A double-blind randomized trial: prophylactic vasopressin reduces hypotension after cardiopulmonary bypass

BACKGROUND: Inhibition of angiotensin-converting enzyme (ACE) predisposes patients to vasodilatory hypotension after cardiopulmonary bypass (CPB). This hypotension has been correlated with arginine vasopressin deficiency and can be corrected by its replacement. In patients receiving ACE inhibition, we investigated whether initiation of vasopressin before CPB would diminish post-CPB hypotension and catecholamine use by avoiding vasopressin deficiency. METHODS: Cardiac surgical patients on ACE inhibitor therapy were randomized to receive vasopressin (0.03 U/min) (n = 13) or an equal volume of normal saline (n = 14) starting 20 minutes before CPB. RESULTS: Vasopressin did not change pre-CPB mean arterial pressure or pulmonary artery pressure. After CPB, the vasopressin group had a lower peak norepinephrine dose than the placebo group (4.6 +/- 2.5 versus 7.3 +/- 3.5 microg/min, p = 0.03), a shorter period on catecholamines (5 +/- 6 versus 11 +/- 7 hours, p = 0.03), fewer hypotensive episodes (1 +/- 1 versus 4 +/- 2, p < 0.01), and a shorter intensive care unit length of stay (1.2 +/- 0.4 versus 2.1 +/- 1.4 days, p = 0.03). CONCLUSIONS: In this cohort, prophylactic administration of vasopressin, at a dose without a vasopressor effect pre-CPB, reduced post-CPB hypotension and vasoconstrictor requirements, and was associated with a shorter intensive care unit stay.     

Heparin-coated cardiopulmonary bypass circuits reduce circulating complement factors and interleukin-6 in paediatric heart surgery

Children are sensitive to the inflammatory side effects of cardiopulmonary bypass (CPB). Our intention was to investigate if the biocompatibility benefits of heparin-coated CPB circuits apply to children. In 20 operations, 19 children were randomized to heparin-coated (group HC, n = 10) or standard (group C, n = 10) bypass circuits. Plasma levels of acute phase reactants, interleukins, granulocytic proteins and complement factors were measured. All were significantly elevated after CPB. Levels of complement factor C3a (851 (791-959)ng/ml [median with quartiles] in group C, 497 (476-573)ng/ml in group HC, p < 0.001), Terminal Complement Complex (114 (71-130) AU/ml in group C, 35.5 (28.9-51.4) AU/ml in group HC, p < 0.001), and interleukin-6 (570 (203-743) pg/ml in group C, 168 (111-206)pg/ml in group HC, p = 0.005), were significantly reduced in group HC. Heparin-coated CPB circuits improve the biocompatibility of CPB during heart surgery in the paediatric patient population, as reflected by significantly reduced levels of circulating complement factors and interleukin-6.     

Effect of modified ultrafiltration on plasma thromboxane B2, leukotriene B4, and endothelin-1 in infants undergoing cardiopulmonary bypass.

BACKGROUND: Plasma thromboxane B2 (TXB2), leukotriene B4 (LTB4), and endothelin-1 (ET-1) levels increase on cardiopulmonary bypass (CPB). Elevated levels of TXB2 and ET-1 have been correlated with postoperative pulmonary hypertension in infants undergoing repair of congenital heart defects. LTB4 is a potent chemotactic cytokine whose levels correlate with leukocyte-mediated injury. Modified ultrafiltration (MUF) has been associated with improved hemodynamics and pulmonary function, in addition to its beneficial effects on fluid balance and blood conservation. Recent investigations have suggested that removal of cytokines may be the cause of the improved cardiopulmonary function seen with MUF. METHODS: Plasma TXB2, ET-1, and LTB4 levels were measured in 34 infants undergoing CPB: 22 underwent MUF (group 1), and 12 did not (group 2). Samples were obtained at various time points. All patients underwent conventional ultrafiltration during the rewarming phase of cardiopulmonary bypass. RESULTS: In group 1, mean end-CPB TXB2 level was 101.2 pg/mL versus 46.9 pg/mL post-MUF (p < 0.05). The mean TXB2 level 1 hour post-CPB (54.1 pg/mL) was not significantly different from the post-MUF level. In group 2, the mean end-CPB TXB2 level was 123.6 pg/mL versus 53.2 pg/mL 1 hour post-CPB. Hence, TXB2 levels decreased by similar amounts and to similar levels by 1 hour post-CPB in both groups. ET-1 levels increased after CPB and were unaffected by MUF: 1.45, 1.80, 2.55 pg/mL at end-CPB, post-MUF, and 1 hour post-CPB, respectively, in group 1; and 1.51, and 2.73 pg/mL at end-CPB and 1 hour post-CPB in group 2. LTB4 levels post-MUF were 119% of pre-MUF values, and were similar at 1 hour post-CPB in both groups. CONCLUSIONS: Despite reduction in TXB2 by MUF, values were similar and approached baseline 1 hour post-CPB in both groups. LTB4 levels increased slightly with MUF. ET-1 levels increased during and post-CPB and were unaffected by MUF. MUF does not appear to have a significant effect on post-CPB levels of TXB2, ET-1, and LTB4. Therefore, the improved hemodynamics observed with MUF do not appear to be related to removal of these cytokines.     

