RESUMEN
At present, the significance of calcium accumulation in the aetiology of coronary artery disease (CAD) in humans is not known, except only to exacerbate the condition. In an attempt to understand ionic disturbances in vasculature derived from cardiovascular abnormalities, soft tissues from hypertensive models were examined. The study hypothesis was to see if basic cardiovascular regulatory sites in hypertensive models accumulated greater amounts of Ca2+. Calcium levels were measured by flame atomic absorption spectrophotometry in tissue derived from two types of hypertensive rabbits. Both models of hypertension developed mean arterial pressures of at least 50 mm Hg greater than those of controls over a 5-wk period. Significant increases in calcium levels were found in left ventricle and aorta derived from both hypertensive groups compared with controls. Renal cortex and medulla were not significantly different among any of the groups. These levels corroborate the findings of others which show increased calcium levels in cardiovascular tissues in experimental hypertension in rabbits. Although there have been several studies that have shown the relationship between calcium, hypertension and CAD, this is the first study to look at calcium accumulation rather that the effects of calcium channel blockers. The link between hypertension and calcium accumulation in a number of tissues may be important in the development of CAD and other cardiac dysfunction.
Asunto(s)
Acetatos , Aorta/metabolismo , Calcio/metabolismo , Ventrículos Cardíacos/metabolismo , Hipertensión/metabolismo , Riñón/metabolismo , Análisis de Varianza , Animales , Presión Sanguínea/fisiología , Cadmio/administración & dosificación , Cadmio/toxicidad , Enfermedad Coronaria/etiología , Enfermedad Coronaria/metabolismo , Modelos Animales de Enfermedad , Ingestión de Líquidos , Femenino , Hipertensión/inducido químicamente , Hipertensión Renal/metabolismo , Hipertrofia Ventricular Izquierda/metabolismo , Corteza Renal/metabolismo , Médula Renal/metabolismo , Nefrectomía/efectos adversos , Conejos , Reproducibilidad de los Resultados , Espectrofotometría Atómica , Distribución TisularRESUMEN
Heart disease remains a major public health issue. In this study we aimed to achieve a greater mathematical and mechanistic understanding of the relationship between exposure to heavy metals and heart disease. Measurements of calcium and cadmium levels were made by flame atomic absorption spectrophotometry in tissue from hypertensive and non-hypertensive rabbits. Relationships between hypertrophy, calcium and cadmium were tested using multiple regression analysis. Multiple linear relationships occurred that showed the dependence of hypertrophy on calcium and cadmium levels, and of calcium accumulation on cadmium and hypertrophy. These data provide an insight into the mechanisms of heavy metal accumulation and the development of cardiovascular hypertrophy.
Asunto(s)
Cadmio/toxicidad , Calcio/toxicidad , Cardiomegalia/inducido químicamente , Hipertensión Renal/inducido químicamente , Hipertensión/inducido químicamente , Animales , Presión Sanguínea , Cadmio/farmacocinética , Calcio/farmacocinética , Cardiomegalia/metabolismo , Femenino , Hipertensión/metabolismo , Hipertensión Renal/metabolismo , Modelos Lineales , ConejosRESUMEN
Signal transduction systems (sts(s)) and acetylcholinesterase (AChE) levels in skeletal muscle distantly located from the site of large body surface area (BSA) burns are due to the systemic effects of burn trauma. Evaluating the guanylate and adenylate cyclase sts(s), by measuring adenosine 3':5'-phosphate (cyclic AMP) and guanosine 3':5'-phosphate (cyclic GMP) by radioimmunoassay with polymorphic forms of AChE demonstrated that the various systems (i.e., cyclic GMP and AChE) interact while under the duress of burn trauma. This trauma emanates from large skin burns (30-50% BSA) that have induced a chronic burn trauma response at postburn day 21. This study showed that a system, with a minimum of 2 components, regulated cyclic AMP levels. This paper provides insight into our current understanding of the effects of burn trauma on cellular signalling and discusses some of the potential implications of recent findings on long term rehabilitative care.
