Hsin-Jung Yang1,2, Damini Dey1,2, Jane Sykes3, Michael Klein4, John Butler3, Michael S Kovacs3, Olivia Sobczyk4, Behzad Sharif1, Xiaoming Bi5, Avinash Kali1,2, Ivan Cokic1, Richard Tang1, Roya Yumul1,6, Antonio H Conte1, Sotirios A Tsaftaris7, Mourad Tighiouart8, Debiao Li1,2, Piotr J Slomka1,6, Daniel S Berman1,6, Frank S Prato3, Joseph A Fisher4, Rohan Dharmakumar9,2,6. 1. Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, California. 2. Department of Bioengineering, University of California, Los Angeles, California. 3. University of Western Ontario, Lawson Health Research Institute, London, Ontario, Canada. 4. Department of Physiology, University of Toronto, Toronto, Ontario, Canada. 5. MR R&D, Siemens Healthcare, Los Angeles, California. 6. Department of Medicine, University of California, Los Angeles, California. 7. School of Engineering, Institute of Digital Communications, University of Edinburgh, Edinburgh, United Kingdom; and. 8. Biostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, Los Angeles, California. 9. Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, California rohandkumar@csmc.edu.
Abstract
Myocardial blood flow (MBF) is the critical determinant of cardiac function. However, its response to increases in partial pressure of arterial CO2 (PaCO2), particularly with respect to adenosine, is not well characterized because of challenges in blood gas control and limited availability of validated approaches to ascertain MBF in vivo. Methods: By prospectively and independently controlling PaCO2 and combining it with 13N-ammonia PET measurements, we investigated whether a physiologically tolerable hypercapnic stimulus (∼25 mm Hg increase in PaCO2) can increase MBF to that observed with adenosine in 3 groups of canines: without coronary stenosis, subjected to non-flow-limiting coronary stenosis, and after preadministration of caffeine. The extent of effect on MBF due to hypercapnia was compared with adenosine. Results: In the absence of stenosis, mean MBF under hypercapnia was 2.1 ± 0.9 mL/min/g and adenosine was 2.2 ± 1.1 mL/min/g; these were significantly higher than at rest (0.9 ± 0.5 mL/min/g, P < 0.05) and were not different from each other (P = 0.30). Under left-anterior descending coronary stenosis, MBF increased in response to hypercapnia and adenosine (P < 0.05, all territories), but the effect was significantly lower than in the left-anterior descending coronary territory (with hypercapnia and adenosine; both P < 0.05). Mean perfusion defect volumes measured with adenosine and hypercapnia were significantly correlated (R = 0.85) and were not different (P = 0.12). After preadministration of caffeine, a known inhibitor of adenosine, resting MBF decreased; and hypercapnia increased MBF but not adenosine (P < 0.05). Conclusion: Arterial blood CO2 tension when increased by 25 mm Hg can induce MBF to the same level as a standard dose of adenosine. Prospectively targeted arterial CO2 has the capability to evolve as an alternative to current pharmacologic vasodilators used for cardiac stress testing.
Myocardial blood flow (MBF) is the critical determinant of cardiac function. However, its response to increases in partial pressure of arterial CO2 (PaCO2), particularly with respect to adenosine, is not well characterized because of challenges in blood gas control and limited availability of validated approaches to ascertain MBF in vivo. Methods: By prospectively and independently controlling PaCO2 and combining it with 13N-ammonia PET measurements, we investigated whether a physiologically tolerable hypercapnic stimulus (∼25 mm Hg increase in PaCO2) can increase MBF to that observed with adenosine in 3 groups of canines: without coronary stenosis, subjected to non-flow-limiting coronary stenosis, and after preadministration of caffeine. The extent of effect on MBF due to hypercapnia was compared with adenosine. Results: In the absence of stenosis, mean MBF under hypercapnia was 2.1 ± 0.9 mL/min/g and adenosine was 2.2 ± 1.1 mL/min/g; these were significantly higher than at rest (0.9 ± 0.5 mL/min/g, P < 0.05) and were not different from each other (P = 0.30). Under left-anterior descending coronary stenosis, MBF increased in response to hypercapnia and adenosine (P < 0.05, all territories), but the effect was significantly lower than in the left-anterior descending coronary territory (with hypercapnia and adenosine; both P < 0.05). Mean perfusion defect volumes measured with adenosine and hypercapnia were significantly correlated (R = 0.85) and were not different (P = 0.12). After preadministration of caffeine, a known inhibitor of adenosine, resting MBF decreased; and hypercapnia increased MBF but not adenosine (P < 0.05). Conclusion: Arterial blood CO2 tension when increased by 25 mm Hg can induce MBF to the same level as a standard dose of adenosine. Prospectively targeted arterial CO2 has the capability to evolve as an alternative to current pharmacologic vasodilators used for cardiac stress testing.
Authors: Shoji Ito; Alexandra Mardimae; Jay Han; James Duffin; Greg Wells; Ludwik Fedorko; Leonid Minkovich; Rita Katznelson; Massimiliano Meineri; Tamara Arenovich; Cathie Kessler; Joseph A Fisher Journal: J Physiol Date: 2008-06-19 Impact factor: 5.182
Authors: Maaike van den Boomen; Mary Kate Manhard; Gert Jan H Snel; SoHyun Han; Kyrre E Emblem; Riemer H J A Slart; David E Sosnovik; Ciprian Catana; Bruce R Rosen; Niek H J Prakken; Christopher T Nguyen; Ronald J H Borra; Kawin Setsompop Journal: Radiology Date: 2020-01-21 Impact factor: 29.146