Pharmacological and Cardioprotective Interventions Potent Long-Term Cardioprotective Effects of Single Low-Dose Insulin-Like Growth Factor-1 Treatment Postmyocardial Infarction

Chronic heart failure after ST-segment–elevation myocardial infarction (MI) remains a public health burden despite current percutaneous interventional and pharmacological treatment. Strategies to reduce infarct size are needed but remain a therapeutic challenge. Insulin-like growth factor-1 (IGF-1) is a known central regulator of cardiac function with prosurvival, proliferative, and differentiation effects in the heart. However, clinical trials of IGF-1related compounds in heart failure were abandoned >1 decade ago because of the side-effect profile of chronically administered drug and presumed therapeutic inefficacy. Importantly, IGF-1 has never been tested clinically for its acute prosurvival effects in the context of MI. The current study examined the potency of IGF-1 at a lower dose and as a single injection that would not be expected to cause the side-effects manifested in previous IGF-1-related studies. Moreover, the authors treated large MIs in pigs in the reperfusion phase to more closely model the scale, hemodynamic, and functional parameters seen in the clinical ST-segment elevation MI setting. They show here that a 1-time bolus of low-dose IGF-1 has potent acute cardioprotective effects on cardiomyocytes within the infarct zone associated with activation of classic prosurvival signaling pathways and that acute cell salvage translates into long-term preservation of cardiac structure and function without the significant side-effects seen in previous trials. These data suggest that low-dose IGF-1 may be a useful adjunctive therapy for acute MI. Further study is warranted to investigate whether low-dose IGF-1 is a safe and effective treatment, particularly in patients with large MIs at risk of developing long-term heart failure.