Abstract 12316: Tc-99m Sestamibi is a Useful Noninvasive Method to Assess Cardiac Mitochondrial Function in vivo
Introduction: Technetium-99m sestamibi (99mTc-MIBI) is used for the diagnosis of myocardial ischemia. The initial uptake of 99mTc-MIBI is dependent on blood perfusion. 99mTc-MIBI washout is correlated with the mitochondrial membrane potential in cultured cardiomyocytes and ex vivo perfused hearts. 99mTc-MIBI washout is increased in patients with heart failure (HF).
Hypothesis: We assessed the hypothesis that 99mTc-MIBI washout is useful for assessing mitochondrial function in an in vivo heart.
Methods and Results: Carbonyl cyanide m-chlorophenylhydrazone (CCCP) decreases the mitochondrial membrane potential. In ex vivo perfused rat hearts, CCCP increased the washout of 99mTc-MIBI. Next, CCCP was intraperitoneally injected into rats (5 mg/kg). The administration of CCCP decreased the systolic function on echocardiography, and decreased phosphocreatine and ATP contents on in situ 31P MR spectroscopy. The 99mTc-MIBI count was analyzed using a gamma camera 15 minutes and 3 hours after injection, and the washout of 99mTc-MIBI was increased in the CCCP group compared with the vehicle group (23.0±4.0 vs. 9.8±1.8%, respectively, mean±SEM, p=0.012). To examine the uptake and retention of 99mTc-MIBI in a hypertrophied and failing heart, we administered 99mTc-MIBI to Dahl salt-sensitive rats fed a high salt diet, which develop hypertension and HF. Dahl rats fed a low salt diet were used as a control. Ten control rats and 26 HF rats were sacrificed 45 minutes after 99mTc-MIBI injection, and another 10 control rats and 26 HF rats were sacrificed 6 hours after the injection. The heart was removed and 99mTc-MIBI radioactivity was directly counted using a scintillation counter.99mTc-MIBI washout was increased in HF rats compared with control rats (23.3±2.2 vs. 14.2±2.1%, respectively, p=0.022). 99mTc-MIBI washout was positively correlated with ANF gene expression in the heart (n=35, R=0.500, p=0.002). Interestingly, 99mTc-MIBI counts per heart were not different between control and HF rats sacrificed 45 minutes after injection, suggesting that blood perfusion of the heart did not change despite an increase in the cardiac mass.
Conclusion: 99mTc-MIBI washout is a useful noninvasive method for assessing the cardiac mitochondrial function in HF.
- © 2011 by American Heart Association, Inc.