Nasal strips and EIPH in the exercising Thoroughbred racehorse.
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Anaerobiosis↗
Biomedical subjects
D C Poole
Publications and source records attributed to D C Poole.
NO inhalation reduces pulmonary arterial pressure but not hemorrhage in maximally exercising horses.
In horses, the exercise-induced elevation of pulmonary arterial pressure (Ppa) is thought to play a deterministic role in exercise-induced pulmonary hemorrhage (EIPH), and thus treatment designed to lower Ppa might reasonably be expected to reduce EIPH. Five Thoroughbred horses were run on a treadmill to volitional fatigue (incremental step test) under nitric oxide (NO; inhaled 80 ppm) and control (N(2), same flow rate as per NO run) conditions (2 wk between trials; order randomized) to test the hypothesis that NO inhalation would reduce maximal Ppa but that this reduction may not necessarily reduce EIPH. Before each investigation, a microtipped pressure transducer was placed in the pulmonary artery 8 cm past the pulmonic valve to monitor Ppa. EIPH severity was assessed via bronchoalveolar lavage (BAL) 30 min postrun. Exercise time did not differ between the two trials (P > 0.05). NO administration resulted in a small but consistent and significant reduction in peak Ppa (N(2), 102.3 +/- 4.4; NO, 98.6 +/- 4.3 mmHg, P < 0.05). In the face of lowered Ppa, EIPH severity was significantly higher in the NO trial (N(2), 22.4 +/- 6.8; NO, 42.6 +/- 15.4 x 10(6) red blood cells/ml BAL fluid, P < 0.05). These findings support the notion that extremely high Ppa may reflect, in part, an arteriolar vasoconstriction that serves to protect the capillary bed from the extraordinarily high Ppa evoked during maximal exercise in the Thoroughbred horse. Furthermore, these data suggest that exogenous NO treatment during exercise in horses may not only be poor prophylaxis but may actually exacerbate the severity of EIPH.
Administration, Inhalation↗
Effects of emphysema on diaphragm microvascular oxygen pressure.
Pulmonary emphysema impairs lung and respiratory muscle function leading to restricted physical capacity and accelerated morbidity and mortality consequent to respiratory muscle failure. In the absence of direct evidence, an O2 supply-demand imbalance within the diaphragm and other respiratory muscles in emphysema has been considered the most likely explanation for this failure. To test this hypothesis, we utilized phosphorescence quenching techniques to measure mean microvascular PO2 (PO2m) within the medial costal diaphragm of control (C, n = 10) and emphysematous (E, elastase instilled, n = 7) hamsters. PO2m and mean arterial pressure (MAP) were measured in the spontaneously breathing anesthetized hamster at inspired O2 percentages of 10, 21, and 100, and across a range of mean MAPs from 40 to 115 mm Hg. At each inspired O2, diaphragm PO2m was significantly (p < 0.05) lower in E animals (10%: C, 19 +/- 3; E, 9 +/- 2; 21%: C, 32 +/- 2; E, 21 +/- 2; 100%: C, 60 +/- 8; E, 36 +/- 9 mm Hg). At 21% inspired O2, the PO2m decrease was correlated with reduced MAP in both C (r = 0.968) and E (r = 0.976) animals. We conclude that diaphragmatic PO2m (and therefore microvascular O2 content) is decreased in emphysematous hamsters reflecting a greater diaphragmatic O2 utilization at rest and a lower O2 extraction reserve. According to Fick's law, this lower PO2m will mandate an exaggerated fall in intramyocyte PO2, which is expected to accelerate muscle glycogen depletion and consequently fatigue. This provides empirical evidence in support of one possible mechanism for respiratory muscle failure in emphysema.
Analysis of Variance↗
Role of the airways in exercise-induced pulmonary haemorrhage.
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Airway Resistance↗
Cardiorespiratory impact of the nitric oxide synthase inhibitor L-NAME in the exercising horse.
