Influence of the heart on the vertical gradient of transpulmonary pressure in dogs

Estimations were made of the vertical gradient of transpulmonary pressure (VGTP) from measurements of esophageal pressure in nine head-up dogs at functional residual capacity (FRC) when alive, when dead, and after total bilateral pneumothorax. The VGTP of 0.4 cmH2O/cm height in the alive state was abolished by pneumothorax, and roentgenograms showed that the heart moved in a caudal-dorsal direction. There was a small but significant increase in the VGTP on going from FRC to near total lung capacity (TLC) in alive head-up dogs. In eight dead head-up dogs heart weight was increased by replacing various amounts of heart blood with Hg. The VGTP was significantly increased from 0.28 to 0.51 cmH2O/cm height. The fractional increase in the VGTP was similar to the fractional increase in heart weight. In five dogs extrapolation to zero heart weight gave an average VGTP of 0.14 cmH2O/cm height. We conclude that the lungs help support the heart in the head-up dog and that the VGTP is in part determined by the pressure distribution required for this support.     

Simulation of the vertical gradient of transpulmonary pressure by stable foams

We describe a simulation of the vertical gradient of transpulmonary pressure (VGTP) using a stable foam, which is suitable for use in studies of the effect of the VGTP on excised lungs. We generated foams that produced linear hydrostatic pressure gradients (HPGs) from 0.18 to 0.44 cmH2O/cm depth, which were stable over time and were reproducible. The HPG was similar under static and dynamic conditions. The foam did not affect lung elastic properties or cause histological changes. We conclude that these stable foams provide a practical, inexpensive simulation of the VGTP and should be useful in studying the effects of the VGTP on regional lung behavior.     

Deformation of the dog lung in the chest wall

Data on the shape of the chest wall at total lung capacity (TLC) and functional residual capacity (FRC) were used as boundary conditions in an analysis of the deformation of the dog lung. The lung was modeled as an elastic body, and the deformation of the lung from TLC to FRC caused by the change in chest wall shape and gravity were calculated. Parenchymal distortions, distributions of regional volume at FRC as a fraction of the volume at TLC, and distributions of surface pressure at FRC are reported. In the prone dog there are minor variations in fractional volume along the cephalocaudal axis. In transverse planes opposing deformations are caused by the change of shape of the transverse section and the gravitational force on the lung, and the resultant fractional volume and pleural pressure distributions are nearly uniform. In the supine dog, there is a small cephalocaudal gradient in fractional volume, with lower fractional volume caudally. In transverse sections the heart and abdomen extend farther dorsally at FRC, squeezing the lung beneath them. The gradients in fractional volume and pleural pressure caused by shape changes are in the same direction as the gradients caused by the direct gravitational force on the lung, and these two factors contribute about equally to the large resultant vertical gradients in fractional volume and pleural pressure. In the prone position the heart and upper abdomen rest on the rib cage. In the supine posture much of their weight is carried by the lung.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulmonary functions of rats trained with mild exercise

The purpose of the present study was to determine if lung function is modified by physical exercise in male and female rats. The animals were subjected to a running program for 5 weeks. At the termination of the program period, the running rats (R) had body weight smaller than the sedentary control rats (S). In male rats, the weights of lung, heart and adrenal glands, which were corrected with body weight, were larger in the R than in the S, and the absolute weight of adrenal glands also increased in the R. The rates of peak flow and maximum expiratory flow at 50% total lung capacity, which were corrected with either body weight, lung weight or total lung capacity, increased in the R. Because of no significant change in the flow resistance and compliance of the lungs, the increases in the rates of these expiratory flows might have been due to increased airway rigidity caused by some mechanisms relating to exercise stimuli. In female rats, on the other hand, the above changes in the R were little or less.     

