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Noninvasive cardiac output monitoring with bioreactance as an alternative to invasive instrumentation for preclinical drug evaluation in beagles.

TitleNoninvasive cardiac output monitoring with bioreactance as an alternative to invasive instrumentation for preclinical drug evaluation in beagles.
Publication TypeJournal Article
Year of Publication2011
AuthorsHeerdt PM, Wagner CL, DeMais M, Savarese JJ
JournalJ Pharmacol Toxicol Methods
Date Published2011 Sep-Oct
KeywordsAnimals, Aorta, Cardiac Output, Dogs, Drug Evaluation, Preclinical, Male, Monitoring, Physiologic, Neuromuscular Blocking Agents, Time Factors

INTRODUCTION: Non-invasive measurement of cardiac output (CO) using bioreactance signals (NICOM) was recently validated in swine and human adults. The present study was designed to test the hypothesis that NICOM flow measurements can accurately measure CO and detect acute drug-induced changes in aortic blood flow (AoQ)≥10% in beagles.

METHODS: Data from 5 anesthetized, open chest beagles used for preclinical screening of novel neuromuscular blocking drugs were analyzed for the study. AoQ was measured beat-to-beat with a probe on the aortic root and averaged over 30s intervals. NICOM CO measurements were simultaneously obtained every 30s. NICOM precision (random variation) and accuracy relative to AoQ were assessed from individual segments of steady-state data. The ability of NICOM to detect acute alterations in AoQ≥10% was determined from other segments with dynamic change.

RESULTS: 516 simultaneous CO measurements between 826 and 2436 mL/min were analyzed. Steady-state measurements (20% of the dataset) revealed an average AoQ-NICOM difference (bias) of 63±38 mL/min, a percent error of 6.1%, and a NICOM precision of 6.1%. Within the acute change dataset, 21/23 events reflecting a ≥10% change in beat-to-beat AoQ were detected by the NICOM (sensitivity of 0.91). In none of 10 instances where drug or fluid injection altered AoQ<10% did the NICOM indicate a change (specificity of 1.0).

DISCUSSION: Continuous, non-invasive measurement of CO by bioreactance provides data that satisfactorily approximates invasive measurement of aortic blood flow in beagles. In addition, despite a 30s interval between measurements, the NICOM appears to have sufficient fidelity to detect and quantify acute, drug-induced changes in CO. These data suggest that the NICOM may represent an alternative to open chest instrumentation for CO measurement in preclinical drug evaluation studies.

Alternate JournalJ Pharmacol Toxicol Methods
PubMed ID21440649