Hypoxic-ischemic and hemorrhagic brain injury are important causes of morbidity and mortality in newborn infants and may result from alterations in cerebral blood flow. Cerebral blood flow may vary directly with systemic blood pressure in sick infants. Many medications used to treat newborn infants are known to have potent effects on the systemic circulation. These medications include dopamine, tolazoline, indomethacin and prostaglandin E-1 (PGE-1). The effects which these medications have on the cerebral circulation of sick newborn infants is unknown. To investigate the effects of these medications on the cerebral circulation, we propose a two part study. In the first part, we will correlate changes measured with the non-invasive, two-dimensional, pulsed Doppler technique in the cerebral and systemic circulation of newborn lambs treated with these medications with invasive measurements of quantitative cerebral blood flow and cardiac output using the radio-active microsphere technique. Thirty term and 10 preterm newborn lambs will have catheters placed in the ascending and descending aorta, left atrium, and inferior vena cava, a Doppler flow probe placed about the ascending aorta and an artificial fontanel created in the skull. One of the 4 medications will be given to 10 lambs in each of the 4 medication groups. The effects of the medications on the cerebral and systemic circulation will be assessed by measuring vascular pressures, cardiac output, and cerebral blood flow: a) before inducing either hypoxemia or hypotension, b) after inducing these conditions, c) after treatment with one of the medications. In the second part of the study, we will use the two-dimensional, pulsed Doppler technique to investigate the effects on the cerebral and systemic circulation of newborn infants who require treatment with the medications. We believe that by having an understanding of the effects of these medications on the cerebral circulation and by demonstrating the reliability of the pulsed Doppler technique we will be able to manage infants who are at risk for brain injury more effectively.
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