Pretreatment with growth hormone-releasing peptide-2 directly protects against the diastolic dysfunction of myocardial stunning in an isolated, blood-perfused rabbit heart model.

Pretreatment with growth hormone-releasing peptide-2 directly protects against the diastolic dysfunction of myocardial stunning in an isolated, blood-perfused rabbit heart model.
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在离体、血液灌注的兔心脏模型中,用生长激素释放肽-2 进行预处理可直接防止心肌顿抑引起的舒张功能障碍。

DOI:
10.1210/en.141.11.3993
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发表时间:
2000
期刊:
影响因子:
4.8
通讯作者:
G. V. Berghe
G. V. Berghe
中科院分区:
医学2区
文献类型:
--
作者:
F. Weekers;E. V. Herck;J. Isgaard;G. V. Berghe

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Brief coronary occlusion followed by reperfusion leads to reversible myocardial dysfunction (stunning) which can induce irreversible damage of other organ systems. We studied the effects of pretreatment with recombinant human GH (rhGH) and the GH-secretagogue GHRP-2 on myocardial stunning in a blood-perfused isolated rabbit heart model. In a first set of experiments, effects of bolus rhGH administration (3.5 mg/kg) (n = 5) into the aortic root of unpretreated animals were compared with those of saline (n = 6). In a second set, animals were pretreated for 14 days with SC rhGH 3.5 mg/kg x day (n = 9) or 160 microg/kg x day GHRP-2 (n = 8) in two divided doses. Body weight and plasma concentrations of rhGH, rabbit GH (rGH) and IGF-I were determined before and at the end of 14 days pretreatment. Hearts were excised and submitted to 15 min ischemia followed by 80 min reperfusion, after which postischemic recovery was compared with nonischemic hearts mounted into the same system. At study end, all hearts were snap-frozen to examine markers of apoptosis. Circulating levels of rabbit GH (rGH) remained identical in all animals. Pretreatment with rhGH for 14 days induced a 142 +/- 116% rise of serum IGF-I vs. 8 +/- 15% with GHRP-2 (P < 0.001) and increased body weight with 6.8 +/- 2.5% vs. 3.4 +/- 3.3% with GHRP-2 (P = 0.01). A bolus injection of rhGH did not alter myocardial function compared with saline allowing data from these experiments to be pooled into one ischemic control group for further analysis of the effect of pretreatment. No difference in postischemic recovery of left ventricular systolic function among the unpretreated, rhGH pretreated and GHRP-2 pretreated hearts was apparent. At the end of reperfusion, a 3-fold higher end-diastolic pressure (EDP) persisted in the unpretreated and rhGH pretreated hearts compared with the nonischemic hearts. In the GHRP-2 pretreated hearts, EDP decreased to half the pressure observed in unpretreated and rhGH pretreated hearts (all P < or = 0.02), a level which was indistinguishable from that in the non-ischemic hearts, suggesting full postischemic recovery of diastolic function. There were no signs of increased apoptosis in the experimental groups. In conclusion, 14 days pretreatment with GHRP-2, but not rhGH, protected selectively against the diastolic dysfunction of myocardial stunning in this model. This observation may open perspectives for GH-secretagogues as cardioprotective agents.
慢性生长激素分泌过多对大鼠左心室内在收缩力、能量学、异肌球蛋白模式和肌球蛋白三磷酸酶活性的影响。
DOI: 10.1172/jci114737
发表时间: 1990
期刊: The Journal of clinical investigation
影响因子: --
作者:
Timsit,J;Riou,B;Bertherat,J;Wisnewsky,C;Kato,NS;Weisberg,AS;Lubetzki,J;Lecarpentier,Y;Winegrad,S;Mercadier,JJ
通讯作者: Mercadier,JJ
DOI: 10.1172/jci117504
发表时间: 1994-10-01
影响因子: 15.9
作者:
GOTTLIEB, RA;BURLESON, KO;ENGLER, RL
通讯作者: ENGLER, RL
DOI: 10.1210/endo.135.3.8070352
发表时间: 1994-09
期刊: Endocrinology
影响因子: 4.8
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DOI: 10.1161/01.cir.93.4.800
发表时间: 1996-02-15
期刊: CIRCULATION
影响因子: 37.8
作者:
Cittadini, A;Stromer, H;Douglas, PS
通讯作者: Douglas, PS
DOI: 10.1172/jci117706
发表时间: 1995-02-01
影响因子: 15.9
作者:
DUERR, RL;HUANG, S;ROSS, J
通讯作者: ROSS, J