Asunto(s)
Acetilcolinesterasa/fisiología , Quemaduras/fisiopatología , AMP Cíclico/fisiología , GMP Cíclico/fisiología , Transducción de Señal/fisiología , Animales , Quemaduras/enzimología , Quemaduras/patología , Centrifugación por Gradiente de Densidad , Guanilato Ciclasa/metabolismo , Masculino , Ratones , Modelos Biológicos , Análisis Multivariante , Músculo Esquelético/enzimología , Músculo Esquelético/patologíaRESUMEN
This work evaluated indirect talk, a system of communication between two secondary messengers which uses a third modulating messenger/compound for communication. It expands on our previous report (6) of mean levels and univariate linear/non-linear relationships. It presents results using multivariate testing with vectorial modeling. The signal transduction systems (sts) studied through 125I-radioimmunoassay involved: adenosine 3':5' -cyclic monophosphate (cAMP); and the guanylate cyclase sts via guanine 3':5' -cyclic monophosphate (cGMP). Through multivariate testing, the dependency of a specified parameter was determined relative to two or more independent parameters. The contributing aspects of each of the independent variables were assigned to either 2- or 3-dimensional axes. Through the vector analyses the topic of indirect talk was well aspected. Multivariate equations showed that communication between two systems occurred. Vectorial analysis showed that the direct/indirect mechanism of that communication (namely, indirect talk) occurred. Such analysis leads to a greater understanding of endotoxemia that adversely affects skeletal muscle.
Asunto(s)
Endotoxinas , Unión Neuromuscular/fisiología , Transducción de Señal/fisiología , Toxemia/fisiopatología , Animales , Peso Corporal , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Masculino , Ratones , Modelos Biológicos , Análisis Multivariante , Estadística como AsuntoRESUMEN
Skeletal muscle weakness is a common problem among burn patients. An understanding of the changes that occur in the phosphatidyl inositol signal transducing system (sts) in skeletal muscle may identify pharmacological agents that would prove useful in the treatment of these patients. This report examines changes that occur in the interrelationships between the polyinositol phosphates of skeletal muscle due to the systemic effects of large body surface area (% BSA) burns. Burn injury was applied to predefined areas corresponding to 0, 20 and 50 per cent BSA of the dorsal and ventral skin surfaces of mice. At postburn day 21, polyinositol phosphate levels were measured in the gastrocnemius muscle by the incorporation of myo[2-(3)H]inositol with separation of the phosphates by anion-exchange chromatography. All data were analysed using analysis of variance and curve fitting routines. In the gastrocnemius, a number of interrelationships were found between the polyinositol phosphates. A relationship between inositol 1 phosphate (I1P) and inositol was the only relationship that was found in all three groups. However, a number of other relationships existed in the 20 and 50 per cent BSA burn group. These data illustrate that changes in polyinositol interrelationships occur in the phosphatidyl inositol signal transducing system due to the systemic effects of large per cent BSA burns.
Asunto(s)
Quemaduras/metabolismo , Inositol/análisis , Músculos/metabolismo , Animales , Modelos Animales de Enfermedad , Inositol/metabolismo , Inositol/fisiología , Masculino , Ratones , Fosfatidilinositoles/fisiología , Transducción de SeñalRESUMEN
In this report, we have used a multiple stepwise regression analysis to determine the best derived multivariate equation between a dependent and multiple independent parameters. All parameters were derived from harvested gastrocnemius muscle subjected to chronic burn trauma. Correlations between seven different parameters were tested. Physiologic tension, calcium, adenosine 3':5' cyclic monophosphate (cAMP), inositol 1,4,5-triphosphate (IP3) and its catabolites comprised one large data matrix. From it, the various parameters were substituted as the dependent variable. The remaining parameters all comprised a multiple independent group. From such a format, the stepwise regression was run. The simultaneous co-governing of independent parameters over one dependent parameter provides a means of mathematically proving multiple correlations. Such findings provide a new perspective in interpreting chemical signalling.
