Experimental Emphysema - Histologic Changes and Alterations in Pulmonary Circulation.
Histologic changes and alterations in pulmonary circulation studied by experimental development of bullous emphysema in laboratory animals
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Histologic changes and alterations in pulmonary circulation studied by experimental development of bullous emphysema in laboratory animals
Doppler technique was used to measure the pulmonary vascular pressure gradients in dogs that received venous air emboli (VAE) at the rate of 0.35 ml/kg per min, at which the spillover of bubbles into the systemic arteries occur. It was found that, in 60 percent of dogs, venous bubbles spilled over into the arterial circulation at the pulmonary vascular pressure gradient of about 34.7 mm Hg. When the pulmonary vascular pressure gradient was raised to about 52 mm Hg, the spillover of venous bubbles occurred 100 percent of time. It is concluded that venous bubbles can cross the lungs of anesthetized dogs when the driving pressures are sufficient to overcome the normal filtering function.
A rapid noninvasive breathing method is used to obtain serial measurements of the pulmonary capillary blood flow, diffusing capacity per unit of alveolar volume, combined pulmonary tissue plus capillary volume, functional residual capacity, and oxygen consumption in five normal subjects undergoing 6 h of sitting, 4 h of sitting while immersed to the neck in thermoneutral water, and 4 h of lying in thermoneutral water to the neck. The rebreathing method employed a test gas mixture containing 0.5% C2H2, 0.3% C(18)O, 10% He, 21% O2, and balance N2. It is shown that immersion to the neck in the seated posture results in significant increases in sodium excretion cardiac output, and diffusing capacity per unit of alveolar volume. The pulmonary tissue plus capillary volume did not change, demonstrating that the central vascular engorgement induced by water immersion is not accompanied by significant extravasation of fluid into the pulmonary interstitial space.
Based on an analysis of unsteady, viscous flow through distensible tubes, a lumped-parameter model for the dynamics of blood flow through the pulmonary vascular bed was developed. The model is nonlinear, incorporating the variation of flow resistance with transmural pressure. Solved using a hybrid computer, the model yields information concerning the time-dependent behavior of blood pressures, flow rates, and volumes in each important class of vessels in each lobe of each lung in terms of the important physical and environmental parameters. Simulations of twenty abnormal or pathological situations of interest in environmental physiology and clinical medicine were performed. The model predictions agree well with physiological data.
In our previous experiments during NASA Shuttle flights SLS 1 and 2 (9-15 days) and EUROMIR flights (30-90 days) we observed that pulmonary blood flow (cardiac output) was elevated initially, and surprisingly remained elevated for the duration of the flights. Stroke volume increased initially and then decreased, but was still above 1 Gz values. As venous return was constant, the changes in SV were secondary to modulation of heart rate. Mean blood pressure was at or slightly below 1 Gz levels in space, indicating a decrease in total peripheral resistance. It has been suggested that plasma volume is reduced in space, however cardiac output/venous return do not return to 1 Gz levels over the duration of flight. In spite of the increased cardiac output, central venous pressure was not elevated in space. These data suggest that there is a change in the basic relationship between cardiac output and central venous pressure, a persistent "hyperperfusion" and a re-distribution of blood flow and volume during space flight. Increased pulmonary blood flow has been reported to increase diffusing capacity in space, presumably due to the improved homogeneity of ventilation and perfusion. Other studies have suggested that ventilation may be independent of gravity, and perfusion may not be gravity- dependent. No data for the distribution of pulmonary blood volume were available for flight or simulated microgravity. Recent studies have suggested that the pulmonary vascular tree is influenced by sympathetic tone in a manner similar to that of the systemic system. This implies that the pulmonary circulation is dilated during microgravity and that the distribution of blood flow and volume may be influenced more by vascular control than by gravity. The cerebral circulation is influenced by sympathetic tone similarly to that of the systemic and pulmonary circulations; however its effects are modulated by cerebral autoregulation. Thus it is difficult to predict if cerebral perfusion is increased and if there is edema in space. Anecdotal evidence suggests there may be cerebral edema early in flight. Cerebral artery velocity has been shown to be elevated in simulated microgravity. The elevated cerebral artery velocity during simulated microgravity may reflect vasoconstriction of the arteries and not increased cerebral blood flow. The purpose of our investigations was to evaluate the effects of alterations in simulated gravity (+/-), resulting in changes in cardiac output (+/-), and on the blood flow and volume distribution in the lung and brain of human subjects. The first hypothesis of these studies was that blood flow and volume would be affected by gravity, but their distribution in the lung would be independent of gravity and due to vasoactivity changing vascular resistance in lung vessels. The vasodilitation of the lung vasculature (lower resistance) along with increased "compliance" of the heart could account for the absence of increased central venous pressure in microgravity. Secondly, we postulate that cerebral blood velocity is increased in microgravity due to large artery vasoconstriction, but that cerebral blood flow would be reduced due to autoregulation.
