Adverse physiologic effects of the thermosensitizing agents amiloride and DIDS in normal dogs: Correlation to amiloride infusion rate
✍ Scribed by Kevin T. Concannon; G. Sylvester Price; Deborah M. Prescott
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 571 KB
- Volume
- 4
- Category
- Article
- ISSN
- 1065-7541
No coin nor oath required. For personal study only.
✦ Synopsis
Amiloride and DIDS (4,4-diisothiocyanato-stilbene-2,2 '-disulfonic acid) have been used to lower intracellular pH and increase thermosensitivity of malignant cells. We previously observed adverse reactions after injection of these drugs in canines and hypothesized that reactions may be mediated by amiloride-induced histamine release. This study was designed to define an amiloride infusion rate unlikely to cause adverse effects in dogs. Plasma concentrations of amiloride were quantified to assess whether infusions in this study produced amiloride concentrations within the range known to produce thermosensitization in vitro. Anesthetized dogs received intravenous amiloride infusions during multiple sessions on different days. The infusion was divided into 1) a loading infusion of either 100,200,300,400,500, or 600 p,g/kg/min given for 25 min and 2) a maintenance infusion of 7.4 pg/kg/min started immediately after the loading infusion and lasting for 2 hr. Infusion resulted in histamine release, and hypotension (240% decrease from baseline) occurred in dogs given amiloride at rates 2500 pg/kg/min. Hypotension appeared to be associated with more rapid amiloride infusion but not with peak plasma concentration. Plasma amiloride concentrations were less than in vitro concentrations shown to produce thermosensitivity.