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.

In vivo Detection of Gastric Cancer in Rats by Electron Paramagnetic Resonance Imaging

“…It has been reported that the levels of endogeneous reducing agents such as thiols and ascorbic acid, which can rapidly reduce the nitroxide, are increased in gastric cancer (40,41). It has also been reported that the blood flow of tumors such as carcinosarcoma can be lower than that in the normal stomach (42). When the infusion rate is low in the endogenous reducing agent-rich tissue, the amount of delivered nitroxide and its contact time with the endogenous reducing agent would be increased, resulting in an increase in the amount of the reduced nitroxide.…”

Muscle Distribution of the Neuromuscular Blocker gallamine Using Microdialysis

“…A blood‐flow limited hybrid PB‐PK model was used to simulate gallamine concentrations in MIF using the following equation: where V MIF is muscle interstitial fluid volume, C A is gallamine arterial plasma concentrations, Q M is muscle blood flow, K p is MIF–plasma partition coefficient, and C MIF is gallamine MIF concentrations. In this simulation, estimates of V MIF and Q M of urethane‐anesthetized rats were obtained from the literature 20,21 . V MIF is approximately 11% of muscle tissue and the percentage of muscle tissue is approximately 50% of the total body weight 20 .…”

Pharmacokinetic-Pharmacodynamic Analysis of the Glucose-Lowering Effect of Metformin in Diabetic Rats Reveals First-Pass Pharmacodynamic Effect

“…Therefore, metformin flux through the portal vein (Q gl ) was calculated as the sum of systemically derived amounts, drug amounts infused in the portal vein (in the case of intraportal infusion), and transfer of metformin from GI wall to liver compartment that was derived from the absorption from GI lumen (for intraduodenal bolus and infusion). Systemically derived drug amounts in the portal vein were calculated as metformin plasma concentrations multiplied by portal blood flow (5.92 Ϯ 0.97 ml/min/100 g body weight; Sakaeda et al, 1998).…”