Costal diaphragmatic O2 and lactate extraction in laryngeal hemiplegic ponies during exercise

Diaphragmatic O2 and lactate extraction were examined in seven healthy ponies during maximal exercise (ME) carried out without, as well as with, inspiratory resistive breathing. Arterial and diaphragmatic venous blood were sampled simultaneously at rest and at 30-s intervals during the 4 min of ME. Experiments were carried out before and after left laryngeal hemiplegia (LH) was produced. During ME, normal ponies exhibited hypocapnia, hemoconcentration, and a decrease in arterial PO2 (PaO2) with insignificant change in O2 saturation. In LH ponies, PaO2 and O2 saturation decreased well below that in normal ponies, but because of higher hemoglobin concentration, arterial O2 content exceeded that in normal ponies. Because of their high PaCO2 during ME, acidosis was more pronounced in LH animals despite similar lactate values. Diaphragmatic venous PO2 and O2 saturation decreased with ME to 15.5 +/- 0.9 Torr and 18 +/- 0.5%, respectively, at 120 s of exercise in normal ponies. In LH ponies, corresponding values were significantly less: 12.4 +/- 1.3 Torr and 15.5 +/- 0.7% at 120 s and 9.8 +/- 1.4 Torr and 14.3 +/- 0.6% at 240 s of ME. Mean phrenic O2 extraction plateaued at 81 and 83% in normal and LH animals, respectively. Significant differences in lactate concentration between arterial and phrenic-venous blood were not observed during ME. It is concluded that PO2 and O2 saturation in the phrenic-venous blood of normal ponies do not reach their lowest possible values even during ME. Also, the healthy equine diaphragm, even with the added stress of inspiratory resistive breathing, did not engage in net lactate production.     

Collateral sources of costal and crural diaphragmatic blood flow

We measured the contribution of aortic, internal mammary, and intercostal arteries to the blood flow to the costal and crural segments of the diaphragm and other respiratory muscles in seven dogs breathing against a fixed inspiratory elastic load. We used radiolabeled microspheres to measure the blood flow with control circulation, occlusion of the aorta distal to the left subclavian artery, combined occlusion of the aorta and both internal mammary arteries, and occlusion of internal mammary arteries alone. With occlusion of the aorta distal to the left subclavian artery, blood flow to the crural diaphragm decreased from 40.3 to 23.5 ml . min-1 X 100 g-1, whereas costal flow did not change significantly (from 41.7 to 38.1 ml . min-1 . 100 g-1). Blood flows to the sternomastoid and scalene muscles (above the occlusion) increased by 200 and 340%, respectively, whereas flows to the other respiratory muscles did not change significantly. Blood flows to organs above the occlusion either remained unchanged or increased, whereas flows to those below the occlusion all decreased. When the internal mammary artery was also occluded, flows to the crural segment decreased further to 12.1 and costal flow decreased to 20.4 ml X min-1 X 100 g-1. Internal mammary arterial occlusion alone in two dogs had no effect on diaphragmatic flow. In conclusion, intercostal collateral vessels are capable of supplying a significant proportion of blood flow to both segments of the diaphragm but the costal segment is better served than the crural segment.     

Cerebral blood flow during submaximal and maximal dynamic exercise in humans

Cerebral blood flow (CBF) in humans was measured at rest and during dynamic exercise on a cycle ergometer corresponding to 56% (range 27-85) of maximal O2 uptake (VO2max). Exercise bouts were performed by 16 male and female subjects, lasted 15 min each, and were carried out in a semisupine position. CBF (133Xe clearance) was expressed as the initial slope index (ISI) and as the first compartment flow (F1). CBF at rest [ISI, 58 (range 45-73); F1, 76 (range 55-98) ml.100 g-1.min-1] increased during exercise [ISI to 79 (57-94) and F1 to 118 (75-164) ml.100 g-1.min-1, P less than 0.01]. CBF did not differ significantly between work loads from 32 (24-33) to 86% (74-96) of VO2max (n = 10). During exercise, mean arterial pressure increased from 84 (60-100) to 101 (78-124) Torr (P less than 0.01) and PCO2 remained unchanged [5.1 (4.6-5.6) vs. 5.4 (4.4-6.3) kPa, n = 6]. These results demonstrate a median increase of 31% (0-87) in CBF by ISI and a median increase of 58% (0-133) in CBF by F1 during dynamic exercise in humans.     