To investigate the role of nitric oxide, NO, in facilitating cardiorespiratory function during exercise, five horses ran on a treadmill at speeds that yielded 50, 80 and 100% of peak pulmonary oxygen uptake (V(O(2)) peak) as determined on a maximal incremental test. Each horse underwent one control (C) and one (NO-synthase inhibitor; N(G)-L-nitro-arginine methyl ester (L-NAME), 20 mg/kg) trial in randomized order. Pulmonary gas exchange (open flow system), arterial and mixed-venous blood gases, cardiac output (Fick Principle), and pulmonary and systemic conductances were determined. L-NAME reduced exercise tolerance, as well as cardiac output (C, 291+/-34; L-NAME, 246+/-38 L/min), body O(2) delivery (C, 74.4+/-5. 5; L-NAME, 62.1+/-5.6 L/min), and both pulmonary (C, 3.07+/-0.26; L-NAME, 2.84+/-0.35 L/min per mmHg) and systemic (C, 1.55+/-0.24; L-NAME, 1.17+/-0.16 L/min per mmHg) effective vascular conductances at peak running speeds (all P<0.05). On the 50 and 80% trials, L-NAME increased O(2) extraction, which compensated for the reduced body O(2) delivery and prevented a fall in V(O(2)). However, at peak running speed in the L-NAME trial, an elevated O(2) extraction (P<0. 05) was not sufficient to prevent V(O(2)) from falling consequent to the reduced O(2) delivery. At the 50 and 80% running speeds (as for peak), L-NAME reduced pulmonary and systemic effective conductances. These data demonstrate that the NO synthase inhibitor, L-NAME, induces a profound hemodynamic impairment at submaximal and peak running speeds in the horse thereby unveiling a potentially crucial role for NO in mediating endothelial function during exercise.
Acid-Base Equilibrium↗
Spinotrapezius muscle microcirculatory function: effects of surgical exteriorization.
Intravital microscopy facilitates insights into muscle microcirculatory structural and functional control, provided that surgical exteriorization does not impact vascular function. We utilized a novel combination of phosphorescence quenching, microvascular oxygen pressure (microvascular PO(2)), and microsphere (blood flow) techniques to evaluate static and dynamic behavior within the exposed intact (I) and exteriorized (EX) rat spinotrapezius muscle. I and EX muscles were studied under control, metabolic blockade with 2,4-dinitrophenol (DNP), and electrically stimulated conditions with 1-Hz contractions, and across switches from 21 to 100% and 10% inspired O(2). Surgical preparation did not alter spinotrapezius muscle blood flow in either I or EX muscle. DNP elevated muscle blood flow approximately 120% (P < 0.05) in both I and EX muscles (P > 0.05 between I and EX). Contractions reduced microvascular PO(2) from 30.4 +/- 4.3 to 21.8 +/- 4.8 mmHg in I muscle and from 33.2 +/- 3.0 to 25.9 +/- 2.8 mmHg in EX muscles with no difference between I and EX. In each O(2) condition, there was no difference (each P > 0.05) in microvascular PO(2) between I and EX muscles (21% O(2): I = 37 +/- 1; EX = 36 +/- 1; 100%: I = 62 +/- 5; EX = 51 +/- 9; 10%: I = 20 +/- 1; EX = 17 +/- 2 mmHg). Similarly, the dynamic behavior of microvascular PO(2) to altered inspired O(2) was unaffected by the EX procedure [half-time (t(1/2)) to 100% O(2): I = 23 +/- 5; EX = 23 +/- 4; t(1/2) to 10%: I = 14 +/- 2; EX = 16 +/- 2 s, both P > 0.05]. These results demonstrate that the spinotrapezius muscle can be EX without significant alteration of microvascular integrity and responsiveness under the conditions assessed.
2,4-Dinitrophenol↗
Respiratory muscle blood flows during physiological and chemical hyperpnea in the rat.