Physical immobilization, inaction due to space travel, a sedentary occupation, or bed confinement due to a chronic illness elicit similar alternations in the metabolism of man and animals (rat, rabbit, dog, mouse). After a preliminary period of weight loss, there is eventually weight gain due to increased lipid storage. Protein catabolism is enhanced and anabolism depressed, with elevated urinary excretion of amino acids, creatine, and ammonia. Glycogen stores are depleted and glyconeogenesis is accelerated. Polyuria develops with subsequent redistribution of body fluids in which the blood volume of the systemic circulation is decreased and that of pulmonary circulation increased. This results in depressed production of vasopressin by the posterior pituitary which further enhances urinary water and salt loss.
A numerical model of the cardiovascular system was used to quantify the influences on cardiac function of intrathoracic pressure and intravascular and intraventricular hydrostatic pressure, which are fundamental biomechanical stimuli for orthostatic response. The model included a detailed arterial circulation with lumped parameter models of the atria, ventricles, pulmonary circulation, and venous circulation. The venous circulation was divided into cranial, central, and caudal regions with nonlinear compliance. Changes in intrathoracic pressure and the effects of hydrostatic pressure were simulated in supine, launch, sitting, and standing postures for 0, 1, and 1.8 G. Increasing intrathoracic pressure experienced with increasing gravity caused 12% and 14% decreases in cardiac output for 1 and 1.8 G supine, respectively, compared to 0 G. Similar results were obtained for launch posture, in which the effects of changing intrathoracic pressure dominated those of hydrostatic pressure. Compared to 0 G, cardiac output decreased 0.9% for 1 G launch and 15% for 1.8 G launch. In sitting and standing, the position of the heart above the hydrostatic indifference level caused the effects of changing hydrostatic pressure to dominate those of intrathoracic pressure. Compared to 0 G, cardiac output decreased 13% for 1 G sitting and 23% for 1.8 G sitting, and decreased 17% for 1 G standing and 31% for 1.8 G standing. For a posture change from supine to standing in 1 G, cardiac output decreased, consistent with the trend necessary to explain orthostatic intolerance in some astronauts during postflight stand tests. Simulated lower body negative pressure (LBNP) in 0 G reduced cardiac output and mean aortic pressure similar to I G standing, suggesting that LBNP provides at least some cardiovascular stimuli that may be useful in preventing postflight orthostatic intolerance. A unifying concept, consistent with the Frank-Starling mechanism of the heart, was that cardiac output was proportional to cardiac diastolic transmural pressure for all postures and gravitational accelerations.
The conversion mechanism was studied in vivo in the pulmonary circulation of the intact anesthetized dog and in vitro in plasma by using L-Leu-angiotensin I, D-Leu-angiotensin I, and des-Leu-angiotensin I which had been synthesized by the solid-phase technique. The results obtained indicate that pulmonary conversion in vivo and plasma conversion in vitro occur via a dipeptidylcarboxypeptidase and that a D-amino acid at the C-terminus prevents conversion.
The lung is profoundly affected by gravity. The absence of gravity (microgravity) removes the mechanical stresses acting on the lung paranchyma itself, resulting in a reduction in the deformation of the lung due to its own weight, and consequently altering the distribution of fresh gas ventilation within the lung. There are also changes in the mechanical forces acting on the rib cage and abdomen, which alters the manner in which the lung expands. The other way in which microgravity affects the lung is through the removal of the gravitationally induced hydrostatic gradients in vascular pressures, both within the lung itself, and within the entire body. The abolition of a pressure gradient within the pulmonary circulation would be expected to result in a greater degree of uniformity of blood flow within the lung, while the removal of the hydrostatic gradient within the body should result in an increase in venous return and intra-thoracic blood volume, with attendant changes in cardiac output, stroke volume, and pulmonary diffusing capacity. During the 9 day flight of Spacelab Life Sciences-1 (SLS-1) we collected pulmonary function test data on the crew of the mission. We compared the results obtained in microgravity with those obtained on the ground in both the standing and supine positions, preflight and in the week immediately following the mission. A number of the tests in the package were aimed at studying the anticipated changes in cardiopulmonary function, and we report those in this communication.