Asunto(s)
Quemaduras/fisiopatología , Calcio/fisiología , AMP Cíclico/fisiología , Fosfatos de Inositol/fisiología , Músculo Liso/fisiopatología , Sistemas de Mensajero Secundario , Animales , Modelos Animales de Enfermedad , Inositol 1,4,5-Trifosfato/fisiología , Masculino , Ratones , Análisis de RegresiónRESUMEN
This paper examines the interaction of endotoxin at the nicotinic2 receptor (ACh-Rpost) with the adenylate cyclase signal transduction system in skeletal muscle. It reports the drug-receptor (DR) dissociation constant (K, 0.05020 +/- .0015 mg/kg) for E. coli endotoxin. It expands on a previous report (1) which presented the relevance of skeletal muscle cAMP as a metabolic indicator and second messenger influenced by endotoxicosis. The use of a murine endotoxic model allowed for the measuring of K for the antagonist. DR affinity measures which relied on the constrained-slope Schild plot measured it. This report assessed dose-response relations of the competitive antagonist dTC (AN) and their modification (AN') by advancing endotoxicosis. The presence of endotoxin at a fixed final concentration (i.e., 7.75 mg/kg) within the body at the end of a two week period caused a rightward shift in the dTC dose-response curve. Endotoxin desensitized cAMP and caused the dTC curve to be shifted rightward. This report differs from typical pharmacological applications where standard agonist curves are obtainable in the presence of an antagonist. This in vivo model did not allow for the measurement of agonist ACh concentration. Therefore, the use of a pair of compounds (i.e., antagonistic dTC and agonistic endotoxin) and their effects (i.e., suppression of active tension and cAMP desensitization, respectively) allowed us to quantitate K. In summary, this report supports the hypothesis linking the nicotinic2 receptor to the adenylate cyclase signal transduction system and illustrates that endotoxicosis perturbed both.
Asunto(s)
Escherichia coli , Lipopolisacáridos/farmacocinética , Receptores Nicotínicos/metabolismo , Acetilcolina/farmacología , Animales , Unión Competitiva/efectos de los fármacos , AMP Cíclico/fisiología , Masculino , Ratones , Contracción Muscular/efectos de los fármacos , Músculos/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Tubocurarina/farmacologíaRESUMEN
Aberrant signal transduction processes within the diaphragm contribute to the weakness of this primary muscle involved in respiration. The importance of this report emphasizes how scald burn injury manifests distant systemic effects which impact on respiration. Scald burn injury from hot water is a common type of thermal injury in three specific patient groups: young children, the elderly, and the mentally and physically handicapped. Multivariate and vectorial analyses are presented within this paper with application to the effects of burn trauma on pharmacological signal transduction systems in the diaphragm. Multivariate equations showed the dependence of IP, on three to five independent variables. The independent variables included: burn size, glycerophosphate, and other polyinositols (inositol 1,4 biphosphate (I1,4P2), inositol 1 phosphate (I1P) and inositol). Graphic illustration of the equations used vectorial analysis. The multivariate analysis gives rise to a wider class of contributing factors than those observed using standard univariate relationships. This may be useful clinically in the identification of therapeutic agents for the treatment of respiratory problems in burn patients.