建立犬肺渐次萎陷动物模型的实验研究

目的:术中定位是微小肺癌手术面临的主要难题,而原因则是肺在术中萎陷造成的巨大形变。我们从研究肺的术中萎陷着手,建立肺渐次萎陷动物模型,模拟肺在术中发生的萎陷,用以研究肺萎陷的过程、规律及影响因素,为微小肺癌的术中定位提供理论基础。本文用渐进的人工气胸模拟肺在术中的渐次萎陷过程,探讨简便、有效的肺渐次萎陷动物模型的制作方法。方法:健康成年犬12只机等分入左、右侧手术组麻醉后移至CT扫描床采用切小口置管和胸腔穿刺两种方式制作人工气胸。向胸膜腔内分次、定量地注射气体,使肺逐渐萎陷直至完全萎陷。通过夹闭气管插管协助稳定肺的萎陷状态。将各萎陷状态分别进行CT扫描。结果:所有实验犬均顺利完成实验麻醉良好,无意外情况发生。9只犬给予气管插管,3只未给予气管插管;4只犬采用切小口置管方式制作气胸,8只采用胸腔穿刺方式。气管插管增加了模型制作难度,但有利于稳定肺的萎陷状态;胸腔穿刺方式相对操作更为简便。随着向胸膜腔内注射气体,肺缓慢而均匀地向肺门方向集中,萎陷进程满意。CT扫描记录了肺从膨胀到萎陷的各阶段,经过后期重建再现了肺的萎陷过程。5只犬出现并发症,均通过改变操作得以纠正,未影响实验进程。结论:本研究建立的肺渐次萎陷动物模型,能够很好地模拟肺在术中的萎陷过程,是研究术中肺萎陷的理想动物模型。     

Nitric oxide synthase inhibition does not affect regulation of muscle sympathetic nerve activity during head-up tilt

To test the hypothesis that systemic inhibition of nitric oxide (NO) synthase does not alter the regulation of sympathetic outflow during head-up tilt in humans, in eight healthy subjects NO synthase was blocked by intravenous infusion of NG-monomethyl-L-arginine (L-NMMA). Blood pressure, heart rate, cardiac output, total peripheral resistance (TPR), and muscle sympathetic nerve activity (MSNA) were recorded in the supine position and during 60 degrees head-up tilt. In the supine position, infusion of L-NMMA increased blood pressure, via increased TPR, and inhibited MSNA. However, the increase in MSNA evoked by head-up tilt during L-NMMA infusion (change in burst rate: 24 +/- 4 bursts/min; change in total activity: 209 +/- 36 U/min) was similar to that during head-up tilt without L-NMMA (change in burst rate: 23 +/- 4 bursts/min; change in total activity: 251 +/- 52 U/min, n = 6, all P > 0.05). Moreover, changes in TPR and heart rate during head-up tilt were virtually identical between the two conditions. These results suggest that systemic inhibition of NO synthase with L-NMMA does not affect the regulation of sympathetic outflow and vascular resistance during head-up tilt in humans.     

Effect of gravity and posture on lung mechanics.

The volume-pressure relationship of the lung was studied in six subjects on changing the gravity vector during parabolic flights and body posture. Lung recoil pressure decreased by approximately 2.7 cmH(2)O going from 1 to 0 vertical acceleration (G(z)), whereas it increased by approximately 3.5 cmH(2)O in 30 degrees tilted head-up and supine postures. No substantial change was found going from 1 to 1.8 G(z). Matching the changes in volume-pressure relationships of the lung and chest wall (previous data), results in a decrease in functional respiratory capacity of approximately 580 ml at 0 G(z) relative to 1 G(z) and of approximately 1,200 ml going to supine posture. Microgravity causes a decrease in lung and chest wall recoil pressures as it removes most of the distortion of lung parenchyma and thorax induced by changing gravity field and/or posture. Hypergravity does not greatly affect respiratory mechanics, suggesting that mechanical distortion is close to maximum already at 1 G(z). The end-expiratory volume during quiet breathing corresponds to the mechanical functional residual capacity in each condition.     

Comparisons of turkey embryos incubated in tenuous or dense gas environments--II. Organ growth

1. Eggs from large white turkeys were incubated in tenuous and dense gas atmospheres. 2. Tenuous gases resulted in heavier embryos until the onset of the plateau stage in oxygen consumption when dense gas environments caused heavier embryos. 3. Tenuous gases decreased heart and lung weight but increased liver weight. 4. Oxygen supplementation in tenuous gases increased liver weights but had no effect on lung or heart weights. 5. The data suggest an interaction of gas density and partial pressures of individual gases which affects breathing and the physiology of developing poult embryos.     

