The effect of Glucagon-Like Peptide-2 on mesenteric blood flow and cardiac parameters in end-jejunostomy short bowel patients

被引:82
作者
Bremholm, Lasse [1 ]
Hornum, Mads [2 ]
Andersen, Ulrik B. [3 ]
Hartmann, Bolette [4 ]
Hoist, Jens Juul [4 ]
Jeppesen, Palle Bekker [5 ]
机构
[1] Univ Copenhagen, Koge Hosp, Dept Gastroenterol, Koge, Denmark
[2] Copenhagen Univ Hosp, Rigshosp, Dept Nephrol, Copenhagen, Denmark
[3] Univ Copenhagen, Glostrup Hosp, Dept Clin Physiol & Nucl Med, Copenhagen, Denmark
[4] Univ Copenhagen, Panum Inst, Dept Biomed Sci, DK-2200 Copenhagen, Denmark
[5] Copenhagen Univ Hosp, Rigshosp, Dept Med Gastroenterol, Copenhagen, Denmark
关键词
GLP-2; Intestinal blood flow; Cardiac parameters; Human; Intestinal failure; DUPLEX ULTRASOUND; NEONATAL PIGLETS; BONE-RESORPTION; GLP-2; HUMANS; OUTPUT; ARTERY;
D O I
10.1016/j.regpep.2011.03.003
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
Background: Exogenous Glucagon-Like Peptide-2 (GLP-2) treatment improves intestinal wet weight absorption in short bowel syndrome (SBS) patients. In healthy subjects, administration of GLP-2 increases small intestinal blood flow. The aim of the study was to evaluate the effect of GLP-2 on mesenteric blood flow and dynamic changes in cardiac parameters in SBS patients with jejunostomy and varying length of remnant small intestine. Methods: 8 SBS patients with end-jejunostomy and less than 200 cm small intestine were given GLP-2, 1600 mu g subcutaneously (SC), or isotonic saline in a double blinded manner. At 0,30 and 60 min plasma GLP-2 was measured, and from 0 to 90 min, blood flow in the superior mesenteric artery (SMA) and the celiac artery (CA) was measured using Doppler ultrasound (US), and cardiovascular variables were measured by continuous impedance cardiography and finger plethysmography. Results: Plasma GLP-2 concentrations increased significantly in the GLP-2 group, whereas no changes were seen in the placebo group. Compared to baseline, GLP-2 SC elicited a 19.4% decrease (p<0.01) in the resistance index (RI) and a 97.6% increase in time averaged maximal velocity (TAMV) in the SMA (P<0.01). In the CA there were no significant changes in RI or TAMV in the GLP-2 or placebo group. Blood flow and length of remaining intestine were correlated (RI: y = 0.14 + 43, R = 0.83, p = 0.01 and TAMV: y = 1.21 + 21.3, R = 0.63, p = 0.09). GLP-2 non significantly increased cardiac output (CO), stroke volume (SV) and significantly increased heart rate (HR) compared to baseline. Conclusion: Subcutaneous GLP-2 increased SMA blood flow in end-jejunostomy SBS patients with less than 200 cm of remaining small intestine. The increase in blood flow correlated with the length of remaining intestine, suggesting that the increase is coupled to the metabolic actions of GLP-2 on the gut rather than effects on the vasculature. (C) 2011 Elsevier B.V. All rights reserved.
引用
收藏
页码:32 / 38
页数:7
相关论文
共 18 条
[1]
Modulation of specific intestinal epithelial progenitors by enteric neurons [J].
Bjerknes, M ;
Cheng, H .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (22) :12497-12502
[2]
The effect of glucagon-like peptide-2 on arterial blood flow and cardiac parameters [J].
Bremholm, Lasse ;
Hornum, Mads ;
Andersen, Ulrik B. ;
Holst, Jens Juul .
REGULATORY PEPTIDES, 2010, 159 (1-3) :67-71
[3]
Glucagon-like peptide-2 increases mesenteric blood flow in humans [J].
Bremholm, Lasse ;
Hornum, Mads ;
Henriksen, Birthe Merete ;
Larsen, Steen ;
Holst, Jens Juul .
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, 2009, 44 (03) :314-319
[4]
GLP-2 rapidly activates divergent intracellular signaling pathways involved in intestinal cell survival and proliferation in neonatal piglets [J].
Burrin, Douglas G. ;
Stoll, Barbara ;
Guan, Xinfu ;
Cui, Liwei ;
Chang, Xiaoyan ;
Hadsell, Darryl .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2007, 292 (01) :E281-E291
[5]
Mediators of glucagon-like peptide 2-induced blood flow: Responses in different vascular sites [J].
Deniz, Mustafa ;
Bozkurt, Ayhan ;
Kurtel, Hizir .
REGULATORY PEPTIDES, 2007, 142 (1-2) :7-15
[6]
Non-invasive beat-to-beat cardiac output monitoring by an improved method of transthoracic bioimpedance measurement [J].
Fortin, J. ;
Habenbacher, W. ;
Heller, A. ;
Hacker, A. ;
Gruellenberger, R. ;
Innerhofer, J. ;
Passath, H. ;
Wagner, Ch. ;
Haitchi, G. ;
Flotzinger, D. ;
Pacher, R. ;
Wach, P. .
COMPUTERS IN BIOLOGY AND MEDICINE, 2006, 36 (11) :1185-1203
[7]
GLP-2-mediated up-regulation of intestinal blood flow and glucose uptake is nitric oxide-dependent in TPN-fed piglets [J].
Guan, XF ;
Stoll, B ;
Lu, XF ;
Tappenden, KA ;
Holst, JJ ;
Hartmann, B ;
Burrin, DG .
GASTROENTEROLOGY, 2003, 125 (01) :136-147
[8]
Structure, measurement, and secretion of human glucagon-like peptide-2 [J].
Hartmann, B ;
Johnsen, AH ;
Orskov, C ;
Adelhorst, K ;
Thim, L ;
Holst, JJ .
PEPTIDES, 2000, 21 (01) :73-80
[9]
Reduction of nocturnal rise in bone resorption by subcutaneous GLP-2 [J].
Henriksen, DB ;
Alexandersen, P ;
Byrjalsen, I ;
Hartmann, B ;
Bone, HG ;
Christiansen, C ;
Holst, JJ .
BONE, 2004, 34 (01) :140-147
[10]
Disassociation of bone resorption and formation by GLP-2 - A 14-day study in healthy postmenopausal women [J].
Henriksen, Dennis B. ;
Alexandersen, Peter ;
Hartmann, Bolette ;
Adrian, Charlotte L. ;
Byrjalsen, Inger ;
Bone, Henry G. ;
Holst, Jens J. ;
Christiansen, Claus .
BONE, 2007, 40 (03) :723-729