Ischemia-reperfusion arrhythmias and lipids: Effect of human high- and low-density lipoproteins on reperfusion arrhythmias

Abstract

The effect of high- and low-density lipoproteins separated from human serum on the postischemic reperfusion arrhythmias was investigated. The hearts were perfused by working heart mode with Krebs Henseleit bicarbonate buffer containing arachidonic acid (1 microgram/ml) for 5 minutes. Whole heart ischemia was induced by the use of a one-way ball valve, and hearts were perfused for 15 minutes followed by 20 minutes of reperfusion. Physiologic concentrations of high- and low-density lipoproteins were constantly infused through the atrial route during ischemic perfusion. Coronary effluent was collected via pulmonary artery cannulation for subsequent radioimmunoassay of thromboxane B2 and 6-keto-prostaglandin F1 alpha, the major stable metabolites of thromboxane A2 and prostacyclin, respectively. The incidence of ventricular arrhythmias during reperfusion was 6/6 (100%), 1/6 (17%), and 6/6 (100%) in control, high-density lipoprotein and low-density lipoprotein infusion groups, respectively. There was no significant difference in coronary flow among the three groups throughout the perfusion. Both thromboxane B2 and 6-keto-prostaglandin F1 alpha increased significantly during ischemia compared with preischemic values in all groups of hearts. However, the ratio of these two parameters varied in control and low-density lipoprotein infusion groups during ischemia, while there was no significant change in the high-density lipoprotein infusion group. These results provide the possibility that arachidonate metabolites may be involved in the regulation of ischemia-reperfusion arrhythmias and that high-density lipoprotein that was infused during ischemia markedly inhibits the incidence of ischemia-reperfusion-induced ventricular arrhythmias, due in part at least, to stabilizing the arachidonate metabolites during ischemic perfusion.

HDL and its sphingosine-1-phosphate content in cardioprotection

“…In addition, the authors have observed a concomitant enhancement of prostaglandin (PG)I 2 release in the microcirculation, a factor generally viewed as salutary in ischemia/reperfusion injury [8,9]. Several years before, another study had shown that HDL attenuated the second major complication of ischemia/reperfusion-the arrhythmogenicity of the injured heart: Mochizuki and co-workers observed that administration of HDL in the same experimental system (the isolated perfused rat heart), dramatically decreased the incidence of ischemia/reperfusion-induced ventricular arrhythmias by a mechanism also involving PGI 2 [10]. Both studies argue in favour of a direct cardioprotective effect of HDL.…”

Therapeutic Potential of HDL in Cardioprotection and Tissue Repair

“…An early study using HDL perfusion in isolated hearts suggested that HDL significantly reduced post-ischaemic arrhythmias (Mochizuki et al 1991). In contrast, perfusion with low-density lipoproteins (LDL) had no effects indicating HDL specificity.…”

“…In contrast, perfusion with low-density lipoproteins (LDL) had no effects indicating HDL specificity. The mechanism was not defined, but it was hypothesised that the lipoprotein stabilised bioactive arachidonic acid metabolites (Mochizuki et al 1991). These antiarrhythmogenic effects were later confirmed in vivo when treatment with rHDL decreased the incidence of post-ischaemic arrhythmias (Imaizumi et al 2008).…”

Low-density lipoproteins inhibit histamine and NaNO2 relaxations of the coronary vasculature and reduce contractile function in isolated rat hearts

“…Previous studies have found that ox-LDL is arrhythmogenic in isolated rat hearts [15] and rabbit Purkinje fibers [16]. It also increased cell tissue factor activity and reduced protein C activation in cultured endothelial cells [17], caused platelet activation [18], and stimulated leucocyte adherence to the endothelium [19,20].…”