Reduction in the level of cardiac cyclic GMP worsens contractile delay in myocardial stunning.
We tested the hypothesis that a reduction in the level of myocardial cyclic GMP would worsen the contractile delay associated with myocardial stunning. Two groups of 12 anesthetized open-chest New Zealand white rabbits were utilized. Myocardial stunning was produced by two 15-min occlusions of the left anterior descending coronary artery followed by 15 min of reperfusion. Either control vehicle (saline + 1% DMSO) or 1H-[1,2,4]oxadiazolo[4, 3-a]quinoxalin-1-one (ODQ 10(-4) M, a guanylate cyclase inhibitor) was topically applied to the left ventricular surface of the rabbit hearts. Left ventricular and aortic pressures along with wall thickness parameters were determined. Coronary blood flow (microspheres) and O(2) extraction (microspectrophotometry) were used to determine myocardial O(2) consumption. Myocardial stunning was observed in the control group through an increased delay in onset of wall thickening (46.2 +/- 7.3 vs 76.6 +/- 17.5 ms). There was no significant effect of stunning on the rate of wall thickening (21.8 +/- 9.5 vs 18.1 +/- 3.4 mm/s) or O(2) consumption (stun 4.6 +/- 0.6, control 4.8 +/- 0.4 ml O(2)/min/100 g). After treatment with ODQ 10(-4) M, both delay (43.9 +/- 9.6 vs 134.1 +/- 30.0 ms) and myocardial O(2) consumption (stun 5.9 +/- 0.6, control 5.9 +/- 0. 7) increased significantly compared to control. There was no significant change in the rate of wall thickening. We conclude that decreasing cyclic GMP worsens stunning by increasing delay in onset of wall thickening and increasing local O(2) costs in the stunned region.
Patel
K N
KN
Heart and Brain Circulation Laboratory, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854-5635, USA.
Weiss
H R
HR
Scholz
P M
PM
D000818:Animals; D003326:Coronary Circulation / Q000502:physiology; D006152:Cyclic GMP / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D017682:Myocardial Stunning / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology; D009569:Nitric Oxide / Q000378:metabolism; D010069:Oxadiazoles / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D011817:Rabbits
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D011810:Quinoxalines; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D006152:Cyclic GMP