Activation of pulmonary mitogen-activated protein kinases during cardiopulmonary bypass

PURPOSE: Cardiopulmonary bypass (CPB) produces an inflammatory response associated with pulmonary dysfunction. Mitogen-activated protein kinases (MAPK) have been shown to mediate pulmonary injury. We hypothesized that MAPK are activated during CPB and potentially contribute to lung injury. METHODS: Pigs were placed on CPB (n = 6) for 90 min, which included 80 min of cardioplegic arrest, followed by 180 min of post-CPB reperfusion. Control animals (n = 6) underwent sternotomy and heparinization only. Lung samples were collected at baseline, during CPB, and during post-CPB reperfusion. Activated forms of extracellular signal-regulated kinases 1/2 (ERK1/2) and p38 were measured by Western blot. Immunohistochemistry was used for tissue localization of activated MAPK. Pulmonary inflammation was determined by histology. Pulmonary edema was estimated by tissue water percentage. RESULTS: Activated ERK1/2 and p38 were increased after 90 min of CPB compared with controls (3.94 +/- 0.61- and 2.49 +/- 0.15-fold increase, respectively; both P < 0.01). At 180 min of post-CPB reperfusion, ERK1/2 activity was increased by nearly 5-fold compared with controls (P < 0.01), whereas p38 activity returned to baseline levels. By immunohistochemistry, activated ERK1/2 and p38 in the CPB group were localized to alveolar epithelial cells, vascular endothelial cells, and bronchial smooth muscle. Histologic signs of lung injury included leukocyte infiltration in the CPB group. Tissue water percentage was increased with CPB (89.9 +/- 1.5% versus 82.5 +/- 1.0%, CPB versus control, P < 0.05). CONCLUSIONS: The results of our study demonstrate that CPB increases pulmonary p38 activity and causes sustained activation of ERK1/2. MAPK activation thus may in part mediate the pulmonary inflammatory response and provide a potential site of intervention to prevent pulmonary dysfunction due to CPB.     

Autoregulation and the CO2 responsiveness of cerebral blood flow after cardiopulmonary bypass

Cerebral blood flow (CBF) was measured by 133Xe clearance to determine whether there were any residual effects of cardiopulmonary bypass (CPB) on the CBF response to changes in arterial PCO2 or blood pressure in the early (3-8 hr) post-CPB period. During CPB, the nine patients studied were managed according to alpha-stat, temperature uncorrected, pH management. The mean +/- SD increase in CBF resulting from an increase in PaCO2 (1.35 +/- 0.5 ml.100 g-1.min-1.mmHg-1 PaCO2) was within the normal range, indicating appropriate CBF response to a change in PaCO2. There were no significant differences in CBF, being 25.7 ml.100 g-1.min-1 at a mean arterial blood pressure of 70 mmHg and 26.5 ml.100 g-1.min-1 at 110 mmHg, demonstrating intact cerebral autoregulation over this pressure range. We conclude that cerebral autoregulation and CO2 responsiveness are preserved in the immediate postoperative period after CPB using alpha-stat pH management.     

