phosphocreatine and Shock

Donation after circulatory death (DCD) could improve cardiac graft availability. However, strategies to optimize cardiac graft recovery remain to be established in DCD; these hearts would be expected to be exposed to high levels of circulatory fat immediately prior to the inevitable period of ischemia prior to procurement.. We investigated whether acute exposure to high fat prior to warm, global ischemia affects subsequent hemodynamic and metabolic recovery in an isolated rat heart model of DCD.. Hearts of male Wistar rats underwent 20min baseline perfusion with glucose (11mM) and either high fat (1.2mM palmitate; HF) or no fat (NF), 27min global ischemia (37°C), and 60min reperfusion with glucose only (n=7-8 per group). Hemodynamic recovery was 50% lower in HF vs. NF hearts (34±30% vs. 78±8% (60min reperfusion value of peak systolic pressure*heart rate as percentage of mean baseline); p<0.01). During early reperfusion, glycolysis (0.3±0.3 vs. 0.7±0.3μmol*min. Acute, pre-ischemic exposure to high fat significantly lowers post-ischemic cardiac recovery vs. no fat despite identical reperfusion conditions. These findings support the concept that oxidation of residual fatty acids is rapidly restored upon reperfusion and exacerbates ischemia-reperfusion (IR) injury. Strategies to optimize post-ischemic cardiac recovery should take pre-ischemic fat levels into consideration.

Topics: Adenosine Triphosphate; Animals; Cytochromes c; Fatty Acids; Glucose; Heart Transplantation; Hemodynamics; In Vitro Techniques; Male; Myocardial Ischemia; Oxygen Consumption; Phosphocreatine; Rats; Rats, Wistar; Recovery of Function; Shock

The mechanisms responsible for acute renal failure in sepsis are not understood. Measurement of tissue ATP might help to understand this process but, in the large animal, it is hampered by major technical difficulties.. To develop a technique to monitor ATP in the kidney of a large mammal during the induction of septic shock and then circulatory arrest.. Implantation of a custom-made phosphorus coil around the left kidney. Induction of septic shock by intravenous E. coli administration. Acquisition of 31 P magnetic resonance (MR) spectroscopic data at 3-tesla before and during septic shock over several hours. Induction of euthanasia and measurement of the same 31 P signal immediately and thirty minutes after circulatory arrest.. Clear reproducible 31 P MR spectra were obtained before and after the induction of septic shock and euthanasia. They indicated limited changes in ATP during septic shock. An expected rapid and dramatic decrease in ATP occurred with euthanasia.. It is possible to sequentially monitor renal bioenergetics in a large mammal during septic shock using an implanted custom-made phosphorus coil and 3-tesla MR technology. This technique offers a novel approach to the investigation of septic renal failure.

Topics: Acute Kidney Injury; Adenosine Triphosphate; Animals; Bacteremia; Disease Models, Animal; Escherichia coli Infections; Female; Kidney; Magnetic Resonance Spectroscopy; Phosphocreatine; Phosphorus Isotopes; Sheep; Shock; Shock, Septic; Thionucleotides

Phosphorus magnetic resonance spectroscopy (31P-MRS) was made to measure changes in brain high energy phosphate compounds, adenosine triphosphate (ATP) and phosphocreatine (PCr), inorganic phosphorus (Pi) and intracellular pH (pHi) during a prolonged period of incomplete brain ischaemia produced, in anaesthetized dogs, by bilateral carotid occlusion together with haemorrhagic hypotension for intervals of up to 300 min. Mean arterial blood pressure (MABP) was lowered in a stepwise fashion, until signs of metabolic decompensation (as estimated by MRS) occurred. At that point MABP was varied against further evidence of metabolic decompensation in an attempt to maintain a more constant degree of insult. At the end of the ischaemic period MABP was restored and the animals observed during a 3 h recovery period. At the end of the recovery period the brains were perfusion-fixed for histological examination. A semi-quantitative method of histological evaluation was used to determine the degree of histological damage. This permitted assignment of an 'ischaemic score' to the tissue sampled from each animal. Comparisons were then made between the magnitude of this 'ischaemic score' and the changes in metabolic and physiological variables (ATP, PCr, pHi and MABP) as well as an estimator of phosphorylation potential (PCr/Pi), which were all measured during the ischaemic insult. Histological examination showed a wide variety of neuronal alterations, including dark and pale type injury, which correlated directly with the metabolic derangements brought about by ischaemia. The degree of damage determined from this histological assessment correlated best with the duration and degree of change in PCr/Pi, supporting the use of this ratio as a critical index of cellular energy state. In particular there was a strong linear relationship between the degree of leucocyte recruitment and changes in PCr/Pi. To summarize, metabolic changes, determined by MRS, correlate with the degree of histological damage, and in turn, the classical descriptions of acute ischaemic neuronal injury appear to be validated by MRS determinations of metabolic changes during ischaemia.

