After a 30-minute equilibration period, the hearts were submitted to low-flow
ischemia for 60 minutes followed by reperfusion for 30 minutes. Functional and metabolic parameters were followed in hearts perfused with or without inhibitors of
NO synthase or NO precursors, which were added 15 minutes before
ischemia but were absent during reperfusion.
Ischemic contracture was delayed and reduced in hearts perfused with 1 mumol/L L-N-monomethylarginine (
L-NMMA) or 1 mumol/L L-N-
arginine methylester, two inhibitors of
NO synthase, but not with D-N-monomethylarginine, the inactive enantiomer of
L-NMMA. The protection was suppressed by addition to the perfusate containing
L-NMMA of 1 mmol/L
L-arginine or 0.1 mmol/L
sodium nitroprusside but not by addition of 10 mumol/L
8-bromo cGMP, a cGMP analogue. The functional protection by 1 mumol/L
L-NMMA was related to a stimulation of glycolysis from exogenous
glucose and a preservation of the
glycogen stores. This resulted in a better maintenance of high-energy
phosphates and a lower
acidosis as measured by 31P nuclear magnetic resonance spectroscopy. During reperfusion, functional recovery was more than doubled, and
enzyme release was halved in
L-NMMA-treated hearts compared with controls. The functional and metabolic protection was maximal at 1 nmol/L to 1 mumol/L
L-NMMA, ie, below the vasoactive concentrations of the inhibitor.
CONCLUSIONS: