Administration of the Rho-kinase inhibitor fasudil before ischemia or just after reperfusion, but not 30 min after reperfusion, protects the stunned myocardium in swine.
OBJECTIVE
We assessed the effect of administration time for fasudil treatment of the stunned myocardium in 40 anesthetized open chest swine.


METHODS
All swine were subjected to 12 min ischemia followed by reperfusion to generate stunned myocardium. Group A (n = 11) received saline in place of fasudil both before ischemia and after reperfusion. Group B (n = 10) received 30 min intravenous fasudil at a rate of 13 mug/kg/min starting 45 min before ischemia and received saline after reperfusion. Groups C (n = 10) and D (n = 9) received saline before ischemia, and received fasudil at a rate of 13 microg kg(-1) min(-1) starting just before reperfusion in group C and 30 min after reperfusion in group D. In both groups, treatment lasted 30 min. Myocardial contractility was assessed by percent segment shortening (%SS).


CONCLUSIONS
Three swine in group A, 2 swine in each of groups B and C, and one swine in group D had ventricular fibrillation or tachycardia after reperfusion and were excluded from further analysis. The changes of %SS from baseline at 90 min after reperfusion in groups B and C were 68 +/- 8% and 75 +/- 8%, respectively, which were significantly higher than in group A or D (47 +/- 10% or 43 +/- 8%).


CONCLUSIONS
We conclude that fasudil administered before ischemia or just after reperfusion, but not 30 min after reperfusion, protects the stunned myocardium.
Shibata
Itsuko
I
Department of Anesthesiology, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Yoshitomi
Osamu
O
Use
Tadasuke
T
Ureshino
Hiroyuki
H
Cho
Sungsam
S
Maekawa
Takuji
T
Hara
Tetsuya
T
Sumikawa
Koji
K
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005260:Female; D007262:Infusions, Intravenous; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control*; D017682:Myocardial Stunning / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D013552:Swine; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D002316:Cardiotonic Agents; D047428:Protein Kinase Inhibitors; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases; C049347:fasudil