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Changes in blood pressure during isometric contractions to fatigue in the cat after brain stem lesions: effects of clonidine.

STUDY OBJECTIVE: The aim was to determine whether areas in the periaqueductal grey matter, medial dorsal raphe, or ventrolateral medulla might be involved with the integration of blood pressure and heart rate during isometric exercise. DESIGN: Cats were anaesthetised with alpha chloralose (75 mg.kg-1) and catheters inserted into the right jugular vein and carotid artery. Isometric contractions were generated using a microprocessor controlled stimulator and sleeve electrode around the tibial nerve. Bilateral lesions were made in the dorsal periaqueductal grey matter (P1.0, LR2.0, HD + 1.5 mm) or two sites in the ventrolateral medulla (P12.0, RL 2.0, HD -10 mm; or P12.0, RL 2.0, HD -8.5 mm). Lesions were also made in the medial dorsal raphé nuclei (P1.0, RL 0.0, HD +1.5 mm). Clonidine was injected into the cerebral aqueduct to determine whether it would exert an antipressor effect during muscle contraction after the lesions were made. Only one site of lesion was made in a group of animals. Bilateral injections of clonidine (250 ng in 0.5 microliter) were made into the intact ventrolateral medulla (P11.5, RL 4.0, HD -8.5 mm) to explore its role further. Fatiguing contractions were performed before and after the lesions were made, or clonidine was injected, and changes in arterial blood pressure and heart rate were measured. Verification of the lesion sites or the microinjection sites, and the extent of the lesion or spread of the clonidine, was made from histological examination of brain tissue after each experiment. EXPERIMENTAL MATERIAL: Adult cats of either sex, n = 20, weight 2.4 (SD 0.4) kg, were used. MEASUREMENTS AND MAIN RESULTS: Fatiguing isometric contractions in control conditions caused mean arterial pressure to increase by 45-50 mm Hg and heart rates by 20-25 beats.min-1. Bilateral lesions in the dorsal periaqueductal grey matter did not alter resting mean arterial pressure but attenuated the pressor response during contractions. Injections of clonidine into the cerebral aqueduct had no further antipressor effects after the lesions. Lesions of the medial dorsal raphé nuclei or injections of clonidine into the intact medial dorsal raphé nuclei did not affect the pressor response to fatiguing isometric contractions. Injections of clonidine into the intact ventrolateral medulla eliminated the pressor response to isometric contractions. Bilateral lesions of the ventrolateral medulla near the rostral lateral border of the inferior olivary tract nuclei (P12.0, LR 2.0, HD -10 mm) also attenuated the muscle pressor response, while subsequent injections of clonidine into the cerebral aqueduct depressed the changes in blood pressure further. CONCLUSIONS: Ergoreceptor information may be processed through the periaqueductal grey matter through the ventrolateral medulla to control arterial blood pressure during isometric exercise to fatigue.

Animals

Effect of uranyl ions on isometric contractions in rabbit atria.

The effects of uranyl ions on isometric contractions of atrial strips of rabbit heart were studied. It was observed that uranyl ions, in a concentration of 1.1 X 10(-5) M, do not alter isometric contraction; 2.2 X 10(-5) M concentration produced a small positive inotropic effect that was magnified at a 4.5 X 10(-5) M concentration; concentrations greater than 1.8 X 10(-5) M produced a negative inotropic effect. There is evidence that the positive inotropic effect is mediated by catecholamine release, in a similar manner to the action of uranyl ions on intestinal smooth muscle preparations. This response was blocked by propranolol and also after tyramine treatment of the preparation. The negative inotropic effect seems to be mediated by a blocking effect on calcium entry through the sarcolemma during activation. Indirect evidence supporting this hypothesis was the observation of a decrease of action of uranyl ions in the presence of isoproterenol and of increased extracellular calcium concentration.

Animals

Release of immunoreactive enkephalinergic substances in the periaqueductal grey of the cat during fatiguing isometric contractions.

