Interaction between cold and altitude exposure on pulmonary circulation of cattle

Hereford calves were exposed in a temperature-controlled hypobaric chamber to environmental temperatures of -2 to 1 degree C (cold) at altitudes of 1,524 m (resident altitude) and 3,048 m 1) to characterize the effects of cold exposure on the pulmonary circulation; 2) to examine the role of cold-induced hypoventilation on the pulmonary circulation; and 3) to examine the interaction between cold and hypoxia on the pulmonary circulation. Cold exposure produced a significant increase in pulmonary arterial pressure (Ppa), pulmonary arterial wedge pressure (Ppaw), and pulmonary vascular resistance (PVR) at both 1,524 and 3,048 m without affecting cardiac output. Concomitantly, cold exposure caused reductions in minute ventilation, respiratory rate, end-tidal O2 tension (PETO2), and arterial O2 tension (PaO2). Tidal volume, end-tidal CO2 tension, and arterial CO2 tension increased. Neither arterial pH nor O2 consumption changed during cold exposure. These results indicated that both pulmonary arterial and venous vasoconstriction were responsible for the pulmonary hypertension associated with cold exposure. Acute exposure to 3,048 m during cold exposure produced increases in Ppa and PVR that were similar to those elicited by cold exposure at 1,524. It was concluded that altitude exposure neither attenuated nor potentiated the effect of cold exposure on the pulmonary circulation; rather, altitude and cold exposure interacted additively. O2 administered during cold exposure to restore PETO2 and PaO2 to control values partially restored Ppa and PVR to control values. This suggested that a portion of the pulmonary hypertension associated with cold exposure was due to hypoxic pulmonary vasoconstriction elicited by the cold-induced alveolar hypoventilation.     

Determinants of an elevated pulmonary arterial pressure in patients with pulmonary arterial hypertension

Given the difficulty of diagnosing early-stage pulmonary arterial hypertension (PAH) due to the lack of signs and symptoms, and the risk of an open lung biopsy, the precise pathological features of presymptomatic stage lung tissue remain unknown. It has been suggested that the maximum elevation of the mean pulmonary arterial pressure (P_pa) is achieved during the early symptomatic stage, indicating that the elevation of the mean P_pa is primarily driven by the pulmonary vascular tone and/or some degree of pulmonary vascular remodeling completed during this stage. Recently, the examination of a rat model of severe PAH suggested that the severe PAH may be primarily determined by the presence of intimal lesions and/or the vascular tone in the early stage. Human data seem to indicate that intimal lesions are essential for the severely increased pulmonary arterial blood pressure in the late stage of the disease.However, many questions remain. For instance, how does the pulmonary hemodynamics change during the course of the disease, and what drives the development of severe PAH? Although it is generally acknowledged that both pulmonary vascular remodeling and the vascular tone are important determinants of an elevated pulmonary arterial pressure, which is the root cause of the time-dependent progression of the disease? Here we review the recent histopathological concepts of PAH with respect to the progression of the lung vascular disease.     

Influence of mechanical ventilation and pulmonary disease on pulmonary artery pressure monitoring.

Mechanical ventilation and respiratory disease impose both theoretical and practical limitations on the interpretation of hemodynamic measurements. To properly interpret such information a thorough understanding of the circulatory changes associated with normal breathing, mechanical ventilation and respiratory disease is vital. There are a variety of factors involved in patients with obstructive lung disease and those receiving mechanical ventilation that complicate the usual interpretation of hemodynamic data obtained from flow-directed catheters. An awareness of the potential pitfalls of hemodynamic monitoring in such situations is important in the efficient use of the hemodynamic data obtained.     

