Anesth Analg 2000;90:778-783
© 2000 International Anesthesia Research Society
CARDIOVASCULAR ANESTHESIA
Epithelium-Dependent Bronchodilatory Activity Is Preserved in Pig Bronchioles After Normothermic Cardiopulmonary Bypass
Kyung W. Park, MD*,
Kaori Sato, MD
,
Hai B. Dai, MD,
Mark E. Comunale, MD*, and
Frank W. Sellke, MD
Departments of
*Anesthesia and Critical Care and
Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
Address correspondence and reprint requests to Kyung W. Park, MD, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215. Address e-mail to kpark{at}caregroup.harvard.edu
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Abstract
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Analogous to vascular endothelium, bronchial epithelium modulates bronchomotor activity by releasing epithelium-derived relaxing factors. Cardiopulmonary bypass (CPB) is associated with endothelial dysfunction. We examined whether CPB may be associated with bronchiolar epithelial dysfunction in pigs. Pigs were exposed to normothermic CPB for 1.5 h and then separated from CPB. Lung tissues were biopsied before and 30 min after CPB. For time control, lung tissues were biopsied at baseline and after 2 hr of anesthesia. Bronchioles measuring about 100 µm were dissected, and the epithelium was either left intact or denuded. Each bronchiolar segment was preconstricted with 10 µM 5-hydroxytryptamine and relaxation responses to nitroprusside 10-9–10-4 M, isoproterenol 10-9–10-4 M, or the inhaled anesthetics halothane or isoflurane 0–2.5 minimum alveolar anesthetic concentration were examined in vitro by videomicroscopy. Bronchiolar segments demonstrated concentration-dependent relaxation responses to each of the dilators examined. Epithelial denudation reduced bronchodilation to isoproterenol, isoflurane, and halothane, but not to nitroprusside. Bronchodilation was not significantly affected by CPB. We conclude that, unlike vascular endothelial function, porcine bronchiolar epithelium-modulated bronchomotor activity is not significantly affected by normothermic CPB.
Implications: Normothermic cardiopulmonary bypass does not result in epithelial dysfunction in pigs. Epithelium-dependent and epithelium-independent bronchodilators may be equally effective before and after cardiopulmonary bypass.
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Introduction
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Just as the vascular endothelium modulates vascular smooth muscle tone by releasing endothelium-derived vasomotor factors (1,2), the bronchial epithelium releases substances that can modulate bronchial smooth muscle tone. Flavahan et al. (3) demonstrated in canine bronchi that the bronchial epithelium released substance(s) that attenuated contractile responses to acetylcholine, histamine, or 5-hydroxytryptamine (5-HT), but enhanced relaxation response to isoproterenol. Previous work in our laboratory using rat bronchioles demonstrated that the bronchodilatory effects of the inhaled anesthetics halothane, isoflurane, sevoflurane, and desflurane were epithelium-dependent and were partially inhibited by the cyclooxygenase inhibitor indomethacin and the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (4,5). Evidence for epithelium-derived relaxing factors (EpDRFs) has also been reported in other species, including pigs (6), guinea pigs (7), and humans (8).
Cardiopulmonary bypass (CPB) is associated with endothelial dysfunction of both systemic (9,10) and pulmonary (11,12) microvessels. Pulmonary endothelial dysfunction appears to be mediated by activation of the complement system and associated with a decrease in translation of endothelial constitutive NO synthase (12). Since one of the EpDRF appears to be NO (4), especially in pigs (6) and humans (8), we hypothesized that CPB may also be associated with bronchiolar epithelial dysfunction. Therefore, we examined the responses of the pig bronchioles to both epithelium-dependent and epithelium-independent dilators before and after normothermic CPB.