Asunto(s)
Quemaduras/metabolismo , Diafragma/metabolismo , Inositol 1,4,5-Trifosfato/metabolismo , Animales , Quemaduras/fisiopatología , Diafragma/fisiopatología , Glicerofosfatos/metabolismo , Inositol/metabolismo , Fosfatos de Inositol/metabolismo , Ratones , Análisis Multivariante , Transducción de Señal , Organismos Libres de Patógenos EspecíficosRESUMEN
Heart disease still pervades all socioeconomic classes within the United States. Understanding the effects of environmentally-related pathogenesis (e.g., heavy metal accumulation) may aid in developing novel treatments for the prevention of heart dysfunction. The aim of this report was to use experimental investigation in an attempt to expand upon the multivariate importance of divalent cation interactions in the development of heart disease. Calcium and cadmium levels were measured by flame atomic absorption spectrophotometry in various tissues derived from two types of hypertensive rabbit models. Both models of hypertension developed mean arterial pressures of at least 50 mm mercury greater than those of controls over a 5 week period. Interrelationships between calcium and cadmium levels were found to exist for both hypertensive groups in the left ventricle, aorta, and renal medulla. The renal cortex showed no such interrelationship for the renal hypertensive group. Multiple interrelationships between calcium and cadmium levels and hypertrophy were also observed. These studies related the importance of endogenous or exogenous (viz, environmental) factors governing cadmium and calcium accumulation in hypertensive rabbits. The resulting relationships between divalent cations and hypertrophy were presented to draw attention to areas which remain unexplored with perspective to cardiovascular disease.
Asunto(s)
Cadmio/metabolismo , Calcio/metabolismo , Cationes Bivalentes/metabolismo , Cardiopatías/etiología , Hipertensión/complicaciones , Animales , Aorta/metabolismo , Presión Sanguínea/efectos de los fármacos , Cadmio/farmacología , Calcio/farmacología , Femenino , Cardiopatías/metabolismo , Cardiopatías/fisiopatología , Ventrículos Cardíacos/metabolismo , Hipertensión/inducido químicamente , Hipertensión/metabolismo , Hipertensión Renal/metabolismo , Hipertensión Renal/fisiopatología , Corteza Renal/metabolismo , Médula Renal/metabolismo , Conejos , Espectrofotometría AtómicaRESUMEN
Common complications among patients with burns are respiratory problems. Inspiration for breathing normally is facilitated by diaphragmatic contractility. However, in burn trauma numerous factors impose on skeletal muscle activity and chest wall function. These present limitations to surgical procedures requiring anesthesia. The hypothesis of this study was that the systemic effects of increasing burn size may result in metabolic changes in the polyinositol part of the phosphatidyl inositol signal transduction system in diaphragm. In this report, rate changes in polyinositol phosphates (i.e., inositol triphosphate (IP3), inositol 1,4 biphosphate (I1,4P2), inositol 1 phosphate (I1P), and inositol) that occurred in diaphragm subjected to the systemic effects of burn trauma were examined. Third-degree burn injury was applied by scalding predefined areas (i.e., 0%, 20%, and 50% body surface area) on the dorsal and ventral surfaces of mice. At postburn day 21 tissues were harvested and the levels of the polyinositol phosphates were measured by incorporation of myo-[2-3H]-inositol with separation of the phosphates by anion-exchange chromatography. All actual levels and rates of formation were analyzed with standard statistical tests and curve-fitting routines. Rate changes of the labelled [3H]-polyinositol phosphates were determined for the control, 20%, and 50% groups. These data show that rate changes occur in the polyinositol part of the phosphatidyl signal transduction system and are caused by the systemic effects of large percent body surface area burns. The changes that occur in the polyinositol phosphates provide insight into dysfunctional processes that can affect skeletal muscle physiology. The long-term goal of these studies is that they will lead to therapeutic advancements in the treatment of respiratory dysfunction in patients with burns.
