phosphocreatine and Burns

In the heart, thermal injury activates a group of intracellular cysteine proteases known as caspases, which have been suggested to contribute to myocyte inflammation and dyshomeostasis. In this study, Sprague-Dawley rats were given either a third-degree burn over 40% total body surface area plus conventional fluid resuscitation or sham burn injury. Experimental groups included 1) sham burn given vehicle, 400 microl DMSO; 2) sham burn given Q-VD-OPh (6 mg/kg), a highly specific and stable caspase inhibitor, 24 and 1 h prior to sham burn; 3) burn given vehicle, DMSO as above; 4) burn given Q-VD-OPh (6 mg/kg) 24 and 1 h prior to burn. Twenty-four hours postburn, hearts were harvested and studied with regard to myocardial intracellular sodium concentration, intracellular pH, ATP, and phosphocreatine (23Na/31P nuclear magnetic resonance); myocardial caspase-1, -3,and -8 expression; myocyte Na+ (fluorescent indicator, sodium-binding benzofurzan isophthalate); myocyte secretion of TNF-alpha, IL-1beta, IL-6, and IL-10; and myocardial performance (Langendorff). Burn injury treated with vehicle alone produced increased myocardial expression of caspase-1, -3, and -8, myocyte Na+ loading, cytokine secretion, and myocardial contractile depression; cellular pH, ATP, and phosphocreatine were stable. Q-VD-OPh treatment in burned rats attenuated myocardial caspase expression, prevented burn-related myocardial Na+ loading, attenuated myocyte cytokine responses, and improved myocardial contraction and relaxation. The present data suggest that signaling through myocardial caspases plays a pivotal role in burn-related myocyte sodium dyshomeostasis and myocyte inflammation, perhaps contributing to burn-related contractile dysfunction.

Topics: Adenosine Triphosphate; Amino Acid Chloromethyl Ketones; Animals; Burns; Calcium; Caspase 1; Caspase 3; Caspase 8; Caspase Inhibitors; Caspases; Cysteine Proteinase Inhibitors; Disease Models, Animal; Heart Diseases; Homeostasis; Hydrogen-Ion Concentration; Interleukin-10; Interleukin-1beta; Interleukin-6; Magnetic Resonance Spectroscopy; Male; Myocardial Contraction; Myocytes, Cardiac; Phosphocreatine; Quinolines; Rats; Rats, Sprague-Dawley; Severity of Illness Index; Signal Transduction; Sodium; Tumor Necrosis Factor-alpha; Ventricular Pressure

We have used a rectangular surface coil and chemical shift imaging to conduct in vivo localized 31P NMR metabolic studies in a rat dorsal skin flap model. This approach permits regional comparisons without manipulation of either coil position or subject within the magnet bore. Both the PCr:Pi ratio (reflecting ischemia insult) and the PCr:ATP ratio (reflecting phosphagen reserves) decreased as functions of time and distance from the vascular pedicle. The maximum change was nearly 6-fold for the PCr:Pi ratio, and 3-fold for the PCr:ATP ratio. Signal contamination from subjacent muscle is constant and does not interfere with the metabolic evaluations of skin flaps. This technique may facilitate a better understanding of cutaneous metabolic derangements, such as burns and skin flaps used in reconstructive surgery, as well as studies of pharmacologic regimens developed for their treatment. It also holds potential for application in the study of congenital and neoplastic metabolic disorders of skin.

Topics: Adenosine Triphosphate; Animals; Burns; Energy Metabolism; Hempa; Ischemia; Magnetic Resonance Spectroscopy; Male; Models, Structural; Muscle, Skeletal; Phosphates; Phosphocreatine; Phosphorus Isotopes; Rats; Rats, Sprague-Dawley; Skin; Skin Diseases; Skin Neoplasms; Surgical Flaps; Time Factors

Skeletal muscle changes associated with severe injury were investigated in male Wistar rats subjected to 30% full thickness scald injury (burn) and thermal injury followed by immediate colonization with 10(8) colony-forming units of Pseudomonas aeruginosa (BI). Freely fed animals (FF) and animals pair fed to the BI animals (PF) served as controls. Thermal injury in conjunction with infection produced a rapid and sustained muscle cellular membrane depolarization (transmembrane potential difference at 12 h after injury: FF 92.1 +/- 0.3 and BI 85.2 +/- 2.3 mV; P less than 0.05). This was followed by body weight loss and skeletal muscle protein wasting (gastrocnemius protein at 7 days: FF 0.35 +/- 0.01 and BI 0.16 +/- 0.03 g; P less than 0.05) and intracellular high-energy phosphate depletion (ATP at 10 days: FF 6.6 +/- 0.4 and BI 4.5 +/- 0.4 mumol/g tissue; P less than 0.05). These body and cellular changes were not accounted for by the anorexia alone. Marked alterations in intracellular free amino acids were also noted in the BI group characterized by increases in levels of all amino acids (total intracellular free amino acids at 7 days: FF 51 +/- 7 and BI 91 +/- 12 mM; P less than 0.05) except intracellular glutamine (at 7 days: FF 6.0 +/- 0.2 and BI 2.4 +/- 0.6 mM; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Actins; Adenosine Triphosphate; Amino Acids; Animals; Burns; DNA; Energy Metabolism; Membrane Potentials; Muscle Proteins; Muscles; Myosins; Phosphocreatine; Potassium; Pseudomonas Infections; Rats; Rats, Inbred Strains; Reference Values; RNA; RNA, Messenger; Sodium

The role of lactate in the metabolism of the healing wound is poorly understood. The purpose of the present studies was to determine if despite a net lactate production, wounded (Wx) tissue could metabolize lactate and use it as an oxidative fuel. The extensor digitorum longus muscles (EDL) of weanling, male, Fischer rats were injured with lambda-carrageenan or injured thermally, and 5 and 3 days later, respectively, were incubated in a standard incubate that contained varying amounts of lactate (0 to 6 mmol/L added). Lactate uptake and oxidation, occurred in lambda-carrageenan Wx EDL, thermally injured EDL and non-Wx EDL in a dose-dependent manner. At lactate concentrations of less than 3 mmol/L in the incubate, there was net lactate production, but at lactate concentrations of 6 mmol/L there was no net lactate production by both Wx and non-Wx EDL. The increase in lactate oxidation was not associated with an alteration in the tissue content of adenosine triphosphate or creatine phosphate. It was associated with a reduction in glucose oxidation in Wx and non-Wx EDL and by a decrease in glucose uptake by Wx EDL. These data suggest that lactate may be used as an oxidative fuel by wounded tissue and in this regard may substitute for glucose.

Topics: Adenosine Triphosphate; Animals; Burns; Carrageenan; Energy Metabolism; Glucose; Hindlimb; Lactates; Lactic Acid; Male; Muscles; Oxidation-Reduction; Phosphocreatine; Rats

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Adult; Animals; Burns; Cats; Child; Energy Metabolism; Extremities; Humans; Hydrogen-Ion Concentration; Kinetics; Magnetic Resonance Spectroscopy; Muscles; Oxygen Consumption; Phosphocreatine; Physical Exertion; Thermodynamics

Topics: Adenosine Triphosphatases; Adenosine Triphosphate; Animals; Burns; Dogs; Hemorrhage; Liver; Male; Phosphocreatine; Resuscitation