Pharmaceutical metabolic down-regulation by protein synthesis inhibition in a conscious rat model

• Published in: Resuscitation 2007-06, Vol.73 (3), p.446-458
• Main Authors: Reynolds, Penny S, Barbee, R. Wayne, Ward, Kevin R
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Anisomycin - pharmacology; Biological and medical sciences; Blood and lymphatic vessels; Blood Gas Analysis; Blood. Blood coagulation. Reticuloendothelial system; Body temperature; Body Temperature - drug effects; Cardiology. Vascular system; Consciousness - drug effects; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Emergency; Heart Rate - drug effects; Intensive care medicine; Lactate; Male; Medical sciences; Motor Activity - drug effects; Oxygen consumption; Oxygen Consumption - drug effects; Pharmacology. Drug treatments; Protein synthesis inhibition; Protein Synthesis Inhibitors - pharmacology; Puromycin - pharmacology; Rat; Rats; Rats, Sprague-Dawley; Respiration - drug effects; Systemic oxygenation
• ISSN: 0300-9572; 1873-1570
• DOI: 10.1016/j.resuscitation.2006.10.025

Summary Pharmaceutically induced metabolic down-regulation may be a useful therapeutic adjunct when tissue oxygen supply is restricted. We hypothesized that protein synthesis inhibition in a non-hibernating species should lower oxygen demand, resulting in aerobic metabolic rate depression at the whole animal level. We compared metabolic responses and measures of systemic oxygenation of conscious catheterized rats given either protein synthesis inhibition (PSI) agents or carrier controls (normal saline and DMSO). Core temperature was measured by implanted transmitters, and VO2 was determined in an open flow-through metabolic chamber at 25 °C. Mean arterial pressure MAP and heart rate HR were determined from arterial pressure transducer tracings; arterial blood gases and lactate were sampled every 15 min. PSI rats exhibited an immediate transient decline in VO2 , followed by a secondary decline to new resting levels; VO2 for the first hour was significantly lower than that for rats receiving DMSO vehicle. Unlike controls, PSI rats showed an overall 3.5 °C decline in core temperature, coupled with increased arterial lactate. There were no differences in MAP and HR of PSI rats compared to controls. Although hypothermic response to toxic agents typical of rodents cannot be ruled out completely, the mild hypothermia and reduced VO2 exhibited by PSI rats may be partially attributed to the action of protein synthesis agents.