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Biomedical subjects

A M Fletcher

Publications and source records attributed to A M Fletcher.

At least 55 records · Page 3Linked to original sources
PubMed1989

Effects of hypertension and sympathetic denervation on cerebral blood flow in newborn pigs.

To investigate the potential role of sympathetic nerves in preventing pronounced increases in cerebral blood flow, we evaluated the effects of abrupt hypertension on the cerebral circulation of newborn pigs with intact cerebral sympathetic innervation and after cerebral sympathetic denervation. Epinephrine infusion was used to induce abrupt increases in mean (+/- SEM) arterial pressure (innervated pigs, 62 +/- 3 mm of Hg to 115 +/- 3 mm of Hg; denervated pigs, 71 +/- 4 mm of Hg to 132 +/- 4 mm of Hg) that remained increased for the 3 minutes of the study. Abrupt hypertension increased blood flow to all brain regions. In denervated pigs, the increased flow to the cerebrum was prolonged, compared with that in pigs with intact sympathetic innervation. Differences between pigs of the innervated and denervated groups were not apparent, with respect to blood flow to any other region (caudate region, brain stem, cerebellum). In newborn pigs, sympathetic nerves may attenuate hypertension-induced increases in blood flow to the cerebrum, but do not appear to affect flow to the rest of the brain.

Animals↗
PubMed1987

Vasopressin responses to asphyxia and hemorrhage in newborn pigs.

Vasopressin may be important in maintenance of arterial pressure and redistribution of cardiac output in hypotensive and asphyxiated newborns. We used chronically instrumented, unanesthetized, 4-day-old pigs to investigate the effects of hypotensive hemorrhage and asphyxia on plasma vasopressin concentration and to determine the effects of cyclooxygenase inhibition on these responses. Asphyxia [arterial O2 partial pressure (PaO2) = 40-50 Torr, arterial CO2 partial pressure (PaCO2) = 60-80 Torr) increases plasma lysine vasopressin (LVP) from 2.2 +/- 0.8 to 52.4 +/- 15.0 microU/ml. Neither the baseline nor stimulated plasma LVP was affected by indomethacin (5 mg/kg) or meclofenamate (5 mg/kg). Hemorrhage (30 ml/kg) increased plasma LVP from 2.8 +/- 0.8 to 163.4 +/- 28.1 (20 min) and 135.1 +/- 18.5 microU/ml (60 min). The effects of vehicle and indomethacin (5 mg/kg) 20 min after hemorrhage on plasma LVP 60 min after hemorrhage were not different. Changes in plasma vasopressin caused by asphyxia and hemorrhage in the unanesthetized newborn pig are similar to the responses observed in adults of other species. This study does not suggest that prostanoids are involved in these responses in newborn pigs.

Animals↗
PubMed1987

Indomethacin does not alter the circulating catecholamine response to asphyxia in the neonatal piglet.

The response of circulating catecholamines to asphyxia in unanesthetized, spontaneously breathing neonatal piglets was measured before and after treatment with indomethacin. Prior to treatment with indomethacin, baseline levels [geometric mean, pg/ml (95% confidence limits)] of D, E, and N were 162 (99-266), 174 (52-579), and 380 (286-506), respectively. Inhalation of 10% O2/9% CO2 for 20 min caused significant increases in arterial levels of all three catecholamines to 389 (230-659, 1514 (993-2306), and 3802 (2731-5293), respectively. Treatment with indomethacin (5 mg/kg, intravenous) did not significantly alter either baseline levels of the catecholamines or the levels after 20 min of the asphyxiating gas. In time control piglets, baseline levels and the response to asphyxia were similar before and after placebo. These results suggest that the circulating catecholamine response to asphyxia of the neonatal piglet is independent of the prostaglandin system.

Animals↗
PubMed1986

Effects of indomethacin on cardiac output distribution in normal and asphyxiated piglets.

