Ann Thorac Surg 2001;72:1321-1326
© 2001 The Society of Thoracic Surgeons
Original article: cardiovascular
Influence of steroids on microvascular perfusion injury of the bowel induced by extracorporeal circulation
Falk–Udo Sack, MDa,
Bettina Reidenbacha,
Ralph Dollner, MDa,
Alexander Schledta,
Martha Maria Gebhard, MDb,
Siegfried Hagl, MDa
a Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany
b Experimental Surgery, University of Heidelberg, Heidelberg, Germany
Accepted for publication May 29, 2001.
Address reprint requests to Dr Sack, Department of Cardiac Surgery, University of Heidelberg, INF II0, 69I20 Heidelberg, Germany
e-mail: falk-udo.sack{at}urz.uni-heidelberg.de
 |
Abstract
|
|---|
Background. Extracorporeal circulation is associated with gastrointestinal complications. By means of intravital microscopic methods, we investigated whether preoperative treatment with steroids can attenuate the impairment of the bowel microcirculation.
Methods. In 20 pigs, a partial left heart bypass (pLHB) was established. A loop of the terminal ileum was exteriorized for intravital-microscopic observation. Seven sham-operated animals served as controls. In 13 animals, pLHB was established for 2 hours with a flow rate of 2,000 mL per minute; 7 of the animals received 20 mg/kg body weight prednisolone preoperatively. The microcirculatory network was analyzed before, during pLHB, and 2 hours after bypass.
Results. Despite unchanged macro-hemodynamics, pLHB resulted in a significant microvascular perfusion injury of the small bowel. Arteriolar vasoconstriction and a reduction of perfused capillaries per unit area (functional capillary density) to 30% of prebypass values could be found. Blood cell velocities were reduced in submucuous collecting venules. In the steroid-treated animals, the functional capillary density remained normal. In addition, arteriolar vasoconstriction could be prevented.
Conclusions. Treatment with prednisolone largely prevents the microcirculatory alterations in the small bowel induced by extracorporeal circulation.
|
Introduction
|
|---|
Cardiac operations with the need of cardiopulmonary bypass (CPB), especially coronary artery bypass surgery, are one of the most frequent surgical procedures performed within the United States. Based on The Society of Thoracic Surgeons database, more than 170,000 coronary artery bypass graft operations are performed annually. The incidence of gastrointestinal complications is about 2.5% with a reported mortality of 14.86% in this patient population [1]. Despite the low incidence, the clinical importance of these complications is evident. Reported mortalities of up to 62% underline the need for investigations aiming at a better understanding of the underlying pathomechanisms [2–4].
The connection between the pathogeneic role of CPB and the development of gastrointestinal complications becomes more and more evident. It is known that CPB may lead to a systemic inflammatory response and induction and release of proinflammatory mediators, and cytokines as a consequence of CPB have been described [5, 6]. This whole-body reaction may influence the microcirculation of the gastrointestinal tract, and the impairment of bowel microvasculature may therefore serve as a trigger for the development of multiorgan failure [7]. Little is known about the response of the bowel microcirculation to extracorporeal circulation. Treatment with steroids may reduce the inflammatory response and the generation and release of inflammatory mediators. However, it is yet to be seen whether pretreatment with steroids results in better gastrointestinal perfusion. The objective of our study was to investigate the effects of extracorporeal circulation on the microvasculature of the small bowel, and the fundamental question was as to whether pretreatment with steroids can prevent impairment of microvascular perfusion.
|
Material and methods
|
|---|
Animals
Twenty landrace pigs with a bodyweight of 22 to 26 kg served as laboratory animals. All animal investigations and care were in accordance with the German animal protection laws. Anesthesia was induced by metomidate-hydrochloride (10 mg/kg IM) and azaperon (8 mg/kg IM) followed by application of ketamine-hydrochloride (7.5 mg/kg IV) and atropin-sulfate (12.5 mg/kg IV). After tracheostomy and intubation, the animals were mechanically ventilated with 40% inspiratory oxygen. All subsequent procedures were performed under general anesthesia maintained by continuous IV infusion of piritramid and midazolam (2.25 and 1.8 mg/kg/h, respectively).
