastin is an extracellular matrix protein that is the primary component of elastic fibers, and is expressed in the great vessels as well as the semilunar and atrioventricular valves. Elastin haploinsufficiency, resulting from mutation or deletion of the elastin gene, is an important clinical problem that is typically characterized by arteriopathy. Herein is described a patient with elastin haploinsufficiency due to partial deletion of the Williams-Beuren syndrome region, resulting in bilateral semilunar valve disease and arteriopathy. Histochemical analysis of the aortic valve revealed decreased and disorganized elastin with loss of the normal trilaminar cusp organization. These findings suggest that elastin has a role in the pathogenesis of semilunar valve disease.

Echocardiography↗
PubMed2005

Glucocorticoid administration reduces cardiac dysfunction after brain death in pigs.

BACKGROUND: Traumatic brain injury and subsequent brain death (BD) account for nearly half of all organ donors, yet only 33% of available hearts are transplanted. Alterations in multiple physiologic pathways after BD can lead to cardiac dysfunction and exclusion from transplantation. Triple hormone resuscitation with methylprednisolone, thyroid hormone and vasopressin has had inconsistent results in the effort to reduce cardiac dysfunction associated with BD, but individual analysis of these agents is limited. The hypothesis was that glucocorticoid administration alone could reduce BD-associated cardiac dysfunction. METHODS: Crossbred pigs (25 to 35 kg) had BD induced by sub-dural balloon inflation. Hemodynamics were measured for 360 minutes after BD. Negative cerebral perfusion pressures and decreased laser Doppler cerebral blood flow confirmed BD. Animals (n = 5/treatment group) received: saline (Group 1); 30 mg/kg methylprednisolone 2 hours before BD (Group 2); or 30 mg/kg methylprednisolone 1 hour after BD (Group 3). Repeated measures analysis of variance and unpaired t-tests were used for appropriate comparisons. RESULTS: Left ventricular (LV) pre-load recruitable stroke work (PRSW) decreased in untreated Group 1 over time (p < 0.001), whereas PRSW in animals treated with glucocorticoids, Groups 2 and 3, was not different from baseline at 360 minutes after BD. Diastolic function measured as LV -dP/dt (minimum derivative of the change in pressure over time) and tau (time constant of isovolumic relaxation) was also preserved 360 minutes after brain death by glucocorticoids in Groups 2 and 3 (p > 0.05). Oxygen delivery 360 minutes after BD was higher in Group 2 compared with Group 1 (p = 0.02) and Group 3 (p = 0.006). CONCLUSIONS: Glucocorticoid therapy before or after BD preserved LV systolic and diastolic function. Glucocorticoids administered after brain death might increase the number of hearts available for transplant by reducing brain death-associated cardiac dysfunction.

Animals↗
PubMed2005

Inhibition of p38 reduces myocardial infarction injury in the mouse but not pig after ischemia-reperfusion.

The MAPK family member p38 is activated in the heart after ischemia-reperfusion (I/R) injury. However, the cardioprotective vs. proapoptotic effects associated with p38 activation in the heart after I/R injury remain unresolved. Another issue to consider is that the majority of past studies have employed the rodent as a model for assessing p38's role in cardiac injury vs. protection, while the potential regulatory role in a large animal model is even more uncertain. Here we performed a parallel study in the mouse and pig to directly compare the extent of cardiac injury after I/R at baseline or with the selective p38 inhibitor SB-239063. Infusion of SB-239063 5 min before ischemia in the mouse prevented ischemia-induced p38 activation, resulting in a 25% reduction of infarct size compared with vehicle-treated animals (27.9 +/- 2.9% vs. 37.5 +/- 2.7%). In the pig, SB-239063 similarly inhibited myocardial p38 activation, but there was no corresponding effect on the degree of infarction injury (43.6 +/- 4.0% vs. 41.4 +/- 4.3%). These data suggest a difference in myocardial responsiveness to I/R between the small animal mouse model and the large animal pig model, such that p38 activation in the mouse contributes to acute cellular injury and death, while the same activation in pig has no causative effect on these parameters.

Animals↗
PubMed2005

Role of the beta-adrenergic receptor kinase in myocardial dysfunction after brain death.

