Free radical reaction products and antioxidant capacity in arterial plasma during coronary artery bypass grafting.

Oxygen free radicals mediate the ischemia-reperfusion damage in animal hearts, but their role in human beings is still controversial because of the low xanthine oxidase level in the human heart. Besides ischemia-reperfusion, cardiac operation also includes other major interventions that might generate free radicals but have not been systematically studied. We studied the cases of nine patients throughout coronary artery operations, including general anesthesia, heparin, protamine and administration of cardioplegic solution, extracorporeal circulation, and heart reperfusion. Arterial plasma was assayed for malondialdehyde, diene conjugates, and fluorescent chromolipids, and plasma antioxidant activity was estimated from the ability to trap peroxyl radicals. Anesthesia, surgical procedures, or heparin administration did not change these parameters. Extracorporeal circulation decreased the plasma concentration of diene conjugates immediately, whereas other compounds remained unaltered. When these concentrations were corrected for hemodilution, the amount of fluorescent chromolipids actually increased after 5 minutes of extracorporeal circulation to 177% +/- 14% (mean +/- standard error of the mean), diene conjugates increased to 138% +/- 12%, and plasma antioxidant capacity increased to 144% +/- 12% of the awake value. Fluorescent chromolipid values remained at 156% to 177% throughout the perfusion and decreased to 130% +/- 13% 1 hour after perfusion. Diene conjugate levels and antioxidant capacity were 123% to 144% and 143% to 161%, respectively, from baseline during perfusion and 119% +/- 5% and 135% +/- 9%, respectively, 1 hour after perfusion. Heart reperfusion or protamine administration showed no additional increases. Malondialdehyde concentrations varied and showed no statistically significant alterations. We conclude that extracorporeal circulation devices induce generation of free radicals and plasma antioxidant activity, which are different from the damage caused by ischemia-reperfusion.

L-Arginine in lung graft preservation and reperfusion.

BACKGROUND: Inhaled nitric oxide has been shown to ameliorate early lung graft dysfunction. It improves oxygenation by inducing pulmonary vasodilatation in well-ventilated lung areas, and it also modulates leukocyte-endothelium interactions. We used a porcine, single lung transplantation model to evaluate whether the benefits of exogenously administered gas could be achieved easier by adding L-arginine, the substrate of endogenous nitric oxide synthesis, as an additive to the flush solution and intravenously during reperfusion. METHODS: Six pig lungs were flushed with modified Euro-Collins solutions containing L-arginine (2 g/liter). After cold (4 degrees C) storage, the left lung was transplanted. Ischemic time was 260 minutes. The recipients received intravenous boluses of L-arginine (30 mg/kg), followed by infusion (20 mg/kg/min) during the first 30 minutes of reperfusion. Six control animals received saline as placebo. We measured the blood flow and pulmonary vascular resistance (PVR) in the transplanted and in the native lung using a right heart bypass model. We measured blood gases, leukocyte counts, plasma free-radical trapping capacity, and diene conjugates in pulmonary venous blood and myeloperoxidase activity of the lung tissue. RESULTS: Pulmonary vascular resistance was 4 to 5-fold higher in the transplanted lung than in the native lung, which received 80% of the total blood flow. L-arginine reduced PVR by 30% in the native lung (p < 0.001), but not in the transplanted lung. L-arginine had no effect on oxygenation or carbon dioxide exchange of the transplanted lung. Nor did L-arginine treatment have any effect on leukocyte sequestration or myeloperoxidase activity in the transplanted lung. The plasma antioxidant capacity in venous blood of the transplanted lung almost doubled shortly during early reperfusion without influence of L-arginine. CONCLUSIONS: L-arginine reduced PVR in the native lung but did not improve pulmonary hemodynamics, gas exchange, or reduce leukocyte sequestration of the transplanted lung.

Effects of acid-base imbalance on pulmonary angiotensin-converting enzyme in vivo.

