MARKED ALTERATIONS IN CIRCULATING INFLAMMATORY CELLS DURING CARDIOMYOPATHY DEVELOPMENT IN A MAGNESIUM-DEFICIENT RAT MODEL

Rodents fed on a Mg-deficient (Mg-D) diet develop cardiomyopathic lesi ons, as well as other types of cardiovascular dysfunction, In the rat, inflammatory cell infiltration of the myocardium begins to occur by w eek 1, and the lesions develop extensively in the third and fourth wee ks on the Mg-D diet, Although the aetiologic mechanisms of Mg-D cardio myopathy are unknown, we have previously reported that once plasma Mg is markedly reduced, one of the earliest molecular markers of the path ophysiological process is elevation of plasma substance P, calcitonin gene-related peptide and prostaglandin E-2, followed by histamine and the inflammatory cytokines (interleukin-1, interleukin-6, and tumor ne crosis factor-or). In order to evaluate the potential role of specific circulating inflammatory cell subpopulations in the mechanisms underl ying pathophysiological changes observed in Mg-deficiency-induced card iomyopathy, we analysed these cells by flow cytochemistry. Leucocyte s ubpopulation pools increased progressively in the Mg-D rats, Elevated circulating Levels of neutrophils and lymphocytes appeared to contribu te to both the acute (week 1-2) and chronic phases (week 3-4) of the i nflammatory responses; monocytes, eosinophils, basophils and large uns tained cells which are lymphoid in stained smears, on the other hand, increased significantly in the third and fourth weeks and thus contrib uted to the chronic inflammatory phase. Changes in the circulating leu cocyte subpopulations paralleled the chronological progression of the cardiomyopathic lesions, particularly in weeks 3 and 4. Since a pronou nced neutrophilia preceded leucocyte infiltration and deposition withi n the myocardial tissue, modifications of the microvascular barrier ma y be a prerequisite for cardiomyopathy in this model of neurogenic inf lammation.