Sympathetic neural influences on muscle blood flow in rats during submaximal exercise

These experiments were designed to estimate the involvement of the sympathetic innervation in regulation of hindlimb muscle blood flow distribution among and within muscles during submaximal locomotory exercise in rats. Blood flows to 32 hindlimb muscles and 13 other selected tissues were measured using the radiolabeled microsphere technique, before exercise and at 0.5, 2, 5, and 15 min of treadmill exercise at 15 m/min. The two groups of rats studied were 1) intact control, and 2) acutely sympathectomized (hindlimb sympathectomy accomplished by bilateral section of the lumbar sympathetic chain and its connections to the spinal cord at L2-L3). There were no differences in total hindlimb muscle blood flow among the two groups during preexercise or at 30 s or 2 min of exercise. However, flow was higher in eight individual muscles at 2 min of exercise in the sympathectomized rats. At 5 and 15 min of exercise there was higher total hindlimb muscle blood flow in the denervated group compared with control. These differences were also present in many individual muscles. Our results suggest that 1) sympathetic nerves do not exert a net influence on the initial elevations in muscle blood flow at the beginning of exercise, 2) sympathetic nerves are involved in regulating muscle blood flow during steady-state submaximal exercise in conscious rats, and 3) these changes are seen in muscles of all fiber types.     

Forearm blood flow follows work rate during submaximal dynamic forearm exercise independent of sex.

To test the hypothesis that sex influences forearm blood flow (FBF) during exercise, 15 women and 16 men of similar age [women 24.3 +/- 4.0 (SD) vs. men 24.9 +/- 4.5 yr] but different forearm muscle strength (women 290.7 +/- 44.4 vs. men 509.6 +/- 97.8 N; P < 0.05) performed dynamic handgrip exercise as the same absolute workload was increased in a ramp function (0.25 W/min). Task failure was defined as the inability to maintain contraction rate. Blood pressure and FBF were measured on separate arms during exercise by auscultation and Doppler ultrasound, respectively. Muscle strength was positively correlated with endurance time (r = 0.72, P < 0.01) such that women had a shorter time to task failure than men (450.5 +/- 113.0 vs. 831.3 +/- 272.9 s; P < 0.05). However, the percentage of maximal handgrip strength achieved at task failure was similar between sexes (14% maximum voluntary contraction). FBF was similar between women and men throughout exercise and at task failure (women 13.6 +/- 5.3 vs. men 14.5 +/- 4.9 ml.min(-1).100 ml(-1)). Mean arterial pressure was lower in women at rest and during exercise; thus calculated forearm vascular conductance (FVC) was higher in women during exercise but similar between sexes at task failure (women 0.13 +/- 0.05 vs. men 0.11 +/- 0.04 ml.min(-1).100 ml(-1).mmHg(-1)). In conclusion, the similar FBF during exercise was achieved by a higher FVC in the presence of a lower MAP in women than men. Still, FBF remained coupled to work rate (and presumably metabolic demand) during exercise irrespective of sex.     

Altered regional blood flow responses to submaximal exercise in older rats.

