Pro-inflammatory S100 proteins are associated with glomerulonephritis and anti-dsDNA antibodies in systemic lupus erythematosus.

Objectives Systemic lupus erythematosus (SLE) is associated with elevated levels of S100A8/A9, pro-inflammatory proteins mainly secreted by activated polymorphonuclear neutrophils (PMNs). The underlying mechanisms for increased S100A8/A9 levels and their relation to the clinical phenotype have not been carefully investigated. We assessed S100A8/A9 and S100A12 levels in SLE patient sera in relation to disease activity, clinical phenotype, presence of anti-dsDNA antibodies and ability to promote phagocytosis of necrotic cells (NCs) by PMNs. Methods Serum levels of S100A8/A9 and S100A12 were measured by ELISA in paired samples of 100 SLE patients at time points of higher and lower disease activity. Serum-mediated phagocytosis of NCs by PMNs was analysed by flow cytometry. Clinical data were recorded at time points of blood sampling. Results Serum levels of S100A8/A9 and S100A12 were increased in SLE patients with high disease activity compared to paired samples at low disease activity ( p = 0.01 and p = 0.008, respectively). Elevated levels of S100A8/A9 were particularly seen in patients with anti-dsDNA antibodies ( p = 0.01) and glomerulonephritis before treatment ( p = 0.02). Immunosuppressive therapy was associated with a reduction of S100A8/A9 serum levels ( p = 0.002). The ability of serum to support phagocytosis of NCs by PMNs was related to increased S100A8/A9 levels ( p = 0.01). Conclusions Elevated serum levels of S100A8/A9 may be used to monitor disease activity and response to treatment in SLE patients, especially in patients with glomerulonephritis. S100A12 may be a marker of disease activity in SLE. Increased S100A8/A9 levels may reflect immune-pathological processes involving phagocytosis of immune complexes by PMNs.

Milrinone and levosimendan during porcine myocardial ischemia -- no effects on calcium overload and metabolism.

BACKGROUND: Although inotropic stimulation is considered harmful in the presence of myocardial ischaemia, both calcium sensitisers and phosphodiesterase inhibitors may offer cardioprotection. We hypothesise that these cardioprotective effects are related to an acute alteration of myocardial metabolism. We studied in vivo effects of milrinone and levosimendan on calcium overload and ischaemic markers using left ventricular microdialysis in pigs with acute myocardial ischaemia. METHODS: Anaesthetised juvenile pigs, average weight 36 kg, were randomised to one of three intravenous treatment groups: milrinone 50 µg/kg bolus plus infusion 0.5 µg/kg/min (n = 7), levosimendan 24 µg/kg plus infusion 0.2 µg/kg/min (n = 7), or placebo (n = 6) for 60 min prior to and during a 45 min acute regional coronary occlusion. Systemic and myocardial haemodynamics were assessed, and microdialysis was performed with catheters positioned in the left ventricular wall. (45) Ca(2+) was included in the microperfusate in order to assess local calcium uptake into myocardial cells. The microdialysate was analysed for glucose, lactate, pyruvate, glycerol, and for (45) Ca(2+) recovery. RESULTS: During ischaemia, there were no differences in microdialysate-measured parameters between control animals and milrinone- or levosimendan-treated groups. In the pre-ischaemic period, arterial blood pressure decreased in all groups while myocardial oxygen consumption remained stable. CONCLUSIONS: These findings reject the hypothesis of an immediate energy-conserving effect of milrinone and levosimendan during acute myocardial ischaemia. On the other hand, the data show that inotropic support with milrinone and levosimendan does not worsen the metabolic parameters that were measured in the ischaemic myocardium.

Thoracic epidural anesthesia does not influence the occurrence of postoperative sustained atrial fibrillation.