The effects of acid-base balance disturbances on pulmonary endothelial angiotensin-converting enzyme (ACE) were studied in anesthetized mechanically ventilated rabbits. Enzyme function was estimated from [3H]benzoyl-Phe-Ala-Pro ([3H]BPAP) utilization under first-order reaction conditions during a single transpulmonary passage and expressed as 1) substrate metabolism (M), 2) Amax/Km (Amax being equal to the product of enzyme mass and the constant of product formation), and 3) (Amax/Km)/100 ml blood flow. When respiratory acidosis/alkalosis was produced by altering respiratory rate at constant airway pressure, substrate (BPAP) utilization varied proportionally to arterial pH and inversely proportionally to arterial PCO2 (PaCO2) (P less than 0.05). Percent BPAP metabolism (%M) ranged from 92 +/- 3 (respiratory alkalosis) to 85 +/- 3 (normal), 82 +/- 3 (respiratory acidosis), and 78 +/- 2% (severe respiratory acidosis). Amax/Km similarly decreased from 899 +/- 129 to 825 +/- 143, 601 +/- 74, and 450 +/- 34 ml/min, respectively, and (Amax/Km)/100 ml blood flow was reduced from 176 +/- 26 to 131 +/- 22, 111 +/- 12, and 97 +/- 5, respectively. However, when respiratory acidosis/alkalosis was produced by altering both respiratory rate and airway pressure, no changes were observed in either %M, Amax/Km or (Amax/Km)/100 ml blood flow. Similarly metabolic alkalosis or acidosis did not alter M, Amax/Km or (Amax/Km)/100 ml blood flow. These results indicate that pulmonary endothelial ACE function can be affected by acid-base disturbances, probably indirectly through changes in perfused microvascular surface area.

Effects of blood flow on lung ACE kinetics: evidence for microvascular recruitment.

The parameter Amax/Km (product of reactant enzyme mass in perfused microvessels and the constant kcat/Km), calculated from in vivo assays of pulmonary endothelial ectoenzymes (e.g., angiotensin-converting enzyme, ACE), can provide estimates of the perfused pulmonary microvascular surface area (PMSA) in the absence of enzyme dysfunction. We examined the relationship between PMSA and pulmonary blood flow (Qb) in anesthetized rabbits placed on total heart bypass, using [3H]benzoyl-Phe-Ala-Pro (BPAP) as the ACE substrate. When Qb was increased from 250 to 1,100 ml/min, at zone 3 conditions, pulmonary arterial pressure increased, pulmonary vascular resistance (PVR) decreased, and Amax/Km increased linearly, reflecting increasing PMSA. When only the left lung was perfused, increasing Qb from 250 to 636 +/- 17 ml/min (the last value representing fully recruited and/or distended vascular bed), PVR decreased, while Amax/Km increased. When Qb was further increased to 791 +/- 44 ml/min, both PVR and Amax/Km remained unchanged, confirming the lack of additional changes in PMSA. We conclude that Amax/Km provides a sensitive indication of PMSA, because it 1) increases with increasing Qb and decreasing PVR, 2) reaches a maximum at Qb values that correspond to the minimal values in PVR, and 3) like PVR, did not change with further increases in Qb. Compared with predicted changes in PMSA produced by either microvascular recruitment alone or distension alone, our data indicate that recruitment is a larger contributor to the observed increase in PMSA.

Effects of alveolar pressure on lung angiotensin-converting enzyme function in vivo.

