Are Pulmonary Capillaries Susceptible to Mechanical ... - Journal

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20 increase in traumspuhmomiary pressumre or Ptnu in tiuese comuditiomss. Measumremsient of blood-gas barrier tluickmuess reveaheci a thsickening of due interstitium at high iuuusg volimmsue, consistent with the presence of eciemsia. Disruptions of the eiuciothehitmmuu with red blood cells protruding into tlse opening were foumudl both on the tisimu mine! thsick sides of time blood-gas harrier. As imu ouur previous sttmdv at low lumumg the batsemuuemmt mmuemiu- brane was continuouus in abouut half of the endothiehiat and epithselial breaks. Exasmmsinautiouu by scamsmuimug electron miii- crosc’op reveauled thiast at highs lummmg ‘ohumne’, the hireatks temucled to be of simsmilatr lemmgtls humt muasrro\s’er thmamu sit low hsmusg s’ohuunme, for a sinsilaur Ptnu. Fewer hreauks we’re’ oriented! perpendictular to time capillary axis while breaks vithm mmuultipie segmsuents of differemut oriemutaitiomu, muot seems at low lung voluuusie, were foummud. They were possibl’ clue to tlse increatseci svssll stress in au directions with thue tmmsiformiu stretchsiuig of time alveolar waull ait high luusg voluumue. Commuparison cif msseasuuremsmesmts 1)51 SE M amid TE M indicated that simsuilar ruptlmres were anasIy’zed by the two techniques.’’ Time mncreaused vumimierabihitv of the pumiumsomman’ caupiltaur- ies to stress failure at high degree of immflation provides at physiologic msuechsanismss for studies sisowiusg increased psulmssomsarx’ mnicrovascuiar pernueabmiit withu o’erimsf1atiomm, ‘‘ It hams imusportant immiplicsutions in tlse criticsul care setting where greaut casre slsouuld lie tsikeuu to 1)rcveuit datussasge to the lung clue to overdistemusioms citmrimug usseclsanicaul vemsti- lation. As poimuted out elsewhere,7 this is often at catchm-22 situmsstion becaumse high imuflaution pressumres mimic! lsighs levels of positive emud-expiratorv pressumre are msecessarx’ to umiaius- tasium arterial Po, at sin ascceptambie level. However, the imscreaseci stress oms tise blood-gats harrier hiecasuse of tIme highs inflaution msmsukes it s’umhmmerable to ruuptture at a lower capihlasrs’ Ptmus, at process fumrther accelerated if pastimologic chamuges hatve occurred. ie, tIme l)lo(ud-gaus baurrier or edt- lagen IV are weakemsed. I z 4o 50 E E F: LUNG VOLUME low high Endo- Epi- thehium thelium Endothelium iii 111 Epi- thelium 1L1 tm 32.5 cm H20 tm 52.5 cm 1120 Downloaded From: http://journal.publications.chestnet.org/ on 07/30/2013 P\TIu(iI’IussI(iu.o;uc (Nsu:#{231}mdFx(:!-;s ou. Sru,ess Fsuiu iii’; u’ Fu;uuu’: 4. I Iistograumiu of auveu’auge mmuuumlhi,’r of’ hu’eaks per uiuitlimumeter houiumdatrv leumgthm oh (‘uudotlme’liuuuuu atmm(I epithmeti m ummstt 20 ( Im1gb hummug soh mummmc) some1 .5 c umm11,0 trauuuspuulmmmuimmaurs- pressure (loss’ luuusg \-ol uuumme),Ate,’i.sk, sigumi I ic’asuutlv greater (p
tions where the extracehlular matrix weakened, for example in Goodpasture’s syndrome where autoantibodies attack type IV collagen,25 causing bleeding in the lung and also glomeruli. We recently obtained evidence that exercise-induced pulmonary hemorrhage (EIPH) in thoroughbred race- horses is caused by stress failure of pulmonary capillaries.26 This study was done in collaboration with Drs. Eric Birks, James Jones, John Pascoe, and Walter Tyler of the School of Veterinary Medicine, University of California, Davis. The lungs of three thoroughbred horses with known EIPH were removed and fixed for electron mi- croscopy after the horse had galloped at high speed (13 to 16 m/s) on a treadmill. Evidence of intrapulmonary bleeding was confirmed by bronchoscopy in one animal, Tissue fixation was either by airways instillation (one animal) or vascular perfusion of glutaraldehyde solution at 30 ± 5 cm H,O Ptm (two animals). Ultrastructural evidence of stress failure of pulmonary capillaries was the presence of a large number of red blood cells in the interstitium, disruption of the capillary endothehiai or alveolar epithehial layers, protemneous material amid red blood cells in the alveolar spaces, interstitial edema, and fluid-filled protrusions of the endothelium into the capillary lumen.26 These are the same appearances we have found in rabbit lungs exposed to high capillary transmurai pressure . Pulmonary vascular pressures are extremely high in thoroughbred horses during galloping. Jones and cowork- ers27 measured pulmonary arterial and heft atrium pressures of up to 120 mm Hg and 70 mm Hg, respectively, in thoroughbreds galloping at speeds up to 10 rn/s,27 indicating that capillary pressures must also be very high. These very high vascular pressures are associated with the extremely