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Dodecafluoropentane emulsion elicits cardiac protection against myocardial infarction through an ATP-Sensitive K+ channel dependent mechanism.

Strom J, Swyers T, Wilson D, Unger E, Chen QM, Larson DF - Cardiovasc Drugs Ther (2014)

Bottom Line: DDFPe treatment reduced infarct size by approximately 72% (36.9 ± 4.2% for vehicle vs 10.4 ± 2.3% for DDFPe; p < 0.01; n = 6-8) at 24 h.Serum cTnI levels were similarly reduced by DDFPe (35.0 ± 4.6 ng/ml for vehicle vs 15.8 ± 1.6 ng/ml for DDFPe; p < 0.01; n = 6-8).Our data indicate a cardiac protective role of DDFPe that persists beyond its retention time in the body and is dependent on mitoK(ATP), an important mediator of ischemic preconditioning induced cardiac protection.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology; College of Medicine, University of Arizona, 1501 N. Campbell Ave, Tucson, AZ, 85724, USA.

ABSTRACT

Purpose: Dodecafluoropentane emulsion (DDFPe) is a perfluorocarbon with high oxygen dissolving, transport, and delivery capacity that may offer the potential to limit ischemic injury prior to clinical reperfusion. Here we investigated the cardiac protective potential of DDFPe in a mouse model of myocardial infarction.

Methods: Myocardial infarction was initiated by permanent ligation of the left anterior descending (LAD) coronary artery. Mice were administered vehicle or 5-hydroxydecanoate (5-HD) intravenously 10 min before LAD occlusion followed by a single intravenous administration of vehicle or DDFPe immediately after occlusion. Heart tissue and serum samples were collected 24 after LAD occlusion for measurement of infarct size and cardiac troponin I (cTnI) levels, respectively.

Results: DDFPe treatment reduced infarct size by approximately 72% (36.9 ± 4.2% for vehicle vs 10.4 ± 2.3% for DDFPe; p < 0.01; n = 6-8) at 24 h. Serum cTnI levels were similarly reduced by DDFPe (35.0 ± 4.6 ng/ml for vehicle vs 15.8 ± 1.6 ng/ml for DDFPe; p < 0.01; n = 6-8). Pretreatment with 5-HD, a mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) inhibitor, blocked the reduction in infarct size (29.2 ± 4.4% for 5-HD vs 35.4 ± 7.4% for 5-HD+DDFPe; p = 0.48; n = 6-8) and serum cTnI levels (27.4 ± 5.1 ng/ml for 5-HD vs 34.6 ± 5.3 ng/ml for 5-HD+DDFPe; p = 0.86; n = 6-8) by DDFPe.

Conclusion: Our data indicate a cardiac protective role of DDFPe that persists beyond its retention time in the body and is dependent on mitoK(ATP), an important mediator of ischemic preconditioning induced cardiac protection.

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Related in: MedlinePlus

DDFPe protects the heart from myocardial infarction. Mice were administered saline vehicle or DDFPe immediately following permanent LAD occlusion. Hearts were perfused with trypan blue 24 h after LAD ligation and harvested for transverse sectioning and TTC staining (a) for assessment of the area at risk (b) and infarct size (c). Prior to trypan blue perfusion, heparin treated blood was collected for plasma preparation and cTnI ELISA analysis (d). n = 6–8. Means ± SEM are indicated next to each group in grey. * indicates significant difference (p < 0.05) between means, while N.S. indicates the means are not significantly different as determined by Student’s t-test
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Fig1: DDFPe protects the heart from myocardial infarction. Mice were administered saline vehicle or DDFPe immediately following permanent LAD occlusion. Hearts were perfused with trypan blue 24 h after LAD ligation and harvested for transverse sectioning and TTC staining (a) for assessment of the area at risk (b) and infarct size (c). Prior to trypan blue perfusion, heparin treated blood was collected for plasma preparation and cTnI ELISA analysis (d). n = 6–8. Means ± SEM are indicated next to each group in grey. * indicates significant difference (p < 0.05) between means, while N.S. indicates the means are not significantly different as determined by Student’s t-test

Mentions: The effect of DDFPe on infarct size was quantified from TTC stained transverse cross sections of hearts from mice undergoing LAD occlusion (representative section image Fig. 1a). While vehicle and DDFPe treatment groups experienced similar sized areas at risk (46.3 ± 2.3 % for vehicle vs 47.9 ± 4.0 % for DDFPe; p = 0.67) (Fig. 1b), mice treated with DDFPe immediately following LAD ligation demonstrated a reduction of infarct size, decreasing from 36.9 % of the area at risk in vehicle treated mice to 10.4 % in mice receiving DDFPe (p < 0.01) (Fig. 1c). Release of troponin I (cTnI), a cardiac specific isoform, into the blood is a widely used marker of MI. Blood plasma ELISA assay for cTnI confirmed a reduction in the extent of cardiac injury in the DDFPe treated mice as plasma levels of cTnI were reduced from 35 ng/ml in vehicle treated mice to 16 ng/ml in the DDFPe group (p < 0.01) (Fig. 1d).Fig. 1


Dodecafluoropentane emulsion elicits cardiac protection against myocardial infarction through an ATP-Sensitive K+ channel dependent mechanism.