OBJECTIVE: Significant cardiac dysfunction after brain death leading to exclusion from procurement for cardiac transplantation is seen in up to 25% of potential organ donors in the absence of structural heart disease. The cause includes uncoupling of the myocardial beta-adrenergic receptor signaling system. The mechanism, however, has not yet been described. This study investigates our hypothesis that brain death causes acute activation of the betaAR kinase and leads to desensitization of myocardial beta-adrenergic receptors and impaired ventricular function. METHODS: Adult pigs underwent a sham operation or induction of brain death by means of subdural balloon inflation (n = 8 in each group). Cardiac function was assessed by using sonomicrometry at baseline and for 6 hours after the operation. beta-Adrenergic receptor signaling was assessed at 6 hours after the operation by measuring myocardial sarcolemmal membrane adenylate cyclase activity, beta-adrenergic receptor density, beta-adrenergic receptor kinase expression, and activity. RESULTS: Induction of brain death led to significantly decreased left ventricular systolic and diastolic function. Basal and isoproterenol-stimulated adenylate cyclase activity was blunted in the brain dead group compared with the sham-operated group (28.3 +/- 4.3 vs 48.3 +/- 7.6 pmol of cyclic adenosine monophosphate.mg(-1) x min(-1) [P = .01] and 54.8 +/- 9.6 vs 114.5 +/- 18 pmol of cyclic adenosine monophosphate x mg(-1) x min(-1) [P < .02]). There was no difference in beta-adrenergic receptor density between the brain dead and sham-operated groups. Myocardial beta-adrenergic receptor kinase expression was 3-fold greater in the brain dead versus sham-operated groups, and membrane beta-adrenergic receptor kinase activity was 2.5-fold greater in the brain dead group compared with that seen in the sham-operated group. CONCLUSION: Induction of brain death leads to significant left ventricular dysfunction in this porcine model. Cardiac beta-adrenergic receptors are clearly uncoupled after brain death, and our data suggest that the mechanism is acute increase of myocardial beta-adrenergic receptor kinase activity, leading to beta-adrenergic receptor desensitization and ventricular dysfunction.

Animals↗
PubMed2005

Brain magnetic resonance imaging abnormalities after the Norwood procedure using regional cerebral perfusion.

OBJECTIVES: Neurologic deficits are common after the Norwood procedure for hypoplastic left heart syndrome. Because of the association of deep hypothermic circulatory arrest with adverse neurologic outcome, regional low-flow cerebral perfusion has been used to limit the period of intraoperative brain ischemia. To evaluate the effect of this technique on brain ischemia, we performed serial brain magnetic resonance imaging in a cohort of infants before and after the Norwood operation using regional cerebral perfusion. METHODS: Twenty-two term neonates with hypoplastic left heart syndrome were studied with brain magnetic resonance imaging before and at a median of 9.5 days after the Norwood operation. Results were compared with preoperative, intraoperative, and postoperative risk factors to identify predictors of neurologic injury. RESULTS: Preoperative magnetic resonance imaging (n = 22) demonstrated ischemic lesions in 23% of patients. Postoperative magnetic resonance imaging (n = 15) demonstrated new or worsened ischemic lesions in 73% of patients, with periventricular leukomalacia and focal ischemic lesions occurring most commonly. Prolonged low postoperative cerebral oximetry (<45% for >180 minutes) was associated with the development of new or worsened ischemia on postoperative magnetic resonance imaging (P = .029). CONCLUSIONS: Ischemic lesions occur commonly in neonates with hypoplastic left heart syndrome before surgical intervention. Despite the adoption of regional cerebral perfusion, postoperative cerebral ischemic lesions are frequent, occurring in the majority of infants after the Norwood operation. Long-term follow-up is necessary to assess the functional effect of these lesions.

Brain Ischemia↗
PubMed2005

Calpain inhibition decreases endothelin-1 levels and pulmonary hypertension after cardiopulmonary bypass with deep hypothermic circulatory arrest.