Comparison of the inflammatory response between miniaturized and standard CPB circuits in aortic valve surgery.

OBJECTIVE: One of the complications of CPB is the systemic inflammatory response syndrome (SIRS). Recent developments tend to minimize the biological impact of CPB in using miniaturized closed circuit with reduced priming volume and less blood-air interface. The benefit of these miniaturized closed circuits in terms of inflammatory response has been proved in coronary surgery. However, in open heart surgery, the CPB circuit is no more closed and the benefit of the miniaturized set-up could disappear. The aim of the study is to compare the SIRS between standard and miniaturized circuits in aortic surgery. METHODS: Forty patients who underwent singular aortic valve replacement were randomly assigned either to a standard CPB (group A, n=20) or to a miniaturized CPB (group B, n=20). Pertinent clinical and surgical data were collected. Hematological parameters (leukocyte and neutrophil counts) and biochemical parameters (C-reactive protein, cytokine tests) were determined pre-, on and post-CPB. RESULTS: There were an increase in leukocyte and neutrophil counts and a decline in hematocrit in both groups. In both groups, there was a raise after CPB, in C-reactive protein, IL-6, TNF-alpha, neutrophil elastase, and IL-10. However, the raises of elastase and TNF-alpha were significantly lower after the weaning of miniaturized CPB (116+/-46 ng/ml and 10+/-4 pg/ml, respectively) compared to standard CPB (265+/-120 ng/ml, P=0.01 and 18+/-7 pg/ml, P=0.03). The raise of IL-10 is also lower with miniaturized circuit (15+/-6 pg/ml) compared to standard circuit (51+/-26, P=0.004). CONCLUSIONS: This study demonstrates in aortic surgery, the lesser inflammatory response of a miniaturized CPB compared to a standard CPB. However, there is always some inflammation after CPB and a small bio-reactive free perfusion circuit is still to be found in open heart surgery.     

Effect of a human urinary protease inhibitor (Ulinastatin) on respiratory function in pediatric patients undergoing cardiopulmonary bypass

BACKGROUND: We performed this prospective randomized study to determine the effect of a human urinary protease inhibitor (Ulinastatin) on respiratory function in pediatric patients undergoing cardiopulmonary bypass. METHODS: Twenty-two children were included in this study. They were randomly allocated to 1 of the following groups; a control group (n=11) or a Ulinastatin group (n=11) in which patients received 5000 U/kg of Ulinastatin. Arterial blood samples were obtained before cardiopulmonary bypass (CPB), immediately after CPB, and 30 min after protamine administration, as well as 3 hours after and 18 hours after CPB, and Interleukin-8 and neutrophil elastase concentration were evaluated. RESULTS: CPB time and aortic clamp time did not differ between the groups. Interleukin 8 and neutrophil elastase concentrations before CPB increased significantly immediately after CPB, these concentrations did not differ between the groups. However, neutrophil elastase concentrations of a Ulinastatin group were significantly lower than that of a control group at 30 min after protamine administration (a Ulinastatin group: 1011.3+/-539.1 mg/ml, a control group: 1619.7+/-595.7 mg/ml, p<0.05) and A-aDO2 of a Ulinastatin group was significantly lower than that of a control group at 2 hours after CPB (a Ulinastatin group: 67.1+/-70.6 mmHg, a control group: 169.2+/-116.3 g, p<0.05). CONCLUSIONS: These results suggest that Ulinastatin suppresses the increase in neutrophil elastase and protects the respiratory function in pediatric patients undergoing cardiopulmonary bypass.     

Cerebrovascular cytokine responses during coronary artery bypass surgery: specific production of interleukin-8 and its attenuation by hypothermic cardiopulmonary bypass.

