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Biomedical subjects

M H Laughlin

Publications and source records attributed to M H Laughlin.

At least 127 records · Page 7Linked to original sources
PubMed1989

No relationship between progressive muscle hyperaemia and temperature in exercising rats.

During prolonged submaximal exercise muscle blood flow has been shown to increase progressively in rats and miniature swine. This study was designed to test the hypothesis that the increases in muscle blood flow are associated with progressive elevations in body temperature in rats. Colonic temperature and muscle blood flow (determined using radioactive microspheres) were measured after 15, 30 and 45 min of exercise in rats exercising on a treadmill at 15 m min-1 on a 0 degree incline. Total hindlimb muscle blood flow increased from 79 +/- 8 ml min-1 100 g-1 at 15 min to 95 +/- 10 ml min-1 100 g-1 at 30 min (P less than 0.05). The greatest increases in blood flow occurred in the deep extensor muscles of the hindlimb. For example, in the red portion of the gastrocnemius muscle, blood flow increased from 197 +/- 15 ml min-1 100 g-1 at 15 min to 285 +/- 17 ml min-1 100 g-1 at 30 min (P less than 0.05). Colonic temperature, however, remained stable at 38.5 degrees C over this period. These data indicate that the progressive hyperaemia in muscle was unrelated to body temperature.

Animals↗
PubMed1989

Naloxone does not affect muscle blood flow during low intensity exercise in rats.

The purpose of this study was to determine whether endogenous opioids are involved in the control of skeletal muscle blood flow during locomotory exercise in rats. The radiolabeled miscrosphere technique was used to measure total and regional muscle blood flow. We first determined whether methionine enkephalin (1,000 micrograms.kg-1 I.V.) would produce vasodilation in muscle vascular beds. We found that methionine enkephalin produced a 36 mm Hg (range of 20-50 mm Hg) drop in mean arterial pressure (Pa), which was associated with decreases in calculated skeletal muscle vascular resistance in anesthetized rats, and that these effects on arterial pressure and skeletal muscle vascular resistance were blocked by the infusion of naloxone (10 micrograms.kg-1). Measurements were then made at 5 min of treadmill exercise at 15 m.min-1 (0 degree incline) and following exercise in both saline-treated (controls) and naloxone (10 micrograms.kg-1)-treated conscious rats. There were no differences between the heart rates, blood pressures, or total muscle blood flows of the two groups. There were also no significant differences between the blood flows to 32 hind limb muscle samples composed of various muscle fiber types. Since naloxone blockade did not affect total or regional muscle blood flow during low intensity exercise, it appears that the endogenous opioids are not required for the normal exercise hyperemia of skeletal muscles.

Animals↗
PubMed1989

Effects of dipyridamole on the cardiovascular response to +Gz stress in miniature swine.

Eight conscious female miniature swine experienced acceleration levels of 3, 5, and 7 +Gz before and after infusion of dipyridamole (1-2 mg.kg-1). Each animal was instrumented to measure ECG, heart level arterial pressure (AP), eye level arterial pressure (ELBP), left arterial pressure (LAP), heart rate (HR), and regional tissue blood flows. Each was also fitted with an abdominal anti-G suit which automatically inflated. Dipyridamole infusion had no direct effect on HR or LAP but AP was significantly reduced. All cardiovascular responses to +Gz were qualitatively similar before and after dipyridamole. Tachycardia always occurred. AP and CNS blood flow were maintained better prior to dipyridamole and AP always fell in proportion to acceleration intensity. +Gz was generally associated with increased blood flow to respiratory muscles and heart, decreased blood flow throughout the viscera and to the eyes. ELBP paralleled AP, but was always lower in direct proportion to the +Gz level. We conclude that dipyridamole reduces arterial pressure thus compromising the ability of the animal to sustain cerebral perfusion pressure (ELBP) during +Gz.

Animals↗
PubMed1988

High-intensity exercise training increases vascular transport capacity of rat hindquarters.

The purpose of this study was to determine whether high-intensity exercise training increases the vascular flow capacity and capillary exchange capacity in isolated rat hindquarters. One group of 20 male Sprague-Dawley rats underwent six bouts of alternating running (2.5 min) and recovery (4.5 min), 5 days/wk at 60 m/min on a 15% grade for 6-10 wk (high-intensity exercise training), while a second group of 20 rats was cage confined (sedentary controls). Experiments were conducted in isolated, maximally dilated (papaverine) hindquarters perfused with an artificial plasma consisting of a Tyrode's solution containing 5 g/100 ml albumin. Vascular flow capacity was evaluated by measuring perfusate flow rate at four different perfusion pressures. Capillary exchange capacity was evaluated by measuring the capillary filtration coefficient. The efficacy of training was demonstrated by significant increases in succinate dehydrogenase activity in the white vastus lateralis and vastus intermedius muscles. Total hindquarter flow capacity was elevated 50-100% in the trained rats. This increased flow capacity was associated with an increase in the capillary filtration coefficient in the maximally vasodilated hindquarters, thus suggesting that the capillary exchange capacity was increased with high-speed exercise training. These results suggest that the vascular transport capacity in rat hindquarter muscles is significantly increased by high-intensity exercise training.

