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Biomedical subjects

O Mathieu-Costello

Publications and source records attributed to O Mathieu-Costello.

At least 37 records · Page 2Linked to original sources

Effects of long-term, high-altitude hypoxia on the capillarity of the ovine fetal heart.

To determine the effect of chronic hypoxia on myocardial capillarity, we exposed pregnant ewes to an altitude of 3,820 m from day 30 to day 139 of gestation and compared the fetus to low-altitude (approximately 300 m) controls. We hypothesized that capillarity would increase in the hypoxic myocardium to optimize oxygen and metabolite flux to hypoxic tissues. Fetal hearts were fixed by retrograde aortic perfusion and processed for microscopy and stereological evaluation. Fiber cross-sectional area and capillary density were measured and standardized to sarcomere length. Capillary volume density and capillary diameter were measured, capillary-to-fiber ratio and capillary length density were calculated, and the capillary anisotropy coefficient was obtained from a table of known values. Capillary-to-fiber ratio, capillary volume density, and the capillary anisotropy coefficient were not different between hypoxia and control groups. Capillary diameter was significantly larger in the right compared with the left ventricle of hypoxic but not control hearts; fiber cross-sectional area tended to be larger in the right ventricle of both groups, but this was not significant. As a result of larger fiber size, capillary density and capillary length density were significantly smaller in the right ventricle of hypoxic but not control fetal hearts. Contrary to our hypothesis, the ovine fetus does not show morphological adaptation in the myocardium after approximately 109 days of high-altitude hypoxic stress.

Altitude↗

Differential microvascular response to disuse in rat hindlimb skeletal muscles.

The aim of the study was to address discrepant findings in the literature regarding coupling between decreased functional demand during disuse and reduced capillarity. We previously reported [K. Tyml, O. Mathieu-Costello, and E. Noble. Microvasc. Res. 49: 17-32, 1995] that severe disuse of rat extensor digitorum longus (EDL) muscle caused by a 2-wk application of tetrodotoxin (TTX) on the sciatic nerve is not accompanied by capillary loss. Using the same animal model, the present study examined whether this absence of coupling could be explained in terms of 1) too short a duration of disuse and 2) muscle-specific response to disuse. Fischer 344 rats were exposed to either no treatment (control) or to 2- or 8-wk TTX applications. Fiber size, capillary density per fiber cross-sectional area, and capillary-to-fiber (C/F) ratio were determined by morphometry in the EDL muscle (control, 2- and 8-wk groups) and in the superficial portion of medial gastrocnemius (Gas) muscle (control, 2 wk). In both muscles, microvascular blood flow was evaluated by intravital microscopy [red blood cell velocity in capillaries (V(RBC))] and by laser Doppler flowmetry (LDF). Regardless of duration of TTX application or muscle type, TTX-induced disuse resulted in a significant reduction of fiber area (44-71%). However, capillary density increased in EDL muscle (both at 2 and 8 wk) but not in Gas muscle. C/F ratio decreased in EDL muscle at 8 wk (18%) and in Gas muscle (39%). This indicates that the effect on capillarity depended on duration of disuse and on muscle type. V(RBC) and LDF signal were significantly larger in EDL than in Gas muscle. Analysis of change in capillarity vs. V(RBC) suggested that the outcome of disuse may be modulated by blood flow. We conclude that the duration of skeletal muscle disuse per se does not dictate capillary loss, and we hypothesize that discrepant findings of coupling between functional demand and capillarity could be due to the presence/absence of flow-related angiogenesis superimposed on the capillary removal process during disuse.

Animals↗

Remodeling of lung interstitium but not resistance vessels in canine pacing-induced heart failure.

We previously showed that pacing-induced heart failure in dogs results in an enhancement of pulmonary vascular reactivity. In the present study we hypothesized that enhanced matrix deposition and structural remodeling of lung resistance microvessels would underlie these functional changes. Using biochemical measures, we found no difference in the normalized lung content of hyaluronan, uronic acid, and collagen between control dogs and dogs paced for 1 mo, although lung dry weight and noncollagen protein content increased significantly in the paced group (P < 0.05). From separate Formalin-fixed lung lobes, 5-microm frozen sections were prepared and stained with Masson's trichrome, and vascular structure was evaluated using standard morphometric techniques. When perivascular fluid cuffs were excluded from the measure of wall thickness, collagen and media volume fractions in any size range did not differ between paced and control groups. Similarly, in the paced group, medial thickness in <400-microm arterial or venular microvessels did not vary significantly from that in the controls. In contrast, the relationship of interstitial fluid pressure to lung water was significantly shifted to the right in the paced group, such that normal tissue pressures were observed, despite the increased water content. We conclude that although 1 mo of pacing-induced heart failure results in altered interstitial function, the attendant pulmonary hypertension and/or hormonal responses are insufficient to induce medial hypertrophy or other remodeling of the extra-alveolar microvasculature.