BACKGROUND: To evaluate whether thoracic epidural anesthesia (TEA) can reduce the incidence of atrial fibrillation (AF) after coronary artery bypass grafting (CABG). METHODS: Forty-one patients undergoing CABG were treated with TEA intraoperatively and postoperatively. Another 80 patients served as the control group. The sympathetic and parasympathetic activities were evaluated by analysis of neuropeptides, catecholamines and heart rate variability (HRV), preoperatively and postoperatively. RESULTS: Postoperative AF occurred in 31.7% of the TEA-treated patients and in 36.3% of the untreated patients (p = 0.77). TEA significantly suppressed sympathetic activity, as indicated by a less pronounced increase of norepinephrine and epinephrine (p = 0.03, p = 0.02) and a significant decrease of neuropeptide Y (p = 0.01) postoperatively in TEA-treated patients compared to untreated patients. The HRV variable expressing sympathetic activity was significantly lower and the postoperative increase in heart rate was significantly less in the TEA group than in the control group after surgery (p = 0.01, p < 0.001). Among patients developing AF, the maximal number of supraventricular premature beats per minute increased significantly in untreated patients postoperatively but remained unchanged in TEA-treated patients (p = 0.004 versus p = 0.86). CONCLUSIONS: TEA has no effect on the incidence of postoperative sustained AF, despite a significant reduction in sympathetic activity.

Thoracic epidural analgesia as an adjunct to general anaesthesia for cardiac surgery. Effects on pulmonary mechanics.

BACKGROUND: A lasting impairment of pulmonary function is common after cardiac surgery. Pain from the sternotomy may contribute to the impairment. Thoracic epidural analgesia (TEA) can efficiently relieve pain in the postoperative phase, but may also affect respiratory muscle function if local anaesthetics are used. We examined the effects of TEA on pulmonary function and ventilation at rest, before and after coronary artery bypass graft surgery (CABG). METHODS: Thirty patients scheduled for CABG were randomized to receive either general anaesthesia alone or general anaesthesia with TEA. Before and after the operation the patients were examined by respiratory inductive plethysmography and spirometric tests. RESULTS: Before the operation, TEA caused significant reductions in forced vital capacity (FVC), forced expired volume in 1 s (FEV1), maximal inspiratory (PImax) and expiratory (PEmax) pressure. The rib cage contribution to tidal volume decreased significantly but the co-ordination of the thoracic and abdominal movements remained essentially unaffected. Minute volume and respiratory frequency did not change significantly. On the first postoperative day a decrease in maximal breathing efforts was found in both groups. No differences between the groups in FVC, FEV1 and PImax were found, but PEmax was significantly greater in the TEA group. Despite the impairment, breathing at rest was largely normal in both groups. CONCLUSIONS: A better pain-relief from TEA after CABG may improve the ability to cough by a greater expiratory muscle strength. FVC, FEV1, PImax and breathing at rest are not affected by TEA after cardiac surgery.

The safety of one, or repeated, vital capacity maneuvers during general anesthesia.

UNLABELLED: A vital capacity maneuver (VCM) (inflating the lungs to 40 cm H(2)O for 15 s) is effective in relieving atelectasis during general anesthesia or after cardiopulmonary bypass (CPB). The study was undertaken to investigate the safety of one or repeated VCM. Five groups of six pigs were studied. Two groups had general anesthesia for 6 h and one group received a VCM every hour. Three other groups received CPB. VCM was performed after CPB in two of these groups. VCM was then repeated every hour in one of the groups. Lung damage was evaluated by extravascular lung water (EVLW) measurement, light microscopy, and the half-time (T(1/2)) of disappearance from the lung of a nebulized aerosol containing (99m)Tc-DTPA. No changes were noted in extravascular lung water. The pigs subjected to VCM decreased their T(1/2). In the groups exposed to repeated VCM, T(1/2) remained lowered (CPB pigs) or decreased over time (non-CPB pigs). No lung damage could be seen on the morphology study. These results suggest that one VCM is a safe procedure. The increase in lung clearance of (99m)Tc-DTPA not associated with an increase in lung water when VCM is repeated may have been caused by an increase in lung volume. Therefore, repeated VCM also appears to be safe. IMPLICATIONS: This study demonstrates in an animal model that inflating the lung once or repeatedly to the vital capacity is a safe procedure. This maneuver, also called the vital capacity maneuver, can be used to relieve lung collapse which occurs in all patients during general anesthesia.