Whether the diaphragm retains a vasodilator reserve at maximal exercise is controversial. To address this issue, we measured respiratory and hindlimb muscle blood flows and vascular conductances using radiolabeled microspheres in rats running at their maximal attainable treadmill speed (96 +/- 5 m/min; range 71-116 m/min) and at rest while breathing either room air or 10% O(2)-8% CO(2) (balance N(2)). All hindlimb and respiratory muscle blood flows measured increased during exercise (P < 0.001), whereas increases in blood flow while breathing 10% O(2)-8% CO(2) were restricted to the diaphragm only. During exercise, muscle blood flow increased up to 18-fold above rest values, with the greatest mass specific flows (in ml. min(-1). 100 g(-1)) found in the vastus intermedius (680 +/- 44), red vastus lateralis (536 +/- 18), red gastrocnemius (565 +/- 47), and red tibialis anterior (602 +/- 44). During exercise, blood flow was higher (P < 0.05) in the costal diaphragm (395 +/- 31 ml. min(-1). 100 g(-1)) than in the crural diaphragm (286 +/- 17 ml. min(-1). 100 g(-1)). During hypoxia+hypercapnia, blood flows in both the costal and crural diaphragms (550 +/- 70 and 423 +/- 53 ml. min(-1). 100 g(-1), respectively) were elevated (P < 0.05) above those found during maximal exercise. These data demonstrate that there is a substantial functional vasodilator reserve in the rat diaphragm at maximal exercise and that hypoxia + hypercapnia-induced hyperpnea is necessary to elevate diaphragm blood flow to a level commensurate with its high oxidative capacity.
Air↗
Effects of skeletal muscle sarcomere length on in vivo capillary distensibility.
The structural integrity of the capillary wall is such that capillary luminal distensibility is largely determined by support provided by the tissue in which it is located. Given that O2 flux density is greatest across the skeletal muscle capillary endothelium, any changes in capillary diameter (dc) would be expected to affect O2 diffusing capacity as well as hemodynamic resistance. We used intravital microscopy techniques to study the maximally vasodilated rat (n = 5) spinotrapezius muscle microcirculation in vivo within the physiological sarcomere length range, at high and low mean arterial pressures (MAP) systematically altered by blood withdrawal and infusion. We tested the hypothesis that in vivo capillary diameter alterations in response to changes of MAP would be reduced at extended sarcomere lengths. At 2.4-microm sarcomere length, mean dc (dc) within the spinotrapezius increased from 5.6 +/- 0.1 to 5.9 +/- 0.1 microm (P < 0.01) as MAP increased from 33 to 94 mm Hg. However, there was absolutely no change (i.e., 5.2 +/- 0.1 vs 5.2 +/- 0.1 microm) in dc in response to changes in MAP at 3.2-microm sarcomere length. Furthermore, at sarcomere lengths <2.8 microm there was a significant increase (P < 0.01) in dc (n = 40) as MAP increased, whereas dc (n = 49) remained unchanged with alterations of MAP when sarcomere length was >/=2.8 microm (P > 0.05). These data suggest that pressure-induced alterations in capillary luminal diameter and thus "in vivo capillary distensibility" are dependent upon the presiding sarcomere length. Furthermore, we conclude that the MAP-induced increases in capillary luminal diameter at the shorter sarcomere lengths are modest ( approximately 5%) and unlikely to affect O2 diffusing capacity and vascular resistance appreciably.
Animals↗
V(O2) recovery kinetics in the horse following moderate, heavy, and severe exercise.
At the onset of exercise, horses exhibit O2 uptake (VO2) kinetics that are qualitatively similar to those of humans. In humans, there is a marked dissymmetry between on- and off-kinetics for VO2. This investigation sought to formally characterize the off-transient (recovery) VO2 kinetics in the horse within the moderate (M), heavy (H), and severe (S) exercise domains. Six horses were run on a high-speed treadmill at M, H, and S exercise intensities (i.e., that speed which yielded approximately 50, 85, 100% peak VO2, respectively, on the maximal incremental test). The time courses for the recovery were modeled by using a three-phase model with a single-exponential (fast component) or double-exponential (fast and slow component) phase 2. The single-exponential phase 2 model provided an excellent fit to the off-transient data, with the exception of one horse in the H domain which was best modeled by a double exponential. The time delay elicited no domain dependency (M, 18.0 +/- 1.0; H, 17.6 +/- 1.1; S, 17.8 +/- 2.0 s; P > 0.05), as was the case for the fast-component time constants (M, 16.3 +/- 2.0 s; H, 13.5 +/- 1.0 s; S, 14.6 +/- 0.3 s; P > 0.05). In the H and S (but not M) domains, the VO2 following resolution of the fast component was elevated above the preexercise baseline (H, 3.0 +/- 1.0 l/min; S, 5.7 +/- 1.1 l/min). This additional postexercise VO2 was correlated to the end-exercise increase in lactate (r = 0.94, P < 0.001) but not the end-exercise pulmonary arterial blood temperature (r = 0.45, P > 0.05). These data indicate that the time delay and subsequent kinetic response of the primary (fast-component) phase of exercise VO2 recovery in the horse is independent of the preceding exercise-intensity domain. However, in the H and S domains, the fast component resolves to an elevated baseline.