high cardiac outputs (>750 mI/mimi/kg) achieved in these animals, which require very high left atrial pressure for adequate ventricular filling.26 At the same time, the extremely high VO,max achieved during maximal exercise (180 mI/mm/kg) requires that the blood- gas barrier be extremely thin. However, exercise-induced hypoxemia in thoroughbreds during heavy exercise was shown to be the result of diffusion limitation,25 indicating that the barrier could not be any thicker without further limitation to VO2m’ax. In other words, selection for increased aerobic performance imposes contradictory requirements on the heart-lung system. In thoroughbreds, those requirements have reached the point of failure of the blood-gas barrier. The selective breeding of thoroughbreds for a large number of generations has pro- vided animals with enormous 0, uptake rates, which necessitate not only a very thin pulmonary blood-gas barrier but also extremely high cardiac outputs, which in turn require pulmonary pressures to be so high that they exceed the mechanical strength of the thin blood-gas barrier, causing failure of pulmonary capillaries and alveolar hemorrhage.26 Interestingly, while a large number of red blood cells were found in the alveoli and interstitium in areas show- ing clear abnormalities macroscopically, actual endothe- hal and epithehial breaks were difficult to find. This was probably due to the reversibility of ruptures once the vascular pressure was reduced, fronu the end of the gallop to tissue fixation 60 to 70 mi’tin later. In addition, platelets and cytoplasmic extension of leukocytes were seen in close vicinity to the exposed basement membrane at the site of disruption of the capillary wall, suggesting platelet and white blood cell activation and the initiation of an inflammatory process.26 As mentioned earlier, inflammatory markers were found in lavage fluid of rabbit lungs perfused at high pressure,24 as well as in bronchoalveolar fluid of patients with HAPE,23 suggesting that stress failure of pulmonary capillaries is the mechanism of HAPE. In summary, pulmonary capillaries are subjected to high mechanical stress in spite of their small radius of curvature, because of the extreme thinness of the alveolar wail, which in turn is required for the adequate transfer of gases by passive diffusion. The contradictory design requirements imposed on the blood-gas barrier, which must be thin enough not to limit diffusion but at the same time very strong to withstand high stresses across such a thin barrier, have only recently been recognized. Stress failure of pulmonary capillaries plays a role in several pathophysiologic conditions causing high-permeability edema and pulmonary hemorrhage. A dramatic example is exercise-induced pulmonary hemorrhage in thoroughbred horses where selective breeding for extreme aerobic performance over a large number of generations has allowed the cardiovascular system to develop beyond the mechanical strength of the pulmonary blood-gas barrier. ACKNOWLEDGMENTS: This work was done in collaboratioms witim Michael Costello, Ann Elliott, Zhenxing Fu, Sanli Kurdak, Yasuo Namnba, Koicimi Tsukinuoto, and Reoato Prediletto. REFERENCES 1 Low FN. The pulmonary alveolar epithelium of laboratory mammals amid man. Anat Bee 1953; 117:241-63 2 Gehr P, Bachofen M, Weibel ER. The normal human lung: ultrastructure and morpisometric eutimation of diffusion capacity. Respir Physioh 1978; 32:121-40 3 West JB, Tsukimoto K, Mathieu-Costelbo 0, et al. Stress failure in pulmonary capillaries. J AppI Physiol 1991; 70:1731- 1 OBS 36th Annual Aspen Lung Conference Downloaded From: http://journal.publications.chestnet.org/ on 07/30/2013 42 4 West JB, Mathieu-Costello 0. Strength of the pulmonary blood-gas barrier. Respir Physiol 1992; 88:141-48 5 Dempsey JA, Hanson PC, Henderson KS. Exercise-induced alveolar hypoxemia in healthy huuman subjects at sea-level. Physiol (Lond) 1984; 355:161-75 6 Wagner PD, Gale GE, Moon RE, et al. Pulmonary gas exchange in humans exercising at sea level and simulated altitude. J AppI Physiot 1986; 61:260-70 7 West JB, Mathieu-Costello 0. Stress failure of pulmonary capillaries in the intensive care setting. Schweiz Med Wschr 1992; 122:751-57 8 West JB, Mathieu-Costetto 0. Stress failure of puilmonary capillaries: role in lung and heart disease. Lancet 1992; 340:762-67 9 Crouch EC, Martin CR, Brody jS. Basement membranes. In: Crystal RC, West JB, Barnes PJ, et al, eds. The lung: scientific foundatiomis. New York: Raven Press Ltd. 1991; 42 1-37 10 Glazier JB, Hughes JMB, Maloney JE. et al. Measurements of capillary dimensions and blood votuume in rapidly frozen lumsgs. J AppI Physiol 1969; 26:65-76
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