Magnesium Inhibits Platelet Activity - an Infusion Study in Healthy Volunteers

 

PDF Download Buy Article Permissions and Reprints

Summary

Magnesium (Mg) has shown the ability to inhibit arterial thrombus formation in some experimental animal studies. This effect may be due to an inhibition of platelet reactivity as in vitro studies have demonstrated that Mg inhibits platelet aggregation. In order to evaluate the in vivo effect of Mg in humans measurements of platelet activity, fibrinolytic activity, as well as measurements of prostacyclin (PGI₂), and nitric oxide (NO) release were performed after infusion of magnesium sulphate (MgSO₄) in healthy volunteers. In a placebo controlled, cross-over study in 14 healthy male subjects, 8 mmol MgSO₄ was given as an intravenous bolus over 15 min followed by 3 mmol MgSO₄/h.

The mean S-Mg concentration increased from 0.85 to 1.50 mM during the Mg infusion period. A transient decrease in blood pressure was observed during the initial bolus infusion of Mg. Haemodynamic parameters were otherwise stable. The bleeding time increased by 48% during the Mg infusion (p <0.005), and in accordance with this, ex vivo platelet aggregation in platelet rich plasma was significantly inhibited, both following collagen (p = 0.02) and ADP (p = 0.04) stimulation. There were no significant changes in plasma beta-thromboglobulin concentration or the excretion of 2,3-dinor-thromboxane B2 in the urine. Neither tissue plasminogen activator (t-PA)_activity, tissue plasminogen activator (t-PA)_antigen nor plasminogen activator inhibitor (PAI)_antigen changed during the Mg infusion period. There was no sign of increased release of PGI₂ from the vessel wall as judged by urinary concentration of 2,3-dinor-6-keto-prostaglandin F_1α. Nor was there any sustained increase in the release of NO, measured as nitrate concentration in urine. However, a transient increase in NO release was observed during one sample period.

In conclusion a reduced platelet activity and increased bleeding time, was found during Mg infusion in healthy volunteers. Fibrinolytic activity showed no changes. An anti-platelet effect may in part be responsible for the beneficial effect of Mg, described in patients with acute myocardial infarction (MI) and preeclampsia.