Surgical procedures
Arterial and venous catheters were inserted into the right carotid artery and jugular vein for continuous blood pressure recordings and fluid replacement, respectively. A left thoracotomy was performed. Depending on the diameter of the main pulmonary artery, a 12- to 14-mm ultrasonic flow probe (Transonic Systems Inc., Ithaca, NY) was placed around the vessel for continuous monitoring of cardiac output. After administration of heparin (300 U/kg), the ascending aorta (14 Fr) and the left atrial appendage (18 Fr) were cannulated for establishing partial left heart bypass (pLHB) with an external roller pump (Stöckert, München, Germany) as a model of extracorporeal circulation. After closure of the thoracotomy, the animals were placed in left lateral position on a criss-cross table of an intravital microscope especially designed for large animals. A small segment of the terminal ileum was exteriorized via a small laparotomy for microscopic observation (Fig 1). The preparation was placed on a movable stage attached to the microscope. Covering the bowel with a luicide foil prevents dehydration of the tissue. The temperature was kept constant at 37°C by application of warm air.
View larger version (84K):
[in this window]
[in a new window]
|
Fig 1. Loop of the terminal illeum, exteriorized. Regions of interest for repetitive intravital-microscopic observations.
|
|
Intravital microscopy
For in vivo microscopy, the microvessels were visualized after intraarterial injection of 1 mL 5% fluorescein isothiocyanate (FITC)-labeled dextran (molecular weight 150,000; Sigma, St. Louis, MO). Fluorescent latex microspheres (1 mm) were injected intraarterially for measurements of blood cell velocity. A modified Leitz Orthoplan microscope with a 100-W, HBO, mercury lamp, attached to a Ploemo-Pack illuminator with filter blocks for epi-illumination was used. With 6.3x and 10x long-distance objectives, a magnification of approximately 180x and 350x can be achieved. The observations were recorded by means of a charge-coupled device camera (Kappa, Gleichen, Germany) and a video system for off-line evaluation. Vessel diameters and blood cell velocities in the small arterioles of the muscular layer and submucosal collecting venules and the muscular capillary network were recorded for the quantification of functional capillary density. Several "regions of interest" were defined for repetitive observations of the same vessel segments during the experiment. The quantitative analysis of the microcirculation was performed off-line by means of a computer-controlled image analysis system (Capimage, Zeintl, Germany). By means of a digitizing tablet connected to a personal computer with a special commercially available software for analyzing the microcirculation, vessel diameters were determined by direct measurement. The blood cell velocities were quantified by frame-to-frame analysis using the injected fluorescent latex beads. The functional capillary density was calculated by measuring the length of the perfused capillaries divided by the area.
Experimental protocol
The animals were divided into three groups. Group I consisted of 7 sham-operated animals (thoracotomy and cannulation) without pLHB serving as controls. In 6 animals, a normothermic, pLHB was established for 2 hours with a continuous flow rate of 50% of the initial cardiac output, which is about 2000 mL per minute (group II), and a further 7 animals were treated as in group II but also received 20 mg/kg body weight prednisolone (Solu-Decortin H; Merck, Darmstadt, Germany) intravenously before surgery (group III). Microcirculatory parameters were recorded before, during pLHB, and up to 2 hours after weaning off bypass. Apart from observation of the microvasculature, cardiac output, heart rate, and systemic arterial and central venous blood pressures were recorded continuously. Arterial blood samples were used for repetitive blood gas analyses.
