Role of tissue factor-mediated coagulation in ischemia/ reperfusion-induced injury of Langendorf-perfused rabbit hearts.

Abstract

BACKGROUND:

Production of oxygen free radicals, and activation of neutrophils and plasma complement contribute to myocardial reperfusion injury, but the role of coagulation has not been assessed.

OBJECTIVE:

To characterize tissue-factor-mediated generation of thrombin and its association with tissue injury during reperfusion from normothermic ischemia of isolated, Langendorf-perfused rabbit hearts.

METHODS:

Activation of coagulation was assessed by addition of 12% rabbit plasma and human fibrinogen to Krebs-Henseleit-buffer perfusate with measurement of levels of human fibrinopeptide A (hFPA) in the heart effluent as an index of thrombin-mediated formation of fibrin.

RESULTS:

Concentrations of hFPA in the effluent were minimal during non-ischemic perfusion (5 +/- 5 ng/ml, n=6) and during 50 min of ischemia (13 +/- 3 ng/ml, n=6), but increased markedly during the first 20 min of reperfusion (to 41 +/- 29 ng/ml, P=0.03 versus before reperfusion). Addition to the perfusate of 10 microg/ml recombinant human tissue-factor-pathway inhibitor, the physiologic inhibitor of tissue-factor-mediated coagulation, abolished increases in the level of hFPA after reperfusion. However, indexes of myocardial injury manifested during reperfusion, including decrease in recovery of left ventricular pressure developed, increase in left ventricular end-diastolic pressure, and increase in activity of creatine kinase in the heart effluent, were not improved by anticoagulation with recombinant human tissue-factor-pathway inhibitor.

CONCLUSION:

Our results do not support the hypothesis that coagulation plays a major role in ischemia/reperfusion injury of Langendorf-perfused rabbit hearts.

• Authors: L Armaganian, G Kam, P R Eisenberg, K B Schechtman, D R Abendschein
• Journal: Coronary artery disease (Coron Artery Dis) Vol. 11 Issue 6 Pg. 481-7 (Sep 2000) ISSN: 0954-6928 [Print] England
• PMID: 10966134 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fibrinolytic Agents
• Lipoproteins
• Peptide Fragments
• tissue factor pathway inhibitor (1-161)
• Fibrinopeptide A
• Thromboplastin
• Creatine Kinase
• Thrombin

Topics

• Animals
• Blood Coagulation (drug effects, physiology)
• Coronary Vessels (physiology)
• Creatine Kinase (blood)
• Fibrinolytic Agents (pharmacology, therapeutic use)
• Fibrinopeptide A (analysis)
• Heart (physiology)
• Humans
• Lipoproteins (pharmacology, therapeutic use)
• Peptide Fragments (pharmacology, therapeutic use)
• Rabbits
• Reperfusion Injury (drug therapy, metabolism, physiopathology)
• Thrombin (biosynthesis)
• Thromboplastin (antagonists & inhibitors, physiology)