缺氧对右心室最大心肌血流量的影响

为了探讨缺氧对冠状血管贮备力的影响,我们观察了缺氧时大鼠血流动力学及右心室最大心肌血流量的变化。结果表明,急性缺氧引起ＰａＯ２、心输出量及氧运送量降低,但右心室心肌血流量增加,右心室最大与安静血流量比值降低。慢性缺氧时ＰａＯ２降低,血球比积和右心室重量指数增加,氧运送量和右心室血流量正常,但最大血流量降低,小动脉增厚、外膜胶元增加。以上结果提示,慢性缺氧对冠状血管贮备减少可能是小动脉壁增厚、外膜胶元增加和血液粘滞性增加及右心室肥大的结果。     

缺氧兔心肌血流量的变化及一氧化氮和腺苷的调节作用

观察了急性缺氧和慢性间断性缺氧兔心肌血流量、心肌组织中腺苷和ｃＧＭＰ含量的变化及Ｎ￣ω－ＮＯ３－Ｌ－精氨酸（Ｌ－ＮＡ）阻断一氧化氮（ＮＯ）生成后的影响。结果表明,急性缺氧兔心肌血流量增加,心肌组织中腺苷和ｃＧＭＰ含量增高;静脉输入Ｌ－ＮＡ后,心肌血流量减少,同时心肌组织中ｃＧＭＰ含量降低,腺苷含量进一步增高。慢性缺氧免心肌血流量无明显变化,红细胞压积（Ｈｃｔ）增高;抑制ＮＯ合成后,右室心肌血流量减少,左室心肌血流量无明显变化。说明ＮＯ和腺苷均参与急性缺氧时冠状血管扩张机制;ＮＯ参与慢性缺氧兔心肌血管基础张力调节。     

抗坏血酸对冠状循环和心肌代謝的影响

本文用Каверина法在猫及兔上进行冠状窦插管,直接記录冠脉血流量,并同时抽取动脉及冠状窦血液,测定氧、糖、乳酸及丙酮酸含量之差,計算心肌对它們的消耗量。部分实驗在稳压装置情况下进行。 靜脉注射抗坏血酸0.2克/公斤,冠脉血流量在兔上平均墳加76％,猫平均增加24％,心肌氧耗量无明显改变,注入抗坏血酸0.4克/公斤,冠脉血流量兔平均增加125％,猫平均增加95％,稳压情况下,猫平均增加62％,心肌氧耗量傾向降低,而糖、乳酸及丙酮酸的心肌消耗量无明显改变。抗坏血酸增加冠脉血流量的作用,并非完全取决于血压,亦不是由于血中乳酸含量增加,而是有直接扩張冠状血管的作用。 靜脉注射抗坏血酸呈現的心脏功能改善与增加冠脉血流量、經济心肌耗氧和不明显地影响心肌糖代謝有关。     

慢性缺氧时心肌血流量的变化及一氧化氮和内皮素—1的调节作用

近年来国内外研究表明急性缺氧时心肌血流量明显增加 ,而慢性缺氧对心肌血流量的影响及其发生机制 ,目前国内外研究甚少 ,且结果不甚相同 ,因此探讨缺氧时心肌血流量的变化及其发生机制 ,对于评估缺氧时心肌供血状态 ,了解心脏高原适应具有理论和实际意义。因此 ,本文观察了慢性间断缺氧大鼠的心肌血流量、血浆、心肌组织ＮＯ(ｎｉｔｒｉｃｏｘｉｄｅ ,ＮＯ)和ＥＴ 1(ｅｎ ｄｏｔｈｅｌｉｎ 1,ＥＴ 1)的含量 ,以期探讨ＮＯ、ＥＴ 1改变、红细胞增多与心肌血流量变化的关系。1　材料和方法(1)实验动物　健康ｗｉｓｔａｒ成年大鼠 6 9只 ,雌雄…     