Antibody-coated microprobes were used to determine whether immunoreactive enkephalins were released in response to fatiguing isometric contractions of the hind-limb muscles in cats anesthetized with alpha-chloralose. Contractions were performed by stimulating the tibial nerve via a microprocessor-controlled stimulator. Microprobes were inserted into the periaqueductal grey (P 0.5-1.0 mm) prior to, during and following fatiguing contractions. During fatiguing contractions, mean arterial blood pressure increased by 76 +/- 9 mmHg above resting and recovery levels. Levels of immunoreactive enkephalins were elevated in the dorsolateral periaqueductal grey during the isometric contraction when compared to resting levels. It is possible that isometric muscle contraction causes the release of Met-enkephalin-like substances in the periaqueductal grey.

Animals

Interaction of halothane and antibiotics on isometric contractions on rat-heart muscle.

Halothane (H), kanamycin (KM), streptomycin (SM), and chloramphenicol (CM) had direct negative inotropic effects on isometric contractions of isolated rat-heart muscles. Potassium penicillin-G did not show any significant changes in isometric contractions. The depression produced by these antibiotics was characterized by an abrupt onset, rapid progression, and rapid complete recovery, which suggests direct physicochemical rather than metabolic effects. On the other hand, the depression produced by H progressed slowly. When KM, SM, or CM were combined with H, there was a greater depression in isometric contractions than seen in the absence of H, suggesting that the innate characteristics of the antibiotics are augmented when any of them is administered together with halothane.

Animals

Effects of carotid artery occlusion on the pressor response induced by sustained isometric contraction in the cat.

The effects of clonidine, a central alpha 2 agonist, on changes in blood pressure caused by muscle afferent nerve (ergoreceptor) activation and baroreceptor manipulation were studied in cats. Prolonged isometric contractions (ergoreceptor activation) of the gastrocnemius and plantaris muscles increased mean arterial pressure by 53 mmHg. This pressor response was not altered by naloxone (0.5 mumol.litre-1) but was eliminated by clonidine (0.5-2.0 micrograms) when injected into the cerebral aqueduct. Brief occlusion of the carotid artery (15-30 s) caused mean arterial pressure to increase by 32-42 mmHg at rest. Neither naloxone nor clonidine altered the magnitude of the reflex pressor response to carotid occlusion. Similar increases in pressure were measured when occlusion was applied during fatiguing isometric contractions; thus baroreceptor induced increases in pressure were superimposed on the ergoreceptor induced blood pressure changes. Naloxone did not affect the changes in pressure caused by either reflex response. Clonidine continued to eliminate the pressor response to muscular contraction but did not affect the pressure increase when the carotid occlusion was applied during contractions. Electrical stimulation of the carotid sinus nerve caused blood pressure to decrease by 36 mmHg during rest and by 41 mmHg during fatiguing isometric contractions. Clonidine did not alter the depressor response to carotid sinus nerve stimulation. These data may indicate that separate pathways centrally mediate the changes in blood pressure caused by ergoreceptor and baroreceptor afferent activation. The integration of the ergoreceptor pathway may involve a catecholaminergic-opioidergic system but the present results do not suggest a similar interaction for the baroreceptor integration.

Animals

Effect of muscle mass on the pressor response in man during isometric contractions.

1. Changes in blood pressure and heart rate were measured in six healthy male subjects during voluntary isometric contractions of the forearm and quadriceps muscles. Arterial pressure was measured directly via a catheter inserted into the radial artery of the non-contracting arm. Each subject exerted two types of contractions: (a) sustained contractions at 70% of the maximum voluntary contraction (MVC) until fatigue occurred and (b) sustained contractions starting at maximum tension (100% MVC), held for a total duration of 1 min. 2. During fatiguing contractions at 70% MVC, there was a progressive increase in blood pressure, reaching a peak level at fatigue. The same level of mean arterial pressure was achieved during contractions of the same relative tension, regardless of the muscle mass. The same trend was observed for the changes in heart rate. 3. During contractions which started with the maximum tension, where tension fell continuously during the 60 s of maximal effort, mean arterial pressure rapidly increased to high levels within a few seconds, and then increased further by 20-30 mmHg during the sustained maximal effort. There was no difference in the initial rapid increases in mean arterial pressure, nor in the final mean arterial pressures reached between contractions of the forearm or quadriceps muscles. There were no differences in the heart rates achieved during these contractions either. 4. There was no significant difference between the mean arterial pressures observed at fatigue of a 70% MVC contraction or at the end of the 60 s maximum effort during handgrip contractions, or during contractions with the quadriceps muscles. 5. These results support the view that muscle mass is not a determinant of the magnitude of the cardiovascular reflexes during fatiguing isometric contractions in man.