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Methods
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In accordance with institutional animal care and use committee standards, Yorkshire pigs of either gender, weighing 20–25 kg, were premedicated with ketamine 10 mg/kg IM, and IV access was established in an ear vein. Each animal was anesthetized with 
-chloralose and urethane (60 and 300 mg/kg IV initially, then 15 and 60 mg/kg every 60 min as needed, respectively). The trachea was intubated, and the pig was ventilated with a Harvard ventilator (Harvard Apparatus, Cambridge, MA). The right femoral artery was dissected and cannulated with a fluid-filled catheter for continuous blood pressure monitoring and blood sampling. The right jugular vein was cannulated for venous access. After median sternotomy, the pig was heparinized (500 units/kg IV initially and 300 units/kg every 90 min) and the distal ascending aorta and the right atrium were cannulated. Activated clotting time was measured intermittently and maintained >300 s. Total CPB was instituted using a bubble oxygenator (Bentley Bio-2; Baxter Healthcare Corp., Irvine, CA) and a standard roller pump (Cardiovascular Instrument Corp., Wakefield, MA). Ventilation of the lungs was stopped. An arterial filter (Bentley Bio-1025; Baxter Healthcare Corp.) was inserted into the circuit distal to the roller pump. Arterial blood gas tensions were maintained at PO2 > 100 mm Hg, pH 7.40 ± 0.05, PCO2 40 ± 5 mm Hg. The systemic temperature was maintained at 37°C. Blood flow was maintained at 80–100 mL/kg/min to maintain a mean perfusion pressure of 50–80 mm Hg. After 1.5 h of CPB, ventilation of the lungs was resumed, and the animal was separated from CPB by increasing cardiac filling. No pharmacological support was required for separation from CPB. After separation from CPB, protamine was administered to neutralize heparin and to return the activated clotting time to preheparinization baseline values. Animals for time control studies underwent median sternotomy, but were not placed on CPB.
Lung tissues were biopsied from the medial segment of the right middle lobe (a) after median sternotomy, but prior to heparinization and institution of CPB and (b) after separation from CPB and protamine administration (1.5 h CPB and 0.5 h post-CPB). For time control, lung tissues were biopsied after median sternotomy and 2 h afterward. The biopsied tissues were placed in cold (4°C) modified Krebs buffer solution (NaCl 120 mM, KCl 5.9 mM, dextrose 11.1 mM, NaHCO3 25 mM, NaH2PO4 1.2 mM, MgSO4 1.2 mM, CaCl2 2.5 mM). Proximal bronchi were identified by their anatomy and aspiration of air bubbles. Distal bronchiolar branches measuring approximately 100 µm in internal diameter were dissected free of surrounding tissues. Each bronchial segment was placed in a tissue chamber, cannulated with dual micropipettes, and secured with 10-0 sutures. The bronchiolar segments was bathed continuously with modified Krebs buffer, exposed to 95% O2:5% CO2 mixture, and maintained at 37°C with a pH of 7.4. The partial pressure of oxygen in the tissue chamber exceeded 400 mm Hg. The bronchiolar segment was filled with Krebs solution, but was not pressurized above atmospheric pressure and was studied in a no-flow state. All pharmacologic agents were added extraluminally. The bronchiolar segment was visualized with an inverted phase-contrast microscope (IMT-2; Olympus, Tokyo, Japan) connected to a video camera. The bronchiolar image was projected onto a television screen (Panasonic, Osaka, Japan). The bronchiolar internal lumen diameter was measured using an optical-density video detection system (Living Systems Instrumentation, Burlington, VT) and recorded. Stability of similarly prepared bronchiolar preparation in our experimental setup for at least 2.5 h has been previously demonstrated (4).