缺氧对肺动脉内皮细胞环氧合酶,血栓素合成酶基因表达的影响

应用分子杂交技术和放射免疫检测方法研究了缺氧对猪肺动脉内皮细胞的环氧合酶（ＣＯＸ）和血栓素合成酶（ＴＸＳ）基因表达及其条件培养基中６ｋｅｔｏＰＧＦ１α和ＴＸＢ２含量的动态变化。发现：６,１２,２４和４８ｈ缺氧组分别与常氧组比,ＣＯＸ１和ＣＯＸ２基因表达增加,并且ＣＯＸ２ｍＲＮＡ在缺氧６和１２ｈ就明显表达增加。在前述的不同缺氧时间组内皮细胞条件培养基中６ｋｅｔｏＰＧＦ１α含量也均显著高于相应常氧对照组（Ｐ＜０．０５）;但ＴＸＳ的ｍＲＮＡ水平及ＴＸＢ２含量在缺氧４８ｈ才有明显增加（Ｐ＜０．０５）。结果表明：（１）缺氧可诱导肺动脉内皮ＣＯＸ基因表达和ＰＧＩ２生成增加,在早期以ＣＯＸ２基因表达增加更为明显,提示可能在肺血管缺氧反应中起调节作用。（２）４８ｈ的缺氧可使内皮细胞ＴＸＳ基因表达及ＴＸＡ２生成增加,它可能在慢性缺氧肺血管反应中起介导作用。     

治疗高血压药物的研究蘿芙木碱对狗冠脉血流及心肌代谢的影响

本文介紹了N_2O減飽和法測定不开胸狗冠脉血流量的方法,并研究了海南島萝芙木根总碱的作用,及其对心肌糖代謝的影响。在X光透視下經靜脉插管至冠状資,从冠状动、靜脉血N_2O減飽和速率之差,計算心肌血流量,并从动、靜脉血氧、糖、乳酸及丙酮酸合量之差,計算心肌的消耗量及利用率。实驗設計采用配对法,进行t測驗个别比較,以分析除去动物个体差异及对照溶剂的影响后萝芙木碱本身的作用。 9只狗之各項正常数值平均数±标准差为:动脉平均压143±17毫米汞柱,冠状竇平均压8±3毫米汞柱,冠脉血流量88±21毫升/100克心肌/分,冠脉阻力1.7±0.4毫米汞柱/毫升/100克心肌/分,动脉血氧合量18.1±1.9容积%,冠状竇血氧含量5.6±1.1容积96,动脉血糖116±24毫克%,冠状竇血糖109±20毫克%,动脉乳酸24±7毫克%,冠状寶乳酸16±5毫克%,动脉丙酮酸1.7±0.5毫克%,冠状竇丙酮酸0.8±0.3毫克%。 靜脉注射萝芙木碱0.1毫克/公斤后,血压立即明显下降約25%,半小时后回升,冠脉血流量变化不显著,冠脉阻力有减低趋势,說明萝芙木碱降压时并不引起冠脉血流减少,冠状血管趋于扩张。心肌对氧、乳酸和丙酮酸的利用率很高,而对血糖消耗很少,說明心肌主要从糖的有氧代謝获取能量。靜脉注射萝芙木碱后,动脉血的乳酸及丙酮酸含量均显著增高,因此能增加心脏的能源供应,改善心肌的营养。萝芙木碱能加強左心室作功量,而心肌氧消耗量并未增高,故計算出心肌机械作功率从15%提高到20%。总結本文結果:萝芙木碱在扩张冠状血管、提高心肌作功率及增加心肌能源供应三方面都有一定的作用,因此对高血压心脏的代偿能力的提高是有利的。     

缺氧心肌收缩蛋白Ca~（2＋），Mg~（2＋）－ATP酶活性研究

将大鼠置于模拟海拔８ｋｍ高度的低压舱内缺氧１周及缺氧后空气中常氧恢复１周和２周,观察了左右心室功能、心肌肥厚、心肌收缩蛋白含量及其Ｃａ￣（２＋）,Ｍｇ￣（２＋）－ＡＴＰ酶活性的动态变化。结果表明,８ｋｍ缺氧１周后肺动脉压及右心室收缩压明显升高,左右心室±ｄｐ／ｄｔｍａｘ及收缩指数明显降低。左右心室肌明显肥厚,心肌收缩蛋白Ｃａ￣（２＋）,Ｍｇ￣（２＋）－ＡＴＰ酶活性明显减低。缺氧后常氧恢复１和２周后,左右心室功能逐渐恢复达到或接近正常水平,心肌肥厚逐渐减轻或恢复正常,心肌收缩蛋白Ｃａ￣（２＋）,Ｍｇ￣（２＋）－ＡＴＰ酶活性也逐渐升高。因此说明：心肌收缩蛋白Ｃａ￣（２＋）,Ｍｇ￣（２＋）－ＡＴＰ酶活性的改变是心功能变化的重要生化基础之一,它的减低是缺氧心肌对环境的代偿适应。     

