Normal adaptation of pulmonary arterial intima to extrauterine life in the pig: ultrastructural studies

Adaptation of the pulmonary arterial intima was studied in injected lung specimens of 34 Large White pigs. Each type of pre- and intra-acinar artery was studied separately using transmission and scanning electron microscopy. Determination of the endothelial surface/volume ratio and volume densities of (1) endothelium and subendothelium, (2) endothelial cytoplasmic organelles and (3) subendothelial connective tissue elements yielded 6832 measurements which comprised a computerized database. At birth, endothelial cell morphology changed more rapidly and to a greater extent in peripheral than in proximal arteries. Endothelial surface/volume ratio increased (p less than 0.0001). Fetal surface projections, junctional interdigitations and overlap became less evident. Adaptational changes were complete in three weeks. Between three weeks and adulthood a reduction in endothelial surface/volume ratio suggested cell growth. In the subendothelium the volume density of collagen and basement membrane and elastin increased (p less than 0.001). The internal elastic lamina, immature in all arteries at birth increased in thickness and integrity until in the adult, only in small muscular arteries did gaps between elastin profiles ensure frequent contact between endothelial and smooth muscle cells. At all ages regional differences in endothelial cell morphology were evident.     

Effect of adaptation to hypoxia on the working properties of muscles and energetics of muscular work

The working properties and heat formation of skeletal muscles were investigated during contraction in laboratory rats adapted to hypoxia and corresponding controls. During indirect electrical stimulation of the muscle the strength of contraction, work, and fatigue ability of the muscle were determined and the increase in temperature of the muscle as a result of the contraction was measured. Adaptation to hypoxia was shown not to affect the strength of contraction of the muscle or the quantity of work done. However, hypoxia leads to a reduction in the temperature effect of muscular contraction, expressed per unit work done. This indicates an increase in the efficiency of muscular work during adaptation to hypoxia. The fatiguability of muscles is increased in hypoxic rats. The changes in the energetics of muscular contraction during adaptation to hypoxia and to cold are different in direction.Laboratory of Thermoregulation, Institute of Clinical and Experimental Medicine, Siberian Branch. Academy of Medical Sciences of the USSR, Novosibirsk. Laboratory of Thermoregulation, Institute of Physiology and Experimental Pathology of Highland Areas, Academy of Sciences of the Kirghiz SSR, Frunze. (Presented by Academician of the Academy of Medical Sciences of the USSR V. P. Kaznacheev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 3, pp. 259–260, March, 1978.     

Pulmonary venous changes in chronic hypoxia

Summary Lung tissue from 14 normal residents of high altitude regions, 10 patients with chronic bronchitis and emphysema, and 1 patient with Pickwickian syndrome was studied with regard to the occurrence of pulmonary vascular changes. In addition to the well-known pulmonary arterial alterations, lesions in small pulmonary veins were found in the great majority of the cases. These changes, consisting of medial hypertrophy and arterialization and of bundles of smooth muscle cells within the venous intima, have not been described before in man. These findings suggest that alveolar hypoxia acts not only on small pulmonary arteries and arterioles but also on veins of small caliber, probably by inducing venoconstriction.     

Neonatal pulmonary hypertension prevents reorganisation of the pulmonary arterial smooth muscle cytoskeleton after birth

The pulmonary arterial smooth muscle cell (SMC) cytoskeleton was studied in tissue from 36 piglets aged from within 5 min of birth to 21 d of age, and in 8 adults. An additional 16 piglets were made pulmonary hypertensive by exposure to hypobaric hypoxia (50.8 kPa) for 3 d. In conduit intrapulmonary elastic arteries α, β and γ actin, the 204, 200 and 196 kDa myosin heavy chain (MHC) isoforms and vinculin were localised by immunohistochemistry. The total actin content, the proportion of monomeric to filamentous α and γ actin and changes in the proportions of the MHC isoforms were determined biochemically. Dividing SMCs were localised and quantified using Ki-67. We found a transient reduction in immunohistochemical expression of γ actin, 204 kDa MHC isoform and vinculin at 3 and 6 d in the inner media, associated with a transient increase in Ki-67 labelling. The actin content also decreased at 3 and 6 d ( P < 0.05), but there was a postnatal, permanent increase in monomeric actin, first the α then the γ isoform. The relative proportions of the MHC isoforms did not change between birth and adulthood in elastic pulmonary arteries but in muscular arteries the 200 kDa isoform increased between 14 d and adulthood. Pulmonary hypertension prevented both the immunohistochemical changes and the postnatal burst of SMC replication and prevented the transient postnatal reduction in actin content. These findings suggest that rapid remodelling of the actin cytoskeleton is an essential prerequisite of a normal postnatal fall in pulmonary vascular resistance.     