Statistical analysis
The statistical procedure included analysis of variance and Student’s t test for comparison between the groups. Paired Student’s t test, including Bonferroni-probabilities for repeated measurements, was performed for analyzing differences within each group (SPSS for Windows 9.0; SPSS Inc, Chicago, IL). All macrohemodynamic parameters are reported as the mean ± standard deviation (SD), and statistical significance was set at p less than 0.05. Changes of microcirculatory parameters within the groups are reported as changes in percent from values before pLHB. The values are expressed as the mean ± SD, and statistical significance was set at p less than 0.05.
|
Results
|
|---|
An important prerequisite for the interpretation of the microcirculatory parameters is that the arterial blood pressures and cardiac output remain unchanged during the experiment in all groups. Systolic blood pressure was kept constant at normal values (Fig 2A). The continuously recorded blood flow in the main pulmonary artery, which reflects the cardiac output, was maintained between 4 to 5 L per minute throughout the experiment (Fig 2B). Central venous pressure was between 4 and 8 mm Hg in all groups. Excessive hemodilution due to the priming of the bypass circuit was avoided. The necessary priming volume for the bypass circuit was 200 mL of normal saline solution. Hematocrit values and hemoglobin values never fell short of 34% and 8.0 mg/dL, respectively. Apart from fluid replacement with Ringer’s lactate, no additional drugs, in particular no IV catecholamines, were administered.
View larger version (9K):
[in this window]
[in a new window]
|
Fig 2. Systolic arterial blood pressure (A) and cardiac output (B) (time points: 0 = before pLHB, 1 = 1-hour pLHB, 2 = 2-hour pLHB, 3 = 1 hour after weaning off pLHB, 4 = 2 hours off pLHB) (pLHB = partial left heart bypass).
|
|
Microcirculation
Within the control group, the arterioles showed no changes in diameter throughout the observation period. In contrast, partial left heart bypass resulted in a significant decrease of the arteriolar diameters after 2 hours of pLHB. This arteriolar vasoconstriction was even more pronounced during the off-bypass period, and no signs of restitution could be observed. Two hours after weaning off bypass, the mean arteriolar diameters were found to be diminished from 38.56 ± 11.4 before pLHB to 31.14 ± 9.05 µm (p < 0.001) at the end of the experiment. Within the steroid group, arteriolar vasoconstriction was not detectable either during extracorporeal circulation or after weaning off bypass (Fig 3), the arteriolar diameters showed no significant changes. However, a significant drop in arteriolar blood cell velocities could be measured in the pLHB group 1 and 2 hours after bypass. Within the steroid-treated group, a reduction of arteriolar blood cell velocities could be observed during and 1 hour postbypass (Fig 4). In the control group, arteriolar blood cell velocities remain unchanged.
View larger version (17K):
[in this window]
[in a new window]
|
Fig 3. Diameter of arterioles (time points: 1 = 1-hour pLHB, 2 = 2-hour pLHB, 3 = 1 hour after weaning off pLHB, 4 = 2 hours off pLHB). *p < 0.05, **p < 0.01, ***p < 0.001. Each data point is based upon approximately 200 single measurements. (pLHB = partial left heart bypass.)
|
|
View larger version (19K):
[in this window]
[in a new window]
|
Fig 4. Blood cell velocities arterioles (time points: see Fig 3). *p < 0.05, **p < 0.01. Each data point is based upon approximately 200 single measurements. (pLHB = partial left heart bypass.)
|
|
The observed reduction of arteriolar blood cell velocities of 10% to 20% compared with prebypass values does not reflect a pathologic perfusion. Despite the observed significant reduction, the absolute velocities measured were in the range of 2.0 to 3.0 mm per second, which is still within the physiologic range.
