Abstract 10905: Tc-99m Sestamibi Washout is a Useful Method to Assess Cardiac Mitochondrial Function and the Increased Risk of a Failing Heart: A Translational Approach to Understand the Metabolic State of the Heart
Background: Since mitochondria are crucial modulators of cardiac energy metabolism and play pivotal roles in heart failure (HF), assessing the mitochondrial function has been thought to be important for the treatment or risk stratification of HF. Technetium-99m sestamibi (99mTc-MIBI), which is widely used in the diagnosis of myocardial ischemia, has been reported to show slow clearance in proportion to the mitochondrial membrane potential in cultured cardiomyocytes.
Hypothesis: We tested the hypothesis that 99mTc-MIBI washout is useful for assessing the mitochondrial function in an in vivo heart and that increased 99mTc-MIBI washout (or decreased retention) would occur in a rat model and patients with HF associated with the severity.
Methods and Results: Carbonyl cyanide m-chlorophenylhydrazone (CCCP 5 mg/kg), a compound known to reduce the mitochondrial membrane potential, was injected intraperitoneally into SD rats 90 minutes after the administration of 99mTc-MIBI. The rats administered CCCP showed a decrease of about 0.6 fold in phosphocreatine and ATP on in situ 31P magnetic resonance spectroscopy (n=4-5, p=0.04). Using myocardial perfusion imaging in the early and delayed phases (interval of 3 hours), the washout rate of 99mTc-MIBI was increased in the CCCP-administered group compared with the vehicle group (23.0+4.0% vs. 9.8+1.8%, respectively, n=7-8, p=0.01). In ex vivo perfused hearts, CCCP decreased the retention of 99mTc-MIBI in a dose-dependent manner, associated with a decreased mitochondrial membrane potential. Next, we administered 99mTc-MIBI to Dahl salt-sensitive rats fed a high salt diet, which develop hypertension and HF. The retention of 99mTc-MIBIwas decreased in the HF group and negatively correlated with the heart weight of rats (n=36, r=-0.84, p<0.001). Finally, we assessed 33 patients (male: 19 patients) with chronic heart failure after the treatment of acute exacerbation. The washout rate of 99mTc-MIBI was positively correlated with BNP levels (r=0.61, p=0.005), but was not with EF.
Conclusions: 99mTc-MIBI washout is thought to be a useful method to assess the cardiac mitochondrial function in an in vivo heart and was increased in HF, suggesting an association with cardiac remodeling in HF.
- © 2012 by American Heart Association, Inc.