Animals↗
PubMed1988

Evidence for lack of importance of oxygen free radicals in Escherichia coli endotoxemia in dogs.

Reactive oxygen species have been proposed as pathophysiological factors responsible for the hypodynamic circulatory response to gram-negative endotoxin. To test this hypothesis, we examined the cardiorespiratory effects of mechanistically different oxygen free radical scavenging agents during Escherichia coli endotoxemia in beagle dogs. Pentobarbital-anesthetized dogs were instrumented for repeated sampling of cardiorespiratory, hematologic, and tissue blood flow (radiolabeled 15-micron microspheres) indexes. Four groups were studied: 1) time-matched control dogs (n = 6); 2) dogs receiving only endotoxin (1.5 mg/kg; n = 6); 3) dogs receiving endotoxin and combination therapy with allopurinol (150 mg/kg) plus superoxide dismutase (5 mg/kg) and catalase (5 mg/kg; n = 6); and 4) dogs receiving endotoxin and deferoxamine (30 mg/kg; n = 5). Measured variables in control dogs were constant during the 4-h study, whereas endotoxin-injected dogs consistently demonstrated the following: 1) maintained reductions in blood pressure (greater than 45%), left ventricular systolic pressure (greater than 43%), left ventricular maximum rate of pressure development (+/- dP/dtmax) (greater than 41%), cardiac index (greater than 33%), and blood flow in all sampled tissues except liver and skeletal muscle; 2) transient tachypnea, bradycardia, and arterial acidosis; and 3) persistent neutropenia and hemoconcentration. Neither of the free radical scavenging protocols significantly improved measured variables during endotoxemia (P greater than 0.05). This lack of efficacy suggests that superoxide anion, hydrogen peroxide, and hydroxyl radical may lack primary pathophysiological importance during the development of E. coli endotoxicosis in intact dogs.

Animals↗
PubMed1988

Systemic adenosine deaminase administration does not reduce active hyperemia in running rats.

The importance of adenosine in controlling the magnitude and distribution of blood flow among and within skeletal muscles in rats during slow locomotor exercise was tested by systemic infusion of adenosine deaminase (ADA). Blood flows were measured using labeled microspheres before exercise and at 0.5, 15, and 30 min of fast treadmill walking at 15 m/min. An initial infusion of ADA (1,000 U/kg) was given 30 min before the first blood flow measurement and a second injection (1,000 U/kg) was given 5 min into exercise. These infusions maintained ADA activity above 5 U/ml blood throughout the experimental period. This plasma concentration of ADA was shown to be sufficient to result in a 64% decrease in muscle adenosine levels during ischemic contraction. Blood flows were measured in all of the muscles of the hindlimb (28 samples) and in various nonmuscular tissues in ADA-treated and control rats. Preexercise blood flows were primarily directed to slow-twitch muscles and exercise blood flows were highest in muscles with fast-twitch oxidative fibers. ADA treatment did not reduce total muscle blood flow or exercise blood flows in any of the muscles at any time. These findings do not support the hypothesis that adenosine plays an essential role in controlling muscle blood flow in skeletal muscles during normal locomotor activity.

Adenosine Deaminase↗
PubMed1988

Regional muscle blood flow capacity and exercise hyperemia in high-intensity trained rats.

The purpose of this study was to determine the effects of high-intensity treadmill exercise training on 1) the regional distribution of muscle blood flow within and among muscles in rats during high-intensity treadmill exercise (phase I) and 2) on the total and regional hindlimb skeletal muscle blood flow capacities as measured in isolated perfused rat hindquarters during maximal papaverine vasodilation (phase II). Two groups of male Sprague-Dawley rats were trained 5 days/wk for 6 wk with a program consisting of 6 bouts/day of 2.5-min runs at 60 m/min up a 15% grade with 4.5-min rest periods between bouts. After training, blood flows were measured with the radiolabeled microsphere technique (phase I) in pair-weighted sedentary control and exercise-trained rats while they ran at 60 m/min (0% grade). In phase II of the study, regional vascular flow capacities were determined at three perfusion pressures (30, 40, and 50 mmHg) in isolated perfused hindquarters of control and trained rats maximally vasodilated with papaverine. The results indicate that this exercise training program produces increases in the vascular flow capacity of fast-twitch glycolytic muscle tissue of rats. However, these changes were not apparent in the magnitude or distribution of muscle blood flow in conscious rats running at 60 m/min, since blood flows within and among muscles during exercise were the same in trained and control rats.