Asunto(s)
Quemaduras/metabolismo , Glicerofosfatos/biosíntesis , Fosfatos de Inositol/biosíntesis , Músculos/metabolismo , Sistemas de Mensajero Secundario/fisiología , Transducción de Señal/fisiología , Animales , Superficie Corporal , Quemaduras/complicaciones , Diafragma/fisiopatología , Glicerofosfatos/fisiología , Inositol/biosíntesis , Fosfatos de Inositol/fisiología , Masculino , Ratones , Trastornos Respiratorios/etiología , Trastornos Respiratorios/fisiopatologíaRESUMEN
Polyinositol phosphates comprise a portion of the phosphatidyl signal transducing system. The most well known is IP3 which stimulates Ca2+ release from Ca2+ sequestering organelles within cells. In this study, polyinositol phosphate changes in the heart subjected to the systemic effects of burn trauma were examined. The hypothesis was that systemic trauma induced by large body surface area (% BSA) burn may perturb the phosphatidylinositol signal transducing system. At postburn day 21 left ventricular tissues were harvested from mice with varying burn sizes (i.e. 0, 20 and 50 per cent). Levels of the polyinositol phosphates were measured by incorporation of myo-[2-3H]inositol with separation of the phosphates by anion-exchange chromatography. Analysis of variance was used for statistical evaluation. Multivariate relationships between the independent polyinositol forms (inositol, Il,4P2 and I1P) existed for control (r2 = 0.71 and 50 per cent burn groups (r2 = 0.78). Numerous interdependent relationships existed within each of the multivariate tests. These analyses confirm that several independent polyinositol phosphates contribute to changes in the second messenger IP3 in ventricular tissue subjected to the systemic effects of burn trauma. Disruption of the polyinositol phosphates may underlie either the cause, or exacerbation, of heart dysfunction and cellular damage in burn patients.
Asunto(s)
Quemaduras/metabolismo , Fosfatos de Inositol/metabolismo , Miocardio/metabolismo , Animales , Quemaduras/patología , Glicerofosfatos/metabolismo , Inositol/metabolismo , Masculino , Ratones , Ratones EndogámicosRESUMEN
In this report, we have used multivariate and vectorial analyses to aid in understanding perturbations in diaphragmatic signal transduction in consequence to burn trauma. This trauma results from shock emanating from skin scald burn. Its respiratory complications are well-known. Relational matrices derived from experimental animal groups of varying body surface area (% BSA) burn size were subjected to individual multiple linear regression and vectorial analyses. Such individual matrices tested the simultaneous dependency of inositol 1,4,5-triphosphate (IP3) on inositol 1,4-biphosphate (I1,4P2), inositol 1-phosphate (I1P) and inositol. Understanding the contribution of multiple independent parameters simultaneously co-governing the dependency of IP3 offers new insight in regulating signal transduction mechanisms under the duress of burn trauma.
Asunto(s)
Quemaduras/metabolismo , Diafragma/metabolismo , Inositol 1,4,5-Trifosfato/metabolismo , Fosfatos de Inositol/metabolismo , Análisis de Varianza , Animales , Superficie Corporal , Diafragma/efectos de los fármacos , Modelos Animales de Enfermedad , Inositol/metabolismo , Masculino , Ratones , Análisis Multivariante , Pomadas , Polímeros , Análisis de Regresión , Transducción de Señal/efectos de los fármacos , Sulfadiazina de Plata/farmacologíaRESUMEN
The novelty of applying three-dimensional graphic capabilities involving area and vector changes was used to understand variations in inositol derivatives and their comodulating influence on calcium (Ca2+) in skeletal muscle under the duress of burn trauma. Burn injury was achieved by scalding of predefined areas (0, 20% and 50%) on the dorsal and ventral surfaces of mice. At day 21, 45Ca2+ influx and efflux procedures were performed. Through multiple regression, the dependency of intracellular Ca2+ was determined with respect to three polyinositol forms each representing independence simultaneously. The contribution of each of these parameters was assigned to a three-dimensional axis. Vector analysis determined the relationship of intracellular Ca2+ to each of the independent parameters in control, 20% and 50% burn groups. Such vector analysis allows for a clear visualization of the interrelationships that exist between secondary (viz, IP3) and tertiary (viz, Ca2+) messenger systems. This clear visualization may allow for a greater understanding of messenger systems that may lead to more effective treatment of the systemic effects of severe burn trauma.