Adult

Effects of hypoxemia with and without acidemia on the isometric contraction time and the electromechanical delay of the fetal myocardium: an experimental study on the ovine fetus.

This study assessed the response of the preejection period during hypoxemia with and without acidemia. In five pregnant ewes, hypoxemia was created during 1 hour followed by fetal infusion of lactic acid during 2 hours. A micromanometer catheter positioned above the fetal aortic valve, an endocavitary phonocardiogram, and a fetal electrocardiogram allowed measurements of the two components of the preejection period--the isometric contraction time and the electromechanical delay. At the onset of hypoxemia, because of changes in isometric contraction time, the preejection period began to shorten. When acidemia was induced, the preejection period modified slowly in the opposite direction and lengthened, initially because of a prolongation of electromechanical delay and later because of an increase in the already shortened isometric contraction time. This process developed slowly and at the end of 2 hours of acidemia, preejection period were back to preexperimental values. It can be concluded that systolic time intervals can be normal and misleading when acidosis complicates hypoxemia.

Acids

The effect of forskolin on the isometric contraction of the isolated hemidiaphragm of the rat.

The effects of forskolin on the parameters of the isometric contraction alone and in combination with aminophylline and isoprenaline were studied on the isolated hemidiaphragm of the rat during direct electrical stimulation. Forskolin (2.6 - 18.2 mumol l-1) produced a concentration-dependent increase in tension developed (Td) and, to a lesser extent, in the maximum rate of rise in tension (dT/dt max). The dose-response curve for the action of forskolin (2.6 - 18.2 mumol l-1) on Td was shifted to the left in the presence of a standard concentration of aminophylline (0.32 mmol l-1). Forskolin (5.2 mumol l-1) produced a further and significant increase in both Td and dT/dt max in the presence of isoprenaline (0.24 mumol l-1) in the bath. In a calcium-free medium, the effects of forskolin (7.80 and 18.2 mumol l-1) on Td and dT/dt max were significantly weaker than in a medium containing calcium. These data indicate that forskolin increases the isometric contraction of the isolated hemidiaphragm probably by activating the adenosine 3':5'-cyclic monophosphate (cyclic AMP) generating system. These effects are possible only in the presence of calcium.

Aminophylline

Energy metabolism in different human skeletal muscles during voluntary isometric contractions.

The energy turnover in contracting skeletal muscle was studied by measuring the rate of temperature rise during voluntary, isometric contractions and circulatory arrest in M. soleus, M. sacrospinalis and M. biceps brachii in 14 males, by thermoelements inserted in the muscles. A linear relationship between rate of temperature rise and force intensity given as per cent of maximal voluntary contraction (MVC) was demonstrated in biceps (r = 0.95), but not so clearly confirmed in soleus (r = 0.73). Muscle biopsies were taken from the same muscles and fibre type distribution was determined histochemically by staining for ATPase. The rate of heat production at MVC showed positive correlation to the percentage of fast twitch (FT) fibres in the muscles (r = 0.90). Linear extrapolation indicates that the maximal energy turnover in human FT fibres is approximately six times that of slow twitch (ST) fibres during voluntary isometric contractions.

Adult

Muscle ATP turnover rate during isometric contraction in humans.

ATP turnover and glycolytic rates during isometric contraction in humans have been investigated. Subjects contracted the knee extensor muscles at two-thirds maximal voluntary force to fatigue (mean +/- SE, 53 +/- 4 s). Biopsies were obtained before and after exercise and analyzed for high-energy phosphates and glycogenolytic-glycolytic intermediates. Total ATP turnover was 190 +/- 7 mmol/kg dry muscle, whereas the average turnover rate was 3.7 +/- 0.2 mmol . kg dry muscle-1 . S-1. The average ATP turnover rate was positively correlated with the percentage of fast-twitch fibers in the postexercise biopsy (r = 0.71; P less than 0.05) and negatively correlated with contraction duration to fatigue (r = -0.88; P less than 0.05). At fatigue, phosphocreatine ranged from 1 to 11 mmol/kg dry muscle (86-99% depletion of value at rest), whereas lactate ranged from 59 to 101. The mean glycolytic rate was 0.83 +/- 0.05 mmol . kg dry muscle-1 . S-1 and was positively correlated with the rate of glucose 6-phosphate accumulation (r = 0.83; P less than 0.05). It is concluded that a major determinant of the ATP turnover rate is the muscle fiber composition, which is probably explained by a higher turnover rate in fast-twitch fibers; fatigue is more closely related to a low phosphocreatine content than to a high lactate content; and the increase in prephosphofructokinase intermediates is important for stimulating glycolysis during contraction.

