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A novel telemetry device for comprehensive assessment of cardiovascular function in conscious dogs
e48
Abstracts
Poster No: 161 A sub-peritoneal approach to telemetry implantation in minipigs: Impact on body temperature and the QTc/CBT relationship Jill A. Dalton, David S. Moddrelle, Kyle P. O'Donohue, Brandon M. Galbraith, Scott W. Ward, Matthew M. Abernathy, Anson L. Phillips, Theodore J. Baird Safety Pharmacology & Neurobehavioral Sciences, MPI Research, Mattawan, MI, USA The minipig has become an increasingly-discussed model in cardiovascular (CV) safety evaluation utilizing implanted telemetric methods. However, there are potential post-surgical complications with implantation of a foreign object which may be exacerbated in the minipig. The aims of this study were 1) to explore overall data quality and longevity resulting from a recently-developed subperitoneal surgical placement procedure, 2) to evaluate the correlation between core body temperature (CBT) data derived via telemetry versus direct measurement, and 3) to evaluate the relationship between CBT and QTc, which has been previously described in canines (van der Linde et al., 2008), but has yet to be fully explored in the minipig. Eight Gottingen minipigs were instrumented for telemetry and CBT, HR, BP, and the ECG were monitored monthly for 24 h each occasion, for 12 months. Animals were dosed once with 11 mg/kg Telazol. CBT values collected via telemetry (BTt) and rectally (BTr) were highly correlated both over the course of the year and following Telazol administration. Over 12 months of periodic recording, no consistent changes in BTt, minimal changes in CV parameters, and only negligible decreases in signal quality were observed. BTt and QTc values collected during Telazol administration were negatively correlated, as has been described in other species. These results demonstrate the advantage of using sub-peritoneal transmitter placement in minipigs towards providing accurate, reliable, and long-term CBT and CV data. doi:10.1016/j.vascn.2011.03.166
Poster No: 162 Telemetric assessment of minimally invasive arterial blood pressure in the minipig: Validation with isoprenaline Stéphane Baudet a, Stéphane Milano a, Olivier Boucheix a, Estelle Chalencon a, Philippe Legé a, Christophe Bory a, Céline Dupuis a, Eric Rieux b, Scott Tiesma b a b
Ricerca Biosciences SAS, Lyon, France Data Sciences International, St. Paul, MN, USA
Non-invasive arterial blood pressure (ABP) measurements by telemetry in toxicology studies are not as well established as ECG capture. Automated tail cuff measurements of ABP are not possible in the Göttigen minipig due to its tail conformation and the stress potentially generated by cuff inflation. We have assessed whether ABP is measurable in freely-moving minipigs by telemetry using a minimally invasive surgery, with attention to surgical access, size of the implant and signal quality. Isoprenaline was used to induce shortterm haemodynamic changes. DSI telemetry implants PA-C10-TOX-LA (“C10-Tox”) and PA-C40 (“C40”) and one male and one female minipig were used. A C40 and a C10-Tox implant were placed respectively in the left sub-clavian (SCL) and femoral (FEM) artery in the male. Two C40 implants were placed each in the left SCL and a collateral of the FEM artery in the female. The SCL ABP signal exhibited more fluctuations and noise than the FEM ABP
signal. Spikes were seen on the C40 signal but not in the C10-Tox in FEM position. Isoprenaline (30 μg/kg, s.c.) induced a prompt and maximal fall in ABP versus control of about 20 mm Hg and a concomitant tachycardia of about 90 bpm. The amplitude and time-course of the haemodynamic effects were similar with either implant. Thus ABP is measurable in the minipig with minimal surgery. PAC10-TOX-LA implantation into the femoral artery yielded the highest quality signals. The financial impact of this approach must be balanced with the ability to detect haemodynamic changes in unstressed animals in the long-term. doi:10.1016/j.vascn.2011.03.167