Asunto(s)
Quemaduras/fisiopatología , Calcio/metabolismo , Músculos/fisiopatología , Transducción de Señal , Animales , Quemaduras/metabolismo , Fosfatos de Inositol/metabolismo , Masculino , Ratones , Ratones Endogámicos , Modelos Biológicos , Análisis Multivariante , Músculos/metabolismo , Análisis de RegresiónRESUMEN
The systemic effects of burn trauma impact on multiple systems of the body, affecting cell metabolism and function. This work examines the multivariate dependency of adenosine 3':5' cyclic monophosphate (cAMP) on three different forms of polyinositol phosphates in burn trauma. Burn injury was achieved by scalding predefined areas corresponding to 0, 20 and 50 per cent of the body surface area (BSA) on the dorsal and ventral surfaces of mice. At day 21, following twitch studies, cAMP levels in the gastrocnemius muscle were measured by 125I-labelled radioimmunoassay procedures. The levels of various polyinositol phosphates (inositol 1 phosphate (I1P), inositol 1,4 biphosphate (I1,4P2) and inositol 1,4,5 triphosphate (I1,4,5P3 or IP3)) were measured using myo-[2-3H]inositol. Through multivariate analysis, the dependency of cAMP was determined with respect to these three polyinositol forms as the independent factors. The contribution of each of these independent parameters was assigned to three-dimensional axes. Vector analysis determined the relationship of cAMP to each of the independent parameters in control, 20 per cent and 50 per cent burn groups. This vector analysis clearly illustrated the changing relationship that existed between the two signal transduction systems (sts) in control and burn groups. An understanding of these changing interrelationships may be useful in developing new means of treatment of a number of the systemic effects of burn trauma.
Asunto(s)
Quemaduras/fisiopatología , AMP Cíclico/metabolismo , Fosfatos de Inositol/fisiología , Transducción de Señal , Animales , Masculino , Ratones , Músculos/metabolismoRESUMEN
This report continues our investigations concerning relative changes in acetylcholinesterase (AChE) activity in response to burn trauma. This experiment was performed in mouse diaphragm. AChE is fundamental to the operating efficiency of the neuromuscular junction. It is through such junctions that all skeletal muscle contraction occurs. This paper tests the hypothesis that burn trauma induces changes in diaphragm AChE with respect to total content, specific molecular forms, and relationships of the polymorphic forms to each other. After mice were exposed to increasing size of body surface area (20%, 30%, and 50%) diaphragms were excised at 3 weeks after burn injury. AChE activity was measured by differential extraction and velocity sedimentation on sucrose gradients. In the sham-treated control groups most of the AChE activity consisted entirely (92%) of the globular forms (S1 and S2). Asymmetric (S3 and S4) and nonextractable (H5) forms made up 2% and 6% of the AChE activity, respectively. In the burn groups all total globular activity was decreased by 1/6 to 1/3 of control groups. For these groups the asymmetric forms (S3 and S4) were increased ninefold to fourteenfold. Nonextractable forms (S5) among the groups were not different. Individual soluble globular forms (S1: 4S, 6.5S, 10S) were reduced by 50% for only the 20% and 30% BSA groups. Residual globular forms (S2) were increased threefold to ninefold. Some of the asymmetric forms (S3: 4S, 10S, 12S, and 16S) were increased fivefold to eightfold among the burn groups. Residual asymmetric (S4) and nonextractable (S5) forms were not different. This report shows that in response to burn trauma the AChE activity of the diaphragm and the interdependence of the polymorphic forms were changed at the chronic postburn period. These findings may aid in understanding the adaptive response of diaphragmatic preservation in burn trauma.
