The passage of gaseous emboli through the pulmonary circulation

Respiration PhysMogy (1967) 3,213-219;

m

North-Holkmd Publishing Company, .4msterdam

PASSAGE OF GASEOUS EMBOLI THROUGH PULMONARY CIRCULATION

THE

L. V. EMBRSON’,H. V. HEMPLEMANAND R. G. LENTLE’ Royal Naval Physiologicai Laboratory, Fort Road, Alverstoke, Hants., England

Abstract. Rats were exposed to pressures of air and oxy-helium varying between 100 and 130 pounds

per square inch for 1 hour. Decompression to atmospheric pressure generated gaseous emboli in the circulatory system, and 37 % of the animals died within 1 hour of reaching atmospheric pressure. Post mortem examination revealed that only the highest pressure used gave bubbles in the pulmonary vein or left auricle. Air injected intravenously failed to appear in the arterial system, but air injected intraarterially did appear intravenously. It is concluded that it is difficult, if not impossible, under normal physiological conditions for gaseous emboli to pass through the pulmonary circulation. Bubbles were seen to grow, and move, back up the arterial circulation, following decompression. This only seemed to occur when the animal was near to death from decompression sickness. Decompression sickness Gaseous emboli

~ygen-helium

mixture

It has been shown that small glass beads of 125 ~1diameter can pass readily from the pulmonary arterial into the pulmonary venous circulation of perfused dog lungs. Larger beads caused a rise in pulmonary blood pressure, but sizes up to 420 ~1could be transported through the lung circulation, possibly by the opening of arterio-venous shunts (NIDEN and A~IADO, 1956). This would seem to indicate that the passage of small gaseous emboli through the lung circulation should also be easily a~omplished. In support of this supposition there is the evidence of WAGNER(1945), who observed the pial vessels of cats following rapid decompression from an air pressure of 75 pounds per square inch. It was observed that post decompression bubbles first appeared in the pial arteries and the deduction was made that “The results of this study seem !to indicate that the occurrence of gas bubbles in the pial vessels is a consequenk of the passage of these bubbles from the lungs through the heart and into the arterial’ system.” Accepted for publication 25 May 1967. 1 PresentAddress: Zoology Department, Exeter University, England. a Present Address: University College Hospital, London, England. 213

214

L. Y. EMERSON,

H. V. ~PL~N

AN?3 R. G. LENTLE

In opposition to the idea that the gas emboli can pass through the pulmonary capillaries there is the experimental evidence of LEVERef al. (19661, who were unable to find any bubbles in the pulmonary vein or left auricle, following rapid decompression of mice from nitrogen-rich atmospheres at 150 lbs per square inch pressure. This absence of bubbles was particularly striking in view of the presence of bubbles in all other main vessels examined. In this laboratory a series of experiments using rats as the experimental animals had also shown the absence of bubbles in the left auricle and pulmonary vein, both as a result of air injected into the vascular system at atmosphe~c pressure and from de~omp~ssion-induced gaseous emboli. The experiments about to be described give more detailed observations over a larger set of conditions for the release of gaseous emboli into the circulation, to see whether these emboli could pass through the pulmonary capillary bed of rats. Mi?thOdS The animals used throughout these experiments were female Wistar rats weighing between 230 and 260 g. Prior to exposure to high pressure each rat was placed in a cylindrical open mesh cage which served to restrict its movements, and also prevented any direct contact with the other rat being exposed at the same time. It is necessary to have some means of separating them, or otherwise they huddle together and upset t:he tem~rature conditions of the experiment. Both rats in their cylindrical cages were lowered into a steel pressure chamber the temperature of which was controlled by immersion in a large bath of thermostatted fluid. Variation of temperature, measured by a thermister probe inside the chamber, did not exceed 0.5 “C. The rats were compressed at a uniform rate of 50 pounds per square inch per minute, and exposed at pressures ranging between 100 and 130 pounds per square inch for 1 hour. This was followed by decompression at a rate of 20 pounds per square inch per minute back to atmospheric pressure, This relatively slow rate of decompression was chosen to avoid the possibility of pulmonary barotrauma. Three principal series of experiments were performed. In the first series the rats were removed from the compression chamber and observed for a period of one hour. If the animals died during this one hour period a post mortem examination of the main arteries and veins of the body took place immediately. If the animals survived the exposure and the one hour post decompression period, they were sacrificed by being given an overdose of intraperitoneally injected nembutal, and their biood vessels were examined as before. If no bubbles visible to the single-lens assisted eye were present, then this vessel was classified as having a bubble score of 0. The value 1, meant that a single bubble or a few tiny bubbles were present. The value 2 meant that several bubbles were present, but there was still plenty of blood in the vessel. Finally, if so much gas was present that hardly any blood could be seen within the vessel, this was given as 3. It was ascertained from measurements with a projection microscope, that bubbles smaller than 0.1 mm diameter would escape observation in the pulmonary vein by this particular technique, unless several came together in a close grouping.