Animals↗

Increased fiber capillarization in flight muscle of finch at altitude.

We examined fiber capillarization and ultrastructure in the highly aerobic flight muscle of six gray crowned rosy finches (Leucosticte arctoa; mass 22.9 +/- 0.5 (SE) g) living at altitude (A; White Mountains of Eastern California; 4000 m) compared to eight sea-level (SL) house finches (Carpodacus mexicanus, mass, 19.8 +/- 0.6 g) of the same subfamily, Carduelinae. Capillary length per fiber volume (A, 10,400 +/- 409 mm(-2); SL, 7513 +/- 423; P < 0.001) and capillary-to-fiber ratio (A, 2.32 +/- 0.07; SL, 1.85 +/- 0.06; P < 0.001) were significantly greater in A, with no difference in fiber cross-sectional area compared to SL. Capillary geometry was significantly different in A, yielding a greater contribution of tortuosity and branching to capillary length than in SL. Capillary-to-fiber surface ratio and fiber mitochondrial volume were both greater in A, but their ratio was similar to SL, indicating a proportional increase in the size of the capillary to fiber interface and fiber mitochondrial volume in A to sustain high levels of aerobic capacity while living at altitude.

Adaptation, Physiological↗

Increased oxidative capacity does not protect skeletal muscle fibers from eccentric contraction-induced injury.

Isometric electrical stimulation was delivered to rabbit dorsiflexor muscles at 10 Hz for 1 s on and 1 s off over 30 min, 5 days/wk for 3 wk to induce an increase in muscle oxidative capacity. Stimulation-trained muscles as well as untrained muscles were then subjected to a 30-min eccentric exercise bout to test whether increased oxidative capacity provided a protective effect against muscle injury. Electrical stimulation results in significant training of both the extensor digitorum longus (EDL) and tibialis anterior (TA) muscles, with EDL citrate synthase (CS) activity increasing an average of 67% (P < 0.0001) and TA CS activity increasing by 27% (P < 0.05). For all parameters measured, the magnitude of change was much greater for EDL than for TA muscle. Dorsiflexor fatigability decreased significantly during the 3-wk training period (P < 0.0001), whereas the EDL TA individually showed strong decreasing trends in fatigability after training. TA and EDL capillary density measured histomorphometrically increased from 839 +/- 56 to 1,026 +/- 71 mm-2 (P = 0.07) and from 589 +/- 37 to 792 +/- 66 mm-2 (P < 0.05), respectively. TA and EDL capillary-to-fiber ratio increased from 1.32 +/- 0.10 to 1.55 +/- 0.16 (P > 0.2) and 1.08 +/- 0.07 to 1.36 +/- 0.14 (P > 0.1), respectively. Type 2A fiber type percentage increased after stimulation training by 68% (P < 0.0001) for the EDL and by 32% (P > 0.1) for the TA at the expense of type 2D fibers. Despite the large training effect for the EDL and the modest training effect for the TA, no differences were observed between stimulation-trained and untrained groups for maximum dorsiflexion torque (P > 0.3) or maximum tetanic tension (P > 0.3) after eccentric contraction-induced injury. Additionally, no significant correlation was observed between CS activity and maximum tetanic tension after eccentric contraction-induced injury for either muscle (P > 0.2). Thus we conclude that increasing muscle oxidative capacity by isometric electrical stimulation training did not protect muscle against eccentric contraction-induced injury.

Animals↗

Increased capillarity in leg muscle of finches living at altitude.