Effects of acute pleural effusion on respiratory system mechanics in dogs

We determined regional (Vr) and overall lung volumes in six head-up anesthetized dogs before and after the stepwise introduction of saline into the right pleural space. Functional residual capacity (FRC), as determined by He dilution, and total lung capacity (TLC) decreased by one-third and chest wall volume increased by two-thirds the saline volume added. Pressure-volume curves showed an apparent increase in lung elastic recoil and a decrease in chest wall elastic recoil with added saline, but the validity of esophageal pressure measurements in these head-up dogs is questionable. Vr was determined from the positions of intraparenchymal markers. Lower lobe TLC and FRC decreased with added saline. The decrease in upper lobe volume was less than that of lower lobe volume at FRC and was minimal at TLC. Saline increased the normal Vr gradient at FRC and created a gradient at TLC. During deflation from TLC to FRC before saline was added, the decrease in lung volume was accompanied by a shape change of the lung, with greatest distortion in the transverse (ribs to mediastinum) direction. After saline additions, deflation was associated with deformation of the lung in the cephalocaudal and transverse directions. The deformation with saline may be a result of upward displacement of the lungs into a smaller cross-sectional area of the thoracic cavity.     

Effects of high-frequency artificial respiration on the rhythm of heart contraction in cats

High-frequency artificial hyperventilation of cat lung with a rate above the initial rhythm of the heart reconstructs the rhythm so that each breathing cycle coincides with one systole of the heart. Synchronization of breathing movements and heart systoles is easily removed by atropine, and cold blockade of vagus nerves by open artificial pneumothorax.     

Spatial distribution of ventilation and perfusion in anesthetized dogs in lateral postures.

We aimed to assess the influence of lateral decubitus postures and positive end-expiratory pressure (PEEP) on the regional distribution of ventilation and perfusion. We measured regional ventilation (VA) and regional blood flow (Q) in six anesthetized, mechanically ventilated dogs in the left (LLD) and right lateral decubitus (RLD) postures with and without 10 cmH(2)O PEEP. Q was measured by use of intravenously injected 15-microm fluorescent microspheres, and VA was measured by aerosolized 1-microm fluorescent microspheres. Fluorescence was analyzed in lung pieces approximately 1.7 cm(3) in volume. Multiple linear regression analysis was used to evaluate three-dimensional spatial gradients of Q, VA, the ratio VA/Q, and regional PO(2) (Pr(O(2))) in both lungs. In the LLD posture, a gravity-dependent vertical gradient in Q was observed in both lungs in conjunction with a reduced blood flow and Pr(O(2)) to the dependent left lung. Change from the LLD to the RLD or 10 cmH(2)O PEEP increased local VA/Q and Pr(O(2)) in the left lung and minimized any role of hypoxia. The greatest reduction in individual lung volume occurred to the left lung in the LLD posture. We conclude that lung distortion caused by the weight of the heart and abdomen is greater in the LLD posture and influences both Q and VA, and ultimately gas exchange. In this respect, the smaller left lung was the most susceptible to impaired gas exchange in the LLD posture.     

Fine needle aspiration cytology of lung lesions: a clinicopathological and cytopathological review of 150 cases with emphasis on the relation between the number of passes and the incidence of pneumothorax

Objective: The aim of this study was to review the lung fine needle aspirations (FNA) that were done in our hospital between January 1998 and April 2004. Interobserver agreement, sample adequacy and the relation between the number of passes and the occurrence of pneumothorax are presented. Study design: One hundred fifty cases of lung FNA from the department of pathology files were identified and the available specimens and patient charts were reviewed. The interobserver agreement was calculated. The relation between the number of passes and the subsequent development of pneumothorax was tested using Mann–Whitney U‐test. Results: The material of 132 patients (88%) out of 150 were retrieved and reviewed. There were 85 cases of non‐small cell lung cancer (NSCLC) (64.4%), nine cases of small cell lung cancer (6.8%), five cases of metastatic cancer (3.8%) and 33 cases were reported negative for cancer (25%). The NSCLC included 36 cases of adenocarcinoma (27.3%), 32 cases of squamous cell carcinoma (24.2%), and 17 cases of large cell undifferentiated carcinoma (12.9%). The interobserver agreement k was 0.93, (95% CI 0.87–0.98). The majority of cases (95.5%) were considered adequate for interpretation. The charts of 138 patients (92%) were reviewed for postprocedure radiologically confirmed pneumothorax. Sixteen patients (11.6%) developed pneumothorax only three of whom (2%) required a chest tube for treatment. The number of passes was identified in 118 patients (85.5%). The number of passes did not have a statistically significant association with the development of a pneumothorax (P = 0.747). Conclusion: Fine needle aspirations to diagnose lung lesions is a safe procedure with a low incidence of pneumothorax. Its findings are reproducible with high interobserver agreement. Immediate adequacy evaluation and triage by a pathologist guarantees adequate sample in most instances. The number of passes was not associated with an increased incidence of pneumothorax.     