慢性缺氧对大鼠肺动脉平滑肌细胞胞内钙的影响及其机制研究

目的:研究慢性缺氧对大鼠肺动脉平滑肌细胞(PASMCs)胞内钙浓度(［Ca²⁺］_i)的影响及L-型钙通道和胞内钙库的作用,为缺氧性肺动脉高压(HPH)发病机制的进一步研究提供理论依据。 方法:复制大鼠缺氧性肺动脉高压动物模型，利用Fura－2/AM钙离子成像方法测定PASMCs在不同钙离子浓度细胞外液及L-型钙通道阻滞剂nifedipine和IP3R钙通道抑制剂肝素干预前后 ［Ca²⁺］_i变化。 结果:(1)缺氧＋含钙外液组PASMCs ［Ca²⁺］_i 显著高于对照＋含钙外液组（P<0.05）。缺氧＋含钙外液组PASMCs ［Ca²⁺］_i显著高于缺氧＋无钙外液组（P<0.05）。(2)缺氧nifedipine组PASMCs［Ca²⁺］_i在加药前后无显著差异（P>0.05）。（3）缺氧未干预组与缺氧肝素组PASMCs ［Ca²⁺］_i无明显差异（P>0.05）。 结论:慢性缺氧可使PASMCs的［Ca²⁺］_i增加。慢性缺氧引起［Ca²⁺］_i增加可能与细胞外钙内流有关，L-型钙通道和IP3R钙通道在调节［Ca²⁺］_i的过程中可能不独立发挥作用。     

Thinning of fetal pulmonary arterial wall and postnatal remodelling: Ultrastructural studies on the respiratory unit arteries of the pig

Summary Adaptation to extra-uterine life and postnatal remodelling of intra-acinar arteries was followed in 34 Large White pigs, from birth to adult life, applying morphometry to light and electronmicroscopic studies. After birth, percentage wall thickness decreased rapidly due to a reduction in overlap of adjacent smooth muscle cells and an increase in smooth muscle cell surface area/volume ratio, (p<0.01 at 12 h), without a reduction in the volume density of smooth muscle cells. Smooth muscle cells appeared immature at birth and synthetic rather than contractile organelles predominated. Between 3 weeks and 6 months myofilament volume density doubled (p< 0.0001). At all ages, pericytes, intermediate and smooth muscle cells showed similar volume densities of contractile and synthetic organelles. Thus, the high fetal pulmonary vascular resistance appeared to be due to the shape and arrangement of smooth muscle and other contractile cells within the vessel wall, rather than an excessive contractility of these cells. After birth rapid remodelling of arterial wall structure achieved a reduction in wall thickness by 30 min, continuing during the first week of life. After 3 weeks, remodelling involved an increase in wall thickness, connective tissue deposition with more collagen than elastin (p<0.0001), and smooth muscle cell differentiation.     

Longitudinal smooth muscle in pulmonary arteries

Summary In lung biopsy specimens of 19 patients with congenital heart disease and pulmonary hypertension, in addition to the common features of plexogenic arteriopathy, longitudinal smooth muscle cells were found in small pulmonary arteries. These cells were arranged in bundles or layers, particularly in the intima but sometimes within the media or adventitia of the arteries. They often caused severe narrowing of the lumen. Corrective surgery of the cardiac defect was performed in 14 patients. The results suggested that even when these changes are wide-spread and severe, they do not stand in the way of a favourable postoperative course. In one patient who underwent a banding procedure of the pulmonary artery, virtually complete regression of the smooth muscle layers could be demonstrated in a second biopsy, taken 5 years later during a corrective operation.     

Response of rats to hyperbaric oxygen after preliminary adaptation to hypoxia

Preliminary adaptation of rats to hypoxia under conditions increasing resistance to many stressproducing agents not only had no protective effect against exposure to hyperbaric oxygen at pressures up to 6 kgf/cm² but, conversely, lowered the resistance of the animals. The latent period of onset of seizures in the adapted rats was shortened especially if exposure to hyperbaric oxygen began 1 or 2 days after the end of adaptation to hypoxia, and was a little shorter in the experiments carried out after 3–4 days. The responses returned completely to normal 1 month after the end of adaptation to hypoxia. The possible causes of development of the phenomena are discussed.I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Academy of Sciences of the USSR Leningrad. (Presented by Academician V. N. Chernigovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 3, pp. 265–267, March, 1978.     

