Frithiof Robert, Eriksson Stefan, Bayard Frida, Svensson Tor, Rundgren Mats
Department of Physiology and Pharmacology, Karolinska Institutet, S-17177, Stockholm, Sweden.
J Physiol. 2007 Sep 15;583(Pt 3):1129-43. doi: 10.1113/jphysiol.2007.139592. Epub 2007 Jul 19.
Acute NaCl loading as resuscitation in haemorrhagic hypovolaemia is known to induce rapid cardiovascular recovery. Besides an osmotically induced increase in plasma volume the physiological mechanisms of action are unknown. We hypothesized that a CNS mechanism, elicited by increased periventricular [Na(+)] and mediated by angiotensin II type 1 receptors (AT(1)), is obligatory for the full effect of hypertonic NaCl. To test this we investigated the cardiovascular responses to haemorrhage and subsequent hypertonic NaCl infusion (7.5% NaCl, 4 ml (kg BW)(-1)) in six conscious sheep subjected to intracerebroventricular (i.c.v.) infusion of artificial cerebrospinal fluid (aCSF; control), mannitol solution (Man; 75 mmol l(-1) [Na(+)], total osmolality 295 mosmol kg(-1)) or losartan (Los; 1 mg ml(-1), AT(1) receptor antagonist) at three different occasions. Man normalized (144 +/- 6 mmol l(-1), mean +/- s.d.) the increase in i.c.v. [Na(+)] seen after aCSF (161 +/- 2 mmol l(-1)). Compared with control, both Man and Los significantly (P < 0.05) attenuated the improvement in mean arterial blood pressure (MAP), cardiac index and mesenteric blood flow (SMBF) in response to intravenous hypertonic NaCl: MAP, rapid response +45 mmHg versus +38 mmHg (Man) and +35 mmHg (Los); after 180 min, +32 mmHg versus +21 mmHg (Man) and +19 mmHg (Los); cardiac index after 180 min, +1.9 l min(-1) (m(2))(-1) versus +0.9 l min(-1) (m(2))(-1) (Man) and +0.9 l min(-1) (m(2))(-1) (Los); SMBF rapid response, +981 ml min(-1) versus +719 ml min(-1) (Man) and +744 ml min(-1) (Los); after 180 min, +602 ml min(-1) versus +372 ml min(-1) (Man) and +314 ml min(-1) (Los). The results suggest that increased periventricular [Na(+)] and cerebral AT(1) receptors contribute, together with plasma volume expansion, to improve systemic haemodynamics after treatment with hypertonic NaCl in haemorrhagic hypovolaemia.
已知急性输注氯化钠作为失血性低血容量复苏手段可促使心血管迅速恢复。除了渗透作用导致血浆量增加外，其生理作用机制尚不清楚。我们推测，由脑室周围[Na⁺]增加引发并由1型血管紧张素II受体（AT₁）介导的中枢神经系统机制，是高渗氯化钠发挥全部作用所必需的。为验证这一点，我们在六只清醒绵羊身上进行了三次实验，分别向其脑室内输注人工脑脊液（aCSF；对照组）、甘露醇溶液（Man；75 mmol·l⁻¹ [Na⁺]，总渗透压295 mosmol·kg⁻¹）或氯沙坦（Los；1 mg·ml⁻¹，AT₁受体拮抗剂），然后观察它们对出血及随后静脉输注高渗氯化钠（7.5% NaCl，4 ml·(kg体重)⁻¹）的心血管反应。甘露醇使脑室内[Na⁺]升高（aCSF组为161±2 mmol·l⁻¹）恢复正常（144±6 mmol·l⁻¹）。与对照组相比，甘露醇和氯沙坦均显著（P<0.05）减弱了静脉输注高渗氯化钠后平均动脉血压（MAP）、心脏指数和肠系膜血流量（SMBF）的改善：MAP，快速反应时分别为+45 mmHg、+38 mmHg（甘露醇组）和+35 mmHg（氯沙坦组）；180分钟后分别为+32 mmHg、+21 mmHg（甘露醇组）和+19 mmHg（氯沙坦组）；180分钟后的心脏指数分别为+1.9 l·min⁻¹·(m²)⁻¹、+0.9 l·min⁻¹·(m²)⁻¹（甘露醇组）和+0.9 l·min⁻¹·(m²)⁻¹（氯沙坦组）；SMBF快速反应时分别为+981 ml·min⁻¹、+719 ml·min⁻¹（甘露醇组）和+744 ml·min⁻¹（氯沙坦组）；180分钟后分别为+602 ml·min⁻¹、+372 ml·min⁻¹（甘露醇组）和+314 ml·min⁻¹（氯沙坦组）。结果表明，脑室周围[Na⁺]增加和脑内AT₁受体，与血浆量扩充一起，有助于在失血性低血容量时用高渗氯化钠治疗后改善全身血流动力学。