Poster No: 163 A novel telemetry device for comprehensive assessment of cardiovascular function in conscious dogs Michael Hoffmann a, Thomas Vormberge a, Thomas Mondritzki b, Hubert Truebel b a b
Bayer Healthcare AG, Safety Pharmacology, Wuppertal, Germany Bayer Healthcare AG, Cardiovascular Research, Wuppertal, Germany
Introduction: Comprehensive assessment of cardiovascular function in conscious animals is often limited by the lack of continuous cardiac output measurements. A new battery-free telemetric device (CardioMEMS, CM) which allows pulmonary pressure readings and calculation of cardiac output is currently in Phase III clinical testing. In preclinical studies these sensors offer the opportunity for simultaneous registration of pulmonary and systemic resistance, heart contractility and ECG when combined with an established telemetry system. Methods: A female beagle dog was equipped with a D70-PCTP transmitter (DSI) and a wireless HF pressure sensor (CM). The 2 catheters of the DSI device were placed into the abdominal aorta and the left ventricle of the heart; ECG electrodes were placed subcutaneously in lead II position. The CM pressure sensor was introduced into a pulmonary artery branch under X-ray control guided with a Swan-Ganz catheter. While the dog was standing in a sling, data of the DSI device was collected continuously. In parallel signals of the CM sensor were captured using specific software, which calculates stroke volume from pulmonary pressure waveform. Results of a basic validation study with short-term intravenous infusion of reference compounds (e.g. SNP and phenylephrine) are presented. Conclusion: To our knowledge this is the first method enabling complete assessment of cardio-hemodynamics and ECG in conscious dogs by combining established telemetry systems and a novel wireless sensor allowing measurement of pressure and flow in the systemic and pulmonary circulation. doi:10.1016/j.vascn.2011.03.168
Poster No: 164 Evaluation of a non-invasive telemetry method for determining blood pressure in dogs R. Brandon Borders, Brian Roche, Tom Vinci, Shawnda Armentrout, Jeremy Smith, Steve Behringer, Ernesto Gonzalez, Brandon Wood, Craig Hassler Battelle Memorial Institute, Columbus, OH 43201, USA
Abstracts
Poster No: 161 A sub-peritoneal approach to telemetry implantation in minipigs: Impact on body temperature and the QTc/CBT relationship Jill A. Dalton, David S. Moddrelle, Kyle P. O'Donohue, Brandon M. Galbraith, Scott W. Ward, Matthew M. Abernathy, Anson L. Phillips, Theodore J. Baird Safety Pharmacology & Neurobehavioral Sciences, MPI Research, Mattawan, MI, USA The minipig has become an increasingly-discussed model in cardiovascular (CV) safety evaluation utilizing implanted telemetric methods. However, there are potential post-surgical complications with implantation of a foreign object which may be exacerbated in the minipig. The aims of this study were 1) to explore overall data quality and longevity resulting from a recently-developed subperitoneal surgical placement procedure, 2) to evaluate the correlation between core body temperature (CBT) data derived via telemetry versus direct measurement, and 3) to evaluate the relationship between CBT and QTc, which has been previously described in canines (van der Linde et al., 2008), but has yet to be fully explored in the minipig. Eight Gottingen minipigs were instrumented for telemetry and CBT, HR, BP, and the ECG were monitored monthly for 24 h each occasion, for 12 months. Animals were dosed once with 11 mg/kg Telazol. CBT values collected via telemetry (BTt) and rectally (BTr) were highly correlated both over the course of the year and following Telazol administration. Over 12 months of periodic recording, no consistent changes in BTt, minimal changes in CV parameters, and only negligible decreases in signal quality were observed. BTt and QTc values collected during Telazol administration were negatively correlated, as has been described in other species. These results demonstrate the advantage of using sub-peritoneal transmitter placement in minipigs towards providing accurate, reliable, and long-term CBT and CV data. doi:10.1016/j.vascn.2011.03.166
