Search PubMed⌕ Search

Biomedical subjects

O Mathieu-Costello

Publications and source records attributed to O Mathieu-Costello.

At least 73 records · Page 4Linked to original sources
PubMed1994

Microcirculatory structure-function relationships in skeletal muscle of diabetic rats.

The effects of streptozotocin-induced diabetes on microcirculatory structure-function relationships in skeletal muscle were studied in control (C) and diabetic (D; 65 mg/kg streptozotocin ip) rats 6-8 wk after injection. Capillary exchange capacity was determined from measurements of capillary filtration coefficient (CFC) and permeability-surface area product (PS) for 51Cr-labeled EDTA in maximally vasodilated (papaverine), isolated hindquarters of C (n = 9) and D (n = 12) rats. Capillary numerical density, length, surface area, capillary geometry, and muscle fiber cross-sectional area were determined using morphometric methods in perfusion-fixed plantaris muscles from a second series of C (n = 5) and D (n = 6) rats. Hindquarters of D rats (61 +/- 3 g) weighed less than C rats (90 +/- 3 g) because of marked muscle atrophy. Minimal total vascular resistance was lower in D rats (P < or = 0.05), indicating an increased flow capacity. CFC was not different in C and D rats (0.0282 +/- 0.0020 vs. 0.0330 +/- 0.0025 ml.min-1.mmHg-1 x 100 g-1, respectively). The relationship between PS and flow was depressed in D rats (P < or = 0.05) compared with C rats, which indicated a reduced capillary diffusing capacity. Plantaris muscle weight was 41% less in D rats (174 +/- 9 vs. 293 +/- 11 mg; P < or = 0.001). Morphometric analysis revealed that muscle fiber cross-sectional area was reduced 39% in D rats, which, despite a lower capillary-to-fiber ratio (1.59 +/- 0.04 vs. 2.12 +/- 0.13; P < or = 0.001), resulted in a 27% increase in capillary density in D rats. Capillary diameter was less in D rats (3.58 +/- 0.12 vs. 4.51 +/- 0.23 microns; P < or = 0.005). Total capillary surface area was reduced 42% in D rats; however, capillary surface area per muscle fiber volume was unchanged in D rats (231 +/- 34 vs. 237 +/- 16 cm-1). These data indicate that there is remodeling of the capillary bed in skeletal muscle of D rats, resulting in a reduction in total microvascular surface area. The reduction in capillary surface area is proportional to the degree of muscle atrophy in D rats such that functional microvascular surface area per tissue mass (e.g., CFC) is unchanged. The lower diffusing capacity (PS) in D rats suggests that either small solute permeability is reduced and/or there is greater perfusion heterogeneity in D rat skeletal muscle.

Animals↗
PubMed1994

Microvascular compression during myocardial ischemia: mechanistic basis for no-reflow phenomenon.

Alterations in fiber size and capillary diameter were highly correlated with perfusion deficits after myocardial ischemia. After 5 (n = 3) and 30 (n = 5) min of global normothermic ischemia, isolated rabbit hearts were perfused with India ink and then with glutaraldehyde. Morphometric techniques were used to determine mean fiber cross-sectional area [a(f)], mean effective capillary diameter [d(c)], total and perfused capillary number per fiber area, and capillary length per fiber volume in subepicardium (Epi) and subendocardium (Endo). Sarcomere length was measured to differentiate between effects of fiber shortening and intracellular edema on a(f). After 30 min of ischemia, a(f) increased 41 (Epi) and 36% (Endo). Of these percentages, fiber shortening accounted for 2 (Epi) and 25% (Endo). Decreased d(c) was correlated with increased a(f) as well as reductions in perfused capillary number and length. Whereas intracellular edema had the greatest overall effect on a(f), fiber shortening accounted for a significant increase of a(f) in Endo, where perfusion deficits were most pronounced. These data support the hypothesis that microvascular compression consequent to increased a(f) contributes to perfusion deficits after myocardial ischemia.

Animals↗
PubMed1994

Protein, cell, and LTB4 concentrations of lung edema fluid produced by high capillary pressures in rabbit.