GASEOUS EMBOLI IN THE PULMONARY

215

CIRCULATION

In the second series of experiments the rats were compressed at 50 psi/min with pure dry air and held at 120 psi for 30 min, followed by decompression back to atmospheric pressure at a rate of 20 psi/min. Immediately on arrival at atmospheric pressure they were anaesthetised with diethyl ether and a median ventral incision made in the abdominal cavity and the viscera deflected so that the posterior dorsal aorta and vena cava were visible. These main vessels were then kept under observation to see where bubbles appeared and at what time after decompression. In the third series of experiments the animals were exposed to raised pressures for a period of 1 hour, and at the end of this time pure gas was blown through the pressure chamber and the oxygen content of the gas gradually reduced to a fatal level. Upon the death of the animal the pressure was reduced, as before, at 20 pounds per square inch per minute. ReSUltS

Tables 1 and 2 summarise the findings of the first series of experiments. The second and third columns of these tables show the results from the two different gas mixtures used. Helium and nitrogen have very different physical properties, and hence the number, size, and ease of formation of bubbles, would be expected to be different for these two gases. The fourth column compares the results obtained by a marked change in the temperature of exposure, which will cause a change in the physiological variables contributing to bubble distribution via the vascular system. Despite these

TABLE

Animals dead within one hour of

Blood vessel

1

termination of decompression-“bubble score” (see text) 3 Rats He/OSat

8 Rats air at

5 Rats air at

15 “c*

15 “c*

1 “C*

Pulmonary veins

0

Left auricle Left ventricle Aorta Posterior vena cava Right auricle Right ventricle Pulmonary arteries Carotid arteries Jugular veins Subclavian veins Renal arteries Renal veins Mesenteric arteries Hepatic portal vein

0 1 8 6 7 8 7 6 5 4 8 7 9 6

3 2 8 24 19 17 17 22 23 12 12 23 18 24 11

All Rats*

0

3

1 10 15 1.5 12 11 14 15 11 11 15 15 15 15

19 41 40 36 36 43 44 28 27 46 40 48 32

* Note: Maximum possible bubble score per vessel equals number of animals

3

X

3.

216

L. V. EMERSON, H, V. HFXWLEMAN AND R. C. LENTHE TABLE 2 Animals surviving one hour after termination Blood vessel

Pulmonary veins Left auricle Left ven#ricSe Aorta Posterior vena cava Right auricle Right ventricle Pulmonary arteries Carotid arteries Jugular veins Subclavian veins Renal arteries Renal veins Mesenteric arteries Hepatic portal vein

11 Rats H&e at 15 “c*

of decompression-“bubble 5 Rats air at 15 “c*

11 Rats air at 1 “C’

score” (see text) All Rats*

0

0

0

0

0

0

0

0

0

1 3 4 3 5 3 2 0 0 2 2 3 2

2

3 6 12 7 13 9 3 0 0 6 10 5 7

0

6 1

3 2 0 0 0 1 6 0 3

3 2 3 5 4 1 0 0 3 2 2 2

* Note: Maximum possible bubble score per vesse1 equals number of animals

x

3.

large changes in the physical and physiological conditions, the results are qualitatively similar in all the columns. The findings of LEVERet al. (1966) that it was unusual to see any bubbles in either the pulmonary vein, or left auricle, were confirmed. Only 1 animal from a total of 43 showed bubbles in the pulmonary vein, This particular animal had been exposed to a pressure greater than any used subsequently and was moribund on arrival at atmospheric pressure. The second point noted was that very few bubbles were seen in the main vessels of animals surviving the 1 hour post-decompression waiting period. Nevertheless it was surprising to find a few animals with considerable volumes of gas in their vessels and yet still behaving in a normal manner prior to being sacrificed at the end of the waiting period. The third fact of importance was that bubbles were present in both arteries and veins, even in those animals surviving for 1 hour. Bubbles in the heart, the posterior vena cava, and the aorta, were quite a consistent finding. The fact that bubbles had been seen in the pulmonary vein of only one rat, and that this was an exceptional case where the exposure pressure had been unusually severe, was considered of such importance that it was decided to check whether very small bubbles could be detected within the ~~munary vein, following death due to decompression sickness. Accordingly on five separate occasions the wall of the pulmonary vein was pierced by a Iength of clear glass capillary tube, and blood was drawn up into the tube by capillary attraction.