OBJECTIVE: Cardiopulmonary bypass in infants and children can result in cardiopulmonary dysfunction through ischemia and reperfusion injury. Pulmonary hypertension and injury are particularly common and morbid complications of neonatal cardiac surgery. Inhibition of calpain, a cysteine protease, has been shown to inhibit reperfusion injury in adult organ systems. The hypothesis is that calpain inhibition can alleviate the cardiopulmonary dysfunction seen in immature animals following ischemia and reperfusion with cardiopulmonary bypass. DESIGN: Animal case study. SETTING: Medical laboratory. SUBJECTS: Crossbred piglets (5-7 kg). INTERVENTIONS: Piglets were cooled with cardiopulmonary bypass to 18 degrees C followed by deep hypothermic circulatory arrest for 120 mins. Animals were rewarmed to 38 degrees C on cardiopulmonary bypass and maintained for 120 mins. Six animals were administered calpain inhibitor (Z-Leu-Leu-Tyr-fluoromethyl ketone; 1 mg/kg, intravenously) 60 mins before cardiopulmonary bypass. Nine animals were administered saline as a control. Plasma endothelin-1, pulmonary and hemodynamic function, and markers of leukocyte activity and injury were measured. MEASUREMENTS AND MAIN RESULTS: Calpain inhibition prevented the increased pulmonary vascular resistance seen in control animals (95.7 +/- 39.4 vs. 325.3 +/- 83.6 dyne.sec/cm, respectively, 120 mins after cardiopulmonary bypass and deep hypothermic circulatory arrest, p = .05). The attenuation in pulmonary vascular resistance was associated with a blunted plasma endothelin-1 response (4.91 +/- 1.72 pg/mL with calpain inhibition vs. 10.66 +/- 6.21 pg/mL in controls, p < .05). Pulmonary function after cardiopulmonary bypass was better maintained after calpain inhibition compared with controls: Po2/Fio2 ratio (507.2 +/- 46.5 vs. 344.7 +/- 140.5, respectively, p < .05) and alveolar-arterial gradient (40.0 +/- 17.2 vs. 128.1 +/- 85.2 mm Hg, respectively, p < .05). Systemic oxygen delivery was higher after calpain inhibition compared with controls (759 +/- 171 vs. 277 +/- 46 mL/min, respectively, p < .001). In addition, endothelial nitric oxide synthase activity in lung tissue was maintained with calpain inhibition. CONCLUSIONS: The reduction in plasma endothelin-1 and maintenance of lung endothelial nitric oxide levels after cardiopulmonary bypass and deep hypothermic circulatory arrest with calpain inhibition were associated with reduced pulmonary vascular resistance. Improved gas exchange and higher systemic oxygen delivery suggest that calpain inhibition may be advantageous for reducing postoperative cardiopulmonary dysfunction commonly associated with pediatric heart surgery and cardiopulmonary bypass.

Animals↗
PubMed2004

Risk of recoarctation should not be a deciding factor in the timing of coarctation repair.

To determine whether early coarctation repair is a significant risk for recoarctation in the modern era, 120 patients, including 87 infants, who underwent isolated coarctation repair at a single institution, were reviewed. At a mean follow-up of 44.4 months, there have were no late reoperations, and 2 patients required balloon aortoplasty. The overall incidence of late reintervention was 1.7%, with only 2.4% (2 of 83) in those <1 year old.

Aortic Coarctation↗
PubMed2004

Preoperative glucocorticoids decrease pulmonary hypertension in piglets after cardiopulmonary bypass and circulatory arrest.

BACKGROUND: Glucocorticoids during cardiopulmonary bypass benefit pediatric patients undergoing repair of congenital heart defects and are routine therapy, but underlying mechanisms have not been fully examined. The hypothesis was that glucocorticoids could improve cardiopulmonary recovery after cardiopulmonary bypass and deep hypothermic circulatory arrest. METHODS: Crossbred piglets (5 to 7 kg) were cooled with cardiopulmonary bypass, followed by 120-min deep hypothermic circulatory arrest. Animals were then warmed to 38 degrees C, removed from bypass, and maintained for 120 min. Methylprednisolone (60 mg/kg) was administered in the cardiopulmonary bypass pump prime (intraoperative glucocorticoids) or 6 hours before bypass (30 mg/kg) in addition to the intraoperative dose (30 mg/kg; preoperative and intraoperative glucocorticoids). Controls (no glucocorticoids) received saline. RESULTS: Pulmonary vascular resistance in controls increased from a baseline of 152 +/- 40 to 364 +/- 29 dynes. s/cm(5) at 2 hours of recovery (p < 0.001). Intraoperative glucocorticoids did not alleviate the increase in pulmonary vascular resistance (301 +/- 55 dynes. s/cm(5) at 2 hours of recovery, p < 0.001). However, animals receiving pre and intraoperative glucocorticoids had no increase in pulmonary vascular resistance (155 +/- 54 dynes. s/cm(5)). Plasma endothelin-1 in controls increased from 1.3 +/- 0.2 at baseline to 9.9 +/- 2.0 pg/mL at 2 hours recovery (p < 0.01), whereas glucocorticoid-treated animals had lower endothelin-1 levels (4.5 +/- 2.1 pg/ml, preoperative and intraoperative glucocorticoids; 4.9 +/- 1.7 pg/mL, intraoperative glucocorticoids) at the end of recovery (p < 0.05). Intracellular adhesion molecule-1 in lung tissue was lower in animals receiving pre and intraoperative glucocorticoids (p < 0.05). Myeloperoxidase activity was elevated in control lungs at 2 hours of recovery compared with glucocorticoid-treated groups (p < 0.05). Inhibitor kappaBalpha, the inhibitor of nuclear factor-kappaB, was higher in lungs of animals receiving glucocorticoids compared with controls (p < 0.05). CONCLUSIONS: Glucocorticoids prevented pulmonary hypertension after cardiopulmonary bypass and deep hypothermic circulatory arrest, which was associated with reduced plasma endothelin-1. Glucocorticoids also reduced pulmonary intercellular adhesion molecule-1 and myeloperoxidase activity. Inhibition of nuclear factor-kappaB, along with reduced neutrophil activation, contributed to glucocorticoid alleviation of pulmonary hypertension after cardiopulmonary bypass and deep hypothermic circulatory arrest.