We previously demonstrated disruptions of the pulmonary capillary endothelium and alveolar epithelium at transmural pressures (Ptm) of 52.5 cmH2O in rabbit by electron microscopy. In the present study, we determined the characteristics of the alveolar edema fluid in this condition by carrying out bronchoalveolar lavage after blood perfusion for 10 min at Ptm of 12.5 (low), 32.5 (intermediate), and 52.5 cmH2O (high). At low Ptm, where our previous studies showed no ultrastructural changes, the volume of alveolar fluid obtained by urea dilution was very small, and the concentrations of proteins, cells, and leukotriene B4 (LTB4) in the bronchoalveolar lavage fluid (BALF) were low. However, at high Ptm the volume of alveolar fluid and the concentrations of total protein and cells in the BALF were greatly increased. The amount of LTB4 in the BALF also increased substantially from 6.0 to 49.5 micrograms (P < 0.001). Intermediate changes were seen at intermediate Ptm. We concluded that exposing pulmonary capillaries to high Ptm results in a high-permeability form of edema. In addition, the presence of LTB4 suggests that chemical mediators are released, possibly as the result of exposure of the reactive capillary endothelial basement membrane, as demonstrated by electron microscopy.

Albumins↗
PubMed1994

Myosin and actin filament lengths in diaphragms from emphysematous hamsters.

In vitro studies of the diaphragm from emphysematous animals have, in some instances, shown an alteration in its sarcomere length-tension relationship and a decreased maximal specific tension. To our knowledge, it has never been determined whether such functional changes may be indicative of ultrastructural adaptations, e.g., changes in filament lengths and thus cross-bridge number. To address this, we compared filament lengths in diaphragms from hamsters in which emphysema was induced by endotracheal instillation of elastase (E) 5 mo before the hamsters were killed with those from control hamsters (C; saline instillation). Diaphragms were then fixed by vascular perfusion with buffered glutaraldehyde in situ at airway pressures set to approximate the physiological range of lung volumes from residual volume (RV) to total lung capacity (TLC). Ultrathin sections (50-70 nm) were taken parallel to the muscle fiber axis and examined by electron microscopy (x33,000). Sarcomere and filament length measurements were calibrated using an actin periodicity of 39 nm and an M-band width of 86 nm to correct for dimensional changes during preparation. Emphysema increased the change in lung volume from -20 to +25 cmH2O airway pressure (from RV to TLC) by approximately 88%, and the displacement volume of excised lung at 0 cmH2O airway pressure was increased by approximately 138% on average. Neither myosin (C = 1.592 +/- 0.027; E = 1.572 +/- 0.035 micron; P = 0.72) nor actin (C = 1.210 +/- 0.035; E = 1.221 +/- 0.014 micron; P = 0.76) filament lengths were affected by emphysema. Thus, filament length changes do not underlie the diaphragm functional adaptations observed previously in emphysema.

Actin Cytoskeleton↗
PubMed1993

Stress failure of pulmonary capillaries in racehorses with exercise-induced pulmonary hemorrhage.

Bleeding into the lungs in thoroughbreds is extremely common; there is evidence that it occurs in essentially all horses in training. However, the mechanism is unknown. We tested the hypothesis that exercise-induced pulmonary hemorrhage (EIPH) is caused by stress failure of pulmonary capillaries. Three thoroughbreds with known EIPH were galloped on a treadmill, and after the horses were killed with intravenous barbiturate the lungs were removed, inflated, and fixed for electron microscopy. Ultrastructural studies showed evidence of stress failure of pulmonary capillaries, including disruptions of the capillary endothelial and alveolar epithelial layers, extensive collections of red blood cells in the alveolar wall interstitium, proteinaceous fluid and red blood cells in the alveolar spaces, interstitial edema, and fluid-filled protrusions of the endothelium into the capillary lumen. The appearances were consistent with the ultrastructural changes we have previously described in rabbit lungs at high capillary transmural pressures. Actual breaks in the endothelium and epithelium were rather difficult to find, and they were frequently associated with platelets and leukocytes that appeared to be plugging the breaks. The paucity of breaks was ascribed to their reversibility when the pressure was lowered and to the fact that 60-70 min elapsed between the gallop and the beginning of lung fixation. Capillary wall stress was calculated from pulmonary vascular pressures measured in a companion study (Jones et al. FASEB J. 6: A2020, 1992) and from measurements of the thickness of the blood-gas barrier and the radius of curvature of the capillaries. The value was as high as 8 x 10(5) dyn/cm2 (8 x 10(4) N/m2), which exceeds the breaking stress of most soft tissues. We conclude that stress failure of pulmonary capillaries is the mechanism of EIPH.

