Biomedical subjects

Jefferson M Lyons

Publications and source records attributed to Jefferson M Lyons.

5 recordsLinked to original sources

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

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↗

PubMedDate not supplied

Compression of an extracardiac fontan following classic fontan revision.

BACKGROUND: The extracardiac Fontan arose as an alternative in order to prevent the classical procedure's sequelea. Complications of the extracardiac Fontan have been described, but this case report aims to highlight the devastating and infrequent complication of external conduit compression. METHODS AND RESULTS: A 25-year-old male underwent Fontan conversion to extracardiac Fontan for atrial arrhythmias and giant right atrium. He developed postoperative respiratory distress, renal failure, and hemorrhagic pancreatitis, which prompted CT scans of his chest and abdomen that demonstrated external compression of the conduit by mediastinal hematoma. Endovascular stenting restored flow through the conduit, but the patient ultimately expired. CONCLUSIONS: External Fontan compression, which can be caused by numerous sources, may lead to significant organ dysfunction and can be difficult to recognize despite invasive monitoring. We report this complication and suggest ringed conduits to be considered to avoid the possibility of external compression.

Adult↗