Brain dysfunction after cardiopulmonary bypass (CPB) is common, and it has been hypothesized that this injury might be due partly to activation of inflammatory processes in the brain. We measured juguloarterial gradients for interleukin-1beta, interleukin-6, and interleukin-8 (IL-8) as indices of local proinflammatory cytokine production in the brain and studied the effect of temperature during CPB on these changes. Twelve patients undergoing coronary artery bypass graft surgery (normothermic CPB n = 6, hypothermic CPB n = 6) were studied. Cytokine levels were measured in paired arterial and jugular bulb samples obtained before, during, and after CPB. Although systemic levels of all three cytokines increased during and after CPB, increases in juguloarterial cytokine gradients were observed only for IL-8. Juguloarterial IL-8 gradients started to increase 1 h post-CPB and were significantly elevated 6 h post-CPB (P < 0.05). At this time point, the median (interquartile range) juguloarterial IL-8 gradients were significantly larger in the normothermic CPB group (25.81 [24.49-39.51] pg/mL) compared with the hypothermic CPB group (6.69 [-0.04 to 15.47] pg/mL; P < 0.05). These data imply specific and significant IL-8 production in the cerebrovascular bed during CPB and suggest that these changes may be suppressed by hypothermia during CPB. IMPLICATIONS: Using juguloarterial gradients to measure cerebrovascular cytokine production is novel in the setting of cardiopulmonary bypass and implicates the cerebral activation of inflammatory processes, which may contribute to brain dysfunction. Hypothermia during cardiopulmonary bypass may significantly attenuate this response.     

A novel technique using echocardiography to evaluate venous cannula performance perioperatively in CPB cardiac surgery.

OBJECTIVE: Transthoracic echocardiography (TTE) has been used clinically to disobstruct venous drainage cannula and to optimise placement of venous cannulae in the vena cava but it has never been used to evaluate performance capabilities. Also, little progress has been made in venous cannula design in order to optimise venous return to the heart lung machine. We designed a self-expandable Smartcanula (SC) and analysed its performance capability using echocardiography. METHODS: An epicardial echocardiography probe was placed over the SC or control cannula (CTRL) and a Doppler image was obtained. Mean (V(m)) and maximum (V(max)) velocities, flow and diameter were obtained. Also, pressure drop (DeltaP(CPB)) was obtained between the central venous pressure and inlet to venous reservoir. LDH and Free Hb were also compared in 30 patients. Comparison was made between the two groups using the student's t-test with statistical significance established when p<0.05. RESULTS: Age for the SC and CC groups were 61.6+/-17.6 years and 64.6+/-13.1 years, respectively. Weight was 70.3+/-11.6 kg and 72.8+/-14.4 kg, respectively. BSA was 1.80+/-0.2 m(2) and 1.82+/-0.2 m(2), respectively. CPB times were 114+/-53 min and 108+/-44 min, respectively. Cross-clamp time was 59+/-15 min and 76+/-29 min, respectively (p=NS). Free-Hb was 568+/-142 U/l versus 549+/-271 U/l post-CPB for the SC and CC, respectively (p=NS). LDH was 335+/-73 mg/l versus 354+/-116 mg/l for the SC and CC, respectively (p=NS). V(m) was 89+/-10 cm/s (SC) versus 63+/-3 cm/s (CC), V(max) was 139+/-23 cm/s (SC) versus 93+/-11 cm/s (CC) (both p<0.01). DeltaP(CPB) was 30+/-10 mmHg (SC) versus 43+/-13 mmHg (CC) (p<0.05). A Bland-Altman test showed good agreement between the two devices used concerning flow rate calculations between CPB and TTE (bias 300 ml+/-700 ml standard deviation). CONCLUSIONS: This novel Smartcanula design, due to its self-expanding principle, provides superior flow characteristics compared to classic two stage venous cannula used for adult CPB surgery. No detrimental effects were observed concerning blood damage. Echocardiography was effective in analysing venous cannula performance and velocity patterns.     