Animals↗
PubMed1993

Pulmonary interstitial edema in the pig after heavy exercise.

During exercise (especially in hypoxia), the alveolar-arterial O2 tension difference increases. This impairment of pulmonary gas exchange is caused partly by diffusion disequilibrium, but it has also been shown that an exercise-induced increase in ventilation-perfusion (VA/Q) inequality develops. Possible explanations of increased VA/Q mismatch include nonuniform pulmonary vasoconstriction, reduced gas mixing in the large airways, airway obstruction, and the development of interstitial pulmonary edema. To directly determine whether the latter develops in high-intensity short-term exercise, we exercised pigs on a motor-driven treadmill at the highest speed that they could sustain for 6-7 min. Heart rate reached 274 +/- 5 min-1 in the exercised group, confirming that the pigs reached a near-maximal level of exercise. While running, the pigs were killed by an intravenous overdose of pentobarbital. Postmortem, the lungs were immediately removed, drained of blood, weighed, and then airway fixed with 10% formaldehyde. Four tissue blocks of the right lung of each pig were taken from the ventral and dorsal areas of the upper and lower lobes, respectively. They were stained with hematoxylin and eosin and prepared for histological examination by light microscopy. There was no difference in the lung-to-body weight ratio between exercised pigs (7.72 +/- 0.87 g/kg) and a nonexercised control group (7.70 +/- 0.68 g/kg). However, we found a significantly higher percentage of pulmonary arteries with perivascular edema in exercised (33.8 +/- 3.4%) than in nonexercised pigs (20.0 +/- 4.0%; P < 0.02). Thus, perivascular edema (and thus possibly also parenchymal interstitial edema) can occur during short-term heavy exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Stress failure of pulmonary capillaries: role in lung and heart disease.

Pulmonary capillaries have extremely thin walls to allow rapid exchange of respiratory gases across them. Recently it has been shown that the wall stresses become very large when the capillary pressure is raised, and in anaesthetised rabbits, ultrastructural damage to the walls is seen at pressures of 40 mm Hg and above. The changes include breaks in the capillary endothelial layer, alveolar epithelial layer, and sometimes all layers of the wall. The strength of the thin part of the capillary wall can be attributed to the type IV collagen in the extracellular matrix. Stress failure of pulmonary capillaries results in a high-permeability form of oedema, or even frank haemorrhage, and is apparently the mechanism of neurogenic pulmonary oedema and high-altitude pulmonary oedema. It also explains the exercise-induced pulmonary haemorrhage that occurs in all racehorses. Several features of mitral stenosis are consistent with stress failure. Overinflation of the lung also leads to stress failure, a common cause of increased capillary permeability in the intensive care environment. Stress failure also occurs if the type IV collagen of the capillary wall is weakened by autoantibodies as in Goodpasture's syndrome. Neutrophil elastase degrades type IV collagen and this may be the starting point of the breakdown of alveolar walls that is characteristic of emphysema. Stress failure of pulmonary capillaries is a hitherto overlooked and potentially important factor in lung and heart disease.

Animals↗
PubMed1992

Stress failure of pulmonary capillaries in the intensive care setting.

