Intracoronary Poloxamer 188 Prevents Reperfusion Injury in a Porcine Model of ST-Segment Elevation Myocardial Infarction

Bartos, Jason A.; Matsuura, Timothy; Tsangaris, Adamantios; Olson, Matthew D.; McKnite, Scott; Rees, Jennifer; Haman, Karen; Shekar, Kadambari Chandra; Riess, Matthias L.; Bates, Frank S.; Metzger, Joseph M.; Yannopoulos, Demetris

doi:10.1016/j.jacbts.2016.04.001

Cited by 35 publications

(65 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…P188 has previously been used to stabilize plasma or sarcolemmal membranes in both ischemia–reperfusion injury and muscular dystrophy models (Bartos et al, ; Townsend et al, ; Yasuda et al, ). It was hypothesized that P188 blocked cellular markers of apoptosis and necrosis that were present in untreated myocytes.…”

Section: Discussionmentioning

confidence: 99%

“…P188 is sometimes referred to as a membrane sealant and has been trialed in both the treatment of ischemia and in membrane stabilization. In myocardial ischemia–reperfusion studies, P188 preserved larger areas of viable myocardium (Bartos et al, ). We hypothesized that inclusion of P188 could improve the survival of myocytes undergoing primary isolation via a Langendorff method.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Membrane stabilizer Poloxamer 188 improves yield of primary isolated rat cardiomyocytes without impairing function

2020

View full text Add to dashboard Cite

Intact cardiomyocytes are used to investigate cardiac contractility and evaluate the efficacy of new therapeutic compounds. Primary enzymatic isolation of adult rodent cardiomyocytes has limitations, including low cardiomyocyte survival, which is likely due to ischemic conditions and/or membrane damage. The addition of Poloxamer 188 (P188) has been used to reduce ischemia‐ and membrane‐related damage in ischemia–reperfusion and muscular dystrophy studies. P188 stabilizes membranes, reducing cell death. Cardiomyocytes were isolated from rats, under three conditions: (1) using standard isolation solutions, (2) with P188 added during cannulation (ischemic event), and (3) with P188 added during cannulation, enzymatic digestion, and trituration. Cell survival was assessed by quantifying the number of rod‐shaped versus contracted cells on the day of isolation and up to 3 days post‐isolation. Adding P188 only during cannulation yielded improved survival on the day of isolation. Little difference in survival was seen among the three conditions in the days post‐isolation. Cardiomyocyte function was assessed by measuring calcium transients and unloaded sarcomere lengths for up to 2 days post‐isolation. P188 did not consistently alter calcium handling or sarcomere shortening in the isolated cardiomyocytes. We conclude that the addition of P188 to the cannulation (e.g., wash) of the isolated heart may improve initial survival of cardiomyocytes upon primary enzymatic isolation.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Membrane stabilizer Poloxamer 188 improves yield of primary isolated rat cardiomyocytes without impairing function

2020

View full text Add to dashboard Cite

show abstract

“…It is believed that P188 inserts into areas of low membrane tension (perhaps areas of membrane damage) due to its amphiphilic and hydrophobic properties 29 . P188 has been shown to reduce infarct size following I/R injury in dogs and pigs when administered acutely 30 – 32 . Moreover, a 30-min intravenous infusion of high dose P188 (460 mg/kg) was shown to acutely (~ 40 h) improve LV ejection fraction and decrease LV end-systolic volume when administered to rats 8 weeks after acute ligation of the left anterior descending artery 27 .…”

Section: Discussionmentioning

confidence: 99%

Ischemia reperfusion injury provokes adverse left ventricular remodeling in dysferlin-deficient hearts through a pathway that involves TIRAP dependent signaling

