The purpose of this research to examine platelet function in a model of intracranial hypertension and to determine if the response of neonatal lamb platelets differs from that of mature sheep. Using neonatal lambs and mature sheep, global incomplete ischemia will be produced for 30 minutes by infusion of artificial cerebral spinal fluid, while the mean arterial pressure is allowed to vary spontaneously and intracranial pressure adjusted accordingly. Following ischemia, baseline and serial measurements during 4 hours of reperfusion will permit evaluation of cerebral blood flow, cerebral blood oxygen consumption and platelet reactivity to known platelet aggregants. The first major aim is to compare and contrast the effects of transient global ischemia on platelet reactivity in neonatal vs. mature animals using platelet aggregation with adenosine diphosphate (ADP), arachidonic acid, and thrombin. Studies will be done with whole blood platelets and washed platelets.
The second aim will be to examine a potential mechanism for ischemia-induced platelet dysfunction by determining if nitric oxide plays a role in platelet activation during cerebral ischemia-reperfusion in neonatal vs. mature sheep. It is intended that findings from the study will buttress the physiologic rationale of nursing care of patients following cardiac arrest, trauma and stroke, and others with cerebral-vascular injury. It is also intended that any detection of age-related variation in post-ischemic platelet function will be used to develop treatment protocols which impact nursing therapy of critically ill neonates.
| Littleton-Kearney, M T; Hurn, P D; Kickler, T S et al. (1998) Incomplete global cerebral ischemia alters platelet biology in neonatal and adult sheep. Am J Physiol 274:H1293-300 |
| Palmon, S C; Williams, M J; Littleton-Kearney, M T et al. (1998) Estrogen increases cGMP in selected brain regions and in cerebral microvessels. J Cereb Blood Flow Metab 18:1248-52 |
