Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026837 (muscle rigidity)
 1,077 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of inosine (INO) on substrate metabolism and rigor formation in ischemic myocardium were examined in isolated rabbit hearts. Metabolite content was assessed in tissue extracts by chemical analysis and in the whole heart by 13C and 31P nuclear magnetic resonance spectroscopy. In ischemic hearts metabolizing either [3-13C]pyruvate or [1-13C]glucose, 1 mM INO increased both total and 13C-labeled alanine content; lactate content was unaffected. At 3 minutes of ischemia, tissue alanine was 1.81 +/- 0.11 microM/g wet wt (mean +/- SEM) in hearts perfused with pyruvate+INO versus 1.23 +/- 0.15 microM/g wet wt in hearts perfused with pyruvate alone (p less than 0.05). INO reduced tissue glycogen during ischemia in pyruvate-perfused hearts. Tissue alanine content in ischemic hearts that were supplied glucose+INO (1.29 +/- 0.13 microM/g wet wt) was greater than in ischemic hearts supplied glucose alone (0.65 +/- 0.14 microM/g wet wt). Alanine was found to originate from pyruvate and was a glycolytic end product in glucose-perfused hearts. INO raised the [3-13C]alanine/[3-13C]lactate ratio in ischemic, intact hearts (glucose = 0.24 +/- 0.07 versus glucose+INO = 0.60 +/- 0.09; pyruvate = 0.49 +/- 0.08 versus pyruvate+INO = 0.89 +/- 0.08). At 7 minutes of ischemia, ATP content fell to 70 +/- 3% with glucose+INO versus 58 +/- 5% with glucose alone. Rigor (stone heart) was delayed from 14.7 +/- 1.3 to 23.2 +/- 1.6 minutes with INO. INO did not change ATP content in ischemic hearts that were supplied pyruvate but delayed rigor (pyruvate = 9.9 +/- 1.2 minutes; pyruvate+INO = 15.6 +/- 1.0 minutes), possibly at the expense of glycogen. Supplemental glucose improved the effectiveness of INO with pyruvate to preserve ATP (pyruvate+glucose = 42 +/- 6%; pyruvate+glucose+INO = 72 +/- 6%) and further delayed rigor (pyruvate+glucose = 13.3 +/- 1.5 minutes; pyruvate+glucose+INO = 20.3 +/- 1.8 minutes). Glucose metabolism supported improved energetic and contractile states in ischemic hearts treated with INO. Thus, cardioprotection of the ischemic heart by INO was associated with preservation of functional integrity and improved energy production due to increased glycolytic activity. Activation of glycolysis in the presence of INO was accommodated by augmented alanine production without the additional accumulation of lactate.
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PMID:Effects of inosine on glycolysis and contracture during myocardial ischemia. 199 56

Rhabomyolysis with myoglobinuria has been added relatively recently to the neurologic complications associated with the increased use of cocaine and the introduction of its alkaloid form (crack). This retrospective study reports our experience with 14 patients who presented with rhabdomyolysis after cocaine use in a municipal hospital over a 3-year period. Seven patients used "crack", 2 intravenous and 3 nasal insufflation. All patients but one had hyperthermia, 11 altered mental status, 8 tachycardia, and 4 muscle rigidity. Nine developed renal failure; 3 of these patients died. Two other patients died of cardiorespiratory arrest. Cocaine-related rhabdomyolysis has a high mortality. The observed association with hyperthermia and other central neurologic features resembles the neuroleptic malignant syndrome. Since chronic cocaine use may alter the availability of dopamine either through transmitter depletion or decrease in the number of dopamine receptors, a common pathogenetic mechanism is possible. However, other mechanisms, which are not mutually exclusive but rather frequently overlapping, may play an important role. These include agitation, hyperthermia, adrenergic overstimulation leading to vasoconstriction and ischemia or calcium release from the sarcoplasmic reticulum resulting in increased entry into the muscle cell leading to cell death; in addition, cocaine has direct toxic effect on the muscles.
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PMID:Rhabdomyolysis and hyperthermia after cocaine abuse: a variant of the neuroleptic malignant syndrome? 748 66

