Assessment of mitochondrial dysfunctions in myocardial ischemia/reperfusion injury with 99mTc-MIBI

Purpose: To evaluate the possibility of using 99mTc-MIBI as the tracer of mitochondrial functions. Methods: Intact mitochondria were prepared from SD rat hearts by differential centrifugation. The acute and chronic myocardial ischemia of dogs were made by surgery. The 99mTc-MIBI mitochondria binding studies in vitro in the presence of CaCl2 or (and) NaCl to mimic reperfusion injury and 99mTc-MIBI myocardial imaging studies in vivo were undertaken with or without intervenient drugs, including cyclosporin A (a inhibitor of mitochondrial inner membrane's pore), diltiazem or magnesium sulfate (the Ca2+/2 Na+ exchanger inhibitors) and nifedipine (the calcium channel antagonist). Results: Though % 99mTc-MIBI binding in vitro was blocked in the present of CaCl2 on (and) NaCl, the full or partial recovery of % 99mTc-MIBI achieved by adding cyclosporin A plus diltiazem or by prolonging the duration of binding depending on CaCl2 concentration. Also, cyclosporin A plus diltiazem could enhance the uptake of 99mTc-MIBI but not that of 125I-microsphere perfusion in ischemic myocardium. the clearance of 99mTc-MIBI from ischemic regions was retarded if the reperfusion injury was prevented by administration of nifedipine. The clearance of 99mTc-MIBI in ischemic myocardium was different from that of livers where the P-glycoprotein gene is highly expressed. Conclusions: The uptake and clearance of 99mTc-MIBI could be affected by myocardial mitochondrial functions