Antiarrhythmic effects of ceruloplasmin during reperfusion in the ischemic isolated rat heart

Abstract

The ability of ceruloplasmin, an important serum antioxidant, to reduce the vulnerability of the isolated rat heart to reperfusion arrhythmias has been investigated. Bovine plasma ceruloplasmin was purified by chromatography on aminoethyl-agarose. Isolated rat hearts were submitted to 15 min of regional ischemia and 10 min of reperfusion. The dose-effect relationship and the role of ceruloplasmin conformational integrity in cardioprotection were established by treatment of ischemic hearts with ceruloplasmin at various concentrations (0.25, 0.5, 1, and 2 microM) and at different degrees of conformational integrity (A610/A280 = 0.02, 0.04, and 0.06), 5 min before reperfusion. Deferoxamine (20-500 microM) was used as a positive control. As negative controls we used chemically inactivated ceruloplasmin (1 microM), heat-denatured ceruloplasmin (1 microM), and albumin (1-4 microM). In the control group during the first 5 min of reperfusion, the incidence of total ventricular fibrillation was 100% and of irreversible ventricular fibrillation was 83%. The incidence of reversible and irreversible ventricular fibrillation was significantly decreased in the ceruloplasmin-treated groups in both a dose and molecular integrity dependent manner. Ceruloplasmin had no effect on the incidence of ventricular tachycardia. Deferoxamine reduced the incidence of ventricular fibrillation to the same degree as ceruloplasmin but at concentrations much higher than those of ceruloplasmin. Chemically inactivated ceruloplasmin, heat-denatured ceruloplasmin, and albumin had no protective effects on reperfusion-induced arrhythmias.

Gamma-irradiated ceruloplasmin affords antifibrillatory protection against ischemia/reperfusion damage in the isolated rat heart

“…At postischemic reperfusion it induced a slight, not significant, increase of HR (5%) and of CF (2%) and a moderate, statistically significant (p 0.05) decrease (16%) of LVP vs. the equilibrium values (before ischemia/reperfusion). CP (1 mM) did not reduce the incidence of reversible ventricular fibrillation (VF 100%), but efficiently reduced the irreversible ventricular fibrillations at IVF 0% (fitting well with data of Atanasiu et al 1995), with recovery and maintenance of normal sinus rhythm over 192 sec (Table II).…”

Clinical and Genetic Association of Serum Ceruloplasmin With Cardiovascular Risk

“…Ceruloplasmin is one of these well-known inflammation-sensitive plasma proteins, found to have protective effects in isolated rat hearts subjected to ischemia–reperfusion 19, 20 . The exact mechanisms for the cardioprotection are unclear, but likely are due to a wide variety of extracellular anti-oxidative ferroxidase and ROS scavenging effects 1 , combined with putative glutathione (GSH)-peroxidase and NO-oxidase/S-nitrosating activities 21 .…”

Protective role of l-tyrosine in the sterilization of Ceruloplasmin therapeutic protein by gamma-irradiation

“…There are several mechanisms expected to govern the therapeutic cardioprotective action of CP (Atanasiu et al, 1995). One of them consists in the ferroxidase function of CP.…”

“…Also known as Ferroxidase I, CP promotes the oxidation of ferrous ions (Fe 2+ -Fe 3+ ), preventing thus the accumulation of highly toxic Fe 2+ ions, strongly involved in releasing of damaging oxygen free radicals (Paulik and Weiss, 1995). Ceruloplasmin presents an interesting therapeutic potential (Atanasiu et al, 1995) as antiarrhythmic and cardioprotector and as neuronoprotector.…”