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Thromb Haemost 2001; 86(05): 1292-1295
DOI: 10.1055/s-0037-1616064
Review Article
Schattauer GmbH

Magnesium Inhibits Arterial Thrombi after Vascular Injury in Rat: In Vivo Impairment of Coagulation

Luciana Mussoni
1   Department of Pharmacological Sciences, University of Milan, Milan, Italy
,
Luigi Sironi
1   Department of Pharmacological Sciences, University of Milan, Milan, Italy
,
Luca Tedeschi
1   Department of Pharmacological Sciences, University of Milan, Milan, Italy
,
Anna Maria Calvio
1   Department of Pharmacological Sciences, University of Milan, Milan, Italy
,
Susanna Colli
1   Department of Pharmacological Sciences, University of Milan, Milan, Italy
,
Elena Tremoli
1   Department of Pharmacological Sciences, University of Milan, Milan, Italy
› Author AffiliationsThis work was supported in part by grants from the European Community (HIFMECH Study, BMH4-CT96-0272) and from the Italian Ministry of University and Scientific Research (MURST 40%).
Further Information

Publication History

Received 28 September 2000

Accepted after resubmission 18 July 2001

Publication Date:
13 December 2017 (online)

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Summary

Magnesium deficiency is associated with a high frequency of cardiac arrhythmia, hypertension and sudden ischemic death. We investigated the in vivo effects of intravenous magnesium administration in a rat model of chemically induced (FeCl3) carotid thrombosis. The infusion of magnesium sulfate (MgSO4) before the topical application of FeCl3 prevented thrombus formation at concentrations of 0.3 M and 0.6 M, and delayed it even at 0.15 M. Similar results were obtained with MgCl2. The infusion of MgSO4 0.6 M seven minutes after FeCl3 application delayed but did not prevent thrombus formation. MgSO4 slightly reduced platelet aggregation ex vivo without affecting plasma clotting tests, but in vivo blood clotting time was markedly prolonged (tail transection method), thus indicating profoundly impaired coagulation. These data provide a rationale for the use of magnesium as an anti-thrombotic agent, but its pharmacological effect critically depends on the timing of administration.

