Reduction of myocardial infarct size by poloxamer 188 and mannitol in a canine model

Justicz, Alexander G.; Farnsworth, William V.; Soberman, Mark S.; Tuvlin, Michael B.; Bonner, Gary D.; Hunter, Robert L.; Martino-Saltzman, David; Sink, James D.; Austin, Garth E.

doi:10.1016/0002-8703(91)90510-o

Cited by 48 publications

(18 citation statements)

References 16 publications

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“…Welbourn et al 29 reported that mannitol pretreatment reduced leukosequestration in lung microscopy in a rat model of lower torso IR injury. In a separate study, Justicz et al 30 showed that mannitol attenuated the histological signs of acute myocardial infarction and reduced the infi ltration of both the infarcted areas and the adjacent tissues with neutrophils in a canine model of cardiac IR injury. However, Schlag et al 31 reported that mannitol did not signifi cantly reduce tissue injury or leukocyte accumulation, but it did attenuate the no-refl ow phenomenon during the fi rst few minutes of reperfusion in a rat model of skeletal muscle IR injury.…”

Section: Discussionmentioning

confidence: 97%

“…The inhibition of oxidative stress markers and the normalization of the natural enzymatic and nonenzymatic antioxidants after mannitol administration can mainly be explained by the antioxidant effects of mannitol. 9,[20][21][22][23][24][25][26]29,30,37 Our data suggest that mannitol may exert its benefi cial effects through a reduction of xanthine oxidase-derived free radicals, resulting in decreased cell membrane damage.…”

Section: Discussionmentioning

confidence: 99%

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Mannitol attenuates acute lung injury induced by infrarenal aortic occlusion-reperfusion in rats

Teke¹,

Adalı

Kelten

et al. 2011

Surg Today

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Mannitol attenuates acute lung injury induced by infrarenal aortic occlusion-reperfusion in rats

Teke¹,

Adalı

Kelten

et al. 2011

Surg Today

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“…Animal models underwent 2 hours of cardiopulmonary bypass with or without pretreatment with PP188. PP188 was associated with potentially beneficial changes in membrane protein expression, reduced capillary leakage, less hemodilution [7], and reduced membrane injury from ischemia and reperfusion [8,11]. …”

Section: Discussionmentioning

confidence: 99%

“…Poloxamer 188 (PP188) is nontoxic surface-active agent that has cytoprotective effects. PP188 is incorporated into the lipid bilayers, thereby decreasing their susceptibility to oxidative stress and inflammation [7-11]. Inhaled anesthetics, propofol, and PP188 provide cardioprotection against ischemia and reperfusion injury via different mechanisms [11], but despite these distinct mechanisms several studies have demonstrated that no additive or superior protection was observed with the combination of these cardioprotective agents [12,13].…”

Section: Introductionmentioning

confidence: 99%

The cardioprotective effect of microemulsion propofol against ischemia and reperfusion injury in isolated rat heart

Hur

Kim

Lee

et al. 2012

Korean J Anesthesiol

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BackgroundLipid-emulsion propofol (LP) has cardioprotective effects against ischemia-reperfusion injury, but it has lipid-related side effects. Microemulsion propofol (MP) is a lipid-free propofol emulsified with 10% purified poloxamer 188 (PP188). PP188 is a nonionic surfactant and has cardioprotective effects. However, some reports have suggested that reduced cardioprotective effects were observed when the cardioprotective agents were used in combination even though each cardioprotective agent has cardioprotective effects. The aims of this study were to examine and compare the cardioprotective effects of MP and LP.Methods50 isolated rat hearts were perfused with modified Kreb's solution. They were divided into 4 groups and underwent 30 minutes of ischemia and 60 minutes of reperfusion. Control group: ischemia-reperfusion was performed without treatment. LP, MP and PP groups: LP, MP and PP188 were infused during the pre-ischemic and reperfusion period, respectively. Hemodynamic parameters and coronary effluent flow rate (CEFR) were measured. Infarct size was determined using triphenyl-tetrazolium staining.ResultsIn the MP group, systolic pressure was maintained near baseline, the systolic pressure was higher than that in the other groups and HR was lower than that in the other groups during reperfusion. Diastolic pressure was transiently increased in the PP group after treatment and at 5 minutes after reperfusion compared with that in the control group and in the the LP group. There were no differences in dP/dtmax and CEFR between groups. Infarct size in the LP, MP and PP groups was smaller than that in the control group, but there were no significant differences between these three groups.ConclusionsMP has cardioprotective effects similar to those of LP. MP can be used for cardiac anesthesia in cases with ischemia-reperfusion injury to avoid the lipid-related side effects of LP.

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“…When used in combination with tissue plasminogen activator or streptokinase, it markedly increases fibrinolysis [19, 20]. In models of acute myocardial infarction (AMI), P188 reduced the infarct size by 40–50 % and improved the left ventricular ejection fraction by about 30 % [21, 22]. Although it is not an anticoagulant, P188 has been shown to diminish thrombotic coronary occlusion after arterial injury and stent placement in a porcine model [23].…”

Section: Introductionmentioning

confidence: 99%

Differential Effects of Commercial-Grade and Purified Poloxamer 188 on Renal Function

Emanuele¹,

Balasubramaniam²

2014

Drugs R D

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Poloxamer 188 (P188) is a non-ionic amphiphilic copolymer with hemorheologic, antithrombotic, anti-inflammatory, and cytoprotective properties. It potentially has clinical utility in diverse diseases, such as acute myocardial infarction, acute limb ischemia, shock, acute stroke, heart failure, and sickle cell crisis. P188 is available as an excipient-grade product, manufactured to National Formulary specifications, which we refer to as P188-NF. During synthesis of P188-NF, polymerization of its polyoxyethylene and polyoxypropylene components generates undesirable low molecular weight (LMW) substances, such as truncated polymers and glycols. In early clinical studies, P188-NF yielded unexpected renal dysfunction. Here, we explore the nature of the renal dysfunction associated with P188-NF and use a purified (more homogenous) form of P188-NF (P188-P) to show that removal of LMW substances is associated with substantially less renal dysfunction. In both a remnant-kidney animal model and in clinical studies, P188-P demonstrates a substantially improved renal safety profile.

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Reduction of myocardial infarct size by poloxamer 188 and mannitol in a canine model

Cited by 48 publications

References 16 publications

Mannitol attenuates acute lung injury induced by infrarenal aortic occlusion-reperfusion in rats

Mannitol attenuates acute lung injury induced by infrarenal aortic occlusion-reperfusion in rats

The cardioprotective effect of microemulsion propofol against ischemia and reperfusion injury in isolated rat heart

Differential Effects of Commercial-Grade and Purified Poloxamer 188 on Renal Function

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