An increased ratio of muscle capillary to fiber number (capillary/fiber number) at altitude has been found in only a few investigations. The highly aerobic pectoralis muscle of finches living at 4,000-m altitude (Leucosticte arctoa; A) was recently shown to have a larger capillary/fiber number and greater contribution of tortuosity and branching to total capillary length than sea-level finches (Carpodacus mexicanus; SL) of the same subfamily (O. Mathieu-Costello, P. J. Agey, L. Wu, J. M. Szewczak, and R. E. MacMillen. Respir. Physiol. 111: 189-199, 1998). To evaluate the role of muscle aerobic capacity on this trait, we examined the less-aerobic leg muscle (deep portion of anterior thigh) in the same birds. We found that, similar to pectoralis, the leg muscle in A finches had a greater capillary/fiber number (1.42 +/- 0.06) than that in SL finches (0.77 +/- 0.05; P < 0.01), but capillary tortuosity and branching were not different. As also found in pectoralis, the resulting larger capillary/fiber surface in A finches was proportional to a greater mitochondrial volume per micrometer of fiber length compared with that in SL finches. These observations, in conjunction with a trend to a greater (rather than smaller) fiber cross-sectional area in A than in SL finches (A: 484 +/- 42, SL: 390 +/- 26 micrometer2, both values at 2.5-micrometer sarcomere length; P = 0.093), support the notion that chronic hypoxia is also a condition in which capillary-to-fiber structure is organized to match the size of the muscle capillary-to-fiber interface to fiber mitochondrial volume rather than to minimize intercapillary O2 diffusion distances.

Altitude↗

Alveolar hypoxia increases gene expression of extracellular matrix proteins and platelet-derived growth factor-B in lung parenchyma.

The walls of pulmonary capillaries are extremely thin, and wall stress increases greatly when capillary pressure rises. Alveolar hypoxia causes pulmonary vasoconstriction and hypertension, and if this is uneven, some capillaries may be exposed to high transmural pressure and develop stress failure. There is evidence that increased wall stress causes capillary remodeling. In this study we exposed Madison strain Sprague-Dawley rats to normobaric hypoxia (10% oxygen) for 6 h or 3 d (short-term group), and for 3 d or 10 d (long-term group). Peripheral lung tissue was then collected and messenger RNA (mRNA) levels were determined for extracellular matrix (ECM) proteins and growth factors. Collagen content (hydroxyproline) was also measured. Levels of mRNA for alpha2(IV) procollagen increased sixfold after 6 h of hypoxia and sevenfold after 3 d of hypoxia, and then decreased after 10 d exposure. Levels of mRNA for platelet-derived growth factor-B (PDGF-B) doubled after 6 h of hypoxia but returned to control values after 3 d. mRNA levels for alpha1(I) and alpha1(III) procollagens and fibronectin were increased after 3 d of hypoxia (by seven- to 12-fold, 1.6- to eightfold, and 12-fold, respectively), then decreased toward control values after 10 d. In contrast, neither levels of mRNA for vascular endothelial growth factor (VEGF) nor collagen content changed. These results suggest that alveolar hypoxia causes vascular remodeling in lung parenchyma, and are consistent with capillary wall remodeling in response to increased wall stress.

Analysis of Variance↗

Fiber capillarization and ultrastructure of pigeon pectoralis muscle after cold acclimation.

We investigated the effect of 2 months of exposure to cold conditions (0-5 C) on capillarization and on fiber size, distribution and ultrastructure in the pectoralis muscle of nine pigeons (Columbia livia; mean body mass 700 31 g) and compared the results with measurements from four control birds (mean mass 715 42 g) kept at normal ambient temperature (22-23 C) for the same period. Superficial and deep portions of the muscles, taken from the central area of the right or left pectoralis major muscle, were perfusion-fixed in situ, processed for electron microscopy and analyzed by morphometry. Aerobic fibers represented the vast majority of fibers (93 1 %, mean s.e.m.) in all samples. After cold-acclimation, fiber sectional area was reduced and capillary density increased proportionally. There was no change in the degree of orientation (anisotropy) of capillaries, capillary-to-fiber ratio or fiber type distribution compared with controls. The volume density of mitochondria and lipid droplets in aerobic fibers and capillary diameter increased in response to cold, while the linear relationship between capillary length per fiber volume and fiber mitochondrial volume density remained unchanged. Capillary surface area, intrafiber lipid deposition and fiber mitochondrial volume density were all correlated in cold-acclimated pigeons. The results indicate a close match between the aerobic capacity of the highly aerobic fibers of the pectoralis muscle and their vascularization to meet the increased energetic demand of shivering.

Acclimatization↗

Skeletal muscle histology and biochemistry of an elite sprinter, the African cheetah.

To establish a skeletal muscle profile for elite sprinters, we obtained muscle biopsy samples from the vastus lateralis, gastrocnemius and soleus of African cheetahs (Acinonyx jubatus). Muscle ultrastructure was characterized by the fiber type composition and mitochondrial volume density of each sample. Maximum enzyme activity, myoglobin content and mixed fiber metabolite content were used to assess the major biochemical pathways. The results demonstrate a preponderance of fast-twitch fibers in the locomotor muscles of cheetahs; 83% of the total number of fibers examined in the vastus lateralis and nearly 61% of the gastrocnemius were comprised of fast-twitch fibers. The total mitochondrial volume density of the limb muscles ranged from 2.0 to 3.9% for two wild cheetahs. Enzyme activities reflected the sprinting capability of the cheetah. Maximum activities for pyruvate kinase and lactate dehydrogenase in the vastus lateralis were 1519.00 +/- 203.60 and 1929.25 +/- 482.35 mumol min-1.g wet wt-1, respectively, and indicated a high capacity for glycolysis. This study demonstrates that the locomotor muscles of cheetahs are poised for anaerobically based exercise. Fiber type composition, mitochondrial content and glycolytic enzyme capacities in the locomotor muscles of these sprinting cats are at the extreme range of values for other sprinters bred or trained for this activity including greyhounds, thoroughbred horses and elite human athletes.

Acinonyx↗

Chronic hypoxia affects capillary density and geometry in pigeon pectoralis muscle.

We examined fiber capillarization and ultrastructure in pectoralis muscle of 11 pigeons (Columbia livia; body mass 603 +/- 12 (SE) g) i.e. nine birds kept at 3800 m for 5 months (three in a small aviary (A1) and five in smaller cages, A2) compared to three sea-level (SL) controls. There was no difference between groups in either the relative area or number of aerobic and glycolytic fibers per total fibers, fiber size or mitochondrial volume density. Hematocrit was significantly greater in A1 and A2 (59 +/- 1%) than SL (50 +/- 2%). In A1, capillary density relative to the sectional area of aerobic/total fibers, capillary diameter and the contribution of tortuosity and branching to capillary length were significantly greater than SL, yielding greater capillary length and surface area per volume of fiber. Capillary length and surface densities very close to those in A1 and significantly greater than SL for the relative sectional area of aerobic/total fibers were also found in four out of five A2 birds, without alteration in capillary geometry or diameter. The size of the capillary-fiber interface (i.e. capillary-to-fiber surface ratio) in aerobic fibers was also greater in A1 and A2 than SL, indicating a greater capacity for oxygen supply of the muscle fibers in the altitude groups.

Altitude↗

Structural and biochemical characteristics of locomotory muscles of emperor penguins, Aptenodytes forsteri.

Structural and biochemical characteristics of the primary muscles used for swimming (pectoralis, PEC and supracoracoideus, SC) were compared to those of leg muscles in emperor penguins (Aptenodytes forsteri). The mass of PEC-SC was four times that of the leg musculature, and mitochondrial volume density in PEC and SC (4%) was two-thirds that in sartorius (S) and gastrocnemius. The differences in muscle mass and mitochondrial density yielded a 2.2-fold greater total mitochondrial content in PEC-SC than leg muscles, which appears to account for the 1.8-fold greater whole-body highest oxygen consumption previously recorded in emperor penguins during swimming compared to walking. Calculation of maximal mitochondrial O2 consumption in PEC-SC and leg muscle yielded value of 5.8-6.9 ml O2 ml-1 min-1, which are similar to those in locomotory muscles of most mammals and birds. A distinct feature of emperor penguin muscle was its myoglobin content, with concentrations in PEC-SC (6.4 g 100 g-1 among the highest measured in any species. This resulted in a PEC-SC O2 store greater than that of the entire blood. In addition, ratios of myoglobin content to mitochondrial volume density and to citrate synthase activity were 4.4 and 2.5 times greater in PEC than in S, indicative of the significant role of myoglobin in the adaptation of muscle to cardiovascular adjustments during diving.

Animals↗

Effect of ischemic cerebral volume changes on behavior.