Recent work shows that when the pressure in pulmonary capillaries is raised to high levels, ultrastructural changes occur in their walls including disruption of the capillary endothelium, alveolar epithelium, or sometimes all layers. Since the calculated wall stresses are extremely high, this condition is referred to as stress failure, and it results in a high permeability type of pulmonary edema, or even frank hemorrhage. Stress failure is believed to play a part in diseases where the capillary pressure is abnormally high, such as neurogenic pulmonary edema, high altitude pulmonary edema, exercise-induced pulmonary hemorrhage in racehorses, and perhaps some cases of the adult respiratory distress syndrome. Stress failure also occurs if the blood-gas barrier is weakened as in Goodpasture's syndrome. Another important cause is overinflation of the lung as may occur with mechanical ventilation and high inflation pressures. Stress failure of pulmonary capillaries is a hitherto overlooked and potentially important factor in the intensive care setting.

Altitude Sickness↗
PubMed1992

Distribution of red blood cell velocity in capillary network, and endothelial ultrastructure, in aged rat skeletal muscle.

Although age-related structural and functional changes in skeletal muscle have been described extensively, little is known about the accompanying hemodynamic and structural changes in the microvasculature. The objective of this study was to use the extensor digitorum longus muscle in mid-aged (12 months) and old (28 months) Fisher 344 male rats to evaluate (1) the distribution of microvascular flow in the resting state, (2) the distribution response to a complete 30-min tourniquet ischemia, and (3) the extent of damage of capillary endothelium. Using intravital video microscopy, the mean resting velocity of red cells in capillaries was found to be 3x larger in old rats while the distribution of velocity within the microvascular bed was as heterogeneous as that in mid-aged rats. The postischemic response was characterized by the same mean peak velocity, but a slower return to velocity to the preischemic level. Within the microvascular bed, there was a less uniform postischemic response among capillaries. No long-term effect of ischemia was seen as velocity was already stable at the preischemic level 20 min after the tourniquet release. There were no differences in the pre- and postischemic densities of perfused capillaries, wet/dry weight ratios, or the occurrence of damaged capillaries. Thus, in this muscle model, aging was associated with an increased resting flow but a remarkably unaffected long-term flow response to a vasodilatory stimulus and endothelial ultrastructure.

Aging↗
PubMed1992

Capillary-to-fiber geometry and mitochondrial density in hummingbird flight muscle.

We investigated structural characteristics for high O2 flux in hummingbird flight muscle, i.e. the most O2 demanding skeletal muscle per unit tissue mass among vertebrates. Pectoralis and supracoracoideus muscles of 3-4 g hummingbirds (Selaphorus rufus) were perfusion fixed in situ, processed for electron microscopy and analyzed by morphometry. Small fiber size (group mean +/- SE, 201 +/- 14 microns 2 at 2.1 microns sarcomere length), large capillary length per fiber volume (8947 +/- 869 mm-2) and high mitochondrial volume density per volume of muscle fiber (34.5 +/- 0.9%) were characteristic features of the muscles. Considering capillary supply and mitochondrial volume on an individual fiber basis showed that the size of the capillary-to-fiber interface (i.e. capillary surface per fiber surface) was also high in the muscles. Comparison with mammalian hindlimb pointed to a major role of the size of the capillary-to-fiber interface in providing a great potential for O2 flux rate from capillary to muscle fiber mitochondria in hummingbird flight muscle.

Animals↗
PubMed1992

High altitude pulmonary edema is caused by stress failure of pulmonary capillaries.

The pathogenesis of high altitude pulmonary edema (HAPE) is disputed. We propose that the mechanism is stress failure of pulmonary capillaries. The main features to be accounted for are the strong association with pulmonary hypertension, the high permeability characteristics of the edema, and the presence of inflammatory markers in the lung lavage fluid. When the capillary pressure is raised to about 40 mmHg in anesthetized rabbits, ultrastructural damage to the capillary walls is seen including breaks in the capillary endothelial layer, alveolar epithelial layer, and sometimes all layers of the wall. This results in a high permeability form of edema with the escape of high molecular weight proteins and blood cells into the alveolar spaces. In addition the basement membrane of the endothelial layer is frequently exposed, and we suggest that this highly reactive surface attracts and activates platelets and neutrophils. The result is the formation of small thrombi which are frequently seen in HAPE, and the presence of inflammatory markers such as leukotriene B4 and the complement fragment C5a in the lung lavage fluid. Hypoxic pulmonary vasoconstriction raises the pressure in some capillaries because the constriction is uneven. Since HAPE has its origin in the high pulmonary artery pressure, the objective of treatment should be to reduce the pressure by descent, administering oxygen, or giving drugs such as calcium channel blockers (e.g. nifedipine) which relax pulmonary vasoconstriction. Stress failure of pulmonary capillaries satisfactorily accounts for the features of HAPE.