脂肪干细胞移植对野百合碱诱发的肺动脉高压大鼠肺动脉压的量效和时效作用

目的探索脂肪干细胞（ADSC）移植治疗野百合碱（MCT）诱导的肺动脉高压（PAH）大鼠的适宜细胞数和干预时间。 方法（1）MCT的建模时效和量效：雄性SD大鼠48只分为正常对照组,20 mg/kg、30 mg/kg、40 mg/kg MCT组分别予腹腔注射生理盐水、MCT 20 mg/kg、30 mg/kg、40 mg/kg,4和8周后,右心室插管法检测平均肺动脉压（mPAP）,称重法计算右心室肥厚指数（RVHI）。（2）ADSC的治疗量效作用：雄性SD大鼠分别予腹腔注射MCT（30只）和生理盐水（30只）,1周后通过颈静脉注射分别移植0.5×10⁶、1.0×10⁶、3.0×10⁶、5.0×10⁶ADSC,其他组予等量生理盐水。移植3周后检测mPAP和RVHI。（3）ADSC的治疗时效作用：雄性SD大鼠30只,分别注射40 mg/kg MCT（24只）和生理盐水（6只）。MCT腹腔注射1 d,1、2周后分别移植1.0×10⁶个ADSC。MCT注射4周后检测mPAP和RVHI。多组间比较采用单因素或双因素方差分析,两两比较采用LSD检验。 结果（1）腹腔注射4周后,30 mg/ kg或40 mg/kg MCT组mPAP和RVHI均升高[mPAP值（24.89±3.31）mmHg,（27.19±2.11）mmHg比（15.80±0.42）mmHg,差异有统计学意义（P均< 0.05）;RVHI值0.42±0.06,0.47±0.04比0.25±0.02,差异有统计学意义（P均< 0.05）]。8周后,20 mg/kg或30 mg/ kg MCT组mPAP和RVHI均恢复正常,而40 mg/kg MCT组大鼠全部死亡。（2）40 mg/ kg MCT诱导的PAH大鼠mPAP和RVHI均升高。移植1.0×10⁶个ADSC可降低PAH大鼠的mPAP[（17.24±0.66）mmHg比（27.19±1.73）mmHg,P < 0.05]。移植0.5×10⁶、3.0×10⁶、5.0× 10⁶个ADSC不能降低PAH大鼠的mPAP和RVHI。（3）MCT腹腔注射1周和2周后,移植1.0×10⁶个ADSC可降低PAH大鼠的mPAP。 结论40 mg/kg MCT造模4周可建立稳定的PAH大鼠模型;造模1或2周后移植1.0×10⁶个ADSC能有效降低PAH大鼠的mPAP。     

Effects of arterial ligation and embolization on pulmonary vascular pressure distribution

The effects of embolization on the longitudinal distribution of pulmonary vascular pressures with respect to vascular compliance were determined by the vascular inflow and outflow occlusion technique in isolated blood-perfused pig lungs treated with papaverine to prevent vasomotor responses. Embolization with microspheres having mean diameters of 75, 200, and 550 microns and with barrier beads (2 X 3 X 3.5 mm) significantly increased the pressure gradient across the relatively compliant middle region (delta Pm) without increasing the gradients across the relatively noncompliant regions on the arterial (delta Pa) or venous (delta Pv) ends of the vasculature. In contrast ligation of several lobar arteries caused delta Pa to increase from 0.9 +/- 0.3 to 5.9 +/- 1.1 mmHg but did not change delta Pm or delta Pv. Assuming that delta Pa and delta Pv measured by vascular occlusion result from cessation of flow through resistances, these data suggest that in isolated pig lungs the vessels at the boundary between the arterial and middle regions defined by the occlusion technique are arteries greater than 2-3 mm diam and smaller than lobar arteries.     