Compared with the feeding arterioles, the nutritive capillary bed seems to be the most susceptible structural unit within the microcirculation. The measurement of functional capillary density, which only counts the perfused capillaries per unit area, revealed a significant impairment after extracorporeal circulation. As compared with prebypass values, functional capillary density significantly decreased to 72.3% after 1 hour of pLHB. A further decrease down to 29.1% at 2 hours after the bypass period (Fig 5) could be observed. This highly significant drop in the nutritional network of the bowel musculature could be prevented by preoperative administration of steroids. Within this particular group, the functional capillary density was not influenced by pLHB. The observed capillaries per area remained perfused throughout the experiment. Analysis of the collecting venules, which drain the capillary bed and the submucous region, did not show any significant change in vessel diameter. The velocities of blood cells within these vessels are significantly influenced by extracorporeal circulation. In untreated animals, the blood cell velocities in collecting venules were found highly significantly reduced, from 1.63 mm/s before pLHB down to 0.65 mm/s 2 hours after bypass. A similar tendency could be observed in steroid-treated animals. Within this group, the venular blood cell velocities decreased from 1.73 to 1.33 mm/s. As compared with the untreated animals, the blood cell velocities in collecting venules of the steroid group were significantly higher during extracorporeal circulation and within the postbypass period (Fig 6). The phenomenon of intravascular sludge formation and hemoconcentration was detectable most frequently in the untreated animals (Fig 7). As a consequence of the extremely low blood cell velocities in these vessels, a separation of corpuscular blood cells and plasma occurs. Especially in collecting venules, the increase in permeability of the vessel wall, reflected by leakage of the macromolecular plasma marker FITC-Dextran, occurred regularly in the pLHB group without steroid treatment. This leakage phenomenon appears as a negative contrast of the observed vessel segment. The bright contrast medium, with a molecular weight of 150,000, leaks into the perivascular tissue, and the lumen of the vessel appears darker than the surrounding tissue. Bright spots next to the outer vessel wall represent areas of increased permeability. However, these observations are not quantified due to the fact that the amount of FITC-Dextran used differed between the individual animals (see Comment).
View larger version (29K):
[in this window]
[in a new window]
|
Fig 5. Functional capillary density (time points: see Figure 3). *p < 0.05, ***p < 0.001. Each column represents the measurements of approximately 30 capillary fields. (pLHB = partial left heart bypass.)
|
|
View larger version (20K):
[in this window]
[in a new window]
|
Fig 6. Blood cell velocities in postcapillary venules (time points: see Figure 3). **p < 0.01, ***p < 0.001, +++ p < 0.001 (+ for comparison between groups). Each data point is based upon approximately 200 single measurements. (pLHB = partial left heart bypass.)
|
|
View larger version (97K):
[in this window]
[in a new window]
|
Fig 7. Hemoconcentration and sludge phenomena (*) within collecting venules after 2 hours partial left heart bypass (pLHB) and 1 hour after weaning off bypass.
|
|
|
Comment
|
|---|
Impaired perfusion and maldistribution of blood flow away from visceral organs as a reaction of CPB has been recognized as a cause for altered gut permeability, mucosal ischemia, and endotoxinemia [8]. There are a variety of different gastrointestinal complications reported in the literature, but the incidence of these is said to be low. However, gastrointestinal complications often lead to multiple organ failure with a reported high mortality rate of 15% to 63% [3, 9, 10].
The use of CPB is associated with a variety of pathophysiological mechanisms that might influence the perfusion of the splanchnic region. Physiologic perfusion can be disturbed by the mode of perfusion (pulsatile/nonpulsatile), and perfusion pressure might be altered with low flow/high flow regimen or with cardio-circulatory arrest. Furthermore, the blood temperature during CPB has a major effect on the splanchnic perfusion [11]. Regarding these different pathophysiological mechanisms, experimental studies of the effects of CPB and the interpretation of the results remain difficult. With our model, several of the above-mentioned mechanisms could be excluded. With the use of a model of partial left heart bypass, perfusion pattern, perfusion pressure, and the temperature could be kept constant at a physiologic level. Moreover, direct observation and quantitative analysis of the tissue and organ of interest allows us to obtain more information on the pathophysiological mechanisms at the level of nutritive perfusion: the microcirculation. However, despite normal macrohemodynamic perfusion measured by heart rate, arterial and venous blood pressure and cardiac output and normal temperature, partial left heart bypass results in a microvascular perfusion injury of the small bowel. The observed arteriolar vasoconstriction together with a reduction of blood cell velocities reflect hypoperfusion at the microvascular level. The nutritive capillary bed is