Asunto(s)
Acetilcolinesterasa/química , Quemaduras/enzimología , Diafragma/enzimología , Acetilcolinesterasa/metabolismo , Adaptación Fisiológica/fisiología , Animales , Quemaduras/fisiopatología , Diafragma/fisiopatología , Ratones , Contracción Muscular/fisiología , Respiración/fisiología , Factores de TiempoRESUMEN
The novelty of applying 3-dimensional graphic capabilities, involving area and vector changes was used to understand variations in inositol derivatives due to the systemic effects of large body surface area (BSA) burns. This report is an attempt to broaden current perspectives on how such changes in inositol forms impact on the disposition of IP3 within skeletal muscle cells. Because it is the first of its type to evaluate systemic effects in this way, it is called the alpha study. Consideration of multiple factors (viz., 5 orders of magnitude) involved in burn trauma in this manner provides new insight into the pharmacologic changes which utilize the IP3 signal transducing system that underlie burn trauma. Such insight would prove beneficial in improving the quality of rehabilitative burn care with respect to skeletal muscle physiology.
Asunto(s)
Quemaduras/fisiopatología , Inosina Trifosfato/fisiología , Transducción de Señal/fisiología , Animales , Fosfatos de Inositol/metabolismo , Masculino , Ratones , Modelos Biológicos , Análisis Multivariante , Análisis de Regresión , Sistemas de Mensajero Secundario/fisiologíaRESUMEN
Skeletal muscle weakness associated with burn trauma prolongs the time of rehabilitation of burn patients. Understanding the underlying chemical changes that impact on physiological tension may provide new therapeutic options for the treatment of burn patients. This report demonstrates the novelty of applying 3-dimensional graphic capabilities, involving area and vector changes to understand variations in inositol derivatives and their co-modulating influence on physiological tension in skeletal muscle. This muscle was distant from the primary anatomical burn site. It was subjected to circulatory shock emanating from burn trauma. Burn injury was achieved by scalding of predefined areas (0, 20% and 50%) on the dorsal and ventral surfaces of mice. At day 21, tension studies via muscle twitch analyses were performed. Through multiple regression, the dependency of physiologic tension was determined with respect to three poly-inositol forms each representing independent parameters simultaneously. The contribution of each of these parameters was assigned to a three-dimensional axis. Relationships of tension on three fixed independent parameters were found only for the 20% and 50% burn groups. Vector analysis on a plane in three-dimensional space determined the relationship of tension to each of the independent parameters in 20% and 50% burn groups. No significant relationship of tension dependency on three fixed poly-inositol variables was found in the control group. Such vector analysis, using solid and differential analytical geometry, allowed for a clear visualization of the interrelationships that existed between secondary messenger systems (viz, IP3) and a resulting physiologic manifestation (viz, tension). This clear visualization allows for a greater understanding of messenger systems that may lead to more effective treatment of skeletal muscle weakness associated with the systemic effects of severe burn trauma.
Asunto(s)
Quemaduras/fisiopatología , Fosfatos de Inositol/fisiología , Músculos/fisiopatología , Transducción de Señal/fisiología , Animales , Quemaduras/metabolismo , Modelos Animales de Enfermedad , Inositol 1,4,5-Trifosfato/metabolismo , Inositol 1,4,5-Trifosfato/farmacología , Fosfatos de Inositol/metabolismo , Masculino , Ratones , Ratones Endogámicos , Análisis Multivariante , Contracción Muscular/efectos de los fármacos , Contracción Muscular/fisiología , Músculos/efectos de los fármacos , Músculos/metabolismo , Análisis de RegresiónRESUMEN
The systemic effects of trauma from large body surface area (% BSA) burns were evaluated in terms of second messenger levels involving polyinositol phosphates as they related to adenosine 3':5'-cyclic monophosphate (cAMP), myoplasmic Ca2+, and active tension. Gastrocnemius muscles were harvested after muscle twitch at postburn day 21. Levels of polyinositols were measured by incorporation of myo-[2-3H]-inositol, with separation of the phosphates by anion-exchange chromatography. Analysis of variance was used for statistical evaluation. Multivariate relationships between the: 1) independent polyinositol forms (3H-inositol, I1P, and I1,4,P2) and dependent I1,4,5,P3 existed for control (R2 = 0.71) and 20% BSA burn (R2 = 0.67) groups; 2) the independent polyinositol forms (I1P, I1,4,P2, and I1,4,5,P3) and dependent cAMP for control (R2 = 0.73), 20% BSA (R2 = 0.99), and 50% BSA (R2 = 0.99) groups; 3) independent polyinositol forms (I1P, I1,4,P2, and I1,4,5,P3) and dependent 45Ca2+ for the control (R2 = 0.99), 20% BSA (R2 = 0.44), and 50% BSA (R2 = 0.82) groups; and 4) independent polyinositol forms (I1P, I1,4,P2, and I1,4,5,P3) and dependent active tension for 20% BSA (R2 = 0.97) and 50% BSA (R2 = 0.64) burn groups. Numerous interrelationships existed with each of the multivariate tests. These analyses confirm that several independent polyinositols contribute to changes in the second messengers of I1,4,5,P3, cAMP, and Ca2+ in skeletal muscle as a result of the systemic trauma of burn injury.
