Administration of vancomycin during cardiopulmonary bypass

Vancomycin was given during cardiopulmonary bypass to 12 anaesthetised patients undergoing open heart surgery. Injection of vancomycin 1 g within 60 s via the venous inlet of the oxygenator resulted in a moderate and transient decrease of mean arterial pressure. This minimal reaction may be attributed to dilution of vancomycin by the extracorporeal circuit volume, to the bypassing of the lungs which are a major site of storage of vasoactive substances, or to the maintenance of adequate perfusion flow during cardiopulmonary bypass. The results suggest that the haemodynamic adverse reactions to vancomycin, given as antibiotic prophylaxis, may be decreased by its administration after initiation of cardiopulmonary bypass.     

Endothelial dysfunction in cerebral microcirculation during hypothermic cardiopulmonary bypass in newborn lambs

Objectives: Inflammatory stimuli or mechanical stresses associated with hypothermic cardiopulmonary bypass could potentially impair cerebrovascular function, resulting in inadequate cerebral perfusion. We hypothesize that hypothermic cardiopulmonary bypass is associated with endothelial or vascular smooth muscle dysfunction and associated cerebral hypoperfusion. Therefore we studied the cerebrovascular response to endothelium-dependent vasodilator, acetylcholine, endothelium-independent nitric oxide donor, sodium nitroprusside, and vasoactive amine, serotonin, in newborn lambs undergoing hypothermic cardiopulmonary bypass (nasopharygeal temperature = 18° C). Methods: Studies were performed on 13 newborn lambs equipped with a closed cranial window, allowing for direct visualization of surface pial arterioles. Six animals were studied while undergoing hypothermic cardiopulmonary bypass, whereas seven served as nonbypass, warm (37° C) controls. Pial arteriolar caliber (range = 111 to 316 μm diameter) was monitored using video microscopy. Results: Topical application of acetylcholine caused a dose-dependent increase in arteriolar diameter in the control group that was absent in animals undergoing hypothermic cardiopulmonary bypass. Hypothermic cardiopulmonary bypass did not alter the vasodilation in response to sodium nitroprusside. Furthermore, the contractile response to serotonin was fully expressed during hypothermic cardiopulmonary bypass. Conclusions: The specific loss of acetylcholine-induced vasodilation suggests endothelial cell dysfunction rather than impaired ability of vascular smooth muscle to respond to nitric oxide. It is speculated that loss of endothelium-dependent regulatory factors in the cerebral microcirculation during hypothermic cardiopulmonary bypass may enhance vasoconstriction, and impaired cerebrovascular function may be a basis for associated neurologic injury during or after hypothermic cardiopulmonary bypass. (J thorac Cardiovasc Surg 1998;15:1047-54)     

Blood-Surface Interactions During Cardiopulmonary Bypass

A bstract The interaction between blood and the synthetic surfaces of the heart-lung machine activates plasma protein systems and blood cells to produce a host of vasoactive substances that mediate the "whole body inflammatory response" associated with cardiopulmonary bypass (CPB). Plasma proteins are instantaneously adsorbed onto nonendothelial surfaces; plasma factor XII is cleaved into two serine proteases; and platelets are activated to aggregate, adhere to adsorbed fibrinogen, and release granule contents. Activation of factor XII initiates coagulation by the intrinsic coagulation pathway and activates complement. Complement stimulates neutrophils to release vasoactive and cytotoxic substances. Endothelial cells, perhaps stimulated by formation of minute quantities of thrombin, produce tissue plasminogen activator, which generates plasmin, a fibrolytic enzyme. Blood becomes a stew of powerful enzymes and chemicals that alters vascular smooth muscle and endothelial cell contraction. Capillary permeability increases, fluid is retained, and function of essentially every organ is temporarily impaired. Attempts to control the morbidity of CPB have focused on reversible inhibitors of specific reactions in blood. Prostanoids and new disintegrins are promising platelet inhibitors that are reversible. Aprotinin and other serine protease inhibitors partially control fibrinolysis and activation of neutrophils. Alternatives to heparin also show promise. Eventually control of the interaction of blood and synthetic surfaces will control the adverse reactions of the heart-lung machine and reduce the bleeding, thrombotic and inflammatory complications of open heart operations.     