Animals↗
PubMed1988

Coronary blood flow reserve during +Gz stress and treadmill exercise in miniature swine.

The purpose of this study was to compare the coronary blood flow reserve (CBFR) that exists during maximal +Gz stress to the CBFR during maximal exercise stress. Maximal exercise stress was defined as an exercise intensity greater than or equal to that necessary to produce maximal levels of O2 consumption (VO2max). Coronary blood flows (CBF) were determined with the use of the microsphere technique in chronically instrumented conscious miniature swine during +Gz stress and exercise stress at 70 and 100% of maximal tolerance (for each stress) before and after maximal coronary vasodilation with 1-2 mg/kg dipyridamole. CBFR was measured as the amount of blood flow increase produced by maximal coronary vasodilation. During exercise at VO2max, dipyridamole produced 20-30% increases in CBF, whereas it induced no coronary vasodilation or changes in CBF during +Gz stress. Dipyridamole also produced decreases in the animals' tolerance to +Gz in that all five animals could maintain a steady state for 60 s at 7 +Gz before dipyridamole, whereas only two of these animals could maintain a steady state for 60 s at 7 +Gz after dipyridamole. These results confirm that CBFR exists during maximal exercise in normal mammals. However, this dose of dipyridamole produced no coronary vasodilation during either level of +Gz stress.

Animals↗
PubMed1988

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.

Animals↗
PubMed1988

Muscle hemodynamics in hereditary myopathy of Labrador retrievers.

Morphologic lesions seen in six 8-month-old Labrador Retrievers with hereditary myopathy were predominantly small- and large-group atrophy of muscle cells of all fiber types. The dogs were intolerant of exercise and fatigued rapidly. An isolated gracilis muscle preparation was used to study the hemodynamic features of the microvasculature. Isogravimetric capillary pressure as well as arterial and venous pressures in the isolated gracilis muscle preparation obtained during maximal vasodilatation were within the range reported for healthy, mixed-breed dogs, as were precapillary, postcapillary, and total vascular resistances. Capillary filtration and osmotic reflection coefficients were not different from those reported in other studies on healthy dogs. All measurements and calculations were repeated during reperfusion, subsequent to a 4-hour period of global ischemia. Postischemic vascular responses were similar to the pattern previously reported in healthy dogs. These studies did not support the hypothesis of a vascular defect as a cause of hereditary myopathy in Labrador Retrievers.

Animals↗
PubMed1988

Coronary blood flow and cardiac adenine nucleotides in E. coli endotoxemia in dogs: effects of oxygen radical scavengers.

The purposes of this study were to determine the effects of E. coli endotoxin shock on coronary blood flow (CBF) and myocardial adenine nucleotides and to determine if reactive oxygen species are major causal factors in these effects of endotoxin. Twenty-three pentobarbital-anesthetized Beagle dogs were instrumented for recording cardiorespiratory parameters, injected i.v. with saline (time-matched controls; n = 6) or endotoxin (1.5 mg/kg; n = 17), and studied for 4 h. Endotoxin dogs also received either i.v. saline (shock controls; n = 6) or i.v. treatment with either deferoxamine (30 mg/kg; n = 5) or triple therapy (n = 6) with a combination of allopurinol (150 mg/kg), superoxide dismutase (SOD) (5 mg/kg), and catalase (CAT) (5 mg/kg). Cardiorespiratory and tissue blood flow variables were constant in sham-shock controls during the study, whereas endotoxin dogs developed typical canine endotoxemia with decreased left ventricular (LV) function. CBF was decreased by approximately 40% (P less than or equal to 0.5) in all endotoxin groups throughout the 4 h study period. However, based on hemodynamic estimates of myocardial O2 demand and endocardial/epicardial blood flow ratios, it seemed that coronary flow was matched to metabolic rate in all endotoxin groups. Endotoxin significantly lowered LV myocardial concentrations of ADP, AMP, NADH, and NADPH (range = 37 to 54%, P less than or equal to 0.05), but ATP, NAD, and NADP concentrations were not changed. The adenylate charge of the myocardium was between 0.91 and 0.95 in all endotoxin groups, suggesting that adequate energy was available in the myocardium during endotoxin shock. The lack of influence of deferoxamine, allopurinol, SOD, and CAT is indirect evidence that oxygen radicals are not primary pathophysiologic mediators in the cardiac response to gram-negative endotoxemia in this endotoxin model.

