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Effect of increased magnesium on recovery from ischemia in rat and rabbit hearts
Abstract:
Perfusates containing high magnesium concentrations have been suggested to have a protective effect for ischemic myocardium, but the mechanism for such an effect is unclear. We investigated the recovery of isolated perfused rabbit and rat hearts from ischemia under varied conditions of increased Mg. Hearts were made ischemic in the presence of normal 1.2 mM Mg or elevated 15 mM Mg. Rabbit hearts, which show minimal alteration in contractility in the presence of 15 mM Mg, were not protected from ischemia by high Mg perfusate. Rat hearts, which have a large negative inotropic response to 15 mM Mg, exhibited significantly better recovery of mechanical function following ischemia in the presence of high Mg than following ischemia with normal Mg. This protective effect was abolished by increasing both Ca and Mg in the perfusate to prevent the decline in contractility that normally occurred with Mg. Reperfusion with 15 mM Mg after ischemia also had no protective effect if the rat heart had been made ischemic in the presence of normal Mg. We conclude that elevated Mg protects ischemic myocardium only under circumstances in which it has a negative inotropic effect before the onset of ischemia, i.e., in the rat heart perfused with normal Ca. These results suggest that the mechanism of protection by high Mg involves sparing of ATP. However, the different responses to Mg of the species studied in these experiments should be a caution against extrapolating such results from rat hearts to other species.
Insights
High magnesium concentrations protect ischemic myocardium in rat hearts but not rabbit hearts. This protective effect, linked to a negative inotropic response, suggests ATP sparing and cautions against species extrapolation.
Area of Science:
- Cardiovascular Physiology
- Myocardial Ischemia Research
- Magnesium in Medicine
Background:
- High magnesium (Mg) concentrations are proposed to protect ischemic myocardium.
- The precise mechanism underlying Mg's cardioprotective effects remains unclear.
- Species-specific responses to Mg may influence its protective capabilities.
Purpose of the Study:
- To investigate the mechanism of Mg's protective effect on ischemic myocardium.
- To compare the effects of elevated Mg on isolated perfused rabbit and rat hearts during ischemia.
- To determine the conditions under which high Mg perfusate confers protection.
Main Methods:
- Isolated perfused rabbit and rat hearts subjected to ischemia.
- Hearts were perfused with normal (1.2 mM) or elevated (15 mM) Mg concentrations.
- Mechanical function recovery and contractility changes were assessed post-ischemia.
Main Results:
- Rat hearts showed significantly better recovery of mechanical function with high Mg perfusate compared to normal Mg.
- Rabbit hearts, exhibiting minimal contractility changes with high Mg, were not protected by elevated Mg.
- The protective effect in rat hearts was abolished when Ca and Mg were increased, preventing Mg-induced negative inotropy.
Conclusions:
- Elevated Mg protects ischemic myocardium specifically when it induces a negative inotropic effect prior to ischemia, as observed in rat hearts.
- The cardioprotective mechanism likely involves adenosine triphosphate (ATP) sparing.
- Differences in species' responses to Mg highlight the need for caution when extrapolating findings from rat models to other species.