Angiotensin-converting enzyme lines the luminal surface of pulmonary capillary endothelial cells. The metabolism of its synthetic substrate, 3H-benzoyl-L-phenylalanyl-L-alanyl-L-proline ([3H]BPAP) has been used as an indicator of pulmonary microvascular function. Because the flow-volume status of the pulmonary capillaries is dependent on intra-alveolar pressure, we have studied the effects of airway pressure on endothelial plasmalemmal angiotensin-converting enzyme function in rabbit lungs in vivo. Static inflation of the lungs to a pressure of 0 or 5 Torr did not change percent transpulmonary metabolism and Amax/Km ratio (defined as E X Kcat/Km and thus, under normal conditions, an indirect measure of perfused endothelial luminal surface area) compared with control measurements during conventional mechanical ventilation. When the inflation pressure was increased to 10 Torr, percent metabolism of [3H]BPAP remained unaltered but Amax/Km decreased to 60% of the control value. This decrease was in close relation to the decrease in pulmonary blood flow. Addition of 5 cmH2O positive end-expiratory pressure (PEEP) to the mechanical ventilation also decreased Amax/Km values and pulmonary blood flow but did not influence percent metabolism of [3H]BPAP. These results suggest that the detected alterations in apparent enzyme kinetics were more likely due to hemodynamic changes than to alterations in angiotensin-converting enzyme function. Thus high static alveolar pressures as well as PEEP probably reduced the fraction of perfused microvessels as reflected in changes in Amax/Km ratios. This information should prove useful in interpreting the response of pulmonary endothelial enzymes to injury.

Inhaled NO and prostacyclin during porcine single lung transplantation.

BACKGROUND: Increased pulmonary vascular resistance (PVR) and decreased arterial oxygenation frequently complicate lung transplantation. Inhaled nitric oxide (NO) and aerosolized prostacyclin (PGI2) both dilate the pulmonary vasculature and improve oxygenation in adult respiratory distress syndrome. We investigated whether similar effects would occur during early reperfusion of a lung graft. METHODS: Eighteen pigs underwent left lung transplantation. We measured blood flow distribution, mean pulmonary artery pressure, PVR, and gas exchange in each lung separately. Animals were randomized into three groups to receive NO (10 ppm/30 minutes, 40 ppm/30 minutes), nebulized PGI2 (25 microg/mL/30 minutes, 50 microg/mL/30 minutes), or no drugs (control). RESULTS: In the transplanted lung, PVR was significantly higher than in the native lung. Pulmonary vascular resistance of the transplanted lung was lower in the NO and PGI2 groups in comparison with the control group. During the first hour of inhalation, NO decreased PVR more than PGI2. Neither drug improved oxygenation in the graft. CONCLUSIONS: Nitric oxide and PGI2 decreased PVR of the transplanted lung slightly, but the effect did not produce a normal pressure in pulmonary vasculature.

Successful treatment of mediastinal gas gangrene due to esophageal perforation.

Esophageal perforation and mediastinal gas gangrene developed in a 55-year-old male after the endoscopic ethanol injection of a Mallory-Weiss ulcer. Initially, extensive gangrene of the esophagus and the mediastinum was treated by esophagectomy; however, an abundance of Clostridium perfringens in the Gram stain verified the presence of gas gangrene. Subsequently, the patient was transferred to a hyperbaric oxygen center, wherein a total of seven hyperbaric treatments were administered. The patient survived, and 4 months later, after having undergone several reoperations because of pleural empyema, mediastinal abscess, splenic rupture, and acalculous cholecystitis, was discharged and is still surviving.

Continuous wound infusion with ropivacaine fails to provide adequate analgesia after caesarean section.

BACKGROUND: Continuous wound infusion with local anaesthetic has been used in post-caesarean pain management with conflicting results. We carried out a study comparing three groups: continuous ropivacaine wound infusion, intrathecal morphine with saline wound infusion and saline wound infusion only. METHODS: Sixty-six women undergoing elective caesarean section under combined spinal-epidural anaesthesia were randomly allocated to receive intrathecal morphine with saline wound infusion or 48 h continuous wound infusion with either ropivacaine or saline. All parturients received oral ketoprofen and intravenous oxycodone patient-controlled analgesia. Consumption of oxycodone, visual analogue scale pain scores (0-10 cm), patient satisfaction, side effects and recovery parameters were recorded for 48 h in a double-blind manner. RESULTS: Continuous wound infusion with ropivacaine failed to reduce oxycodone consumption or pain scores compared with saline control. In the first 24 h intrathecal morphine reduced mean oxycodone consumption compared to the ropivacaine wound infusion group (26 mg vs. 48 mg, P=0.007) and saline wound infusion group (26 mg vs. 45 mg, P=0.021). The first 24-h mean pain score was also lower in the intrathecal morphine group vs. the saline wound infusion group (1.3 vs. 2.2, P=0.021). Pain scores were not significantly different between intrathecal morphine and ropivacaine wound infusion groups. Pruritus was more common with intrathecal morphine. CONCLUSION: Compared to saline control, continuous wound infusion with ropivacaine failed to reduce the use of intravenous oxycodone patient-controlled analgesia or pain scores. Intrathecal morphine decreased oxycodone consumption by 46% in the first 24 h after surgery when compared to continuous ropivacaine wound infusion.