Keywords

Magnesium - thrombosis - animal model - platelets - coagulation
 

  • References

  • 1 McLean RM. Magnesium and its therapeutic uses: a review. American J Med 1994; 96: 63-76.
    CrossrefPubMedGoogle Scholar
  • 2 Woods KL, Ravn HB. Magnesium. In: Clinical trials in cardiovascular disease. Hennekens CH. ed. Philadelphia: Saunders Company; 1999: 119-30.
    Google Scholar
  • 3 Yamori Y, Mizushima S. A review of the link between dietary magnesium and cardiovascular risk. J Cariovasc Risk 2000; 7: 31-5.
    PubMedGoogle Scholar
  • 4 Oto A. Magnesium treatment in acute myocardial infarction: an unresolved consensus. Eur Hearth J 1999; 20: 86-8.
    PubMedGoogle Scholar
  • 5 Horner SM. Efficacy of intravenous magnesium in acute myocardial infarction in reducing arrhythmias and mortality. Circulation 1992; 86: 774-9.
    CrossrefPubMedGoogle Scholar
  • 6 Woods Kl, Fletcher S, Roffe C, Haider Y. Intravenous magnesium sulphate in suspected acute myocardial infarction: results of the Second Leicester-Intravenous Magnesium Intervention Trials (LIMIT-2). Lancet 1992; 339: 1553-8.
    CrossrefPubMedGoogle Scholar
  • 7 Woods Kl, Fletcher S. Long-term outcome after intravenous magnesium sulphate in suspected myocardial infarction: the second Leicester-Intravenous Magnesium Intervention Trials (LIMIT-2). Lancet 1994; 343: 816-9.
    CrossrefPubMedGoogle Scholar
  • 8 ISIS-4 Collaborative Group.. Fourth International Study of Infarct Survival. ISIS-4: A randomized factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58 050 patients with suspected acute myocardial infarction. Lancet 1995; 345: 669-85.
    CrossrefPubMedGoogle Scholar
  • 9 Antman EM. Magnesium in acute MI. Timing is critical. Circulation 1995; 92: 2367-72.
    CrossrefPubMedGoogle Scholar
  • 10 Ravn HB. Pharmacological effects of magnesium on arterial thrombosis. Mechanism of action? Magnesium Res 1999; 12: 191-9.
    PubMedGoogle Scholar
  • 11 Acland R. Prevention of thrombosis with topical magnesium sulphate. Lancet 1971; I: 1179-80.
    PubMedGoogle Scholar
  • 12 Toft G, Ravn HB, Hjortdal VE. Intravenously and topically applied magnesium in the prevention of arterial thrombosis. Thromb Res 2000; 99: 61-9.
    CrossrefPubMedGoogle Scholar
  • 13 Kurtz KD, Main BW, Sandusky GE. Rat model of arterial thrombosis induced by ferric chloride. Thromb Haemost 1990; 60: 269-80.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Dejana E, Villa S, de Gaetano G. Bleeding time in rats: a comparison of different experimental conditions. Thromb Res 1982; 48: 108-11.
    PubMedGoogle Scholar
  • 15 Christensen CW, Rieder MA, Silverstein EL, Gencheff NE. Magnesium sulfate reduces myocardial infarct size when administered before but not after coronary reperfusion in a canine model. Circulation 1995; 92: 2617-21.
    CrossrefPubMedGoogle Scholar
  • 16 Herzog WR, Schlossberg ML, MacMurdy KS, Edenbaum LR, Gerber MJ, Vogel RA, Serebruany VL. Timing of magnesium therapy affects experimental infarct size. Circulation 1995; 92: 2622-6.
    CrossrefPubMedGoogle Scholar
  • 17 Ravn HB, Kristensen SD, Hjortdal VE, Thygesen K, Husted SE. Early administration of intravenous magnesium inhibits arterial thrombus formation. Arterioscler Thromb Vasc Biol 1997; 17: 3620-5.
    CrossrefPubMedGoogle Scholar
  • 18 Shechter M, Mertz CN, Paul-Labrador M, Meisel SR, Rude RK, Molloy MD, Dwyer JH, Shah PK, Kaul S. Oral magnesium supplementation inhibits platelet-dependent thrombosis in patients with coronary artery disease. Am J Cardiol 1999; 84: 152-6.
    PubMedGoogle Scholar
  • 19 Schumacher WA, Heran CL, Steinbacher TE, Youssef S, Ogletree ML. Superior activity of a thromboxane receptor antagonist as compared with aspirin in rat models of arterial and venous thrombosis. J Cardiovasc Pharmacol 1993; 22: 526-33.
    CrossrefPubMedGoogle Scholar
  • 20 Cirillo R, Lippi A, Subissi A, Agnelli G, Criscuoli M. Experimental pharmacology of hirunorm: a novel synthetic peptide thrombin inhibitor. Thromb Haemost 1996; 76: 384-92.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 Elg M, Gustafsson D, Deinum J. The importance of enzyme inhibition kinetics for the effect of thrombin inhibitors in a rat model of arterial thrombosis. Thromb Haemost 1997; 78: 1286-92.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 22 Lockyer S, Kambayashi J. Demonstration of flow and platelet dependency in a ferric chloride-induced model of thrombosis. J Cardiovasc Pharmacol 1999; 33: 718-25.
    CrossrefPubMedGoogle Scholar
  • 23 Buczko W, de Gaetano G. Effect of high doses of aspirin and salicylate on bleeding time in rats. Thromb Res 1983; 32: 631-4.
    CrossrefPubMedGoogle Scholar
  • 24 Iseri LT, French JH. Magnesium: Nature’s physiological calcium blocker. Am Heart J 1984; 108: 188-93.
    CrossrefPubMedGoogle Scholar