The ischemic lung: Role of the bronchial arteries in lung function

A patient with a dissecting aortic aneurysm, Type 1, developed acute pulmonary edema unexplained by the usual etiologic factors. Pathologic evidence that bronchial arterial circulation was interrupted led us to hypothesize that pulmonary edema could be due to ischemia of the bronchial circulation. To test this hypothesis, two chronic studies were done in dogs. The first study consisted of selective ligation of the right posterior bronchial artery at its origin at the fifth or sixth intercostal artery. After recovery from surgery, biopsies were taken from the ipsilateral and contralateral lung at time periods from 5 hours to 11 days. Ischemic damage was found in seven of eight dogs (87.5%), and was confined to the right lung. Histological examination revealed initial congestion within 8 hours, followed by pulmonary edema within 72 hours, and finally, disruption of alveolar septa with small emphysematous bullae on the eleventh postoperative day. The left lung remained normal in histological appearance. The second study consisted of transplanting the bronchial artery to the pulmonary artery to create a low pressure system and low O(2) content, and to simulate a regional shock situation. In five of six dogs (83.3%), the anastomosis was occluded within 72 hours, probably due to pressure competition from small collateral bronchial circulation. However, in these five dogs, pulmonary vascular resistance increased by 53%, intrapulmonary shunting increased by 83%, and the alveolar-to-arterial oxygen gradient increased by 150 mm Hg. Pulmonary edema was again confined to the right lung. Bronchial arteriograms demonstrated the extensive and variable distribution of the bronchial circulation in dogs. In the sixth dog, the anastomosis remained patent with a left-to-right shunt, due to a larger bronchial arterial collateral circulation. In this animal, the pulmonary arterial resistance, intrapulmonary shunting, and alveolar-arterial O(2) gradient were normal. Pulmonary edema was absent in lung biopsies. Bronchial circulation is discussed with respect to its clinical implications for lung transplants, shock, thoracic aneurysms, and mediastinal surgery. The results of this study suggest that the systemic bronchial circulation is important for normal lung function.     

Higher Plasma Myostatin Levels in Cor Pulmonale Secondary to Chronic Obstructive Pulmonary Disease

Objective

To analyze plasma myostatin levels and investigate their relationship with right ventricular (RV) function in patients with cor pulmonale secondary to chronic obstructive pulmonary disease (COPD).

Methods

The study recruited 81 patients with advanced COPD and 40 age-matched controls. The patients were divided into two groups: those with cor pulmonale and those without. Echocardiography was used to evaluate RV function and morphology, and the value of tricuspid annular plane systolic excursion (TAPSE) less than 16 mm was considered RV dysfunction. Plasma myostatin levels were analyzed by enzyme-linked immunosorbent assay, and B-type natriuretic peptide (BNP) levels were analyzed as a comparison of myostatin.

Results

The data detected cor pulmonale in 39/81 patients, with the mean value of TAPSE of 14.3 mm. Plasma myostatin levels (ng/mL) were significantly higher in patients with cor pulmonale (16.68 ± 2.95) than in those without (13.56 ± 3.09), and much higher than in controls (8.79±2.79), with each p<0.01. Significant differences were also found in plasma BNP levels among the three groups (p<0.05). Multivariate regression analysis suggested that myostatin levels were significantly correlated with the values of TAPSE and RV myocardium performance index among the COPD patients, and that BNP levels were significantly correlated only with systolic pulmonary arterial pressure, with each p<0.05.

Conclusions

Plasma myostatin levels are increased in COPD patients who have cor pulmonale. Stronger correlations of plasma myostatin levels with echocardiographic indexes of the right heart suggest that myostatin might be superior to BNP in the early diagnosis of cor pulmonale in COPD.     

