Abstract 13873: Abnormalities in Myocardial Energetics in Collateral Dependent Myocardium in Response to Increased Workload
Introduction: In a canine model of moderately well developed coronary collateral vessels, blood flow (MBF) to the collateral region (COL) is similar to normal myocardium (NORM) at rest but the increase in MBF during exercise is impaired. This study examined whether abnormalities in high energy phosphates (HEP) exist in COL, and whether these abnormalities indicate ischemia when cardiac work is increased.
Methods: Collateral development was stimulated in dogs with intermittent 2-minute coronary occlusions performed at 15 minute-intervals for 3 hours each day. Initial distal coronary pressures during occlusion were 10–20 mmHg. When this pressure exceeded 35mmHg (2 to 3 weeks of occlusions), the artery was permanently occluded. 31P magnetic resonance spectroscopy (MRS) was performed 5 to 7 days after permanent coronary occlusion to measure HEP while 1H MRS was used to detect deoxymyoglobin (Mb-δ) at baseline (BL) and during infusion of dobutamine and dopamine (DD).
Results: During basal conditions MBF (microspheres) was similar in COL and NORM regions, and PCr/ATP in the COL region was 2.22±0.14 which was similar to normal dogs (2.21±0.1). DD increased the RPP (30.3±5.2 vs 13.7±1.9, p<0.05). The increase in MBF was less in COL as compared to NORM (0.81±0.08 vs 1.25±0.1 ml/min per g, p<0.05). Moreover, in the COL region PCr/ATP decreased from 2.22±0.14 to 1.79±0.2 (p<0.05), while in normal hearts PCr/ATP during DD was 2.10±0.1. The pseudo-first-order rate constant of ATP production via CK (kf) did not change during DD. However, the ATP production rate via CK was reduced by 30.6±1.2% during DD. Despite the subnormal increase in MBF and the decrease of PCr/ATP in COL, Mb-δ was not detected.
Conclusions: Increasing cardiac work with DD resulted in decreased PCr/ATP with decreased flux through creatine kinase, but without evidence for oxygen insufficiency. This lack of evidence of ischemia despite impaired blood flow suggests an intrinsic ability of the myocardium to maintain energy homeostasis during periods of increased work indicative of a hibernating state.
- © 2010 by American Heart Association, Inc.