Myocardial 99mTc-sestamibi extraction and washout in hypertensive heart failure using an isolated rat heart

Abstract

Purpose: Myocardial mitochondria are the primary part of energy production for healthy cardiac contraction. And mitochondrial dysfunction would play an important role in progressive heart failure. In the recent years, myocardial washout of (99m)Tc-sestamibi [((99m)Tc-hexakis-2-methoxy-2-methylpropyl isonitrile (MIBI)] has been introduced to be a potential marker in patients with heart failure. The objective of this study was to clarify MIBI extraction and washout kinetics using isolated perfusion system in hypertension induced model of myocardial dysfunction.

Methods: Six-week-old Dahl-salt sensitive rats, allotted to 4 groups; a 5-week high-salt group (5 wk-HS), 12-week high-salt group (12 wk-HS) and two age-matched, low-salt diet control groups (5 wk-LS and 12 wk-LS). The rats in 5 wk-HS and 12 wk-HS groups were fed a high-salt diet (containing 8% NaCl). Cardiac function was examined by echocardiography before removing heart. Hearts were perfused according to the Langendorff method at a constant flow rate, in which 20-min MIBI washin was conducted followed by 25-min MIBI washout. Whole heart radioactivity was collected every sec by an external gamma detector. The myocardial extraction, K(1) (ml/min) and washout rate, k(2) (min(-1)) were generated.

Results: High-salt diet groups showed significant high-blood pressure. Echocardiography revealed thickened LV walls in 5 wk-HS, and reduced cardiac function in 12 wk-HS, compared to each age-matched control group. K(1) showed no significant difference among all groups (5 wk-HS: 2.36 ± 1.07, 5 wk-control: 2.59 ± 0.28, 12 wk-HS: 1.91 ± 0.90, and 12 wk-control: 2.84 ± 0.57). k(2) in 5 wk-HS was comparable to that in the age matched control group (0.00030 ± 0.00039 vs -0.000010 ± 0.00044), but it was increased remarkably in 18 wk-HS compared to the age matched control group (0.0025 ± 0.0011 vs 0.000025 ± 0.000041, P<.01), and 5 wk-HS (P<.01).

Conclusion: In the course of hypertensive heart disease, MIBI washout was increased in the transitional state from hypertrophied to dilated and failing heart, while MIBI extraction remained intact.