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Relationship between mitochondrial volume density and capillarity in hamster muscles.

Mitochondrial volume density and lipid droplet-volume density were stereologically determined from electron micrographs of muscle fibers from three hamster muscles: retractor, sartorius, and soleus. The number of capillaries around a fiber, length of capillary-fiber contact, and muscle fiber area were also measured. Glycolytic fibers of the retractor and sartorius had larger cross-sectional areas, lower mitochondrial-volume densities, fewer subsarcolemmal aggregates of mitochondria, and lower capillary-fiber contact length in comparison to oxidative fibers of the retractor and soleus. Values for mitochondrial volume density in the different muscles correlated well (r = 0.97) with resting O2 consumption. The mitochondrial volume densities for each muscle correlated well (r = 0.99) with O2 diffusion coefficients of these muscles. Our results indicate that an analysis of the adequacy of O2 supply to an individual muscle fiber must take into account an interplay among fiber size, percent of the muscle fiber perimeter in contact with a capillary (capillary-fiber contact), and O2 demand of the fiber estimated by mitochondrial volume density.

Animals↗

Effect of hemorrhage on regional morphometric indexes of cerebral capillarity.

This study was performed to determine whether the brain can increase the number of perfused capillaries and arterioles supplying it regionally during hemorrhage. This was done using a technique to simultaneously determine total and perfused regional arteriolar and capillary morphology. Conscious Long-Evans rats served as unbled controls or were bled 65 mmHg or to 40-45 mmHg and stabilized for 30 min. Regional cerebral blood flow was determined using [14C]iodoantipyrine in half of these animals and fluorescein isothiocyanate-dextran was injected in the other half for determination of perfused cerebral microvascular morphometric indexes. The total microvasculature was labeled postmortem via an alkaline phosphatase stain. Regional cerebral blood flow was significantly increased in animals bled to 65 mmHg. During hemorrhage to 40-45 mmHg, cerebral blood flow was reduced 50% (from 59 +/- 28 to 26 +/- 11 ml X min-1 X 100 g-1, mean +/- SD) with no regional redistribution. For all treatments, total capillary density ranged from 400 to 500 capillaries/mm2, and in controls 47% were perfused. Animals bled to 65 mmHg did not mobilize their unperfused microvascular reserve even though they showed a slight tendency to do so. During hemorrhage to 40-45 mmHg, this percent increased significantly to 57% with the largest increase occurring in the pons. Approximately 51% of arterioles were perfused in controls and this was not different compared with the percent perfused during hemorrhage. Despite the overall lack of mobilization of unperfused arterioles, some regions within the brain significantly mobilized their reserves with severe hemorrhage, e.g., hippocampus (78%), hypothalamus (67%), and medulla (73%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Coronary vasodilator reserve, capillarity, and mitochondria in trained hypertensive rats.

To test the hypothesis that exercise training can reverse the decrements in coronary reserve, capillary density, and mitochondrial volume density evident during established hypertension, we trained spontaneously hypertensive (SHR) and normotensive (WKY) rats on a treadmill over a 3-mo period. At 7 mo of age we used microspheres to evaluate myocardial perfusion in conscious rats. Exercise training did not alter hypertension or left ventricular hypertrophy but did increase maximal O2 consumption in both SHR and WKY. A decrement in left and right ventricular coronary reserve in SHR, compared with WKY, was indicated by 1) a smaller increment in myocardial perfusion during maximal vasodilation with dipyridamole and 2) a higher minimal coronary vascular resistance per unit mass. Exercise training had no significant effect on any index of myocardial perfusion in SHR or WKY. A 12% decrement in capillary numerical density in the endomyocardium of SHR was not reversed by exercise training. We estimated the volume densities of mitochondria, myofibrils, and sarcoplasm using electron microscopy and point-counting stereology on perfusion-fixed hearts. None of the parameters in either SHR or WKY was changed by exercise training. It is concluded that exercise training does not reverse the decrements in coronary reserve and capillary numerical density associated with hypertension in adult rats. Moreover the previously observed enhancement of mitochondrial volume density due to exercise in young hypertensive rats was not observed in adult SHR.

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↗

Arteriolar reactivity and capillarization in chronically stimulated rat limb skeletal muscle post-MI.

The purpose of this study was to assess whether electrical stimulation-induced increases in muscular activity could improve capillary supply and correct previously documented abnormal vasodilator and vasoconstrictor responses of arterioles in limb skeletal muscle post-myocardial infarction (MI). Extensor digitorum longus (EDL) muscle from rats with surgically induced MI ( approximately 30% of the left ventricle) was chronically stimulated (Stim) 8 h/day for 6 +/- 1 days, at 11 wk post-MI. Third- (3A) and fourth-order (4A) arterioles in EDL from nine MI rats and four MI+Stim rats were compared with those of 11 controls (Con). Compared with Con rats, MI alone caused a reduction in the resting diameter of 3A and 4A arterioles, which was completely reversed by MI+Stim. However, Stim did not correct the attenuated vasodilator response to 10(-4) M adenosine seen in 4A arterioles from MI rats compared with Con. The constrictor response of both 3A and 4A vessels in MI rats to low doses of acetylcholine (10(-9) M, 10(-8) M) and norepinephrine (10(-9) M) was accentuated in MI+Stim. The proportion of oxidative fibers in EDL was unaffected by MI or MI+Stim combination. However, Stim significantly increased (P < 0.05) the capillary-to-fiber ratio in this muscle compared with Con. Thus, although the increase in muscle activity induced by chronic electrical stimulation normalized the reduction in resting vessel diameter seen after MI, it failed to correct the abnormalities in vasoreactivity of these same vessels.

Animals↗

Fibre type distribution, capillarization and enzymatic profile of locomotor and nonlocomotor muscles of horses and steers.