Ischemia causes long-term effects on brain volume and neurologic function but the relationship between the two is poorly characterized. We studied the relationships between brain volume and three measures of rodent behavior after cerebral ischemia was induced by injecting several thousand microspheres into the internal carotid arteries of rats. Forty eight hours later, each subject was rated using a global neurologic rating scale. Several weeks later, the subjects were tested for open field activity and visual spatial learning. Post-mortem we measured the volume of the cerebral hemispheres and estimated the volume densities of cortex, white matter, hippocampus, basal ganglia, thalamus, ventricle, and visible infarction. Ischemia caused significant impairment, as measured by the global rating scale; the probability of an abnormal rating was correlated with the number of microspheres trapped in the brains. Visual spatial learning was significantly impaired by ischemia, but this deficit was independent of the count of microspheres, whether the subject was abnormal at 48 h, and whether the left or right hemisphere was embolized. Cerebral hemisphere volume was reduced from 430 mm3 to 376 mm3 (P < 0.05). The cortex was reduced from 22 to 19% of cerebrum (P < 0.05) and the white matter compartment was reduced to similar degree. The lesion volume was 6% of cerebrum, comparable to that seen with other ischemia methods. The global outcome rating was significantly related to total cerebral volume, but not to volume changes in any single compartment. On the other hand, visual spatial learning was significantly influenced by volume changes in the cortex and white matter, but not by the topography of the visible infarctions. Open field activity was not altered by infarction. Our data suggests that the total volume of brain tissue lost to infarction may partially determine global neurological rating independently of the topography of the volume loss. Integrative functions such as learning may depend more on the integrity of specific compartments and less on the total volume of intact brain. The volume of visible cystic infarction was not related to long term behavioral outcome. These results should be confirmed using another method of inducing ischemia.

Animals↗

Effect of pulmonary emphysema on diaphragm capillary geometry.

In emphysema, the diaphragm shortens by losing sarcomeres. We hypothesized that unless capillaries undergo a similar shortening, capillary geometry must be altered. Without quantifying this geometry, capillary length and surface area per fiber volume, which are critical measurements of the structural potential for blood-tissue exchange, cannot be resolved. Five months after intratracheal elastase (E) or saline (control; C) instillation, diaphragms from male Syrian golden hamsters were glutaraldehyde perfusion fixed in situ at reference lung positions (residual volume, functional residual capacity, total lung capacity) to provide diaphragms fixed over a range of sarcomere lengths. Subsequently, diaphragms were processed for electron microscopy and analyzed morphometrically. Emphysema increased lung volume changes from -20 to 25 cmH2O airway pressure (i.e., passive vital capacity) and excised lung volume (both P < 0.001). In each region of the costal diaphragm (i.e., ventral, medial, dorsal), sarcomere number was reduced (all P < 0.05). Capillary-to-fiber ratio increased (C = 2.2 +/- 0.1, E = 2.8 +/- 0.1; P < 0.01) and fibers hypertrophied (C = 815 +/- 35, E = 987 +/- 67 microns2; P < 0.05; both values at 2.5 microns sarcomere length). Capillary geometry was markedly altered by the loss of sarcomeres in series. Specifically, the additional capillary length derived from capillary tortuosity and branching was increased by 183% at 2.5 microns sarcomere length compared with C values (C, 359 +/- 43; E, 1,020 +/- 158 mm-2, P < 0.01). This significantly increased total capillary length (C, 3,115 +/- 173; E, 3,851 +/- 219mm-2 at 2.5 microns, P < 0.05) and surface area (C, 456 +/- 13; E, 519 +/- 24 cm-1, P < 0.05) per fiber volume. Thus emphysema substantially alters diaphragm capillary geometry and augments the capillary length and surface area available for blood-tissue exchange.

Animals↗

Very high pressures are required to cause stress failure of pulmonary capillaries in thoroughbred racehorses.

Thoroughbred horses develop extremely high pulmonary vascular pressures during galloping, all horses in training develop exercise-induced pulmonary hemorrhage, and we have shown that this is caused by stress failure of pulmonary capillaries. It is known that the capillary transmural pressure (Ptm) necessary for stress failure is higher in dogs than in rabbits. The present study was designed to determine this value in horses. The lungs from 15 Thoroughbred horses were perfused with autologous blood at Ptm values (midlung) of 25, 50, 75, 100 and 150 mmHg, and then perfusion fixed, and samples (dorsal and ventral, from caudal region) were examined by electron microscopy. Few disruptions of capillary endothelium were observed at Ptm < or = 75 mmHg, and 5.3 +/- 2.2 and 4.3 +/- 0.7 breaks/mm endothelium were found at 100 and 150 mmHg Ptm, respectively. Blood-gas barrier thickness did not change with Ptm. At low Ptm, interstitial thickness was greater than previously found in rabbits but not in dogs. We conclude that the Ptm required to cause stress failure of pulmonary capillaries is between 75 and 100 mmHg and is greater in Thoroughbred horses than in both rabbits and dogs.