降纤酶佐治肺心病的疗效观察

目的　观察降纤酶佐治慢性肺源性心脏病 (肺心病 )的临床疗效。　方法　 84例肺心病患者随机分为治疗组和对照组各 4 2例。对照组给予常规治疗 ,治疗组在常规治疗的基础上加用降纤酶 ,第 1天 1 0 u,以后每天 5 u,加在生理盐水 1 0 0 ml中静脉滴注 ,连用 1 0天。治疗前后对两组患者进行血气分析以及血常规、肝和肾功能、血液流变学检测 ,并记录临床症状体征。　结果　治疗组显效率 66.7%、总有效率97.6% ,对照组显效率 3 5 .7%、总有效率 85 .7% ,两组比较有显著性差异 (P <0 .0 5 ) ;治疗组治疗后血气分析、血液流变学、血红蛋白 (Hb)等指标较治疗前明显改善 (P <0 .0 0 1 ) ;对照组治疗后除血气分析有显著性差异 (P <0 .0 1 )外 ,其余指标较治疗前无明显变化 (P >0 .0 5 ) ;治疗组治疗后上述指标较对照组更为显著改善 (P <0 .0 1 )。　结论　降纤酶佐治肺心病能迅速控制病情 ,疗效显著 ,值得临床推广应用     

Functional, morphologic and histochemical changes in the myocardium and their role in the development of cor pulmonale following pulmonary resection]

Functional, morphological and histochemical alterations were studied in 32 dogs within the period of 5 days--18 months after resection of 32-80% of the pulmonary tissue. According to the presence of hypertrophy of the heart right ventricle wall, morphological changes of the myocardium and disorders in the functional features of the cardiovascular activity all the animals were divided into 4 groups: 1--control animals; 2--experimental animals without hypertrophy of the right ventricle wall; 3--experimental animals with hypertrophy of the right ventricle wall in the stage of compensation; 4--experimental animals with hypertrophy of the right ventricle wall in the stage of decompensation. In the myocardium of the second group animals a decrease of aerobic processes and an increase of anaerobic ones were found to take place. The aerobic processes increased and the anaerobic processes decreased in the myocardium of dogs having hypertrophy of the right ventricle wall in the stage compensation. In the muscle of the decompensated pulmonary heart there occurred a pronounced decrease of aerobic and anaerobic processes, a disturbance of the protein and fat metabolism. All this resulted in a decreased contractive function of the myocardium with distrubed hemodynamics. The investigations have shown the interrelationships of morphological, histochemical and ECG alterations in the dynamics of the pulmonary heart development after resection of lungs.     

Cardiovascular responses of the rat to a prostaglandin endoperoxide analog

In the anaesthetized rat, injection of the prostaglandin endoperoxide analog, U 44069, in the right ventricle is vasopressor both in the pulmonary and the systemic circulation. When a moderate dose is used, the hypertensive response of the systemic vascular bed changes in an hypotension. The toxicity seems to be cumulative. At high doses, a vascular collapse is observed sometimes with pulmonary oedema. These findings correlate with the EKG pattern typical for an acute cor pulmonale.     

Compensatory and adaptive changes in the heart after pulmonary resection (morphometric analysis)

The experiment has been performed in 124 non-inbred dogs by means of a complex of morphometrical methods in order to study compensatory-adaptive processes in the heart after pulmonary resection various in its volume. After 58% resection, and especially after 67-75% resection of the lung mass, a stable pulmonary arterial hypertension appears; it results in development of a chronic cor pulmonale and terminates in its decompensation. Application of extrapulmonary arterio-venous anastomosis, before 67-75% of the pulmonary parenchyma is resected, decreases hypertension in the pulmonary circulation, improves adaptive changes of the heart in the newly formed conditions of hemodynamics, preventing development of its failure.     

Susceptibility to pulmonary hypertension in inbred strains of mice exposed to cigarette smoke.

