phosphocreatinine and Disease-Models--Animal

Topics: Adenosine Triphosphate; Animals; Benzhydryl Compounds; Blood Glucose; Diabetes Mellitus; Disease Models, Animal; Energy Metabolism; Glucosides; Ketones; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Mice, Inbred C57BL; Myocytes, Cardiac; Phosphocreatine; Sodium-Glucose Transporter 2 Inhibitors; Ventricular Function

To determine whether epinephrine increases lactate concentration in sepsis through hypoxia or through a particular thermogenic or metabolic pathway.. Prospective, controlled experimental study in rats.. Experimental laboratory in a university teaching hospital.. Three groups of anesthetized, mechanically ventilated male Wistar rats received an intravenous infusion of 15 mg/kg Escherichia coli O127:B8 endotoxin. Rats were treated after 90 min by epinephrine ( n=14), norepinephrine ( n=14), or hydroxyethyl starch ( n=14). Three groups of six rats served as time-matched control groups and received saline, epinephrine, or norepinephrine from 90 to 180 degrees min. Mean arterial pressure, aortic, renal, mesenteric and femoral blood flow, arterial blood gases, lactate, pyruvate, and nitrate were measured at baseline and 90 and 180 min after endotoxin challenge. At the end of experiments biopsy samples were taken from the liver, heart, muscle, kidney, and small intestine for tissue adenine nucleotide and lactate/pyruvate measurements.. Endotoxin induced a decrease in mean arterial pressure and in aortic, mesenteric, and renal blood flow. Plasmatic and tissue lactate increased with a high lactate/pyruvate (L/P) ratio. ATP decreased in liver, kidney, and heart. The ATP/ADP ratio did not change, and phosphocreatinine decreased in all organs. Epinephrine and norepinephrine increased mean arterial pressure to baseline values. Epinephrine increased aortic blood flow while renal blood low decreased with both drugs. Plasmatic lactate increased with a stable L/P ratio with epinephrine and did not change with norepinephrine compared to endotoxin values. Nevertheless epinephrine and norepinephrine when compared to endotoxin values did not change tissue L/P ratios or ATP concentration in muscle, heart, gut, or liver. In kidney both drugs decreased ATP concentration.. Our data demonstrate in a rat model of endotoxemia that epinephrine-induced hyperlactatemia is not related to cellular hypoxia.

Topics: Acidosis, Lactic; Adenosine Diphosphate; Adenosine Triphosphate; Animals; Blood Gas Analysis; Disease Models, Animal; Drug Evaluation, Preclinical; Endotoxemia; Energy Metabolism; Epinephrine; Escherichia coli Infections; Glycolysis; Hemodynamics; Humans; Kidney; Lactic Acid; Liver; Myocardium; Nitrates; Norepinephrine; Phosphocreatine; Pyruvates; Rats; Rats, Wistar; Tissue Distribution

We have developed a closed chest animal model that allows noninvasive monitoring of cardiac high energy phosphate metabolism before, during, and for at least 3 weeks after a myocardial infarction. Ten beagles underwent 2 h of coronary occlusion followed by 3 weeks of reperfusion. Myocardial high energy phosphates from 12-ml voxels were noninvasively tracked using 31P two-dimensional chemical shift imaging. Gadolinium enhanced 1H MRI identified the zone at risk, and radioactive microspheres assessed regional blood flow and partition coefficients. Occlusion of the left anterior descending coronary artery produced infarcts that were 13.7+/-8.8% (mean+/-SD) of the left ventricular volume. Rapid changes in the phosphocreatine and inorganic phosphate levels were observed during occlusion, whereas adenosine triphosphate levels decreased more slowly. All metabolites recovered to base-line levels 2 weeks after occluder release. Multiple inorganic phosphate peaks in the infarct voxel spectra indicated that more than one metabolically compromised tissue zone developed during occlusion and reperfusion. Microsphere data indicating three distinct blood flow zones during ischemia and reperfusion (<0.3, 0.3-0.75, and >0.75 ml/min/g) supported the grouping of pH values into three distinct metabolic distributions.

Topics: Adenosine Triphosphate; Animals; Blood Flow Velocity; Contrast Media; Disease Models, Animal; Dogs; Female; Follow-Up Studies; Gadolinium DTPA; Hydrogen-Ion Concentration; Image Enhancement; Image Processing, Computer-Assisted; Magnetic Resonance Spectroscopy; Microspheres; Myocardial Infarction; Myocardial Reperfusion; Phosphocreatine; Phosphorus Isotopes

Topics: Animals; Arrhythmias, Cardiac; Cats; Coronary Vessels; Disease Models, Animal; Heart Ventricles; Ligation; Myocardial Infarction; Phosphocreatine; Sympathetic Nervous System; Ventricular Fibrillation