Changes of ghrelin and brain natriuretic peptide levels in systemic vascular resistance after cardiopulmonary bypass.

• Autores: A. Rahman
• Localización: Journal of physiology and biochemistry, ISSN-e 1877-8755, ISSN 1138-7548, Vol. 64, Nº. 3, 2008, págs. 221-230
• Idioma: inglés
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• Resumen

  • The application of cardiopulmonary bypass (CPB) using a heart-lung machine in open heart surgery is associated with numerous pathophysiological changes in the vascular system and the neurohormonal environment. In this study our purpose was to investigate whether the hormones brain natriuretic peptide (BNP) and ghrelin are involved in changes in the systemic vascular resistance index (SVRI) after CPB, using data from 20 patients who had undergone coronary artery bypass grafting accompanied by CPB. Hemodynamic measurements were obtained using a thermodilution catheter and included cardiac index and systemic vascular resistance index. Blood samples were taken before CPB, after CPB, and at 0 and 24 h postoperatively. The blood levels of total and acylated ghrelin were quantified by radioimmunoassay.

    Blood levels of BNP were measured by a fluorescence immunoassay kit. The SVRI was significantly higher at the end of CPB and at 0 h postoperatively than before CPB (end of CPB: 4282±1035 dyne . s . cm-5 . m-2 , 0 h postoperatively: 3239±635 dyne . s . cm-5 .m-2 vs. before CPB: 2289±330 dyne . s . cm-5 .m-2, p < 0.05). Total and acylated ghrelin levels decreased until 0 h postoperatively but the change was not statistically significant. However, at 24 h after surgery, they showed a statistically significant increase over the initial ghrelin values (total before CPB: 1413.71 ± 287.93 pg/ml vs. 24 h postoperatively: 1736.85 ± 236.89 pg/ml; acylated ghrelin before CPB:

    55.85 ± 25.53 pg/ml vs. 24 h postoperatively: 106.28 ± 30.86 pg/ml; p < 0.05 for both).

    BNP values were markedly lower after than before CPB (before CPB: 69.07 ± 48 pg/ml vs. after CPB: 21.96 ± 13 pg/ml, p<0.05) and reached a maximum value 24 h postoperatively (before CPB: 56.3 ± 42 vs. after CPB: 454.7 ± 229 pg/ml, p<0.05).

    J Physiol Biochem, 64 (3), 221-230, 2008 Cardiopulmonary bypass (CPB) has been reported to cause a pattern of changes in systemic vascular resistance (SVR) (22). These changes have been attributed to hemodilution, decreased blood viscosity, baroreceptor reflexes, hyperkalemia, and especially alterations in vasoactive substances (5). However, the key vasoactive substance involved has not yet been clearly identified. The changes in SVR may be also caused in part by hormonal changes.

    One of the major challenges during cardiac surgery is to protect the heart from ischemia-reperfusion injury (1). It has been shown that myocardial ischemia causes acute changes in circulating brain natriuretic peptide (BNP), which is mainly produced by the cardiac ventricle. Left ventricular hypertrophy (LVH) or left ventricular dysfunction is associated with increased BNP levels, and in patients with coronary insufficiency or heart failure, BNP has prognostic significance. BNP is also thought to be a counter-regulatory hormone that protects the heart from injury (29). This protection may result from its diuretic, natriuretic and vascular smooth muscle relaxing effects (29). Both in vivo and ex vivo studies have also indicated that human BNP induces dosedependent relaxation of human arteries, resulting, for instance, in increased forearm blood flow (25, 31, 33).

    Another recently-discovered cardioprotective hormone is ghrelin (4). It was first isolated from the stomach and identified as an endogenous ligand for the GH secretagogue receptor (GHS-R) that alters cellular metabolism (11). Ghrelin is present in two forms in biological fluids. One form, acylated ghrelin, has a caprylic (octanoic) acid residue attached to the 3rd serine of the N-terminal region (2, 12).

    This acylated form (active ghrelin) is thought to be essential for attaching to growth hormone secretagogue receptor 1a (GHSRA-1a). The other form, des-acylated ghrelin (inactive ghrelin), contains no caprylic acid residue (12). Des-acylated ghrelin is not totally inactive; it influences cell proliferation and adipogenesis and counteracts the metabolic action of active ghrelin (3, 30). Both forms of ghrelin might be important in cardioprotection because human and animal data have shown that they both have effects on the cardiovascular system (4). Another recent report has demonstrated that ghrelin is a potent vasodilator in isolated human arteries (32). Furthermore, intracerebroventricular administration of ghrelin suppresses the sympathetic nervous system, resulting in decreased arterial pressure (13, 20).

    To the best of our knowledge, there have been no reports of the significance of serum ghrelin and BNP concentrations in A. RAHMAN, S. AYDIN, M.K. BAYAR and ÿI. SAHIN 222 J Physiol Biochem, 64 (3), 2008 There was a weak negative correlation between the changes in SVRI and total and acylated ghrelin levels after the CPB period, but this was not statistically significant.

    However, there was a statistically significant negative correlation between SVRI and BNP after CPB and at 24 h postoperatively (r:-0.709, p<0.01 and r:-0.649, p<0.03, respectively). Taken together, our results show that the observed initial increases in ghrelin and/or BNP in the postoperative period (at 24 h) might be causally related to the decrease in the SVRI in the same period. However, further investigations are needed to clarify the significance of this observation with respect to that of SVRI.