The state of cerebral hemodynamics in conditions of prolonged adaptation to hypercapnic hypoxia

Intermittent hypercapnic hypoxia was accompanied by increases in cerebral vascular resistance, decreases in the reactivity of cerebral vessels to hypercapnia, and increases in the collateral reserve and rate of autoregulation of brain blood flow. These changes were an important component of the mechanism increasing the tolerance of the brain to ischemia in response to training with hypercapnic hypoxia. Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 94, No. 2, pp. 191–197, February, 2008.     

Mechanism of lowering of the basal metabolism during adaptation to hypoxia

During adaptation of rats to periodic hypoxia in a pressure chamber the oxygen consumption fell by 40%. This decrease was still found in a state of deep anesthesia and, consequently, it was independent of adaptive changes in cortical regulation of the animals' motor activity. Half of this decrease in oxygen consumption still continued during exposure of the animal to cold, noradrenalin, and 2,4-dinitrophenol (DNP), which uncouples oxidative phosphorylation. The economic utilization of oxygen during adaptation to hypoxia cannot thus be completely explained by an increase in the degree of coupling of oxidation with phosphorylation.Laboratory of Pathophysiology of the Heart, Institute of General Pathology and Pathophysiology, Academy of Medical Sciences of the USSR, Moscow. Central Research Laboratory, Ivanovo Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 9, pp. 287–289, September, 1978.     

Tissue homeostasis of the myocardium in newborn albino rats exposed to intrauterine hypoxia

Somatometric indexes were modified in the offspring of rats exposed to hypobaric hypoxia. DNA synthesis and tissue mitotic index increased in 5-day-old male rats, but underwent less pronounced changes in females. Our results indicate that hypoxia modulates morphogenesis of the myocardium. We revealed sex differences in the reaction of newborn albino rats to intrauterine hypoxia. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 7, pp. 29–32, July, 2004     

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.     

慢性低氧大鼠膈肌纤维横截面积变化

本文通过建立慢性常压和减压低氧大鼠模型 ,采用肌球蛋白ATP酶 (mATP酶 )组化方法将肌纤维分为Ⅰ、ⅡA和ⅡB三种类型和显示毛细血管 ,用计算机图象分析系统测定肌纤维横截面积 (CSA)和毛细血管密度变化 ,观测慢性低氧大鼠膈肌不同类型纤维CSA变化 ,探讨其与毛细血管密度变化的关系。慢性低氧大鼠肌纤维CSA均不同程度缩小 ,CSA缩小与毛细血管密度增加显著相关。膈肌CSA缩小使毛细血管相对密度增加 ,有利于氧运输和弥散 ,膈肌氧化能力增强。     

急性缺氧对大鼠远端肺静脉平滑肌细胞内钙浓度的影响

目的:研究急性缺氧对大鼠远端肺静脉平滑肌细胞(PVSMC)细胞内钙浓度([Ca2+]i)的影响及L型电压依赖性钙通道(VDCC)阻断剂硝苯地平的作用,为缺氧性肺动脉高压发病机制的进一步研究提供理论依据.方法:胶原酶消化法培养大鼠远端PVSMC,利用荧光显微镜和细胞内钙浓度检测系统观测急性缺氧(4％O2)、高钾(60 mmol/L KCl)溶液对PVSMC的[Ca2+]i影响及硝苯地平的干预作用.结果:对照组PVSMC的[Ca2+]i随时间变化维持基线水平;缺氧组PVSMC急性缺氧后,[Ca2+]i迅速升高并维持平台水平,△[Ca2+]i达82.83 nmol/L士23.03 nmol/L;硝苯地平干预组PVSMC予急性缺氧和5μmol/L硝苯地平干预后,[Ca2+]i升高幅度较小;高钾溶液孵育PVSMC后,[Ca2+]i迅速增高,5 μmol/L硝苯地平能完全阻断PVSMC的[Ca2+]i对高钾溶液的反应.结论:急性缺氧可使大鼠远端PVSMC的[Ca2+]i升高,其机制可能与激活PVSMC的VDCC和另外的非VDCC依赖的钙通道导致细胞外Ca2+内流有关.     

Increased α1-adrenoceptor activity of the rat heart during adaptation to intermittent hypoxia

Research Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. Research Institute of Experimental Cardiology, All-Union Cardiologic Scientific Center, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. D. Ado.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 111, No. 6, pp. 570–572, June, 1991.