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Early endothelial damage and leukocyte accumulation in piglet brains following cardiac arrest

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Abstract

This study examined the early microvascular and neuronal consequences of cardiac arrest and resuscitation in piglets. We hypothesized that early morphological changes occur after cardiac arrest and reperfusion, and that these findings are partly caused by post-resuscitation hypertension. Three groups of normothermic piglets (37.5°–38.5°C) were investigated: group 1, non-ischemic time controls; group 2, piglets undergoing 8 min of cardiac arrest by ventricular fibrillation, 6 min of cardiopulmonary resuscitation (CPR) and 4 h of reperfusion; and group 3, non-ischemic hypertensive controls, receiving 6 min of CPR after only 10 s of cardiac arrest followed by 4-h survival. Immediately following resuscitation, acute hypertension occurred with peak systolic pressure equal to 197 ±15 mm Hg usually lasting less than 10 min. In reacted vibratome sections, isolated foci of extravasated horseradish peroxidase were noted throughout the brain within surface cortical layers and around penetrating vessels in group 2. Stained plastic sections of leaky sites demonstrated variable degrees of tissue injury. While many sections were unremarkable except for luminal red blood cells and leukocytes, other specimens contained abnormal neurons, some appearing irreversibly injured. The number of vessels containing leukocytes was higher in group 2 than in controls (3.8±0.6% vs 1.4±0.4% of vessels, P<0.05). Evidence for irreversible neuronal injury was only seen in group 2. Endothelial vacuolization was higher in groups 2 and 3 than in group 1 (P<0.05). Ultrastructural examination of leaky sites identified mononuclear and polymorphonuclear leukocytes adhering to the endothelium of venules and capillaries only in group 2. The early appearance of luminal leukocytes in ischemic animals indicates that these cells may contribute to the genesis of ischemia reperfusion injury in this model. In both groups 2 and 3 endothelial cells demonstrated vacuolation and luminal discontinuities with evidence of perivascular astrocytic swelling. Widespread microvascular and neuronal damage is present as early as 4 h after cardiac arrest in infant piglets. Hypertension appears to play a role in the production of some of the endothelial changes.

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Authors and Affiliations

  1. Department of Pediatrics (R-131) Pediatric Critical Care Medicine, University of Miami School of Medicine, Post Office Box 016960, 33101, Miami, FL, USA

    Manuel J. Caceres, Charles L. Schleien & Barry Gelman

  2. Department of Anesthesiooogy, University of Miami School of Medicine, Miami, Florida, USA

    Charles L. Schleien

  3. Clinical Pediatrics, University of Miami School of Medicine, Miami, Florida, USA

    John W. Kuluz

  4. Department of Neurology, University of Miami School of Medicine, Miami, Florida, USA

    W. Dalton Dietrich

Authors
  1. Manuel J. Caceres
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  2. Charles L. Schleien
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  3. John W. Kuluz
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  4. Barry Gelman
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  5. W. Dalton Dietrich
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Caceres, M.J., Schleien, C.L., Kuluz, J.W. et al. Early endothelial damage and leukocyte accumulation in piglet brains following cardiac arrest. Acta Neuropathol 90, 582–591 (1995). https://doi.org/10.1007/BF00318570

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  • DOI: https://doi.org/10.1007/BF00318570

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