Animals↗

High lung inflation increases mRNA levels of ECM components and growth factors in lung parenchyma.

Remodeling of pulmonary capillaries occurs after chronic increases in capillary pressure (e.g., mitral stenosis). Also, remodeling of pulmonary arteries begins within 4 h of increased wall stress and is endothelium dependent. We have previously shown that high lung inflation increases wall stress in pulmonary capillaries. This study was designed to determine whether high lung inflation induces remodeling of the extracellular matrix (ECM) in lung parenchyma. Open-chest rabbits were ventilated for 4 h with 9-cmH2O positive end-expiratory pressure (PEEP) on one lung and 1-cmH2O PEEP on the other (High-PEEP group), or with 2-cmH2O PEEP on both lungs (Low-PEEP group). An additional untreated control group was also included. We found increased levels of mRNA in both lungs of High-PEEP rabbits (compared with both the Low-PEEP and untreated groups) for alpha1(III) and alpha2(IV) procollagen, fibronectin, basic fibroblast growth factor, and transforming growth factor-beta1. In contrast, alpha2(I) procollagen and vascular endothelial growth factor mRNA levels were not changed. We conclude that high lung inflation for 4 h increases mRNA levels of ECM components and growth factors in lung parenchyma.

Animals↗

Fiber capillarization in flight muscle of pigeons native and flying at altitude.

We examined structural characteristics for fiber O2 supply in the highly aerobic flight muscle of 5 pigeons (Columbia livia; body mass 223--317 g) native and actively flying at altitude (La Paz, Bolivia; 3750 m). Whereas deep sites were significantly more aerobic and highly vascularized than superficial in altitude (A) but not sea-level (SL) group, both sites showed a number of similarities between the two groups. The cross-sectional area of aerobic fibers (> or = 90% of fiber number) linearly increased with body mass (r 0.84; P < 0.0005) but was not smaller in A for their body mass, and there was no reduction in the size of glycolytic fibers compared to SL. The relationships between fiber capillarization and the sectional area of aerobic fibers in transverse sections or mitochondrial volume density were not altered in A compared to SL. The results indicate that the factors which determine the relationships between fiber capillarization and ultrastructure in the muscles were not altered by the adaptation to altitude. Differences between samples were related to the relative sectional area of aerobic fibers and mitochondrial volume density, not the chronic exposure to altitude.

Altitude↗

Structural basis for oxygen delivery: muscle capillaries and manifolds in tuna red muscle.

We summarize our morphometric data on fiber vascularization and aerobic capacity in red muscle of tuna (Katsuwonus pelamis), compared to intensely aerobic flight muscles of hummingbird (Selasphorus rufus, BW 3-4 g) and bat (Eptesius fuscus, BW 15-16 g, Pipistrellus hesperus, BW 3-5 g). Three characteristic features of high flux paths for oxygen: (a) small fiber size, (b) dense capillary network and (c) high mitochondrial volume density were found in tuna, but they were not as pronounced as in hummingbird and bat flight muscles. A particular arrangement of capillary manifolds, also seen in flight muscle of birds but not in bats, was found in tuna, forming dense envelopes of capillary branches around portions of muscle fibers. However, all indexes of fiber capillarization were relatively low in tuna red muscle for its mitochondrial volume, compared with other intensely aerobic muscles. Capillary length per unit volume of mitochondria, and capillary surface per mitochondrial inner (and outer) membrane surface area, were about one half of those in hummingbird or bat flight muscles. Consistent differences exist in the size of the capillary network for the size of the mitochondrial compartment in highly aerobic red muscle of tuna compared with bird and mammal.

Aerobiosis↗

Intracoronary gene transfer of fibroblast growth factor-5 increases blood flow and contractile function in an ischemic region of the heart.

Increased coronary blood vessel development could potentially benefit patients with ischemic heart disease. In a model of stress-induced myocardial ischemia, intracoronary injection of a recombinant adenovirus expressing human fibroblast growth factor-5 (FGF-5) resulted in messenger RNA and protein expression of the transferred gene. Two weeks after gene transfer, regional abnormalities in stress-induced function and blood flow were improved, effects that persisted for 12 weeks. Improved blood flow and function were associated with evidence of angiogenesis. This report documents, for the first time, successful amelioration of abnormalities in myocardial blood flow and function following in vivo gene transfer.

Adenoviruses, Human↗