Strom J, Swyers T, Wilson D, Unger E, Chen QM, Larson DF - Cardiovasc Drugs Ther (2014)

DDFPe protects the heart from myocardial infarction. Mice were administered saline vehicle or DDFPe immediately following permanent LAD occlusion. Hearts were perfused with trypan blue 24 h after LAD ligation and harvested for transverse sectioning and TTC staining (a) for assessment of the area at risk (b) and infarct size (c). Prior to trypan blue perfusion, heparin treated blood was collected for plasma preparation and cTnI ELISA analysis (d). n = 6–8. Means ± SEM are indicated next to each group in grey. * indicates significant difference (p < 0.05) between means, while N.S. indicates the means are not significantly different as determined by Student’s t-test
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4260113&req=5

Fig1: DDFPe protects the heart from myocardial infarction. Mice were administered saline vehicle or DDFPe immediately following permanent LAD occlusion. Hearts were perfused with trypan blue 24 h after LAD ligation and harvested for transverse sectioning and TTC staining (a) for assessment of the area at risk (b) and infarct size (c). Prior to trypan blue perfusion, heparin treated blood was collected for plasma preparation and cTnI ELISA analysis (d). n = 6–8. Means ± SEM are indicated next to each group in grey. * indicates significant difference (p < 0.05) between means, while N.S. indicates the means are not significantly different as determined by Student’s t-test
Mentions: The effect of DDFPe on infarct size was quantified from TTC stained transverse cross sections of hearts from mice undergoing LAD occlusion (representative section image Fig. 1a). While vehicle and DDFPe treatment groups experienced similar sized areas at risk (46.3 ± 2.3 % for vehicle vs 47.9 ± 4.0 % for DDFPe; p = 0.67) (Fig. 1b), mice treated with DDFPe immediately following LAD ligation demonstrated a reduction of infarct size, decreasing from 36.9 % of the area at risk in vehicle treated mice to 10.4 % in mice receiving DDFPe (p < 0.01) (Fig. 1c). Release of troponin I (cTnI), a cardiac specific isoform, into the blood is a widely used marker of MI. Blood plasma ELISA assay for cTnI confirmed a reduction in the extent of cardiac injury in the DDFPe treated mice as plasma levels of cTnI were reduced from 35 ng/ml in vehicle treated mice to 16 ng/ml in the DDFPe group (p < 0.01) (Fig. 1d).Fig. 1

Bottom Line: DDFPe treatment reduced infarct size by approximately 72% (36.9 ± 4.2% for vehicle vs 10.4 ± 2.3% for DDFPe; p < 0.01; n = 6-8) at 24 h.Serum cTnI levels were similarly reduced by DDFPe (35.0 ± 4.6 ng/ml for vehicle vs 15.8 ± 1.6 ng/ml for DDFPe; p < 0.01; n = 6-8).Our data indicate a cardiac protective role of DDFPe that persists beyond its retention time in the body and is dependent on mitoK(ATP), an important mediator of ischemic preconditioning induced cardiac protection.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology; College of Medicine, University of Arizona, 1501 N. Campbell Ave, Tucson, AZ, 85724, USA.

ABSTRACT

Purpose: Dodecafluoropentane emulsion (DDFPe) is a perfluorocarbon with high oxygen dissolving, transport, and delivery capacity that may offer the potential to limit ischemic injury prior to clinical reperfusion. Here we investigated the cardiac protective potential of DDFPe in a mouse model of myocardial infarction.

Methods: Myocardial infarction was initiated by permanent ligation of the left anterior descending (LAD) coronary artery. Mice were administered vehicle or 5-hydroxydecanoate (5-HD) intravenously 10 min before LAD occlusion followed by a single intravenous administration of vehicle or DDFPe immediately after occlusion. Heart tissue and serum samples were collected 24 after LAD occlusion for measurement of infarct size and cardiac troponin I (cTnI) levels, respectively.

Results: DDFPe treatment reduced infarct size by approximately 72% (36.9 ± 4.2% for vehicle vs 10.4 ± 2.3% for DDFPe; p < 0.01; n = 6-8) at 24 h. Serum cTnI levels were similarly reduced by DDFPe (35.0 ± 4.6 ng/ml for vehicle vs 15.8 ± 1.6 ng/ml for DDFPe; p < 0.01; n = 6-8). Pretreatment with 5-HD, a mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) inhibitor, blocked the reduction in infarct size (29.2 ± 4.4% for 5-HD vs 35.4 ± 7.4% for 5-HD+DDFPe; p = 0.48; n = 6-8) and serum cTnI levels (27.4 ± 5.1 ng/ml for 5-HD vs 34.6 ± 5.3 ng/ml for 5-HD+DDFPe; p = 0.86; n = 6-8) by DDFPe.

Conclusion: Our data indicate a cardiac protective role of DDFPe that persists beyond its retention time in the body and is dependent on mitoK(ATP), an important mediator of ischemic preconditioning induced cardiac protection.

Show MeSH
Related in: MedlinePlus