Effect of geomagnetic activity on rat resistance to hypoxia

Resistance to acute hypoxia in rats was evaluated by the life span after elevation to an altitude of 11,500 m at 13.00-21.00 (local time) in different seasons of one year. Geomagnetic activity was evaluated using local K index for Moscow and planetary Kp index. Total 24-h geomagnetic activity had a great impact on the life span of rats. The effects of local and planetary geomagnetic activities coincided in about 70% cases. An increase in geomagnetic activity was responsible for prolongation, decrease (2-3 times more often than prolongation), and phase changes in the life span of rats, which were the most pronounced in the case of medium geomagnetic activity, during the second half of the year (in summer and particularly in autumn), in the middle and end of the day, in rats with low resistance to hypoxia.     

Beta2-adrenergic attenuation of capillary pressure autoregulation during hemorrhagic hypo tension,a mechanism promoting transcapillary fluid absorption in skeletal muscle

The aim of this study was to evaluate a possible humoral β₂-adrenergic effect on the capillary pressure autoregulation capacity in cat skeletal muscle during bleeding. For this purpose capillary pressure autoregulation in response to graded decrease in arterial pressure was studied in sympathectomized muscle in the control state, and during haemorrhagic hypovolaemia in the presence and absence of selective β₂-adrenoceptor blockade (ICI 118,551). The study was performed with a technique that permits continuous recordings of average capillary pressure in absolute terms and of the regional pre- and postcapillary vascular resistance, from which the pre- to post capillary resistance ratio could be determined. In the pre-haemorrhagic control state, an experimental decrease in arterial pressure from 100 to 50 mmHg caused a fall of capillary pressure from 17.6 by only 1.7 mmHg (ΔP_A/ΔP_c= 29), demonstrating an efficient capillary pressure autoregulation. This autoregulation was accomplished by a decrease in pre- to post capillary resistance ratio in turn being a result of active precapillary dilatation and a passive increase in post capillary vascular resistance. Haemorrhage per se, via a humoral α-adrenergic preferentially precapillary vaso-constriction, caused a decrease in capillary pressure to 16.8 mmHg at arterial pressure 100 mmHg. A superimposed decrease in arterial pressure to 50 mmHg resulted in a capillary pressure fall by 3.7 mmHg (ΔP_A/ΔP_e= 14), indicating impaired autoregulation capacity. This attenuation to a great extent could be ascribed to adrenaline-induced B₂-adrenoceptor stimulation, since β₂-blockade restored the Δ arterial pressure/capillary pressure ratio to 20. Low-dose isoprenaline infusion in the control state similarly caused marked impairment of capillary pressure autoregulation. The β₂-adrenergic attenuation of capillary pressure autoregulation appears to be a beneficial effect in haemorrhagic hypotension, since it lowers capillary pressure passively in relation to the arterial pressure fall, thereby reinforcing the a-adrenergic active capillary pressure decrease, leading to more effective transcapillary fluid absorption and, hence, improved replenishment of plasma volume.     

Effect of alveolar hypoxia on reactivity of pial vessels in normotensive and spontaneously hypertensive rats

Intravital television microscopy revealed reduced reactivity of pial arterioles in response to alveolar hypoxia in spontaneously hypertensive rats (SHR) compared to normotensive (WKY) rats, which manifested in decreased number of dilatory reactions and in less prononced vascular dilation.     

Effect of lithium hydroxybutyrate on hemodynamics and respiration in rats with different resistance to hypoxia

Acute experiments on narcotized rats showed that intravenous infusion of GABA derivative lithium hydroxybutyrate induced different changes in hemodynamic and respiratory parameters in animals with high and low resistance to hypoxia. Rats highly resistant to hypoxia better tolerated lithium hydroxybutyrate treatment compared to low resistant animals. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 1, pp. 16–20, January, 2006     

Changes in hemodynamics and respiration in rats with different resistance to acute hypoxia

Effects of acute hypoxia on hemodynamics and respiration were studied in acute experiments on narcotized rats. The animals were divided into groups characterized by high, low-, and medium- resistance to hypoxia by the time of respiration arrest during inhalation of gas mixture containing 3% O₂. Hemodynamic parameters of highly resistant animals were higher than in low-resistant rats throughout the entire hypoxic period. The development of a rare (with prolonged inspiratory phase) respiratory rhythm in highly resistant rats is an adaptive reaction, which allows them longer tolerate hypoxia compared to low-resistant animals. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 7, pp. 24–28, July, 2004     

Effects of alveolar and perfusion hypoxia and hypercapnia on pulmonary vascular resistance in the lamb.