侧脑室内注射血管紧张素-（1-7）对大鼠肺动脉压和体动脉压的影响

目的:探讨血管紧张素-(1-7)对大鼠肺动脉压和体动脉压的影响机制。方法:以PAP和BAP为指标,在氨基甲酸乙酯麻醉、三碘季胺酚制动、呼吸机控制呼吸的SD大鼠上观察血管紧张素-(1-7)对大鼠PAP和BAP的影响,连续观察60minPAP和BAP曲线变化,并与对照组和生理盐水组比较。结果:给药后大鼠PAP和BAP明显升高,其中在5、10、15、30、45min与对照组和生理盐水组比较差异显著(P<0.01)。结论:血管紧张素-(1-7)具有中枢性升高肺动脉压和体动脉压的作用,侧脑室预先注射血管紧张素(1-7)特异性阻断剂A-779可部分阻断血管紧张素(1-7)的升压效应。     

Respective contribution of age, mean arterial pressure, and body weight on central arterial distensibility in SHR

In spontaneously hypertensive rats (SHR), carotid and aortic distensibilities measured at operational blood pressure (BP) are reduced. Increased body weight and mean arterial pressure (MAP) are both known to reduce distensibility independently. However, whether, after adjustment to body weight and mean BP, distensibility remains reduced in SHR has never been investigated. Carotid and abdominal aorta distensibilities were measured under anesthesia in SHR at 5, 12, 52, and 78 wk of age, and measurements were compared with age-matched normotensive Wistar rats. Each age group was composed of 9 or 10 animals. We determined distensibility using echo-tracking techniques of high resolution. Compared with Wistar rats, carotid and aortic distensibilities measured at operational MAP are reduced in SHR. This reduction is accentuated with age, particularly for the carotid artery. After adjustment to body weight and MAP, carotid and aortic distensibilities become identical in Wistar and SHR (or even slightly increased in SHR) but continue to be reduced with age, mainly for the carotid artery. In conclusion, in SHR, age and high BP do not have a parallel and similar influence on the reduction of arterial distensibility. Aging constantly reduces arterial distensibility, whereas MAP levels contribute to maintenance of arterial function.     

Influence of local geomagnetic storms on arterial blood pressure

This study attempts to assess the influence of local geomagnetic storms at middle latitudes on some human physiological parameters. The blood pressure (bp), heart rate and general well-being of 86 volunteers were measured, the latter by means of a standardised questionnaire, on work days in autumn, 2001 (1 Oct to 9 Nov), and in spring, 2002 (8 April to 28 May). These timespans were chosen as periods of maximal expected geomagnetic activity (GMA). Altogether, 2799 recordings were obtained and analysed. A four factor analysis of variance (MANOVA) was employed to check the significance of the influence of four factors (local GMA level; sequence of the days of measurements covering up to 3 days before and after geomagnetic storms; sex and the presence of medication) on the physiological parameters under consideration. Post hoc analysis was performed to elicit the significance of differences in the factors' levels. Arterial bp was found to increase with the increase of the GMA level, and systolic and diastolic bp were found to increase significantly from the day before till the second day after the geomagnetic storm. These effects were present irrespective of sex and medication.     

高原鼠兔肺动脉血管功能及形态变化

目的研究肺循环对慢性缺氧的适应机理.方法在4300m的高度捕捉到高原适应动物鼠兔,带到2260m的高度并和10只Wistar大鼠在模拟4300m和5000m高度的低压仓内进行了肺动脉压的测定,观察肺组织学和组织免疫化学的改变.结果在2260m,鼠兔的Ppa明显低于Wistar大鼠,二者分别为(1.5±0@07)kPa和(2.9±1.1)kPa(P＜0.01).随着海拔高度的增加,鼠兔的Ppa上升不明显,而Wistar大鼠增加显著.左右心室比重鼠兔为0.22,而Wistar大鼠为0.45.鼠兔的Hb,Hct和2.3-DPG均低于大鼠.大鼠肺小血管周围可见肥大细胞(7.1±0.33)mm2,免疫组化染色mastcelltyptase颗粒呈阳性,鼠兔未发现肥大细胞及此种免疫反应.肺小动脉中层较鼠兔厚,分别为27.21%和9.22%,壁的厚度和Ppa有很好的(r=0.763).结论鼠兔无低氧性肺血管收缩,是一种遗传性适应.大鼠肥大细胞通过激活某些生长因子,在肺血管的再建过程中可能起一定作用.