Thoracic epidural anesthesia as an adjunct to general anesthesia for cardiac surgery: effects on ventilation-perfusion relationships.

OBJECTIVE: To determine the effects of thoracic epidural anesthesia (TEA) on ventilation-perfusion (VA/Q) relationships, atelectasis, and oxygenation before and after coronary artery bypass graft surgery (CABG). DESIGN: Prospective, controlled, unblinded, randomized trial. SETTING: Cardiothoracic clinic at a major university referral center. PARTICIPANTS: Twenty-eight patients undergoing elective CABG. INTERVENTIONS: Perioperative and postoperative TEA was added to general anesthesia (GA) in 14 patients, and 14 patients receiving GA alone served as controls. MEASUREMENTS AND MAIN RESULTS: VA/Q relationships were measured by the multiple inert gas elimination technique, and, 20 hours postoperatively, atelectasis was assessed by computerized tomographic scans. Arterial and mixed venous blood gases and hemodynamic variables were measured by standard techniques. TEA per se caused no change in shunt, VA/Q matching, or oxygenation. Induction of GA in the control group and induction of TEA caused similar reductions in mean arterial pressure. The TEA patients needed less morphine analgesia postoperatively and were extubated earlier. Extubation caused significant improvement in VA/Q matching. On the first postoperative day, a slight reduction in PaCO2 was seen in the TEA group, but no differences in shunt, VA/Q matching, or oxygenation compared with the GA group. Both groups showed extensive bilateral atelectasis. CONCLUSION: TEA can reduce respirator time and the need for morphine analgesics after CABG without negative effects on VA/Q matching, oxygenation, or atelectasis formation.

Effect of CPAP during cardiopulmonary bypass on postoperative lung function. An experimental study.

BACKGROUND: Respiratory failure secondary to cardiopulmonary bypass (CPB) remains a major complication after cardiac surgery. We tested the hypothesis that post-CPB lung function impairment can be prevented by continuous positive airway pressure (CPAP) applied during the CPB. METHODS: In 6 pigs, CPAP with 5 cmH2O pressure was applied during CPB. Six other pigs served as control, i.e. the lungs were open to the atmosphere during CPB. After median sternotomy, the right atrial appendage as well as the ascending aorta were cannulated. The total CPB duration was 90 min with 45 min cardioplegic arrest. Ventilation-perfusion distribution was measured with the multiple inert gas elimination technique and atelectasis by CT-scanning. RESULTS: Large atelectasis appeared after CPB, corresponding to 14.5% +/- 5.5 (percent of the total lung area) in the CPAP group and 18.7% +/- 5.2 in the controls (P = 0.20). Intrapulmonary shunt increased and PaO2 decreased after the CPB in both groups. CONCLUSIONS: We conclude that in this pig model post-CPB atelectasis is not effectively prevented by CPAP applied during CPB.

Atelectasis and gas exchange after cardiac surgery.

BACKGROUND: Sometimes a high intrapulmonary shunt occurs after cardiac surgery, and impairment of lung function and oxygenation can persist for 1 week after operation. Animal studies have shown that postoperative shunt can be explained by atelectasis. In this study the authors tried to determine if atelectasis can explain shunt in patients who have had cardiac surgery. METHODS: Nine patients having coronary artery bypass graft surgery and nine patients having mitral valve surgery were examined using the multiple inert gas elimination technique before and after operation. On the first postoperative day, computed tomography scans were made at three levels of the thorax. RESULTS: Before anesthesia, the average shunt was low (2+/-3%; range, 0-13%), but on the first postoperative day shunt had increased to 12+/-60% (range, 3-28%). The computed tomography scans showed bilateral dependent densities in all patients but one. The mean area of the densities was 8+/-8% (range, 0-37%) of total lung area, corresponding to a calculated fraction of collapsed lung tissue of 20+/-14% (range, 0-59%). In the basal region, the calculated amount of collapsed tissue was 28+/-19% (range, 0-73%). One mitral valve patient was an outlier and had a large shunt both before and after the operation. CONCLUSIONS: Large atelectasis in the dorsal part of the lungs was found on the first postoperative day after cardiac surgery. However, there was no clear correlation between atelectasis and measured shunt fraction.

