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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

Proposed Model of Cardiac Protection by DDFPe. Blue indicates periods of ischemia (I), while red represents periods of reperfusion (R) or oxygen delivery by DDFPe. The red to blue color fade-in depicted during DDFPe period represents the proposed gradual decrease in oxygen delivery that occurs as DDFPe is eliminated from the system
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Fig4: Proposed Model of Cardiac Protection by DDFPe. Blue indicates periods of ischemia (I), while red represents periods of reperfusion (R) or oxygen delivery by DDFPe. The red to blue color fade-in depicted during DDFPe period represents the proposed gradual decrease in oxygen delivery that occurs as DDFPe is eliminated from the system

Mentions: In order to elucidate a potential role of mitoKATP and IPC in DDFPe-induced cardiac protection, the mitoKATP inhibitor 5-HD was utilized. 5-HD was chosen over glibenclamide based on greater specificity for the mitoKATP over the sarcoplasmic KATP channel [22–24]. Pretreatment with 5-HD prior to LAD occlusion did not appreciably alter infarct size (36.9 ± 4.2 % for vehicle vs 29.2 ± 4.4 % for 5-HD) or cTnI release (35.0 ± 4.6 ng/ml for vehicle vs 27.4 ± 5.1 ng/ml for 5-HD). However, 5-HD pretreatment blocked the decrease in infarct size associated with DDFPe alone, supporting an IPC-like event mediated by mitoKATP as the mechanism of DDFPe cardiac protection, as illustrated in Figure 4.


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)

Proposed Model of Cardiac Protection by DDFPe. Blue indicates periods of ischemia (I), while red represents periods of reperfusion (R) or oxygen delivery by DDFPe. The red to blue color fade-in depicted during DDFPe period represents the proposed gradual decrease in oxygen delivery that occurs as DDFPe is eliminated from the system
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig4: Proposed Model of Cardiac Protection by DDFPe. Blue indicates periods of ischemia (I), while red represents periods of reperfusion (R) or oxygen delivery by DDFPe. The red to blue color fade-in depicted during DDFPe period represents the proposed gradual decrease in oxygen delivery that occurs as DDFPe is eliminated from the system
Mentions: In order to elucidate a potential role of mitoKATP and IPC in DDFPe-induced cardiac protection, the mitoKATP inhibitor 5-HD was utilized. 5-HD was chosen over glibenclamide based on greater specificity for the mitoKATP over the sarcoplasmic KATP channel [22–24]. Pretreatment with 5-HD prior to LAD occlusion did not appreciably alter infarct size (36.9 ± 4.2 % for vehicle vs 29.2 ± 4.4 % for 5-HD) or cTnI release (35.0 ± 4.6 ng/ml for vehicle vs 27.4 ± 5.1 ng/ml for 5-HD). However, 5-HD pretreatment blocked the decrease in infarct size associated with DDFPe alone, supporting an IPC-like event mediated by mitoKATP as the mechanism of DDFPe cardiac protection, as illustrated in Figure 4.

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