• References

• 1 Sprenglers ED, Kluft C. Plasminogen activator inhibitors. Blood 1987; 69: 381-387
  PubMedGoogle Scholar
• 2 Rånby M, Bergsdorf N, Nilsson T. Enzymatic properties of the one- and two-chain form of tissue plasminogen activator. Thromb Res 1982; 27: 175-183
  CrossrefPubMedGoogle Scholar
• 3 Todd AS. The histological localization of fibrinolysin activator. J Pathol Bact 1959; 78: 281-283
  CrossrefPubMedGoogle Scholar
• 4 Danø K, Andreasen JA, Grpndahl-Hansen J, Kristensen P, Nielsen LS, Skriver L. Plasminogen activators, tissue degradation, and cancer. Adv Cancer Res 1985; 44: 139-239
  PubMedGoogle Scholar
• 5 Estreicher A, Wohlwend A, Belin D, Schleuning W-D, Vassalli J-D. Characterization of the cellular binding site for the urokinase-type plasminogen activator. J Biol Chem 1989; 264: 1180-1189
  PubMedGoogle Scholar
• 6 van Hinsberg VW, van der Berg EA, Fiers W, Dooijewaard G. Tumor necrosis factor induces the production of urokinase-type plasminogen activator by human endothelial cells. Blood 1990; 75: 1991-1998
  PubMedGoogle Scholar
• 7 Craig H, Lundgren MD, Hirofumi SawaMD, Burton E, Sobel MD, Satoshi FujiMD. Modulation of expression of monocyte/macrophage plasminogen activator activity and its implications for attenuation of vasculopathy. Circulation 1994; 90: 1927-1934
  CrossrefPubMedGoogle Scholar
• 8 Vassalli JD, Sappino A-P, Belin D. The plasminogen activator/plasmin system. J Clin Invest 1991; 88: 1067-1072
  CrossrefPubMedGoogle Scholar
• 9 Wiman B, Hamsten A. Impaired fibrinolysis and risk of thromboembolism. Prog Cardiovasc Dis 1991; 34: 179-192
  CrossrefPubMedGoogle Scholar
• 10 Schneiderman J, Sawdey MS, Keeton MR, Bordin GM, Bernstein EF, Dilley RB, Loskutoff J. Increased type 1 plasminogen activator inhibitor gene expression in atherosclerotic human arteries. Prot Natl Acad Sci USA 1992; 89: 6998-7002
  CrossrefPubMedGoogle Scholar
• 11 Juhan-Vague I, Alessi MC. Plasminogen activator inhibitor 1 and athero-thrombosis. Thromb Haemost 1993; 70: 138-143
  Article in Thieme ConnectPubMedGoogle Scholar
• 12 Lupu F, Bergonzelli GE, Heim DA, Cousin E, Genton CY, Bachmann F, Kruithof EKO. Localization and production of plasminogen activator inhibitor-1 in human healthy and atherosclerotic arteries. Arterioscler Thromb 1993; 13: 1090-1100
  CrossrefPubMedGoogle Scholar
• 13 Chomiki N, Henry M, Alessi MC, Anfonsso F, Juhan-Vague I. Plasminogen activator inhibitor-1 expression in human liver and healthy or atherosclerotic vessel walls. Thromb Haemost 1994; 72: 44-53
  PubMedGoogle Scholar
• 14 Cordell JL, Falini B, Erber WN, Ghosh AK, Abdulazis Z, MacDonald S, Pulford KAF, Stein H, Mason DY. Immunoenzymatic labeling of mono-clonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem 1984; 32: 219-229
  CrossrefPubMedGoogle Scholar
• 15 Buø L, Lynberg T, Jørgensen L, Johansen H, Aasen AO. Location of plasminogen activator (PA) and PA inhibitor in human colorectal adenocarcinomas. APMIS 1993; 101: 235-241
  CrossrefPubMedGoogle Scholar
• 16 Hamsten A, Wiman B, de Faire U, Blombäck M. Increased plasma levels of a rapid inhibitor of tissue plasminogen activator in young survivors of myocardial infarction. N Eng J Med 1985; 313: 1557-1563
  CrossrefPubMedGoogle Scholar
• 17 Juhan-Vague I, Alessi MC, Vague P. Increased plasma plasminogen activator inhibitor-1 levels. A possible link between insulin resistance and atherothrombosis. Diabetologia 1991; 34: 457-462
  PubMedGoogle Scholar
• 18 Lupu F, Heim DA, Bachmann F, Hurni M, Kakkar VV, Kruithof EKO. Plasminogen activator expression in human atherosclerotic lesions. Arterioscler Thromb Vase Biol 1995; 15: 1444-1455
  CrossrefPubMedGoogle Scholar
• 19 Raghunath PN, Tomaszewski JE, Brady ST, Caron RJ, Okada SS, Barnathan ES. Plasminogen activator system in human coronary atherosclerosis. Arterioscler Thromb Vase Biol 1995; 15: 1432-1443
  CrossrefPubMedGoogle Scholar
• 20 Horie T, Sekigushi M, Hirosawa K. Coronary thrombosis in pathogenesis of acute myocardial infarction: Histopathological study of 108 necropsied cases using serial section. Br Heart J 1978; 40: 153
  CrossrefPubMedGoogle Scholar
• 21 Falk E. Plaque rupture with severe preexisting stenosis precipitating coronary thrombosis: Characteristics of coronary atherosclerotic plaques underlying fatal occlusive thrombi. Br Heart J 1983; 50: 127
  CrossrefPubMedGoogle Scholar
• 22 Amman V, Nilsson A, Stemme S, Risberg B, Rymo L. Expression of plasminogen activator inhibitor-1 mRNA in healthy, atherosclerotic and thrombotic human arteries and veins. Thromb Res 1994; 76: 487-499
  CrossrefPubMedGoogle Scholar
• 23 Jakobsson A. Induction and inhibition of experimental angiogenesis. Thesis Vasastadens Bokbinderi AB; Göteborg: 1994
  Google Scholar
• 24 Reilly CF, MacFall RC. Platelet-derived growth factor and transforming growth factor B (beta) regulate plasminogen activator inhibitor 1 synthesis in vascular smooth muscle cells. J Biol Chem 1991; 266: 9419-9427
  PubMedGoogle Scholar
• 25 Clowes AW, Clowes MM, Au YPT, Reidy MA, Belin D. Smooth muscle cells express urokinase during mitogenisis and tissue-type plasminogen activator during migration in injured rat carotid artery. Circ Res 1990; 67: 61-67
  CrossrefPubMedGoogle Scholar
• 26 Gown A, Tsukada T, Ross R. Human atherosclerosis: II: immunocytochemical analysis of the cellular composition of human atherosclerotic lesions. Am J Pathol 1986; 125: 191-207
  PubMedGoogle Scholar
• 27 Nathan CF. Secretory products of macrophages. J Clin Invest 1987; 79: 319-326
  CrossrefPubMedGoogle Scholar
• 28 Schleef RR, Bevilacqua MP, Sawdey M, Gimbrone MA, Loskutoff DJ. Cytokine activation of vascular endothelium. J Biol Chem 1988; 263: 5797-5803
  PubMedGoogle Scholar
• 29 Amman V, Stemme S, Rymo L, Risberg B. Interferon-γ modulates the fibrinolytic response in cultured human endothelial cells. Thromb Res 1995; 77: 431-440
  CrossrefPubMedGoogle Scholar