Low molecular weight dextran sulfate prevents complement activation and delays hyperacute rejection in pig-to-human xenotransplantation models

Dextran sulfate of 5000 molecular weight (DXS 5000) is known to block complement activation as well as the intrinsic coagulation cascade by potentiation of C inhibitor. The effect of DXS 5000 on hyperacute rejection (HAR) was tested in pig-to-human xenotransplantation models. For in vitro testing, a cytotoxicity assay was used with the pig kidney cell line PK15 as target cells and fresh, undiluted human serum as antibody and complement source. Ex vivo pig lung perfusion was chosen to assess DXS 5000 in a physiologic model. Pig lungs were perfused with fresh, citrate-anticoagulated whole human blood to which 1 or 2 mg/ml DXS 5000 were added; the lungs were ventilated and the blood de-oxygenated. Pulmonary vascular resistance (PVR) and blood oxygenation (deltapO2) were monitored throughout the experiment. Autologous pig blood and human blood without DXS 5000 served as controls. In the PK 15 assay DXS 5000 led to a complete, dose-dependent inhibition of human serum cytotoxicity with an average IC50 of 43 +/- 18 microg/ml (n=8). Pig lungs perfused with untreated human blood (n=2) underwent HAR within 105 +/- 64 min, characterized by increased PVR, decrease of deltapO2, and generalized edema. Microscopically, capillary bleeding as well as deposition of human antibodies, complement and fibrin could be observed. Addition of DXS 5000 (n=4) prolonged lung survival to 170 +/- 14 min for 1 mg/ml and 250 +/- 42 min for 2 mg/ml. and PVR values as well as edema formation were comparable to control lungs that were perfused with autologous pig blood (n=2). Activation of complement (activation products in serum, deposition on lung tissue) and the coagulation system (fibrin monomers) were significantly diminished as compared to human blood without DXS 5000. Binding of anti-Gal antibodies was not influenced, and in vitro experiments showed no evidence of complement depletion by DXS 5000. In conclusion, DXS 5000 is an efficient complement inhibitor in pig-to-human xenotransplantation models and therefore a candidate for complement-inhibitory/anti-inflammatory therapy either alone or in combination with other substances and warrants further investigation.     

Mannitol and dopamine in patients undergoing cardiopulmonary bypass: a randomized clinical trial

In this prospective, randomized, placebo-controlled, double-blinded study, we determined the effects of two commonly used adjuncts, mannitol and dopamine, on beta(2)-microglobulin (beta(2)M) excretion rates in patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass (CPB). beta(2)M excretion rate has been described as a sensitive marker of proximal renal tubular function. One-hundred patients with a preoperative serum creatinine level 相似文献   

In vivo evaluation of a phosphorylcholine coated cardiopulmonary bypass circuit

A complete phosphorylcholine coated cardiopulmonary bypass circuit, including the Dideco D901 oxygenator, was tested for gas transfer, blood path resistance, and biocompatibility in a standardized setting. Blood compatibility was tested by measuring complement and platelet activation. Three dogs (mean body weight 28 +/- 3 kg) were placed on cardiopulmonary bypass at a flow rate of 600 mL/min during 6 hours. The animals were weaned from cardiopulmonary bypass and sacrificed electively after 7 days. Oxygen and carbon dioxide transfer were 26.6 +/- 2.4 mL/min and 33.0 +/- 1.9 mL/min, respectively. Mean pressure drop across the oxygenator was 52.6 +/- 0.2 mmHg. The respective baseline values for thromboxane B2, prostaglandin E2 and platelet factor 4 were 1817 +/- 283 pg/mL, 12783 +/- 2109 pg/mL, and 0.35 +/- 0.08 IU/mL. Thromboxane B2 and prostaglandin E2 increased slightly to 2881 +/- 868 pg/mL and 18083 +/- 3144 pg/mL at 30 minutes of bypass, whereas platelet factor 4 values remained stable curing the procedure. Concentrations of complement split products C5a were only mildly increased. After use scanning electron microscopy was performed on the inner housing, heat exchanger, and outer surface of the hollow fibers. No thrombi nor organized cellular deposits were found on any of the components. Phosphorylcholine coating of CPB seems to be very promising regarding platelet activation and complement activation.     