Assessment of cardiac autonomic modulation during graded head-up tilt by symbolic analysis of heart rate variability

Two symbolic indexes, the percentage of sequences characterized by three heart periods with no significant variations (0V%) and that with two significant unlike variations (2UV%), have been found to reflect changes in sympathetic and vagal modulations, respectively. We tested the hypothesis that symbolic indexes may track the gradual shift of the cardiac autonomic modulation during an incremental head-up tilt test. Symbolic analysis was carried out over heart period variability series (250 cardiac beats) derived from ECG recordings during a graded head-up tilt test (0, 15, 30, 45, 60, 75, and 90 degrees ) in 17 healthy subjects. The percentage of subjects showing a significant linear correlation (Spearman rank-order correlation) with tilt angles was utilized to evaluate the performance of symbolic analysis. Spectral analysis was carried out for comparison over the same series. 0V% progressively increased with tilt angles, whereas 2UV% gradually decreased. The decline of 2UV% was greater than the increase of 0V% at low tilt angles. Linear correlation with tilt angles was exhibited in a greater percentage of subjects for 0V% and 2UV% than for any spectral index. Our findings suggest that symbolic analysis performed better than spectral analysis and, thus, is a suitable methodology for assessment of the subtle changes of cardiac autonomic modulation induced by a graded head-up tilt test. Moreover, symbolic analysis indicates that the changes of cardiac sympathetic and vagal modulations observed during this protocol were reciprocal but characterized by different absolute magnitudes.     

Expiratory muscle contribution to tidal volume in head-up dogs

A change from the supine to the head-up posture in anesthetized dogs elicits increased phasic expiratory activation of the rib cage and abdominal expiratory muscles. However, when this postural change is produced over a 4- to 5-s period, there is an initial apnea during which all the muscles are silent. In the present studies, we have taken advantage of this initial silence to determine functional residual capacity (FRC) and measure the subsequent change in end-expiratory lung volume. Eight animals were studied, and in all of them end-expiratory lung volume in the head-up posture decreased relative to FRC [329 +/- 70 (SE) ml]. Because this decrease also represents the increase in lung volume as a result of expiratory muscle relaxation at the end of the expiratory pause, it can be used to determine the expiratory muscle contribution to tidal volume (VT). The average contribution was 62 +/- 6% VT. After denervation of the rib cage expiratory muscles, the reduction in end-expiratory lung volume still amounted to 273 +/- 84 ml (49 +/- 10% VT). Thus, in head-up dogs, about two-thirds of VT result from the action of the expiratory muscles, and most of it (83%) is due to the action of the abdominal rather than the rib cage expiratory muscles.     

Coordination of growth and differentiation in the fetal lung

The male fetal lung begins to synthesize surfactant later in gestation than the female. This delay appears to be caused by androgens. We hypothesized that male fetal lung differentiation is delayed as a consequence of an extended phase of growth which is elicited by androgens. We observed that in vivo fetal lung protein synthesis relative to DNA synthesis peaked earlier in gestation in the female fetal lung and that this event was synchronous with the onset of differentiation. Pregnant rats were treated with dihydrotestosterone (DHT) during pregnancy, and fetal lung growth parameters were measured. Lung wet weight, dry weight, and DNA and protein concentrations were significantly elevated by DHT treatment. Type II cells and fibroblasts were isolated from lungs of DHT-treated fetuses. The number of total cells recovered was increased by 30%; the number of type II cells recovered was increased by 87%; and the number of fibroblasts recovered was increased by 42%. The type II cells which were recovered exhibited increased incorporation of [3H]thymidine into DNA and a reduced ratio of radiolabeled protein to radiolabeled DNA compared to that of cells from control lungs. Further studies were done in vitro with fibroblasts and type II cells isolated from untreated fetal rat lungs. Treatment of the fibroblasts with DHT during culture caused an increase in thymidine incorporation into DNA. This effect was not blocked by simultaneous treatment with cortisol, which normally causes reduced DNA synthesis and induces fibroblast differentiation. Treatment of the type II cells with DHT in culture caused a dose-dependent increase in cell number but a decrease in synthesis of disaturated phosphatidylcholine. These studies provide more direct evidence of the interrelationships between the control of growth and the control of differentiation in the fetal lung. DHT, a signal which delays the onset of expression of differentiation, also induces growth. We conclude that the controls of growth and of differentiation of the fetal lung are reciprocally linked.     

