Abstract 2631: Reactive Oxygen Species (ROS) Generation and Recovery Of Myocardial Function After Low Flow Reperfusion In The Whole Heart
We hypothesize that some levels of CPR generated low-flow may in fact worsen myocardial recovery compared with no-flow of similar duration. To test this hypothesis we determined the effect of low-flow reperfusion simulating CPR, on myocardial ROS production, cellular redox changes and recovery of contractile function in the whole heart.
Methods: Isolated perfused male Sprague Dawley rat hearts were subjected to either 20 minutes of global ischemia followed by full reperfusion with 85 mm Hg perfusion (Control) or 3 minutes of global ischemia followed by 17 minutes of low-flow with perfusion pressure of 20 mm Hg before full reperfusion at 20 minutes (CPR model). Full reperfusion was for 30 minutes in all hearts. A fiberoptic spectrometer measured fluorescence on the left ventricular wall. Hearts were preloaded with 2 probes, dihydrofluorescein (an intracellular probe) and amplex red (an extracellular probe), both of which are oxidized and fluoresce in the presence of reactive oxygen species (ROS). NADH autofluorescence, a measure of cellular redox state, and LV contractile function were continuously measured. Changes in fluorescence and function were normalized to baseline and compared between groups using ANOVA.
Results: At the end of the 30 minute reperfusion period, rate pressure product (RPP in mmHg/min) was significantly reduced in CPR modeled hearts (RPP = 6,733 ± 3,720) (p<0.01) as compared to Control (RPP = 17,000 ± 1,873). CPR type low-flow resulted in a significant decrease in [NADH] compared with control (p<0.05). In CPR modeled hearts, a reduction in the intracellular ROS burst (fluorescein signal), but an increase in the extracellular ROS burst (amplex red signal) was seen at the onset of full reperfusion (20 minutes) compared with Control (p<0.01).
Conclusions: It is well understood that under CPR conditions, the level of low-flow can be quite variable. However, at some level of low-flow, recovery of myocardial function may be worse than recovery following a similar duration of no-flow. This depressed myocardial function may be ROS mediated, as this level of low-flow alters the compartmentalizded ROS burst seen at full reperfusion.