The beneficial effect of low pH during cardiac ischemia on reperfusion injury has often been attributed to its energy-saving effect due to inhibition of contraction. The role of low pH on Ca2+ accumulation and muscle tension was assessed in energy-depleted tissue by changing the pH of the medium from 7.4 to 6.2 at onset of rigor development during metabolic inhibition (MI), i.e., in the energy-depleted phase. Cytosolic free Ca2+ ([Ca2+]i) and intracellular H+ (pHi) were measured in rat trabeculae at 20 degrees C with fura 2 and 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein, respectively, and tension was recorded. The preparations were energy depleted by stimulation at 1 Hz in glucose-free Tyrode solution with 2 mM NaCN. Rigor developed within 20 min, indicating energy depletion. Resting [Ca2+]i was followed during 50 min (group I) or 100 min (group II) of rigor, and recovery was followed for 60 min in glucose-containing Tyrode solution at 0.2-Hz stimulation. Resting [Ca2+]i rose within 50 min (group I) but stabilized in the 50- to 100-min period (group II). All preparations from group I (n = 5) resumed contraction in the recovery period but in group II (n = 10) 70% failed to recover, and [Ca2+]i remained elevated compared with those that recovered. An extracellular pH of 6.2, resulting in similar pHi, from onset of rigor development (group III) led to only a modest rise in [Ca2+]i during the 100-min rigor period, and all preparations resumed contraction after approximately 3 min in normal medium. ATP was very low in all groups at the end of MI but was still significantly lower in group II than in groups I and III. A beneficial energy-sparing effect of low pH during the rigor phase can therefore not be excluded. We conclude that 1) the capacity of trabeculae to recover from MI depends on the time period and magnitude of the [Ca2+]i rise in the energy-depleted phase and 2) low pH in energy-depleted trabeculae protects against Ca overload, improving recovery after normalization of perfusion conditions.
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PMID:Exposure of energy-depleted rat trabeculae to low pH improves contractile recovery: role of calcium. 773 52

The incidence of lower extremity ischemia secondary to acute aortic dissection is relatively low, however, the presenting symptoms are variable in term of severity. We report here in two cases of such circumstances who were successively differently treated. Case one was a 60 years old male presented with severe left leg pain. Even after the initiation of cardiopulmonary bypass, the leg ischemia did not improve, therefore selective leg perfusion was additionally performed through direct left femoral artery cannulation. The surgery toward dissection was completed by mean of simultaneous graft replacement of ascending aorta and aortic arch. The leg ischemia after the aortic procedure however had persisted, femorofemoral bypass was created to relieve the mal-perfusion. Case two was a 37 years old male admitted with severe left leg pain associated with sensory-motor nerve dysfunction with muscle rigidity. In this particular patient, femoro-femoral bypass was firstly reconstructed as the mean of leg salvage procedure. After we learned there was no serious reperfusion symptom manifested, we performed radical surgery toward the aorta. We believe that the decision making of surgical treatment for acute type A dissection complicated with the presence of lower extremity ischemia is based on the severeness of mal-perfusion.
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PMID:[Acute type A aortic dissection with leg ischemia]. 984 78