Samples were taken at slaughter from heart and both locomotor and nonlocomotor muscles from animals of similar body weight but adapted to different levels of activity: three horses and three steers. All samples were analyzed biochemically to measure the activity of key metabolic enzymes. The skeletal muscles were analyzed histochemically for fibre type composition, fibre area and capillary supply. The general pattern of differences in fibre type composition and metabolic profile between muscle groups was similar in both horses and steers. The hearts of both species had high citrate synthase (CS), 3-OH-acylCoA-dehydrogenase (HAD) and hexokinase (HK) and low lactate dehydrogenase (LDH) activities. In both species, deep portions of muscles and muscles localized deeper in the body had a more oxidative metabolic profile than superficial portions and muscles. Taking all muscles into account, it was found that CS and HAD were higher and LDH lower in horse than in steer muscles. Horse muscles contained more type IIA fibres and had a higher capillary supply than steer muscles. There was no difference between the two species regarding mean fibre area. The adaptation of the horse to a higher level of activity in comparison with steers was reflected in a higher oxidative capacity, better vascularization and a larger proportion of type IIA fibres. It was also obvious from these results that the ATPase fibre-typing system does not reflect the metabolic profile of a muscle.

3-Hydroxyacyl CoA Dehydrogenases↗

Left ventricular function after extended hypothermic preservation of the heart is dependent on functional coronary capillarity.

BACKGROUND: A growing body of knowledge has led to the hypothesis that injury to the microcirculation during hypothermic myocardial preservation may result in decreased contractility of hearts upon reperfusion. METHODS AND RESULTS: To test this hypothesis, we examined the relationship between no-reflow and left ventricular function after hypothermic cardiac preservation after reperfusion with solutions containing dilute whole blood (DWB) or washed red blood cells (K2RBC). Rat hearts were arrested with high-potassium cardioplegia, then flushed and stored for 6 hours in low-potassium cardioplegia at 4 degrees C. Hearts were reperfused at a constant flow rate (4 mL/min) with K2RBC for 60 minutes (group 1, n = 5) or DWB for 7 minutes followed by 53 minutes of K2RBC (group 2, n = 5). Left ventricular developed pressure (LVDP) was measured with an intraventricular balloon. Immediately after functional assessment, hearts were perfused with an india ink solution to mark flow, then glutaraldehyde. Morphometric techniques were used to determine the degree of capillary compression [delta d(c)], perfused capillary number per fiber area [QA(0)P], and perfused capillary surface area per fiber volume [Sv(c,f)P]. Capillaries were moderately compressed in both groups after reperfusion (group 1, 19 +/- 1%; group 2, 20 +/- 1%). QA(0)P and Sv(c,f)P were highly correlated with delta d(c) in hearts reperfused with K2RBC (r = .92 and r = .92; P < .01). Although statistically significant, the correlation was not as strong in DWB-reperfused hearts (r = .66 and r = .67; P < .05). LVDP was correlated to QA(0)P and Sv(c,f)P (r = .86 and r = .87, respectively) for groups 1 and 2. CONCLUSIONS: The weaker correlation between capillary perfusion and capillary compression in DWB-reperfused hearts suggests that factors other than compression contribute to no-reflow after hypothermic preservation. Regardless of the composition of the reperfusate, recovery of left ventricular function after hypothermic ischemia is directly related to coronary capillary perfusion upon reperfusion.

Animals↗

[Effects of hypoxia alone or exercise combined on capillarization of rat gastrocnemius muscle and its mechanism].

OBJECTIVE: To study the effects of hypoxia and hypoxia-combined-exercise on capillary density and vascular endothelial growth factor (VEGF) and its receptor KDR of skeletal muscle in rats. METHODS: Myosin-ATPase histochemistry was used to assay the size and capillary density of skeletal muscle. VEGF and its receptor KDR were studied by immunohistochemistry. RESULTS: Five-week hypoxia (simulated 5,000 m altitude) resulted in a decrease in cross-sectional area of skeletal muscle fiber and an increase in capillary density (CD), but the capillary/fiber ratio (C/F) remained unchanged. After 5-week-exercise at high altitude (1 h/d, 6 d/w), the muscle fibers did not undergo atrophy. At the same time, CD and C/F were increased. VEGF protein was found primarily in the matrix between muscle fibers; VEGF receptor-KDR was shown mainly in endothelial cells of capillary. VEGF was more strongly stained in the skeletal muscle of hypoxia-combined-exercise rats than the other two groups. CONCLUSION: Hypoxia itself can not induce neovascularization, while hypoxia-combined-exercise rats show capillary proliferation in skeletal muscle. VEGF and its receptor might play roles in this process.

Animals↗

[Features of capillarization and mitochondria from gastrocnemius and pectoral muscle fibers in chickens of various age].

Using light and electron microscopy, more rapid morphological development of m. gastrocnemius as compared to m. pectoralis was demonstrated in chicken by the 10th day. In m. pectoralis some immature fibers with centrally located nuclei are found, its muscle fibers are generally thinner, contain smaller mitochondria which occupy lesser relative volume, and are surrounded by capillaries, the density of which is half of that in m. gastrocnemius. In both muscles the mitochondria were found to be evenly distributed over the section area of the fibers. In adult birds as well as in chicken capillary density in both oxidative m. gastrocnemius and glycolytic m. pectoralis corresponds to the mitochondrial content in their fibers. In both muscles there exists a distinct concentration of oxygen-absorbing structures within a narrow peripheral zone of the fibers irrespective of the location and number of the surrounding capillaries. This phenomenon is more expressed in m. gastrocnemius. In m. pectoralis mitochondria are smaller at fibers' periphery and larger in their center.

Animals↗