Adenosine Triphosphate

Effect of topical cheek surface anesthesia on isometric contractions of the human masseter muscle.

To study the possibility of interactions between buccal cutaneous sensory receptors and voluntary maximum isometric contractions of the masseter muscles, six adult subjects exercised maximum teeth clenching before and after spraying the right cheek surface with aerosol containing 20% benzocaine. The right cheek and masseter muscle served as the experimental side, the left cheek and masseter muscle as the control side. Isometric motor outputs, on the right and left sides, were monitored by integrated surface electromyography over periods of 10 seconds. Topical surface anesthesia provided no evidence of motor modulation by cutaneous tactile receptors. Before and after anesthesia, the two muscles showed nearly identical and well-coordinated motor innervation patterns. It is suggested that the cortical motor commands of maximum isometric contractions, with recruitment of practically all available motor units, overrule all modulatory inputs except those of fatigue.

Adult

Heat production of rat anococcygeus muscle during isometric contraction.

Heat production, unloaded shortening velocity (Vus), and load-bearing capacity (LBC) were studied in the isolated rat anococcygeus muscle during isometric contractions at 27 degrees C. The relation between the total suprabasal heat produced and the stress-time integral for isometric contractions of various durations was curvilinear, demonstrating a decreasing slope as contractile duration increased. The rate of heat production at 600 s was approximately 68% of the peak value of 6.55 mW/g that occurred at 10 s. At the same time, force rose from a mean of 92 mN/mm2 at 10 s to a value of 140 mN/mm2 at 600 s. This produced a nearly threefold increase in the economy of force maintenance. The decline in the rate of heat production was accompanied by a decline in Vus from 0.56 Lo/s at 10 s to 0.28 Lo/s at 600 s, where Lo is the length for optimal force development. This suggests the fall in the rate of heat production was caused, at least in part, by a slowing of cross-bridge kinetics. The ratio of LBC to developed tension at 10 s was not significantly different from the ratio at 600 s, suggesting that the increase in tension was due to an increased number of attached cross bridges. The decline in heat production, therefore, appears contradictory, since an increased number of attached cross bridges would predict an increased rate of energy expenditure. The observations can be reconciled if either 1) the increase in force is caused by a progressive increase in the attachment time of a constant number of cross bridges that cycle at a lower frequency or 2) the decline in energy expenditure caused by the slowing of cross-bridge cycling is sufficient to mask the increase caused by the recruitment of additional cross bridges.

Animals

Amplitude of the surface electromyogram during fatiguing isometric contractions.

Five voluntee subjects held isometric handgrip contractions at specific submaximal tensions until the required tension could no longer be maintained. At the start of those contractions, the amplitude of the surface electromyogram (EMG) was linearly related to the tension exerted; the amplitude of the EMG increased linearly throughout these substained contractions by a constant amount--about 30% of the maximum. During sustained contractions, brief, intermittent maximal efforts showed that strength declined linearly at all tensions. At 25% maximal voluntary contraction (MVC), there was a linear fall in the EMG amplitude associated with the brief maximal efforts, but the fall in strength was more rapid than the fall in EMG amplitude. At 70% MVC, there was no fall in the EMG amplitude in response to the brief maximal efforts, while the muscle strength fell linearly.

Adult

The effect of adrenaline infusion on the regulation of glycogenolysis in human muscle during isometric contraction.