To investigate the possible effect of hypobaria on ventilation (VE) at high altitude, we exposed nine men to three conditions for 10 h in a chamber on separate occasions at least 1 week apart. These three conditions were: altitude (PB = 432, FIO2 = 0.207), normobaric hypoxia (PB = 614, FIO2 = 0.142) and normoxic hypobaria (PB = 434, FIO2 = 0.296). In addition, post-test measurements were made 2 h after returning to ambient conditions at normobaric normoxia (PB = 636, FIO2 = 0.204). In the first hour of exposure VE was increased similarly by altitude and normobaric hypoxia. The was 38% above post-test values and end-tidal CO2 (PET(CO2) was lower by 4 mmHg. After 3, 6 and 9 h, the average VE in normobaric hypoxia was 26% higher than at altitude (p < 0.01), resulting primarily from a decline in VE at altitude. The difference between altitude and normobaric hypoxia was greatest at 3 h (+ 39%). In spite of the higher VE during normobaric hypoxia, the PET(CO2) was higher than at altitude. Changes in VE and PET(CO2) in normoxic hypobaria were minimal relative to normobaric normoxia post-test measurements. One possible explanation for the lower VE at altitude is that CO2 elimination is relatively less at altitude because of a reduction in inspired gas density compared to normobaric hypoxia; this may reduce the work of breathing or alveolar deadspace. The greater VE during the first hour at altitude, relative to subsequent measurements, may be related to the appearance of microbubbles in the pulmonary circulation acting to transiently worsen matching. Results indicate that hypobaria per se effects ventilation under altitude conditions.
To compare the relative contributions of gravity and vascular structure to the distribution of pulmonary blood flow, we flew with pigs on the National Aeronautics and Space Administration KC-135 aircraft. A series of parabolas created alternating weightlessness and 1.8-G conditions. Fluorescent microspheres of varying colors were injected into the pulmonary circulation to mark regional blood flow during different postural and gravitational conditions. The lungs were subsequently removed, air dried, and sectioned into approximately 2 cm(3) pieces. Flow to each piece was determined for the different conditions. Perfusion heterogeneity did not change significantly during weightlessness compared with normal and increased gravitational forces. Regional blood flow to each lung piece changed little despite alterations in posture and gravitational forces. With the use of multiple stepwise linear regression, the contributions of gravity and vascular structure to regional perfusion were separated. We conclude that both gravity and the geometry of the pulmonary vascular tree influence regional pulmonary blood flow. However, the structure of the vascular tree is the primary determinant of regional perfusion in these animals.
Exposure to high altitudes can result in the evolved-gas condition referred to as decompression sickness (DCS). Ultrasonic monitoring techniques have clearly demonstrated the presence of venous gas emboli (VGE) during decompression. Although important to DCS research and our understanding of the physiological mechanisms of this condition, Venus gas emboli have not been considered clinically hazardous, unless in extreme numbers. Arterial gas emboli (AGE), on the other hand, are generally viewed with great concern. Arterial gas emboli can enter the cerebral arterial circulation and arrest blood flow resulting in potentially serious injury. Left ventricular gas emboli were observed with echo imaging in five volunteer subjects during exposure to simulated altitude. These serendipitous findings occurred during altitude exposure under 3 separate research protocols involving 79 subject exposures. The voluntary, fully informed consent of the subjects used in this research was obtained as required by AFR 169-3. A Hewlett-Packard SONOS 1000 Echo Imaging System was used to monitor for precordial gas emboli. The improved resolution of the SONOS 1000 appears to account for these new findings. Four subjects had high incidence DCS and VGE during previous research flights. One subject only had one flight. The altitudes and AGE onset times for the five cases were: (1) 25,500 ft/2:23, (2) 29,000 ft/0:27, (3) 19,500 ft/3:49, (4) 29,500 ft/3:15, and (5) 29,500 ft/1:31. In all five cases, at the time of AGE onset, the VGE scores were high from all monitored locations. Four of the cases were symptomatic at the time of AGE onset (pain and skin mottling). No cerebral manifestations were observed. All subjects were immediately recompressed to ground level and successfully treated with 2 hours of post-breathing or with hyperbaric oxygen therapy. In conclusion, previously undetected AGE were demonstrated--with and without DCS symptoms--during exposure to altitude. It appears that this gas transferred from the venous side to the arterial side via either intracardiac defects or the pulmonary circulation. The clinical and operational implications of this finding are yet to be determined.
