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Isoproterenol-Induced Myocardial Injury: A Systematic Comparison of Subcutaneous versus Intraperitoneal Delivery in a Rat Model


Address for correspondence and reprint requests: Jon C. George, M.D., Division of Cardiovascular Medicine, Temple University Hospital, 9th Floor Parkinson Pavilion, Philadelphia, PA 19140. Fax: (215) 707-4521; E-mail:


Introduction: Isoproterenol (ISO)-induced myocardial injury is widely used as an experimental animal model; however, the optimal route of delivery, i.e., subcutaneous (SC) versus intraperitoneal (IP) has not been clarified. We systematically compared changes in cardiac function (echocardiography, Doppler and strain imaging) and exercise capacity induced by ISO via SC versus IP delivery. Methods: Twelve rats were used in this study and classified into three groups: Control (n = 2), SC-ISO (n = 5), and IP-ISO (n = 5), each receiving serial injections of ISO (100 mcg/kg) for 5 days (days 1–5). All rats underwent echocardiographic analysis of left ventricular function and functional capacity (FC) assessment on a treadmill protocol at baseline and post treatment. Hearts were excised and weighed at the end of the study. Results: Left ventricular (LV) systolic and diastolic dysfunctions were adequately induced by both SC and IP delivery: ≥13% reduction in fractional shortening, ≥12% increase in wall motion score index, and ≥35% increase in myocardial performance index; ≥49% increase in E/A ratio; ≥9% decline in anterior wall tissue velocity; ≥12% decline in circumferential and radial tissue strain and strain rates; ≥20% decline in FC; and ≥40% increase in echocardiographic LV mass and gross heart weight in both groups. Conclusion: Short-duration ISO administration with serial injections via SC and IP routes induces significant myocardial dysfunction and impairs FC with few differences between both modalities. (Echocardiography 2010;27:716-721)