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The Effect of Agmatine on Ischemic and Nonischemic Isolated Rat Heart

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

Ariel Finkelstein

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

Jacob Gurevich

Department of Thoracic and Cardiovascular Surgery, Sourasky Tel-Aviv Medical Center

Eliau Brazowski

Department of Thoracic and Cardiovascular Surgery, Sourasky Tel-Aviv Medical Center

Faina Rosenfeld

Institute of Pathology, Diagnostic and Cancer Research Center, Tel-Aviv Medical Center, Tel-Aviv, Israel

Itchak Shapira

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

Jacob George

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

Shlomo Laniado

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

Gad Keren

Institute of Pathology, Diagnostic and Cancer Research Center, Tel-Aviv Medical Center, Tel-Aviv, Israel

Objective: The natural polyamines play a protective role during ischemic injury. We stud ied the effects of agmatine on ischemic and nonischemic isolated rat hearts.

Methods: Thirty-one rats were randomly assigned to one of four experimental groups. Six teen rats were injected with saline (group 1, n = 9; group 3, n = 7), and 15 rats were injected with 100 mg/kg of agmatine (group 2, n = 8; group 4, n = 7). Injections were given twice: 24 hours and 1 hour before the experiment. Using the modified Langendorf model, rat hearts were perfused with Krebs-Henseleit solution for 105 minutes during phase 1 of the experi ment (groups 1 and 2). During phase 2, hearts were exposed to 45 minutes of global ischemia (groups 3 and 4).

Results: During phase 1, no statistically significant differences were observed between the agmatine and the control groups. During phase 2, agmatine caused a significant increase in left ventricular pressure (P < .003). At the end of reperfusion, P(max) was 111 % ± 10% from the baseline levels versus only 82% ± 5% in the control group. After 20 minutes of reper fusion, dP/dt (first-time derivative of the ventricular pressure) in the agmatine group reached full recovery of 106% ± 12% versus only 64% ± 14% in the saline group (P = .059). Agmatine also caused a significant increase in coronary flow rate (P < .004) through out the reperfusion period. Quantitative immunohistochemical staining disclosed reduced cell damage in the agmatine-treated hearts (P < .02) versus the control group.

Conclusion: Agmatine injection given before induced ischemia improves hemodynamic recovery by mechanisms that may be attributed to its vasodilatory properties.

Key Words: polyamines • agmatine • ischemia • isolated heart.

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 4, No. 3, 151-158 (1999)
DOI: 10.1177/107424849900400304


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