We examined the effects of 20 minutes' cerebral ischemia on cerebral microcirculatory responses to topical norepinephrine and systemic hypotension in three groups (sham-operated control, 2 -3 hours posUschemla, and 24 hours postischemia) of anesthetized newborn pigs equipped with closed cranial windows. Cerebral ischemia may eliminate the prostanoid vasodilator system from the cerebral circulation. Norepinephrine (10~4 M) decreased pial arteriolar diameters similarly in all three groups (27%, 28%, and 21%, respectively), but only the sham-operated group exhibited pial arteriolar dilation in response to hypotension (28% at 33 mm Hg). Two-three and 24 hours after cerebral ischemia, hypotension decreased pial arteriolar diameters (21% and 17%, respectively). In sham-operated piglets, norepinephrine and hypotension increased cortical periarachnoid cerebrospinal fluid prostanoid concentrations. However, neither norepinephrine nor hypotension altered cerebral prostanoid production 2-3 or 24 hours after cerebral ischemia. Therefore, we conclude that after cerebral ischemia, autoregulatory pial arteriolar dilation in response to hypotension is absent, while vasoconstriction in response to norepinephrine is intact. (Stroke 1989;20:541-546)

Treatment of unanesthetized newborn pigs with indomethacin trihydrate (5 +/- 1 mg/kg, intravenous) decreased cerebral blood flow uniformly throughout the brain by 18-28% without changing cardiac output, arterial pressure, or arterial blood gases and pH. Breathing 10% O2, 9% CO2 with the balance N2 (hypoxia/hypercapnia) caused cerebral blood flow to increase from 102 +/- 12 to 218 +/- 19 ml/100 g . min. Intravenous administration of indomethacin during hypoxia/hypercapnia caused a uniform decrease in cerebral flow throughout the brain to levels (94 +/- 5 ml/100 g . min) indistinguishable from those when the piglet was breathing ambient air. Further, 2.5 h later, the cerebral hyperemia caused by hypoxia/hypercapnia was attenuated markedly (129 +/- 19 ml/100 g . min). Vehicle treatment did not alter resting cerebral blood flow or cerebral hyperemia in response to hypoxia/hypercapnia. Measurements of 6-keto-prostaglandin F1 alpha, thromboxane B2, and prostaglandin E2 demonstrated that intravenously administered indomethacin crossed the blood-brain barrier of newborn pigs in sufficient quantity to inhibit prostanoid release into the cerebrospinal fluid passing over the surface of the brain. The mechanism by which indomethacin reduces cerebral blood flow and attenuates cerebral hyperemia cannot be determined from the present experiments. We conclude that intravenous administration of indomethacin decreases cerebral blood flow and attenuates cerebral hyperemia induced by severe, combined hypoxia/hypercapnia in newborn pigs.

Brain circulation after 20 min of total brain ischemia was examined in unanesthetized newborn pigs. Except in the cerebrum, reactive hyperemia was observed throughout the brain, peaking by 5 min and subsiding by 20 min of reperfusion. Brain blood flow after 15 min of reperfusion matched the control. Blood flow to the cerebrum then decreased at 40 and 90 min reperfusion, while the rest of the brain was unaffected. Blood flow to the cerebrum returned to control by 24 h. Cerebral vascular resistance doubled by 15 min reperfusion, remained elevated at 90 min reperfusion, but returned to control by 24 h. Cerebral oxygen consumption followed a pattern similar to blood flow. Ninety minutes postischemia, hypercapnia-induced hyperemia was greatly attenuated in the cerebrum, reduced modestly in the diencephalon-mesencephalon, but unaffected in the rest of the brain. Thus 20 min of global brain ischemia in piglets does not produce reactive hyperemia in the cerebrum that is detectable at 5 min reperfusion but does in the remainder of the brain. Subsequent hemodynamic abnormalities apparently are confined to the cerebrum. Blood flow throughout the brain returns to normal by 24 h. Thus cerebral hemodynamic effects of total global ischemia are regionally dependent.

Ultraviolet (UV) radiation suppresses certain immunologic responses, such as contact hypersensitivity (CH). Some previous studies, using sunlamps emitting nonsolar-spectrum UV or excessive UV doses, have questioned the ability of sunscreens to prevent UV-induced immune suppression. Our study evaluated the immune protection capacities of commercial sunscreen lotions in relation to the effects of UV spectrum and dose. C3H mice were exposed to a fixed UV dose from Kodacel-filtered FS sunlamps that caused maximum Langerhans cell depletion and suppression of CH. Kodacel film blocks UV energy below 290 nm, thus eliminating immune-suppressive effects of UVC (200-290 nm) not present in sunlight. CH was equally suppressed in unprotected and placebo-lotion-treated, UV-exposed mice. Mice protected with sun protection factor (SPF)-15 and SPF-30 sunscreens mounted normal CH responses. SPF-4 and SPF-8 sunscreen-protected mice had CH responses significantly greater than those of unprotected mice. Direct effects of UV spectral differences on the immune protection value of an SPF-15 sunscreen were determined by exposing mice to UV radiation from unfiltered and Kodacel-filtered sunlamps and a 1000-W xenon lamp solar simulator (UV spectrum nearly equivalent to sunlight). The sunscreen immune protection value was 30 times the minimum immune suppression dose for the solar simulator, while being 7.5 times this dose for Kodacel-filtered and 2 times the dose for unfiltered sunlamps. These results demonstrate that commercial sunscreen lotions prevent UV-induced immune suppression at a level exceeding the labeled SPF when tested with an environmentally relevant UV source.

TiO(2) provided neither the same level of UVA attenuation nor the same degree of UVA protection on human skin as did products containing photostabilized avobenzone or ZnO. Hence, TiO(2) cannot be considered a substitute for avobenzone or ZnO in providing high levels of UVA protection to human skin. Use of proper formulation strategies can ensure that avobenzone losses are minimized to the extent that they have no impact on a product's ability to deliver sustained protection, even over periods of prolonged exposure to UVR.