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The Effect of Agmatine Administration on Ischemic-Reperfused Isolated Rat Heart

Jacob George, MD

Cardiovascular Research Laboratory, Department of Cardiology, Tel-Aviv Medical Center, Israel

Yoram Wollman, PhD

Department of Nephrology, Tel-Aviv Medical Center, Israel

Itchak Shapira, MD

Shlomo Laniado, MD

Gad Keren, MD

Cardiovascular Research Laboratory, Department of Cardiology, Tel-Aviv Medical Center, Israel

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 µM/L Ag pre-ischemia (n=7); group 2, hearts receiving 100 µM/L Ag preand post-ischemia, (n=7); group 3, hearts receiving 250 µM/L Ag preischemia (n=7); group 4, hearts receiving 250 µM/L Ag preand 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.

Conclusion: Low doses of Ag given preand post-ischemia, and high doses given only preischemia have favorable, protective effects on the hemodynamic recovery of isolated rat heart undergoing global ischemia and reperfusion.

Key Words: polyamines • agmatine • ischemia • isolated heart

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 6, No. 1, 37-45 (2001)
DOI: 10.1177/107424840100600105


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