Effects of Dexamethasone on Intravascular and Extravascular Fluid Balance in Patients Undergoing Coronary Bypass Surgery with Cardiopulmonary Bypass

Background: Cardiac surgery with cardiopulmonary bypass is often associated with postoperative hemodynamic instability. In this regard beneficial effects of corticosteroids are known. The purpose of this study was to investigate whether these effects are due mainly to a modification of the intravascular and extravascular volume status or whether a more direct improvement of cardiovascular performance by corticosteroids is the underlying mechanism.

Methods: Twenty patients undergoing elective coronary bypass grafting were included in this randomized double-blind study. Patients of the treatment group received 1 mg/kg-1 dexamethasone after induction of anesthesia. In addition to the use of standard monitors and detailed fluid balance assessments, the transpulmonary double-indicator technique was used to measure extravascular lung water, total blood volume, and intrathoracic blood volume. Measurements were done after induction of anesthesia and 1 h, 6 h, and 20 h after the end of surgery.

Results: After cardiopulmonary bypass, no relevant increase in extravascular lung water was observed, despite highly positive fluid balances in all patients. A significantly smaller increase in extravascular fluid content was observed in the dexamethasone group. Total blood volume and intrathoracic blood volume did not differ in the two groups. Patients pretreated with dexamethasone had a decreased requirement for vasoactive substances and, in contrast with the control group, no increase in pulmonary artery pressure.     

Effects of dexamethasone on intravascular and extravascular fluid balance in patients undergoing coronary bypass surgery with cardiopulmonary bypass

BACKGROUND: Cardiac surgery with cardiopulmonary bypass is often associated with postoperative hemodynamic instability. In this regard beneficial effects of corticosteroids are known. The purpose of this study was to investigate whether these effects are due mainly to a modification of the intravascular and extravascular volume status or whether a more direct improvement of cardiovascular performance by corticosteroids is the underlying mechanism. METHODS: Twenty patients undergoing elective coronary bypass grafting were included in this randomized double-blind study. Patients of the treatment group received 1 mg/kg-1 dexamethasone after induction of anesthesia. In addition to the use of standard monitors and detailed fluid balance assessments, the transpulmonary double-indicator technique was used to measure extravascular lung water, total blood volume, and intrathoracic blood volume. Measurements were done after induction of anesthesia and 1 h, 6 h, and 20 h after the end of surgery. RESULTS: After cardiopulmonary bypass, no relevant increase in extravascular lung water was observed, despite highly positive fluid balances in all patients. A significantly smaller increase in extravascular fluid content was observed in the dexamethasone group. Total blood volume and intrathoracic blood volume did not differ in the two groups. Patients pretreated with dexamethasone had a decreased requirement for vasoactive substances and, in contrast with the control group, no increase in pulmonary artery pressure. CONCLUSIONS: Extravascular fluid but not extravascular lung water is increased in patients after surgery with cardiopulmonary bypass. Pretreatment of adult patients with 1 mg/kg-1 dexamethasone before coronary bypass grafting decreases extravascular fluid gain and seems to improve postoperative cardiovascular performance. This effect is not caused by a better intravascular volume status.     

The impact of heparin-coated circuits on hemodynamics during and after cardiopulmonary bypass

This study was performed to investigate if heparin-coated extracorporeal circuits can reduce the systemic inflammatory reaction with the subsequent release of vasoactive substances during and after cardiopulmonary bypass. Fifty-one patients scheduled for coronary artery bypass grafting were perfused with either a heparin-coated or an uncoated circuit. During bypass the mean arterial pressure was maintained as near as possible to 60 mm Hg. Mediators for inflammation, hemodynamic, and oxygen parameters were determined during and after bypass. To reach the target mean arterial pressure in the first hour of bypass the pump flow in the uncoated group had to be increased (P<0.05), consequently the systemic vascular resistance index decreased (P<0.05). After bypass more inotropic support was necessary in this group to reach this pressure. In the coated group less bradykinin, complement activation, and elastase was generated during bypass (P<0.05). The results of this study suggest that heparin coating not only improves biocompatibility, but also ameliorates the hemodynamic instability during and after bypass.     

