phosphocreatine and Hypotension

Topics: Adenosine Triphosphate; Animals; Blood Pressure; Brain; Brain Chemistry; Brain Damage, Chronic; Brain Edema; Carbon Dioxide; Cats; Cerebrovascular Circulation; Cerebrovascular Disorders; Electroencephalography; Heart Arrest; Humans; Hypotension; Hypoxia; Hypoxia, Brain; Indicator Dilution Techniques; Ischemia; Lactates; Mathematics; Oxygen; Phosphocreatine; Prognosis; Vasomotor System

This study was conducted to determine if mechanisms that reduce right coronary (RC) blood flow (RCBF) and right ventricular (RV) oxygen consumption (MVO2) during moderate RC hypotension preserve RV high-energy phosphates. RC arteries of anesthetized dogs were cannulated and perfused with arterial blood supplied by a pressurized extracorporeal circuit. RC perfusion pressure (RCPP) was either kept constant at 100 mmHg or reduced to 60 or 30 mmHg for 20 min followed by a freeze-clamp biopsy of RV. Left ventricular (LV) biopsy was also performed to compare energy metabolism between RV and LV.RCBF and MVO2 significantly decreased when RCPP was reduced to 60 mmHg, but RV segment shortening (%SS) was unchanged; ATP, creating phosphate (CrP) and phosphorylation state of CrP ([CrP]/[Cr][Pi]) did not differ from control values. RV %SS, CrP, and phosphorylation state fell markedly at 30 mmHg RCPP. At 100 mmHg RCPP, CrP phosphorylation state in RV was only 35% of that in LV. These results indicate that RV increases its energetic efficiency without significant changes in high-energy phosphates or CrP phosphorylation state during moderate RC hypotension. Furthermore, the RV myocardium maintains a much lower energy level than LV myocardium, commensurate with its lower energy requirements.

Topics: Adenosine Triphosphate; Animals; Blood Pressure; Coronary Circulation; Coronary Vessels; Dogs; Drug Stability; Energy Metabolism; Female; Hemodynamics; Hypotension; Male; Myocardium; Phosphocreatine; Ventricular Function, Right

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

To clarify the effect of hypovolemic hypotension on high-energy phosphate metabolism in head injury, sequential changes in in vivo phosphorus-31 magnetic resonance (31P MR) spectra were compared in 35 rats after impact injury with and without hypotension. Fourteen rats were subjected to hypotension alone (mean arterial blood pressure (MABP) of either 40 or 30 mm Hg for 60 minutes), seven to fluid-percussion impact injury (4 to 5 atm) alone, and 14 to impact injury and hypotension (MABP of 40 to 30 mm Hg). Impact injury alone caused a transient decrease in the phosphocreatine (PCr) level and an increase in the inorganic phosphate (Pi) value. While hypotension alone produced only small changes on 31P MR spectra, impact injury plus hypotension caused pronounced changes. Impact injury and an MABP of 40 mm Hg caused a 50% decrease in PCr concentration and an approximately twofold increase in Pi level, which were significantly greater than values in rats with impact injury alone. Impact injury and an MABP of 30 mm Hg also caused a significant decrease in adenosine triphosphate value, which was not observed in rats with impact injury alone or with an MABP of 30 mm Hg alone. Decreases in intracellular pH were greater in rats with impact injury and hypotension. After traumatic injury, the brain is extremely vulnerable to hypovolemic hypotension, as reflected in the loss of high-energy phosphates in brain.

Topics: Animals; Brain; Brain Injuries; Hypotension; Magnetic Resonance Spectroscopy; Male; Phosphates; Phosphocreatine; Rats; Rats, Inbred Strains; Time Factors

Changes in cerebral high-energy phosphate stores and lactate concentration (as evidence for cerebral protection) were studied in dogs treated with etomidate during incomplete global ischemia, which was of a magnitude insufficient to abolish neuronal synaptic activity (as evidenced by electrical activity on EEG). In six dogs the effects of etomidate (5 mg X kg-1) on the rates of adenosine triphosphate (ATP) and phosphocreatine (PCr) depletion and lactate accumulation during 9 min of oligemic hypotension to 31 mmHg were compared with six untreated dogs. In the dogs treated with etomidate the cerebral energy stores of ATP and PCr and the cerebral energy charge were maintained at higher levels than in the untreated dogs, and the cerebral lactate accumulation was significantly less. This effect of etomidate is similar to that of other anesthetics (thiopental and isoflurane) in this model. The authors conclude that in circumstances of ischemia that are insufficient to abolish neuronal synaptic activity, etomidate may improve tolerance of the brain to ischemia by decreasing cerebral metabolism through its suppression of neuronal synaptic activity.

