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Ann Thorac Surg 1997;63:648-652
© 1997 The Society of Thoracic Surgeons

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Original Article: Cardiovascular

Time Course of Endothelin-1 and Nitrate Anion Levels After Cardiopulmonary Bypass in Congenital Heart Defects

Departments of Pediatric Cardiac Surgery and Cardiology, Tokyo Women's Medical College, Heart Institute of Japan, Tokyo, Japan

Accepted for publication September 24, 1996.

	Abstract

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Background. The endothelium-derived vasoconstrictor endothelin-1 (ET-1) may be involved in pulmonary hypertension (PH), but production of the endothelium-derived vasodilator nitric oxide (NO) after cardiopulmonary bypass (CPB) in congenital heart disease is unclear.

Methods. Twenty patients (age, 4 months to 12 years) were divided into three groups: severe PH (mean pulmonary-to-systemic arterial pressure ratio >0.5) and high pulmonary flow (n = 8), mild PH (mean pulmonary-to-systemic arterial pressure ratio <0.35) and high pulmonary flow (n = 6), and no PH and low pulmonary flow (n = 6). The mean pulmonary-to-systemic arterial pressure ratio was calculated and blood samples were taken, and NO₃-, an NO metabolite, was measured.

Results. Levels of ET-1 in the group with severe PH and high pulmonary flow were higher than in the other groups until 6 hours after CPB, and NO₃- was not changed significantly in the group with severe PH and high pulmonary flow and or the group with mild PH and high pulmonary flow during CPB. Endothelin-1 in the group with no PH and low pulmonary flow was higher than in the group with mild PH and high pulmonary flow after CPB, and NO₃- in the group with no PH and low pulmonary flow significantly decreased after CPB. A positive correlation was obtained between mean pulmonary-to-systemic arterial pressure ratio and ET-1 (r = 0.742 before CPB; r = 0.689 after CPB).

Conclusions. Imbalance between increased ET-1 and constant NO after CPB in the group with severe PH and high pulmonary flow could contribute to dominant effects of ET-1, which may injure the lung. The increased ET-1 and the decreased NO after CPB in the group with no PH and low pulmonary flow may induce a mechanism of protective vasoconstriction against an acute increase in pulmonary flow.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
The endothelium is a source of several relaxing and constricting factors, and it has been proposed that interactions between relaxing and constricting factors contribute to the normal physiology of blood flow regulation and play a role in cardiovascular disease [1]. Endothelin (ET) is a potent vasoconstrictive peptide with 21 amino acid residues that has multiple biologic actions [2]. There are three ET isoforms (ET-1, ET-2, and ET-3), and ET-1 is selectively cardiopulmonary derived [3]. Increases in circulating ET have been documented in states of severe cardiovascular stress, including cardiogenic shock, acute myocardial infarction, congestive heart failure, and essential hypertension [3].

Regarding the pulmonary circulation, previous studies reported an elevated ET-1 level in patients with pulmonary hypertension (PH) and suggested that endothelium-derived vasoconstrictor ET-1 may be involved in the pathophysiology of PH [4, 5]. A few investigators indirectly showed endothelium-derived vasodilator nitric oxide (NO) production after cardiopulmonary bypass (CPB) in congenital heart disease with PH by investigating the responses to acetylcholine [6, 7]. In ischemia/reperfusion, previous studies have shown that endothelium-derived ET-1 becomes dominant, whereas the production of endothelium-derived NO becomes impaired, and this imbalance could contribute to ischemia/reperfusion injury [8]. However, little consideration has been given to the balance of ET-1 and NO in patients with PH.

Production of NO is the only route to form nitrate (NO₃^-), and nitrite anions in mammals and the plasma NO₃^- levels directly reflect the plasma NO levels. In the present study, we examined the time course of plasma ET-1 and NO₃^- concentrations and attempted to explore the influence of ET-1 and NO on pulmonary vascular tone in congenital heart disease after CPB.