severely jeopardized with a reduction of the functional capillary density to approximately 30% as compared with prebypass values. In the submucous collecting venules, a significant reduction of blood cell velocity and an increased permeability of the vessel wall leads to a hemoconcentration that might aggravate the impairment of capillary perfusion. These observed phenomena in the collecting venules reflect an increase in outflow impedance from the capillary bed. This does not only affect the capillary perfusion of the muscle, but also impairs the drainage from the capillaries of the mucosa. A reduction in flow in this particular type of collecting venule inevitably leads to hypoperfusion of the mucosa. The impairment of mucosal perfusion due to CPB has already been proven by other authors using indirect methods like tonometry and laser Doppler [12–14]. However, the value of tonometry is mainly limited to clinical studies; the values obtained with this method are indirect measures of perfusion as they only measure the intramucosal pH [15]. Quantification of perfusion at the level of microcirculation is not possible. However, the advantage of tonometry is based on the applicability in clinical monitoring [16]. The increase in permeability of the vascular wall is reflected by the extravasation of the plasma marker FITC, with the consequence of intravascular hemoconcentration and sludge formation (see Fig 7). Quantification of paravascular leakage could not be performed with standard techniques of densitometry usually used in intravital microscopic studies in smaller animals. Due to the need of repetitive injections of the dye depending on the number of observed sites of interest in this large animal, the dosage of FITC is not the same in each animal. Although these differences in dosage are small, the measurement and the comparison of gray-values determined with densitometry within the vessel and on the area adjacent to the outer vessel wall would not be correct. This increase in permeability is also detectable in patients undergoing cardiac operations with CPB [17]. However, the observed perfusion failure of the microcirculation is not predictable from the measured hemodynamic parameters. Normal cardiac output and blood pressure do not exclude the possibility of microvascular impairment during extracorporeal circulation. The induction of an inflammatory response with the release of cytokines, induction of leukocyte-endothelium interaction, and generation of oxygen-free radicals might be the major pathomechanism for the development of the microvascular perfusion injury. In clinical as well as in experimental studies, the relationship between CPB and the production of cytokines has been demonstrated [18–21]. The contact of blood and blood cells with foreign surfaces like bypass circuits and the mechanical stress induced by the pump mechanism (especially roller pumps) are major prerequisites for the induction of cytokine release. Moreover, activation of polymorphonuclear leukocytes and the generation of oxygen free radicals are induced by extracorporeal circulation [6, 22]. The effects of activated leukocytes, cytokines, and oxygen free radicals on the microcirculation have been studied in several models and tissues [23–25]. Treatment with steroids is one of the therapeutic options for prophylactic inhibition of cytokine release, leukocyte activation, and generation of oxygen free radicals in connection with cardiopulmonary bypass [26–28]. Dernek and associates and Engelmann and associates could clearly demonstrate the inhibitory effect of steroids on proinflammatory cytokine release [29, 30]. However, laboratory findings do not necessarily reflect any effect in terms of improved tissue perfusion. In our study, we could demonstrate that prophylactic administration of steroids blunt the microvascular perfusion injury induced by extracorporeal circulation. The most significant effect could be found on capillary perfusion. In contrast to untreated animals, the functional capillary density remained normal during and after extracorporeal circulation. However, the reduction of blood cell velocities in arterioles as well as in venules could not be prevented by steroid administration. Compared with the untreated animals, the dramatic reduction of blood cell velocity in collecting venules was significantly less pronounced in steroid-treated animals. The beneficial effects of steroids were achieved by administration of the substance before operation. It is known that surgery itself or even sternotomy may trigger the release of cytokines; however, the optimal timing for steroid administration remains controversial [31]. The fear that the immunosuppressive potential of steroids at a high dosage may trigger release of endotoxines could be eliminated by several investigations [32]. The dosage used in our experiments is based on the experience gained from a clinical study in our hospital showing that 20 mg/kg Prednisolone IV will lead to a significant reduction of proinflammatory cytokines in patients undergoing CABG surgery with CPB.
However, the rationale and indication for prophylactic administration of steroids are still controversial. Further investigations are necessary to underline the beneficial effects of steroid treatment during extracorporeal circulation. More attention should be paid to direct hemodynamic effects rather than laboratory findings.
