Author + information
- Received June 22, 2019
- Revision received January 3, 2020
- Accepted January 23, 2020
- Published online March 23, 2020.
- Guiomar Mendieta, MSc, MDa,b,
- Soumaya Ben-Aicha, MSca,
- Manuel Gutiérrez, MD, PhDc,
- Laura Casani, PhDa,c,
- Monika Aržanauskaitė, MDa,
- Francesc Carreras, MD, PhDd,
- Manel Sabate, MD, PhDb,
- Lina Badimon, PhDa,e,∗ and
- Gemma Vilahur, PhDa,e,∗∗ (, )@HospitalSantPau
- aCardiovascular Research Center-ICCC, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain
- bDepartment of Cardiology, Clinic Hospital, Barcelona, Spain
- cRadiology, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain
- dCardiology, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain
- eCiberCV, Institute Carlos III, Barcelona, Spain
- ↵∗Address for correspondence:
Dr. Gemma Vilahur, Cardiovascular ICCC Program, Research Institute–Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Avda. S. Antoni María Claret 167, 08025 Barcelona, Spain.
Background Beyond lipid-lowering, statins exert cardioprotective effects. High-dose statin treatment seems to reduce cardiovascular complications in high-risk patients. The ideal timing and administration regime remain unknown.
Objectives This study compared the cardioprotective effects of intravenous statin administration during myocardial infarction (MI) with oral administration immediately post-MI.
Methods Hypercholesterolemic pigs underwent MI induction (90 min of ischemia) and were kept for 42 days. Animals were distributed in 3 arms (A): A1 received an intravenous bolus of atorvastatin during MI; A2 received an intravenous bolus of vehicle during MI; and A3 received oral atorvastatin within 2 h post-MI. A1 and A3 remained on daily oral atorvastatin for the following 42 days. Cardiac magnetic resonance analysis (days 3 and 42 post-MI) and molecular/histological studies were performed.
Results At day 3, A1 showed a 10% reduction in infarct size compared with A3 and A2 and a 50% increase in myocardial salvage. At day 42, both A1 and A3 showed a significant decrease in scar size versus A2; however, A1 showed a further 24% reduction versus A3. Functional analyses revealed improved systolic performance in A1 compared with A2 and less wall motion abnormalities in the jeopardized myocardium versus both groups at day 42. A1 showed enhanced collagen content and AMP-activated protein kinase activation in the scar, increased vessel density in the penumbra, higher tumor necrosis factor α plasma levels and lower peripheral blood mononuclear cell activation versus both groups.
Conclusions Intravenous administration of atorvastatin during MI limits cardiac damage, improves cardiac function, and mitigates remodeling to a larger extent than when administered orally shortly after reperfusion. This therapeutic approach deserves to be investigated in ST-segment elevation MI patients.
↵∗ Drs. Badimon and Vilahur contributed equally to this work.
This work was supported by the Fundació Investigació Marato TV3 #20154310 (to Dr. Vilahur), Plan Nacional de Salud (PGC2018-094025-B-I00 to Dr. Vilahur and SAF2016-76819-R to Dr. Badimon) from the Spanish Ministry of Science and Innovation, and funds FEDER “Una Manera de Hacer Europa”; a grant from the Spanish Society of Cardiology (Beca FEC Investigación Básica/2016 to Dr. Vilahur); and CIBERCV (to Dr. Badimon). The Generalitat of Catalunya (Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat, 2017 SGR 1480) and the Fundación Investigación Cardiovascular-Fundación Jesus Serra also provided continuous support. Drs. Badimon and Vilahur are the authors of the patent that includes the use of statins for intravenous administration. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received June 22, 2019.
- Revision received January 3, 2020.
- Accepted January 23, 2020.
- 2020 The Authors