Lowest hematocrit on bypass and adverse outcomes associated with coronary artery bypass grafting. Northern New England Cardiovascular Disease Study Group

BACKGROUND: Cardiac surgery patients' hematocrits frequently fall to low levels during cardiopulmonary bypass. METHODS: We investigated the association between nadir hematocrit and in-hospital mortality and other adverse outcomes in a consecutive series of 6,980 patients undergoing isolated coronary artery bypass graft surgery. The lowest hematocrit during cardiopulmonary bypass was recorded for each patient. Patients were divided into categories based on their lowest hematocrit. Women had a lower hematocrit during bypass than men but both sexes are represented in each category. RESULTS: After adjustment for preoperative differences in patient and disease characteristics, the lowest hematocrit during cardiopulmonary bypass was significantly associated with increased risk of in-hospital mortality, intra- or postoperative placement of an intraaortic balloon pump and return to cardiopulmonary bypass after attempted separation. Smaller patients and those with a lower preoperative hematocrit are at higher risk of having a low hematocrit during cardiopulmonary bypass. CONCLUSIONS: Female patients and patients with smaller body surface area may be more hemodiluted than larger patients. Minimizing intraoperative anemia may result in improved outcomes for this subgroup of patients.     

Pathophysiology of Cardiopulmonary Bypass: Current Issues

Much of the research related to cardiopulmonary bypass in recent years has been directed toward defining the changes in plasma and blood cells during bypass. In this review, recent information is reexamined for six areas of current interest. These areas are complement activation, immune response, anaphylactic reactions, coagulation, and cerebral dysfunction. Complement may be activated by either the classical or alternate pathway during cardiopulmonary bypass and protamine administration. Membrane oxygenators appear to diminish the degree of complement activation. Complement is a major factor in the whole body inflammatory response; which often accompanies cardiopulmonary bypass. A product of complement activation, C5a- desArg, causes activation and aggregation of granulocytes. Other products of complement activation lead to lysis of blood cells including granulocytes and red cells. Bubble oxygenators appear to have a distinct disadvantage compared to membrane oxygenators regarding infection. Airborne microorganisms are more likely to be entrained into circulating blood with bubble oxygenators than with membrane oxygenators. Bubble oxygenators cause a greater decrease in leukocyte number and function than membrane oxygenators. Anaphylactic reactions have been associated with use of antibiotics, blood products, protamine, and volume expanders during cardiopulmonary bypass. Protamine reactions may be on an immunological basis or due to direct toxicity of the drug. Free radicals including superoxide, hydrogen peroxide, and the hydroxyl radical may be generated during cardiopulmonary bypass and reperfusion. Free radical scavengers including; vitamin E, coenzyme Q, vitamin C, mannitol, and glutathione have been studied. The avoidance of blood transfusion because of risk of transmitted infection including AIDS has become a major goal in cardiac surgery. Factors that correlate with increased transfusion requirement include low hematocrit, female gender, increased age, small body size, low ejection fraction, reoperation, and emergency operation. Heparin resistance due to antithrombin III deficiency is being recognized more commonly. Antithrombin III deficiency may be corrected with fresh frozen plasma. Patients with heparin induced thrombocytopenia may be difficult to manage. Several management protocols are suggested. The most straightforward appears to be the use of aspirin preoperatively and platelet transfusions postoperatively. The incidence of cerebral dysfunction after cardiopulmonary bypass depends on the sensitivity of the test or indicator used. Perioperative stroke is associated with intrinsic cerebrovascular disease and atherosclerosis of the ascending aorta. Retinal angiograms during cardiopulmonary bypass show that microemboli are very common. Cerebroplegia has been shown to extend the period of safe circulatory arrest in animals. Much of the new knowledge concerning cardiopulmonary bypass is the result of close collaboration between cardiac surgeons and nonsurgical scientists.     