Cardiopulmonary bypass reduces the minimum alveolar concentration for isoflurane

OBJECTIVE: The purpose of this investigation was to determine the influence of cardiopulmonary bypass (CPB) on the minimum alveolar concentration (MAC) of isoflurane in a rat model of CPB. DESIGN: Prospective. SETTING: University research laboratory. PARTICIPANTS: Sprague-Dawley rats. INTERVENTIONS: Using tail-clamp methodology, the pre- and post-CPB MAC for isoflurane was studied. METHODS AND MAIN RESULTS: Rats were anesthetized with isoflurane, intubated, ventilated, and surgically prepared for CPB, after which they were randomized to either Sham-operated or CPB groups. The CPB group (n = 10) underwent 90 minutes of normothermic nonpulsatile CPB. The Sham group (n = 13) were cannulated but did not undergo CPB. Pre- and post-CPB MAC determinations were compared within groups using a paired Student t test. The CPB group had a pre-CPB baseline isoflurane MAC of 1.09% +/- 0.11% versus 1.09% +/- 0.08% in the Sham group (p = 0.90). Twenty minutes after CPB, the CPB group exhibited a decrease in MAC to 0.98% +/- 0.14% (p = 0.0026, compared with baseline). The MAC in the Sham group was unchanged (p = 0.5852, compared with baseline). Two hours after CPB, the MAC in the CPB group remained lower compared with baseline at 0.99% +/- 0.14% (p = 0.0032). CONCLUSIONS: CPB resulted in a small (10%) but significant reduction in the MAC for isoflurane. The mechanism behind this reduction in MAC is not clear but may be related to CPB-induced cerebral injury.     

Prostaglandin synthesis inhibitor affects humoral conditions and oxygen metabolism during normothermic cardiopulmonary bypass

We have reported that infusion of prostaglandin synthesis inhibitor (PGSI) reduced the severity of hypotension during normothermic cardiopulmonary bypass (CPB). In the present study, we investigated the effects of PGSI on humoral conditions and whole body oxygen metabolism during normothermic CPB conducted for 60 min in 8 adult goats. The PGSI group (n = 4) was administered 100 to 150 mg of flurbiprofen, a potent PGSI, before and during CPB, and the control group (n = 4) was administered noradrenaline (NA) to restore hypotension. The prostaglandin E2 (PGE2) and NA concentrations in the PGSI group were significantly lower than those of the control group (PGE2 8.8 +/- 1.0 versus 30.3 +/- 11.5 pg/ml, NA 431 +/- 197 versus 3847 +/- 2,153 pg/ml). The adrenaline concentration was not significantly different between the groups. The oxygen consumption and the oxygen extraction rate were not significantly different between the groups, but the blood lactate level in the PGSI group was lower than that of the control group (34.3 +/- 7.6 versus 43.7 +/- 3.8 mg/dl). In conclusion, PGSI improves humoral disorder and thus prevents inadequate tissue oxygen delivery.     

Effects of cardiopulmonary bypass on eicosanoid metabolism during pediatric cardiovascular surgery

Cardiopulmonary bypass in children with congenital heart disease is associated with significant morbidity manifested by increased complement degradation products, heightened pulmonary vascular activity, and coagulopathy. In adults with cardiac disease, the prostaglandins (eicosanoids) have been shown to contribute to the pathophysiologic response to extracorporeal circulation. This study assessed the effect of cardiopulmonary bypass in infants and children on two potent eicosanoids: thromboxane, a vasoconstrictor and platelet aggregating agent, and prostacyclin, a vasodilator and platelet disaggregating agent. The biochemical profiles of thromboxane and prostacyclin were evaluated in temporal relationship to selected parameters of platelet loss and pulmonary vascular hemodynamics during and after cardiopulmonary bypass. Twenty-one children, aged 3 days to 9 years, with congenital heart defects who were undergoing repair with cardiopulmonary bypass were studied. Nine pediatric patients undergoing palliative heart operations with no cardiopulmonary bypass served as the control group. In the group having cardiopulmonary bypass, the thromboxane concentration significantly increased during bypass (195 +/- 10 to 910 +/- 240 pg/ml, +/- standard error of the mean, p less than 0.005), whereas the control group demonstrated no significant change in thromboxane concentration. The highest thromboxane values were seen in the youngest patients (p less than 0.002). There was no significant correlation between thromboxane changes with alterations in pulmonary vascular resistance, platelet loss, duration of cardiopulmonary bypass or aortic cross-clamping. Prostacyclin levels rose significantly in both the bypass group (100 +/- 20 to 570 +/- 80 pg/ml, p less than 0.01) and in the control group (109 +/- 44 to 589 +/- 222 pg/ml, p less than 0.01), which apparently is due to surgical manipulation of vascular endothelium. These data show that eicosanoid production is significantly altered in children during cardiopulmonary bypass. Although thromboxane, a potent vasoconstrictor, is produced in significant amounts during and after cardiopulmonary bypass, our data show that thromboxane does not directly mediate changes in pulmonary artery hypertension and is not quantitatively related to platelet loss during pediatric cardiovascular operations.     