Altitude Sickness↗
PubMed1992

Geometry of blood-tissue exchange in bat flight muscle compared with bat hindlimb and rat soleus muscle.

We investigated the relationship between capillary-to-fiber geometry and muscle aerobic capacity by comparing the bat flight muscle (pectoralis muscle), i.e., an ultimate case of extreme O2 demand in a mammalian skeletal muscle, with bat hindlimb and rat soleus muscles. At a given sarcomere length (2.1 microns), fiber cross-sectional area was considerably smaller in bat muscles (pectoralis 318 +/- 10 microns 2, hindlimb 447 +/- 35 microns 2) than in rat soleus muscle (2,027 +/- 125 microns 2). Capillary number per fiber cross-sectional area was much greater in bat pectoralis (6,394 +/- 380/mm2) than in bat hindlimb and rat soleus muscle (2,865 +/- 238 and 1,301 +/- 129/mm2, respectively; all values normalized to 2.1-microns sarcomere length). At the same sarcomere length (2.1 microns), the degree of tortuosity and branching of capillaries were significantly greater in bat pectoralis than in bat hindlimb and rat soleus muscle. In bat flight muscle, capillary length per fiber volume was very high (9,025 +/- 342/mm2). It was 2.2- and 5.4-fold larger than in bat hindlimb and rat soleus, respectively. Mitochondria occupied 35.3 +/- 1.2, 16.5 +/- 1.3, and 6.1 +/- 0.9% of the muscle fiber volume in bat pectoralis, hindlimb, and rat soleus muscles, respectively. There was a strong correlation between capillary length (as well as capillary surface) per fiber volume and mitochondrial volume density in all muscles. Considering capillary supply and mitochondrial volume on an individual fiber basis, we found that 1) the number of capillaries around a fiber was linearly related to mitochondrial volume per micron length of fiber in the muscles but that 2) capillary surface per fiber surface, at given mitochondrial volume per micron length of fiber, was about twice as large in bat pectoralis as in rat soleus muscle, whereas in bat hindlimb it was intermediate between that in bat pectoralis and that in rat soleus muscle. This was due to the differences in fiber size (rat soleus greater than bat muscles) and capillary-to-fiber ratio (bat pectoralis greater than hindlimb) between the muscles. It is notable that in the bat, the substantially greater O2 transfer capacity of the flight muscle compared with hindlimb was achieved by increasing the size of the capillary-to-fiber interface, i.e., capillary-to-fiber surface, via an increase in capillary number rather than by substantially reducing fiber size.

Animals↗
PubMed1992

High lung volume increases stress failure in pulmonary capillaries.

We previously showed that when pulmonary capillaries in anesthetized rabbits are exposed to a transmural pressure (Ptm) of approximately 40 mmHg, stress failure of the walls occurs with disruption of the capillary endothelium, alveolar epithelium, or sometimes all layers. The present study was designed to test whether stress failure occurred more frequently at high than at low lung volumes for the same Ptm. Lungs of anesthetized rabbits were inflated to a transpulmonary pressure of 20 cmH2O, perfused with autologous blood at 32.5 or 2.5 cmH2O Ptm, and fixed by intravascular perfusion. Samples were examined by both transmission and scanning electron microscopy. The results were compared with those of a previous study in which the lung was inflated to a transpulmonary pressure of 5 cmH2O. There was a large increase in the frequency of stress failure of the capillary walls at the higher lung volume. For example, at 32.5 cmH2O Ptm, the number of endothelial breaks per millimeter cell lining was 7.1 +/- 2.2 at the high lung volume compared with 0.7 +/- 0.4 at the low lung volume. The corresponding values for epithelium were 8.5 +/- 1.6 and 0.9 +/- 0.6. Both differences were significant (P less than 0.05). At 52.5 cmH2O Ptm, the results for endothelium were 20.7 +/- 7.6 (high volume) and 7.1 +/- 2.1 (low volume), and the corresponding results for epithelium were 32.8 +/- 11.9 and 11.4 +/- 3.7. At 32.5 cmH2O Ptm, the thickness of the blood-gas barrier was greater at the higher lung volume, consistent with the development of more interstitial edema. Ballooning of the epithelium caused by accumulation of edema fluid between the epithelial cell and its basement membrane was seen at 32.5 and 52.5 cmH2O Ptm. At high lung volume, the breaks tended to be narrower and fewer were oriented perpendicular to the axis of the pulmonary capillaries than at low lung volumes. Transmission and scanning electron microscopy measurements agreed well. Our findings provide a physiological mechanism for other studies showing increased capillary permeability at high states of lung inflation.

