Author + information
- Received November 28, 1994
- Revision received April 7, 1995
- Accepted April 20, 1995
- Published online September 1, 1995.
- A. James Liedtke, MD, FACC*,
- Britta Renstrom, PhD,
- Stephen H. Nellis, PhD,
- Jennifer L. Hall, MS and
- William C. Stanley, PhD
- ↵*Address for correspondence: Dr. A. James Liedtke, Cardiology Section. H6/349, University of Wisconsin Hospital and Clinics, 600 Highland Avenue. Madison, Wisconsin 53792-3248.
Objectives This study sought to evaluate the functional and metabolic consequences of imposing a chronic external coronary stenosis around the left anterior descending coronary artery for 4 days in an intact pig model.
Background A clinical condition termed hibernating myocardium has been described wherein as a result of chronic sustained or intermittent coronary hypoperfusion, heart muscle minimizes energy demands by decreasing mechanical function and thus avoids cell death. The use of chronic animal models to simulate this disorder may assist in establishing causative associations among determinants to explain this phenomenon.
Methods A hydraulic cuff occluder was placed around the left anterior descending coronary artery in eight pigs. Coronary flow velocity was reduced by a mean (±SE) of 49 ± 5% of prestenotic values, as estimated by a Doppler velocity probe. After 4 days the pigs were prepared with extracorporeal coronary circulation and evaluated at flow conditions dictated by the cuff occluder. Substrate utilizations were described using equilibrium labeling with [U-14C]palmitate and [5-3H]glucose. Results were compared with a combined group of 21 acute and chronic (4 day) sham animals.
Results Four days of partial coronary stenosis significantly decreased regional systolic shortening by 54%. Myocardial oxygen consumption was maintained at aerobic levels, and rest coronary flows were normal. Fatty acid oxidation was decreased by 43% below composite sham values, and exogenous glucose utilization was increased severalfold. Alterations in myocardial metabolism were accompanied by a decline in tissue content of adenosine triphosphate.
Conclusions These data suggest that chronic coronary stenosis in the absence of macroscarring imparts an impairment in mechanical function, whereas coronary flow and myocardial oxygen consumption are preserved at rest. The increases in glycolytic flux of exogenous glucose are similar to observations on glucose uptake assessed by fluorine-18 2-deoxy-2-fluoro-d-glucose in patients with advanced coronary artery disease. We speculate that intermittent episodes of ischemia and reperfusion are the cause of this phenomenon.
This work was supported in part by PHS Grant HL-32350, National Heart, Lung, and Blood Institute. National Institutes of Health, Bethesda, Maryland; and by grants from the Rennebohm Foundation of Wisconsin, the Oscar Mayer Cardiovascular Research Fund and American Heart Association Grants-inAid 91-GA-11/92-GS-26 of the Wisconsin Affiliate (the Dave McClain Research Grant), Madison, Wisconsin and 92-729 of the National Center, Dallas, Texas.
- Received November 28, 1994.
- Revision received April 7, 1995.
- Accepted April 20, 1995.
- American College of Cardiology