title: Blood flow rate in normal and tumor-bearing rats in conscious state, under urethane anesthesia, and during systemic hypothermia.
abstract: The blood flow rates of 14 tissues in the body were determined by microsphere method using normal and tumor-bearing rats kept conscious or under urethane anesthesia. The effects on the blood flow rate in the tissues were assessed for multimodal therapy, systemic hypothermia for ischemic brain injury, and local hyperthermia and angiotensin II-induced hypertensive chemotherapy for cancer. Urethane anesthesia showed no effect on cardiac output, while there was a tendency of decrease of blood flow rate and % of cardiac output in each tissue other than muscle tissue, in which they increased as a counterbalance, in normal and tumor-bearing rats. Systemic hypothermia gave results similar to those of urethane anesthesia in normal rats, but for tumor-bearing rats, it decreased cardiac output, and consequently the blood flow rate in most tissues. Brain blood flow rate was about half of that in the conscious rats. Local hyperthermia also decreased the cardiac output and blood flow rate in each tissue, including the tumor tissue. Angiotensin II-induced hypertension showed no effect on cardiac output, had various effects on blood flow rate in each tissue, and led to no increase in the tumor blood flow rate. Simulations based on the physiological pharmacokinetic modeling suggested that intramuscular injection of a lung-specific derivative of ceftazidime would provide the ideal biodistribution to ensure its optimal therapeutic efficacy during systemic hypothermia. This methodology, namely the pharmacokinetic simulation based on the physiological values of the body, will provide a useful piece of information on drug delivery systems under various conditions.
authors.affiliation: Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sakaeda
authors.forename: K
authors.initials: K
authors.lastname: Fukumura
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: S
authors.initials: S
authors.lastname: Matsumura
authors.forename: E
authors.initials: E
authors.lastname: Matsuura
authors.forename: K
authors.initials: K
authors.lastname: Hirano
mesh_terms: D000771:Anesthesia, Intravenous; D018686:Anesthetics, Intravenous; D000804:Angiotensin II / Q000633:toxicity; D000818:Animals; D002302:Cardiac Output; D002442:Ceftazidime / Q000493:pharmacokinetics; D002511:Cephalosporins / Q000493:pharmacokinetics; D003243:Consciousness; D005334:Fever / Q000503:physiopathology; D006439:Hemodynamics; D006859:Hydrogen / Q000097:blood; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology; D007036:Hypothermia, Induced; D017078:Laser-Doppler Flowmetry; D008297:Male; D008863:Microspheres; D008954:Models, Biological; D009374:Neoplasms, Experimental / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow; D014520:Urethane
chemical_list: D018686:Anesthetics, Intravenous; D002511:Cephalosporins; D000804:Angiotensin II; D014520:Urethane; D006859:Hydrogen; D002442:Ceftazidime