The effects of ventilatory hypoxia and hypercapnia and perfusion hypoxia and hypercapnia on pulmonary vascular resistance were studied in the intact lamb using right heart techniques to isolate and perfuse the left lower lobe. Ventilatory hypoxia increased vascular resistance in the left lower lobe by constricting predominantly vessels upstream from small lobar veins, presumably small arteries. The response to hypoxia was not blocked by phentolamine and diphenhydramine in doses that markedly decreased pressor responses to norepinephrine and histamine in the lung. Perfusion hypoxia did not alter vascular resistance in the perfused lobe. Ventilatory hypercapnia increased vascular resistance in the lung by constricting mainly upstream vessels, whereas perfusion hypercapnia decreased resistance by dilating upstream vessels. These data indicate that histamine and catecholamines are not involved in the response to alveolar hypoxia. These results suggest that the sensor site for ventilatory hypoxia is close to the alveolus since the response is unrelated to lobar arterial Po2. It is concluded that systemic reflexes are not necessarily involved in the response of the pulmonary vascular bed to ventilatory hypoxia or hypercapnia and that the magnitude and rapidity of this response suggest that it may represent an important local mechanism for the control of ventilation-perfusion relationships in this species.     

氯胺酮和咪唑安定对大鼠离体肺脏血管阻力的影响

目的探讨不同剂量氯胺酮和咪唑安定对大鼠离体肺脏血管阻力(PVR)的影响。方法成年雄性Wistar大鼠32只,体重200~280g,随机分成4组(n=8):氯胺酮组(K组)、咪唑安定组(M组)、N-硝基-L-精氨酸甲酯(L-NAME)+氯胺酮组(L-NAME+K组)和L-NAME+M组。制备离体大鼠肺灌注模型,K组经蠕动泵远端泵管注入氯胺酮2、20、40mg·kg~(-1),M组注入咪唑安定0.3、3、6mg·kg~(-1),均以剂量递增方式顺次加入,注药间隔10min;L-NAME+K组和L-NAME+M组预先经储血槽侧管各注入100μmol·L~(-1)L-NAME,平衡20 min后,经蠕动泵远端泵管分别加入氯胺酮40mg·kg~(-1)或咪唑安定6mg·kg~(-1)。持续描记肺动脉压(PAP)波形,记录PAP基础值(PAPb)、给药后的峰值(PAPp),并计算肺血管阻力(PVR)基础值(PVRb)、给药后的峰值(PVRp)和PVR的变化率。结果 K组、M组各剂量氯胺酮和咪唑安定均可使PVR降低,呈剂量依赖性。与K组40mg·kg~(-1)比较,L-NAME+K组PVR变化率无明显差异(P0.05);与M组6mg·kg~(-1)比较,L-NAME+M组PVR变化率亦无明显差异(P0.05)。结论氯胺酮和咪唑安定可剂量依赖性引起肺血管扩张,其作用与一氧化氮(内皮源性舒张因子)的释放无关。     

Effect of regional hypoxia and blood flow on capillary permeability in canine myocardium

