Lack of cardioprotection by single-dose magnesium prophylaxis on isoprenaline-induced myocardial infarction in adult Wistar rats

Abstract

Aim: Magnesium (Mg(2+)) is effective in treating cardiovascular disorders such as arrhythmias and pre-eclampsia, but its role during myocardial infarction (MI) remains uncertain. In this study, we investigated the effects of Mg(2+)pre-treatment on isoprenaline (ISO) -induced MI in vivo.

Methods: Rats divided into four groups were each pre-treated with either MgSO4 (270 mg/kg intraperitoneally) or an equivalent volume of physiological saline, prior to the ISO (67 mg/kg subcutaneously) or saline treatments. One day post-treatment, the electrocardiogram and left ventricular blood pressures were recorded. Infarcts were determined using 2,3,5-triphenyltetrazolium chloride staining, and serum markers of lipid peroxidation were measured with spectrophotometric assays.

Results: Mg(2+) pre-treatment neither altered the ISO-induced infarct size compared with ISO treatment alone (p > 0.05), nor reversed the low-voltage electrocardiogram or the prominent Q waves induced by ISO, despite a trend to decreased Q waves. Similarly, Mg(2+) did not prevent the ISO-induced decrease in peak left ventricular blood pressure or the decrease in minimal rate of pressure change. Mg(2+) did not reverse the ISO-induced gain in heart weight or loss of body weight. Neither ISO nor Mg(2+) altered the concentrations of lipid peroxidation markers 24 hours post MI induction.

Conclusion: Although Mg(2+) had no detrimental effects on electrical or haemodynamic activity in ISO-induced MI, the lack of infarct prevention may detract from its utility in MI therapy.

Fig. 1.

ISO-induced MI and the effects of Mg²⁺ pre-treatment. A: Timeline of experimental protocol. The horizontal bar represents a 24-hour timeline with a break in the scale. The times at which rats were treated and at which in vivo and tissue measurements were done are indicated by arrows. B: Pictures of TTC-stained ventricular slices cut from four different hearts of rats treated with saline only (control), ISO and saline (ISO), ISO and Mg²⁺ (ISO + Mg), or Mg²⁺ and saline (Mg). Viable myocardium stained red (TTC positive), whereas areas of irreversible infarcts appeared white (TTC negative). C: Summary data of infarct size in whole ventricles. The infarct size is expressed as a percentage of the TTC‑negative area to the total ventricular area. Data are presented as mean ± SEM (n = 8–10 rats per group); *p < 0.05 (treatment vs control).

Fig. 2.

Effects of various treatments on the ECG waveforms. Segments of original lead II ECG traces recorded from individual rats under various treatments, A: saline (control), B: ISO, C: ISO + Mg²⁺, and D: Mg²⁺.

Fig. 3.

Effects of ISO and Mg²⁺ treatments on haemodynamic parameters in four different groups of rats. A: The maximum left ventricular (LV) blood pressure, B: LV end-diastolic pressure, C: maximal rate of LV pressure change (dP/dt max), D: minimal rate of LV pressure change (dP/dt min), E: systolic duration, and F: diastolic duration. Data are presented as mean ± SEM (n = 8–10 rats per group); *p < 0.05; **p < 0.01 and ***p < 0.001 (treatment vs control).

Fig. 4.

Effects of ISO and Mg²⁺ on the plasma concentrations of markers of lipid peroxidation in four different groups of rats. Plasma concentrations of conjugated dienes (A), and thiobarbituric acid-reactive substances (B), measured 24 hours after administration of the drugs. Data are presented as mean ± SEM (n = 8–10 rats per group).