一氧化氮对急、慢性缺氧大鼠血流动力学及缺氧性肺血管收缩反应的影响

观察了吸入０．００４％的一氧化氮（ＮＯ）对急、慢性缺氧大鼠血流动力学、缺氧性肺血管收缩反应（ＨＰＶ）、血气及高铁血红蛋白（ＭｅｔＨｂ）的影响。结果表明：（１）常氧吸入ＮＯ时能明显降低慢性缺氧大鼠肺动脉平均压（Ｐｐａ）和肺血管阻力（ＰＶＲ）,但对正常大鼠的Ｐｐａ和ＰＶＲ无明显影响;（２）慢性缺氧大鼠急性缺氧时ＨＰＶ较正常大鼠弱,吸入ＮＯ不但降低两者的急性缺氧肺动脉高压,且完全逆转两者的ＨＰＶ;（３）吸入ＮＯ对急、慢性缺氧大鼠体循环血流动力学、血气及ＭｅｔＨｂ含量无明显影响。提示吸入ＮＯ能选择性降低急、慢性缺氧性肺动脉高压,且逆转ＨＰＶ。     

缺氧对培养的肺动脉内皮细胞血管紧张素Ⅱ分泌的影响

缺氧是否通过影响血管内皮细胞的分泌功能而参与缺氧性肺动脉高压的发生尚不清楚。本实验动态观察了缺氧对培养的新生小牛内皮细胞（ＰＡＥＣ）的血管紧张素Ⅱ（ＡＴⅡ）分泌的影响。结果发现：２．５％Ｏ２缺氧早期（１．５ｈ）,ＰＡＥＣ的ＡＴⅡ分泌增加（Ｐ＜０．０１ｖｓ常氧组）,缺氧后期与常氧组无明显差别;０％Ｏ２缺氧早期（１．５－６ｈ）,ＡＴⅡ分泌明显降低（Ｐ＜０．０１ｖｓ常氧组及２．５％Ｏ２组）,后期ＡＴⅡ分泌明显增高（Ｐ＜０．０１ｖｓ常氧组及２．５％Ｏ２组）;无论缺氧还是常氧条件下,ＮＯ供体ＳＩＮ１显著抑制ＡＴⅡ的分泌（Ｐ＜０．０１）,而内源性ＮＯ抑制剂硝基精氨酸则明显促进ＡＴⅡ分泌（Ｐ＜０．０１）;０％Ｏ２缺氧２４ｈ后,ＰＡＥＣ细胞内ｃＧＭＰ含量明显降低（Ｐ＜０．０５）。上述结果表明缺氧可通过抑制ＰＡＥＣ的内源性ＮＯ产生而促进ＡＴⅡ的分泌,ＰＡＥＣ自分泌的改变可能参与缺氧性肺动脉高压的发生过程。     

肝素通过增加细胞周期抑制因子p27 减轻大鼠低氧性肺动脉高压

目的:研究肝素防治大鼠低氧性肺动脉高压的作用机制。方法:复制慢性低氧性肺动脉高压大鼠模型,将大鼠分为常氧对照组(Hypoxia),常氧加肝素组(Normoxia+H),缺氧模型组(Hypoxia)及缺氧加肝素组(Hypoxia+H)共四组。待模型复制完毕后,测定大鼠RVPSP和RV/LV+S,然后进行组织病理分析,测定MA%和MT%以确定肺动脉高压的程度。利用Western-blot实验与RT-PCR实验检测肺动脉中p27蛋白水平及RNA水平的变化。结果:慢性低氧显著增加了大鼠RVPSP、RV/LV+S、MA%和MT%,引起了大鼠肺动脉压力的增高、右心室肥厚和肺中小动脉的中膜增厚及外膜增生,肝素的使用减轻了慢性缺氧条件下大鼠的RVPSP和RV/LV+S,降低了MA%和MT%,有效降低了肺动脉高压、右心室肥厚,并减轻了肺中小动脉的中膜增厚和外膜增生。Western-blot实验发现使用肝素的缺氧组大鼠肺动脉中p27蛋白表达增加,而RT-PCR实验发现p27的转录水平变化不显著。结论:结果显示肝素可能通过增加p27的表达,从而抑制肺动脉平滑肌细胞的增殖,减轻了肺动脉血管的狭窄及降低了肺动脉高压。     