After 30 min of equilibration in the tissue chamber, a baseline measurement of the bronchiolar internal lumen diameter was obtained (Dbaseline). The bronchiolar segment was preconstricted with 10 µM 5-HT, a dose that had been found previously to produce consistent bronchoconstriction (4), and the constricted diameter was measured (Dconst). In our porcine bronchiolar segments, 10 µM 5-HT produced about 25% reduction in diameter. The segment was then exposed to increasing concentrations of isoproterenol 10-9–10-4 M, nitroprusside 10-9–10-4 M, the inhaled anesthetic halothane or isoflurane 0–2.5 minimum alveolar anesthetic concentration (13,14). Halothane or isoflurane was administered by adding either anesthetic to the 95% O2:5% CO2 mixture bubbling the Krebs solution, using an in-line bubble-through vaporizer. We demonstrated previously (15) that, in our tissue chamber system, less than 10 min for isoflurane and 15 min for halothane are required to reach steady-state concentrations after introducing the respective anesthetic in the tissue chamber, and that the millimolar concentrations and partial pressures of the anesthetics remain consistently proportional to their concentrations in the gas mixture bubbled into the buffer solution. When administering either anesthetic, the anesthetic content in the gas mixture was monitored continuously using a Rascal II gas analyzer (Ohmeda, Salt Lake City, UT) that had been calibrated to industrial standards. At each concentration of the bronchodilators used, the bronchiolar segment was allowed to reach the steady state for 3 min for either isoproterenol or nitroprusside, for 10 min for isoflurane, or for 15 min for halothane. The steady-state bronchiolar diameter was then measured (Drelax) and % relaxation from 5-HT-preconstricted state was calculated as follows: 
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To determine epithelial dependence of the bronchomotor effect of the dilators used, some bronchial segments, not exposed to CPB, were denuded of the epithelial layer by passing a fine Hamilton wire (Hamilton Co., Reno, NV) into the bronchial lumen (4). This technique has been demonstrated to produce functional denudation of the epithelium, but incomplete anatomic denudation (4). These segments were then equilibrated, preconstricted with 5-HT, and subjected to a bronchodilator, as previously described.
At the end of each experiment, the tissue chamber was flushed with fresh Krebs buffer, and the bronchiole was reequilibrated at 37°C. KCl was added to achieve a final concentration of 100 mM to test for bronchoconstriction and then nitroprusside to a concentration of 10 µM to test for bronchodilatory response. Only those bronchiolar segments that constricted by at least 15% in response to KCl and then dilated at least 60% to nitroprusside were considered still viable and included for data analysis. KCl and nitroprusside have been shown to modulate bronchial segments in an epithelium-independent manner (4,16) and therefore may be used to test bronchiolar segments both before and after CPB, even if CPB affected epithelial function.
No pig contributed more than one bronchiolar segment to any one experimental group; therefore, n for each group represents the number of animals and the number of bronchiolar segments. Bronchomotor responses to various bronchodilators (a) with and without epithelial denudation, (b) at baseline and 2 h later (time control), and (c) before and after CPB were compared by two-way analysis of variance, with a repeated-measures factor, with post-hoc Neumann-Keuls test for between groups comparison and a stratified z test for identification of concentrations at which significant differences in responses were obtained, when the initial analysis of variance yielded a significant P value. P < 0.05 was considered significant. All statistics were calculated using True Epistat software (Epistat Services, Richardson, TX). All data are presented as the means ± SD.
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Results
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Epithelial denudation significantly attenuated dilatory responses of pig bronchioles to the ß-adrenergic agonist isoproterenol (Epithelium-intact: n = 5, baseline diameter 93 ± 4 µm; epithelium-denuded: n = 5, baseline diameter 97 ± 9 µm) (P < 0.02) (Fig. 1a). Similar results were obtained for the inhaled anesthetics isoflurane (Epithelium-intact: n = 5, baseline diameter 91 ± 5 µm; epithelium-denuded: n = 5, baseline diameter 93 ± 8 µm) and halothane (Epithelium- intact: n = 5, baseline diameter 89 ± 5 µm; epithelium-denuded: n = 5, baseline diameter 90 ± 12 µm) (P < 0.05 each) (Fig. 1, b and c). However, epithelial denudation did not affect dilatory responses to nitroprusside significantly (Epithelium-intact: n = 5, baseline diameter 91 ± 6 µm; epithelium-denuded: n = 5, baseline diameter 96 ± 6 µm) (P = 0.91) (Fig. 1d).
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Figure 1. Percent dilation of 5-hydroxytryptamine preconstricted pig bronchioles versus (a) log concentration of isoproterenol, (b) concentration of isoflurane, (c) concentration of halothane, or (d) log concentration of nitroprusside with intact or denuded epithelium. Bronchiolar dilation to isoproterenol, isoflurane, and halothane was significantly attenuated by epithelial denudation (P < 0.02, 0.05, and 0.05, respectively). However, dilation to nitroprusside was unaffected by epithelial denudation (P = 0.91). Data are presented as mean ± SD. *P < 0.05 versus intact epithelium.
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Dilatory responses to any of the dilators used were unchanged between the baseline and the 2-h time control in four animals (Fig. 2, a–d).
