[The cytoprotective effect of magnesium in global myocardial ischemia].
BACKGROUND
Administration of magnesium in the therapy of ischaemic heart diseases does not belong to the standard procedures. The results of clinical trials with application of this cation are mutually contradictive, mechanisms of its effect are not solved yet. Many physicians consider magnesium to represent a classical placebo, or an uncertain light sedative. MAIN PURPOSE AND OBJECTIVES: The study is aimed at proving the direct effect of magnesium on the heart muscle under ischaemic conditions which exclude the placebo effects. These conditions are mostly fulfilled by the model of isolated heart.


METHODS
The authors used isolated rabbit hearts according to Langedorff with Krebs-Henseleit (KH) perfusion solution, the only variable of which is represented by concentration of magnesium. The following groups of patients were formed: 1. Control group-30-minute perfusion with normal Mg concentration (0.5 mmol/l) in KH solution. 2. Hypomagnesemia-30-minute perfusion with KH solution Mg-free. 3. Normomagnesemia+ischaemia-30-minute perfusion with normal concentration succeeded by a 60-minute global ischaemia. 4. Hypomagnesiaemia+ischaemia-30-minute perfusion with KH solution magnesium-free succeeded by a 60-minute global ischaemia. 5. Hypermagnesiemia +ischaemia-30-minute perfusion with increased Mg concentration in KH solution to 2.0 mmol/l succeeded by a 60-minute global ischaemia. The investigated parameters: after completion of perfusion the authors isolated mitochondria and evaluated individual parameters of oxidative phosphorylation by means of oxygraph/Gilson/with Clark's oxygen electrode. The calcium uptake by mitochondria was observed by means of calcium-sensitive electrode Orion (oxygraph Gilson). The formation of free oxygen radicals was observed indirectly by spectrophotometric assessment of malondialdehyde production. Concentration of mitochondrial nucleotides (AMP, ADP, ATP) was assessed by using HPLC.


RESULTS
Hypomagnesemia lasting 30 minutes had a negative effect on the index of oxidative phosphorylation (ADP:O p < 0.005) the uptake of calcium (p < 0.002), ATP concentration in mitochondrial ATP (p < 0.05) and the production of free radicals significantly increased (p < 0.001). Normomagnesemia indicated practically no cytoprotective effect before global ischaemia of myocardium lasting for 60 minutes. Hypermagnesemia indicated a direct cytoprotective effect before global ischaemia affecting respiration of isolated heart mitochondria in state of S3 (p < 0.001), respiration control index RCI (p < 0.001), the rate of oxidative phosphorylation OPR (p < 0.001) and on the index of oxidative phosphorylation ADP:O (p < 0.05) on the uptake of calcium by mitochondria (p < 0.002) and on concentration of mitochondrial nucleotides ATP (p < 0.002). It was remarkable that also under conditions of moderate hypomagnesemia the production of malondialdehyde increased.


CONCLUSIONS
Under our experimental conditions it was confirmed that magnesium yields direct cytoprotective effect on the subcellular level of the myocardium prior to global ischaemia, providing the process takes place under the condition of hypermagnesemia. (Tab. 1, Fig. 12, Ref. 45.) Key words: hypomagnesemia, normomagnesemia, hypermagnesemia, Langendorff's global ischaemia, mitochondrial metabolism, cytoprotective effect.
Bada
V
V
III. interná klinika Lekárskej fakulty Univerzity Komenského v Bratislave, Slovakia.
Kucharská
J
J
Gvozdjáková
A
A
Herichová
I
I
Gvozdják
J
J
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004562:Electrocardiography; D005609:Free Radicals / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D011817:Rabbits
D005609:Free Radicals; D000255:Adenosine Triphosphate; D008274:Magnesium; D002118:Calcium