Cor pulmonale is a significant cause of morbidity and mortality in patients with emphysema, but it is not known whether alveolar destruction is directly involved in the disease pathogenesis. The purpose of this study was to examine the relationship between susceptibility to smoking-induced cor pulmonale and alveolar destruction in eight inbred strains of mice: 129XI/SvJ, A/J, A/HeJ, BALB/cJ, C3H/HeJ, C57BL/6J, DBA/2J, and SWR/J. The mice were exposed to filtered air or mainstream cigarette smoke at a concentration of 250 mg/m(3) for 5.5 h/day, 5 days/wk for 5 mo, housed for 4 more months, and killed. The ratio of the weight of the right ventricle/left ventricle plus septum [RV/(LV + S)] was used to assess right ventricular hypertrophy. Alveolar mean linear intercept was used to quantify severity of alveolar destruction. Morphometric determination of blood vessel muscularization was done on sections from four mouse strains. Smoke exposure resulted in significant increases in RV/(LV + S) in the A/J and A/HeJ strains compared with air-exposed controls. The magnitude of the smoking-induced increase in RV/(LV + S) decreased as a function of the genetic distance of the other strains from the A/J and A/HeJ strains. Pulmonary vascular muscularization was significantly increased in smoke-exposed A/J and BALB/cJ mice but not in C3H/HeJ and C57BL/6 mice. Also, mouse strain susceptibility to smoking-induced pulmonary vascular muscularization did not correlate with changes in mean linear intercept. The data from this study suggest that alveolar destruction by itself is not sufficient to cause smoking-induced cor pulmonale in inbred mice.     

缺氧性肺动脉高压大鼠肺腺泡内动脉肌化与内皮结构变化的关系

利用右心导管术、光镜、微机辅助测量及透射电镜,综合观察分析了不同时间减压缺氧(5000m高度)对大鼠肺腺泡内动脉(IAA)内皮结构和肌化的影响及与肺动脉高压(PH)的关系。发现:(1)缺氧24h,IAA即有明显肌化;随缺氧时间延长,ф<50μm的外周血管肌化百分率持续增加,与肺动脉压增高及右室肥厚密切相关。揭示IAA肌化为PH形成的重要原因。(2缺氧24h,IAA内皮是显著胞内水肿;缺氧7d,出现内皮下水肿,内皮增生、肥厚;缺氧14d,内皮下水肿严重,内弹力层大部消失,内皮增生、肥厚继续加重;缺氧21及40d,内皮下水肿减轻,但增生、肥厚更重。结合肺动脉压及IAA肌化变化分析,提示因不同缺氧时间段IAA内皮结构不同程度的变化,其参与导致动脉肌化的机制有所不同。     

Myocardial reaction of the right ventricle to lung resection

Right-sided pulmonectomy (resection of 63-65% of the lung parenchyma) in white noninbred rats resulted in development of chronic cor pulmonale, that develops according to the stages: I--from the time of the operation up to the 10th-15th days after the operation--the stage of acute disturbances and mobilization forces of the organism; II--from the 11th-15th up to the 90th day is the stage of a relative steady compensatory hypertrophy of the cardiac right ventricle; III--after the 90th day--the stage of decompensation. The hypertrophy of the right ventricle myocardium transfers into its dilatation. Amount of cardiomyocytes and their nuclei in 1 mg of the right ventricle tissue progressively decreases, quantity of multinuclear cardiomyocytes increases, ploidy of the nuclei changes: number of tetraploid nuclei decreases, octaploid nuclei appear. Lethality among the animals is 56%.     

超声心动图检查对慢性肺源性心脏病患者右心功能的诊断价值

目的:探讨超声心动图检查对慢性肺源性心脏病患者右心功能的诊断价值。方法:选取2016年8月至2017年12月间本院收治的35例慢性肺源性心脏病患者作为实验组,并选择同期健康体检者35例作为对照组,全部受试者均给予超声心动图检查。分别比较两组右房横径(RA)、右室前后径(RV)、肺动脉平均压(MPAP)、射血分数(EF)、舒张晚期A波峰值流速与舒张早期E波峰值流速的比值(A/E)和右心室Tei指数。同时比较实验组采用常规12导联心电图检查及超声心动图检查的诊断阳性率、右心扩大阳性率和右心扩大伴心衰阳性率。结果:与对照组相比,实验组RA、RV以及MPAP均升高,组间比较差异有统计学意义(P0.05)。与对照组相比,实验组EF明显降低,而A/E值、Tei指数明显升高,组间比较差异有统计学意义(P0.05)。实验组超声心动图检查的诊断阳性率、右心扩大阳性率和右心扩大伴心衰阳性率均高于常规12导联心电图检查(P0.05)。结论:应用超声心动图检查能够有效诊断慢性肺源性心脏病患者的右心功能,而且操作简单方便,诊断阳性率较高。     

Expiratory muscle activity during pulmonary edema in the anesthetized dog.