Topics: Adenosine Triphosphate; Animals; Brain Ischemia; Dogs; Electroencephalography; Energy Metabolism; Etomidate; Hypotension; Lactates; Lactic Acid; Phosphates; Phosphocreatine

Rats were subjected to 30 minutes of hypoxic-hypotension and then allocated to one of four treatment groups. Group I was resuscitated by restoration of FIO2 = 30% and reinfusion of shed blood plus an equal volume of additional saline. Group II received in addition nifedipine, 10 micrograms/kg, and groups III and IV received in addition either verapamil, 0.2 mg/kg or 1 mg/kg, respectively. Significantly (P less than 0.01) higher concentrations of creatine phosphate and ATP were present in the brain after nifedipine and after 1 mg/kg verapamil treatment.

Topics: Adenosine Triphosphate; Animals; Brain; Cerebrovascular Circulation; Hypotension; Hypoxia, Brain; Male; Nifedipine; Phosphates; Phosphocreatine; Rats; Rats, Inbred Strains; Verapamil

Experiments on dogs with long-term hypotony caused by blood loss have demonstrated irreversible lesions in the majority of cardiomyocytes and hypodynamic condition of the heart with a high content of macroergic phosphates in the myocardium. Intravenous injection of sodium hydroxybutyrate in a dose of 180-200 mg/kg after 60 min of hypotony seems to improve energy transport and utilization in the ischemic myocardium. It increases the working capacity and power of the heart muscle, pump function of the heart and makes longer the period of ultrastructural changes in cardiomyocytes.

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Creatine; Dogs; Energy Metabolism; Heart; Hemodynamics; Hemorrhage; Hydroxybutyrates; Hypotension; Myocardium; Phosphocreatine; Sodium Oxybate

The relative performance of whole blood and saline, a balanced salt-albumin solution, and Fluosol-43 were compared in an experimental animal model of combined hypoxia and hypotension. The test fluids were evaluated in terms of their respective ability to restore mean arterial pressure and provide adequate oxygen to restore and maintain a normal brain cytochrome a,a3 redox state, restore and sustain normal cerebral cortical ATP and creatinine phosphate concentrations (CP), and return cerebral cortical lactate concentrations to normal after the hypoxic-hypotensive period. With regard to ATP, CP, lactate, and cytochrome a,a3, all three test fluids performed equally well inasmuch as there were no significant differences between groups. None of the test regimens resulted in normal ATP concentration post-hypoxic hypotension. Although CP concentrations were lower than baseline after resuscitation, the difference was not statistically significant. Fluosol-43 resuscitation resulted in a significantly higher (p less than 0.05) mean arterial pressure by 120 minutes post-resuscitation. It was concluded that Fluosol-43 is an acceptable resuscitative fluid, most beneficial at extremely low hematocrits, but that selection of Fluosol-43 over balanced salt-albumin could not be supported when post-resuscitation hematocrits were in the 20 to 25% range.

Topics: Adenosine Triphosphate; Animals; Brain; Brain Chemistry; Fluorocarbons; Hypotension; Hypoxia; Lactates; Male; Oxygen Consumption; Phosphocreatine; Rats; Rats, Inbred Strains; Resuscitation; Shock, Septic

Rats were "stressed" by a 30-min period of hypoxia (FIO2 = 7.5%) and hypotension (x arterial pressure = 30 mm Hg), and then "resusciated" by restoring FIO2 = 30% and reinfusing shed blood to restore arterial pressure toward baseline values. Concentrations of brain phosphocreatine, ATP and lactate were measured after "stress" and 20, 60, and 120 min after "resuscitation". A biphasic response was noted in which ATP was initially restored to baseline values by "resuscitation", and then progressively decreased. Physiologic mechanisms to explain the observed data are presented.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Blood Pressure; Brain; Carbon Dioxide; Energy Metabolism; Hypotension; Hypoxia; Lactates; Male; Oxygen; Partial Pressure; Phosphocreatine; Rats

