Beneficial effects of H290/51, a new lipid peroxidation inhibitor, on functional recovery after ischemia and reperfusion in isolated cold-arrested rat hearts.
Lipid peroxidation is one of the major mechanisms involved in free radical-mediated postischemic myocardial injury. In the present study, a newly synthetized lipid peroxidation inhibitor H290/51 [cis-7methyl-9-methoxy-5,5a,b,10b- tetrahydroindeno(2,1-6 indole)] was evaluated for its effects on myocardial functional recovery during reperfusion after 30-min global ischemia in isolated cold-arrested rat hearts. Administration of 200 and 800 nM H290/51 at initiation of global ischemia markedly improved the functional recovery, whereas 50 nM H290/51 had no significant effects. The percent recovery of cardiac output (CO), left ventricular developed pressure (LVDP), and LVdP/dtmax at the end of the 30-min reperfusion period in the working mode was much higher in the groups receiving 200 and 800 nM H290/51 than that in vehicle group (CO 73 +/- 5 and 60 +/- 5 vs. 23 +/- 7%; LVDP 79 +/- 5 and 73 +/- 8 vs. 43 +/- 10%; LV dP/dtmax 78 +/- 5 and 69 +/- 4 vs. 45 +/- 10%). The indenoindole compound H290/51 reduced ischemia/reperfusion-induced cardiac dysfunction.
Wang
Q D
QD
Department of Cardiology, Karolinska Hospital, Stockholm, Sweden.
Uriuda
Y
Y
Li
X S
XS
Nordlander
R
R
Sjöquist
P O
PO
Rydén
L
L
D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left / Q000187:drug effects
D000975:Antioxidants; C088233:H290-51; D007211:Indoles