Ischemic preconditioning prior to aortic cross-clamping protects high-energy phosphate levels, glucose uptake, and myocyte contractility.
BACKGROUND
We hypothesized that indices of myocyte contractility and metabolism could be preserved with ischemic preconditioning in a model of reversible ischemia similar to that occurring during routine cardiac surgery. Regional measures of metabolism and function have not been studied in conjunction with individual myocyte function during postischemic recovery of preconditioned myocardium.


METHODS
In 16 dogs, myocardium supplied by the left anterior descending artery (LAD) was preconditioned with intermittent LAD ischemia and reperfusion. Following preconditioning, the heart was made globally ischemic for 20 min at normothermia by aortic cross-clamping while on cardiopulmonary bypass. In 10 animals, serial measurements of LAD and remote region adenosine triphosphate (ATP) levels, glucose uptake, and wall thickening were obtained with full-thickness drill biopsies, positron emission tomography (PET), and 2-D echocardiography, respectively. In the remaining 6 animals, cardiac myocytes were isolated after 1 h of reperfusion for measurement of myocyte contractility and intracellular calcium transients.


RESULTS
ATP levels were higher in the preconditioned LAD region than in the remote region at end of ischemia (3.17 +/- 0.33 nmol/mg vs 2.59 +/- 0.30 nmol/mg, P = 0.006). Similarly, preconditioned region glucose uptake was 40% higher than remote region glucose uptake at 2 days postischemia (0.35 +/- 0.06 micromol/min/g vs 0.25 +/- 0.05 micromol/min/g, P = 0.019). There were no differences in regional wall thickening as measured by 2-D echo either immediately following ischemia or at 2 days. Individual myocyte contractile response to increasing concentrations of extracellular calcium was preserved in cells from preconditioned myocardium, but it was severely depressed in remote region myocytes.


CONCLUSIONS
We conclude that regional ischemic preconditioning prior to prolonged ischemia protects myocardial glucose uptake and myocyte contractile function. The beneficial effects on glucose metabolism suggest that preconditioning may have sustained protective effects on cell metabolism.
Division of Cardiothoracic Surgery, University of Minnesota and Minneapolis VA Medical Center, 55417, USA.
Douglas
D
Baldwin
Y
Y
Chandrashekhar
Edward
E
McFalls
Inder
I
Anand
Daosheng
D
Liu
Diane
D
Jaimes
David
D
Marx
Herbert
H
Ward
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001011:Aorta; D003250:Constriction; D004285:Dogs; D005260:Female; D005947:Glucose / Q000378:metabolism*; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010725:Phosphocreatine / Q000378:metabolism*; D013997:Time Factors; D014463:Ultrasonography
D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D005947:Glucose