Repeated vital capacity manoeuvres after cardiopulmonary bypass: effects on lung function in a pig model.

Respiratory failure following cardiopulmonary bypass (CPB) is a major complication after cardiac surgery. A vital capacity inflation of the lungs, performed before the end of CPB, may improve gas exchange, but the necessity to repeat it is unclear. Therefore, we studied 18 pigs undergoing hypothermic CPB. A vital capacity manoeuvre (VCM) was performed in two groups and consisted of inflating the lungs for 15 s to 40 cm H2O at the end of CPB. In one group, VCM was repeated every hour. The third group served as controls. Atelectasis was studied by CT scan. Intrapulmonary shunt increased after bypass in the controls and improved spontaneously 3 h later without returning to baseline values. From 3 to 6 h after CPB, there was no more improvement and more than 10% atelectasis remained at 6 h. In contrast, the two groups treated before termination of CPB with VCM showed only minor atelectasis and no abnormal changes in gas exchange directly after bypass or later. We conclude that the protective effect of VCM remained for 6 h after bypass, and there was no extra benefit on gas exchange by repeating the VCM.

Use of a vital capacity maneuver to prevent atelectasis after cardiopulmonary bypass: an experimental study.

BACKGROUND: Respiratory failure secondary to cardiopulmonary bypass (CPB) remains a major complication after cardiac surgery. The authors previously found that the increase in intrapulmonary shunt was well correlated with the amount of atelectasis. They tested the hypothesis that post-CPB atelectasis can be prevented by a vital capacity maneuver (VCM) performed before termination of the bypass. METHODS: Eighteen pigs received standard hypothermic CPB (no ventilation during bypass). The VCM was performed in two groups and consisted of inflating the lungs during 15 s to 40 cmH2O at the end of the bypass. In one group, the inspired oxygen fraction (FIO2) was then increased to 1.0. In the second group, the FIO2 was left at 0.4. In the third group, no VCM was performed (control group). Ventilation-perfusion distribution was measured with the inert gas technique and atelectasis by computed tomographic scanning. RESULTS: Intrapulmonary shunt increased after bypass in the control group (from 4.9 +/- 4% to 20.8 +/- 11.7%; P < 0.05) and was also increased in the vital capacity group ventilated with 100% oxygen (from 2.2 +/- 1.3% to 6.9 +/- 2.9%; P < 0.01) but was unaffected in the vital capacity group ventilated with 40% oxygen. The control pigs showed extensive atelectasis (21.3 +/- 15.8% of total lung area), which was significantly larger (P < 0.01) than the proportion of atelectasis found in the two vital capacity groups (5.7 +/- 5.7% for the vital capacity group ventilated with 100% oxygen and 2.3 +/- 2.1% for the vital capacity group ventilated with 40% oxygen. CONCLUSION: In this pig model, postcardiopulmonary bypass atelectasis was effectively prevented by a VCM.

Atelectasis is a major cause of hypoxemia and shunt after cardiopulmonary bypass: an experimental study.