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Twenty children underwent open heart operations with CPB for congenital heart disease and were divided into three groups: (1) those with severe PH (mean pulmonary-to-systemic arterial pressure ratio [Pp/Ps] >0.5) and high pulmonary blood flow (pulmonary to systemic flow ratio [Qp/Qs] >1) (s-PH group) (n = 8; ventricular septal defect 1, double-outlet right ventricle 3, common atrioventricular canal 1, total anomalous pulmonary venous connection 2, single right ventricle 1), (2) those with mild PH (Pp/Ps <0.35) and high pulmonary blood flow (Qp/Qs >1) (m-PH group) (n = 6; ventricular septal defect 4, double-outlet right ventricle 2), and (3) those with no PH (Pp/Ps <0.30) and low pulmonary blood flow (Qp/Qs <1) (LF group) (n = 6; tetralogy of Fallot 4, single right ventricle 1, double-outlet right ventricle 1). The children were 3 months to 12 years old (1.2 ± 1.1 years old in the s-PH group; 5.9 ± 4.2 years old in the m-PH group; 2.5 ± 1.3 years old in the LF group), and there were no significant differences in age among the three groups (Table 1). Permission to conduct this study was given by the Ethical Committee of the Tokyo Women's Medical College.

Bioassay of Plasma Endothelin-1 and Nitrate Concentrations
Concentrations of plasma ET-1 were measured by a commercially available ET-1, 21 specific radioimmunoassay system (SRL, Tokyo, Japan). Briefly, plasma ET-1 was absorbed with octadecylsilyl silica, washed with 40% methanol and acetone, then eluted with 60% methanol. After evaporation with nitrogen gas, the dried residue was dissolved in 0.05 mol/L Tris-HCL buffer. Either standard ET-1 (Peptide Institute Inc, Osaka, Japan) or sample was incubated with rabbit anti–ET-1 antiserum (Peninsula Laboratories Inc, Belmont, CA). Thereafter, [¹²⁵I] ET-1 (Amersham International, Amersham, UK) was added and the mixture was incubated. Bound and free ligands were separated with goat anti-rabbit immunoglobulin G serum (Eiken Chemical Co. Ltd, Tokyo, Japan). The concentrations of ET-1 were expressed in pg/mL.

The concentration of NO₃^-, an NO metabolite, was measured by commercially available high performance liquid chromatography (SRL). Briefly, the deproteinized plasma sample was reduced by high performance liquid chromatography. It was reacted with naphthyl-ethylenediamine and its absorbance was read at 540 nm by a flow-through ultraviolet/visible spectrophotometer (Model 440; Waters Associations, Milford, MA) (µmol/L). In terms of sensitivity, chemiluminescence is better than high performance liquid chromatography, but we chose high performance liquid chromatography because it is a much more specific and stable method.

Measurements
Concentrations of ET-1 were measured at all time points (immediately before CPB, before rewarming, after rewarming, immediately after CPB, and 3, 6, and 24 hours after CPB). Concentrations of NO₃^- were measured immediately before and after CPB. Correlation coefficients between Pp/Ps and ET-1 were calculated both before and after CPB.

Statistics
All values are expressed as mean ± standard deviation and were analyzed by a statistical analysis system (SPSS). One-way analysis of variance and repeated-measures two-way analysis of variance were used to compare differences between groups. Data were compared using the Student-Newman-Keuls test if analysis of variance was significant. A p value less than 0.05 was considered significant.

	Results

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Plasma Endothelin-1 Bioassay
Before CPB, the ET-1 concentration in the s-PH group (4.34 ± 0.95 pg/mL) was higher than that in the other two groups (2.78 ± 0.57 pg/mL in the m-PH group; 2.82 ± 0.39 pg/mL in the LF group) (Fig 1). After CPB, ET-1 concentrations in each group were higher than before CPB (significantly higher at all time points after CPB in the s-PH group and LF groups; significantly higher at 3 and 6 hours after CPB in the m-PH group). The ET-1 concentration immediately after CPB in the LF group (6.00 ± 1.66 pg/mL) was significantly higher than that in the m-PH group (3.72 ± 1.53 pg/mL). Endothelin-1 concentrations until 6 hours after CPB in the s-PH group were higher than those in the other two groups. (Actually, mild PH crisis had occurred in 2 cases in the s-PH group 6 hours after CPB.) No correction was attempted for the hemodilution of CPB because the uncorrected plasma level has more physical significance than the corrected value, and this correction cannot be done accurately.

