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Comparative analysis of Data Sciences International PhysioTel™ D70 and PhysioTel™ Digital Telemetry Platforms
Abstracts
0092 Evaluation of cardiac contractility by invasive and noninvasive methodologies: Comparison of LV-dP/dtmax with echocardiography parameters in anesthetized healthy beagle dogs Kathy Derakhchan, Weston Sutherland, Ray W. Chui, Hugo M. Vargas Amgen Inc., Safety and Exploratory Pharmacology, Toxicology Sciences, Thousand Oaks, CA, USA It has been shown that left ventricular pressure (LVP)- and echocardiographic-based measures of cardiac contractility (CC) demonstrate a linear positive correlation in conscious dogs treated with positive and negative inotropes (Cools et al., 2014). We examined the relationship between these invasive and non-invasive endpoints of CC when assessed simultaneously in dogs under chloralose anesthesia. Fifteen male beagle dogs were anesthetized with morphine/alphachloralose, ventilated, and instrumented with a LVP catheter for the measurement of LV-dP/dtmax (maximal rate of rise of LVP). Twodimensional M-mode echocardiography traces were used for ejection fraction (EF) and fractional shortening (FS) calculation. Inotropes were administered in a rising dose-paradigm intravenously; vehicle (25% HPβCD:10% PEG400) treatment was used as control. CC (LV-dP/dtmax, EF, and FS) was simultaneously measured at the end of each 30-min infusion period (Cmax). Both invasive and non-invasive techniques were able to accurately measure CC changes for all inotropes tested. LVdP/dtmax and EF and FS were linearly correlated (R2 = 0.61; 190 data pairs). In the range of 1800–5800 mm Hg/s, a change in LV-dP/dtmax of 1000 mm Hg/s corresponded to a change of ~6% in EF, and ~7% in FS in the anesthetized dog model. These data correlations were different with LV-dP/dtmax values lower than 1800 and higher than 5800 mm Hg/s. Conclusion: LVP and echocardiographic measures of CC were correlated in the anesthetized dog model, with a similar linear relationship as seen in conscious dogs (Cools et al., 2014). These current results also imply that chloralose-based anesthesia has little impact on CC in the dog.
doi:10.1016/j.vascn.2015.08.091
0093 Blood pressure, heart rate, temperature, and central nervous system evaluation of cyanide intoxication in juvenile and adult mice M. Hawk, T. Vinci, K. Henderson, B. Roche, G. Ritchie, S. Behringer, K. Knostman
185
Twenty percent of KCN exposed mice experienced ECG events within 5 min post-dose including bradycardia, left ventricular premature contractions (VPCs), and a large Ta wave. At 30-min post-dosing, ECGs included PR prolongation, alternans, and Ta prolongation. The bradycardia and VPCs as well as the PR and Ta prolongation appear to be KCN effects in a small percentage of mice, most likely due to effects on the SA node. No KCN related histological findings through Study Day 42 were noted. This model of KCN-induced changes in CV and CNS parameters can be used to screen novel therapeutics for CN intoxication. doi:10.1016/j.vascn.2015.08.092
0094 Comparative analysis of Data Sciences International PhysioTel™ D70 and PhysioTel™ Digital Telemetry Platforms Kenneth Kearney, Rhea Pittman, Phil Atterson WIL Research, Ashland, OH, USA Telemetric evaluations are largely conducted as part of the safety pharmacology core battery to satisfy ICH S7A and ICH S7B requirements for assessment of changes in hemodynamic and electrocardiographic measurements, respectively. Such evaluations have allowed for the collection of conscious ambulatory data from unanesthetized animal models. However; historically, acquisition limitations have precluded social housing of animals during the telemetric evaluation period due to signal interference. Technological advances in telemetry implanted devices and supporting hardware now offer benefits of greater signal quality, and greater durations of implantation (due to upgraded battery usage and device construction), with the added capacity to offer group housing during the collection period. The current study was conducted to investigate the enhancements offered by the PhysioTel Digital (digital) platform. Telemetric data were compared between moxifloxacin-treated animals using each telemetry platform. During collection of the PhysioTelD70 (legacy) transmitter data, single housed animals were treated in a latin square crossover design, while group-housed animals were evaluated in an escalating dose design following moxifloxacin treatment with the use of the digital system. The digital telemetry system offers appeal by way of study setup efficiencies and while satisfying expectations for group housing of social animals. doi:10.1016/j.vascn.2015.08.093