Evans

Weinheimer

Kovács

et al. 2020

Sci Rep

View full text Add to dashboard Cite

cardiac myocytes have multiple cell autonomous mechanisms that facilitate stabilization and repair of damaged sarcolemmal membranes following myocardial injury. Dysferlin is a protein which facilitates membrane repair by promoting membrane resealing. Although prior studies have shown that dysferlin-deficient (Dysf −/−) mouse hearts have an impaired recovery from acute ischemia/ reperfusion (I/R) injury ex vivo, the role of dysferlin in mediating the recovery from myocardial injury in vivo is unknown. Here we show that Dysf −/− mice develop adverse LV remodeling following i/R injury secondary to the collateral damage from sustained myocardial inflammation within the infarct zone. Backcrossing Dysf −/− mice with mice lacking signaling through the Toll-Interleukin 1 Receptor Domain-Containing Adaptor Protein (Tirap −/−), attenuated inflammation and abrogated adverse LV remodeling following I/R injury. Subsequent studies using Poloxamer 188 (P188), a membrane resealing reagent, demonstrated that P188 did not attenuate inflammation nor prevent adverse LV remodeling in Dysf −/− mice following i/R injury. Viewed together these studies reveal a previously unappreciated role for the importance of membrane sealing and the resolution of inflammation following myocardial injury. The sarcolemmal phospholipid bilayer membrane that envelopes cardiac myocytes is essential for cell viability by providing a structural barrier function that separates the cytosolic components of the cell from the extracellular environment, as well as a crucial functional role by integrating important cellular functions, such as excitation contraction coupling. Given the importance of the sarcolemma to cell viability, it is not surprising that cardiac myocytes have multiple cell autonomous mechanisms that facilitate stabilization and repair of damaged sarcolemmal membranes. These include sarcolemma phospholipid rearrangements at the site of very small disruptions/ injury in order to promote membrane resealing, as well as several endogenous mechanisms that are activated in order to repair damage to preserve muscle cell integrity and viability (reviewed in 1,2). In myocardial ischemia-reperfusion (I/R) injury the integrity of the cardiac sarcolemma is severely stressed during ischemia and reperfusion, which leads to membrane tears, blebbing and rupture, and directly contributes to cardiac myocyte dysfunction and cardiac myocyte cell death 3. The loss of sarcolemmal barrier function can also lead to additional myocardial damage days to weeks following reperfusion secondary to the brisk inflammatory response that ensues following the release of damage associated molecular patterns [DAMPs] by dying cells. DAMPs released by necrotic cardiac myocytes are sufficient to provoke a brisk inflammatory response in the heart that requires intact signaling through Toll-like receptors (TLR4) that are present on the cell surface of cardiac myocytes and cardiac resident immune cells 4,5 .

show abstract

“…The coronary occlusion protocol has been described previously 3 , 6 , 7 . A 6-F Amplatz Left 0.75 short-tipped guide catheter was engaged into the left main coronary artery under fluoroscopic guidance.…”

Section: Methodsmentioning

confidence: 99%

Role of Epinephrine and Extracorporeal Membrane Oxygenation in the Management of Ischemic Refractory Ventricular Fibrillation

Bartos

Voicu

Matsuura

et al. 2017

JACC: Basic to Translational Science

Self Cite

View full text Add to dashboard Cite

CONDENSED ABSTRACT xtracorporeal membrane oxygenation (ECMO) is used in cardiopulmonary resuscitation (CPR) of refractory cardiac arrest. We used a 2×2 study design to compare ECMO versus CPR and epinephrine versus placebo in a porcine model of ischemic refractory ventricular fibrillation (VF). Pigs underwent 5 minutes of untreated VF, 10 minutes of CPR, and were randomized to receive epinephrine versus placebo for another 35 minutes. Animals were further randomized to LAD reperfusion at minute 45 with ongoing CPR versus veno-arterial ECMO cannulation at minute 45 of CPR and subsequent LAD reperfusion. Four-hour survival was improved with ECMO while epinephrine showed no effect.

show abstract

Intracoronary Poloxamer 188 Prevents Reperfusion Injury in a Porcine Model of ST-Segment Elevation Myocardial Infarction

Cited by 35 publications

References 24 publications

Membrane stabilizer Poloxamer 188 improves yield of primary isolated rat cardiomyocytes without impairing function

Membrane stabilizer Poloxamer 188 improves yield of primary isolated rat cardiomyocytes without impairing function

Ischemia reperfusion injury provokes adverse left ventricular remodeling in dysferlin-deficient hearts through a pathway that involves TIRAP dependent signaling

Role of Epinephrine and Extracorporeal Membrane Oxygenation in the Management of Ischemic Refractory Ventricular Fibrillation

Contact Info

Product

Resources

About