The effect of agmatine administration on ischemic-reperfused isolated rat heart.
BACKGROUND
The natural polyamine Agmatine (Ag) plays a significant role in protection of nerve cell ischemic injury. A previous report indicated that Ag given intraperitoneally to rats enhanced the recovery of the heart from ischemic injury. Based on this initial observation, a larger investigation was undertaken to explore a dose-response effect and possible mechanisms underlying the protective effects.


METHODS
Using the modified Langendorff model, 36 isolated hearts were divided into five groups: group 1, hearts receiving 100 microM/L Ag pre-ischemia (n=7); group 2, hearts receiving 100 microM/L Ag pre- and post-ischemia, (n=7); group 3, hearts receiving 250 microM/L Ag pre-ischemia (n=7); group 4, hearts receiving 250 microM/L Ag pre- and postischemia (n=7); and group 5, hearts receiving Krebs-Hensleit solution served as control (n=8). The study design included 20 minutes of perfusion, 30 minutes of global ischemia, and 30 minutes of reperfusion.


RESULTS
After ischemia, group 2 developed higher left ventricular pressure P(max) (P<0.01), improved first-derivative of the rise (dP/dt max; P<0.02), and fall (dP/dt min; P<0.04) in left ventricular pressure, and the area calculated under the left-ventricle developed pressure curve (pressure-time integral; P<0.015), but coronary flow was not significantly increased (P=0.06) compared to the control group. Group 1 had improved diastolic recovery: dP/dt min (P<0.05) and coronary flow (P<0.03), compared with the control group. Group 3 had improved P(max) (P<0.01), dP/dt min (P<0.01), and coronary flow (P<0.02); group 4 had no improvement in all hemodynamic parameters.


CONCLUSIONS
Low doses of Ag given pre- and post-ischemia, and high doses given only pre-ischemia have favorable, protective effects on the hemodynamic recovery of isolated rat heart undergoing global ischemia and reperfusion.
Greenberg
S
S
Cardiovascular Research Laboratory, Department of Cardiology, Tel-Aviv Medical Center, Israel.
George
J
J
Wollman
Y
Y
Shapira
I
I
Laniado
S
S
Keren
G
G
D000376:Agmatine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics; D007263:Infusions, Parenteral; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications* / Q000662:veterinary; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control* / Q000662:veterinary; D051381:Rats; D017208:Rats, Wistar; D016277:Ventricular Function, Left
D000376:Agmatine