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The time window for therapy with peptide nanofibers combined with autologous bone marrow cells in pigs after acute myocardial infarction.

Chang MY, Chang CH, Chen CH, Cheng B, Lin YD, Luo CY, Wu HL, Yang YJ, Chen JH, Hsieh PC - PLoS ONE (2015)

Bottom Line: NS) improvements, respectively.The +dP/dt and -dP/dt, infarct size and interstitial collagen content were also improved in the NF/MNC-1D and -4D groups but not in the -7D group.Injection of NF/MNC at 1 or 4 days, but not at 7 days post-MI, improves cardiac performance and prevents ventricular remodeling, confirming the importance of early intervention when using this therapy for acute MI.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan.

ABSTRACT

Background: We previously showed that injection of peptide nanofibers (NF) combined with autologous bone marrow mononuclear cells (MNC) immediately after coronary artery ligation improves cardiac performance in pigs. To evaluate the clinical feasibility, this study was performed to determine the therapeutic time window for NF/MNC therapy in acute myocardial infarction (MI).

Methods and results: A total of 45 adult minipigs were randomly grouped into 7 groups: sham or MI plus treatment with NS (normal saline), or NF or MNC alone at 1 day (1D) post-MI, or NF/MNC at 1, 4, or 7 days post-MI (N≥6). Cardiac function was assessed by echocardiography and ventricular catheterization. Compared with the NS control, pigs treated with NF/MNC at 1 day post-MI (NF/MC-1D) had the greatest improvement in left ventricle ejection fraction (LVEF; 55.1±1.6%; P<0.01 vs. NS) 2 months after MI. In contrast, pigs treated with either NF/MNC-4D or NF/MNC-7D showed 48.9±0.8% (P<0.05 vs. NS) and 43.5±2.3% (n.s. vs. NS) improvements, respectively. The +dP/dt and -dP/dt, infarct size and interstitial collagen content were also improved in the NF/MNC-1D and -4D groups but not in the -7D group. Mechanistically, MNC quality and the states of systemic inflammation and damaged heart tissue influence the therapeutic efficiency of NF/MNC therapy, as revealed by another independent study using 16 pigs.

Conclusions: Injection of NF/MNC at 1 or 4 days, but not at 7 days post-MI, improves cardiac performance and prevents ventricular remodeling, confirming the importance of early intervention when using this therapy for acute MI.

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Related in: MedlinePlus

NF/MNC injection protects myocardial function depending on the injection time.(A) Following surgical ligation of the mid-left anterior descending coronary artery to induce MI, the pigs underwent intramyocardial injection of NF and/or MNC at 1, 4, or 7 days and were sacrificed at 2 months after MI. Echocardiography and ventricular catheterization were used to measure cardiac function. (B) Showing are histograms of the left ventricle ejection fraction (LVEF, %), (C) the interventricular septum (IVS) systolic, and (D) diastolic thicknesses. Data are presented as the mean±SEM. *P<0.05, **P<0.01, ***P<0.001.
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pone.0115430.g002: NF/MNC injection protects myocardial function depending on the injection time.(A) Following surgical ligation of the mid-left anterior descending coronary artery to induce MI, the pigs underwent intramyocardial injection of NF and/or MNC at 1, 4, or 7 days and were sacrificed at 2 months after MI. Echocardiography and ventricular catheterization were used to measure cardiac function. (B) Showing are histograms of the left ventricle ejection fraction (LVEF, %), (C) the interventricular septum (IVS) systolic, and (D) diastolic thicknesses. Data are presented as the mean±SEM. *P<0.05, **P<0.01, ***P<0.001.

Mentions: The experimental flow chart is shown in Fig. 2A. Again we confirmed by echocardiography that the LVEF decreased significantly immediately after the MI surgery prior to the injection of any materials (Fig. 2B). Autologous MNCs were extracted, mixed with NFs and injected into the infarct area at 1, 4, or 7 days post-MI. Two months after MI, echocardiography revealed that the LVEF of the MI+NF/MNC-1D group (55.1±1.6%) was significantly higher than that of the NS (44.3±1.4%), NF-1D (46.5±0.5%), and MNC-1D (46.3±0.4%) groups (P<0.001, Fig. 2B). Interestingly, the MI+NF/MNC-4D group (48.5±0.8%) also had a greater LVEF (P<0.01), but the MI+NF/MNC-7D group (45.3±1.9%) demonstrated no improvement in the LVEF compared with the control group or the groups that received NF or MNC alone. Consistent with these results, the interventricular septum (IVS) systolic and diastolic thicknesses, which were verified by echocardiography, also displayed a similar trend of improvement due to NF/MNC injection at 1 day or 4 days, but not at 7 days post-MI (Fig. 2C and 2D).


