Biomedical subjects
Publications and source records attributed to P Olley.
We studied tone in the human ductus arteriosus and show that the constriction to oxygen is due to inhibition of voltage-gated potassium channels and, in the acute phase, is independent of endothelin-1.
OBJECTIVE: We studied the ontogeny of the expression of cyclooxygenase-1 and cyclooxygenase-2 in the ductus arteriosus and evaluated their functional significance. STUDY DESIGN: The expression of cyclooxygenase-1 and cyclooxygenase-2 was studied in ductus arteriosus of fetal (at approximately 75% gestation) and term newborn pig. Effects of selective inhibitors of cyclooxygenase-1 and cyclooxygenase-2 on ductal patency were evaluated by Doppler ultrasonography. RESULTS: Ductus arteriosus of the fetus expressed virtually only cyclooxygenase-1 immunoreactive protein and activity. In contrast, the ductus of the term newborn pig (<45 minutes old) contained proteins of both cyclooxygenase-1 and cyclooxygenase-2, but the latter contributed to >90% of prostaglandin E2 formation. The selective cyclooxygenase-2 inhibitor DuP697 reduced prostaglandin E2 levels in the ductus arteriosus, albeit not in plasma, but did not affect ductal patency in the newborn pig (<1(1/2) hours old); in contrast, the cyclooxygenase-1 inhibitor valeryl salicylate, like indomethacin, markedly reduced levels of prostaglandin E2 in the plasma and ductus arteriosus and caused significant constriction of the ductus arteriosus. CONCLUSION: The ductus arteriosus of the term newborn pig, in contrast to that of the fetus, expresses cyclooxygenase-2, but circulating prostaglandins, arising mostly from cyclooxygenase-1, seem to exert the major control on ductal patency in vivo. Our data suggest that cyclooxygenase-2 inhibitors might be better alternatives for the fetus than nonselective cyclooxygenase blockers if indicated for maternal conditions such as inflammation or for tocolysis.
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Pulsed Doppler evaluation of pulmonary venous flow was performed in three groups of patients who had undergone either a Mustard or Senning procedure. Group I consisted of 43 patients in sinus rhythm who had undergone the Mustard procedure 9 months or more before the Doppler examination and 16 who were evaluated immediately after surgery. Group II consisted of 12 patients in sinus rhythm who had undergone the Senning procedure 9 months or more before the Doppler evaluation. Group III consisted of eight patients with mid baffle obstruction of the pulmonary venous atrium and seven with isolated stenosis of the pulmonary vein of which all but one had previously had associated mid baffle obstruction. In those without obstruction, the pulmonary venous flow pattern mirrored the left atrial pressure trace, with peak forward flow occurring during the x and y descent. Obstruction produced a specific high-velocity turbulent pattern, whether at the mid baffle or pulmonary venous level. This technique provides reliable noninvasive information about pulmonary venous flow after the Mustard or Senning procedure.
A "phantom" was used to validate 1) estimates of different depths of a constant radioactivity source, and 2) the calculation of different volumes using a constant depth and different attenuation coefficients. Using data from this in vitro study, scintigraphic estimates of right ventricular volume and ejection fraction were compared with those obtained by cineangiography in 36 children with either a normal right ventricle or various right ventricular diseases. The static program accurately estimates the distance from the radiation source to the collimator surface (r = 0.99). Radionuclide count methods best predict "phantom" volumes using attenuation coefficients between 0.11(-1) and 0.13(-1) cm. A coefficient of 0.10(-1) underestimates, whereas 0.15(-1) cm grossly overestimates actual volumes. In vivo data were therefore analyzed using an attenuation coefficient of 0.11(-1) with right ventricular counts corrected using either right ventricular or left ventricular background. Closest agreement between scintigraphic and cineangiographic volumes was obtained using right ventricular background, although end-diastolic volumes larger than 100 ml were substantially underestimated. On the basis of this study, the use of two different attenuation coefficients is suggested: the smaller 0.11(-1) cm to calculate end-systolic and end-diastolic volumes and the larger 0.15(-1) cm for volumes greater than 100 ml.
The specificity of radioimmunoassay and fluorescence polarization immunoassay procedures for the measurement of digoxin has been assessed. Many steroids and lipids have been found to interfere and give false positive results for digoxin under the conditions of the study. Caution is recommended in the interpretation of digoxin measurements made by immunoassay procedures.
From 1968 to 1976 inclusive, 69 neonates with diaphragmatic hernias had corrective surgery within 18 hr of birth and the survival rate was 41%. During the same time, all babies with similar hernias who were operated on later than 18 hr from the time of birth survived. Our present interest has been focused on the pulmonary artery and its hypertension with the subsequent development of right to left shunting through the patent ductus arteriosus. During 1977 and 1978, we attempted to enter 19 consecutive newborns 18 hr of age or less with symptomatic Bochdalek diaphragmatic hernias into a "Collins protocol" for treatment. This included four stages: newborn nursery initial resuscitation, operation, cardiac catheterization, and ICU monitoring and pharmacological therapy. There was a total of seven survivors (36%), however for a number of reasons only eight babies really had a complete entry into this protocol and of these eight, five survived. Although this study is far from complete, some initial information and concepts are forthcoming. It is now apparent to us that there are three distinct groups into which these very early newborns fall: minimal pulmonary hypoplasia, unilateral hypoplasia and bilateral hypoplasia. The first group probably does not need pharmacologic support, while in the last it probably does not help. Further interest in other more specific pulmonary pharmacologic agents is now being considered as well as some way of early recognition of which baby is going to fit into which group, so that only the ones that need this treatment will get it.
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