AT2 receptor mediates the cardioprotective effects of AT1 receptor antagonist in post-myocardial infarction remodeling

There are two subtypes of angiotensin (Ang) II receptors, AT1R and AT2R. It is established that clinical use of specific AT1R blocker (ARB) improves the long-term prognosis of heart failure. However, scientific basis for such effects of ARB is incompletely understood. The present study was designed to determine whether ARB inhibits the left ventricular (LV) remodeling that occurs early after myocardial infarction (MI) and whether the benefit of ARB is mediated by blockade of AT1R itself or by stimulation of AT2R resulting from AT1R blockade. MI was induced in AT2R-knockout mice and wild-type mice. Administration of valsartan, an ARB, or vehicle was started soon after the surgery and continued for two weeks. Infarction caused significant increase in end diastolic and end systolic LV dimensions, LV/body weight ratio, and myocyte cross-sectional area (MCSA) in both strains to a similar extent. Lung/body weight ratio, an index of pulmonary congestion, was also significantly increased in both strains, but the magnitude of increase was significantly larger in knockout mice. Valsartan significantly reduced LV dimensions, LV/body weight ratio, MCSA, and lung/body weight ratio in wild-type mice. In knockout mice, however, valsartan failed to inhibit the increases in LV dimensions and LV/body weight ratio. After the treatment, lung/body weight ratio in the mutant strain was significantly larger than that in the wild-type mice. Valsartan attenuates acute phase post-infarction remodeling and ameliorates heart failure, and a large part of its cardioprotective effect was mediated by AT2R.     

Venous hydrostatic indifference point as a marker of postnatal adaptation to orthostasis in swine.

The postulate that venous adaptation assists postural baroreflex regulation by shifting the hydrostatic indifference point (HIP) toward the heart was investigated in eight midazolam-sedated newborn piglets. Whole body head-up (+15, +30, and +45 degrees ) and head-down (-15 and -30 degrees ) tilt provided a physiological range of orthostatic strain. HIP for all positive tilts shifted toward the heart (P < 0.05), +45 degrees HIP shifted most [6.7 +/- 0.3, 5.9 +/- 0.5, and 3.6 +/- 0.3 (SE) cm caudal to right atrium on days 1, 3, and 6, respectively]. HIP for negative tilts (3.0 +/- 0.2 cm caudal to right atrium) did not shift with postnatal age. Euthanasia on day 6 caused 2.1 +/- 0.3-cm caudal displacement of HIP for positive and negative tilts (P < 0.05). HIP proximity to right atrium was not altered by alpha-, beta-adrenoceptor and cholinoceptor blockade on day 5. It is concluded that early HIP migration reflects enhancement of venous pressure control to head-up orthostatic strain. The effect is independent of baroreflex-mediated adrenoceptor and cholinoceptor mechanisms.     

No evidence for mesothelial cell contact across the costal pleural space of sheep