BACKGROUND: Respiratory failure after cardiopulmonary bypass (CPB) remains a major complication after cardiac surgery. The authors tested the hypothesis that atelectasis is an important factor responsible for the increase in intrapulmonary shunt after CPB. METHODS: Six pigs received standard CPB (bypass group). Six other pigs had the same surgery but without CPB (sternotomy group). Another six pigs were anesthetized for the same duration but without any surgery (control group). The ventilation-perfusion distribution was measured with the inert gases technique, extravascular lung water was quantified by the double-indicator distribution technique, and atelectasis was analyzed by computed tomography. RESULTS: Intrapulmonary shunt increased markedly after bypass but was unchanged over time in the control group (17.9 +/- 6.2% vs. 3.5 +/- 1.2%; P < 0.0001). Shunt also increased in the sternotomy group (10 +/- 2.6%; P < 0.01 compared with baseline) but was significantly lower than in the bypass group (P < 0.01). Extravascular lung water was not significantly altered in any group. The pigs in the bypass group showed extensive atelectasis (32.3 +/- 28.7%), which was significantly larger than in the two other groups. The pigs in the sternotomy group showed less atelectasis (4.1 +/- 1.9%) but still more (P < 0.05) than the controls (1.1 +/- 1.6%). There was good correlation between shunt and atelectasis when all data were pooled (R2 = 0.67; P < 0.0001). CONCLUSIONS: Atelectasis is produced to a much larger extent after CPB than after anesthesia alone or with sternotomy and it explains most of the marked post-CPB increase in shunt and hypoxemia. Surgery per se contributes to a lesser extent to postoperative atelectasis and gas exchange impairment.

The ventilation-perfusion relation and gas exchange in mitral valve disease and coronary artery disease. Implications for anesthesia, extracorporeal circulation, and cardiac surgery.

BACKGROUND: Patients with mitral valve disease (MVD) are at greater risk for respiratory complications after cardiac surgery compared with patients with coronary artery disease (CAD). The authors hypothesized that ventilation-perfusion (VA/Q) inequality is more pronounced in patients with MVD before and after induction of anesthesia and during and after surgery when extracorporeal circulation (ECC) is used. METHODS: In patients with MVD (n = 12) or with CAD (n = 12), VA/Q distribution was determined using the multiple inert gas elimination technique. Intrapulmonary shunt (Qs/Qr) defined as regions with VA/Q < 0.005 [% of total perfusion (Qr)], perfusion of "low" VA/Q areas (0.005 < or = VA/Q < 0.1, [% of Qr]), ventilation of "high" VA/Q regions (10 < or = VA/Q < or = 100 [% of total ventilation VE]), and dead space (VA/Q > 100 [% of VE]) were calculated from the retention/excretion data of the inert gases. Recordings were obtained while patients spontaneously breathed air in the awake state, during mechanical ventilation after induction of anesthesia, after separation of patients from ECC, and 4 h after operation. RESULTS: Qs/Qr was low in the awake state (MVD group, 3% +/- 3%; CAD group, 3% +/- 4%) and increased after induction of anesthesia to 10% +/- 8% (MVD group, P < 0.05) and 11% +/- 7% (CAD group, P < 0.01). Qs/Qr increased further after separation from ECC (MVD group, 24% +/- 9%, P < 0.01; CAD group, 23% +/- 7%, P < 0.01). Similarly, alveolar-arterial oxygen tension difference (PA-aO2) increased from 168 +/- 54 mmHg (anesthetized state) to 427 +/- 138 mmHg after ECC (MVD group, P < 0.01) and from 153 +/- 65 mmHg to 377 +/- 101 mmHg (CAD group, P < 0.01). In both groups, PA-aO2 was correlated with Qs/Qr. Four hours after operation, Qs/Qr had decreased significantly to 8% +/- 6% (CAD group) and 10% +/- 6% (MVD group). PA-aO2 and Qs/Qr showed no significant differences between the CAD and MVD groups. CONCLUSIONS: Qs/Qr is the main pathophysiologic mechanism of gas exchange impairment during cardiac surgery for MVD or CAD. Impairment of pulmonary gas exchange secondary to general anesthesia, cardiac surgery, and ECC are comparable for patients undergoing myocardial revascularization or mitral valve surgery.

Thoracolumbar epidural blockade as adjunct to high dose fentanyl/midazolam anesthesia in coronary surgery: effects of sternotomy.

