NITRIC OXIDE RELEASE DURING MYOCARDIAL ISCHAEMIA AND REPERFUSION
A.M. Prasan*, H.C.K. McCarron, Y. Zhang, R.W. Jeremy.
Department of Medicine, University of Sydney, Sydney, New South Wales.
Background: Nitric oxide (NO) is widely considered to be protective against myocardial ischaemia/reperfusion (I/R) injury, leading to suggestions that NO supplementation is a desirable therapeutic goal.
Methods: Isolated rabbit hearts (n=6) were perfused at 37ºC with Krebs-Henseleit solution. A quartz electrode (30 mm), coated with porphyrin and nafion was advanced into the coronary sinus. The electrode system was specific for NO and was calibrated using saturated NO solution (1pA current change equated to 1nM [NO] change). Reference and counter electrodes were inserted into the right atrium and organ bath, respectively, and continuous [NO] measurements were made each 500ms by differential amperometry (Bio-Logic Systems). After 10 minutes control perfusion, normothermic low-flow global ischaemia (1-3 ml/min) was imposed for 60 mins, followed by 60 mins reperfusion at mean perfusion pressure 80 mmHg.
Results: left ventricular developed pressure was 82±14 mmHg before ischaemia and 55±16 mmHg after 60 minutes reflow (p<0.01). There was an early increase in NO release from myocardium (peak at 13±4 minutes after onset of ischaemia, peak current = 3.06±0.47nA vs basal current = 2.54±0.36 p<0.01) which declined during later ischaemia and decreased further during reperfusion (Table).
ISCHAEMIA REPERFUSION
|
Peak |
30 mins |
60 mins |
5 mins |
30 mins |
|
|
D[NO](nM) |
513±159 |
282±82† |
146±86# |
159±112# |
-56±69# |
Values are mean±sem. D[NO] = change in [NO] relative to baseline
#p<0.01, †p<0.05 vs peak [NO]
Conclusion: Net increase in NO release for ischaemic myocardium does not support the hypothesis of NO deficiency during ischaemia. Reduced NO release during reperfusion is more likely due to oxygen free radical scavenging than impaired synthesis of NO.