Limiting edema in neonatal cardiopulmonary bypass with narrow-range molecular weight hydroxyethyl starch.

The marked edema observed in neonatal cardiopulmonary bypass is thought to result from pathologic increases in capillary permeability. Pentafraction is a subfraction of hydroxyethyl starch that is thought to be of appropriate size and shape to be retained by leaking capillaries and seal endothelial gaps in capillary basement membranes. To test the hypothesis that pentafraction would reduce edema in neonatal cardiopulmonary bypass, we established a model of edema formation in neonatal bypass in which neonatal piglets underwent 2 hours of normothermic cardiopulmonary bypass with crystalloid prime and no myocardial ischemia. Before initiation of bypass, experimental animals (n = 11) received intravenous pentafraction, 3 gm/kg. Control animals (n = 10) received an equivalent volume of saline. Hemodynamic parameters, animal weight, fluid redistribution, and percent tissue water of individual organs were assessed during and after bypass. Pentafraction treatment resulted in significant differences in (1) lowered percent body weight gain from baseline (11% versus 48%), (2) lowered volume requirement to maintain venous reservoir during cardiopulmonary bypass (148 ml/kg versus 581 ml/kg), (3) less fluid loss from the peritoneum (11 ml/kg versus 115 ml/kg), and (4) lowered percent tissue water of kidney, pancreas, stomach, jejunum, colon, and skeletal muscle (p less than 0.05 by unpaired t test). Pentafraction had no effect on hemodynamic parameters during bypass nor in percent tissue water of heart, lung, liver, spleen, skin, or brain. In summary, pentafraction lessened weight gain and fluid requirements during cardiopulmonary bypass, favorably influencing the percent tissue water of certain organs. If pentafraction functions as proposed, it may have wide applicability not only in cardiopulmonary bypass (or extracorporeal membrane oxygenation) but also in other clinical scenarios with altered capillary permeability.     

Incidence and significance of abnormal hepatic venous Doppler flow velocities before cardiac surgery

OBJECTIVE: The purpose of this study was to determine the incidence and significance of abnormal hepatic Doppler venous flow velocities as signs of an abnormal right ventricular filling pattern before cardiac surgery. DESIGN: Retrospective and prospective validation study. Setting: Tertiary care hospital. PARTICIPANTS: Cardiac surgical patients (121 patients). INTERVENTIONS: Not applicable. MEASUREMENTS: Demographic, hemodynamic, and echocardiographic variables; vasoactive support; and difficult separation from bypass were compared between patients with or without abnormal hepatic venous Doppler flow. Logistic regression analysis was performed to identify predictors of difficult separation from bypass. Abnormal hepatic venous flow was observed in 23 (29%) and 17 patients (41%) in the retrospective and prospective study. Abnormal hepatic venous flow before surgery was associated with more vasoactive support in both the retrospective (p = 0.0362) and prospective study (p = 0.0163). In the prospective study, abnormal hepatic venous flow was associated with a higher Parsonnet score (p = 0.0005), more atrial fibrillation (p < 0.0001), pacemaker requirement (p = 0.0124), mitral valve replacement (p = 0.0325), reoperation (p = 0.0050), lower mean arterial pressure to pulmonary artery pressure ratio (p = 0.0127), higher wall motion score index (p = 0.0491), and higher incidence of abnormal right ventricular systolic function (p = 0.0139). Abnormal hepatic venous flow was not found to be an independent predictor of difficult separation from bypass. CONCLUSIONS: Abnormal hepatic venous flow velocities before cardiac surgery are frequent and are associated with increased need for vasoactive support after cardiopulmonary bypass. However, it is not an independent predictor of difficult separation from bypass and worse outcome.     