Adenine Nucleotides↗
PubMed1987

Effects of [Met5]enkephalin on regional blood flow and vascular resistance in rabbits.

Methionine enkephalin [( Met5]enkephalin) has different cardiovascular effects, depending on species and routes of peptide administration. In anesthetized animals [Met5]enkephalin decreases blood pressure and heart rate. The site(s) and the mechanism of the hypotensive effects of the peptide are not known. The main purpose of this study was to test the hypothesis that [Met5]enkephalin dilates specifically a certain vascular bed which may account for the hypotensive effect of the peptide. Anesthetized male rabbits were instrumented for the measurement of blood pressure, heart rate, electrocardiogram and renal nerve activity. Four different microspheres (15 microns) were infused into the left ventricle in 10-15 s in either saline or with [Met5]enkephalin (1 mg/kg). Upon completion of the last microsphere injection the animals were killed and 35 tissues samples were taken for the determination of blood flow. Blood flows to many organs such as brain, glandular and cardiac tissues were not altered significantly by [Met5]enkephalin. However, [Met5]enkephalin increased blood flow to skeletal muscular bed. The increase in muscle blood flow was antagonized by naloxone, a specific opioid antagonist. These results suggest that the hypotensive action of [Met5]enkephalin in anesthetized rabbit is in part due to its vasodilatory effect in skeletal muscle.

Animals↗
PubMed1987

Intestinal hyperemia in experimental diabetes mellitus.

Intestinal blood flows were measured using the radioactive microsphere technique in anesthetized, fasted (18-24 h) rats 4 wk after administration of streptozotocin (65 mg/kg body wt) or its vehicle. Blood flow was increased along the length of the small bowel in diabetic rats relative to normal animals. In an attempt to define the mechanisms underlying the intestinal hyperemic response to diabetes, we employed an in situ, blood perfused, isolated rat jejunum-ileum preparation. Intestinal blood flow was increased by 37%, while intestinal vascular resistance was reduced by 39% in diabetic rats relative to control animals. Cross-perfusion of control intestinal preparations with arterial blood from diabetic rats produced a 30% increase in blood flow and a 24% reduction in vascular resistance. Increasing plasma osmolarity, plasma glucose concentration, or plasma glucagon concentration in control animals to levels measured in diabetic animals produced reductions in vascular resistance that were qualitatively similar to that seen in the diabetic intestine. Intestinal vascular sensitivity to norepinephrine was assessed by constructing dose-response curves in control and diabetic animals. The mean ED50 values for norepinephrine were increased in diabetic rats relative to control animals. These results indicate that the intestinal hyperemic response in diabetes may be related to increased levels of circulating vasodilators, including hyperosmolarity and glucagon, and a reduced vascular sensitivity to norepinephrine.

Animals↗
PubMed1987

Skeletal muscle blood flow capacity: role of muscle pump in exercise hyperemia.

An appreciation for the potential of skeletal muscle vascular beds for blood flow (blood flow capacity) is required if one is to understand the limits of the cardiorespiratory system in exercise. To assess this potential, an index of blood flow capacity that can be objectively measured is required. One obvious index would be to measure maximal muscle blood flow (MBF). However, a unique value for maximal MBF cannot be measured, since once maximal vasodilation is attained MBF is a function of perfusion pressure. Another approach would be to measure maximal or peak vascular conductance. However, peak vascular conductance is different among skeletal muscles composed of different fiber types and is a function of perfusion pressure during peak vasodilation within muscle composed of a given fiber type. Also, muscle contraction can increase or decrease blood flow and/or the apparent peak vascular conductance depending on the experimental preparation and the type of muscle contraction. Blood flows and calculated values of conductance appear to be greater during rhythmic contractions (with the appropriate frequency and duration) than observed in resting muscle during what is called "maximal" vasodilation. Moreover, dynamic exercise in conscious subjects produces the greatest skeletal muscle blood flows. The purpose of this review is to consider the interaction of the determinants of muscle blood flow during locomotory exercise. Emphasis is directed toward the hypothesis that the "muscle pump" is an important determinant of perfusion of active skeletal muscle. It is concluded that, during normal dynamic exercise, MBF is determined by skeletal muscle vascular conductance, the perfusion pressure gradient, and the efficacy of the muscle pump.

Animals↗
PubMed1987

Vascular transport capacity of hindlimb muscles of exercise-trained rats.