Animals↗
Impaired capillary hemodynamics in skeletal muscle of rats in chronic heart failure.
Skeletal muscle blood flow is reduced and O(2) extraction is increased at rest in chronic heart failure (CHF). Knowledge of red blood cell (RBC) flow distribution within the capillary network is necessary for modeling O(2) delivery and exchange in this disease. Intravital microscopy techniques were used to study the in vivo spinotrapezius muscle microcirculation in rats with CHF 7 wk after myocardial infarction and in sham-operated controls (sham). A decrease in mean muscle fiber width from 51.3 +/- 1.9 microm in sham to 42.6 +/- 1.4 microm in CHF rats (P < 0.01) resulted in an increased lineal density of capillaries in CHF rats (P < 0.05). CHF reduced (P < 0.05) the percentage of capillaries supporting continuous RBC flow from 87 +/- 5 to 66 +/- 5%, such that the lineal density of capillaries supporting continuous RBC flow remained unchanged. The percentage of capillaries supporting intermittent RBC flow was increased in CHF rats (8 and 27% in sham and CHF, respectively, P < 0.01); however, these capillaries contributed only 2.3 and 3.3% of the total RBC flux in sham and CHF rats, respectively. In continuously RBC-perfused capillaries, RBC velocity (252 +/- 20 and 144 +/- 9 microm/s in sham and CHF, respectively, P < 0.001) and flux (21.4 +/- 2.4 and 9.4 +/- 1.1 cells/s in sham and CHF, respectively, P < 0.01) were markedly reduced in CHF compared with sham rats. Capillary "tube" hematocrit remained unchanged (0.22 +/- 0.02 and 0.19 +/- 0.02 in sham and CHF, respectively, P > 0.05). We conclude that CHF causes spinotrapezius fiber atrophy and reduces the number of capillaries supporting continuous RBC flow per fiber. Within these capillaries supporting continuous RBC flow, RBC velocity and flux are reduced 45-55%. This decreases the potential for O(2) delivery but enhances fractional O(2) extraction by elevating RBC capillary residence time. The unchanged capillary tube hematocrit suggests that any alterations in muscle O(2) diffusing properties in CHF are mediated distal to the RBC.
Animals↗
Evidence of skeletal muscle metabolic reserve during whole body exercise in patients with chronic obstructive pulmonary disease.
When freed from central cardiorespiratory limitations, healthy human skeletal muscle has exhibited a significant metabolic reserve. We studied the existence of this reserve in 10 severely compromised (FEV1 = 0.97 +/- SE 0.01) patients with chronic obstructive pulmonary disease (COPD). To manipulate O2 supply and O2 demand in locomotor and respiratory muscles, subjects performed both maximal conventional two-legged cycle ergometry (large muscle mass) and single-leg knee extensor exercise (KE, small muscle mass) while breathing room air (RA), 100% O2, and 79% helium + 21% O2 (HeO2). With each gas mixture, peak ventilation, peak heart rate, and perceived breathlessness were lower in KE than cycle exercise (p < 0. 05). Arterial O2 saturation and maximal work capacity increased in both exercise modalities while subjects breathed 100% O2 (work: +10% bike, +25% KE, p < 0.05). HeO2 increased maximal work capacity on the cycle (+14%, p < 0.05) but had no effect on KE. HeO2 resulted in the greatest maximum minute ventilation in both bike and KE (p < 0. 05) but had no effect on arterial O2 saturation. Thus, a skeletal muscle metabolic reserve in these patients with COPD is evidenced by: (1) greater muscle mass specific work in KE; (2) greater work rates with higher fraction of inspired oxygen (FIO2); (3) an even greater effect of FIO2 during KE (i.e., when the lungs are less challenged); and (4) the positive effect of HeO2 on bicycle work rate. This skeletal muscle metabolic reserve suggests that reduced whole body exercise capacity in COPD is the result of central restraints rather than peripheral skeletal muscle dysfunction, while the beneficial effect of 100% O2 (with no change in maximum ventilation) suggests that the respiratory system is not the sole constraint to oxygen consumption.