Topics: Adenosine Triphosphate; Animals; Brain; Brain Chemistry; Brain Ischemia; Dogs; Magnetic Resonance Imaging; Phosphates; Phosphocreatine; Phosphorus Isotopes; Shock

Sequential 31P nuclear magnetic resonance (NMR) spectra were measured in adult dogs to determine the relationship between cardiac function and myocardial intracellular pH (pHi) and phosphorylated energy metabolites during 2 h of hemorrhagic shock. Simultaneous measurements of coronary blood flow (radioactive microspheres), arterial and coronary sinus pH, blood gases, and oxygen content were performed. In addition, changes in brain NMR spectra were correlated with changes in cerebral blood flow during shock. Two hurs of hypovolemic shock resulted in significant decreases in phosphocreatine (PCr), PCr-to-ATP ratio, and pHi, whereas Pi rose significantly relative to baseline values. Return of shed blood and crystalloid fluid resuscitation improved cerebral and coronary perfusion and returned cardiac contractile function to near baseline values. We conclude that severe and sustained hemorrhagic shock produced significant alterations in brain and heart phosphorylated metabolites as well as significant intracellular acidosis; however, these changes in energy metabolites were reversible with adequate fluid resuscitation from shock.

Topics: Adenosine Triphosphate; Animals; Blood Volume; Brain; Cerebrovascular Circulation; Coronary Circulation; Dogs; Energy Metabolism; Hemorrhage; Hypotension; Male; Myocardium; Nucleotides; Phosphocreatine; Phosphorus; Resuscitation; Shock

The results of this study demonstrated that muscle ATP levels were sustained in hemorrhagic shock despite marked deterioration of muscle function as indicated by a decline in PD. This indicated that energy depletion was not the primary basis of the cellular dysfunction in hemorrhagic shock. Cellular dysfunction and metabolic abnormalities in the liver occurred earlier during the course of hemorrhagic shock than in muscle. Other studies were cited in which it was suggested that inhibition of the membrane bound sodium and potassium active transport mechanism is the likely cause of tissue electrolyte and fluid shifts observed during prolonged periods of hemorrhagic shock.

Topics: Adenosine Triphosphate; Animals; Female; Hemodynamics; Hydrogen-Ion Concentration; Lactates; Liver; Liver Circulation; Membrane Potentials; Muscles; Papio; Phosphocreatine; Primates; Shock; Shock, Hemorrhagic

Topics: Adenosine Triphosphate; Animals; Blood Pressure; Capillaries; Cats; Constriction, Pathologic; Membrane Potentials; Microcirculation; Muscles; Phosphocreatine; Shock

Topics: Adenosine Triphosphate; Animals; Dogs; Hydrogen-Ion Concentration; Lactates; Membrane Potentials; Muscles; Phosphocreatine; Shock

The relevance of two direct techniques for monitoring of cellular function during tissue hypoxia has been evaluated. Tissue pH and cellular transmembrane potentials were registered in canine skeletal muscle during intestinal exteriorization shock and during prolonged local tourniquet ischemia. The obtained pH and transmembrane potential changes were correlated to simultaneous changes in high-energy phosphagen (ATP + CP) and lactate levels in skeletal muscle. In control dogs no significant changes in either of the studied variables occurred. Intestinal exteriorization shock as well as local tourniquet ischemia resulted in a gradual increase in tissue lactate and a concomitant decrease in tissue pH and transmembrane potentials. In both experimental situations there was a close correlation between the transmembrane potential reduction and the tissue lactate increase. Tissue pH registrations, on the other hand, did not similarly reveal the full extent of the tissue lactate increase under the two experimental conditions. Possible reasons for this discrepancy are discussed. On the basis of the present results it may therefore be concluded that the transmembrane potential seems to be a better variable for revealing the full extent of cellular metabolic deterioration during various situations with tissue hypoxia.

Topics: Adenosine Triphosphate; Animals; Blood Pressure; Dogs; Electrophysiology; Hindlimb; Hydrogen-Ion Concentration; Ischemia; Lactates; Membrane Potentials; Muscles; Phosphocreatine; Shock

Topics: Adenosine Triphosphate; Animals; Barbiturates; Biological Transport; Cell Membrane Permeability; Chromatography, Paper; Digitalis Glycosides; Dogs; Guinea Pigs; Heart; Heart Failure; Hypoxia; Myocardium; Phenylbutazone; Phosphates; Phosphocreatine; Potassium; Rats; Renal Dialysis; Shock; Sodium; Water-Electrolyte Balance

Topics: Animals; Brain; Coenzymes; Electric Stimulation; Phosphocreatine; Rats; Shock