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W C Stanley

Publications and source records attributed to W C Stanley.

60 records · Page 4Linked to original sources
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Decreased interstitial glucose and transmural gradient in lactate during ischemia.

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.

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Alanine, glutamate, and ammonia exchanges in acutely ischemic swine myocardium.

Coronary artery disease causes an increase in glutamate uptake and alanine output by the heart. We assessed the effects of acute myocardial ischemia on alanine and glutamate exchange and ammonia production in 10 anesthetized open-chest domestic swine (46.9 +/- 0.7 kg). Coronary blood flow was controlled through an extracorporal perfusion circuit. After a nonischemic control period (aerobic) the blood flow in the left anterior descending coronary artery was reduced by 60%. Arterial and anterior interventricular venous samples where drawn before and during 35 min of ischemia. Subendocardial blood flow, measured using radiolabeled microspheres, decreased from 1.27 +/- 0.16 to 0.25 +/- 0.09 (ml/g)/min, and left-ventricular wall-thickening fell to 47% of aerobic values. Ischemia resulted in a significant increase in the rate of glucose uptake (p less than 0.05) and a switch to net lactate production (p less than 0.01). Ischemia did not affect the rates of alanine output (-0.9 +/- 1.0 vs. -0.3 +/- 0.3 mumol/min) or glutamate uptake (-0.4 +/- 1.1 vs. 0.3 +/- 0.6 mumol/min), but did increase the venous-arterial difference for ammonia (-4.1 +/- 4.1 to 52.7 +/- 5.5 microM, p less than 0.0001) and the ammonia output (-0.33 +/- 0.24 to 1.34 +/- 0.14 mumol/min, p less than 0.0001). In conclusion, acute ischemia did not stimulate greater alanine output or glutamate uptake. However, acute ischemia did cause an increase in anaerobic glycolysis rate and ammonia output, which reflects a profound disruption in myocardial energy metabolism.

Alanine↗
PubMedDate not supplied

In vivo models of myocardial metabolism during ischemia: application to drug discovery and evaluation.

This review examines the in vivo techniques that are available for evaluation of the metabolic effects and efficacy of agents intended for the treatment of myocardial ischemia. Energy substrate metabolism is complex, and requires simultaneous measurement of a variety of processes in order to obtain a thorough understanding of the biochemical mechanisms underlying any functional response. Small animals (from the mouse to the rabbit) are generally not very useful in the study of cardiac metabolism in vivo because it is not possible to sample the coronary venous drainage and measure the rate of substrate uptake or metabolite efflux. Anesthetized open-chest swine or dog models allows simultaneous serial measurement of myocardial substrate use, and repeated tissue sampling for the activities and contents of key enzymes and metabolites. The swine model is particularly good because pigs, like humans, lack innate collateral vessels, thus one can induce regional myocardial ischemia in the left anterior descending coronary artery and sample the venous effluent from the anterior interventricular vein. In this review the biochemical and physiological methods that can be used in conjunction with this preparation are described.

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