Effects of purified poloxamer 407 gel on vascular occlusion and the coronary endothelium

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Abstract

Objective:

Vascular occlusion during off-pump coronary surgery often results in sub-optimal visualization and endothelial damage of the target vessel. We have previously reported the safety of purified poloxamer 407, a gel with reverse thermosensitive properties, in a model of off-pump coronary occlusion. The aim of this study was to evaluate different gel concentrations and their effects on coronary occlusion time, myocardial contractility, endothelial function, and markers of myocardial injury and apoptosis.

Methods:

Yorkshire swine (30-35 kg) underwent sternotomy and mid-LAD occlusion using either microvascular clamps (n = 6) or varying quantities of three different concentrations (20%; n = 6, 22.5%; n = 3, and 25%; n = 3) of purified poloxamer 407 gel. Distal LAD flow, left ventricular pressure, and in vitro microvascular reactivity were assessed. Molecular markers of myocardial injury and apoptosis were assessed using Western blotting.

Results:

Duration of ischemia correlated significantly with the amount of injected gel for the 20% and 22.5% formulations (Spearman r = 0.64, p = 0.02 and r = 0.85, p = 0.03, respectively) but not for the 25% gel (r = 0.22, p = 0.66). There were no significant differences in LV contractility (maximum + dp/dt) (p = 0.86) as well as LAD flow (p = 0.25) during reperfusion in the four groups. Microvessel relaxation to adenosine diphosphate in the ischemic territory was impaired with higher concentrations of the gel, 22.5% (−14.8 ± 7.5% vs control at 10−5 mol/L, p ≪ 0.05) and 25% gel (−24.0 ± 7.6% vs control at 10−5 mol/L, p ≪ 0.001) but not with the 20% gel. Endothelium-independent relaxation to sodium nitroprusside was preserved in all groups. Cleaved poly(ADP-ribose) polymerase, a marker of myocardial injury and apoptosis, was elevated in the ischemic myocardium in all groups (p = 0.02 vs non-ischemic myocardium) with no significant differences between the groups (p = 0.70). Phosphorylation of Bad, an anti-apoptotic protein, was significantly reduced in the ischemic territory (p = 0.04). No changes were observed in other markers of myocardial apoptosis.

Conclusions:

Purified poloxamer 407 gel is effective for temporary coronary vascular occlusion. Coronary artery occlusion time is related to gel concentration and the quantity of gel injected. The higher gel concentrations may cause endothelial dysfunction of the distal vasculature and therefore should be avoided.

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