GASEOUS EMBOLI IN THE PULMONARY

CIRCULATION

217

This column of blood was examined microscopically for the presence of small bubbles. None could be found. A similar test on the blood in the vena cava showed the presence of small bubbles about 0.1 mm in diameter. It was concluded that if bubbles are present in the pulmonary vein then they must either be smaller than red blood corpuscles or very small in numbers. In the second series of experiments where the aorta and posterior vena cava were watched for the appearance of bubbles the following observations were made on 10 animals exposed to 120 pounds per square inch pressure of air, and then decompressed at the standard rate of 20 pounds per square inch per minute. Initially there were no bubbles visible in either the aorta or the posterior vena cava. After a while small bubbles first appeared in the iliac veins and flowed with the blood into the posterior vena cava and towards the heart. Gradually the size of bubbles in the vena cava increased. No bubbles, as yet had been seen in the aorta. Finally large bubbles were seen to enter the aorta mainly from the iliac arteries, and proceeded to flow towards the heart. This flow was not smooth, since the heart was still beating and thus the bubbles in both aorta and vena cava at this stage were seen to oscillate backwards and forwards. As the bubbles in the aorta flowed in the retrograde direction towards the heart the heart beat began to weaken and then ceased. In the third series of experiments where the animals were killed whilst at depth by means of substituting inert gas for oxygen the post mortem examination revealed the following facts. When highly soluble argon gas had been used at a pressure of 150 pounds per square inch then every tissue and vessel of the body showed large numbers of bubbles. However when less soluble nitrogen was used and the pressure of exposure lowered to 130 pounds per square inch it was noted that initially no bubbles were visible in the vena cava or the aorta but that after a few seconds a pronounced crepitation occurred and bubbles could be seen forcing themselves up the minor arteries and veins into both main vessels. It was thought profitable at this juncture to check whether air injected intravenously fails to appear in the arterial circulation as occurs in dogs and rabbits. (GRAMENITSKII and SAVICH, 1964). This was confirmed using anaesthetised rats and injecting 0.5 cc of air into the posterior vena cava. No air was seen to come down the arteries under observation in the abdominal cavity. A further experiment was then pet-for ed on a second animal, by putting a similar quantity of air into the aorta, when a l! er a few seconds a great deal of it was seen to be returning up the vena cava towards the heart. It was evident that air could readily pass through tissues supplied by the systemic circulation but could not pass at all, or only in very small amounts which escaped observation, through the pulmonary bed. This confirmed with injected air at atmospheric pressure the findings in the first series of experiments, where the air had been released from a super-saturated state. It is difficult, if not impossible, under normal physiological conditions to pass bubbles through the pulmonary bed.

If one considers the possibility of pushing gas through blood vessels the size of