Aged↗
A comparison of the microcirculation in the rat spinotrapezius and diaphragm muscles.
Of all skeletal muscles examined in the rat, the spinotrapezius (S) and diaphragm (D) have the closest fiber-type composition. However, their oxidative capacities differ by two- to threefold. We have developed an intravital microscopy preparation to study diaphragm microcirculation in vivo. Using this preparation and the standard spinotrapezius model first described by S. D. Gray (1973, Microvasc. Res. 5, 395-400), we tested the hypothesis that pronounced microcirculatory differences would exist between these two muscles as a function of their disparate oxidative capacities. The lineal density of all capillaries in the spinotrapezius was 33.6 +/- 1.5 compared to 65.1 +/- 3.3 capillaries/mm in the diaphragm (P < 0.001). In the diaphragm compared with the spinotrapezius muscle, a significantly (P < 0.05) greater proportion of capillary countercurrent flow (D, 29 +/- 6% vs 8 +/- 6%) existed. Within both muscles, there was a similar proportion of capillaries supporting red blood cell (RBC) flow (S, 89 +/- 7% vs D, 92 +/- 2%). However, the diaphragm supported significantly (P < 0.001) greater intracapillary RBC velocities (D, 302 +/- 11 vs S, 226 +/- 9 micron/s) and fluxes (D, 33.4 +/- 1.1 vs S, 19.2 +/- 2.1 cells/s) compared with the spinotrapezius. Capillary "tube" hematocrit was greater (P = 0.01) in the diaphragm (0.32 +/- 0.02) than in the spinotrapezius (0.22 +/- 0.03) muscle. These data demonstrate that microcirculatory flow characteristics in resting muscle can be regulated independent of muscle fiber-type composition and may be related to muscle oxidative capacity.
Animals↗
Skeletal muscle microcirculatory structure and hemodynamics in diabetes.
Within skeletal muscle, insulin-dependent (Type 1) diabetes produces straighter, narrower capillaries. To test the hypothesis that these microvascular alterations would be associated with impaired capillary hemodynamics, intravital microscopy techniques were used to study the in vivo spinotrapezius muscle microcirculation of age-matched control (C) and streptozotocin (STZ) induced diabetic (D) rats. D rats exhibited a marked reduction in body weight (C, 266 +/- 5 g; D, 150 +/- 6 g; P < 0.001). At resting sarcomere lengths (i.e. approximately 2.7 microm), the additional capillary length arising from tortuosity and branching was less in D muscle (C, 10.5 +/- 0.8%; D, 5.3 +/- 1.0%, P < 0.01). Capillary diameter was reduced in D muscle (C, 5.4 +/- 0.1 microm; D, 4.6 +/- 0.1 microm; P < 0.001), and was positively correlated (r = 0.71) with the decreased proportion of capillaries sustaining flow (C, 85 +/- 5%; D, 53 +/- 3%; P < 0.001). Within those 'flowing' capillaries, red blood cell (RBC) velocity and flux were reduced 29 and 43%, respectively in D muscle (both P < 0.05). This reduced calculated O2 delivery by 57% per unit tissue width and 41% per unit muscle mass. Capillary 'tube' hematocrit was unchanged from control values (C, 0.22 +/- 0.02; D, 0.22 +/- 0.02). We conclude that, in the diabetic state, microvascular remodeling is associated with a reduced proportion of 'flowing' capillaries and a reduction in RBC velocity and flux in these vessels such that skeletal muscle O2 delivery is markedly reduced.
Animals↗
Effect of heart failure on muscle capillary geometry: implications for 02 exchange.
