title: Decreased interstitial glucose and transmural gradient in lactate during ischemia.
abstract: The purpose of this investigation was to assess the effects of ischemia and reperfusion on the transmural levels of glucose and lactate in the interstitium in 11 open-chest swine. Microdialysis probes were used to estimate changes in interstitial metabolities across the ventricular wall. Probes were placed in the subepicardium and the subendocardium of the left anterior descending (LAD) coronary artery perfusion bed and in the midmyocardium of the circumflex (CFX) perfusion bed. The LAD coronary artery was cannulated and perfused with blood from the femoral artery through an extracorporal perfusion circuit. Ischemia was induced in the LAD perfusion bed by reducing the flow of the LAD perfusion pump by 60% for 50 min, and was followed by 30 min of reperfusion. Regional myocardial blood flow was assessed with fluorescent microspheres. Ischemia resulted in a transmural gradient in blood flow, with the most severe reduction in flow occurring in the subendocardium (p < 0.05). We found a significant reduction in interstitial glucose in both the LAD subepicardium (1.26 +/- 0.24 mM) (p = 0.0009) and subendocardium (0.89 +/- 0.21 mM) (p = 0.0001) during ischemia compared to the aerobic (non-ischemic) period (1.97 +/- 0.25 mM, 2.03 +/- 0.29 mM for the subepicardium and subendocardium, respectively). This coincided with a significant reduction in glucose delivery (LAD pump flow * arterial glucose) to the LAD perfusion bed during ischemia (54.5 +/- 8.5 mumol/min) compared to aerobic values (182.1 +/- 25.3 mumol/min) (p < 0.05). Interstitial lactate levels were significantly increased during ischemia in the LAD subendocardium (3.39 +/- 0.46 mM) compared to the aerobic values (1.73 +/- 0.46 mM) (p < 0.0029). A transmural gradient in interstitial lactate levels was observed during ischemia: this gradient was not seen during the aerobic period and was negated upon reperfusion. In conclusion, ischemia resulted in a decrease in interstitial glucose in both the LAD subepicardium and subendocardium, and an increase in interstitial lactate in the LAD subendocardium. Further, a transmural gradient in interstitial lactate levels was observed during ischemia, with the highest lactate values appearing in the subendocardium.
authors.affiliation: Institute of Pharmacology, Syntex Discovery Research, Palo Alto, CA.
authors.forename: J L
authors.initials: JL
authors.lastname: Hall
authors.forename: L A
authors.initials: LA
authors.lastname: Hernandez
authors.forename: J
authors.initials: J
authors.lastname: Henderson
authors.forename: L A
authors.initials: LA
authors.lastname: Kellerman
authors.forename: W C
authors.initials: WC
authors.lastname: Stanley
mesh_terms: D000818:Animals; D003331:Coronary Vessels / Q000473:pathology; D004699:Endocardium / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000032:analysis*; D006439:Hemodynamics; D007773:Lactates / Q000032:analysis*; D019344:Lactic Acid; D017202:Myocardial Ischemia / Q000378:metabolism*; D015425:Myocardial Reperfusion; D012039:Regional Blood Flow; D013552:Swine
chemical_list: D007773:Lactates; D019344:Lactic Acid; D005947:Glucose