title: Arterial CO2as a Potent Coronary Vasodilator: A Preclinical PET/MR Validation Study with Implications for Cardiac Stress Testing.
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 PaCO2and combining it with13N-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; bothP< 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 CO2tension when increased by 25 mm Hg can induce MBF to the same level as a standard dose of adenosine. Prospectively targeted arterial CO2has the capability to evolve as an alternative to current pharmacologic vasodilators used for cardiac stress testing.
authors.affiliation: Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, California.|Department of Bioengineering, University of California, Los Angeles, California.
authors.forename: Hsin-Jung
authors.initials: HJ
authors.lastname: Yang
authors.affiliation: Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, California.|Department of Bioengineering, University of California, Los Angeles, California.
authors.forename: Damini
authors.initials: D
authors.lastname: Dey
authors.affiliation: University of Western Ontario, Lawson Health Research Institute, London, Ontario, Canada.
authors.forename: Jane
authors.initials: J
authors.lastname: Sykes
authors.affiliation: Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Klein
authors.affiliation: University of Western Ontario, Lawson Health Research Institute, London, Ontario, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Butler
authors.affiliation: University of Western Ontario, Lawson Health Research Institute, London, Ontario, Canada.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Kovacs
authors.affiliation: Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Olivia
authors.initials: O
authors.lastname: Sobczyk
authors.affiliation: Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Behzad
authors.initials: B
authors.lastname: Sharif
authors.affiliation: MR R&D, Siemens Healthcare, Los Angeles, California.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Bi
authors.affiliation: Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, California.|Department of Bioengineering, University of California, Los Angeles, California.
authors.forename: Avinash
authors.initials: A
authors.lastname: Kali
authors.affiliation: Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Ivan
authors.initials: I
authors.lastname: Cokic
authors.affiliation: Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Richard
authors.initials: R
authors.lastname: Tang
authors.affiliation: Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, California.|Department of Medicine, University of California, Los Angeles, California.
authors.forename: Roya
authors.initials: R
authors.lastname: Yumul
authors.affiliation: Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Antonio H
authors.initials: AH
authors.lastname: Conte
authors.affiliation: School of Engineering, Institute of Digital Communications, University of Edinburgh, Edinburgh, United Kingdom; and.
authors.forename: Sotirios A
authors.initials: SA
authors.lastname: Tsaftaris
authors.affiliation: Biostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Mourad
authors.initials: M
authors.lastname: Tighiouart
authors.affiliation: Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, California.|Department of Bioengineering, University of California, Los Angeles, California.
authors.forename: Debiao
authors.initials: D
authors.lastname: Li
authors.affiliation: Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, California.|Department of Medicine, University of California, Los Angeles, California.
authors.forename: Piotr J
authors.initials: PJ
authors.lastname: Slomka
authors.affiliation: Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, California.|Department of Medicine, University of California, Los Angeles, California.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Berman
authors.affiliation: University of Western Ontario, Lawson Health Research Institute, London, Ontario, Canada.
authors.forename: Frank S
authors.initials: FS
authors.lastname: Prato
authors.affiliation: Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Fisher
authors.affiliation: Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, California rohandkumar@csmc.edu.|Department of Bioengineering, University of California, Los Angeles, California.|Department of Medicine, University of California, Los Angeles, California.
authors.forename: Rohan
authors.initials: R
authors.lastname: Dharmakumar
mesh_terms: D000241:Adenosine / Q000008:administration & dosage*; D000818:Animals; D002245:Carbon Dioxide / Q000097:blood*; D023921:Coronary Stenosis / Q000097:blood* / Q000000981:diagnostic imaging*; D004285:Dogs; D005080:Exercise Test / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D064847:Multimodal Imaging / Q000379:methods; D049268:Positron-Emission Tomography / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014665:Vasodilator Agents
chemical_list: D014665:Vasodilator Agents; D002245:Carbon Dioxide; D000241:Adenosine
keywords: cardiac stress testing; coronary artery disease; hypercapnia; myocardial perfusion