Nitric oxide contributes to right coronary vasodilation during systemic hypoxia

As arterial partial pressure of O(2) (Pa(O(2))) is reduced during systemic hypoxia, right ventricular (RV) work and myocardial O(2) consumption (MVo(2)) increase. Mechanisms responsible for maintaining RV O(2) demand/supply balance during hypoxia have not been delineated. To address this problem, right coronary (RC) blood flow and RV O(2) extraction were measured in nine conscious, instrumented dogs exposed to normobaric hypoxia. Catheters were implanted in the right ventricle for measuring pressure, in the ascending aorta for measuring arterial pressure and for sampling arterial blood, and in an RC vein. A flow transducer was placed around the RC artery. After recovery from surgery, dogs were exposed to hypoxia in a chamber ventilated with N(2), and blood samples and hemodynamic data were collected as chamber O(2) was reduced progressively to approximately 8%. After control measurements were made, the chamber was opened and the dog was allowed to recover. N(omega)-nitro-L-arginine (L-NNA) was then administered (35 mg/kg, via RV catheter) to inhibit nitric oxide (NO) production, and the hypoxia protocol was repeated. RC blood flow increased during hypoxia due to coronary vasodilation, because RC conductance increased from 0.65 +/- 0.05 to 1.32 +/- 0.12 ml x min(-1) x 100 g(-1) x L-NNA blunted the hypoxia-induced increase in RC conductance. RV O(2) extraction remained constant at 64 +/- 4% as Pa(O(2)) was decreased, but after L-NNA, extraction increased to 70 +/- 3% during normoxia and then to 78 +/- 3% during hypoxia. RV MVo(2) increased during hypoxia, but after L-NNA, MVo(2) was lower at any respective Pa(O(2)). The relationship between heart rate times RV systolic pressure (rate-pressure product) and RV MVo(2) was not altered by l-NNA. To account for L-NNA-mediated decreases in RV MVo(2), O(2) demand/supply variables were plotted as functions of MVo(2). Slope of the conductance-MVo(2) relationship was depressed by L-NNA (P = 0.03), whereas the slope of the extraction-MVo(2) relationship increased (P = 0.003). In summary, increases in RV MVo(2) during hypoxia are met normally by increasing RC blood flow. When NO synthesis is blocked, the large RV O(2) extraction reserve is mobilized to maintain RV O(2) demand/supply balance. We conclude that NO contributes to RC vasodilation during systemic hypoxia.     

Protein remodeling of extracellular matrix in rat myocardium during four-day hypoxia: the effect of concurrent hypercapnia

The combination of long-term hypercapnia and hypoxia decreases pulmonary vascular remodeling and attenuation of right ventricular (RV) hypertrophy. However, there is limited information in the literature regarding the first stages of acclimatization to hypercapnia/hypoxia. The purpose of this study was to investigate the effect of four-day hypoxia (10% O2) and hypoxia/hypercapnia (10% O2 + 4.4% CO2) on the protein composition of rat myocardium. Expression of the cardiac collagen types and activities of matrix metalloproteinases (MMPs) and of their tissue inhibitor TIMP-1 were followed. The four-day hypoxia changed protein composition of the right ventricle only in the hypercapnic condition; remodeling was observed in the extracellular matrix (ECM) compartments. While the concentrations of pepsin-soluble collagenous proteins in the RV were elevated, the concentrations of pepsin-insoluble proteins were decreased. Furthermore, the four-day hypoxia/hypercapnia increased the synthesis of cardiac collagen due to newly synthesized forms; the amount of cross-linked particles was not affected. This type of hypoxia increased cardiac collagen type III mRNA, while cardiac collagen type I mRNA was decreased. MMP-2 activity was detected on the zymographic gel through appearance of two bands; no differences were observed in either group. mRNA levels for MMP-2 in the RV were significantly lower in both the hypoxic and hypoxic/hypercapnic animals. mRNA levels for TIMP-1 were reduced in the RV of both the hypoxic and hypoxic/hypercapnic animals. Hypoxia with hypercapnia increased the level of mRNA (6.5 times) for the atrial natriuretic peptide (ANP) predominantly in the RV. The role of this peptide in remodeling of cardiac ECM is discussed.     