Pulmonary hypertension and leukosequestration after lower torso ischemia.

Ischemia stimulates thromboxane (Tx) synthesis. This study tests the hypothesis that the cardiopulmonary dysfunction that may follow aortic declamping is related to Tx. Anesthetized dogs (N = 15) were subjected to 4 hours of infrarenal aortic cross-clamping. In untreated control animals (N = 7), plasma levels of TxB2 rose from 654 +/- 74 pg/mL to 1238 +/- 585 pg/mL at 5 min (p less than 0.05), and to 3174 +/- 912 pg/mL 3 hours after declamping (p less than 0.05). Mean pulmonary artery pressure (MPAP) rose 5 min after declamping from 13 +/- 2 mmHg to 21 +/- 2 mmHg (p less than 0.05). Cardiac Index (CI) declined during ischemia from 181 +/- 30 mL/kg.min to 128 +/- 16 mL/min.kg (p less than 0.05), and to 80 +/- 8 mL/min.kg after 4 hours of reperfusion (p less than 0.05). Platelet counts declined but platelets labeled with In 111 did not accumulate in the lungs, whereas quantitative counts of polymorphonuclear leukocytes (PMN) in the lungs 4 hours after declamping yielded 213 +/- 33 PMN/25 high power fields (HPF) in dependent areas of the lung and 153 +/- 26 PMN/25 HPF in nondependent areas. The wet/dry weight ratio of the lungs was not elevated, although foci of proteinaceous exudate and PMNs in alveoli were noted. Another group of dogs (N = 8) were pretreated by random choice with the Tx synthase inhibitor OKY-046 2 mg/kg IV every 2 hours, which led to: lower TxB2 levels at baseline 95 +/- 35 pg/mL (p less than 0.05), 5 min after ischemia 140 +/- 93 pg/mL and after 3 hours of reperfusion 122 +/- 36 (p less than 0.05); lower MPAP, 16 +/- 2 mmHg (p less than 0.05); higher CI throughout (p less than 0.05); normal histology and reduced pulmonary PMN sequestration both in dependent 127 +/- 15 PMN/25 HPF and nondependent areas of the lungs 95 +/- 11 PMN/25 HPF (p less than 0.05). In animals undergoing sham ischemia (N = 3), levels of TxB2 and cardiopulmonary function remained unchanged from baseline. There were 150 PMN/25 HPF in dependent and 85 PMN/25 HPF in nondependent lung areas. The results indicate that ischemia-generated Tx mediates a rise in MPAP, a fall in CI, and PMN entrapment in the lungs.     

Arachidonic acid metabolism and effectiveness of aprotinin treatment during cardiopulmonary bypass]

Arachidonic acid metabolism was investigated in 30 open heart cases, utilizing nonpulsatile cardiopulmonary bypass (CPB), consisted of 15 untreated cases (Group I) and 15 cases treated with aprotinin mostly given into CPB circuit during CPB (Group II). In group I, arterial blood concentration of thromboxane B2 (TXB2, stable metabolite of thromboxane A2, pg/ml) significantly increased from 45.9 +/- 40.5 preoperatively to 560.2 +/- 381.5 (p less than 0.01) at 30 minutes of CPB (total bypass) and to 830.5 +/- 591.1 (p less than 0.005) at the end of CPB (partial bypass). TXB2 levels in pulmonary artery (PA) and left atrium (LA) did not significantly increase just before, 5 minutes of CPB as compared with preoperative value. At the end of CPB TXB2 levels in PA (625.0 +/- 186.3) and LA (817.0 +/- 320.0) were significantly higher than preoperative value. However there was no significant difference between PA and LA values. Contrarily in group II TXB2 levels were significantly suppressed as compared with the value at each corresponding time in group I. beta-thromboglobulin levels also changed almost parallel to TXB2 levels in both groups. In conclusion, arachidonic acid metabolic disorders could occur in CPB circuit rather than in pulmonary circulation during CPB. Aprotinin administration into CPB circuit suppressed to some extent the platelet activation.     