Maximal aerobic capacity and the ability to sustain submaximal exercise (Ex) declines with advancing age. Whether altered muscle blood flow (BF) plays a mechanistic role in these effects remains to be resolved. The present investigation determined the effects of aging on the hemodynamic and regional BF response to submaximal Ex in rats. Heart rate (HR), mean arterial pressure (MAP), and BF to different organs (kidneys, splanchnic organs, and 28 hindlimb muscles) were determined at rest and during submaximal treadmill Ex (20 m/min, 5% grade) with radiolabeled microspheres in young (Y; 6-8 mo old, 339 +/- 8 g, n = 9) and old (O; 27-29 mo old, 504 +/- 18 g, n = 7) Fischer 344 x Brown Norway rats. Results demonstrated that HR, MAP, and BF to the pancreas, small and large intestine, and total hindlimb musculature were similar between Y and O rats at rest. BF to the kidneys, spleen, and stomach were 33, 60, and 43% lower, respectively, in O compared with Y rats. BF to the total hindlimb musculature increased (P < 0.05) during Ex and was similar for both Y and O rats (Y: 16 +/- 3 to 124 +/- 7 vs. O: 20 +/- 3 to 137 +/- 12 ml.min-1.100 g-1). However, in O vs. Y rats, BF was reduced in 6 (highly oxidative) and elevated in 8 (highly glycolytic) of the 28 individual hindquarter muscles or muscle parts examined (P < 0.05). During Ex, BF to the spleen and stomach decreased (P < 0.05) from rest in Y rats, whereas BF decreased in the kidneys, pancreas, spleen, stomach, as well as the small and large intestines of O rats. In conclusion, these data demonstrate that, despite similar increases in total hindlimb BF in Y and O rats during submaximal Ex, there is a profound BF redistribution from highly oxidative to highly glycolytic muscles.     

Influence of respiratory muscle work on VO(2) and leg blood flow during submaximal exercise.

The work of breathing (W(b)) normally incurred during maximal exercise not only requires substantial cardiac output and O(2) consumption (VO(2)) but also causes vasoconstriction in locomotor muscles and compromises leg blood flow (Q(leg)). We wondered whether the W(b) normally incurred during submaximal exercise would also reduce Q(leg). Therefore, we investigated the effects of changing the W(b) on Q(leg) via thermodilution in 10 healthy trained male cyclists [maximal VO(2) (VO(2 max)) = 59 +/- 9 ml. kg(-1). min(-1)] during repeated bouts of cycle exercise at work rates corresponding to 50 and 75% of VO(2 max). Inspiratory muscle work was 1) reduced 40 +/- 6% via a proportional-assist ventilator, 2) not manipulated (control), or 3) increased 61 +/- 8% by addition of inspiratory resistive loads. Increasing the W(b) during submaximal exercise caused VO(2) to increase; decreasing the W(b) was associated with lower VO(2) (DeltaVO(2) = 0.12 and 0.21 l/min at 50 and 75% of VO(2 max), respectively, for approximately 100% change in W(b)). There were no significant changes in leg vascular resistance (LVR), norepinephrine spillover, arterial pressure, or Q(leg) when W(b) was reduced or increased. Why are LVR, norepinephrine spillover, and Q(leg) influenced by the W(b) at maximal but not submaximal exercise? We postulate that at submaximal work rates and ventilation rates the normal W(b) required makes insufficient demands for VO(2) and cardiac output to require any cardiovascular adjustment and is too small to activate sympathetic vasoconstrictor efferent output. Furthermore, even a 50-70% increase in W(b) during submaximal exercise, as might be encountered in conditions where ventilation rates and/or inspiratory flow resistive forces are higher than normal, also does not elicit changes in LVR or Q(leg).     

Pulmonary blood flow distribution in anesthetized ponies.

Results of recent investigations in humans and dogs indicate that gravity-independent factors may be important in determining the distribution of pulmonary blood flow. To further evaluate the role of gravity-independent factors, pulmonary blood flow distribution was examined using 15-microns radionuclide-labeled microspheres in five prone ponies over 5 h of pentobarbital sodium anesthesia. The ponies were killed, and the lungs were excised and dried by air inflation (pressure 45 cmH2O). The dry lungs were cut into transverse slices 1-2 cm thick along the dorsal-ventral axis, parallel to gravity. Radioactivity of pieces cut from alternate slices was measured with a gamma well counter. The main finding was a preferential distribution of pulmonary blood flow to dorsal-caudal regions and higher flow in the center of each lung slice when compared with the slice periphery. Flow was lowest in cranial and ventral areas. Differences of +/- 2 SD were observed between core and peripheral blood flow. No medial-lateral differences were found. Pulmonary blood flow distribution did not change over 5 h of anesthesia, and the basic flow pattern was not different in the left vs. right lung. These results suggest that in the intact prone mechanically ventilated pony (inspired O2 fraction greater than or equal to 0.95) factors other than gravity are primary determinants of pulmonary blood flow.     

