Grosman-Rimon Liza, Tumiati Laura C, Fuks Avi, Jacobs Ira, Lalonde Spencer D, Cherney David Z I, Rao Vivek
Division of Cardiovascular Surgery, Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada; Department of Exercise Sciences, Faculty of Kinesiology and Physical Education, University of Toronto, Toronto, Ontario, Canada.
Division of Cardiovascular Surgery, Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada.
J Thorac Cardiovasc Surg. 2016 Jan;151(1):219-27. doi: 10.1016/j.jtcvs.2015.09.015. Epub 2015 Sep 18.
We examine the hypothesis that cyclic guanosine monophosphate (cGMP) levels are elevated in recipients of continuous-flow left ventricular assist devices (CF-LVADs) and that elevated cGMP levels are associated with a risk of gastrointestinal (GI) bleeding events.
The levels of cGMP, nitric oxide, platelet activation markers, platelet-derived growth factors (PDGF) AB/BB and AA, and the inflammatory mediator C-reactive protein (CRP) were examined in 19 CF-LVAD recipients, 21 patients who had heart failure, and 19 healthy control-group participants.
The median level of cGMP was significantly higher in CF-LVAD recipients, compared with healthy participants (6.6 vs 2.1 pmol/mL, u = 62.5; P = .001; r = -0.55). Median cGMP levels in the heart failure group (12.5 pmol/L) were higher, compared with both CF-LVAD recipients (u = 75.0; P = .001; r = -0.53) and healthy participants (u = 4.0; P < .001; r = -0.83). Compared with the healthy group, median CRP levels were significantly higher in CF-LVAD recipients (2.9 vs 8.0 mg/L; u = 58.0; P < .001; r = -0.63) and heart failure patients (2.9 vs 7.0 mg/L; u = 59.0; P < .001; r = -0.65). In the subgroup of patients supported with the HeartMate II (Thoratec Corporation, Pleasanton, Calif), pulsatility index was significantly negatively correlated with cGMP levels (r = -0.73; P < .05), indicating that low pulsatility index is associated with higher cGMP levels. High cGMP levels were significantly associated with GI bleeding events, but not with bleeding events in general.
The primary finding of this study is that GI bleeding in CF-LVAD recipients is associated with significantly elevated cGMP levels, despite high levels of CRP, which interfere with cGMP production. Further studies are required to determine whether elevated cGMP levels can be used as a clinical marker for increased risk of GI bleeding in CF-LVAD recipients.
我们检验以下假设,即连续流左心室辅助装置(CF-LVAD)接受者的环磷酸鸟苷(cGMP)水平升高,且cGMP水平升高与胃肠道(GI)出血事件风险相关。
检测了19例CF-LVAD接受者、21例心力衰竭患者和19名健康对照组参与者的cGMP、一氧化氮、血小板活化标志物、血小板衍生生长因子(PDGF)AB/BB和AA以及炎症介质C反应蛋白(CRP)的水平。
与健康参与者相比,CF-LVAD接受者的cGMP中位数水平显著更高(6.6对2.1 pmol/mL,u = 62.5;P = 0.001;r = -0.55)。心力衰竭组的cGMP中位数水平(12.5 pmol/L)高于CF-LVAD接受者(u = 75.0;P = 0.001;r = -0.53)和健康参与者(u = 4.0;P < 0.001;r = -0.83)。与健康组相比,CF-LVAD接受者(2.9对8.0 mg/L;u = 58.0;P < 0.001;r = -0.63)和心力衰竭患者(2.9对7.0 mg/L;u = 59.0;P < 0.001;r = -0.65)的CRP中位数水平显著更高。在使用HeartMate II(Thoratec公司,加利福尼亚州普莱森顿)支持的患者亚组中,搏动指数与cGMP水平显著负相关(r = -0.73;P < 0.05),表明低搏动指数与较高的cGMP水平相关。高cGMP水平与GI出血事件显著相关,但与一般出血事件无关。
本研究的主要发现是,尽管CRP水平较高会干扰cGMP的产生,但CF-LVAD接受者的GI出血与cGMP水平显著升高相关。需要进一步研究以确定升高的cGMP水平是否可作为CF-LVAD接受者GI出血风险增加的临床标志物。