Pediatric cardiopulmonary bypass adaptations for long-term survival of baboons undergoing pulmonary artery replacement

Cardiopulmonary bypass (CPB) protocols of the baboon (Papio cynocephalus anubis) are limited to obtaining experimental data without concern for long-term survival. In the evaluation of pulmonary artery tissue engineered heart valves (TEHVs), pediatric CPB methods are adapted to accommodate the animals' unique physiology enabling survival up to 6 months until elective sacrifice. Aortic access was by a 14F arterial cannula and atrial access by a single 24F venous cannula.The CPB circuit includes a 3.3 L/min flow rated oxygenator, 1/4" x %" arterial-venous loop, 3/8" raceway, and bubble trap. The prime contains 700 mL Plasma-Lyte, 700 units heparin, 5 mL of 50% dextrose, and 20 mg amiodarone. Heparinization (200 u/kg) targets an activated clotting time of 350 seconds. Normothermic CPB was initiated at a 2.5 L/m2/min cardiac index with a mean arterial pressure of 55-80 mmHg. Weaning was monitored with transesophageal echocardiogram. Post-CPB circuit blood was re-infused. Chest tubes were removed with cessation of bleeding. Extubation was performed upon spontaneous breathing. The animals were conscious and upright 3 hours post-CPB. Bioprosthetic valves or TEHVs were implanted as pulmonary replacements in 20 baboons: weight = 27.5 +/- 5.6 kg, height = 73 +/- 7 cm, body surface area = 0.77 m2 +/- 0.08, mean blood flow = 1.973 +/- .254 L/min, core temperature = 37.1 +/- .1 degree C, and CPB time = 60 +/- 40 minutes. No acidosis accompanied CPB. Sixteen animals survived, four expired. Three died of right ventricular failure and one of an anaphylactoid reaction. Surviving animals had normally functioning replacement valves and ventricles. Baboon CPB requires modifications to include high systemic blood pressure for adequate perfusion into small coronary arteries, careful CPB weaning to prevent ventricular distention, and drug and fluid interventions to abate variable venous return related to a muscularized spleno-splanchnic venous capacity.     

Does cardiopulmonary bypass alter enflurane requirements for anesthesia?

This study on dogs determined whether the requirement for enflurane anesthesia was different pre- versus postcardiopulmonary bypass (CPB). Male mongrel dogs (n = 16) were anesthetized with enflurane in oxygen. Tracheal intubation was performed, monitors placed, and end-tidal enflurane concentration measured via a Puritan-Bennett Anesthesia Agent Monitor. MAC was determined by the tail-clamp method. CPB was then initiated using aortoatrial (n = 6, group 1) or femoral artery-vein (n = 4, group 2) cannulation or none (n = 6, group 3, control). CPB was maintained for 1 h using a bubble oxygenator, a crystalloid prime, and flows of approximately 70-80 ml/kg with a mean systemic pressure maintained between 50-70 mmHg. Following separation from CPB, MAC was again determined. The reduction in enflurane MAC following CPB was 30.1 +/- 21.5% (mean +/- SD; P less than 0.05 vs. pre-CPB) in group 1 but there was a wide range of reduction produced (3.8-58.8%). The degree of MAC reduction (19.8 +/- 8.6%; P less than 0.05 vs. pre-CPB) produced by CPB in group 2 was much less variable in degree (range 13.0-32.4%) but did not differ from group 1. Although pre- versus post-CPB mean systemic pressure fell from 83 +/- 13 to 69 +/- 15 mmHg (P less than 0.05), this is above the level likely to produce a reduction in MAC. No other significant hemodynamic changes were observed. Temperature pre- versus post-CPB was not different. The degree of hemodilution and acid-base disturbances are unlikely to be the explanation.(ABSTRACT TRUNCATED AT 250 WORDS)