Tracheobronchial perfusion during exercise in ponies

Tracheobronchial circulation during exercise has previously not been examined. Therefore blood flow to the trachea and bronchi (up to 7th generation of branching) was studied in seven healthy adult ponies at rest and during the 3rd and 10th min of exercise performed at a treadmill speed setting of 25 km/h. The ambient air temperature varied from 19 to 20 degrees C and humidity from 35 to 45%. To determine blood flow radionuclide-labeled 15-microns-diameter microspheres were injected into the left ventricle via a catheter advanced from the left carotid artery (exposed using local anesthesia), and a reference sample was obtained from the aorta. Adequate mixing of microspheres with blood was demonstrated by similar perfusion values for left and right kidneys. Exercise increased heart rate (194 +/- 9 and 200 +/- 7 beats/min) and mean aortic pressure (169 +/- 8 and 156 +/- 4 mmHg) of ponies at 3rd and 10th min. Tracheal blood flow (6.7 +/- 0.5 ml.min-1 x 100 g-1) of resting ponies was only one-third of the bronchial blood flow (21.6 +/- 4.9 ml.min-1 x 100 g-1) Significant changes in tracheal perfusion did not occur at 3rd or 10th min of exercise. Although bronchial perfusion also did not change at the 3rd min of exercise, it rose dramatically to 202.8 +/- 30.3 ml.min-1 x 100 g-1 during the 10th min. Concomitantly, renal blood flow decreased at 10th min of exertion. The large increase in bronchial blood flow at 10th min of exertion may have been necessitated by the need to help dissipate body heat.     

Independence of exercise hyperpnea and acidosis during high-intensity exercise in ponies

We investigated arterial PCO2 (PaCO2) and pH (pHa) responses in ponies during 6-min periods of high-intensity treadmill exercise. Seven normal, seven carotid body-denervated (2 wk-4 yr) (CBD), and five chronic (1-2 yr) lung (hilar nerve)-denervated (HND) ponies were studied during three levels of constant load exercise (7 mph-11%, 7 mph-16%, and 7 mph-22% grade). Mean pHa for each group of ponies became alkaline in the first 60 s (between 7.45 and 7.52) (P less than 0.05) at all work loads. At 6 min pHa was at or above rest at 7 mph-11%, moderately acidic at 7 mph-16% (7.32-7.35), and markedly acidic at 7 mph-22% (7.20-7.27) for all groups of ponies. Yet with no arterial acidosis at 7 mph 11%, normal ponies decreased PaCO2 below rest (delta PaCO2) by 5.9 Torr at 90 s and 7.8 Torr by 6 min of exercise (P less than 0.05). With a progressively more acid pHa at the two higher work loads in normal ponies, delta PaCO2 was 7.3 and 7.8 Torr by 90 s and 9.9 and 11.4 Torr by 6 min, respectively (P less than 0.05). CBD ponies became more hypocapnic than the normal group at 90 s (P less than 0.01) and tended to have greater delta PaCO2 at 6 min. The delta PaCO2 responses in normal and HND ponies were not significantly different (P greater than 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)     

Neural control of muscle blood flow during exercise.

Activation of skeletal muscle fibers by somatic nerves results in vasodilation and functional hyperemia. Sympathetic nerve activity is integral to vasoconstriction and the maintenance of arterial blood pressure. Thus the interaction between somatic and sympathetic neuroeffector pathways underlies blood flow control to skeletal muscle during exercise. Muscle blood flow increases in proportion to the intensity of activity despite concomitant increases in sympathetic neural discharge to the active muscles, indicating a reduced responsiveness to sympathetic activation. However, increased sympathetic nerve activity can restrict blood flow to active muscles to maintain arterial blood pressure. In this brief review, we highlight recent advances in our understanding of the neural control of the circulation in exercising muscle by focusing on two main topics: 1) the role of motor unit recruitment and muscle fiber activation in generating vasodilator signals and 2) the nature of interaction between sympathetic vasoconstriction and functional vasodilation that occurs throughout the resistance network. Understanding how these control systems interact to govern muscle blood flow during exercise leads to a clear set of specific aims for future research.     