The Renin-Angiotensin-Aldosterone System and Hematologic Changes During Pulsatile and Nonpulsatile Cardiopulmonary Bypass

Abstract: The effects of pulsatile and nonpulsatile cardiopulmonary bypass using a roller pump on levels of vasoactive hormones and hematologic changes were studied in 32 patients subjected to elective primary coronary artery bypass graft surgery. Seventeen patients had nonpulsatile perfusion (nonpulsatile group) and 15 patients had pulsatile perfusion (pulsatile group) during the period of cardiac arrest. Vasoactive hormones (plasma renin, angiotensin II, aldosterone, epinephrine, and norepinephrine) were measured in these patients. In order to clarify hematologic changes, plasma free hemoglobin, number of platelets, platelet factor 4, and β -thromboglobulin were measured. There were no significant differences between the pulsatile and nonpulsatile groups with regard to vasoactive hormones and damage of platelets. In the pulsatile group, however, the rise of plasma free hemoglobin levels was significantly higher than that in the nonpulsatile group during and after cardiopulmonary bypass. We did not see the benefit of pulsatile perfusion using a roller pump on vasoactive hormones. Evidence of increased hemolysis with pulsatile flow was demonstrated in our cases.     

Role of nitric oxide in a temperature dependent regulation of systemic vascular resistance in cardiopulmonary bypass.

OBJECTIVES: Nitric oxide is the most potent vasodilator among inflammation-mediated vasoactive substances. Tepid cardiopulmonary bypass has been known to maintain low vascular resistance and nitric oxide may also be involved. There has been no previous clinical study elucidating a role of nitric oxide in a temperature dependent regulation of systemic vascular resistance in cardiopulmonary bypass. METHODS: Thirty-one patients who underwent valvular surgery were randomly divided into two comparable groups; consisting of the hypothermic cardiopulmonary bypass (28 degrees C:14 patients) and the tepid cardiopulmonary bypass group (34 degrees C:17 patients). The serum levels of nitric oxide (NO(2)(-)+NO(3)(-)), prostaglandin E(2), bradykinin, 6-keto PGF1alpha, thromboxane B(2), endothelin-1, systemic vascular resistance index were measured before, 0, 12 and 24 h after cardiopulmonary bypass. RESULTS: The pattern of change in systemic vascular resistance index and nitric oxide during and after cardiopulmonary bypass were significantly different between the two groups (P=0.0008, P=0.02). The tepid group showed significantly lower levels of systemic vascular resistance index after cardiopulmonary bypass than the hypothermic group (0 h: 2278+/-735 vs. 4387+/-1289, 12 h: 1827+/-817 vs. 2817+/-1146 and 24 h: 1690+/-548 vs. 2761+/-641 dyne s cm(-5) m(2), P=0.0001, P=0.03, P=0. 0006). The nitric oxide levels were significantly higher at 0, 12 and 24 h after cardiopulmonary bypass in the tepid group than those in the hypothermic group (84.7+/-33.3 vs. 46.3+/-18.1, 69.8+/-31.1 vs. 40.1+/-17.5 and 80.1+/-38.5 vs. 39.1+/-15.6 micromol/l, P=0.008, P=0.03, P=0.01). The prostaglandin E(2) levels in the tepid group was significantly higher just after cardiopulmonary bypass than that in the hypothermic group (37.3+/-20.0 vs. 15.8+/-8.6 pg/ml, P=0.02). The bradykinin level in the hypothermic group was significantly higher just after cardiopulmonary bypass than that in the tepid group (2.40+/-0.32 vs. 1.85+/-0.21 log(10) (pg/ml), P=0.005). Only nitric oxide showed a significant negative correlation with the systemic vascular resistance index both during and after cardiopulmonary bypass (r=-0.60, P<0.0001) as compared with prostaglandin E(2) and bradykinin. CONCLUSIONS: These findings demonstrated that serum nitric oxide levels in tepid cardiopulmonary bypass were significantly higher than those in hypothermic cardiopulmonary bypass. Nitric oxide correlated with systemic vascular resistance. Thus, nitric oxide may play a pivotal role in a temperature dependent regulation of systemic vascular resistance in cardiopulmonary bypass.     