Poster No: 162 Telemetric assessment of minimally invasive arterial blood pressure in the minipig: Validation with isoprenaline Stéphane Baudet a, Stéphane Milano a, Olivier Boucheix a, Estelle Chalencon a, Philippe Legé a, Christophe Bory a, Céline Dupuis a, Eric Rieux b, Scott Tiesma b a b
Ricerca Biosciences SAS, Lyon, France Data Sciences International, St. Paul, MN, USA
Non-invasive arterial blood pressure (ABP) measurements by telemetry in toxicology studies are not as well established as ECG capture. Automated tail cuff measurements of ABP are not possible in the Göttigen minipig due to its tail conformation and the stress potentially generated by cuff inflation. We have assessed whether ABP is measurable in freely-moving minipigs by telemetry using a minimally invasive surgery, with attention to surgical access, size of the implant and signal quality. Isoprenaline was used to induce shortterm haemodynamic changes. DSI telemetry implants PA-C10-TOX-LA (“C10-Tox”) and PA-C40 (“C40”) and one male and one female minipig were used. A C40 and a C10-Tox implant were placed respectively in the left sub-clavian (SCL) and femoral (FEM) artery in the male. Two C40 implants were placed each in the left SCL and a collateral of the FEM artery in the female. The SCL ABP signal exhibited more fluctuations and noise than the FEM ABP
signal. Spikes were seen on the C40 signal but not in the C10-Tox in FEM position. Isoprenaline (30 μg/kg, s.c.) induced a prompt and maximal fall in ABP versus control of about 20 mm Hg and a concomitant tachycardia of about 90 bpm. The amplitude and time-course of the haemodynamic effects were similar with either implant. Thus ABP is measurable in the minipig with minimal surgery. PAC10-TOX-LA implantation into the femoral artery yielded the highest quality signals. The financial impact of this approach must be balanced with the ability to detect haemodynamic changes in unstressed animals in the long-term. doi:10.1016/j.vascn.2011.03.167
Poster No: 163 A novel telemetry device for comprehensive assessment of cardiovascular function in conscious dogs Michael Hoffmann a, Thomas Vormberge a, Thomas Mondritzki b, Hubert Truebel b a b
Bayer Healthcare AG, Safety Pharmacology, Wuppertal, Germany Bayer Healthcare AG, Cardiovascular Research, Wuppertal, Germany
Introduction: Comprehensive assessment of cardiovascular function in conscious animals is often limited by the lack of continuous cardiac output measurements. A new battery-free telemetric device (CardioMEMS, CM) which allows pulmonary pressure readings and calculation of cardiac output is currently in Phase III clinical testing. In preclinical studies these sensors offer the opportunity for simultaneous registration of pulmonary and systemic resistance, heart contractility and ECG when combined with an established telemetry system. Methods: A female beagle dog was equipped with a D70-PCTP transmitter (DSI) and a wireless HF pressure sensor (CM). The 2 catheters of the DSI device were placed into the abdominal aorta and the left ventricle of the heart; ECG electrodes were placed subcutaneously in lead II position. The CM pressure sensor was introduced into a pulmonary artery branch under X-ray control guided with a Swan-Ganz catheter. While the dog was standing in a sling, data of the DSI device was collected continuously. In parallel signals of the CM sensor were captured using specific software, which calculates stroke volume from pulmonary pressure waveform. Results of a basic validation study with short-term intravenous infusion of reference compounds (e.g. SNP and phenylephrine) are presented. Conclusion: To our knowledge this is the first method enabling complete assessment of cardio-hemodynamics and ECG in conscious dogs by combining established telemetry systems and a novel wireless sensor allowing measurement of pressure and flow in the systemic and pulmonary circulation. doi:10.1016/j.vascn.2011.03.168
Poster No: 164 Evaluation of a non-invasive telemetry method for determining blood pressure in dogs R. Brandon Borders, Brian Roche, Tom Vinci, Shawnda Armentrout, Jeremy Smith, Steve Behringer, Ernesto Gonzalez, Brandon Wood, Craig Hassler Battelle Memorial Institute, Columbus, OH 43201, USA