The candidate received residency training in Pediatrics and Anesthesiology, and subspeciality training in Pediatric Critical Care Medicine, during which he was instrumental in developing an infant pediatric cardiopulmonary resuscitation (CPR) model in piglets. Presently, in addition to patient care and teaching activities, on the Anestesia and Critical Care faculty the candidate has been a major participant in the laboratories of Dr. Richard Traystman (sponsor of the candidate) performing CPR experiments. During prolonged CPR in infants, neither cerebral blood flow (CBF) nor cerebral metabolism is sustained. Prolonged CPR in infants is an important clinical issue because of the long periods that infants often need CPR administered and the poor outcome frequently obtained following cardiac arrest and CPR.
In aim 1, the mechanism of this failure will be evaluated and mechanical maneuvers designed to preserve CBF and cerebral O2 uptake will be tested.
In aim 2 we will determine if equipotent doses of different classes of adrenergic drugs given during CPR have different effects on the recovery of cerebral metabolism, regional CBF and electrical function. We will find out if the blood brain barrier is disrupted during CPR or during the cerebral hyperemia that follows cardioversion, or if circulating epinephrine gains entry into the brain by saturating the enzymatic barrier for catecholamines. After a period of cardiac arrest, external chest compression partially reestablishes CBF until the circulation is fully restored by cardioversion. Depending on the level of CBF attained during CPR, partial cerebral ischemia may continue. Reperfusion injury associated with O2 derived free radical production may begin with CPR.
In aim 3, we will determine whether modest levels of cerebral reoxygenation achieved with CPR generates superoxide radical and if cerebral O2 delivery must reach a critical level for free radical generation to occur, comparing this to full reperfusion following cardioversion.
In aim 4, we will determine how free radical scavengers can best be administered during CPR to inhibit free radical appearance and whether these agents during CPR improves recovery and brain metabolism, electrical function, CBF and neurological outcome. These studies will add much to the clinical practice of CPR in infants. In addition, the CIA will provide experience and supervision which will facilitate the applicant's development as an effective and independent investigator.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
1K08NS001293-01
Application #
3084182
Study Section
Neurological Disorders Program Project Review A Committee (NSPA)
Project Start
1988-04-01
Project End
1993-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Schleien, C L; Eberle, B; Shaffner, D H et al. (1994) Reduced blood-brain barrier permeability after cardiac arrest by conjugated superoxide dismutase and catalase in piglets. Stroke 25:1830-4;discussion 1834-5
Shaffner, D H; Schleien, C L; Koehler, R C et al. (1994) Effect of vest cardiopulmonary resuscitation on cerebral and coronary perfusion in an infant porcine model. Crit Care Med 22:1817-26
Schleien, C L (1993) Physiology of cardiopulmonary resuscitation in children. Crit Care Med 21:S321-3
Schleien, C L; Koehler, R C; Shaffner, D H et al. (1991) Blood-brain barrier disruption after cardiopulmonary resuscitation in immature swine. Stroke 22:477-83
Gervais, H W; Schleien, C L; Koehler, R C et al. (1991) Effect of adrenergic drugs on cerebral blood flow, metabolism, and evoked potentials after delayed cardiopulmonary resuscitation in dogs. Stroke 22:1554-61
Schleien, C L; Koehler, R C; Shaffner, D H et al. (1990) Blood-brain barrier integrity during cardiopulmonary resuscitation in dogs. Stroke 21:1185-91
Schleien, C L; Berkowitz, I D; Traystman, R et al. (1989) Controversial issues in cardiopulmonary resuscitation. Anesthesiology 71:133-49
Schleien, C L; Koehler, R C; Gervais, H et al. (1989) Organ blood flow and somatosensory-evoked potentials during and after cardiopulmonary resuscitation with epinephrine or phenylephrine. Circulation 79:1332-42