By means of intravital microscopy in an experimental setting of extracorporeal circulation, direct observation of the impairment of microvascular perfusion is possible. The value and the efficacy of different treatment modalities at the microvascular level of the gut in response to extracorporeal circulation can be observed. As a consequence of our laboratory findings, clinical studies are necessary to reproduce the beneficial effects of pretreatment with steroids in patients undergoing CPB. To make the step from the laboratory to the clinical setting, treatment of patients with steroids in a blinded, randomized, and prospective study will be the next step.
|
References
|
|---|
-
STS U.S. Cardiac Surgery Database. STS National Database. 2000.
-
Allen R.C., Schneider J., Longenecker L., Kosinski A.S., Smith R.B., Lumsden A.B. Acute lower extremity ischemia after cardiac surgery. Am J Surg 1993;166:124-129.[Medline]
-
Christenson J.T., Schmuziger M., Maurice J., Simonet F., Velebit V. Gastrointestinal complications after coronary artery bypass grafting. J Thorac Cardiovasc Surg 1994;108:899-906.[Abstract/Free Full Text]
-
Ott M.J., Buchman T.G., Baumgartner W.A. Postoperative abdominal complications in cardiopulmonary bypass patients: a case-controlled study. Ann Thorac Surg 1995;59:1210-1213.[Abstract/Free Full Text]
-
Kirklin J.K. The postperfusion syndrome: inflammation and the damaging effects of cardiopulmonary bypass. In: Tinkler J.H., ed. Cardiopulmonary bypass: current concepts and controversies. London: Saunders, 1989.
-
Zahler S., Massoudy P., Hartl H., Hahnel C., Meisner H., Becker B.F. Acute cardiac inflammatory responses to postischemic reperfusion during cardiopulmonary bypass. Cardiovascular Research 1999;41:722-730.[Abstract/Free Full Text]
-
Landow L., Andersen L.W. Splanchnic ischaemia and its role in multiple organ failure. Acta Anaesthesiologica Scandinavica 1994;38:626-639.[Medline]
-
Pesonen E.J., Korpela R., Peltola K., et al. Regional generation of free oxygen radicals during cardiopulmonary bypass in children. J Thorac Cardiovasc Surg 1995;110:768-773.[Abstract/Free Full Text]
-
Halm M.A. Acute gastrointestinal complications after cardiac surgery. Am J Crit Care 1996;5:109-118.
-
Johnston G., Vitikainen K., Knight R., Annest L., Garcia C. Changing perspective on gastrointestinal complications in patients undergoing cardiac surgery. Am J Surg 1992;163:525-529.[Medline]
-
Croughwell N.D., Newman M.F., Lowry E., et al. Effect of temperature during cardiopulmonary bypass on gastric mucosal perfusion. Br J Anaesth 1997;78:34-38.[Abstract/Free Full Text]
-
Bastien O., Piriou V., Aouifi A., Evans R., Lehot J.J. Effects of dopexamine on blood flow in multiple splanchnic sites measured by laser Doppler velocimetry in rabbits undergoing cardiopulmonary bypass. Br J Anaesth 1999;82:104-109.[Abstract/Free Full Text]
-
Booker P.D., Davis A.J., Franks R. Gut mucosal perfusion in infants undergoing cardiopulmonary bypass: effect of preoperative captopril. Br J Anaesth 1997;79:14-18.[Abstract/Free Full Text]
-
Haisjackl M., Germann R., Hasibeder W., et al. Mucosal tissue oxygenation of the porcine jejunum during normothermic cardiopulmonary bypass. Br J Anaesth 1999;82:738-745.[Abstract/Free Full Text]
-
Groeneveld A.B.J., Kolkman J.J. A review of splanchnic tonometry: physiological principles and methodological considerations. J Crit Care 1994;9:198-210.[Medline]
-
Landow L., Phillips D.A., Heard S.O., Prevost D., Vandersalm T.J., Fink M.P. Gastric tonometry and venous oximetry in cardiac surgery patients. Crit Care Med 1991;19:1226-1233.[Medline]
-
Ohri S.K., Bowles C.T., Siddiqui A., et al. The effect of cardiopulmonary bypass on gastric and colonic mucosal perfusion: a tonometric assessment. Perfusion 1994;9:101-108.[Abstract/Free Full Text]
-
Duval E.L., Kavelaars A., Veenhuizen L., van Vught A.J., van de Wal H.J., Heijnen C.J. Pro- and anti-inflammatory cytokine patterns during and after cardiac surgery in young children. Eur J Pediatrics 1999;158:387-393.[Medline]
-
Gu YJ, Mariani MA, Boonstra PW, Grandjean JG, van Oeveren W. Complement activation in coronary artery bypass grafting patients without cardiopulmonary bypass: the role of tissue injury by surgical incision. 1999;116:892–8.