The cardiovascular response to 1 h of 60-deg head-down tilt was studied in 12 male subjects, ages 30-39 years, to simulate the early effects of weightlessness. Fluid shifts, hemodynamic variables, and indices of myocardial contractility were evaluated by utilizing electrocardiography, systolic time intervals, impedance cardiography, sphygmomanometry, and measurement of calf circumference. Most cardiovascular variables remained stable throughout the initial 30 min of the protocol, even though translocation of fluid from the legs to the thorax commenced immediately with the onset of head-down tilt. In contrast, minutes 30-60 were characterized by reduced stroke volume, cardiac output, mean stroke ejection rate, and Heather index concomitant with an elevation in mean arterial pressure. Intrathoracic fluid volume continued to increase, while leg volume continued to decrease. This latter physiological response suggests intrathoracic sequestration of fluid volume; blood was apparently redistributed to the pulmonary circulation rather than being retained in the great veins.
A whole-body mathematical model (10) for simulating intracranial pressure dynamics. In one embodiment, model (10) includes 17 interacting compartments, of which nine lie entirely outside of intracranial vault (14). Compartments (F) and (T) are defined to distinguish ventricular from extraventricular CSF. The vasculature of the intracranial system within cranial vault (14) is also subdivided into five compartments (A, C, P, V, and S, respectively) representing the intracranial arteries, capillaries, choroid plexus, veins, and venous sinus. The body's extracranial systemic vasculature is divided into six compartments (I, J, O, Z, D, and X, respectively) representing the arteries, capillaries, and veins of the central body and the lower body. Compartments (G) and (B) include tissue and the associated interstitial fluid in the intracranial and lower regions. Compartment (Y) is a composite involving the tissues, organs, and pulmonary circulation of the central body and compartment (M) represents the external environment.
INTRODUCTION: Pulmonary altitude decompression sickness (DCS) is a rare condition. 'Chokes' which are characterized by the triad of substernal pain, cough, and dyspnea, are considered to be associated with severe accumulation of gas bubbles in the pulmonary capillaries and may rapidly develop into a life-threatening medical emergency. This study was aimed at characterizing early symptomatology and the appearance of venous gas emboli (VGE). METHODS: Symptoms of simulated-altitude DCS and VGE (with echo-imaging ultrasound) were analyzed in 468 subjects who participated in 22 high altitude hypobaric chamber research protocols from 1983 to 2001 at Brooks Air Force Base, TX. RESULTS: Of 2525 subject-exposures to simulated altitude, 1030 (41%) had symptoms of DCS. Only 29 of those included DCS-related pulmonary symptoms. Of these, only 3 subjects had all three pulmonary symptoms of chokes; 9 subjects had two of the pulmonary symptoms; and 17 subjects had only one. Of the 29 subject-exposures with pulmonary symptoms, 27 had VGE and 21 had severe VGE. The mean onset times of VGE and symptoms in the 29 subject-exposures were 42 +/- 30 min and 109 +/- 61 min, respectively. In 15 subjects, the symptoms disappeared during recompression to ground level followed by 2 h of oxygen breathing. In the remaining 14 cases, the symptoms disappeared with immediate hyperbaric oxygen treatment. CONCLUSIONS: Pulmonary altitude DCS or chokes is confirmed to be a rare condition. Our data showed that when diagnosed early, recompression to ground level pressure and/or hyperbaric oxygen treatment was 100% successful in resolving the symptoms.
Pulmonary and femoral arterial blood oxygen saturation decrease due to pulmonary arterial- venous shunting in anesthetized dogs subject to forward acceleration
Effect of oxygen breathing in resorption of gas embolism in vascular system of cats and on course of pulmonary pressure trauma
Blood saturation decrease due to regional pulmonary arterial venous shunting during exposure to transverse acceleration