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(Circulation. 1996;94:808-816.)
© 1996 American Heart Association, Inc.

Articles

Noninvasive Quantification of Regional Myocardial Metabolic Rate of Oxygen by ¹⁵O₂ Inhalation and Positron Emission Tomography

Experimental Validation

Yusuke Yamamoto, MD; Ranil de Silva, MBBS, PhD; Christopher G. Rhodes, MSc; Hidehiro Iida, DSc; Adriaan A. Lammertsma, PhD; Terry Jones, DSc; Attilio Maseri, MD, FRCP

the Cyclotron Unit, MRC Clinical Sciences Centre and Cardiovascular Research Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.

Correspondence to Ranil de Silva, MBBS, PhD, Cyclotron Unit, MRC Clinical Sciences Centre, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.

Background The purpose of this study was to validate a novel method for noninvasive quantification of regional myocardial oxygen consumption (MMRO₂, mL·min^-1·100 g^-1) and oxygen extraction fraction (OEF) by use of positron emission tomography (PET) and inhalation of ¹⁵O-labeled molecular oxygen gas (¹⁵O₂).

Methods and Results Twenty-four measurements were performed in eight closed-chest anesthetized greyhounds at baseline and during infusions of adenosine (100 to 200 µg·kg^-1·min^-1), isoproterenol (1 to 10 µg/min), and propranolol (5 mg bolus+0.2 to 1 mg/min) with morphine (5 mg slow infusion+0.2 to 0.5 mg/min) to obtain a wide range of oxidative metabolism. The PET imaging protocol consisted of ¹⁵O₂ emission (OEF and MMRO₂), transmission, [¹⁵O]CO emission (blood pool), and [¹⁵O]CO₂ emission (myocardial blood flow: MBF_pet, mL·min^-1·g^-1) scans. OEF was calculated from the PET data (OEF_pet) by three different analytical techniques: steady-state, 5-minute, and 8-minute autoradiographic analyses. Reference measurements of MBF (MBF_ref) and OEF (OEF_ref) were obtained during ¹⁵O₂ inhalation with radiolabeled microspheres and paired arterial and coronary sinus blood sampling, respectively. MMRO₂ was calculated from the PET (MMRO_2pet) and the reference (MMRO_2ref) data as follows: MMRO₂=OEFxMBFx(O₂ content of arterial blood). OEF measured by the steady-state PET method was well correlated with the reference data over the range 0.16 to 0.73 (OEF_pet=1.03 OEF_ref -0.01, r=.97), as was MMRO₂ over the range 2.4 to 27.5 mL·min^-1·100 g^-1 (MMRO_2pet=0.98 MMRO_2ref +0.91, r=.94). OEF_pet calculated by use of the 5-minute and 8-minute autoradiographic analyses were equally well correlated with the reference measurements (r=.95 and r=.97, respectively). There were no significant differences between values of MMRO_2pet calculated by use of the steady-state, 5-minute, and 8-minute autoradiographic analyses (P=NS by ANOVA). Regional values of MBF_pet, OEF_pet, and MMRO_2pet were homogeneously distributed and similar to the whole-heart values both at baseline and during the various pharmacological interventions.

Conclusions Accurate quantification of OEF and MMRO₂ is feasible with ¹⁵O₂ inhalation and PET imaging using both the steady-state and autoradiographic analytical approaches. These studies suggest the applicability of this method for quantitative assessments of regional cardiac oxidative metabolism in clinical studies.

Key Words: myocardium • metabolism • oxygen • tomography

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