Noninvasive Quantification of Regional Myocardial Metabolic Rate of Oxygen by 15 O 2 Inhalation and Positron Emission Tomography

Author:

Yamamoto Yusuke1,de Silva Ranil1,Rhodes Christopher G.1,Iida Hidehiro1,Lammertsma Adriaan A.1,Jones Terry1,Maseri Attilio1

Affiliation:

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

Abstract

Background The purpose of this study was to validate a novel method for noninvasive quantification of regional myocardial oxygen consumption (MMR o 2 , mL·min −1 ·100 g −1 ) and oxygen extraction fraction (OEF) by use of positron emission tomography (PET) and inhalation of 15 O-labeled molecular oxygen gas ( 15 O 2 ). 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 15 O 2 emission (OEF and MMR o 2 ), transmission, [ 15 O]CO emission (blood pool), and [ 15 O]CO 2 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 15 O 2 inhalation with radiolabeled microspheres and paired arterial and coronary sinus blood sampling, respectively. MMR o 2 was calculated from the PET (MMR o 2pet ) and the reference (MMR o 2ref ) data as follows: MMR o 2 =OEF×MBF×(O 2 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 MMR o 2 over the range 2.4 to 27.5 mL·min −1 ·100 g −1 (MMR o 2pet =0.98 MMR o 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 MMR o 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 MMR o 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 MMR o 2 is feasible with 15 O 2 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.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine

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