Pancreatic complications following cardiopulmonary bypass. Factors influencing mortality.

Pancreatic complications following cardiopulmonary bypass are infrequent but are associated with high mortality. All cases of pancreatic complications following cardiopulmonary bypass from 1972 to 1987 at a single institution were retrospectively reviewed. Of 5621 patients who underwent cardiopulmonary bypass, 25 (0.44%) sustained pancreatic complications. There were 15 cases of acute pancreatitis and 10 cases of pancreatic necrosis, with 11 deaths in the group reviewed, a mortality rate of 44%. Factors that were correlated with mortality associated with pancreatic complications in this study include preoperative hypotension, preoperative use of inotropic agents, and renal failure (preoperative and postoperative). Factors that have been previously associated with mortality from pancreatic complications in other studies, such as fluid sequestration, respiratory failure, sepsis, tachycardia, hypocalcemia, age greater than 55 years, and abnormal laboratory findings, were not found to be significantly associated with mortality in this study. Of the five patients for whom complete data were available, not one patient received greater than 800 mg of calcium per square meter of body surface area in the perioperative period. While the exact mechanism of pancreatic injury remains unclear, based on experimental studies and clinical correlation, it is likely that pancreatic ischemia remains a significant contributing factor. We conclude that no factor specifically associated with cardiopulmonary bypass was correlated significantly with mortality.     

Modification of cardiopulmonary hemodynamics and vasoactive mediators by extracorporeal membrane oxygenation in newborn lambs

We asked if prolonged venoarterial extracorporeal membrane oxygenation (ECMO) causes alterations in cardiopulmonary hemodynamics that might be reflected in arbiters of vascular tone: thromboxane, prostacylin, norepinephrine, and epinephrine. Newborn lambs undergoing ECMO demonstrated significant augmentation of systemic and pulmonary arterial blood pressure that was temporally related to rises in all vasoactive mediators measured. Although the prostanoids returned to baseline within 30 minutes, the catecholamines remained elevated significantly throughout bypass. Long-term bypass, however, was not associated with sustained systemic hypertension. Pulmonary hypertension was achieved only after 6 hours of bypass. These acute and chronic changes may exacerbate a pathological state for which ECMO is indicated.     

Hypertension as a risk factor for cerebral injury during cardiopulmonary bypass. Protein S100B and transcranial Doppler findings

We studied 22 patients aged 53-78 years scheduled for cardiac surgery under cardiopulmonary bypass. Blood pressure, cardiac output, transcranial Doppler blood flow velocity, arterial blood gases, body temperature and protein S100B, as a marker for cerebral integrity, were evaluated in normotensive and hypertensive patients. Pre-operative mean (SD) arterial blood pressure was 93 (11) mmHg in the normotensive group compared with 116 (15) mmHg in the hypertensive group. We found an increase in protein S100B levels in both groups. Serum protein S100B concentrations in the hypertensive group were significantly higher than in the normotensive group (p < 0.001). The highest mean (SD) values were 2.04 (0.65) micromol x l(-1) in the normotensive group and 7.02 (4.55) micromol x l(-1) in the hypertensive group. These results suggest that cardiopulmonary bypass is associated with a significantly higher rate of cerebral injury in hypertensive patients than in normotensive patients. This may be due to altered autoregulation and insufficient cerebral perfusion. Modifications of cardiopulmonary bypass management for hypertensive patients might be made to decrease the risk of cerebral injury.     

Single lung transplantation retrospective analysis of intraoperative cardiovascular problems

