Increasing cardiac contractility after myocardial infarction exacerbates cardiac injury and pump dysfunction
Authors: Steven R Houser
Remus Berretta
Abdelkarim Sabri
Mikhail Kolpakov
Naser Jaleel
Wei Wang
Hiroyuki Nakayama
Xiaoying Zhang
Mingxin Tang
Erhe Gao
Annarosa Leri
Walter J Koch
Jan Kajstura
Hongyu Zhang
Xiongwen Chen
Scott M MacDonnell
David M Harris
Jeffery D Molkentin
Yingxin Li
Journal: Circulation Research (2010)
Discipline: CLINICAL MEDICINE
Keywords: Myocardial infarction; heart failure; myocyte death; myocyte contractility; post-MI cardiac pump dysfunction
Affiliations: Temple University, School of Medicine, Philadelphia, PA 19140, USA.

Abstract:  Rationale: Myocardial infarction (MI) leads to heart failure (HF) and premature death. The respective roles of myocyte death and depressed myocyte contractility in the induction of HF after MI have not been clearly defined and are the focus of this study. Objectives: We developed a mouse model in which we could prevent depressed myocyte contractility after MI and used it to test the idea that preventing depression of myocyte Ca(2+)-handling defects could avert post-MI cardiac pump dysfunction. Methods and results: MI was produced in mice with inducible, cardiac-specific expression of the Œ≤2a subunit of the L-type Ca(2+) channel. Myocyte and cardiac function were compared in control and Œ≤2a animals before and after MI. Œ≤2a myocytes had increased Ca(2+) current; sarcoplasmic reticulum Ca(2+) load, contraction and Ca(2+) transients (versus controls), and Œ≤2a hearts had increased performance before MI. After MI, cardiac function decreased. However, ventricular dilation, myocyte hypertrophy and death, and depressed cardiac pump function were greater in Œ≤2a versus control hearts after MI. Œ≤2a animals also had poorer survival after MI. Myocytes isolated from Œ≤2a hearts after MI did not develop depressed Ca(2+) handling, and Ca(2+) current, contractions, and Ca(2+) transients were still above control levels (before MI). Conclusions: Maintaining myocyte contractility after MI, by increasing Ca(2+) influx, depresses rather than improves cardiac pump function after MI by reducing myocyte number. 

Retracted: No

PubPeer comments:
 2020 Correction. https: www.ahajournals.org doi 10.1161 RES.0000000000000353 For the article u201cIncreasing Cardiac Contractility After Myocardial Infarction Exacerbates Cardiac Injury and Pump Dysfunction (Circ Res. 2010;107:800-809. doi: 10.1161 CIRCRESAHA.110.219220), an investigation by Harvard Medical School and Brigham and Womenu2019s Hospital (BWH) has determined that there were issues with some of the data provided by the authors at that institution and reported in the Supplemental Material for the article, specifically Online Figure II. As the original primary data was generated elsewhere and included as part of the Harvard Medical School BWH investigation, the authors performed a new set of experiments to generate new data to correct Online Figure II. To replicate the original findings the authors conducted new experiments on 4 u03b22a and 3 Wild Type control mice. Myocardial infarction (MI) was induced by the techniques described in the original study, by the same surgeon. Since all of the data in the original Online Figure II was from animals 3 days after MI, the authors focused on this time period. Hearts were fixed and prepared for histological analyses as described previously. All methods were identical to those used in the original study. Hearts were perfusion fixed, sectioned, stained and analyzed as described in the original report. Investigators were blinded to the type of heart they were studying until all measurements were completed. The revised Online Figure II and quantitation are consistent with the original finding of an increase in apoptotic cell death in the u03b22a mice in the infarct border zone 3 days after MI. The new data showed that the number of apoptotic cardiac cells 3 days after MI were almost identical in the original and newly studied mice. Online Figure II and the corresponding legend have been corrected to reflect the new results. The American Heart Association and all co-authors have approved the new data and corrected Online Figure II. The corrected version of this article is available at www.ahajournals.org doi full CIRCRESAHA.110.219220 ,