Reduction of chronic hypoxic pulmonary hypertension in the rat by beta-aminopropionitrile

We administered antifibrotic agent beta-aminopropionitrile (BAPN) to rats exposed to 10% O2-90% N2 for 3 wk to prevent excess vascular collagen accumulation. Groups of Sprague-Dawley rats studied were air breathing, hypoxic, and hypoxic treated with BAPN, 150 mg/kg twice daily intraperitoneally. After the 3-wk period, we measured mean right ventricular pressure (RVP), the ratio of weight of right ventricle to left ventricle plus septum (RV/LV + S), and hydroxyproline content of the main pulmonary artery (PA) trunk. Hypoxia increased RVP from 14 to 29 mmHg; RVP was 21 mmHg in hypoxic BAPN-treated animals. Hypoxia increased the RV/LV + S ratio from 0.28 to 0.41; the ratio was 0.32 in hypoxic BAPN-treated animals. Hypoxia increased PA hydroxyproline from 20 to 239 micrograms/artery; hydroxyproline was 179 micrograms/artery in hypoxic BAPN-treated animals. Thus BAPN prevented pulmonary hypertension, right ventricular hypertrophy, and excess vascular collagen produced by hypoxia. We conclude that vascular collagen contributes to the maintenance of chronic hypoxic pulmonary hypertension.     

Mechanisms of oxygen demand/supply balance in the right ventricle

Few studies have investigated factors responsible for the O2 demand/supply balance in the right ventricle. Resting right coronary blood flow is lower than left coronary blood flow, which is consistent with the lesser work of the right ventricle. Because right and left coronary artery perfusion pressures are identical, right coronary conductance is less than left coronary conductance, but the signal relating this conductance to the lower right ventricular O2 demand has not been defined. At rest, the left ventricle extracts approximately 75% of the O2 delivered by coronary blood flow, whereas right ventricular O2 extraction is only ~50%. As a result, resting right coronary venous PO2 is approximately 30 mm Hg, whereas left coronary venous PO2 is approximately 20 mm Hg. Right coronary conductance does not sufficiently restrict flow to force the right ventricle to extract the same percentage of O2 as the left ventricle. Endogenous nitric oxide impacts the right ventricular O2 demand/supply balance by increasing the right coronary blood flow at rest and during acute pulmonary hypertension, systemic hypoxia, norepinephrine infusion, and coronary hypoperfusion. The substantial right ventricular O2 extraction reserve is used preferentially during exercise-induced increases in right ventricular myocardial O2 consumption. An augmented, sympathetic-mediated vasoconstrictor tone blunts metabolically mediated dilator mechanisms during exercise and forces the right ventricle to mobilize its O2 extraction reserve, but this tone does not limit resting right coronary flow. During exercise, right coronary vasodilation does not occur until right coronary venous PO2 decreases to approximately 20 mm Hg. The mechanism responsible for right coronary vasodilation at low PO2 has not been delineated. In the poorly autoregulating right coronary circulation, reduced coronary pressure unloads the coronary hydraulic skeleton and reduces right ventricular systolic stiffness. Thus, normal right ventricular external work and O2 demand/supply balance can be maintained during moderate coronary hypoperfusion.     

Effects of gestational age on myocardial blood flow and coronary flow reserve in pressure-loaded ovine fetal hearts