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Figure 2. Time control studies: Percent dilation of 5-hydroxytryptamine preconstricted pig bronchioles versus (a) log concentration of isoproterenol, (b) concentration of isoflurane, (c) concentration of halothane, or (d) log concentration of nitroprusside at baseline after median sternotomy and 2 h later. Bronchodilation to these agents did not change significantly between the baseline and 2 h later (P  0.10 each). Data are presented as mean ± SD.
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Dilatory responses of pig bronchioles to isoproterenol were not significantly changed by CPB (Pre-CPB: n = 7, baseline diameter 96 ± 7 µm; post-CPB: n = 7, baseline diameter 101 ± 8 µm) (P = 0.65) (Fig. 3a). Neither were responses to nitroprusside significantly changed by CPB (Pre-CPB: n = 7, baseline diameter 99 ± 5 µm; post-CPB: n = 7, baseline diameter 98 ± 7 µm) (P = 0.70) (Fig. 3b).
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Figure 3. Percent dilation of 5-hydroxytryptamine preconstricted pig bronchioles versus (a) log concentration of isoproterenol, (b) log concentration of nitroprusside, (c) concentration of halothane, or (d) concentration of isoflurane before and after normothermic cardiopulmonary bypass (CPB). Bronchiolar segments demonstrated concentration-dependent dilation to these agents. Bronchodilation to none of the agents tested was significantly affected by CPB (P 0.10 each). Data are presented as mean ± SD.
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Likewise, dilatory responses of pig bronchioles to halothane were not significantly altered by CPB (Pre-CPB: n = 8, baseline diameter 99 ± 8 µm; post-CPB: n = 8, baseline diameter 98 ± 5 µm) (P = 0.27) (Fig. 3c). Additionally, responses to isoflurane were not significantly changed by CPB (Pre-CPB: n = 8, baseline diameter 104 ± 7 µm; post-CPB: n = 8, baseline diameter 108 ± 7 µm) (P = 0.10) (Fig. 3d).
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Discussion
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The most important findings of this study are that, as in rats (4), dilation of pig bronchioles to isoflurane and halothane is attenuated by epithelial denudation and that, unlike pulmonary vascular endothelium, pig bronchiolar epithelium does not become dysfunctional after normothermic CPB. Responses of pig bronchiolar segments to both the epithelium-dependent dilator isoproterenol and the epithelium-independent dilator nitroprusside were preserved after CPB. Likewise, responses to halothane and isoflurane were not affected by CPB.
Bronchial epithelium presents many functional analogies to vascular endothelium. First, both play roles in modulating the tone and caliber of the subjacent smooth muscle layer, whether bronchial or vascular. Since the first demonstration of bronchomotor role of the epithelium in dogs by Flavahan et al. (3), similar findings have been demonstrated in many other species (4–8). In pigs, removal of epithelium reduced relaxation to isoproterenol and accentuated constriction to acetylcholine and histamine (6). Second, bronchial epithelium may release both relaxing and contracting factors to modulate bronchial tone and caliber, similar to endothelium-derived endothelin and NO. Whereas epithelial removal caused a leftward shift in the concentration-response curve for acetylcholine, indicating that epithelium releases relaxing substance(s) to modulate responses to acetylcholine, epithelial removal also reduced the maximum response to acetylcholine, as well as to KCl (6). The latter observation suggests that epithelium may also release a contracting factor. Third, EpDRFs include both NO and prostaglandin substances (4). Coupled release of or synergism between NO and prostaglandins has been described in many biological systems. Examples include modulation of bronchodilation (4), agonist-induced vasodilation (17), flow-induced vasodilation (18), and modulation of platelet aggregation (19). Because of these similarities between vascular endothelium and bronchial epithelium, we hypothesized that after CPB, which is associated with endothelial dysfunction (9–12), there may be epithelial dysfunction.
In order to test the hypothesis, we examined pig bronchiolar responses to both epithelium-dependent and epithelium-independent bronchomotor drugs before and after normothermic CPB. We first verified that, in the species we used and under our experimental conditions, drugs we used were indeed epithelium-dependent or -independent as previously published. We confirmed that isoflurane, halothane, and isoproterenol were epithelium-dependent, as in other species (4,20), whereas nitroprusside was not. Bronchodilation to none of these drugs was significantly attenuated by CPB. Our findings, therefore, disproved the hypothesis, at least under the conditions of this study.