The regulation of glycogenolysis in human muscle during isometric contraction without and with adrenaline infusion has been investigated. The content of cAMP in muscle increased three-fold during the infusion. Total glycogen phosphorylase and synthetase activities were unchanged during contraction without and with adrenaline infusion. The fraction of phosphorylase in the a form was in resting muscle 26% and at the end of contraction 24%. During adrenaline infusion phosphorylase a increased to 80%. Contraction during continued infusion resulted in a decrease of phosphorylase a to 42%, despite persistently increased cAMP content in muscle. The activity of synthetase I decreased to about half of the initial value during adrenaline infusion and contraction both without and with the infusion. The rate of glycogenolysis in muscle during contraction was not significantly changed by the infusion. Phosphocreatine (PCr) decreased during the contraction and the decrease was similar without and with adrenaline infusion. The amount of inorganic phosphate (Pi) accumulated in muscle during contraction was lower when adrenaline was given due to a greater accumulation of hexose-monophosphates. It is concluded that the rate of glycogenolysis in muscle during contraction without and with adrenaline infusion is a function both of phosphorylase in the form a form and the availability of Pi at the active site of the enzyme.

Adult

G-1,6-P2 in human skeletal muscle after isometric contraction.

The content of glucose 1,6-bisphosphate (G-1,6-P2), an in vitro activator of phosphofructokinase (a rate-limiting enzyme for glycolysis), and the glycolytic rate in skeletal muscle during isometric contraction have been determined. Subjects contracted the knee extensor muscles at two-thirds maximal voluntary force to fatigue. Biopsies from the quadriceps femoris muscle were obtained before and immediately after contraction. G-1,6-P2 increased in all subjects from a mean of 101 +/- 15 (SE) mumol/kg dry wt at rest to 128 +/- 24 at fatigue (P less than 0.05). Muscle glucose did not change significantly, whereas hexosemonophosphates were significantly increased after contraction. The glycogenolytic and glycolytic rate averaged 70.0 +/- 13.8 and 47.3 +/- 6.7 mmol.kg dry wt-1.min-1, respectively, and the glycolytic rate was positively correlated with the accumulation rates of fructose 6-phosphate (F-6-P) (r = 0.95, P less than 0.01) and G-6-P (r = 0.96, P less than 0.01). Phosphocreatine and ATP decreased by 87 and 17%, respectively, whereas ADP increased by 31% after contraction. These data demonstrate that intense, short-term isometric contraction results in an elevation of the muscle content of G-1,6-P2. The increase in G-1,6-P2 could not be accounted for by the side reactions of phosphoglucomutase or phosphofructokinase. It remains to be determined whether the observed increase in G-1,6-P2 is sufficient to account for the high glycolytic rate during intense exercise. The lack of increase in muscle glucose while G-6-P increased (which will inhibit hexokinase) suggests that the debranching enzyme complex was not active during contraction.

Adenine Nucleotides

Sustained isometric contraction of skeletal muscle results in release of immunoreactive neurokinins in the spinal cord of the anaesthetized cat.

Antibody microprobes were used to study release of immunoreactive neurokinins in the dorsal horn of the anaesthetized spinal cat following sustained isometric contraction of ipsilateral hindlimb muscles. Microprobes had immobilized antibodies to neurokinin A (NKA) on their outer surfaces and bound a proportion of released molecules when inserted in the central nervous system. Bound molecules were detected in autoradiographs as zones of reduced binding of 125I-NKA in which microprobes were incubated after withdrawal from the spinal cord. The left hindlimb was immobilized using an epoxy bandage splint and isometric contraction of muscles induced by intermittent tetanic stimulation of a ventral root. A basal presence of immunoreactive neurokinins was detected and this was increased by sustained isometric muscle contraction. It is probable that ergoreceptors contain and release neurokinins.

Anesthesia, General

Effect of muscle length on surface EMG wave forms in isometric contractions.

To elucidate the influence of muscle length on surface EMG wave form, comparisons were made of surface EMGs of the biceps and triceps brachii muscles during isometric contractions at different muscle lengths. Muscle lengths were altered by setting the elbow joint angle at several intervals between the limits of extension and flexion. The intensity of the isometric contractions was 25% of maximum voluntary contraction at the individual joint angles. Slowing was obvious in the EMG wave forms of biceps as muscle length increased. The so-called 'Piper rhythm' appeared when the muscle was more than moderately lengthened. The slowing trend with muscle lengthening, though less marked, was also seen in triceps. Zero-cross analysis revealed quasi-linear relationships between muscle length and slowing. Frequency analysis confirmed the development of 'Piper rhythm'. An attempt was made to interpret the slowing associated with muscle lengthening in terms of the propagation of myoelectric signals in muscle fibers. given the effect of muscle length on EMG wave forms, a careful control of joint angle may be required in assessing local making fatigue when using EMG spectral indices.

Adult