Serial changes of natural antithrombotics during myocardial ischemia-reperfusion in swine. Effects of magnesium, diltiazem, and a novel Mac-1 inhibitor

V. L. Serebruany, William Raymond Herzog, P. A. Gurbel

Research output: Contribution to journalArticle

Abstract

Plasma antithrombin-III (AT-III), protein S, and protein C were measured during myocardial stunning (MS) and acute myocardial infarction (AMI). The effects of magnesium (Mg), diltiazem, and a Mac-1 inhibitor on their plasma levels were elucidated. Forty-nine open-chest swine underwent brief (8 min), or prolonged (50 min) coronary artery occlusion followed by reperfusion. During MS an increase in the plasma AT-III (from 98.5 ± 3.38% to 138.1 ± 3.6%) during the early occlusion phase, without any further changes was observed. The profile of total protein S was not changed during MS. Protein C increased at the end of occlusion (from 45.3 ± 1.8% to 55.7 ± 1.4%) reaching a peak (64.5 ± 1.4%) at the beginning of reperfusion. When compared with controls, no significant differences were found in the antithrombotics profile during MS after pretreatment with Mac-1 inhibitor. For the AMI, the AT-III decreased during occlusion (from 98.5 ± 3.4% to 61.0 ± 3.6%). The protein S decreased during occlusion with the lowest level at 1 h of reperfusion (from 71.8 ± 2.2% to 46.7 ± 1.0%), followed by an increase during late reperfusion (59.2 ± 1.5%). Contrarily, protein C increased during occlusion and early reperfusion(from 44.7 ± 2.6% to 79.4 ± 2.4%), but declined to 49.6 ± 2.5% thereafter. In both Mg and diltiazem-treated swine, protein C was higher at the end of occlusion and during the entire reperfusion period compared with controls. Mg and diltiazem therapy was associated with the slight elevation of plasma AT-III. The patterns for protein S level during ischemia-reperfusion were similar with the controls. Protein S was higher at the end of occlusion and through the entire reperfusion in the NPC 15669-treated animals when compared with the controls. Mac-1 inhibition was associated with the elevated protein C during late reperfusion. Ability of Mg, diltiazem, and a Mac-1 inhibitor to favorably modulate the plasma level of antithrombotics have direct clinical implications for the use of these agents in patients with acute coronary artery syndromes.

Original languageEnglish (US)
Pages (from-to)632-640
Number of pages9
JournalBlood Coagulation and Fibrinolysis
Volume7
Issue number6
StatePublished - 1996
Externally publishedYes

Fingerprint

Myocardial Reperfusion
Diltiazem
Magnesium
Reperfusion
Myocardial Ischemia
Swine
Protein S
Myocardial Stunning
Protein C
Antithrombin III
Coronary Vessels
Myocardial Infarction
Antithrombin Proteins
Coronary Occlusion
Proxy
Acute Coronary Syndrome
Thorax
Ischemia

Keywords

  • acute myocardial infarction
  • animal model
  • antithrombin III
  • diltiazem
  • Mac-1 inhibitor
  • magnesium
  • myocardial stunning
  • protein C
  • protein S

ASJC Scopus subject areas

  • Hematology

Cite this

Serial changes of natural antithrombotics during myocardial ischemia-reperfusion in swine. Effects of magnesium, diltiazem, and a novel Mac-1 inhibitor. / Serebruany, V. L.; Herzog, William Raymond; Gurbel, P. A.

In: Blood Coagulation and Fibrinolysis, Vol. 7, No. 6, 1996, p. 632-640.