UNLABELLED: There is strong evidence that chronic heart chronic heart failure (CHF) impairs skeletal muscle function independent of blood flow and bulk O2 delivery. PURPOSE: This investigation sought to determine whether alterations in muscle capillary geometry and surface area that are thought to be primary determinants of the efficacy for blood-tissue 02 exchange might be altered in CHF and contribute to these changes. METHODS: Plantaris (fast twitch) and soleus (slow twitch) muscles from control (C) and 6- to 7-wk post myocardial infarcted (CHF) rates were perfusion-fixed in situ. These muscles were analyzed using morphometric techniques that facilitated determination of muscle sarcomere length fiber cross-sectional area, capillary tortuosity and branching coefficient (c(K,0)), capillary length, volume, and surface area. RESULTS: Normalized to a sarcomere length of 2.1 microns, plantaris fiber cross-sectional area decreased by 21% (P < 0.05), and capillary-to-fiber ratio decreased from 2.05 +2- 0.07 in C to 1.79 +2- 0.04 (P < 0.05) in CHF, but these variables were unchanged in soleus. These was no change in c(K,0) or capillary diameter in either muscle, and thus capillary length and surface area per fiber volume remained unchanged. From the measured fiber atrophy and capillary involution in plantaris reductions of total muscle capillary length, volume, and surface area of 11%, 9% and 17%, respectively, are estimated. CONCLUSION: These changes, coupled with reduced blood flow may impair the effective matching of muscle fiber 02 delivery to 02 requirement during repeated muscle contractions (i.e. exercise). The scenario is expected to reduce intramyocyte 02 partial pressure and thereby contribute to the greater fatigability characteristic of the CHF condition.
Animals↗
Effects of emphysema on diaphragm blood flow during exercise.
Chronic hyperinflation of the lung in emphysema displaces the diaphragm caudally, thereby placing it in a mechanically disadvantageous position and contributing to the increased work of breathing. We tested the hypothesis that total and regional diaphragm blood flows are increased in emphysema, presumably reflecting an increased diaphragm energetic demand. Male Syrian Golden hamsters were randomly divided into emphysema (E; intratracheal elastase 25 units/100 g body wt) and control (C; saline) groups, and experiments were performed 16-20 wk later. The regional distribution of blood flow within the diaphragm was determined by using radiolabeled microspheres in hamsters at rest and during treadmill exercise (walking at 20 feet/min, 20% grade). Consistent with pronounced emphysema, lung volume per unit body weight was greater in E hamsters (C, 59.3 +/- 1.8; E, 84.5 +/- 5.0 ml/kg; P < 0.001) and arterial PO2 was lower both at rest (C, 74 +/- 3; E, 59 +/- 2 Torr; P < 0.001) and during exercise (C, 93 +/- 3; E, 69 +/- 4 Torr; P < 0.001). At rest, total diaphragm blood flow was not different between C and E hamsters (C, 47 +/- 4; E, 38 +/- 4 ml . min-1 . 100 g-1; P = 0.18). In both C and E hamsters, blood flow at rest was lower in the ventral costal region of the diaphragm than in the dorsal and medial costal regions and the crural diaphragm. During exercise in both C and E hamsters, blood flows increased more in the dorsal and medial costal regions and in the crural diaphragm than in the ventral costal region. Total diaphragm blood flow was greater in E hamsters during exercise (C, 58 +/- 7; E, 90 +/- 14 ml . min-1 . 100 g-1; P = 0.03), as a consequence of significantly higher blood flows in the medial and ventral costal regions and crural diaphragm. In addition, exercise-induced increases in intercostal (P < 0.005) and abdominal (P < 0.05) muscle blood flows were greater in E hamsters. The finding that diaphragm blood flow was greater in E hamsters during exercise supports the contention that emphysema increases the energetic requirements of the diaphragm.
Animals↗
Pulmonary emphysema decreases hamster skeletal muscle oxidative enzyme capacity.
