A Na+-H+ exchange inhibitor (SM-20550) protects from microvascular deterioration and myocardial injury after reperfusion.
Na+-H+ exchange inhibitors may reduce myocardial damage after reperfusion. However, their effects on microvascular deterioration are not known. We examined the potency of a novel Na+-H+ exchange inhibitor, SM-20550 [ N-(Aminoiminomethyl)-1,4-dimethyl-1H-indole-2-carboxamide methanesulfonate], and its effects on microvascular damage after reperfusion. In an in vitro study, the Na+-H+ exchange inhibiting activity of SM-20550 was about 10 times greater than that of ethylisopropyl amiloride. In in vivo experiments, we occluded the left circumflex coronary artery in 29 dogs for 2 h and then reperfused for 5 h. SM-20550 was administered either before ischemia (n = 11) or before reperfusion (n = 7). Another 11 dogs served as controls. We found that SM-20550 not only improved coronary vasodilator responses to acetylcholine and adenosine after reperfusion, but also reduced infarct size (P < 0.01). Intramyocardial bleeding, which should reflect microvascular damage, was not found in dogs with SM-20550 treatment. Infarct size was correlated inversely with collateral blood flow in control (both, P < 0.01) but not in SM-20550-treated animals. Furthermore, SM-20550 significantly suppressed ventricular fibrillation during both ischemia and reperfusion. These results suggest that protective effects of Na+-H+ exchange inhibitors on reperfused myocardium are due at least in part to microvascular protection.
Ito
Y
Y
The Second Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan.
Imai
S
S
Ui
G
G
Nakano
M
M
Imai
K
K
Kamiyama
H
H
Naganuma
F
F
Matsui
K
K
Ohashi
N
N
Nagai
R
R
D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000578:Amidines / Q000494:pharmacology*; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D004285:Dogs; D005260:Female; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009203:Myocardial Infarction / Q000473:pathology; D017202:Myocardial Ischemia / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D000578:Amidines; D007211:Indoles; C121094:SM 20550; D017923:Sodium-Hydrogen Exchangers; D014665:Vasodilator Agents; D009195:Peroxidase; D000241:Adenosine; D000109:Acetylcholine