Anaesthesia for patients with a transplanted organ.

Increasing numbers of individuals leading normal lives have transplanted organs. They may appear in any hospital for treatment of trauma or general diseases. Common anaesthesia methods can be used for these patients, but safe conduct of anaesthesia requires knowledge of the immunosuppression, risk factors, and altered physiology or drug actions. This article reviews the anaesthesia-related literature on patients with transplanted organs.

Monitoring of pulmonary endothelial enzyme function: an animal model for a simplified clinically applicable procedure.

The authors present a simple and clinically applicable method for the serial monitoring of pulmonary microvascular enzyme function in vivo. This method requires the intravenous injection of trace amounts of a radiolabelled substrate and the collection of a single arterial blood sample. Simultaneous measurement of pulmonary blood flow, (e.g., by dye- or thermo-dilution) and the determination of blood hematocrit are also needed for the calculations. This method was compared to the multiple blood sample indicator dilution method in normal anesthesized rabbits. Both methods gave identical results for the metabolism of the synthetic, hemodynamically inactive tripeptide, 3H-benzoyl-Phe-Ala-Pro (3H-BPAP), by pulmonary microvascular endothelial angiotensin converting enzyme. The parameters measured were: 1) substrate utilization, expressed linearly and logarithmically, and 2) the apparent first order reaction constant. The new method was also used for the simultaneous measurement of single pass, transpulmonary metabolism of 3H-BPAP by angiotensin converting enzyme and of 5'-adenosine monophosphate by 5'-nucleotidase in rabbits in vivo. The authors propose that similar enzyme kinetic measurements could be used in clinical studies to test their usefulness as an aid in the early diagnosis of incipient pulmonary endothelial dysfunction, e.g., adult respiratory distress syndrome.

Signs of massive intraoperative pulmonary embolism with extensive invasive monitoring.

A 71-year-old patient suffered a massive pulmonary tumor embolism during removal of a renal carcinoma. He had extensive invasive monitoring, and the data were stored for later analysis. This shows that most of the known signs of pulmonary embolism were present in the tracings. It is discussed how none of them alone was sufficient for clinical diagnosis, but the comparison of several simultaneous variables together may be of great help. This report shows also the importance of the data-storing devices in the anesthesia monitors to make these comparisons possible in quickly changing emergency situations.

The effect of nitecapone on early graft function in experimental single lung transplantation.

Nitecapone is an antioxidant molecule which has been shown to protect the heart against ischemia-reperfusion injury. We investigated whether a similar effect could be detected on lung graft preservation in a porcine model of single lung transplantation. Donors received either nitecapone or placebo in a modified Euro-Collins pulmonary flush solution. After cold storage for 19 h the left lung was transplanted. Patients in the nitecapone group received a nitecapone infusion during the graft reperfusion. A right-side heart bypass was used to measure flow distribution and pulmonary vascular resistance (PVR) in the recipient's transplanted and native lungs, respectively. Pulmonary vein blood samples were analyzed for blood gases, free radical trapping capacity and diene conjugates. PVR was high in the transplanted lung, which received only 20% of the blood flow. Oxygen tension in the transplanted lung was low (2.3-26.7 kPa). Nitecapone treatment increased the plasma free radical trapping capacity threefold. In spite of this increase in antioxidative capacity nitecapone could not protect the lung against ischemia-reperfusion injury when pulmonary hemodynamics, gas exchange or plasma diene conjugates were used as measures of lung graft function.