The present study tests the hypothesis that the changes in myocardial lactate metabolism in the early period of coronary surgery are caused by raised adrenergic activity, and that these are preventable by the addition of thoracolumbar epidural blockade to high dose fentanyl/midazolam anesthesia. Twenty-seven male beta 1-blocked patients undergoing coronary surgery were included in a prospective, controlled, randomized study. High dose fentanyl/midazolam anesthesia alone (control) or supplemented with thoracolumbar epidural blockade (treatment) was used. Measurements were performed before the induction of anesthesia and after sternotomy. After sternotomy adrenaline (A) and noradrenaline (NA) had decreased and were both in the low range, especially in the epidural group (P < 0.01). Arterial pressures decreased in both groups, especially in the epidural group, where coronary perfusion pressure (CPP) decreased from 61 (42-88) to 48 (33-64) mm Hg; Systemic vascular resistance (SVR) decreased with 30% in the epidural group (P < 0.01), but not significantly in the control group. The myocardial fractional extraction of lactate decreased in both groups, from 33 (10-45) to 13 (0-42)% in the control group (P < 0.01), and from 36 (19-43) to 10 (2-20)% in the epidural group. It is concluded that high dose fentanyl/midazolam anesthesia prevents hyperadrenergic activity in the early phase of coronary surgery, but cannot eliminate changes in myocardial lactate metabolism. The addition of the thoracolumbar epidural blockade to high dose fentanyl/midazolam anesthesia offers no obvious benefits in the early phase of coronary surgery.

Low-molecular-weight heparin (Fragmin) versus heparin for anticoagulation during cardiopulmonary bypass in open heart surgery, using a pig model.

Fragmin and heparin were studied in pigs during 120 min of cardiopulmonary bypass (CPB) and up to 240 min postoperatively, with respect to clotting, bleeding and the effects of protamine. Thirty-three pigs received bolus injections of 300 IU/kg with or without additional dosage during CPB and with or without subsequent protamine sulphate. Doses of Fragmin 60% higher were necessary to prevent clotting. These had 100% higher anti-FXa levels but about 50% shorter activated coagulation time (ACT) compared with heparin. Anti-FXa increased with cumulative doses of heparin and Fragmin but ACT and activated partial thromboplastin time (aPTT) did not, indicating a larger loss of thrombin inhibition compared with anti-FXa in both drugs during CPB. Thrombin inhibition was crucial for prevention of clotting. Protamine efficiently normalized ACT in the Fragmin group but left a residual 20% anti-FXa, which did not increase the bleeding tendency. Fragmin could adequately be monitored with ACT and would be a safe alternative to heparin in CPB.

Fragmin (LMWH) vs heparin for anticoagulation during in vitro recycling of human blood in cardiopulmonary bypass circuits: dose-dependence and mechanisms of clotting.

Low-molecular-weight heparin (LMWH) (Fragmin) vs heparin was studied in vitro in order to investigate its antithrombotic efficacy in the isolated thrombogenic link of cardiopulmonary bypass (CPB). Fresh human blood (400 ml) with various dosages of the anticoagulant was recycled in a CPB circuit for 120 min. The standard dosage of heparin (1,500 IU, n = 6) was compared with a lower dosage (1,000 IU, n = 3) and several dosages of Fragmin (IU anti-FXa): 750 (n = 1), 1,500 (n = 3), 2,100 (n = 4) and 2,500 (n = 3). Clotting occurred in three Fragmin experiments at dosages of 750, 1,500 and 2,100 IU. This was associated with short activated clotting time (ACT) and activated partial thromboplastin time (aPTT) but was independent of the levels of anti-FXa, FVIII, von Willebrand factor and prothrombin complex. It was concluded that at least twice the dose of Fragmin (anti-FXa), compared with heparin, was required, suggesting that thrombin inhibition is crucial for the antithrombotic efficacy of heparin in CPB circuits. Absence of fibrinolytic markers suggests that the well known enhancement of fibrinolysis often seen during CPB, is not due to heparin interaction with normally circulating blood components, but rather to interaction with the vessel walls or to the surgical trauma itself.

Ventilation-perfusion inequality in patients undergoing cardiac surgery.