View larger version (21K): [in this window] [in a new window]   Fig 1. . Time course of endothelin-1 ( ET-1) level. (CPB = cardiopulmonary bypass; LF = low pulmonary blood flow; m-PH = mild pulmonary hypertension; s-PH = severe pulmonary hypertension.)

View larger version (14K): [in this window] [in a new window]   Fig 2. . Correlation between mean pulmonary-to-systemic arterial pressure ratio ( Pp/Ps) and endothelin-1 (ET-1) level before cardiopulmonary bypass.

View larger version (14K): [in this window] [in a new window]   Fig 3. . Correlation between mean pulmonary-to-systemic arterial pressure ratio ( Pp/Ps) and endothelin-1 (ET-1) level after cardiopulmonary bypass.

View larger version (14K): [in this window] [in a new window]   Fig 4. . Nitrate ( NO3-) level before and after cardiopulmonary bypass (CPB). Other abbreviations are as in Figure 1.

	Comment

Top Footnotes Abstract Introduction Material and Methods Results Comment References

Concentrations of ET-1 in the s-PH group were higher than in the other two groups both before and after CPB. Because ET mRNA is widely present in various tissues [11], increased ET in these pathophysiologic states could originate from several sources, including heart, lung, and peripheral vasculature. Recent investigations have established that pharmacologic concentrations of the ET family result in potent coronary, pulmonary, renal, and systemic vasoconstriction [12]. Relating to the pulmonary circulation, ET-1 is an important vascular regulatory peptide of endothelial origin in the lung. We drew the blood sample from the pulmonary vein or left atrium directly and measured Pp/Ps simultaneously; a close correlation between ET-1 levels and Pp/Ps was shown both immediately before and after CPB. Komai and associates [5] have shown a similar close correlation between ET-1 levels and pulmonary arterial pressure, although their data were obtained from cardiac catheterization before and after the operation. Endothelin-1 seems to play an important role in the pulmonary circulation both before and after CPB.

The ET-1 concentration may differ depending on age. Circulating ET-1 levels are reported to be highest during the newborn period, especially on the first day of life, and gradually decrease with age [13]; almost constant levels are achieved after 1 month of age. The age distribution of our patients was 3 months to 12 years old, and this study seemed to show little influence on the ET-1 levels by age difference.

Another important finding was that the plasma NO₃^- level did not decrease after CPB in the PH groups and did decrease significantly after CPB in the LF group. Regarding NO and ischemia/reperfusion injury, we have reported that there is close correlation between NO and reperfusion injury. Diminished NO production might occur after reperfusion, as observed by the decreased reaction to acetylcholine. As for the actions of NO, NO is reported to have two opposite effects. One is the cytotoxic effect due to the formation of peroxynitrite from NO plus superoxide (O₂⁺) [14], and another is the tissue-sparing effect based upon vasodilatory [15], antineutrophil [16], and antiplatelet [17] actions, as well as direct quenching of superoxide free radicals [18] within ischemic tissues.

In patients with low pulmonary blood flow such as tetralogy of Fallot, pulmonary blood flow increases immediately after intracardiac repair, which results in acute volume overload not only to the pulmonary vascular bed, but also to the left side of the heart, which is usually undersized preoperatively. This change likely causes the elevation of intracapillary blood pressure at the alveolar level, thus predisposing to or causing pulmonary edema, unless some mechanism protects this process. As is reported, PH due to increased blood flow or due to mitral stenosis is associated with an increase in the circulating plasma ET-1 level [1], which is considered to be acting as a protective mechanism to prevent pulmonary edema. Thus, the data showing that the ET-1 level was higher in the LF group than in the m-PH group at some points in the postoperative course (see Fig 1) indicate the physiologic importance of the increase in ET-1 in the LF group. In this context, the decrease of NO₃^- after CPB in the LF group is intriguing because the vasodilatory substance should have a harmful effect in this group, although the mechanism is still not clear and we do not have any evidence to support this notion.

