Comparisons between electromagnetic and X-beam transit-time flow measurements for evaluating drug actions on cardiac output in the conscious dog.
BACKGROUND
Cardiac output remains an important preclinical measurement for evaluating the cardiovascular effects of drugs. We evaluated the performance of the Triton Active Redirection Transit-Time, ART(2), which represents a new class of X-beam flow systems and compared it in vivo and in vitro to an electromagnetic flow (EMF) system for measuring large vessel flow.


METHODS
In vivo, simultaneous aortic flow measurements were obtained during alpha- and beta-adrenergic receptor stimulation in 5 conscious dogs instrumented with both ART(2) and EMF probes on their ascending aortas. In vitro, simultaneous measurements of volume flow using the ART(2), EMF, and timed-volume collection were made using a novel benchtop flow apparatus that ensured probe alignment and precise timed-volume flow measurements. Accuracy and sensitivity of both systems were assessed by recording flow measurements while varying rates, temperature and hematocrit.


RESULTS
In vivo aortic flow measurements between ART(2) and EMF were closely correlated (linear regression r(2) values ranged from 0.84 to 0.99), with the ART(2) system recording lower flow values than the EMF. In vitro ART(2) flow rates were in excellent agreement with timed-volume flow, while EMF flow rates were lower (p<0.05) and exhibited more variation and dependency upon temperature or hematocrit than the ART(2). Saline flows measured by ART(2) and EMF averaged 97+/-2% and 91+/-5% accuracy, respectively, over the temperature range 32 degrees C to 42 degrees C. For blood hematocrit values between 35% and 45%, ART(2) accuracy averaged 98+/-2%, compared to 89+/-5% accuracy with the EMF.


CONCLUSIONS
The ART(2) flow measurements in conscious dogs correlated closely to concurrent measurements obtained with the EMF over a wide range of flow rates, even though the absolute aortic flow values differed. Since it accurately measured flow in vitro, the ART(2) system is an appropriate alternative for evaluating cardiovascular effects of disease progression or drug administration in experimental animals.
Department of Cardiovascular, Metabolic and Endocrine Diseases, Pfizer Global Research and Development, MS 4057, Eastern Point Road, Groton, CT 06340, USA.
David M
DM
Flynn
Eric A
EA
Wolfgang
David L
DL
Raunig
Delvin R
DR
Knight
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000502:physiology*; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology*; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D055590:Electromagnetic Phenomena; D006400:Hematocrit; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D013696:Temperature; D013997:Time Factors
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D010656:Phenylephrine; D007545:Isoproterenol