BACKGROUND: Impaired gas exchange is a major complication after cardiac surgery with the use of extracorporeal circulation. Blood gas analysis gives little information on underlying mechanisms, in particular if the impairment is multifactorial. In the current study we used the multiple inert gas technique with recordings of hemodynamics to analyze the separate effects of intrapulmonary shunt (QS/QT), ventilation-perfusion (VA/Q) mismatch, and low mixed venous oxygen tension on arterial oxygenation during cardiac surgery. METHODS: VA/Q distribution was studied in nine patients undergoing coronary artery revascularization surgery. The obtained data related to VA/Q distribution were perfusion of lung regions with VA/Q < 0.005 (QS/QT), perfusion of lung regions with 0.005 < VA/Q < 0.1 ("low"-VA/Q regions), ventilation of lung regions with 10 < VA/Q < 100 ("high"-VA/Q regions), and ventilation of lung regions with VA/Q > 100 (dead space [VD/VT]). In addition, arterial and mixed venous oxygen and carbon dioxide tensions and systemic and pulmonary hemodynamics were analyzed. Recordings were made before and after induction of anesthesia, after sternotomy, 45 min after separation from extracorporeal circulation, 4 h postoperatively during mechanical ventilation, and on the 1st postoperative day during spontaneous breathing. RESULTS: In the awake state, QS/QT was 4 +/- 4%, and perfusion of low-VA/Q regions was 3 +/- 5%. The sum of QS/QT and low-VA/Q units correlated with the alveolar-arterial oxygen tension gradient (PA-aO2) (r = 0.63, P < 0.05). After induction of anesthesia, QS/QT increased to 10 +/- 9% (P = 0.069). Sternotomy had little effect on shunt, but QS/QT increased to 22 +/- 8% (P < 0.01) after separation from extracorporeal circulation, which was correlated with a significantly higher PA-aO2 (r = 0.77, P < 0.05). Postoperatively, gas exchange improved rapidly, as assessed by a decrease of PA-aO2 from 341 +/- 77 to 97 +/- 36 mmHg (P < 0.01) and a reduced QS/QT (5 +/- 4%, P < 0.05). On the 1st postoperative day, arterial oxygen tension was significantly lower than preanesthesia values (58 +/- 6 vs. 68 +/- 8 mmHg, P < 0.05). QS/QT had increased to 11 +/- 6% (P < 0.05), but little perfusion of low-VA/Q units was observed. A correlation was found between PA-aO2 and QS/QT (r = 0.82, P < 0.03). CONCLUSIONS: QS/QT is a major component of impaired gas exchange before, during, and after cardiac surgery. QS/QT increases after induction of general anesthesia, probably because of development of atelectasis. After separation from extracorporeal circulation, accumulation of extravascular lung water or further collapse of lung tissue may aggravate QS/QT. Postoperatively, oxygenation improves, possibly because of recruitment of previously nonventilated alveoli or resolution of extravascular lung water. During spontaneous breathing, additional mechanisms such as altered mechanics of the chest, perfusion of low-VA/Q regions, and decreased mixed venous oxygen tension may contribute to impaired gas exchange.

Myocardial metabolism 8 hours after coronary surgery: effects of dopamine.

Myocardial substrate metabolism is abnormal in the early period after cardiac surgery. Myocardial uptake of substrates remains restricted 6 hours postoperatively and cannot match the demand during periods of increased energy requirements. We investigated the relationship between myocardial oxidative rate and substrate uptake in 22 men c. 8 hours after coronary surgery. Myocardial energy demand was raised experimentally by infusing dopamine. The influence of selective beta 1-blockade was analyzed. The uptake of free fatty acids dominated (34.74 +/- 8.83 mmol/min*10(-3) and sufficed to explain the oxygen consumption in basal postoperative conditions (0.468 +/- 0.051 mumol/min) and during amplified energy requirements (0.881 +/- 0.117, r = 0.71). Although the capacity to adjust substrate uptake to energy requirements thus was regained, the uptake of glucose and of lactate (6.14 +/- 13.13 and 2.29 +/- 20.31 mmol/min*10(3) respectively) was marginal, which may be important for ischaemic tolerance. Metoprolol influenced oxygen consumption during amplified adrenergic activity, but did not markedly affect substrates.