The present study evaluated the reflex response of the expiratory muscles to pulmonary congestion and edema. The electromyograms of two thoracic and four abdominal expiratory muscles were recorded in 12 anesthetized dogs. Pulmonary edema was induced by rapid saline infusion in six dogs and injection of oleic acid into the pulmonary circulation in the remaining six dogs. Both forms of pulmonary edema reduced pulmonary compliance, interfered with gas exchange, and induced a rapid and shallow breathing pattern. The electrical activity of all abdominal muscles was suppressed during both forms of pulmonary edema. In contrast, the electromyogram activity of the thoracic expiratory muscles was not significantly affected by pulmonary edema. Acute pulmonary arterial hypertension produced in two dogs by inflating a balloon in the left atrium had no effect on ventilation or expiratory muscle electrical activity. In two vagotomized dogs, pulmonary edema did not inhibit the expiratory muscles. We conclude that pulmonary edema suppresses abdominal but not thoracic expiratory muscle activity by vagal reflex pathway(s). Extravasation of fluid into the lung appears to be more important than an increase in pulmonary vascular pressure in eliciting this response.     

Hypoxic pulmonary vasoconstriction does not affect hydrostatic pulmonary edema formation

We studied the effects of regional hypoxic pulmonary vasoconstriction (HPV) on lobar flow diversion in the presence of hydrostatic pulmonary edema. Ten anesthetized dogs with the left lower lobe (LLL) suspended in a net for continuous weighing were ventilated with a bronchial divider so the LLL could be ventilated with either 100% O2 or a hypoxic gas mixture (90% N2-5% CO2-5% O2). A balloon was inflated in the left atrium until hydrostatic pulmonary edema occurred, as evidenced by a continuous increase in LLL weight. Left lower lobe flow (QLLL) was measured by electromagnetic flow meter and cardiac output (QT) by thermal dilution. At a left atrial pressure of 30 +/- 5 mmHg, ventilation of the LLL with the hypoxic gas mixture caused QLLL/QT to decrease from 17 +/- 4 to 11 +/- 3% (P less than 0.05), pulmonary arterial pressure to increase from 35 +/- 5 to 37 +/- 6 mmHg (P less than 0.05), and no significant change in rate of LLL weight gain. Gravimetric confirmation of our results was provided by experiments in four animals where the LLL was ventilated with an hypoxic gas mixture for 2 h while the right lung was ventilated with 100% O2. In these animals there was no difference in bloodless lung water between the LLL and right lower lobe. We conclude that in the presence of left atrial pressures high enough to cause hydrostatic pulmonary edema, HPV causes significant flow diversion from an hypoxic lobe but the decrease in flow does not affect edema formation.     

Lung mechanics in hypervolemic pulmonary edema.

Extravascular thermal volume of the lung (ETVL) is a double indicator dilution technique of use in measuring pulmonary edema. ETVL and lung mechanics measurements were followed to find a less invasive monitor of pulmonary edema than the double indicator dilution technique. Pulmonary edema was induced by overloading the dogs' circulation with dextran. Phases of overload were defined on the basis of a previous electron microscopic study (Noble et al., Can. Anesthetists Soc. J. 21:275, 1974) of lung biopsies relating anatomic changes to physiologic measurements of ETVL and central blood volume (CBV). Congestion occurred when CBV was elevated and ETVL was not, interstitial edema when ETVL was elevated but smaller than 60% above control and alveolar edema when ETVL greater than 85% above control. Once the dogs were in alveolar edema, they were mechanically ventilated with 4, 8, 12, and 16 cmH2O end-tidal pressure (CPPV). Mean functional residual capacity (FRC) for all 15 dogs did not change up to the time CPPV was applied. Pulmonary resistance did not rise until alveolar edema was present. Once in pulmonary edema, lung compliance always fell as lung water increased. In individual dogs, the compliance fall was directly proportional to the rising lung water. However, the variations in slope and beginning point among dogs made it difficult to predict the amount of lung water from dynamic compliance values. PaO2 fell markedly in alveolar edema as a result of a widened A-a gradient. CPPV did not decrease lung water but did increase FRC and PaO2.     

