Extracorporeal circulation does not induce intra-alveolar release of Endothelin 1, but only a modest overproduction in pulmonary circulation.

OBJECTIVE: To investigate whether ECC may produce regional liberation of inflammatory mediators capable of inducing vascular effects and organ damage. EXPERIMENTAL DESIGN: Comparative study [corrected]. SETTING: Cardiac surgery department in a University hospital. PATIENTS: Fifteen patients undergoing coronary artery bypass grafting (CABG, group A) and ten patients operated for infrarenal abdominal aortic aneurysm (controls, group B) have been studied. MEASURES: Levels of Interleukin 1beta (IL1), Tumor Necrosis Factor alpha (TNF), Interleukin 6 (IL6), and Endothelin 1 (ET1) were measured in pulmonary capillary, arterial, and venous blood and in bronchoalveolar lavages (BAL) before, during and after extracorporeal circulation (ECC) or surgical intervention. RESULTS: TNF-alpha (never >35 pg/ml) and IL1beta (range 20-300 pg/ml) values did not change over time for both groups. IL6 concentrations in all samples of group A increased between five and twenty fold, during and after ECC (from 3-5 pg/ml up to 240 pg/ml, p<0.001). This trend was similar in controls after surgical stress. Endothelin 1 was always undetectable in the BAL fluid, with a modest, but significant increase in pulmonary capillary blood of group A, after ECC, (from 11+/-4 pg/ml to 18+/-5 pg/ml, p<0.001). This increment correlated well with the PVR increase, but was transient and after 24 hours, ET1 values returned to baseline levels. Mean values of ET1 increased also in controls, but not significantly. CONCLUSIONS: ECC may induce ET1 liberation in pulmonary circulation with transient pulmonary vasoconstriction, but wihout intra-alveolar release, or lung damage. Augmented concentrations of IL6 probably express a response to surgical procedure rather than an effect exclusively related to ECC.

Exogenous reactive oxygen species deplete the isolated rat heart of antioxidants.

The effects of reactive oxygen species (ROS) on myocardial antioxidants and on the activity of oxidative mitochondrial enzymes were investigated in the following groups of isolated, perfused rat hearts. I: After stabilization the hearts freeze clamped in liquid nitrogen (n = 7). II: Hearts frozen after stabilization and perfusion for 10 min with xanthine oxidase (XO) (25 U/l) and hypoxanthine (HX) (1 mM) as a ROS-producing system (n = 7). III: Like group II, but recovered for 30 min after perfusion with XO + HX (n = 9). IV: The hearts were perfused and freeze-clamped as in group III, but without XO + HX (n = 7). XO + HX reduced left ventricular developed pressure and coronary flow to approximately 50% of the baseline value. Myocardial content of hydrogen peroxide (H2O2) and malondialdehyde (MDA) increased at the end of XO + HX perfusion, indicating that generation of ROS and lipid peroxidation occurred. Levels of H2O2 and MDA normalized during recovery. Superoxide dismutase, reduced glutathione and alpha-tocopherol were all reduced after ROS-induced injury. ROS did not significantly influence the tissue content of coenzyme Q10 (neither total, oxidized, nor reduced), cytochrome c oxidase, and succinate cytochrome c reductase. The present findings indicate that the reduced contractile function was not correlated to reduced activity of the mitochondrial electron transport chain. ROS depleted the myocardium of antioxidants, leaving the heart more sensitive to the action of oxidative injury.

Paralysis has no effect on chest wall and respiratory system mechanics of mechanically ventilated, sedated patients.

OBJECTIVE: To evaluate the separate effects of sedation and paralysis on chest wall and respiratory system mechanics of mechanically ventilated, critically ill patients. SETTING: ICU of the University "La Sapienza" Hospital, Rome. PATIENTS AND PARTICIPANTS: 13 critically ill patients were enrolled in this study. All were affected by disease involving both lungs and chest wall mechanics (ARDS in 4 patients, closed chest trauma without flail chest in 4 patients, cardiogenic pulmonary oedema with fluidic overload in 5 patients). MEASUREMENTS AND RESULTS: Respiratory system and chest wall mechanics were evaluated during constant flow controlled mechanical ventilation in basal conditions (i.e. with the patients under apnoic sedation) and after paralysis with pancuronium bromide. In details, we simultaneously recorded airflow, tracheal pressure, esophageal pressure and tidal volume; with the end-inspiratory and end-expiratory airway occlusion technique we could evaluate respiratory system and chest wall elastance and resistances. Lung mechanics was evaluated by subtracting chest wall from respiratory system data. All data obtained in basal conditions (with the patients sedated with thiopental or propofol) and after muscle paralysis were compared using the Student's t test for paired data. The administration of pancuronium bromide to sedated patients induced a complete muscle paralysis without producing significant modification both to the viscoelastic and to the resistive parameters of chest wall and respiratory system. CONCLUSIONS: This study demonstrates the lack of additive effects of muscle paralysis in mechanically ventilated, sedated patients. Also in view of the possible side effects of muscle paralysis, our results question the usefulness of generalized administration of neuromuscular blocking drugs in mechanically ventilated patients.