Air Pressure↗
PubMed1992

Capillary and fiber geometry in rat diaphragm perfusion fixed in situ at different sarcomere lengths.

To determine the potential range of diaphragm sarcomere lengths in situ and the effect of changes in sarcomere length on capillary and fiber geometry, rat diaphragms were perfusion fixed in situ with glutaraldehyde at different airway pressures and during electrical stimulation. The lengths of thick (1.517 +/- 0.007 microns) and thin (1.194 +/- 0.048 microns) filaments were not different from those established for rat limb muscle. Morphometric techniques were used to determine fiber cross-sectional area, sarcomere length, capillary orientation, and capillary length and surface area per fiber volume. All measurements were referenced to sarcomere length, which averaged 2.88 +/- 0.08 microns at -20 to -25 cmH2O airway pressure (residual volume) and 2.32 +/- 0.05 microns at +20 to +26 cmH2O airway pressure (total lung capacity). The contribution of capillary tortuosity and branching to total capillary length was dependent on sarcomere length and varied from 5 to 22%, consistent with that shown previously for mammalian limb muscles over this range of sarcomere lengths. Capillary length per fiber volume [Jv(c,f)] was significantly greater at residual volume (3,761 +/- 193 mm-2) than at total lung capacity (3,142 +/- 118 mm-2) and correlated with sarcomere length [l; r = 0.628, Jv(c,f) = 876l + 1,156, P less than 0.01; n = 18]. We conclude that the diaphragm is unusual in that the apparent in situ minimal sarcomere length is greater than 2.0 microns.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Short-term reversibility of ultrastructural changes in pulmonary capillaries caused by stress failure.

We previously showed that when the pulmonary capillaries in anesthetized rabbits are exposed to a transmural pressure (Ptm) of approximately 40 mmHg, stress failure of the walls occurs with disruption of the capillary endothelium, alveolar epithelium, or sometimes all layers. The present study was designed to determine whether some of the ultrastructural changes are rapidly reversible when the capillary pressure is reduced. To test this, the Ptm was raised to 52.5 cmH2O for 1 min of blood perfusion and then reduced to 12.5 cmH2O for 3 min of saline-dextran perfusion, followed by intravascular fixation at the same pressure. In another group of animals, the pressure was elevated for 1 min of blood and 3 min of saline-dextran before being reduced. The results were compared with previous studies in which the capillary pressures were maintained elevated at 52.5 cmH2O during the entire procedure. Control studies were also done at sustained low pressures. The results showed that the number of endothelial and epithelial breaks per millimeter and the total fraction area of the breaks were reduced when the pressure was lowered. For example, the number of endothelial breaks per millimeter decreased from 7.1 +/- 2.1 to 2.4 +/- 0.7, and the number of epithelial breaks per millimeter fell from 11.4 +/- 3.7 to 3.4 +/- 0.7. There was evidence that the breaks that closed were those that were initially small and were associated with an intact basement membrane. The results suggest that cells can move along their underlying matrix by rapid disengagement and reattachment of cell adhesion molecules, causing breaks to open or close within minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Capillary geometrical changes with fiber shortening in rat myocardium.