Dimethylthiourea does not ameliorate reperfusion lung injury in dogs or rabbits

We previously demonstrated that in vivo reperfusion of a dog lung after 48 h of pulmonary arterial (PA) ischemia results in pulmonary edema with a significant infiltrate of polymorphonuclear leukocytes. We hypothesized that the injury resulted from production of hydroxyl radical by activated neutrophils. In the current study, we attempted to prevent the injury in both dogs and rabbits with dimethylthiourea (DMTU), a scavenger of hydroxyl radical. After 48 h of left PA occlusion in 18 dogs, DMTU was administered to 9 animals and 9 were not treated. The occlusion was then released, and the dogs were killed 4 h later. Reperfusion resulted in a drop in leukocyte count and left lung edema, but there was no difference between treated and untreated animals. The wet-to-dry ratios of the lungs in the treated group were 5.76 +/- 0.44 (SE) on the reperfused left side and 4.50 +/- 0.06 (P less than 0.05) on the right side. In the untreated groups the comparable ratios were 5.73 +/- 0.31 and 4.92 +/- 0.10 (P less than 0.05 for right vs. left). Histological examination revealed significant differences between the right and left lungs in the extent of intra-alveolar granulocytes and macrophages but did not reveal differences between the treated and untreated animals. To ensure that neither the model nor the lack of response to DMTU was species specific, we then developed a rabbit model of reperfusion edema.(ABSTRACT TRUNCATED AT 250 WORDS)     

High surface tension pulmonary edema induced by detergent aerosol

The effect of the detergent dioctyl sodium sulfosuccinate on pulmonary extravascular water volume (PEWV) was studied in adult anesthetized mongrel dogs. The detergent was dissolved as a 1% solution in a vehicle of equal volumes of 95% ethanol and normal saline and administered by ultrasonic nebulizer attached to the inspiratory tubing of a piston ventilator. Two hours following detergent aerosol PEWV measured gravimetrically was increased compared with either animals receiving no aerosol or those receiving an aerosol of vehicle alone. Loss of surfactant activity and increased alveolar surface tension were demonstrated by Wilhelmy balance studies of minced lung extracts, by a fall in static compliance, and by evidence of atelectasis and instability noted by gross observation and by in vivo microscopy. No significant changes in colloid oncotic pressure or pulmonary microvascular hydrostatic pressure were observed. These data suggest that pulmonary edema can be induced by increased alveolar surface tension and support the concept that one of the major roles of pulmonary surfactant is to prevent pulmonary edema.     

Circadian variation in onset of acute cardiogenic pulmonary edema is independent of patients' features and underlying pathophysiological causes

BACKGROUND: The present study aimed to confirm the existence of a circadian pattern in the onset of acute pulmonary edema (APE) and to verify whether sex, age, preexisting diseases, and clinical causes determining the event may influence it. SUBJECTS AND METHODS: The study considered all consecutive cases of APE observed at the St. Anna General Hospital of Ferrara, Italy, during a 7-year period from January 1, 1992, to December 31, 1998. The sample population was divided into subgroups by sex, age (<75 and > or =75 years), presence or absence of diabetes and hypertension, clinical causes determining the event (i.e., acute myocardial infarction (AMI), pulmonary embolism, arrhythmias). The most important associated or concomitant diseases were also considered (i.e., coronary heart disease and angina, previous myocardial infarction, chronic cardiac failure, dilatative cardiopathy, chronic atrial fibrillation, valvular disease, chronic obstructive pulmonary disease, chronic cor pulmonale, malignancy, chronic renal failure). Time of symptom onset of each event was recorded accurately, then tabulated into 24 increments of 1h (e.g., 06:00 to 06:59 was reported as 6 A.M.). For statistical chronobiological analysis, partial Fourier series were used. RESULTS: During the 7-year period, 1321 consecutive cases of APE in 1014 different subjects were observed. The majority of events occurred at night, and statistical analysis showed a 24h rhythmicity both in the total sample population and in all considered subgroups, with the only exception being patients with pulmonary embolism and arrhythmias, for which the small number of cases made the study of rhythms in APE impossible. CONCLUSIONS: The nighttime preference in the occurrence of APE appears to be quite independent of all demographic features or underlying pathophysiological causes.     