The purpose of this study was to determine whether chronic exercise training is associated with increased vascular flow capacity and capillary exchange capacity in skeletal muscles. One group of male Sprague-Dawley rats was cage confined for a period of 13-17 wk (sedentary control, C) and a second was trained for 1 h/day at a speed of 30 m/min up a 5 degrees incline for 13-17 wk (exercise trained, ET). Studies were conducted with maximally dilated (papaverine) isolated hindquarters of 13 C rats and 10 ET rats perfused with Tyrode's solution containing 5% albumin. Vascular flow capacity was estimated by measuring total and regional flows at three to five different perfusion pressures. Capillary exchange capacity was estimated by measuring maximal capillary filtration coefficients and capillary diffusion capacity for 51Cr-ethylenediaminetetraacetic acid (51Cr-EDTA). The efficacy of the training was shown by significant increases in succinate dehydrogenase activities of the vastus intermedius muscle. Total hindquarter flow capacity was 50% higher in the ET rats. Regional flow data indicated that the higher total flow was due to increased muscle flow (85%), with the high-oxidative muscle tissue having the greatest increases (e.g., 200% increase in red gastrocnemius muscle). The maximal capillary diffusion capacity values for the ET rats were 70% greater than control values. However, the capillary filtration capacity values of the C and ET rats were not different. We conclude that the vascular transport capacity of the high-oxidative areas of extensor muscles is increased by endurance training.

Animals↗
PubMed1987

Distribution of blood flow in muscles of miniature swine during exercise.

The purpose of this study was to determine how the distribution of blood flow within and among the skeletal muscles of miniature swine (22 +/- 1 kg body wt) varies as a function of treadmill speed. Radiolabeled microspheres were used to measure cardiac output (Q) and tissue blood flows in preexercise and at 3-5 min of treadmill exercise at 4.8, 8.0, 11.3, 14.5, and 17.7 km/h. All pigs (n = 8) attained maximal O2 consumption (VO2max) (60 +/- 4 ml X min-1 X kg-1) by the time they ran at 17.7 km/h. At VO2max, 87% of Q (9.9 +/- 0.5 l/min) was to skeletal muscle, which constituted 36 +/- 1% of body mass. Average total muscle blood flow at VO2max was 127 +/- 14 ml X min-1 X 100 g-1; average limb muscle flow was 135 +/- 17 ml X min-1 X 100 g-1. Within the limb muscles, blood flow was distributed so that the deep red parts of extensor muscles had flows about two times higher than the more superficial white portions of the same muscles; the highest muscle blood flows occurred in the elbow flexors (brachialis: 290 +/- 44 ml X min-1 X 100 g-1). Peak exercise blood flows in the limb muscles were proportional (P less than 0.05) to the succinate dehydrogenase activities (r = 0.84), capillary densities (r = 0.78), and populations of oxidative (slow-twitch oxidative + fast-twitch oxidative-glycolytic) fiber types (r = 0.93) in the muscles. Total muscle blood flow plotted as a function of exercise intensity did not peak until the pigs attained VO2max, although flows in some individual muscles showed a plateau in this relationship at submaximal exercise intensities. The data demonstrate that blood flow in skeletal muscles of miniature swine is distributed heterogeneously and varies in relation to fiber type composition and exercise intensity.

Animals↗
PubMed1987

Adrenoreceptor effects on rat muscle blood flow during treadmill exercise.

The purpose of this study was to examine the effects of the adrenergic receptors on the distribution of blood flow within and among skeletal muscles in rats. Blood flow was measured with the radiolabeled microsphere technique before exercise and during treadmill exercise at 15 or 60 m/min. Alpha- (phentolamine) or beta- (propranolol) adrenergic blocking drugs were administered, and then blood flow was measured and results compared with those from saline-treated rats. Before exercise, alpha-blockade caused increases in total muscle blood flow and in all fast-twitch muscles, whereas muscles composed of greater than 20% slow-twitch fibers showed no effect. During exercise at 15 m/min, the normal increase in total muscle blood flow was attenuated by alpha-blockade. Compared with controls, blood flow was less in the high-oxidative (fast and slow) muscle fiber areas of extensor muscles, whereas blood flow to white areas of extensor muscles was increased. beta-Blockade tended to decrease muscle blood flow before exercise and during exercise at 15 m/min with no apparent relationship between the effects of blockade on blood flow and muscle fiber type. These effects of beta-blockade were not apparent during exercise at 60 m/min. We conclude that before exercise alpha-receptor effects are limited to fast muscle, whereas beta-receptor influences are independent of fiber type, beta-receptors contribute to the initial hyperemia of exercise at 15 m/min, and beta-receptor influence is inversely related to metabolic rate.

Adrenergic alpha-Antagonists↗