Aminophylline therapy during endotoxemia in anesthetized spontaneously breathing rats.
Phosphodiesterase inhibitors, such as pentoxifylline and aminophylline, may reduce inflammatory cytokine-induced endothelial permeability. We tested the hypothesis that aminophylline treatment may ameliorate the pulmonary and extrapulmonary effects of endotoxemia in a rat model. In anesthetized rats, a tracheotomy was performed along with catheterization of a femoral vein and artery. Anesthesia, fluid balance, and normothermia were maintained throughout the 6-h experiment. A stable hemodynamic and gas-exchange baseline was established at which time the rats were randomly divided into three groups. Group I received aminophylline (1mg/kg) over 30 min followed by 0.5mg/kg/h. Group II received a single dose of endotoxin (4 mg/kg) while Group III received both aminophylline and endotoxin as described for Groups I and II, respectively. Gas-exchange profiles, mean arterial blood pressure, and heart rate were determined every 2h. At hour 6, the rats were euthanized and lung, kidney, and heart tissue were removed for determination of water content. As our control group, we utilized data from our previously published study involving an identical surgical procedure with normal saline. Endotoxemia produced characteristic respiratory and hemodynamic signs of sepsis including hypotension, hyperventilation, tachycardia, and renal and pulmonary edema. Aminophylline treatment failed to prevent these endotoxemia-induced respiratory and hemodynamic manifestations of sepsis, but significantly improved the acid-base imbalance that developed during surgical procedures in saline-treated control rats. Further studies are warranted to determine potentially beneficial doses of aminophylline and resulting theophylline serum concentrations under such septic conditions.
Division of Critical Care Medicine, Miami Children's Hospital, Miami, FL, USA.
Harun
H
Fakioglu
Javier
J
Gelvez
Dan
D
Torbati
Mark L
ML
Glover
Jose L
JL
Olarte
Maria T
MT
Camacho
Jack
J
Wolfsdorf
D000136:Acid-Base Equilibrium / Q000187:drug effects / Q000502:physiology; D000628:Aminophylline / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D002245:Carbon Dioxide / Q000097:blood / Q000737:chemistry; D004195:Disease Models, Animal; D004338:Drug Combinations; D004487:Edema / Q000150:complications / Q000503:physiopathology; D019446:Endotoxemia / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D006985:Hyperventilation / Q000209:etiology / Q000401:mortality / Q000503:physiopathology; D016857:Hypocapnia / Q000139:chemically induced / Q000401:mortality / Q000503:physiopathology; D007022:Hypotension / Q000139:chemically induced / Q000503:physiopathology; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D010100:Oxygen / Q000097:blood / Q000737:chemistry; D010313:Partial Pressure; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage / Q000009:adverse effects; D011654:Pulmonary Edema / Q000150:complications / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects*; D013610:Tachycardia / Q000139:chemically induced / Q000503:physiopathology
D004338:Drug Combinations; D011135:Polysaccharides, Bacterial; D002245:Carbon Dioxide; D000628:Aminophylline; D010100:Oxygen