Mismatch between uniform increase in cardiac glucose uptake and regional contractile dysfunction in pacing-induced heart failure

Abstract

Increased glucose utilization and regional differences in contractile function are well-known alterations of the failing heart and play an important pathophysiological role. We tested whether, similar to functional derangement, changes in glucose uptake develop following a regional pattern. Heart failure was induced in 13 chronically instrumented minipigs by pacing the left ventricular (LV) free wall at 180 beats/min for 3 wk. Regional changes in contractile function and stress were assessed by magnetic resonance imaging, whereas regional flow and glucose uptake were measured by positron emission tomography utilizing, respectively, the radiotracers [13N]ammonia and 18F-deoxyglucose. In heart failure, LV end-diastolic pressure was 20 ± 4 mmHg, and ejection fraction was 35 ± 4% (all P < 0.05 vs. control). Sustained pacing-induced dyssynchronous LV activation caused a more pronounced decrease in LV systolic thickening (7.45 ± 3.42 vs. 30.62 ± 8.73%, P < 0.05) and circumferential shortening (−4.62 ± 1.0 vs. −7.33 ± 1.2%, P < 0.05) in the anterior/anterior-lateral region (pacing site) compared with the inferoseptal region (opposite site). Conversely, flow was reduced significantly by ∼32% compared with control and was lower in the opposite site region. Despite these nonhomogeneous alterations, regional end-systolic wall stress was uniformly increased by 60% in the failing LV. Similar to wall stress, glucose uptake markedly increased vs. control (0.24 ± 0.004 vs. 0.07 ± 0.01 μmol·min−1·g−1, P < 0.05), with no significant regional differences. In conclusion, high-frequency pacing of the LV free wall causes a dyssynchronous pattern of contraction that leads to progressive cardiac failure with a marked mismatch between increased glucose uptake and regional contractile dysfunction.