The effect of hypoxia and blood flow on the capillary permeability-surface area product (PS) of ⁵¹Cr-EDTA was investigated in canine myocardium of open chest anesthetized dogs at constant aortic pressure, heart rate, and cardiac output. PS was determined by bolus injection of ⁵¹Cr-EDTA into the left anterior descending coronary artery (LAD) and external registration of the response curve. Vascular conductance (G) and PS were measured: (1) during pump perfusion of LAD with arterial blood (control state), and (2) during vasodilation obtained by LAD perfusion with deoxygenated blood at same blood flow as in control state, and (3) during increased blood flow with deoxygenated blood. Mean value of G in control state was 1.31 ml. min^-l. (100 g)^-1 (mmHg)^-1. The ratio G-hypoxialG-control used to assess the extent of vasodilation was 2.42 (range 1.67–3.56) during hypoxia and unchanged flow and 2.82 (range 1.81447) during hypoxia and increased flow. Mean value of PS in control state was 36 ml. (100 g)^-1. min^-1. With maximum vasodilation and constant blood flow PS increased to 47.3 ml.(100 g)-¹.min-¹ (37%) and during increased blood flow to 69.0 ml.(100 g)^-1. min^-1 (96%). The increase in PS most likely reflects an increase in capillary surface area available for exchange of ⁵¹Cr-EDTA indicating a 1.4– to 2-fold recruitment of capillaries.     

Effect of BQ123 on vasoconstriction as a result of either hypoxia or endothelin-1 in perfused rat lungs

A possible role of endothelin (ET)-1 in mediating hypoxic pulmonary vasoconstriction (HPV) was examined by comparing haemodynamic differences between ET-1-induced vasoconstriction and HPV in isolated perfused rat lungs. An ET_A receptor antagonist (BQ123) was also employed to assess the effects of ET-1. The pulmonary arterial pressure (Ppa) was significantly increased by alveolar hypoxia (3% O₂) and by ET-1 (5 nM). The pulmonary microvascular pressure was not changed by hypoxia, but increased more than two-fold by ET-1 (P < 0.01). Hypoxia significantly increased pulmonary arterial resistance (P < 0.01) while ET-1 significantly increased pulmonary venous resistance (P < 0.01), and slightly increased arterial resistance. Lung weight was increased by ET-1 and decreased by hypoxia, accompanied by similar Ppa responses in both cases. BQ123 (10^-6 m and 10^-5 m ) did not influence the changes in Ppa and lung weight induced by hypoxia or angiotensin II (0.3 μg). BQ123 did, however, suppress (P < 0.05) the increase in Ppa and lung weight induced by 5 nM ET-1. Thus, it appears unlikely that ET-1 is involved in changes in pulmonary vascular tone during acute HPV.     

Effect of adaptation to high-altitude hypoxia and subsequent disadaptation on conditioned reflex retention

After adaptation to high-altitude hypoxia the degree of retention of a conditioned active avoidance reflex is considerably increased. Only half as many combinations of the conditioned and unconditioned stimuli were required to reach the necessary level when the retention of the reflex was tested 24 h after its formation in adapted rats as in the control. This level of adaptation was produced 1 and 5 days after the end of a course of exposures to hypoxia. During disadaptation, the increase in the degree of retention of the reflex which had been achieved disappeared 10 and 27 days after the end of exposure to hypoxia.Laboratory of Pathophysiology of the Heart, Institute of General Pathology and Pathophysiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 5, pp. 526–527, May, 1977.     