-
Orime Y., Shiono M., Hata H., et al. Cytokine and endothelial damage in pulsatile and nonpulsatile cardiopulmonary bypass. Artificial Organs 1999;23:508-512.[Medline]
-
Wan S., Leclerc J.L., Vincent J.L. Cytokine responses to cardiopulmonary bypass: lessons learned from cardiac transplantation. Ann Thorac Surg 1997;63:269-276.[Abstract/Free Full Text]
-
Kamler M., Jakob H., Lehr H.A., Gebhard M.M., Hagl S. Direct visualization of leukocyte/endothelial cell interaction during extracorporeal circulation (ECC) in a new animal model. Eur J Cardiothorac Surg 1997;11:973-980.[Abstract]
-
Björk J., Arfors K.E. Oxygen radicals and leukotriene B4 induced increase in vascular leakage by PMN-leukocytes. Agents and Actions 1984;11(Suppl):63-73.
-
Menger M.D., Steiner D., Messmer K. Microvascular ischemia-reperfusion injury in striated muscle: significance of "no reflow". Am J Physiol 1992;263:H1892-H1900.[Abstract/Free Full Text]
-
Zimmerman B.J., Grisham M.B., Granger D.N. Mechanisms of oxidant-mediated microvascular injury following reperfusion of the ischemic intestine. Basic Life Sciences 1988;49:881-886.[Medline]
-
Hill G.E., Alonso A., Thiele G.M., Robbins R.A. Glucocorticoids blunt neutrophil CD11b surface glycoprotein upregulation during cardiopulmonary bypass in humans. Anesthesia Analgesia 1994;79:23-27.[Abstract/Free Full Text]
-
Loubser P.G. Effect of methylprednisolone on complement activation during heparin neutralization. J Cardiovasc Pharmacol 1997;29:23-27.[Medline]
-
Toft P., Christiansen K., Tonnesen E., Nielsen C.H., Lillevang S. Effect of methylprednisolone on the oxidative burst activity, adhesion molecules and clinical outcome following open heart surgery. Scand Cardiovasc J 1997;31:283-288.[Medline]
-
Dernek S., Tunerir B., Sevin B., Aslan R., Uyguc O., Kural T. The effects of methylprednisolone on complement, immunoglobulins and pulmonary neutrophil sequestration during cardiopulmonary bypass. Cardiovasc Surg 1999;7:414-418.[Medline]
-
Engelman R.M., Rousou J.A., Flack J.E., Deaton D.W., Kalfin R., Das D.K. Influence of steroids on complement and cytokine generation after cardiopulmonary bypass. Ann Thorac Surg 1995;60:801-804.[Abstract/Free Full Text]
-
Wan S., DeSmet J.M., Antoine M. Steroid administration in heart and heart lung transplantation: is the timing adequate?. Ann Thorac Surg 1996;61:674-678.[Abstract/Free Full Text]
-
Karlstad M.D., Patteson S.K., Guszcza J.A., Langdon R., Chesney J.T. Methylprednisolone does not influence endotoxin translocation during cardiopulmonary bypass. J Cardiothorac Vasc Anesth 1993;7:23-27.[Medline]
This article has been cited by other articles:
|
|
|
|
 
E. A. Hessel II
Abdominal Organ Injury After Cardiac Surgery
Seminars in Cardiothoracic and Vascular Anesthesia,
September 1, 2004;
8(3):
243 - 263.
[Abstract]
[PDF]
|
|
|
Top
Abstract
Introduction