Research output: Contribution to journalArticle

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abstract = "Plasma antithrombin-III (AT-III), protein S, and protein C were measured during myocardial stunning (MS) and acute myocardial infarction (AMI). The effects of magnesium (Mg), diltiazem, and a Mac-1 inhibitor on their plasma levels were elucidated. Forty-nine open-chest swine underwent brief (8 min), or prolonged (50 min) coronary artery occlusion followed by reperfusion. During MS an increase in the plasma AT-III (from 98.5 ± 3.38{\%} to 138.1 ± 3.6{\%}) during the early occlusion phase, without any further changes was observed. The profile of total protein S was not changed during MS. Protein C increased at the end of occlusion (from 45.3 ± 1.8{\%} to 55.7 ± 1.4{\%}) reaching a peak (64.5 ± 1.4{\%}) at the beginning of reperfusion. When compared with controls, no significant differences were found in the antithrombotics profile during MS after pretreatment with Mac-1 inhibitor. For the AMI, the AT-III decreased during occlusion (from 98.5 ± 3.4{\%} to 61.0 ± 3.6{\%}). The protein S decreased during occlusion with the lowest level at 1 h of reperfusion (from 71.8 ± 2.2{\%} to 46.7 ± 1.0{\%}), followed by an increase during late reperfusion (59.2 ± 1.5{\%}). Contrarily, protein C increased during occlusion and early reperfusion(from 44.7 ± 2.6{\%} to 79.4 ± 2.4{\%}), but declined to 49.6 ± 2.5{\%} thereafter. In both Mg and diltiazem-treated swine, protein C was higher at the end of occlusion and during the entire reperfusion period compared with controls. Mg and diltiazem therapy was associated with the slight elevation of plasma AT-III. The patterns for protein S level during ischemia-reperfusion were similar with the controls. Protein S was higher at the end of occlusion and through the entire reperfusion in the NPC 15669-treated animals when compared with the controls. Mac-1 inhibition was associated with the elevated protein C during late reperfusion. Ability of Mg, diltiazem, and a Mac-1 inhibitor to favorably modulate the plasma level of antithrombotics have direct clinical implications for the use of these agents in patients with acute coronary artery syndromes.",
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T1 - Serial changes of natural antithrombotics during myocardial ischemia-reperfusion in swine. Effects of magnesium, diltiazem, and a novel Mac-1 inhibitor

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N2 - Plasma antithrombin-III (AT-III), protein S, and protein C were measured during myocardial stunning (MS) and acute myocardial infarction (AMI). The effects of magnesium (Mg), diltiazem, and a Mac-1 inhibitor on their plasma levels were elucidated. Forty-nine open-chest swine underwent brief (8 min), or prolonged (50 min) coronary artery occlusion followed by reperfusion. During MS an increase in the plasma AT-III (from 98.5 ± 3.38% to 138.1 ± 3.6%) during the early occlusion phase, without any further changes was observed. The profile of total protein S was not changed during MS. Protein C increased at the end of occlusion (from 45.3 ± 1.8% to 55.7 ± 1.4%) reaching a peak (64.5 ± 1.4%) at the beginning of reperfusion. When compared with controls, no significant differences were found in the antithrombotics profile during MS after pretreatment with Mac-1 inhibitor. For the AMI, the AT-III decreased during occlusion (from 98.5 ± 3.4% to 61.0 ± 3.6%). The protein S decreased during occlusion with the lowest level at 1 h of reperfusion (from 71.8 ± 2.2% to 46.7 ± 1.0%), followed by an increase during late reperfusion (59.2 ± 1.5%). Contrarily, protein C increased during occlusion and early reperfusion(from 44.7 ± 2.6% to 79.4 ± 2.4%), but declined to 49.6 ± 2.5% thereafter. In both Mg and diltiazem-treated swine, protein C was higher at the end of occlusion and during the entire reperfusion period compared with controls. Mg and diltiazem therapy was associated with the slight elevation of plasma AT-III. The patterns for protein S level during ischemia-reperfusion were similar with the controls. Protein S was higher at the end of occlusion and through the entire reperfusion in the NPC 15669-treated animals when compared with the controls. Mac-1 inhibition was associated with the elevated protein C during late reperfusion. Ability of Mg, diltiazem, and a Mac-1 inhibitor to favorably modulate the plasma level of antithrombotics have direct clinical implications for the use of these agents in patients with acute coronary artery syndromes.

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