Animals↗
PubMed2004

Sildenafil citrate alleviates pulmonary hypertension after hypoxia and reoxygenation with cardiopulmonary bypass.

BACKGROUND: Sudden reoxygenation of hypoxic neonates undergoing cardiac operation exacerbates the systemic inflammatory response to cardiopulmonary bypass secondary to reoxygenation injury, worsening cardiopulmonary dysfunction. Reports suggest sildenafil decreases pulmonary hypertension and may affect myocardial function. Sildenafil's efficacy for treating postbypass cardiopulmonary dysfunction remains unknown. STUDY DESIGN: Fourteen neonatal piglets (5 to 7 kg) underwent 90 minutes of hypoxia, 60 minutes of reoxygenation with cardiopulmonary bypass, and 120 minutes of recovery. Six animals received 50 mg oral sildenafil and eight received saline at hypoxia. Data are presented as mean +/- SD. RESULTS: Sildenafil prevented the high pulmonary vascular resistance observed in controls (controls baseline 81 +/- 37 dynes. s/cm(5) versus recovery 230 +/- 93 dynes. s/cm(5), p = 0.004; sildenafil baseline 38 +/- 17 dynes. s/cm(5) versus recovery 101 +/- 60 dynes. s/cm(5), p = 0.003). Despite lower pulmonary vascular resistance after sildenafil, arterial endothelin-1 (ET-1) was increased in both groups (control baseline 1.3 +/- 0.5 pg/mL versus recovery 4.5 +/- 3.7 pg/mL, p = 0.01; sildenafil baseline 1.3 +/- 0.3 pg/mL versus recovery 9.8 +/- 4.9 pg/mL, p = 0.003). Intravenous nitric oxide (NO) levels were preserved after sildenafil treatment (sildenafil baseline 340 +/- 77 nM versus recovery 394 +/- 85 nM). IV NO levels in controls were decreased when compared with baseline (control baseline 364 +/- 83 nM versus recovery 257 +/- 97 nM, p = 0.028). Although levels of exhaled NO decreased in both groups, the sildenafil-treated animals had higher levels of exhaled NO when compared with controls at the end of recovery (0.6 +/- 0.4 parts per billion versus 1.8 +/- 0.9 parts per billion, respectively, p = 0.029). CONCLUSIONS: Sildenafil alleviated pulmonary hypertension after reoxygenation with cardiopulmonary bypass. Despite increased ET-1 levels, pulmonary vascular resistance was lower with sildenafil treatment, suggesting sildenafil's effect on the pulmonary vasculature is capable of countering vasoconstriction by ET-1. Further study into the role of sildenafil in perioperative therapy and its interactions with ET-1 are warranted.

Animals↗
PubMed2004

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 degrees 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-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-kappaB in the cytosol and decreased nuclear factor-kappaB 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-kappaB-dependent pathways.

Analysis of Variance↗
PubMed2003

Glucocorticoids preserve calpastatin and troponin I during cardiopulmonary bypass in immature pigs.