Asunto(s)
Quemaduras/fisiopatología , Sistemas de Mensajero Secundario/fisiología , Animales , Calcio/metabolismo , Cromatografía por Intercambio Iónico , AMP Cíclico/metabolismo , Glicerofosfatos/metabolismo , Inositol/metabolismo , Inositol 1,4,5-Trifosfato/metabolismo , Fosfatos de Inositol/metabolismo , Masculino , Ratones , Contracción MuscularRESUMEN
Respiratory problems are common among burn patients, and an understanding of the changes that occur in the phosphatidyl inositol signal transducing system (s.t.s.) in diaphragm muscle may identify pharmacological agents that would be useful in the treatment of these patients. This report examines changes that occur in polyinositol phosphates of diaphragm muscle due to the systemic effects of large (> 30 per cent) body surface area (per cent BSA) burns. Burn injury was applied to specific per cent BSA of the dorsal and ventral skin surfaces of mice. At postburn day 21, polyinositol phosphate levels were measured in the diaphragm by the incorporation of myo-[2-3H]inositol with separation of the phosphates by anion-exchange chromatography. All data were analysed using analysis of variance and curve fitting. In the diaphragm, levels of [3H]inositol, inositol-1,4,5 trisphosphate (IP3), inositol-1,4 bisphosphate (I1,4P2) and inositol-1 phosphate (I1P) increased with increasing burn size. Furthermore, a variety of independent relationships existed between the various phosphates in each burn group (i.e. control, 20 per cent and 50 per cent BSA burn). These data indicate that the systemic effects of burn trauma result in changes in the polyinositol phosphate part of the phosphatidyl inositol signal transducing system of diaphragm muscle.
Asunto(s)
Quemaduras/metabolismo , Diafragma/metabolismo , Fosfatos de Inositol/metabolismo , Animales , Superficie Corporal , Masculino , RatonesRESUMEN
The purpose of this report was to see if changes in polyinositol phosphates occurred with increasing percentage body surface area (% BSA) burn. Burn injury was applied to predefined areas of the dorsal and ventral skin surface of mice. After a 10-min stimulation period involving muscle twitch, polyinositol phosphate levels at 3 weeks postburn were measured by the incorporation of myo[2-3H]inositol with separation of the phosphates by anion-exchange chromatography. Analysis of variance was used for all statistical evaluations. In gastrocnemius muscle an increase (P < 0.001) occurred for levels of [3H]inositol, inositol-1, phosphate (I1P), and inositol-1,4,5-trisphosphate (I1,4,5P3) for the 50 per cent BSA burn group. However, levels of inositol-1;4,biphosphate (I1,4P2) decreased (P < 0.001). Positive correlations were found between [3H]inositol, I1P and IP3 and 50 per cent BSA burn. A negative correlation between I1,4P2 and percentage BSA burn was found. These data provide evidence that polyinositol phosphate metabolism in skeletal muscle was altered due to large burn size.