血必净对烧伤犬血管通透性和液体需求量的影响

目的探讨血必净对烧伤犬血管通透性和液体需求量的影响。 方法将24只雄性比格犬按照随机数字表法分成3组：乳酸林格氏液复苏组(LR组),乳酸林格氏液复苏＋血必净组(LR＋XBJ组)和对照组(OC组),每组8只。所有犬麻醉后行颈主动脉和静脉置管并插入尿管。3组犬均静脉注射丙泊酚(2 mg/kg)进行全身麻醉,OC组犬仅进行颈动静脉置管,未致伤;LR组和LR＋XBJ组犬进行颈动静脉置管后,量取背部50%总体表面积,备皮后3%凝固汽油均匀涂抹并点燃,持续燃烧30 s,致50%总体表面积全层烧伤。伤后12 h,给予犬丁丙诺啡(10 μg/kg)止痛。LR组根据Parkland公式静脉输入乳酸林格氏液(1%总体表面积为4 mL/kg,前8 h输入1/2,后16 h输入另1/2);LR＋XBJ组在输入乳酸林格氏液(输入量和时间同LR组)的基础上,在伤后即刻和伤后4 h分别给予血必净注射1次,每次2 mL/kg。OC组仅输入与LR组和LR＋XBJ组等量的乳酸林格氏液。检测伤后即刻,伤后1、2、4、6、8和24 h 7个时间点各组犬血流动力学指标[平均动脉压(MAP)、心输出量指数(CI)、血管外肺水指数(ELWI)和肺血管通透性指数(PVPI)]、血浆容量、红细胞压积、尿累积量与累计净输入量、各脏器组织(心脏、肺脏、肾脏、小肠)含水率、血管通透性、中性粒细胞浸润数量及髓过氧化物酶(MPO)和中性粒细胞弹性蛋白酶(NE)活性。数据比较采用单因素方差分析、t检验和χ²检验。 结果伤后即刻,3组间MAP、CI、ELWI、PVPI比较差异均无统计学意义(P值均大于0.05);伤后1、2、4、6、8和24 h,LR组和LR＋XBJ组的MAP、CI、ELWI、PVPI比OC组均明显降低,3组间比较差异均有统计学意义(P值均小于0.05);伤后1、2、4、6、8和24 h,LR组的MAP和CI与LR＋XBJ组比较,差异均无统计学意义(P值均大于0.05);伤后1、2、4 h,LR组的ELWI和PVPI与LR＋XBJ组比较,差异均无统计学意义(P值均大于0.05),而伤后6、8、24 h LR组的ELWI和PVPI与LR＋XBJ组比较,差异均有统计学意义(P值均小于0.05)。伤后即刻,3组间血浆容量和红细胞压积比较差异均无统计学意义(P值均大于0.05);伤后1、2、4、6、8和24 h,LR组和LR＋XBJ组的血浆容量和红细胞压积比OC组均明显降低,3组间比较差异均有统计学意义(P值均小于0.05);伤后1、2、6、8、24 h,LR组的血浆容量与LR＋XBJ组比较,差异均无统计学意义(P值均大于0.05),伤后4 h LR组的血浆容量与LR＋XBJ组比较,差异有统计学意义(P<0.05);伤后1、6、8、24 h,LR组的红细胞压积与LR＋XBJ组比较,差异均无统计学意义(P值均大于0.05),伤后2、4 h LR组的红细胞压积与LR＋XBJ组比较,差异均有统计学意义(P值均小于0.05)。伤后即刻,伤后1、2、4、6、8、24 h, LR组和LR＋XBJ组尿量比较差异均无统计学意义(P值大于0.05);伤后即刻,伤后1、2 h,LR组的累积净输入量与LR＋XBJ组比较,差异均无统计学意义(P值均大于0.05),而伤后4、6、8、24 h LR组的累积净输入量与LR＋XBJ组比较,差异均有统计学意义(P值均小于0.05)。伤后24 h,LR组和LR＋XBJ组的心脏、肺脏、肾脏、小肠中的含水率、血管通透性和中性粒细胞浸润数量比OC组均明显增加,3组间比较差异均有统计学意义(P值均小于0.05);伤后24 h,LR组心脏、肾脏中的含水率和血管通透性与LR＋XBJ组比较,差异均无统计学意义(P值均大于0.05),肺脏、小肠中的含水率和血管通透性与LR＋XBJ组比较,差异均有统计学意义(P值均小于0.05);伤后24 h,LR组肾脏组织中的中性粒细胞浸润数量与LR＋XBJ组比较,差异无统计学意义(P>0.05),心脏、肺脏、小肠中的中性粒细胞浸润数量与LR＋XBJ组比较,差异均有统计学意义(P值均小于0.05)。伤后24 h,LR组和LR＋XBJ组的心脏、肺脏、肾脏、小肠中的MPO和NE含量比OC组均明显增加,3组间比较差异均有统计学意义(P值均小于0.05);伤后24 h,LR组心脏、肾脏组织中的MPO含量与LR＋XBJ组比较,差异均无统计学意义(P＝0.05、P>0.05),肺脏、小肠中的MPO含量与LR＋XBJ组比较,差异均有统计学意义(P值均小于0.05);伤后24 h,LR组肾脏组织中的NE含量与LR＋XBJ组比较,差异无统计学意义(P>0.05),心脏、肺脏、小肠中的NE含量与LR＋XBJ组比较,差异均有统计学意义(P值均小于0.05)。 结论血必净注射液能抑制蛋白酶引起的血管通透性升高和组织水肿,明显降低烧伤犬复苏液体需求量。     

