High Definition Oscillometry: a novel technique for non‐invasive blood pressure monitoring in the cynomolgus monkey (Macaca fascicularis)

Abstract

Our results demonstrate, using telemetry as reference, the accuracy of HDO-based non-invasive blood pressure measurements in macaques to detect drug-related cardiovascular changes.

Measurement of hyper- and hypotension during repeated dose toxicity studies in either freely moving or physically restrained cynomolgus monkeys

“…This has stimulated efforts to develop technology and animal study designs which allow a better assessment of drug-induced cardiovascular effects in toxicology studies. Currently, the majority of studies utilize techniques which require physical restraint and although the methods for non-invasive blood pressure detection have improved (Schmelting, Niehoff, Egner, Korte, & Weinbauer, 2009) there is still a concern of insufficient sensitivity (Sarazan et al, 2011).…”

“…Further for oncology drugs, ICH S9 states: "An assessment of the pharmaceutical's effect on vital organ functions (including cardiovascular, respiratory and central nervous systems) should be available before the initiation of clinical studies; such parameters could be included in general toxicology studies" (ICH, 2009). Currently, non-invasive blood pressure measurements using HDO technology are performed during routine toxicology studies (Mitchell, McMahon, Beck, & Sarazan, 2010;Schmelting et al, 2009). While offering the advantage of being non-invasive, unfortunately, this technique requires physical restraint and affords snapshot measurements only generally on single occasions over the course of the study.…”

Non-invasive blood pressure measurement in ferrets ( Mustela putorius furo ) using high definition oscillometry

“…These findings suggest that BP measurements using the HDO device are highly reproducible, as was also demonstrated during study 3, in which the repeatability coefficient and ICCs for SAP, MAP and DAP showed excellent agreement between measurements. In addition, within-ferret CVs were relatively low, similar to those in dogs and macaques (Schmelting et al, 2009;Chetboul et al, 2010), thereby underlining the high reproducibility and thus precision of the measurements.…”

“…HDO has been evaluated previously in dogs, cats, horses, cheetahs and monkeys (Schmelting et al, 2009;Meyer et al, 2010;Petri9 c et al, 2010;Wernick et al, 2010;Martel et al, 2013;Rysnik et al, 2013;Seliškar et al, 2013;Mietsch and Einspanier, 2015;Sant Cassia et al, 2015;Tünsmeyer et al, 2015), but not ferrets.…”

Functional Assessments in Nonhuman Primate Toxicology Studies to Support Drug Development

“…In general, cuff-based ABP methods are inferior and are not recommended for safety assessment evaluations of new drugs, especially in primates [25,27,38]. A new cuff technology called high-definition oscillometry (HDO) may offer improved accuracy and sensitivity for the noninvasive detection of arterial pressure in cynomolgus monkeys, but it still requires the manual restraint of the monkey, which is a significant issue [39,40].…”