Prospective studies place the frequency of major stroke following surgery utilizing cardiopulmonary bypass (CPB) at 5%, with half the patients so affected suffering long-term disability. Neuropsychologic performance is acutely impaired in 20-60% of cardiac surgical patients, with 7-15% of patients permanently affected. Our long-term objective is to understand the pathogenesis of these injuries, and to develop techniques and therapies to eliminate or ameliorate them. We believe the process of CPB is likely to affect outcome of neurologic insults which occur during CPB. This process affects the cerebral vasculature, pumping functions, and the blood itself. Hemodilution, hypothermia, non-pulsatile flow, and blood gas management may each compromise compensatory mechanisms which ordinarily maintain neuronal viability, namely increases in cerebral blood flow (CBF) and oxygen extraction.
Our specific aims are to determine whether the following affect cerebral oxygen availability and autoregulatory processes during CPB: 1) hypothermia (25 degrees C) alone; 2) hypothermic blood gis management (alpha-stat vs pH-stat); 3) blood rheology (pentoxitylline); and 4) pulsatile perfusion. Using information derived from these studies, specific bypass management strategies will then be tested to attempt to ameliorate acute neurologic injuries. These questions will be addressed using a rabbit model of CPB we have developed. The cerebral circulation will be """"""""challenged"""""""" with either progressive hypoxemia or hypotension during CPB. Oxygen availability will be assessed by measurements of cerebral oxygen extraction, blood flow, metabolic rates for oxygen and glucose, plus electrophysiology. CBF is measured via individually validated microsphere technique, and cerebral metabolism as the product of CBF and cerebral arteriovenous content difference. We anticipate pH-stat management, pentoxifylline, and pulsatile flow will improve oxygen availability during hypothermic CPB. We will then use a transorbital middle cerebral artery occlusion to produce focal cerebral ischemia and attempt to use knowledge thus far gained to find optimal CPB technique with respect to neurologic outcome. The latter will be assessed using standard techniques to quantify infarct volume. We believe understanding of the cerebral physiology of CPB will permit development of techniques which ameliorate neurologic injury.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL047159-01
Application #
3366387
Study Section
Special Emphasis Panel (SRC (MM))
Project Start
1991-08-01
Project End
1995-05-31
Budget Start
1991-08-01
Budget End
1992-05-31
Support Year
1
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Iowa
Department
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Enomoto, S; Hindman, B J; Dexter, F et al. (1996) Rapid rewarming causes an increase in the cerebral metabolic rate for oxygen that is temporarily unmatched by cerebral blood flow. A study during cardiopulmonary bypass in rabbits. Anesthesiology 84:1392-400
Reasoner, D K; Ryu, K H; Hindman, B J et al. (1996) Marked hemodilution increases neurologic injury after focal cerebral ischemia in rabbits. Anesth Analg 82:61-7
Hindman, B J; Dexter, F; Smith, T et al. (1995) Pulsatile versus nonpulsatile flow. No difference in cerebral blood flow or metabolism during normothermic cardiopulmonary bypass in rabbits. Anesthesiology 82:241-50
Dexter, F (1995) Mathematical analysis of haemodilution's direct effect on rate of brain cooling during cardiopulmonary bypass. Med Biol Eng Comput 33:24-6
Hindman, B J; Dexter, F; Cutkomp, J et al. (1995) pH-stat management reduces the cerebral metabolic rate for oxygen during profound hypothermia (17 degrees C). A study during cardiopulmonary bypass in rabbits. Anesthesiology 82:983-95;discussion 24A
Dexter, F; Hindman, B J (1995) Theoretical analysis of cerebral venous blood hemoglobin oxygen saturation as an index of cerebral oxygenation during hypothermic cardiopulmonary bypass. A counterproposal to the ""luxury perfusion"" hypothesis. Anesthesiology 83:405-12
Hindman, B J; Dexter, F; Cutkomp, J et al. (1995) Diaspirin cross-linked hemoglobin does not increase brain oxygen consumption during hypothermic cardiopulmonary bypass in rabbits. Anesthesiology 83:1302-11
Hindman, B J; Dexter, F; Ryu, K H et al. (1994) Pulsatile versus nonpulsatile cardiopulmonary bypass. No difference in brain blood flow or metabolism at 27 degrees C. Anesthesiology 80:1137-47
Dexter, F; Hindman, B J (1994) Computer simulation of brain cooling during cardiopulmonary bypass. Ann Thorac Surg 57:1171-8;discussion 1178-9
Dexter, F; Hindman, B J; Cutkomp, J et al. (1994) Blood warms as it flows retrograde from a femoral cannulation site to the carotid artery during cardiopulmonary bypass. Perfusion 9:393-7

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