title: 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 [(13)N]ammonia and (18)F-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 approximately 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 micromol x min(-1) x 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.
authors: Sector of Medicine, Scuola Superiore Sant'Anna, Piazza Martiri della Libertà, 56122 Pisa, Italy.
authors: Vincenzo
authors: V
authors: Lionetti
authors: Letizia
authors: L
authors: Guiducci
authors: Anca
authors: A
authors: Simioniuc
authors: Giovanni D
authors: GD
authors: Aquaro
authors: Claudia
authors: C
authors: Simi
authors: Daniele
authors: D
authors: De Marchi
authors: Silvia
authors: S
authors: Burchielli
authors: Lorenza
authors: L
authors: Pratali
authors: Marcello
authors: M
authors: Piacenti
authors: Massimo
authors: M
authors: Lombardi
authors: Piero
authors: P
authors: Salvadori
authors: Alessandro
authors: A
authors: Pingitore
authors: Danilo
authors: D
authors: Neglia
authors: Fabio A
authors: FA
authors: Recchia
mesh_terms: D000818:Animals; D002303:Cardiac Output, Low / Q000209:etiology* / Q000378:metabolism*; D002304:Cardiac Pacing, Artificial / Q000009:adverse effects*; D005947:Glucose / Q000378:metabolism*; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism; D013552:Swine; D013556:Swine, Miniature; D018487:Ventricular Dysfunction, Left / Q000209:etiology* / Q000378:metabolism*
chemical_list: D005947:Glucose