The time window for therapy with peptide nanofibers combined with autologous bone marrow cells in pigs after acute myocardial infarction.

Chang MY, Chang CH, Chen CH, Cheng B, Lin YD, Luo CY, Wu HL, Yang YJ, Chen JH, Hsieh PC - PLoS ONE (2015)

NF/MNC injection protects myocardial function depending on the injection time.(A) Following surgical ligation of the mid-left anterior descending coronary artery to induce MI, the pigs underwent intramyocardial injection of NF and/or MNC at 1, 4, or 7 days and were sacrificed at 2 months after MI. Echocardiography and ventricular catheterization were used to measure cardiac function. (B) Showing are histograms of the left ventricle ejection fraction (LVEF, %), (C) the interventricular septum (IVS) systolic, and (D) diastolic thicknesses. Data are presented as the mean±SEM. *P<0.05, **P<0.01, ***P<0.001.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4355625&req=5

pone.0115430.g002: NF/MNC injection protects myocardial function depending on the injection time.(A) Following surgical ligation of the mid-left anterior descending coronary artery to induce MI, the pigs underwent intramyocardial injection of NF and/or MNC at 1, 4, or 7 days and were sacrificed at 2 months after MI. Echocardiography and ventricular catheterization were used to measure cardiac function. (B) Showing are histograms of the left ventricle ejection fraction (LVEF, %), (C) the interventricular septum (IVS) systolic, and (D) diastolic thicknesses. Data are presented as the mean±SEM. *P<0.05, **P<0.01, ***P<0.001.
Mentions: The experimental flow chart is shown in Fig. 2A. Again we confirmed by echocardiography that the LVEF decreased significantly immediately after the MI surgery prior to the injection of any materials (Fig. 2B). Autologous MNCs were extracted, mixed with NFs and injected into the infarct area at 1, 4, or 7 days post-MI. Two months after MI, echocardiography revealed that the LVEF of the MI+NF/MNC-1D group (55.1±1.6%) was significantly higher than that of the NS (44.3±1.4%), NF-1D (46.5±0.5%), and MNC-1D (46.3±0.4%) groups (P<0.001, Fig. 2B). Interestingly, the MI+NF/MNC-4D group (48.5±0.8%) also had a greater LVEF (P<0.01), but the MI+NF/MNC-7D group (45.3±1.9%) demonstrated no improvement in the LVEF compared with the control group or the groups that received NF or MNC alone. Consistent with these results, the interventricular septum (IVS) systolic and diastolic thicknesses, which were verified by echocardiography, also displayed a similar trend of improvement due to NF/MNC injection at 1 day or 4 days, but not at 7 days post-MI (Fig. 2C and 2D).

Bottom Line: NS) improvements, respectively.The +dP/dt and -dP/dt, infarct size and interstitial collagen content were also improved in the NF/MNC-1D and -4D groups but not in the -7D group.Injection of NF/MNC at 1 or 4 days, but not at 7 days post-MI, improves cardiac performance and prevents ventricular remodeling, confirming the importance of early intervention when using this therapy for acute MI.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan.

ABSTRACT

Background: We previously showed that injection of peptide nanofibers (NF) combined with autologous bone marrow mononuclear cells (MNC) immediately after coronary artery ligation improves cardiac performance in pigs. To evaluate the clinical feasibility, this study was performed to determine the therapeutic time window for NF/MNC therapy in acute myocardial infarction (MI).

Methods and results: A total of 45 adult minipigs were randomly grouped into 7 groups: sham or MI plus treatment with NS (normal saline), or NF or MNC alone at 1 day (1D) post-MI, or NF/MNC at 1, 4, or 7 days post-MI (N≥6). Cardiac function was assessed by echocardiography and ventricular catheterization. Compared with the NS control, pigs treated with NF/MNC at 1 day post-MI (NF/MC-1D) had the greatest improvement in left ventricle ejection fraction (LVEF; 55.1±1.6%; P<0.01 vs. NS) 2 months after MI. In contrast, pigs treated with either NF/MNC-4D or NF/MNC-7D showed 48.9±0.8% (P<0.05 vs. NS) and 43.5±2.3% (n.s. vs. NS) improvements, respectively. The +dP/dt and -dP/dt, infarct size and interstitial collagen content were also improved in the NF/MNC-1D and -4D groups but not in the -7D group. Mechanistically, MNC quality and the states of systemic inflammation and damaged heart tissue influence the therapeutic efficiency of NF/MNC therapy, as revealed by another independent study using 16 pigs.

Conclusions: Injection of NF/MNC at 1 or 4 days, but not at 7 days post-MI, improves cardiac performance and prevents ventricular remodeling, confirming the importance of early intervention when using this therapy for acute MI.

Show MeSH
Related in: MedlinePlus