Journal
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Volume 293, Issue 5, Pages H2747-H2756Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00592.2007
Keywords
heart failure; pacing; mismatch; dyssynchrony; glucose uptake
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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 [N-13] ammonia and F-18-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 infero-septal region (opposite site). Conversely, flow was reduced significantly by similar to 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 mu mol center dot min(-1)center dot 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.
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