The long-term goal of this research is to evaluate alternative methods of myocardial preservation and to assess the significance of risk factors such as hypoxemia or age in children who must undergo cardiopulmonary bypass. Three hypotheses will be tested in an animal model: (1) The presence of chronic hypoxemia prior to global ischemia and reperfusion (GIR) is associated with more severe cardiac deficits after GIR than is seen in hearts from normoxic animals; (2) The administration of an oxygen free radical scavenging solution (ORS) prior to GIR improves the subsequent cardiac status compared to potassium-containing (KCS) cardioplegic solutions or control (NaCl); (3) The neonatal heart suffers more severe damage from GIR than does the adult heart. Hearts from 4 groups of neonatal (10 day old) and adult (8 weeks old) New Zealand white rabbits, raised under normoxic or hypoxic conditions will be studied in an isolated heart apparatus. Following control electrophysiological (E) and ventricular function (F) measurements, the hearts will alternatively receive NaCl, ORS, or KCS prior to 60 minutes of hypothermic (15 degrees C) ischemia. The initial studies will be repeated after 5 minutes and 45 minutes of reperfusion (E) or at 45 minutes after reperfusion (F). Tissue will then be collected for cellular E studies, papillary muscle contractile measurements, histopathology including electron microscopy, and wet weight/dry weight determination. Hearts from an additional control group of normoxic 10 day old rabbits will undergo similar E and F measurements. However, these hearts will be maintained at normal perfusion conditions for 1 hr. 45 min, with subsequent E, F, and other studies conducted as already described. These studies will test the stated hypotheses and provide a data base for future development of methods of myocardial preservation in the infant.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL035680-02
Application #
3349806
Study Section
(SRC)
Project Start
1985-09-30
Project End
1988-09-29
Budget Start
1986-09-30
Budget End
1987-09-29
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Florida
Department
Type
Schools of Veterinary Medicine
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Pace, Betty S; Shartava, Archil; Pack-Mabien, Ardie et al. (2003) Effects of N-acetylcysteine on dense cell formation in sickle cell disease. Am J Hematol 73:26-32
Buss, D D; Hennemann 3rd, W W; Posner, P (1987) Maturation of coronary responsiveness to exogenous adenosine in the rabbit. Basic Res Cardiol 82:290-6