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Myocardial contractile function during postischemic low-flow reperfusion: critical thresholds of NADH and O₂ delivery

¹Department of Emergency Medicine, ²Dorothy M. Davis Heart and Lung Research Institute, ³Department of Biophysics, and ⁴Division of Pulmonary and Critical Care Medicine, Ohio State University, Columbus, Ohio 43210

Submitted 12 May 2003 ; accepted in final form 2 September 2003

The degree of myocardial oxygen delivery (DO₂) that is necessary to reestablish functional contractile activity after short-term global ischemia in heart is not known. To determine the relationship between DO₂ and recovery of contractile and metabolic functions, we used tissue NADH fluorometric changes to characterize adequacy of reperfusion flow. Isolated perfused rat hearts were subjected to global ischemia and were reperfused at variable flow rates that ranged from 1 to 100% of baseline flow. Myocardial function and tissue NADH changes were continuously measured. NADH fluorescence rapidly increased and plateaued during ischemia. A strong inverse logarithmic correlation between NADH fluorescence and reperfusion DO₂ was demonstrated (r = –0.952). Left ventricular function (rate-pressure product) was inversely related to NADH fluorescence at reperfusion flows from 25 to 100% of baseline (r = –0.922) but not at lower reperfusion flow levels. An apparent reperfusion threshold of 25% of baseline DO₂ was necessary to resume contractile function. At very low reperfusion flows (1% of baseline), another threshold flow was identified at which NADH levels increased beyond that observed during global ischemia (3.4 ± 3.0%, means ± SE, n = 9), which suggests further reduction of the cellular redox state. This NADH increase at 1% of baseline reperfusion flow was blocked by removing glucose from the perfusate. NADH fluorescence is a sensitive indicator of myocardial cellular oxygen utilization over a wide range of reperfusion DO₂ values. Although oxygen is utilized at very low flow rates, as indicated by changes in NADH, a critical threshold of 25% of baseline O₂ is necessary to restore contractile function after short-term global ischemia.

ischemia; oxygen delivery; cardiac function; glucose

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