To test the hypothesis that coronary flow and coronary flow reserve are developmentally regulated, we used fluorescent microspheres to investigate the effects of acute (6 h) pulmonary artery banding (PAB) on baseline and adenosine-enhanced right (RV) and left ventricular (LV) blood flow in two groups of twin ovine fetuses (100 and 128 days of gestation, term 145 days, n = 6 fetuses/group). Within each group, one fetus underwent PAB to constrict the main pulmonary artery diameter by 50%, and the other twin served as a nonbanded control. Physiological measurements were made 6 h after the surgery was completed; tissues were then harvested for analysis of selected genes that may be involved in the early phase of coronary vascular remodeling. Within each age group, arterial blood gas values, heart rate, and mean arterial blood pressure were similar between control and PAB fetuses. Baseline endocardial blood flow in both ventricles was greater in 100 than 128-day fetuses (RV: 341 +/- 20 vs. 230 +/- 17 ml*min(-1)*100 g(-1); LV: 258 +/- 18 vs. 172 +/- 23 ml*min(-1)*100 g(-1), both P < 0.05). In both age groups, RV and LV endocardial blood flows increased significantly in control animals during adenosine infusion and were greater in PAB compared with control fetuses. After PAB, adenosine further increased RV blood flow in 128-day fetuses (from 416 +/- 30 to 598 +/- 33 ml*min(-1)*g(-1), P < 0.05) but did not enhance blood flow in 100-day animals (490 +/- 59 to 545 +/- 42 ml*min(-1)*100 g(-1), P > 0.2). RV vascular endothelial growth factor and Flk-1 mRNA levels were increased relative to controls (P < 0.05) in 128 but not 100-day PAB fetuses. We conclude that in the ovine fetus, developmentally related differences exist in 1) baseline myocardial blood flows, 2) the adaptive response of myocardial blood flow to acute systolic pressure load, and 3) the responses of selected genes involved in vasculogenesis to increased load in the fetal myocardium.     

Effects of aging on the cardiac remodeling induced by chronic high-altitude hypoxia in rat

Effects of chronic high-altitude hypoxia on the remodeling of right ventricle were examined in three age groups of rats: 2, 6, and 18 mo. The extent of right ventricular (RV) hypertrophy (RVH) showed an age-associated diminution. RV cell size and pericellular fibrosis showed a significant increase in the 2- and 6-mo-old exposed rats but not in the 18-mo-old exposed rats compared with control. A hyperplasic response was underscored in the three exposed age groups but appeared less pronounced in the 18-mo-old rats. A significant decrease in the transient outward potassium current (Ito) density was observed in RV cell only in the 2-mo-old exposed group compared with the control group. In the control group, there was a clear tendency for Ito density to decrease as a function of age. The sustained outward current density was modified neither by the hypoxia condition nor by the age. Neither the cytochrome c oxidase activity nor the heat shock protein 72 content in the RV was altered after hypoxic exposure regardless of age. The norepinephrine content in the RV was significantly decreased in each age group exposed to hypoxia when compared with their age-matched control group. Our findings indicate that the remodeling (at morphological and electrophysiological levels) induced by chronic hypoxia in the RV can be decreased by the natural aging process.     

Changes in the expression and/or activation of regulatory proteins in rat hearts adapted to chronic hypoxia

Chronic intermittent high altitude (IHA) hypoxia results in long-term adaptation protecting the heart against acute ischemia/reperfusion injury; however, molecular mechanisms of this phenomenon are not completely elucidated so far. The present study was aimed at investigation of a modulating effect of IHA hypoxia on the expression and/or activation of selected regulatory proteins, with particular emphasis on differential responses in the right ventricle (RV) and left ventricle (LV). Adult male Wistar rats were exposed to IHA hypoxia of 7000 m simulated in a hypobaric chamber (8 h/day, 25 exposures), and protein contents and activities in myocardial fractions were determined by Western blot analysis. In markedly hypertrophic RV of hypoxic rats, gelatinolytic activity of MMP-2 and protein levels of carbonic anhydrase IX (a marker of hypoxia) were significantly enhanced. Study of mitogen-activated protein kinases (MAPKs) revealed no differences in the contents of total p38-MAPK in both ventricles between the IHA and normoxic control rats, whereas activation of p38-MAPK was decreased in the RV and moderately increased in the LV of IHA rats as compared to controls. Extracellular signal regulated kinase-2 (ERK-2) was partially up-regulated in the RV of IHA rats, and, in addition, expression of acidic fibroblast growth factor (aFGF), a potential activator of ERK cascade, was also significantly increased. In contrast, expression of ERKs in the LV as well as their activities in both ventricles, were not affected by IHA hypoxia. Differential effects of IHA hypoxia on c-Jun-N-terminal protein kinases (JNKs) in the RV and LV were also observed. As compared with the controls, total content of JNKs was increased in the RV of the IHA rats, while expression of JNKs in the LV was down-regulated. IHA hypoxia changed neither total levels of Akt kinase in both RV and LV, nor Akt kinase activity in the RV. However, increased levels of activated phospho-Akt kinase were found in the LV of IHA rats. The results demonstrate that adaptation of rat hearts to chronic IHA hypoxia is associated with disctinct changes in the levels and/or activation of several regulatory proteins in two ventricles. The latter could be attributed to both myocardial remodeling and cardioprotection induced by chronic hypoxia.     