Factors contributing to pulmonary vascular endothelial dysfunction after CPB (12) may not be applicable to bronchiolar epithelium. First, whereas there is nearly complete diversion of blood flow away from the pulmonary circulation, the bronchial circulation, which is part of the systemic circulation, continues to receive blood flow even on CPB. Pulmonary endothelial dysfunction is more severe after total CPB than after partial CPB (21), indicating that pulmonary endothelial dysfunction is in part due to diversion of blood flow. Second, products of complement activation contribute to endothelial dysfunction after CPB (12). Complement activation occurs on CPB due to contact with the foreign surface (22) and variable degrees of ischemia and endotoxemia (23), although activation is attenuated by hypothermia, heparinization, and hemodilution (24). After separation from CPB, protamine–heparin complexes can additionally activate the complement system (22). Products of complement activation would be more readily accessible to the vascular endothelium. The mechanical barrier for the products of complement activation in reaching the bronchiolar epithelium would include the endothelial cells and basement membrane, the interstitial tissue, the bronchiolar smooth muscle, and the epithelial basement membrane. Such a barrier may not be insurmountable, since massive complement activation, such as in an anaphylactoid reaction to an IV administered medication, has effects on bronchial activity.
Lastly, it should be noted that a limitation of our study is that epithelial dysfunction was examined under a very specific set of conditions for CPB, namely, 1.5 h of normothermic CPB with a 0.5 h reperfusion period. It is possible that hypothermic CPB may have different effects on epithelial function from normothermic CPB. However, as described, moderate hypothermia attenuates complement activation (24), and we have noted that even endothelial function is better preserved in the cerebral circulation after hypothermic CPB (25°C) than normothermic CPB (25). Moderate hypothermia may be even less likely to be associated with epithelial dysfunction than normothermia. On the other hand, we cannot exclude the possibility that a longer period of CPB may have resulted in epithelial dysfunction. Finally, whether administration of cardioplegia and the consequent changes in electrolytes may have any effect on epithelial function was not addressed in this study.
In summary, we have demonstrated that there is no significant bronchiolar epithelial dysfunction in pigs after normothermic CPB, as measured by responses to epithelium-dependent bronchodilators. To the extent that our findings are clinically applicable, epithelium-dependent bronchodilators may be used just as effectively after as before normothermic CPB.
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Acknowledgments
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This study was supported in part by U.S. Public Health Service Grant RO1 HL-46716 and by a grant from the Beth Israel Anesthesia Foundation.
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Footnotes
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Presented in part at the 1999 Society of Cardiovascular Anesthesiologists Annual Meeting, Chicago, IL, April 24–28, 1999.
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References
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-
Moncada S, Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med 1993;329:2002–12.[Free Full Text]
-
Masaki T, Kimura S, Yanagisawa M, Goto K. Molecular and cellular mechanism of endothelin regulation: implications for vascular function. Circulation 1991;84:1457–66.[Free Full Text]
-
Flavahan NA, Aarhus LL, Rimele TJ, Vanhoutte PM. Respiratory epithelium inhibits bronchial smooth muscle tone. Physiol 1985;58:834–8.
-
Park KW, Dai HB, Lowenstein E, et al. Isoflurane- and halothane-mediated dilation of distal bronchi in the rat depends on the epithelium. Anesthesiology 1997;86:1078–87.[ISI][Medline]
-
Park KW, Dai HB, Lowenstein E, Sellke FW. Epithelial dependence of the bronchodilatory effect of sevoflurane and desflurane in rat distal bronchi. Anesth Analg 1998;86:646–51.[Abstract]
-
Stuart-Smith K, Vanhoutte PM. Airway epithelium modulates the responsiveness of porcine bronchial smooth muscle tone. J Appl Physiol 1988;65:721–7.[Abstract/Free Full Text]
-
Burgaud JL, Javellaud J, Oudart N. Do perfused small caliber airways of guinea-pig release an epithelium-dependent relaxing factor? Pulm Pharmacol 1993;6:217–24.[ISI][Medline]
-
Knight DA, Adcock JA, Phillips MJ, Thompson PJ. The effect of epithelium removal on human bronchial smooth muscle responsiveness to acetylcholine and histamine. Pulm Pharmacol 1990;3:198–202.[Medline]
-
Park KW, Dai HB, Lowenstein E, et al. Effect of isoflurane on the ß-adrenergic and endothelium-dependent relaxation of pig cerebral microvessels after cardiopulmonary bypass. Stroke Cerebrovasc Dis 1998;7:168–78.