The current study showed an increased level of ET-1 after ischemia/reperfusion and the continuous presence of NO before and after pulmonary ischemia in the PH groups, and an increased level of ET-1 after ischemia/reperfusion and a decreased level of NO after CPB in the LF group. These results lead us to hypothesize that an imbalance of endothelium-derived vasodilators and vasoconstrictors exists after hypothermic pulmonary ischemia and reperfusion. This imbalance then plays an important role in pulmonary ischemia/reperfusion injury. In ischemia/reperfusion, endothelium-derived ET-1 becomes dominant, whereas the production of endothelium-derived NO becomes constant or impaired, and this imbalance contributes to ischemia/reperfusion injury in the PH group and to protective vasoconstriction in the LF group.

An alternative mechanism by which an ET-1/NO imbalance could influence postischemic recovery is suggested by the recent observation that ET-1 increases neutrophil adhesion to endothelial cells by inducing leukocyte integrin expression and thus causes endothelial functional damage [19]. Because NO has been shown to inhibit the expression of endothelial adhesion molecules [20], to inhibit neutrophil-endothelial adhesion [21], and to improve the recovery of endothelial function [22], an imbalance of ET-1 and NO could also enhance pulmonary postischemia/reperfusion injury through accumulation of activated neutrophils in the pulmonary circulation. It is also noteworthy that NO normally inhibits the release of ET-1 [23, 24] and that ET normally stimulates the release of NO [25].

These conclusions are limited by the possibility that other substances could influence the pulmonary vascular tone other than ET and NO: Thromboxane A₂ may be another endothelium-derived constricting factor besides ET, and prostacyclin and others may be other endothelium-derived relaxing factors besides NO [1]. Non–endothelium-derived agents such as catecholamines, renin, angiotensin, atrial natriuretic peptide, brain natriuretic peptide, and others may also influence the pulmonary vascular tone as well as endothelium-derived factors.

In summary, the results of the current studies suggest that an imbalance between an increased ET-1 and a constant NO level after CPB could contribute to the dominant effect of endothelium-derived vasoconstrictor ET-1 in the PH groups and may cause a more injurious effect on a lung with endothelial dysfunction after CPB. Increased ET-1 and decreased NO after CPB in the LF group may induce vasoconstriction in a protective mechanism against an acute increase in pulmonary blood flow to avoid pulmonary edema.

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Address reprint requests to Dr Hiramatsu, Department of Pediatric Cardiac Surgery, Tokyo Women's Medical College, Heart Institute of Japan, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162 Japan.

