Altered vasoconstrictor and dilator responses after a "two-hit" model of sequential hemorrhage and bacteremia.
Altered vasoconstrictor and dilator responses after a "two-hit" model of sequential hemorrhage and bacteremia.
复制标题
在连续出血和菌血症的“两次打击”模型后改变血管收缩剂和扩张剂反应。
DOI：
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发表时间：
1999
影响因子：
2.2
通讯作者：
R. Garrison
中科院分区：
文献类型：
--
作者：
Shaun A. Price;David A. Spain;Mark A. Wilson;Patrick D. Harris;R. Garrison
背景
多器官功能障碍(MOD)的“两次打击”理论认为，最初的侮辱，如出血(HEM)，会使宿主对第二次应激(如感染)做出异常反应。这一理论的免疫学/炎症成分已经得到了很好的检验；然而，对血管反应性的影响却知之甚少。我们假设，对第二次病理生理应激反应的改变，使血管系统处于基础状态。
方法
雄性SpragueDawley大鼠接受固定容量的HEM复苏(H/R)或假手术(Sham)。48h后，给动物静脉注射大肠杆菌或生理盐水1h，然后将胸主动脉环置于含有Krebs缓冲液的器官浴中，Krebs缓冲液中充气95%O2和5%CO2。获得苯肾上腺素(Phe)和乙酰胆碱(ACH)的累积剂量-反应曲线。测量最大收缩力值(Fmax)，计算PD2值(受体敏感性)。
结果
仅H/R可导致收缩肌张力升高和扩张器张力减弱。大肠杆菌对Phe的反应使Fmax下降50%，而在H/R组下降76%，受体敏感性(PD2)在H/R组更大程度地降低(3倍对2倍)。这些动物的ACH受体敏感性也有更显著的提高(7倍对2倍)。
结论
出血使血管系统对随后的应激反应发生改变。当感染被添加为“二次打击”时，对肾上腺素能药物的反应性降低，扩张器张力增加。这些数据可能解释了在大出血后继发感染后出现MODS的患者临床上出现的心血管紊乱。
BACKGROUND
The "two-hit" theory of multiple organ dysfunction (MOD) proposes that an initial insult, such as hemorrhage (HEM), primes the host for an abnormal response to a second stress such as infection. The immunologic/inflammatory component of this theory has been well examined; however, the effects on vascular responsiveness are poorly understood. We hypothesized that HEM primes the vasculature for an altered response to a second pathophysiologic stress.
METHODS
Male Sprague-Dawley rats underwent a fixed-volume HEM with resuscitation (H/R) or sham procedure (Sham). At 48 h, animals were given iv E. coli or saline and followed for 1 h. Thoracic aortic rings were then placed in organ baths containing Krebs buffer aerated with 95% O2, 5% CO2. Cumulative dose-response curves to phenylephrine (PHE) and acetylcholine (ACH) were obtained. Maximum force of contraction (Fmax) was measured and pD2 values (receptor sensitivity) were derived.
RESULTS
H/R alone resulted in heightened constrictor tone and blunted dilator tone. E. coli reduced Fmax in response to PHE by 50% in Sham vs 76% in H/R. Receptor sensitivity (pD2) to PHE was reduced to a greater degree in H/R (3-fold vs 2-fold). These animals also had a more pronounced enhancement of ACH receptor sensitivity (7-fold vs 2-fold).
CONCLUSIONS
Hemorrhage primes the vasculature for an altered response to a subsequent stress. When infection is added as a "second hit," responsiveness to adrenergic agents is diminished and dilator tone is increased. These data may explain the cardiovascular derangements seen clinically in patients who develop MODS after major hemorrhage followed sequentially by infection.
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