218

L. V. EMERSON, H. V. HEMPLEMAN ANDR. G. LENTLE

capillaries then it becomes clear that unless the bubbles are smaller in diameter than the capillaries, considerable pressures will be required due to the surface tension effect. Taking for example a capillary of 10 /J diameter and using a surface tension value for blood of 50 dynes/cm (WALDER,1947), calculation shows that the pressure necessary to force gas through such a capillary will be 0.2 x lo6 dynes per square centimetre, which is very nearly 150 mm Hg pressure. Thus a reasonable systolic blood pressure will ensure ready passage of gas through a good deal of the tissue capillary bed. It is a totally different situation in the pulmonary capillary bed where the pressure in the pulmonary artery is an order of magnitude lower, approximately 30-40 mm Hg. From both the decompression experiments and also those where air was injected into the venous system it would seem that only very small Arnold of gas can pass through the pulmonary circulation, unless minute bubbles of a diameter less than the average red cells are formed. This latter possibility seems unlikely as the excess pressure inside such bubbles causing them to re-dissolve is of the order of 200 mm Hg. Thus if bubbles are observed first in the arterial vessels and later in the venous vessels following decompression, then this could mean that the bubbles are formed in the arteries, or that they are formed in the tissue capillary bed and have somehow managed to move for a time contrary to the main direction of blood flow before being caught into the main stream flow and swept into the field of view. Some time will then be spent before this gas re-appears in the venous outflow. The idea that bubbles are formed in the arteries is a simple one which would be discounted because arterial blood is assumed to be cleared of excess inert gas. However if one examines the situation more closely it is seen that many arterial vessels pass close to, or through, regions of poor blood supply with low oxygen requirements. This means that whereas the arterial oxygen content of the blood will change little when passing through or near, such parts of the body the blood inert gas content may change markedly by diffusion from the surrounding tissue. The limits of this situation can be assessed in a semi-quantitative manner. In the case of a small artery of a diameter the order of 0.2 mm it will only be necessary to consider diffusion distances of the order of 20 p separating the lumen of the vessel from the tissues. ROUGHTON(1952) considered diffusion in systems of physiological interest and it is clear from his work, that diffusion of molecules of nitrogen over distances of this order will only take fractions of a second. Thus there is a strong possibility that following decompression the smaller arteries and arterioles carry a considerable volume of dissolved inert gas in excess of the ambientpressure. With regard to the second possibility that bubbles could flow in a direction contrary to the arterial blood flow and hence distribute themselves randomly throughout the circulation, this is exactly what was observed in the second series of experiments. If for some reason there is a cessation of venous outflow in any tissue then the bubbles enlarge and back up the arterial vessel or vessels supplying this tissue until they reach the junction with another artery in which blood flow is still active. At this junction point the embolus does not enlarge further but commences injecting small bubbles

GASJ3XJS EMBOLI IN THE PULMONARY

CIRCULATION

219

into the active artery. These are then swept on down to help re-create a similar situation in other tissues. An interesting observation made in these rats was that when bubbles had coalesced and were big enough to Gil the lumen of main arteries, such as the iliac and abdominal aorta, they could be seen moving towards the heart. The mechanics of this situation is far from clear but the observations made on numerous occasions are undoubted. When bubbles are seen to be tracking up to the heart in both the aorta and the vena cava the heart beat becomes irregular, and weaker, and ceases altogether after two or three minutes. So far as can be assessed from the evidence accummulated here and from other workers it would seem that following decompression, bubbles are formed mainly in the arterial network. These small bubbles pass through the tissue bed and grow in size. If the rate of bubble growth is sufficient to block up the capillaries, or if there is a closure of the minor vessels, then growth back up the arterial network will commence. Once this process has commenced it tends to accelerate, because blockage of one minor artery causes bubbles to grow back up the artery and this feeds gas into other arteries, thus helping to block these as well. In addition the bubbles prevent the elimination of dissolved gas via the blood stream, and hence diffusion of dissolved gas into the bubbles increases. These events lead to circulatory embarrassment, faulty action of the heart, blockage of the pulmonary artery, and hence to the death of the animal. References GRAME~W, P. M. and A. A. SAVICH (1964). Results of Experimental Analysis of Decompression Air Embolism. Chapter III. The effect of the gas medium and pressure on body functions. M. P. Brestkin. Translated from the Russian original by Israel Program for Scientific Translations for N.A.S.A., Jerusalem, 1965. LEVER,M. J., K. W. MILLER, W. D. M. PATONand E. B. %UTH (1966). Experiments on the genesis of bubbles as a result of rapid decompression. J. Physiol. (Land.) 184: 964969. N~EN, A. H. and D. M. AVIADO JR. (1956). Effects of pulmonary embolism on the pulmonary circulation with special reference to arterio-venous shunts in the lung. Circulation Res. 4: 67-73. ROUGHTON,F. J. W. (1952). Diffusion and chemical reaction velocity in cylindrical and spherical systems of physiological interest. Proc. Roy. Sot. B. 140: 203-229. WAGNER, C. E. (1945). Observations of gas bubbles in pial vessels of cats following rapid decompression from high pressure atmospheres. J. Neurophysiol. 8 : 29-32. WALDER,D. N. (1947). Studies in the susceptibility to decompression sickness. M.D. Thesis, University of Bristol.