	References

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 

1. Lüscher TF, Boulanger CM, Yang Z, Noll G, Dohi Y. Interactions between endothelium-derived relaxing and contracting factors in health and cardiovascular disease. Circulation 1993;87(Suppl 5):36–43.
2. Yanagisawa M, Kurihara H, Tomobe Y, et al. Novel potent vasoconstrictor peptide produced by vascular endothelial cell. Nature 1988;3321:411–5.
3. Nayler WG. The endothelins. Berlin: Springer-Verlag, 1990:1–188.
4. Yoshibayashi M, Nishioka K, Nakao K, et al. Plasma endothelin concentrations in patients with pulmonary hypertension associated with congenital heart defects. Circulation 1991;84:2280–5.[Abstract/Free Full Text]
5. Komai H, Adatia IT, Elliott MJ, de Leval MR, Haworth SG. Increased plasma levels of endothelin-1 after cardiopulmonary bypass in patients with pulmonary hypertension and congenital heart disease. J Thorac Cardiovasc Surg 1993;106:473–8.
6. Wessel DL, Adatia I, Giglia TM, Thompson JE, Kulik TJ. Use of inhaled nitric oxide and acetylcholine in the evaluation of pulmonary hypertension and endothelial function after cardiopulmonary bypass. Circulation 1993;88:2128–38.[Abstract/Free Full Text]
7. Shafique T, Johnson RG, Dai HB, Weintraub RM, Sellke FW. Altered pulmonary microvascular reactivity after total cardiopulmonary bypass. J Thorac Cardiovasc Surg 1993;106:479–86.[Abstract]
8. Hiramatsu T, Forbess JM, Miura T, Roth SJ, Cioffi MA, Mayer JE Jr. Effects of endothelin-1 and L-arginine after cold ischemia on recovery in lamb hearts. Ann Thorac Surg 1996;61:36–41.
9. Brunner F, du Toit E, Opie LH. Endothelin release during ischemia and reperfusion of isolated perfused rat hearts. J Mol Cell Cardiol 1992;24:1291–305.[Medline]
10. Hynyen M, Saijonmaa O, Tickkanen I, Heinonen J, Fyhrquist F. Increased plasma endothelin immunoreactivity during cardiopulmonary bypass. J Thorac Cardiovasc Surg 1992;103:1024–5.
11. Nunez DJR, Brown MJ, Davenport AP, Neylon CB, Schofield JP, Wyse RK. Endothelin-1 mRNA is widely expressed in porcine and human tissues. J Clin Invest 1990;85:1537–41.
12. Goetz KL, Wang BC, Nadwed JB, Zhu JL, Leadley RJ Jr. Cardiovascular, renal, and endocrine responses to intravenous endothelin in conscious dogs. Am J Physiol 1988;255:R1064–8.[Abstract/Free Full Text]
13. Kojima T, Fukada Y, Takedatsu M, Hirata Y, Kobayashi Y. Circulating levels of endothelin and atrial natriuretic factor during postnatal life. Acta Paediatr 1992;81:676–7.[Medline]
14. Beckman JS, Crow JP. Pathological implications of nitric oxide, superoxide and peroxynitrite formation. Biochem Soc Trans 1993;21:330–4.[Medline]
15. Amezcua JL, Palmer RMJ, De Souza BM, Moncada S. Nitric oxide synthesized from L-arginine regulates vascular tone in the coronary circulation of the rabbit. Br J Pharmacol 1990;97:1119–24.[Medline]
16. McCall T, White BJR, Boughton-Smith NK, Moncada S. Inhibition of FMLP-induced aggregation of rabbit neutrophils by nitric oxide. Br J Pharmacol 1988;85:517P.
17. Furlong B, Henderson AH, Lewis MJ, Smith JA. Endothelium-derived relaxing factor inhibits in vitro platelet aggregation. Br J Pharmacol 1987;90:687–92.[Medline]
18. Rubanyi GM, Ho EH, Cantor EH, Lumma WC, Parker-Botelho LH. Cytoprotective function of nitric oxide: inactivation of superoxide radicals produced by human leukocytes. Biochem Biophys Res Commun 1991;181:1392–7.[Medline]
19. Lopez Farre A, Riesco A, Espinosa G, et al. Effects of endothelin-1 on neutrophil adhesion to endothelial cells and perfused hearts. Circulation 1993;88:1166–71.[Abstract/Free Full Text]
20. De Caterina R, Shin WS, Liao JK, Libby P. Nitric oxide inhibits cytokine-induced expression of endothelial leukocyte adhesion molecules [Abstract]. Circulation 1994;90: Pt2I–29.
21. Kubeo P, Suzuki M, Granger N. Nitric oxide: an endogenous modulation of leukocyte adhesion. Proc Natl Acad Sci USA 1991;88:4651–5.[Abstract/Free Full Text]
22. Hiramatsu T, Forbess JM, Miura T, Mayer JE Jr. Effects of L-arginine and L-NAME on recovery of neonatal lamb hearts after cold cardioplegic ischemia: evidence for an important role for endothelial production of nitric oxide. J Thorac Cardiovasc Surg 1995;109:81–7.[Abstract/Free Full Text]
23. DeNucci G, Thomas R, D'Orleans-Juste P, Antunes E, Walder TD, Vane JR. Pressor effects of circulating endothelin are limited by its removal in the pulmonary circulation and by the release of prostacyclin and endothelium-derived relaxing factor. Proc Natl Acad Sci USA 1988;85:9797–800.[Abstract/Free Full Text]
24. Boulanger C, Lüscher TF. Release of endothelium from porcine aorta inhibition by endothelium-derived nitric oxide. J Clin Invest 1990;85:587–90.
25. Lüscher TF, Yang Z, Tschudi M, et al. Interactions between endothelin-1 and endothelium-derived relaxing factor in human arteries and veins. Circ Res 1990;66:1088–94.[Abstract/Free Full Text]

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This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Yasuharu Imai Yoshinori Takanashi Shuichi Hoshino Makoto Nakazawa Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hiramatsu, T. Articles by Nakazawa, M. Search for Related Content PubMed PubMed Citation Articles by Hiramatsu, T. Articles by Nakazawa, M.