-
Stahl GL, Reenstra WR, Frendl G. Complement-mediated loss of endothelium-dependent relaxation of porcine coronary arteries: role of the terminal membrane attack complex. Circ Res 1995;76:575–83.[Abstract/Free Full Text]
-
Shafique T, Johnson RG, Dai HB, et al. Altered pulmonary microvascular reactivity after total cardiopulmonary bypass. Cardiovasc Surg 1993;106:479–86.
-
Park KW, Tofukuji M, Metais C, et al. Attenuation of endothelium-dependent dilation of pig pulmonary arterioles after cardiopulmonary bypass is prevented by monoclonal antibody to complement C5a. Anesth Analg 1999;89:42–8.[Abstract/Free Full Text]
-
Eger EI II, Johnson BH, Weiskopf RB, et al. Minimum alveolar concentration of I-653 and isoflurane in pigs: definition of a supramaximal stimulus. Anesth Analg 1988;67:1174–6.[Abstract/Free Full Text]
-
Lerman J, Oystin JP, Gallagher TM, et al. The minimum alveolar concentration (MAC) and hemodynamic effects of halothane, isoflurane, and sevoflurane in newborn swine. Anesthesiology 1990;73:717–21.[ISI][Medline]
-
Park KW, Dai HB, Lowenstein E, Sellke FW. Vasomotor responses of rat coronary arteries to isoflurane and halothane depend on preexposure tone and vessel size. Anesthesiology 1995;83:1323–30.[ISI][Medline]
-
Vanhoutte PM. Epithelium-derived relaxing factor(s) and bronchial reactivity. Allergy Clin Immunol 1989;83:855–61.[ISI][Medline]
-
De Nucci G, Gryglewski RJ, Warner TD, Vane JR. Receptor-mediated release of endothelium-derived relaxing factor and prostacyclin from bovine aortic endothelial cells is coupled. Sci USA 1988;85:2334–8.
-
Park KW, Dai HB, Lowenstein E, Sellke FW. Flow-induced dilation of rat coronary microvessels is attenuated by isoflurane but enhanced by halothane. Anesthesiology 1998;89:132–42.[ISI][Medline]
-
Houston DS, Robinson P, Gerrard JM. Inhibition of intravascular platelet aggregation by endothelium-derived relaxing factor: reversal by red blood cells. Blood 1990;76:953–8.[Abstract/Free Full Text]
-
Stuart-Smith K, Vanhoutte PM. Hetreogencity in the effects of epithelium removal in the canine bronchial tree. J Appl Physiol 1987;63:2510–5.[Abstract/Free Full Text]
-
Friedman M, Johnson RG, Wang SY, et al. Pulmonary microvascular responses to protamine and histamine: effect of cardiopulmonary bypass. J Thorac Cardiovasc Surg 1994;108:1092–9.[Abstract/Free Full Text]
-
Knudsen F, Andersen LW. Immunologic aspects of cardiopulmonary bypass. J Cardiothorac Anesth 1990;4:245–58.[Medline]
-
Nilsson L, Kulander L, Nystrom S-O, Eriksson O. Endotoxins in cardiopulmonary bypass. Surg 1990;100:777–80.
-
Moore FD, Warner KG, Assousa S, et al. The effects of complement activation during cardiopulmonary bypass: attenuation by hypothermia, heparin, and hemodilution. Surg 1988;208:95–103.
-
Stamler A, Wang SY, Li J, et al. Moderate hypothermic reduces cardiopulmonary bypass-induced impairment of cerebrovascular responses to platelet products. Ann Thorac Surg 1996;62:191–8.[Abstract/Free Full Text]
Accepted for publication December 29, 1999.
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Abstract
Introduction