In 62 dogs, hypotension to a mean arterial pressure of either 40 or 50 torr (equivalent to a cerebral perfusion pressure of 30 or 40 torr, respectively) for one hour was induced by hemorrhage (oligemia), trimethaphan, halothane, or sodium nitroprusside. Before and during the period of hypotension, the following were measured: mean arterial blood pressure, cardiac output, whole-body O2 consumption, cerebral blood flow, cerebral O2 consumption, arterial blood gases, blood O2 content, and lactate, pyruvate, glucose, epinephrine, and norepinephrine concentrations. At the end of the period of hypotension, brain biopsies were taken for determination of adenosine triphosphate, phosphocreatine, lactate, and pyruvate concentrations. In an additional eight dogs following one hour of hypotension (at 40 torr) induced by one of the four techniques, the brains were perfused with carbon black, removed, and examined. In another ten dogs following hypotension (at 40 torr) induced with either halothane or trimethaphan, the animals were observed for three days and then killed for examination of the brain. Dogs maintained at a mean arterial pressure of 40 torr, despite differences in cerebral blood flow, demonstrated metabolic disturbances compatible with systemic and cerebral hypoxia. These were greatest in those dogs given nitroprusside in excess of 1.0 mg/kg, presumably due to cyanide toxicity. In dogs maintained at 50 torr, metabolic disturbances were minimal or absent in the halothane- and nitroprusside-treated dogs but were still apparent in the oligemic and trimethaphan-treated dogs. Carbon black infusions revealed no evidence of non-homogeneous flow. Three of the ten dogs observed for three days had persistent post-hypotension neurologic dysfunction. Two of these were given trimethaphan. The results suggest that the systemic and cerebral effects of halothane and nitroprusside (at doses less than 1.0 mg/kg) are similar and at a mean arterial pressure of 50 torr are of little consequence. By contrast, hypotension induced by trimethaphan or oligemia results in detectable metabolic alterations even at a pressure of 50 torr.

Topics: Adenosine Triphosphate; Animals; Brain Chemistry; Cerebrovascular Circulation; Dogs; Ferricyanides; Halothane; Hemodynamics; Hemoglobins; Hemorrhage; Hypotension; Lactates; Nitroprusside; Phosphocreatine; Trimethaphan

Several indices of energy exchange and protein-amino acid metabolism in the myocardium were studied experimentally in dogs subjected to long-term hypotension (Wiggers' technique, arterial pressure of 40 mm Hg for 3 hours). It was established that by the end of the fixed period of hypotension the myocardial content of adenosine triphosphate, creatinephosphate, glycogen decreased significantly, while the amount of nonorganic phosphorus, lactic and pyruvic acids increased. At the same time the content of watersoluble protein fraction and of most of the 18 identified amino asids decreases in the cardiac muscle. Fractionated intravenous injections of adenosine triphosphate or 1,6-diphosphate fructose permitted to prevent the development of energy deficit, and, to a great extent, that of protein-amino acid metabolism disorders in dogs subjected to long-term hypotension.

Topics: Adenosine Triphosphate; Albumins; Animals; Dogs; Energy Metabolism; Fructosephosphates; Globulins; Glycogen; Hypotension; Lactates; Myocardium; Phosphocreatine; Phosphorus; Pyruvates; Time Factors

Topics: Adenine Nucleotides; Animals; Brain; Brain Chemistry; Carbon Dioxide; Carbonates; Cerebrovascular Circulation; Halothane; Hydrogen-Ion Concentration; Hyperventilation; Hypotension; Lactates; Male; Oxygen; Phosphocreatine; Pyruvates; Rats; Regional Blood Flow

Topics: Acid-Base Equilibrium; Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Anesthesia; Animals; Asphyxia; Barbiturates; Bicarbonates; Brain; Carbon Dioxide; Hydrogen-Ion Concentration; Hypotension; Lactates; Male; Nitrous Oxide; Phenobarbital; Phosphocreatine; Pyruvates; Rats

Topics: Acidosis; Adenosine Triphosphatases; Adenosine Triphosphate; Amino Acids; Animals; Blood Glucose; Blood Pressure; Blood Proteins; Blood Transfusion; Blood Volume; Disease Models, Animal; Dogs; Fructose; Glycogen; Hydrogen-Ion Concentration; Hyperbaric Oxygenation; Hypotension; Lactates; Methods; Phosphates; Phosphocreatine; Pulse; Pyruvates; Respiration

Topics: Acid-Base Equilibrium; Adenine Nucleotides; Adenosine Triphosphate; Animals; Brain Chemistry; Cerebrovascular Circulation; Extracellular Space; Hydrogen-Ion Concentration; Hypotension; Lactates; Phosphocreatine; Pyruvates; Rats

Topics: Adenine Nucleotides; Adenosine Triphosphate; Animals; Arteries; Bicarbonates; Brain; Brain Chemistry; Carbon Dioxide; Extracellular Space; Hydrogen-Ion Concentration; Hypotension; Lactates; Oxygen; Phosphocreatine; Pyruvates; Rats

Topics: Adenosine Triphosphate; Animals; Brain; Brain Edema; Cerebellum; Cerebral Cortex; Cerebrovascular Circulation; Chlorides; Dogs; Electroencephalography; Extracorporeal Circulation; Female; Hypotension; Hypotension, Controlled; Lactates; Male; Medulla Oblongata; Nucleosides; Perfusion; Phosphocreatine; Potassium; Pyruvates; Sodium; Trimethaphan; Water-Electrolyte Balance

Topics: Adult; Femoral Artery; Heart Diseases; Hemodynamics; Humans; Hypotension; Phosphocreatine; Pulse; Raynaud Disease