Pleural space width was measured by four morphological approaches using either frozen hydrated or freeze-substituted blocks of chest wall and lung. Anesthetized sheep were held in the lateral (n = 2), sternal recumbent (n = 2), or vertical (head-up; n = 2) position for 30 min. The ribs and intercostal muscles were excised along a 20-cm vertical distance of the chest wall region, which was sprayed with liquid Freon 22, cooled with liquid nitrogen, to facilitate the fastest possible freezing of the visceral and parietal pleura. We measured pleural space width in frozen hydrated blocks by reflected-light and low-temperature scanning electron microscopy and in freeze-substituted, fixed, and embedded tissue blocks by light and transmission electron microscopy. We combined the data from the two groups of sheep held sternally recumbent and vertical because the results were comparable. The average arithmetic mean data for pleural space width determined by reflected-light analysis for samples near the top (18.5 microns) and bottom (20.3 microns) of the chest, separated by 15 cm of lung height, varied inversely with lung height (n = 4; P less than 0.009). The average harmonic mean data demonstrated a similar gravity-dependent gradient (17.3 and 18.8 microns, respectively; P less than 0.02). Therefore a slight vertical gradient of approximately -0.10 micron/cm of lung height was found for costal pleural space width. Pleural space width in the most dependent recesses, such as the costodiaphragmatic recess, reached 1-2 mm. We never found any contacts between the visceral and parietal pleura with either of the frozen hydrated preparations. No points of mesothelial cell contact were revealed in the light- and transmission electron microscopic views of the freeze-substituted tissue, despite an apparent narrower pleural space associated with the tissue-processing steps. We conclude that the pleural space has a slightly nonuniform width, contacts if they occur must be very infrequent, and pleural liquid clearance is probably facilitated by liquid accumulation in dependent regions where lymphatic pathways exist.     

Protective effect of alpha-human atrial natriuretic polypeptide (alpha-hANP) on chemical-induced pulmonary edema

It has been established that alpha-hANP, the newly discovered peptide extracted from human cardiac atria, has potent natriuretic and hypotensive actions. Our present investigation is the first to demonstrate that alpha-hANP is capable of protecting against pulmonary edema caused by various chemicals, using isolated perfused guinea pig lung system. Lungs were perfused via pulmonary artery with Krebs-Ringer bicarbonate buffer at 5.0 ml/min, and wet weight of lungs and perfusion pressure of pulmonary artery (Pa) were monitored. Bolus injection of Triton-X or CHAPS into cannulated pulmonary artery produced edema as indicated by a massive increase in wet weight and a slight increase in Pa. Constant infusion of alpha-hANP through pulmonary artery at 200 ng/ml was effective in causing decrease in wet weight of lung. Perfusion of lung with paraquat or PGF2 alpha, and repeated bolus injection of arachidonic acid or PGE2 caused elevation in both wet weight of lung and Pa. The treatment with alpha-hANP similar to that described above also protected against edema caused by paraquat or arachidonic acid. Bolus administration of epinephrine induced a slight increase in wet weight and Pa, and alpha-hANP was effective in decreasing the elevated lung wet weight and Pa of lungs. Infusion or bolus administration of alpha-hANP into control lungs increased cGMP level in outflow perfusate as well as in lung tissue significantly. In lungs with edema which were induced by Triton-X or paraquat, there was a slight increase in cGMP level in Triton-X treated and no increase in paraquat treated lung tissues. In either cases, was there any increase in cGMP level in perfusate. The specific binding study of [125I]alpha-hANP revealed that the lack of increase in cGMP was not due to a loss of receptor in Triton-X or paraquat treated lungs. Thus our study demonstrated that alpha-hANP had a direct anti-edematic action(s) in lung which was not secondary to the systemic natriuretic and/or hypotensive action(s).     

Effect of Pulmonary-Generated Reactive Oxygen Species on Left-Ventricular Dysfunction Associated with Cardio-Pulmonary Ischemia–Reperfusion Injury

The purpose of the present study was to demonstrate the contribution of pulmonary-generated reactive oxygen species (ROS) on cardiac dysfunction using a rat model of ischemia–reperfusion (IR) injury. Three groups of rats were subjected to regional IR injury in (i) lung, (ii) heart, (iii) lung + heart. A fourth (control) group of rats were instrumented using the same methods but without induction IR. Hemodynamic data were recorded in real time. Blood from the proximal aorta was sampled during baseline, ischemia, and reperfusion, mixed with α-phenyl-N-tert-butylnitrone (PBN) for measuring ROS by electron paramagnetic resonance spectrometry. Data were analyzed by a two-way analysis of variance. The results showed that the lung IR generated an increased burst of ROS that resulted in significant cardiac dysfunction, including hypotension and ECG changes. The results indicated that generation of ROS as a result of acute IR lung injury may be sufficiently large enough to cause direct cardiac dysfunction that is independent of injury caused to the myocardium as a result of regional myocardial IR injury alone.