游泳运动对低氧性肺动脉高压大鼠肺组织apelin及其受体表达的影响

目的:探讨游泳运动对大鼠肺组织新的小分子活性肽apelin及其受体(APJ)表达的影响。方法:45只雄性大鼠随机分成三组:正常对照组、低氧组(七周)和游泳组(低氧+游泳锻炼七周组,低氧3周后,于每天入低氧舱前行无负重游泳运动60 min,每天1次)。七周后测定各组大鼠平均肺动脉压(mPAP)、右心室与左心室加室间隔的重量比[RV/(LV+S)]、肺细小动脉管壁面积/管总面积(WA/TA)、管腔面积/管总面积(CA/TA)及中膜厚度(PAMT)。免疫蛋白印迹与免疫组化法测定肺组织apelin/APJ的蛋白表达。结果:①低氧组mPAP和RV/(LV+S)比正常对照组分别高73.6%和31.2%(P均<0.01),而游泳组比低氧组分别低21.1%和8.9%(P均<0.05)。②低氧组WA/TA和PAMT较正常对照组分别高70.8%和102%,而游泳组较低氧组分别低24.8%和40.1%(P均<0.01)。低氧组CA/TA较正常对照组低15.1%,而游泳组较低氧组高10.3%(P均<0.01)。③低氧组肺组织apelin蛋白表达较正常对照组上调374%(P<0.01),而APJ蛋白表达下调87.1%(P均<0.01);游泳组肺组织apelin蛋白表达较低氧组下调48%,而APJ蛋白表达上调287%(P均<0.01)。④apelin蛋白主要在血管外膜及炎症细胞胞浆内表达,APJ蛋白主要在血管内膜、外膜及炎症细胞上表达。结论:游泳运动减缓肺动脉高压和肺血管重塑作用可能与调节肺组织apelin/APJ系统的表达有关。     

Continuous inhalation of carbon monoxide induces right ventricle ischemia and dysfunction in rats with hypoxic pulmonary hypertension

We aimed to investigate the toxicity of carbon monoxide (CO) in rats with right ventricle (RV) remodeling induced by hypoxic pulmonary hypertension (PHT). A group of Wistar rats was exposed to 3-wk hypobaric hypoxia (H). A second group was exposed to 50 ppm CO for 1 wk (CO). A third group was exposed to chronic hypoxia including 50 ppm CO during the third week (H+CO). These groups were compared with controls. RV and left ventricle (LV) functions were assessed by echocardiography and transparietal catheterization. Ventricular perfusion was estimated with the fluorescent microsphere method. Results were confirmed by histology. PHT induced RV hypertrophy and function enhancement. In the H group, RV shortening fraction (RVSF; 71 +/- 12% vs. 41 +/- 2%) and RV end-systolic pressure (RVESP; 54 +/- 6 vs. 19 +/- 2 mmHg) were increased compared with controls. Moreover, myocardial perfusion was increased in the RV (36 +/- 2% vs. 22 +/- 2%) and decreased in the LV (64 +/- 3% vs. 78 +/- 2%). In the H+CO group, RVSF (45 +/- 3% vs. 71 +/- 12%) and RVESP (38 +/- 3 vs. 54 +/- 6 mmHg) were decreased compared with the H group. RV perfusion was decreased in the H+CO group compared with the H group (21 +/- 5% vs. 36 +/- 2%), and LV perfusion was increased (79 +/- 5% vs. 64 +/- 3%). PHT and RV hypertrophy were still present in the H+CO group, and fibroses localized in the RV were detected. Similar lesions were observed in an additional group exposed simultaneously to hypoxia and 50 ppm CO over 3 wk. We demonstrated that rats with established PHT were more sensitive to CO, which dramatically alters the RV adaptive response to PHT, leading to ischemic lesions.