Potential Role of Neutrophil Anti‐Adhesion Therapy in Myocardial Stunning, Myocardial Infarction, and Organ Dysfunction After Cardiopulmonary Bypass

Edward D. Verrier, Irving Shen

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Abstract When activated neutrophils are recruited and bind to endothelial tissues, they release leukotrienes, proteolytic enzymes, and free radicals. The latter has been implicated in myocardial stunning following periods of ischemia and reperfusion, as may occur following cardiopulmonary bypass (CPB). The neutrophil surface complex CD11/CD18 promotes the neutrophil‐endothelial adhesion process. Monoclonal antibodies have been developed that can block neutrophil adhesion to the endothelium by preventing CD11/CD18 binding to adhesion molecules (ICAM‐1 or ELAM‐1) located on endothelial cells. We used monoclonal IgG antibody 60.3 to block neutrophil adherence and thereby potentially reduce myocardial stunning. Pretreatment of rabbits subjected to myocardial ischemia/reperfusion with either monoclonal 60.3 or saline resulted in only a small increase in the rate of recovery of preload recruitable stroke work index during reperfusion. More severe occlusion may have been needed to see significant results. We also evaluated the effects of anti‐neutrophil therapy in animal models of CPB. Rhesus monkeys were subjected to deep hypothermia and CPB, followed by 24 hours of fluid resuscitation. Animals receiving monoclonal 60.3 (N = 3) showed less weight gain, less infused resuscitative fluid, and higher terminal hematocrit and PaO2 than controls (N = 3). Anti‐neutrophil therapy may prevent multiorgan system failure in certain high risk patients.

Original languageEnglish (US)
Pages (from-to)309-312
Number of pages4
JournalJournal of Cardiac Surgery
Volume8
Issue number2 S
DOIs
StatePublished - 1993
Externally publishedYes

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Myocardial Stunning
Cardiopulmonary Bypass
Neutrophils
Myocardial Infarction
Reperfusion
Endothelium
Monoclonal Antibodies
Myocardial Reperfusion
Leukotrienes
Therapeutics
Hypothermia
Macaca mulatta
Hematocrit
Resuscitation
Weight Gain
Free Radicals
Myocardial Ischemia
Peptide Hydrolases
Ischemia
Endothelial Cells

ASJC Scopus subject areas

  • Surgery
  • Cardiology and Cardiovascular Medicine

Cite this

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abstract = "Abstract When activated neutrophils are recruited and bind to endothelial tissues, they release leukotrienes, proteolytic enzymes, and free radicals. The latter has been implicated in myocardial stunning following periods of ischemia and reperfusion, as may occur following cardiopulmonary bypass (CPB). The neutrophil surface complex CD11/CD18 promotes the neutrophil‐endothelial adhesion process. Monoclonal antibodies have been developed that can block neutrophil adhesion to the endothelium by preventing CD11/CD18 binding to adhesion molecules (ICAM‐1 or ELAM‐1) located on endothelial cells. We used monoclonal IgG antibody 60.3 to block neutrophil adherence and thereby potentially reduce myocardial stunning. Pretreatment of rabbits subjected to myocardial ischemia/reperfusion with either monoclonal 60.3 or saline resulted in only a small increase in the rate of recovery of preload recruitable stroke work index during reperfusion. More severe occlusion may have been needed to see significant results. We also evaluated the effects of anti‐neutrophil therapy in animal models of CPB. Rhesus monkeys were subjected to deep hypothermia and CPB, followed by 24 hours of fluid resuscitation. Animals receiving monoclonal 60.3 (N = 3) showed less weight gain, less infused resuscitative fluid, and higher terminal hematocrit and PaO2 than controls (N = 3). Anti‐neutrophil therapy may prevent multiorgan system failure in certain high risk patients.",
author = "Verrier, {Edward D.} and Irving Shen",
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PY - 1993

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N2 - Abstract When activated neutrophils are recruited and bind to endothelial tissues, they release leukotrienes, proteolytic enzymes, and free radicals. The latter has been implicated in myocardial stunning following periods of ischemia and reperfusion, as may occur following cardiopulmonary bypass (CPB). The neutrophil surface complex CD11/CD18 promotes the neutrophil‐endothelial adhesion process. Monoclonal antibodies have been developed that can block neutrophil adhesion to the endothelium by preventing CD11/CD18 binding to adhesion molecules (ICAM‐1 or ELAM‐1) located on endothelial cells. We used monoclonal IgG antibody 60.3 to block neutrophil adherence and thereby potentially reduce myocardial stunning. Pretreatment of rabbits subjected to myocardial ischemia/reperfusion with either monoclonal 60.3 or saline resulted in only a small increase in the rate of recovery of preload recruitable stroke work index during reperfusion. More severe occlusion may have been needed to see significant results. We also evaluated the effects of anti‐neutrophil therapy in animal models of CPB. Rhesus monkeys were subjected to deep hypothermia and CPB, followed by 24 hours of fluid resuscitation. Animals receiving monoclonal 60.3 (N = 3) showed less weight gain, less infused resuscitative fluid, and higher terminal hematocrit and PaO2 than controls (N = 3). Anti‐neutrophil therapy may prevent multiorgan system failure in certain high risk patients.

AB - Abstract When activated neutrophils are recruited and bind to endothelial tissues, they release leukotrienes, proteolytic enzymes, and free radicals. The latter has been implicated in myocardial stunning following periods of ischemia and reperfusion, as may occur following cardiopulmonary bypass (CPB). The neutrophil surface complex CD11/CD18 promotes the neutrophil‐endothelial adhesion process. Monoclonal antibodies have been developed that can block neutrophil adhesion to the endothelium by preventing CD11/CD18 binding to adhesion molecules (ICAM‐1 or ELAM‐1) located on endothelial cells. We used monoclonal IgG antibody 60.3 to block neutrophil adherence and thereby potentially reduce myocardial stunning. Pretreatment of rabbits subjected to myocardial ischemia/reperfusion with either monoclonal 60.3 or saline resulted in only a small increase in the rate of recovery of preload recruitable stroke work index during reperfusion. More severe occlusion may have been needed to see significant results. We also evaluated the effects of anti‐neutrophil therapy in animal models of CPB. Rhesus monkeys were subjected to deep hypothermia and CPB, followed by 24 hours of fluid resuscitation. Animals receiving monoclonal 60.3 (N = 3) showed less weight gain, less infused resuscitative fluid, and higher terminal hematocrit and PaO2 than controls (N = 3). Anti‐neutrophil therapy may prevent multiorgan system failure in certain high risk patients.

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