Battelle, Columbus, OH, USA 0095 Cyanide (CN) affects high energy demand organ systems such as the central nervous (CNS), cardiovascular (CV), and pulmonary systems. A mouse model of oral KCN intoxication was developed to screen and evaluate novel therapeutics. Adult and juvenile CD-1 mice were dosed orally with 8 mg/kg KCN, a toxic but generally non-lethal dose. Sensory, motor, cognitive, and behavioral changes were evaluated up to 42 days post-dose. Telemetry was used for CV and body temperature measures. KCN reduced sensorimotor responsiveness or spontaneous locomotor activity in juvenile and adult mice at 30 min post-dose. Core body temperature decreases at 30 min postchallenge consistent with the general malaise observed. Significant CNS changes were noted 30 min post-dose and decreases in spontaneous locomotor activity and/or rectal temperature on Days 7, 14, 28, and 42. KCN caused immediate effects related to bradycardia, hypotension, and hypothermia with recovery 1 to 3 h post-dosing.
Effects of blood pressure on electro-mechanical window in anesthetized rabbits Vudhiporn Limprasutra, Nakkawee Saengkluba, Anusak Kijtawornrata,b, Suwanakiet Sawangkoona,b, Robert L. Hamlinc,d a
Department of Physiology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand b Research Study and Testing of Drug's Effect Related to Cardiovascular System in Laboratory Animal, Bangkok, Thailand c QTest Labs, LLC, Columbus, OH, USA d The Ohio State University, Columbus, OH, USA The electro-mechanical window (EMW) is a biomarker for predicting the risk of drug-induced ventricular arrhythmias; however,
0092 Evaluation of cardiac contractility by invasive and noninvasive methodologies: Comparison of LV-dP/dtmax with echocardiography parameters in anesthetized healthy beagle dogs Kathy Derakhchan, Weston Sutherland, Ray W. Chui, Hugo M. Vargas Amgen Inc., Safety and Exploratory Pharmacology, Toxicology Sciences, Thousand Oaks, CA, USA It has been shown that left ventricular pressure (LVP)- and echocardiographic-based measures of cardiac contractility (CC) demonstrate a linear positive correlation in conscious dogs treated with positive and negative inotropes (Cools et al., 2014). We examined the relationship between these invasive and non-invasive endpoints of CC when assessed simultaneously in dogs under chloralose anesthesia. Fifteen male beagle dogs were anesthetized with morphine/alphachloralose, ventilated, and instrumented with a LVP catheter for the measurement of LV-dP/dtmax (maximal rate of rise of LVP). Twodimensional M-mode echocardiography traces were used for ejection fraction (EF) and fractional shortening (FS) calculation. Inotropes were administered in a rising dose-paradigm intravenously; vehicle (25% HPβCD:10% PEG400) treatment was used as control. CC (LV-dP/dtmax, EF, and FS) was simultaneously measured at the end of each 30-min infusion period (Cmax). Both invasive and non-invasive techniques were able to accurately measure CC changes for all inotropes tested. LVdP/dtmax and EF and FS were linearly correlated (R2 = 0.61; 190 data pairs). In the range of 1800–5800 mm Hg/s, a change in LV-dP/dtmax of 1000 mm Hg/s corresponded to a change of ~6% in EF, and ~7% in FS in the anesthetized dog model. These data correlations were different with LV-dP/dtmax values lower than 1800 and higher than 5800 mm Hg/s. Conclusion: LVP and echocardiographic measures of CC were correlated in the anesthetized dog model, with a similar linear relationship as seen in conscious dogs (Cools et al., 2014). These current results also imply that chloralose-based anesthesia has little impact on CC in the dog.