Degradation of troponin I (TnI) by calpain occurs with myocardial stunning in ischemia-reperfusion injury. Glucocorticoids attenuate myocardial ischemia-reperfusion injury, but their effect on TnI degradation is unknown. A piglet model was used to test the hypotheses that cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) are associated with TnI degradation and that TnI alterations could be prevented by glucocorticoid treatment. Piglets were cooled to 18 degrees C, subjected to 2 h of circulatory arrest, rewarmed to 37 degrees C, and allowed to recover for 2 h. Methylprednisolone was administered 6 h before surgery (3 0 mg/kg) and at initiation of CPB (30 mg/kg). The untreated group received saline. Left ventricular tissue was collected after recovery and analyzed by Western blot for TnI, calpain, and calpastatin (the natural inhibitor of calpain). CPB/DHCA animals had 27.4 +/- 0.2% of total detected TnI present in degraded form. Glucocorticoid treatment significantly decreased the percentage of degraded TnI (12.0 +/- 0.1%, p < 0.05). Calpain I and calpain II increased after CPB/DHCA compared with non-CPB/DHCA controls (p < 0.05), with or without glucocorticoid treatment. Calpastatin significantly decreased in untreated CPB/DHCA animals compared with non-CPB/DHCA controls (p < 0.05), but levels were preserved by glucocorticoids. Glucocorticoids were associated with preservation of maximum rate of increase of left ventricular pressure at 95 +/- 10% of baseline, whereas maximum rate of increase of left ventricular pressure decreased to 62 +/- 12% of baseline without steroids. TnI degradation occurs after CPB/DHCA in neonatal pigs. Reduction in reperfusion injury by glucocorticoids may depend partly on preservation of calpastatin activity and intact TnI.

Age Factors↗
PubMed2003

Impaired systemic ventricular relaxation affects postoperative short-term outcome in Fontan patients.

OBJECTIVES: Systemic ventricular end-diastolic pressure has been used as a predictor of outcome in patients undergoing the Fontan operation. However, this index only evaluates late diastolic function and does not assess active ventricular relaxation during the phase of early diastole, a key component of systemic venous pathway flow. This study sought to examine whether impaired preoperative systemic ventricular relaxation, expressed as the time constant of isovolumic relaxation (tau), affects short-term postoperative outcome in Fontan patients. METHODS: All patients who underwent Fontan operation between May 1998 and November 2001 were enrolled. Tau was calculated from digitized preoperative systemic ventricular pressure tracings. Standard preoperative invasive indices were also recorded and analyzed. These independent variables were then entered into a multiple stepwise regression model, with length of intensive care unit stay, length of hospital stay, and prolonged pleural effusion as outcome variables. RESULTS: Twenty-seven patients fulfilled inclusion criteria. Systemic left ventricle predominated, and all patients had undergone prior staged palliation. Extracardiac Fontan was the commonest operative technique. Of the independent variables examined, tau was the only statistically significant predictor of length of intensive care unit stay (P <.001) and length of hospital stay (P =.002). None of the independent variables predicted pleural effusion greater than 10 days. CONCLUSIONS: Tau was the only significant preoperative invasive predictor of short-term outcome in the Fontan patients. This illustrates the importance of systemic ventricular relaxation and highlights the need for a more comprehensive assessment of diastolic function before the Fontan operation.

Adolescent↗
PubMed2003

Biventricular repair after Norwood palliation.

BACKGROUND: In general, neonates with severe left ventricular outflow tract obstruction, aortic valvar stenosis or atresia, and arch hypoplasia with either interruption or coarctation, and a small left ventricle undergo Norwood palliation followed classically by a bidirectional cavopulmonary shunt and eventual modified Fontan. However, a subset of patients, usually neonates with a ventricular septal defect, may have adequate left ventricle and mitral valve sizes making them candidates for future biventricular repair (BVR). In view of the long-term advantage of BVR, the feasibility and outcome of this approach was studied. Additionally, echocardiographic data were reviewed in an attempt to develop objective prognostic criteria for selection of patients suitable for BVR. METHODS: During a 4-year period, 8 of 58 infants undergoing Norwood palliation were identified as potential two-ventricle candidates. Their mean age was 6 days. Diagnoses included aortic atresia (n = 1), or aortic valve stenosis and subaortic stenosis (n = 7), with an interrupted aortic arch in 3 and coarctation in 4. All patients had a ventricular septal defect and a left ventricle that was considered to be apex forming. Mean mitral valve size was 11 mm (z-score = -1.7). Mean aortic valve size was 4.1 mm (mean z-score = -8.4). RESULTS: All 8 patients survived Norwood palliation. Six subsequently underwent BVR with ventricular septal defect closure and a right ventricle to pulmonary artery conduit at a mean age of 7 months. One patient is awaiting repair, and 1 underwent a cavopulmonary shunt. At the time of BVR, mean mitral valve z-score was essentially unchanged at -1.4 (14 mm). No early deaths or late deaths occurred during a mean follow-up of 32 months. CONCLUSIONS: A small subset of patients requiring Norwood palliation as newborns may be candidates for eventual BVR with low risk. In general, patients suitable for BVR have a mitral valve z-score of more than -3 and a normal-sized left ventricle. Recognition of neonatal BVR candidates enables consideration of complete neonatal repair. However, single-stage repair needs to be compared with the excellent results obtainable with the staged approach.

Aorta, Thoracic↗