BACKGROUND: Analysis of haemodynamic problems during single-lung transplantation and of methodologies employed for their treatment. METHODS: Design of the study: clinical retrospective study. SETTING: General University Hospital. PATIENTS: patients with irreversible lung disease, either parenchymal or vascular, undergoing single lung transplantation. INTERVENTIONS: recording of circulatory failure episodes and treatment with pharmacologic support or cardiopulmonary bypass. Modifications occurring during the study period with respect to drugs administered. Evaluation of the consequences of cardiopulmonary bypass on the postoperative outcome, namely on the duration of mechanical ventilation and length of stay in the intensive care unit. RESULTS: During the last 9 years 69 single-lung transplantations have been performed. In 50% of cases a pharmacologic support has been employed; the drug association dobutamine/nitroprusside has been gradually replaced by the association norepinephrine/nitric oxide for the treatment of right ventricular failure. Twenty patients required cardiopulmonary bypass and this caused a significant increase of the duration of mechanical ventilation and length of stay in the intensive care unit. CONCLUSIONS: Hemodynamic changes during lung transplantation are complex and often severe, leading to a clinical status of right ventricular failure, that sometime requires a mechanical circulatory support. The introduction of nitric oxide in clinical practice significantly contributed to the optimization of intraoperative cardiocirculatory profile of patients, leading to a reduction in the use of vasoactive drugs and cardiopulmonary bypass.     

Sialic acid is an indicator of inflammation due to cardiopulmonary bypass but not myocardial damage

BACKGROUND: The aim of the present study was to investigate whether serum sialic acid is associated with the inflammatory response of cardiopulmonary bypass (CPB) or not, since cardiopulmonary bypass is known to produce a systemic inflammatory syndrome. METHODS: In 20 patients in whom elective coronary bypass grafting was done, arterial and coronary sinus blood sampling was done simultaneously. The timing of samplings was 8-10 min after the institution of CPB, just before the application of aortic clamping (T1) and 2 min after cross clamp removal (T2), when there was coronary circulation, but no myocardial activation. RESULTS: Sialic acid, CK-MB, lactate levels were significantly higher at T2 than those at T1 for both arterial and coronary sinus samples. Increase at T2 time point for SA, CK-MB and lactic acid at coronary sinus were closely correlated with the systemic increase of these substances also. Actually, increase of systemic and coronary sinus CK-MB levels was also correlated with the duration of aortic cross-clamping and cardiopulmonary bypass. Probably due to consumption, a negative correlation with the decrease of fibrinogen at coronary sinus was found with the duration of aortic cross-clamping. CONCLUSIONS: Our study showed a strong and consistent association between serum SA concentration and the inflammatory process. There are previous reports that show sialic acid levels associated with ischemic insult to myocardium. We are able to show that serum TSA correlates well with some of the acute phase proteins but this was not true with ischemic markers after cardioplegic arrest.     

Mitogen-activated protein kinase pathways and cardiac surgery

Mitogen-activated protein kinases are serine-threonine protein kinases that are involved in several processes important to cardiac surgery such as vascular permeability, cytokine production, vasomotor function, and reperfusion injury. Mitogen-activated protein kinases are expressed in multiple cell types including cardiomyocytes, vascular endothelial cells, and vascular smooth muscle cells. Mitogen-activated protein kinases function in cellular signal transduction cascades and are activated by a diverse range of stimuli including ischemia, shear stress, and vasoactive agents. Three major mitogen-activated protein kinase families were identified as the extracellular signal-regulated kinases, c-Jun NH(2)-terminal protein kinases, and p38 kinases. Extensive investigation has established roles for extracellular signal-regulated kinases, c-Jun NH(2)-terminal protein kinases, and p38 kinases in cardiovascular signal transduction pathways. Activity of these signal cascades may contribute to the increased pulmonary vascular permeability and myocardial reperfusion injury observed after cardiac surgery with cardioplegia and cardiopulmonary bypass. Recent findings from our laboratory suggest that alterations in the activity of myocardial extracellular signal-regulated kinase pathways occur as a result of cardioplegia-cardiopulmonary bypass in humans. In addition, these differences in extracellular signal-regulated kinase activity were shown to mediate coronary microcirculatory dysfunction associated with cardioplegia-cardiopulmonary bypass. The resulting deficit in coronary microcirculatory regulation may potentially lead to detrimental effects on organ perfusion and function. As mitogen-activated protein kinase pathways are further characterized, our potential to develop methods to prevent morbidity associated with cardiac surgery and cardiopulmonary bypass may be greatly improved.     

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.