Skeletal muscle oxidative enzyme capacity is impaired in patients suffering from emphysema and chronic obstructive pulmonary disease. This effect may result as a consequence of the physiological derangements because of the emphysema condition or, alternatively, as a consequence of the reduced physical activity level in these patients. To explore this issue, citrate synthase (CS) activity was measured in selected hindlimb muscles and the diaphragm of Syrian Golden hamsters 6 mo after intratracheal instillation of either saline (Con, n = 7) or elastase [emphysema (Emp); 25 units/100 g body weight, n = 8]. Activity level was monitored, and no difference between groups was found. Excised lung volume increased with emphysema (Con, 1.5 +/- 0.3 g; Emp, 3.0 +/- 0.3 g, P < 0.002). Emphysema significantly reduced CS activity in the gastrocnemius (Con, 45.1 +/- 2.0; Emp, 39.2 +/- 0.8 micromol . min-1 . g wet wt-1, P < 0.05) and vastus lateralis (Con, 48.5 +/- 1.5; Emp, 44.9 +/- 0.8 micromol . min-1 . g wet wt-1, P < 0.05) but not in the plantaris (Con, 47.4 +/- 3.9; Emp, 48.0 +/- 2.1 micromol . min-1 . g wet wt-1, P < 0.05) muscle. In contrast, CS activity increased in the costal (Con, 61.1 +/- 1.8; Emp, 65.1 +/- 1.5 micromol . min-1 . g wet wt-1, P < 0.05) and crural (Con, 58.5 +/- 2.0; Emp, 65.7 +/- 2.2 micromol . min-1 . g wet wt-1, P < 0.05) regions of the diaphragm. These data indicate that emphysema per se can induce decrements in the oxidative capacity of certain nonventilatory skeletal muscles that may contribute to exercise limitations in the emphysematous patient.
Animals↗
Diaphragm structure and function in health and disease.
The diaphragm is the primary muscle of inspiration, and as such uncompromised function is essential to support the ventilatory and gas exchange demands associated with physical activity. The normal healthy diaphragm may fatigue during intense exercise, and diaphragm function is compromised with aging and obesity. However, more insidiously, respiratory diseases such as emphysema mechanically disadvantage the diaphragm, sometimes leading to muscle failure and death. Based on metabolic considerations, recent evidence suggests that specific regions of the diaphragm may be or may become more susceptible to failure than others. This paper reviews the regional differences in mechanical and metabolic activity within the diaphragm and how such heterogeneities might influence diaphragm function in health and disease. Our objective is to address five principal areas: 1) Regional diaphragm structure and mechanics (GAF). 2) Regional differences in blood flow within the diaphragm (WLS). 3) Structural and functional interrelationships within the diaphragm microcirculation (DCP). 4) Nitric oxide and its vasoactive and contractile influences within the diaphragm (MBR). 5) Metabolic and contractile protein plasticity in the diaphragm (SKP). These topics have been incorporated into three discrete sections: Functional Anatomy and Morphology, Physiology, and Plasticity in Health and Disease. Where pertinent, limitations in our understanding of diaphragm function are addressed along with potential avenues for future research.
Aging↗
In vivo microvascular structural and functional consequences of muscle length changes.
As muscles are stretched, blood flow and oxygen delivery are compromised, and consequently muscle function is impaired. We tested the hypothesis that the structural microvascular sequellae associated with muscle extension in vivo would impair capillary red blood cell hemodynamics. We developed an intravital spinotrapezius preparation that facilitated direct on-line measurement and alteration of sarcomere length simultaneously with determination of capillary geometry and red blood cell flow dynamics. The range of spinotrapezius sarcomere lengths achievable in vivo was 2.17 +/- 0.05 to 3.13 +/- 0.11 microns. Capillary tortuosity decreased systematically with increases of sarcomere length up to 2.6 microns, at which point most capillaries appeared to be highly oriented along the fiber longitudinal axis. Further increases in sarcomere length above this value reduced mean capillary diameter from 5.61 +/- 0.03 microns at 2.4-2.6 microns sarcomere length to 4.12 +/- 0.05 microns at 3.2-3.4 microns sarcomere length. Over the range of physiological sarcomere lengths, bulk blood flow (radioactive microspheres) decreased approximately 40% from 24.3 +/- 7.5 to 14.5 +/- 4.6 ml.100 g-1.min-1. The proportion of continuously perfused capillaries, i.e., those with continuous flow throughout the 60-s observation period, decreased from 95.9 +/- 0.6% at the shortest sarcomere lengths to 56.5 +/- 0.7% at the longest sarcomere lengths and was correlated significantly with the reduced capillary diameter (r = 0.711, P < 0.01; n = 18). We conclude that alterations in capillary geometry and luminal diameter consequent to increased muscle sarcomere length are associated with a reduction in mean capillary red blood cell velocity and a greater proportion of capillaries in which red blood cell flow is stopped or intermittent. Thus not only does muscle stretching reduce bulk blood (and oxygen) delivery, it also alters capillary red blood cell flow dynamics, which may further impair blood-tissue oxygen exchange.
Animals↗