In experimental and clinical studies, an objective assessment of peripheral muscle resistance represents one of the key elements in determining the efficacy of therapeutic manipulations (e.g. pharmacological, surgical) aimed to ameliorate clinical signs of spasticity and/or rigidity. In the present study, we characterize a newly developed limb flexion resistance meter which permits a semi-automated, computer-controlled measurement of peripheral muscle resistance (PMR) in the lower extremities during a forced flexion of the ankle in the awake rat. Ischemic paraplegia was induced in Sprague-Dawley rats by transient aortic occlusion (10 min) in combination with systemic hypotension (40 mm Hg). After ischemia the presence of spasticity component was determined by the presence of an exaggerated EMG activity recorded from gastrocnemius muscle after nociceptive or proprioceptive afferent activation and by velocity-dependent increase in muscle resistance. Rigidity was induced by high dose (30 mg/kg, i.p.) of morphine. Animals with defined ischemic spasticity or morphine-induced rigidity were then placed into a plastic restrainer and a hind paw attached by a tape to a metal plate driven by a computer-controlled stepping motor equipped with a resistance transducer. The resistance of the ankle to rotation was measured under several testing paradigms: (i) variable degree of ankle flexion (40 degrees, 50 degrees, and 60 degrees), (ii) variable speed/rate of ankle flexion (2, 3, and 4 sec), (iii) the effect of inhalation anesthesia, (iv) the effect of intrathecal baclofen, (v) the effect of dorsal L2-L5 rhizotomy, or (vi) systemic naloxone treatment. In animals with ischemic paraplegia an increased EMG response after peripheral nociceptive or proprioceptive activation was measured. In control animals average muscle resistance was 78 mN and was significantly increased in animals with ischemic spasticity (981-7900 mN). In ischemic-spastic animals a significant increase in measured muscle resistance was seen after increased velocity (4 > 3 > 2 sec) and the angle (40 degrees > 50 degrees > 60 degrees) of the ankle rotation. In spastic animals, deep halothane anesthesia, intrathecal baclofen or dorsal rhizotomy decreased muscle resistance to 39-80% of pretreatment values. Systemic treatment with morphine induced muscle rigidity and corresponding increase in muscle resistance. Morphine-induced increase in muscle resistance was independent on the velocity of the ankle rotation and was reversed by naloxone. These data show that by using this system it is possible to objectively measure the degree of peripheral muscle resistance. The use of this system may represent a simple and effective experimental tool in screening new pharmacological compounds and/or surgical manipulations targeted to modulate spasticity and/or rigidity after a variety of neurological disorders such as spinal cord traumatic or ischemic injury, multiple sclerosis, cerebral palsy, or Parkinson's disease.
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PMID:Measurement of peripheral muscle resistance in rats with chronic ischemia-induced paraplegia or morphine-induced rigidity using a semi-automated computer-controlled muscle resistance meter. 1630 23

Ischemic preconditioning has a powerful protective potential against a reperfusion-induced injury of the post-ischemic myocardium. Cardiomyocyte hypercontracture, i.e. excessive cell shortening, is an essential mechanism of the reperfusion-induced injury. Rigor contracture, i.e. Ca(2+)-independent contracture, has been shown to be an import component of the reperfusion-induced hypercontracture. Since rigor contracture is dependent on the rapidity of the metabolic recovery during reoxygenation, we hypothesized that preconditioning of the cardiomyocyte mitochondria may improve mitochondrial function to restore the energy balance during the initial phase of reoxygenation and may thus prevent rigor contracture. For this purpose adult rat cardiomyocytes were exposed to anoxia with subsequent reoxygenation. For preconditioning, cells were pre-treated with the mitochondrial ATP-sensitive K(+) channel opener diazoxide. Pre-treatment with 100 micromol/l diazoxide significantly reduced the reoxygenation-induced hypercontracture of cardiomyocytes due to an attenuation of the Ca(2+)-independent rigor-type contracture, which was accompanied by an acceleration of the phosphocreatine resynthesis during the initial phase of reoxygenation. Treatment with the mitochondrial ATP-sensitive K(+) channel antagonist 5-hydroxydecanoate (500 micromol/l) during preconditioning phase abolished these protective effects. Similarly, partial suppression of the mitochondrial function with 100 micromol/l NaCN during the reoxygenation phase abolished the diazoxide effects. Finally, in isolated rat hearts, preconditioning with diazoxide prior to global ischemia significantly improved left ventricular function and attenuated hypercontracture during reperfusion. This effect could be abolished by the treatment with 100 micromol/l NaCN during reperfusion. Taken together, pharmacological preconditioning of cardiomyocytes with diazoxide protects against the reoxygenation-induced rigor hypercontracture due to an improvement of the energy recovery at the onset of reoxygenation.
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PMID:Preconditioning with diazoxide prevents reoxygenation-induced rigor-type hypercontracture. 1940 25