Diaphragmatic O2 and lactate extraction during submaximal and maximal exertion in ponies

Diaphragmatic O2 and lactate extraction were studied in 10 healthy ponies at rest and during treadmill exercise. The phrenic vein was aseptically catheterized via a lateral thoracotomy 8-35 days before the study. Arterial and phrenic venous blood samples were obtained simultaneously at rest and at 30-s intervals during 4 min of exertion. Three levels of exertion were studied (moderate, 10 mi/h; heavy, 15 mi/h; maximal, 20 mi/h), and a rest period of at least 90 min was allowed between them. Each pony was studied twice at least 2-3 days apart. At rest the diaphragmatic venous PO2, O2 saturation, arteriovenous O2 content difference, and O2 extraction were 43.2 +/- 2.0 Torr, 76.1 +/- 3.2%, 3.14 +/- 0.43 ml/dl, and 23.60 +/- 3.61%, respectively. Significant decrease in phrenic venous PO2 and O2 saturation occurred within 30 s of exercise. Phrenic venous PO2 decreased to 20.3 +/- 1.0, 18.9 +/- 1.1, and 15.4 +/- 0.9 Torr at 120 s of moderate, heavy, and maximal exercise, respectively. Corresponding values of phrenic venous O2 saturation were 33.6 +/- 2.2, 25.8 +/- 2.1, and 17.9 +/- 0.5%, respectively. Diaphragmatic arteriovenous O2 content difference expanded to 13.11 +/- 0.49, 15.00 +/- 0.60, and 16.90 +/- 0.60 ml/dl at 120 s of moderate, heavy, and maximal exercise, respectively, as O2 extraction rose to 65.93 +/- 1.98, 73.90 +/- 1.99, and 80.95 +/- 0.47%, respectively. During heavy and maximal exercise, the diaphragmatic venous lactate concentration remained similar to the arterial concentration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inspiratory muscle fatigue increases sympathetic vasomotor outflow and blood pressure during submaximal exercise

The purpose of this study was to elucidate the influence of inspiratory muscle fatigue on muscle sympathetic nerve activity (MSNA) and blood pressure (BP) response during submaximal exercise. We hypothesized that inspiratory muscle fatigue would elicit increases in sympathetic vasoconstrictor outflow and BP during dynamic leg exercise. The subjects carried out four submaximal exercise tests: two were maximal inspiratory pressure (PI(max)) tests and two were MSNA tests. In the PI(max) tests, the subjects performed two 10-min exercises at 40% peak oxygen uptake using a cycle ergometer in a semirecumbent position [spontaneous breathing for 5 min and with or without inspiratory resistive breathing for 5 min (breathing frequency: 60 breaths/min, inspiratory and expiratory times were each set at 0.5 s)]. Before and immediately after exercise, PI(max) was estimated. In MSNA tests, the subjects performed two 15-min exercises (spontaneous breathing for 5 min, with or without inspiratory resistive breathing for 5 min, and spontaneous breathing for 5 min). MSNA was recorded via microneurography of the right median nerve at the elbow. PI(max) decreased following exercise with resistive breathing, whereas no change was found without resistance. The time-dependent increase in MSNA burst frequency (BF) appeared during exercise with inspiratory resistive breathing, accompanied by an augmentation of diastolic BP (DBP) (with resistance: MSNA, BF +83.4%; DBP, +23.8%; without resistance: MSNA BF, +19.2%; DBP, -0.4%, from spontaneous breathing during exercise). These results suggest that inspiratory muscle fatigue induces increases in muscle sympathetic vasomotor outflow and BP during dynamic leg exercise at mild intensity.