doi:10.1016/j.vascn.2015.08.091
0093 Blood pressure, heart rate, temperature, and central nervous system evaluation of cyanide intoxication in juvenile and adult mice M. Hawk, T. Vinci, K. Henderson, B. Roche, G. Ritchie, S. Behringer, K. Knostman
185
Twenty percent of KCN exposed mice experienced ECG events within 5 min post-dose including bradycardia, left ventricular premature contractions (VPCs), and a large Ta wave. At 30-min post-dosing, ECGs included PR prolongation, alternans, and Ta prolongation. The bradycardia and VPCs as well as the PR and Ta prolongation appear to be KCN effects in a small percentage of mice, most likely due to effects on the SA node. No KCN related histological findings through Study Day 42 were noted. This model of KCN-induced changes in CV and CNS parameters can be used to screen novel therapeutics for CN intoxication. doi:10.1016/j.vascn.2015.08.092
0094 Comparative analysis of Data Sciences International PhysioTel™ D70 and PhysioTel™ Digital Telemetry Platforms Kenneth Kearney, Rhea Pittman, Phil Atterson WIL Research, Ashland, OH, USA Telemetric evaluations are largely conducted as part of the safety pharmacology core battery to satisfy ICH S7A and ICH S7B requirements for assessment of changes in hemodynamic and electrocardiographic measurements, respectively. Such evaluations have allowed for the collection of conscious ambulatory data from unanesthetized animal models. However; historically, acquisition limitations have precluded social housing of animals during the telemetric evaluation period due to signal interference. Technological advances in telemetry implanted devices and supporting hardware now offer benefits of greater signal quality, and greater durations of implantation (due to upgraded battery usage and device construction), with the added capacity to offer group housing during the collection period. The current study was conducted to investigate the enhancements offered by the PhysioTel Digital (digital) platform. Telemetric data were compared between moxifloxacin-treated animals using each telemetry platform. During collection of the PhysioTelD70 (legacy) transmitter data, single housed animals were treated in a latin square crossover design, while group-housed animals were evaluated in an escalating dose design following moxifloxacin treatment with the use of the digital system. The digital telemetry system offers appeal by way of study setup efficiencies and while satisfying expectations for group housing of social animals. doi:10.1016/j.vascn.2015.08.093
Battelle, Columbus, OH, USA 0095 Cyanide (CN) affects high energy demand organ systems such as the central nervous (CNS), cardiovascular (CV), and pulmonary systems. A mouse model of oral KCN intoxication was developed to screen and evaluate novel therapeutics. Adult and juvenile CD-1 mice were dosed orally with 8 mg/kg KCN, a toxic but generally non-lethal dose. Sensory, motor, cognitive, and behavioral changes were evaluated up to 42 days post-dose. Telemetry was used for CV and body temperature measures. KCN reduced sensorimotor responsiveness or spontaneous locomotor activity in juvenile and adult mice at 30 min post-dose. Core body temperature decreases at 30 min postchallenge consistent with the general malaise observed. Significant CNS changes were noted 30 min post-dose and decreases in spontaneous locomotor activity and/or rectal temperature on Days 7, 14, 28, and 42. KCN caused immediate effects related to bradycardia, hypotension, and hypothermia with recovery 1 to 3 h post-dosing.
Effects of blood pressure on electro-mechanical window in anesthetized rabbits Vudhiporn Limprasutra, Nakkawee Saengkluba, Anusak Kijtawornrata,b, Suwanakiet Sawangkoona,b, Robert L. Hamlinc,d a
Department of Physiology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand b Research Study and Testing of Drug's Effect Related to Cardiovascular System in Laboratory Animal, Bangkok, Thailand c QTest Labs, LLC, Columbus, OH, USA d The Ohio State University, Columbus, OH, USA The electro-mechanical window (EMW) is a biomarker for predicting the risk of drug-induced ventricular arrhythmias; however,