Thoracic intravascular and extravascular fluid volumes in cardiac surgical patients.

BACKGROUND: One possible mechanism of impaired oxygenation in cardiac surgery with extracorporeal circulation (ECC) is the accumulation of extravascular lung water (EVLW). Intrathoracic blood volume (ITBV) and pulmonary blood volume (PBV) also may increase after separation from ECC, which can influence both cardiac performance and pulmonary capillary fluid filtration. This study tested whether there were any relationships between lung fluid accumulation and pulmonary gas exchange during the perioperative period of cardiac surgery and ECC. METHODS: Ten patients undergoing myocardial revascularization were studied. ITBV, PBV, and EVLW were determined from the mean transit times and decay times of the dye and thermal indicator curves obtained simultaneously in the descending aorta. Gas exchange was assessed by arterial and mixed venous partial pressure of oxygen (PO2) and carbon dioxide (PCO2), and calculation of alveolo-arterial PO2 gradient (PA-aO2) and venous admixture (QVA/QT). Recordings were made after induction of anesthesia, after sternotomy, 15 min after separation from ECC, and 4 and 20 h postoperatively. RESULTS: After induction of anesthesia, EVLW (6.0 +/- 1.0 ml/kg, mean +/- SD), PBV (3.6 +/- 1.3 ml/kg), and ITBV (18.4 +/- 2.7 ml/kg) were within normal ranges. Oxygenation was moderately impaired, as indicated by an increased PA-aO2 (144 +/- 46 mmHg) and QVA/QT (11 +/- 4%). After separation from ECC, EVLW had increased to 9.1 +/- 2.6 ml/kg, which was accompanied by an increase of ITBV (26.0 +/- 4.4 ml/kg) and PBV (5.6 +/- 1.9 ml/kg). PAa-O2 (396 +/- 116 mmHg) and QVA/QT (29 +/- 7%) also were increased. ITBV and PBV remained increased 4 and 20 h postoperatively, but EVLW decreased to presurgery values. No correlations were found between thoracic intravascular and extravascular fluid volumes and gas exchange. CONCLUSIONS: Cardiac surgery with the use of ECC induces alterations of thoracic intravascular and extravascular fluid volumes. Postoperatively, increased ITBV and PBV need not be associated with higher EVLW. Thus, sufficient mechanisms protecting against lung edema formation or providing resolution of EVLW probably are maintained after ECC. Since oxygenation is impaired during and after cardiac surgery, it is concluded that mechanisms other than or in addition to changes of ITBV, PBV, and EVLW predominantly influence gas exchange.

Myocardial uptake and release of lactate after high dose neurolept endotracheal intubation in coronary surgery.

To evaluate the relationship between the hemodynamic and ECG variables used in routine surveillance of coronary surgery and myocardial lactate metabolism, 23 middle-aged, male, beta 1-blocked patients about to undergo coronary surgery were monitored before and after endotracheal intubation with high dose (30 micrograms/kg) fentanyl-midazolam anesthesia. The induction of anesthesia was followed by a mean arterial pressure decrease (from 98 +/- 4 to 76 +/- 3 mm Hg) and heart rate increase (from 53 +/- 3 to 66 +/- 2 beats/min). After intubation the hemodynamic variables were stable except for a further, transient increase in heart rate (to 69 +/- 2 beats/min). The myocardial uptake of lactate decreased after intubation, from 48 +/- 5 mumol/min to a lowest level of 24 +/- 3 mumol/min. A lactate release was exhibited in 7/23 patients (30%). No ST-segment changes were observed. The correlation between the myocardial lactate uptake/release and hemodynamic or ECG variables was unimpressive or non-existent (r < or = 0.20). Thus, a reduced uptake and even a release of lactate occurred irrespective of the ST-segment, heart rate, or systemic or pulmonary artery pressures. In conclusion, endotracheal intubation in patients with coronary disease was consistently (17/23 patients) followed by a reduced myocardial uptake of lactate, in spite of high dose neurolept anesthesia and beta 1-blockade. This metabolic event was not consistently related to hemodynamic changes.