缺氧和酵母多糖对清醒山羊肺动脉压和肺内液体的影响

作者采用山羊慢性肺淋巴瘘模型,观察了缺氧和酵母多糖活化的血浆对清醒山羊肺动脉压、肺血管壁通透性和肺组织间液形成的影响。缺氧时肺动脉压显著升高,这可能是肺毛细血管前肌性小动脉收缩的结果。为缺氧动物输入酵母多糖活化的血浆,肺动脉压在缺氧增高的基础上又有短暂升高,接着出现肺血管扩张,缺氧性肺动脉增压反应受抑。酵母多糖活化的血浆可致山羊肺微血管壁受损,缺氧(模拟4000米高原)并未加重其损伤。     

缺氧对犬肺循环血流动力学和流变学参数的影响

本文观察了缺氧引起的犬肺循环血流动力学及流变学参数的变化。结果表明：缺氧能显著降低心输出血流量,造成肺动脉高压,经计算获得肺血管阻力明显增加。缺氧还使犬的全血粘度增加,从高、低切变率条件下还原粘度的明显改变上看,这种全血粘度的增加与红细胞刚性指数和聚集指数的上升直接相关。     

Effect of hypoxia and dexamethasone on inflammation and ion transporter function in pulmonary cells

Dexamethasone has been found to reduce the incidence of high-altitude pulmonary oedema. Mechanisms explaining this effect still remain unclear. We assessed the effect of dexamethasone using established cell lines, including rat alveolar epithelial cells (AEC), pulmonary artery endothelial cells (RPAEC) and alveolar macrophages (MAC), in an environment of low oxygen, simulating a condition of alveolar hypoxia as found at high altitude. Inflammatory mediators and ion transporter expression were quantified. Based on earlier results, we hypothesized that hypoxic conditions trigger inflammation. AEC, RPAEC and MAC, pre-incubated for 1 h with or without dexamethasone (10(-7) mol/l), were subsequently exposed to mild hypoxia (5% O(2), or normoxia as control) for 24 h. mRNA and protein levels of cytokine-induced neutrophil chemoattractant-1, monocyte chemoattractant protein-1 and interleukin-6 were analysed. mRNA expression and functional activity of the apical epithelial sodium channel and basolateral Na(+)/K(+)-ATPase were determined using radioactive marker ions. In all three types of pulmonary cells hypoxic conditions led to an attenuated secretion of inflammatory mediators, which was even more pronounced in dexamethasone pretreated samples. Function of Na(+)/K(+)-ATPase was not significantly influenced by hypoxia or dexamethasone, while activity of epithelial sodium channels was decreased under hypoxic conditions. When pre-incubated with dexamethasone, however, transporter activity was partially maintained. These findings illustrate that long-term hypoxia does not trigger an inflammatory response. The ion transport across apical epithelial sodium channels under hypoxic conditions is ameliorated in cells treated with dexamethasone.     

缺氧和空气栓塞对清醒山羊肺动脉增压反应及肺内液体交换的影响

作者采用山羊慢性肺淋巴瘘方法,观察缺氧、空气栓塞单独和复合作用,对清醒山羊肺动脉压、肺微血管壁通透性和肺内液体交换的影响。实验结果表明:①缺氧所致的成年山羊肺动脉压增高,可能是毛细血管前阻力血管收缩的结果。成年山羊在模拟4000m高原缺氧1小时,未致肺微血管壁通透性增高;②肺血管空气栓塞可致肺动脉压和微血管壁通透性增高;③缺氧和空气栓塞复合作用时,肺动脉增压反应的幅度并非两者单独作用的叠加;④空气栓塞引起的肺血管壁通透性增高未为缺氧所加重。