Capillary-to-fiber geometrical relations constitute an integral component of peripheral gas exchange. Determination of capillary length and surface area density necessitates quantification of capillary orientation (i.e., tortuosity and branching). In skeletal muscle, capillary tortuosity increases in a curvilinear fashion at reduced sarcomere length, and this compensates for decreased capillary density as fiber cross-sectional area increases. To investigate these relations in myocardium, rat hearts were glutaraldehyde perfusion-fixed in calcium- or barium-induced "systole" to provide varying degrees of fiber shortening. Morphometric techniques were used to analyze capillary geometry in subepicardium (EPI) and subendocardium (ENDO) using 1-micron sections cut transverse and longitudinal to the muscle fiber axis. Capillary density on transverse and longitudinal sections, capillary diameter, fiber cross-sectional area, and sarcomere length were determined in each region. Capillary surface density was computed, and values were related to sarcomere length and compared with published data for diastolic hearts. Sarcomere length in systole ranged from 2.06 +/- 0.03 to 1.35 +/- 0.02 microns (EPI) and from 1.93 +/- 0.04 to 1.44 +/- 0.04 microns (ENDO). Fiber cross-sectional area (EPI, 344 +/- 13 microns2; ENDO, 343 +/- 12 microns2) was significantly larger, and capillary density on transverse sections was significantly smaller (EPI, 4,105 +/- 318 mm-2; ENDO, 4,145 +/- 267 mm-2) than in hearts arrested in diastole. Compared with skeletal muscle, capillary tortuosity was substantially less increased by fiber shortening. Capillary tortuosity and branching did not differ between EPI and ENDO and contributed a maximum of 33% (range, 13-33%) to capillary length density and surface area at a sarcomere length of 1.45 +/- 0.04 microns. Compared with diastolic hearts, capillary length density decreased on average by 19.6% (EPI) and 17.7% (ENDO); similarly, capillary surface density decreased 19.9% (EPI) and 13.7% (ENDO). We conclude that, with fiber shortening in the heart, fiber cross-sectional area increases and capillary numerical density decreases as predicted from reduced sarcomere length. Combined with the minimal geometrical changes of the capillary bed at shorter fiber lengths, this results in a lower capillary length and surface area per fiber volume in systole. Consequently, the structural potential for O2 diffusion into myocytes is determined, in part, by fiber length.

Animals↗
PubMed1992

Stress failure of alveolar epithelial cells studied by scanning electron microscopy.

Stress failure of capillary walls has previously been demonstrated in anesthetized rabbit lungs at high capillary transmural pressures, and the ultrastructural changes in the walls have been described with transmission electron microscopy. In the present study, the pattern of alveolar epithelial disruptions was studied using scanning electron microscopy (SEM). Lungs of anesthetized rabbits were perfused with autologous blood at capillary transmural pressures of 12.5, 32.5, 52.5, and 72.5 +/- 2.5 cm H2O and fixed by intravascular perfusion. Samples for SEM were processed by critical point-drying and freeze-drying, and the results of the two techniques agreed well. Out of a total of 433 alveolar epithelial breaks examined, 93% were elongated, with the remainder being roughly circular; 68% of the elongated breaks were oriented perpendicular to the capillary axis, suggesting that the surface tension of the alveolar lining layer played an important role in protecting the blood-gas barrier against stress failure. Most of the breaks involved the full blood-gas barrier, but 17% were limited to the epithelial cells. This finding is consistent with our earlier conclusion that the extracellular matrix, particularly the type IV collagen, is responsible for much of the strength of the blood-gas barrier. The dimensions of the elongated breaks of the epithelium were approximately 4 microns (length) and 1 micron (width). They varied little with pressure, suggesting that once the disruption had occurred the stresses were greatly relieved. Breaks affecting the complete blood-gas barrier tended to be larger than those confined to the epithelium, again consistent with the protective role of the extracellular matrix. Almost no breaks occurred at intercellular junctions although many were seen within 1 micron of the junctions. This finding suggests that the junctions themselves have considerable mechanical strength, but that their rigidity may make the cell in the vicinity of the junction more vulnerable to mechanical failure.

Animals↗