Time course sequences of angiotensin converting enzyme and chymase-like activities during development of right ventricular hypertrophy induced by pulmonary artery constriction in dogs

ACE and chymase play crucial roles in the establishment of pressure overload-induced cardiac hypertrophy. In the present study, time sequences of ACE and chymase-like activities, and their correlation with hypertrophic changes including free wall thickness and cardiac fibrosis, were elucidated in dogs with constant pressure overload to the right ventricle. Pulmonary artery banding (PAB) was applied so that the diameter of the main pulmonary artery was reduced to 60% of the original size, right ventricular pressure was elevated by about 70%, and pulmonary artery flow was increased by about three times of that in sham operation groups. These increases remained unchanged 15, 60, and 180 days after PAB, suggesting that constant right ventricular pressure overload was obtained, at least during this period. The diameter of the right ventricular myocyte was slightly increased and the percentage of fractional shortening was decreased 15 days after PAB. Right ventricular wall thickness and interstitial collagenous fiber were, however, not different from those of sham-operated dogs, suggesting that this period is a period of adaptation to the overload. Sixty days after PAB, the diameter of the right ventricular myocyte was further increased, and right ventricular wall thickness and interstitial collagenous fiber were also increased. These changes were almost identical even 180 days after PAB. Thus, stable hypertrophy was elicited from 60 through 180 days after PAB. ACE activity was facilitated at the adaptation period to the overload (15 days after PAB), but chymase activity was not facilitated at this period. On the other hand, both ACE and chymase-like activities were unchanged in the earlier phase (60 days after PAB) of stable hypertrophy, but facilitated in the latter phase (180 days after PAB). These findings suggest the pathophysiologic roles of these enzymes may be different over the time course of pressure overload-induced hypertrophy.     

"Closing volume" changes in alloxan-induced pulmonary edema in anesthetized dogs.

"Closing volume" (CV) was measured by the single-breath oxygen (SBO2) test in six dogs (alloxan group) before and after alloxan 100-200 mg/kg iv) was injected. CV increased significantly (P less than 0.05) from 32 +/- 3.2% (base line) to 45 +/- 3.5 % in period 1 (0-30 min after alloxan), but vital capacity (VC), respiratory system pressure volume (PV) curves, and alveolar plateau slopes did not change. No radiologic evidence of pulmonary edema was demonstrated in two dogs studied in period 1. CV decreased to 20 +/- 3.9% during period 2 (30-80 min after alloxan) and was associated with tracheal frothing, decreased VC, changes in the PV curve, and alveolar plateau slope, as well as histologic evidence of severe pulmonary edema. CV was 29 +/- 3.0%, and there were no changes in VC, PV curves, or alveolar plateau slopes in 6 other dogs studied for 2 h (control group). CV increased during period 1 before pulmonary edema could be demonstrated by changes in VC, PV curves, or radiography, but in period 2 lung function was so altered that CV by the SBO2 technique gave no useful information.     

An encephalomyocarditis virus epizootic in a baboon colony.

Approximately 80 baboon deaths were caused by encephalomyocarditis virus (EMCV) infection in a 3060 member research and production colony. The epizootic extended over a 9-month period and occurred in baboons ranging from 1 day to 22 years of age. Acute death was the most common history. When clinical disease was detected, it was characterized by labored respiration associated with acute congestive heart failure. The salient necropsy findings were pulmonary congestion and edema, hydropericardium, hydrothorax, ascites, lymph node and splenic hypertrophy, and pale white-to-tan mottled hearts. The most significant histologic lesion was nonsuppurative necrotizing myocarditis. Placental infection with fetal loss occurred. Diagnosis was confirmed by light microscopy, transmission electron microscopy, virus culture, and serology. Rarely, EMCV-induced antibody persisted in surviving baboons for more than 24 months. EMCV-infected feral rats were the probable source of the virus and their control stopped the epizootic. No EMCV neutralizing antibody was detected in colony support personnel or chimpanzees.