We determined the effect of breathing 9% CO2/10% O2/81% N2 (asphyxia) on cardiac output distribution (microspheres) in 4-5 day old unanesthetized, chronically instrumented piglets prior to and following intravenous indomethacin administration. Thirty minutes of asphyxia caused PaCO2 to increase from 35 +/- 2 mmHg to 66 +/- 2 mmHg, PaO2 to decrease from 73 +/- 4 mmHg to 41 +/- 1 mmHg, and pH to decrease from 7.52 +/- 0.05 to 7.21 +/- 0.07. Arterial pressure was increased slightly but cardiac output was not changed significantly. Asphyxia caused blood flow to the brain, diaphragm, liver, heart, and adrenal glands to increase while causing decreases in blood flow to the skin, small intestine, and colon. Blood flows to the stomach and kidneys tended to decrease, but the changes were not significant. Treatment with indomethacin during asphyxia did not alter arterial pressure or cardiac output but decreased cerebral blood flow to the preasphyxiated level and decreased adrenal blood flow about 20%. Indomethacin did not alter blood flow to any other systemic organ. At this time the piglet was allowed to breathe air for 2.5 hr undisturbed. Two and a half hours after indomethacin administration, blood flows to all organs returned to the preasphyxia control levels with the exception of cerebral blood flow which was reduced (93 +/- 13 to 65 +/- 7 ml/100 g X min). Three hours after indomethacin administration, the cerebral hyperemia caused by asphyxia was less (134 +/- 17 ml/100 g X min) than prior to indomethacin (221 +/- 15 ml/100 g X min). Indomethacin did not alter the asphyxia-induced changes to any other systemic organ.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Effects of sodium chloride on pregnant sheep with reduced uteroplacental perfusion pressure.

This study investigated the effects of NaCl supplementation (5 mEq/kg/day) on the arterial pressure of pregnant and nonpregnant sheep with and without reduction of uteroplacental perfusion pressure. In pregnant sheep receiving NaCl supplementation during the third trimester, reduction of aortic pressure caudal to the kidneys to 65% of the upstream pressure (occlusion) caused a progressive increase in mean arterial pressure from 89 +/- 3 to 110 +/- 3 mm Hg over 2 weeks. Occlusion was accompanied by a decrease in urine flow. Six of seven sheep died or were killed because of severe respiratory distress. No abnormalities were detected in nonpregnant sheep or pregnant sheep receiving NaCl supplementation only. Pregnant sheep that were occluded but received no supplementary NaCl did not become hypertensive but aborted about 2 weeks after occlusion. These results indicate that reduction of uteroplacental perfusion pressure causes hypertension in NaCl-supplemented pregnant sheep but not in sheep receiving a normal, low sodium diet.

Animals↗
PubMed1986

Maintenance of cerebral circulation during hemorrhagic hypotension in newborn pigs: role of prostanoids.

The possibility that the prostanoid system contributes to the capability of the newborn piglet to maintain cerebral blood flow and cerebral metabolic rate during hypotension was investigated. The effect of hemorrhage on net (arterial-to-venous) cerebral prostacyclin production and the effects of indomethacin on cerebral hemodynamic response to hemorrhage and on the cerebral oxygen utilization following hemorrhage were determined in chronically instrumented, unanesthetized newborn pigs. Hemorrhage decreased arterial pressure about 35% but did not affect cerebral blood flow or cerebral O2 consumption. Hemorrhage was accompanied by an increase in net cerebral 6-keto-PGF1 alpha production from 4.0 +/- 1.1 to 15.3 +/- 4.9 ng/100g X min (mean +/- SEM). Indomethacin treatment of piglets following hemorrhage inhibited the net cerebral production of 6-keto-PGF1 alpha and caused a decrease in blood flow (approximately equal to 40%) to all brain regions within 20 minutes. The decrease in cerebral blood flow was the result of an increase in cerebral vascular resistance of 57 and 180%, 20 and 40 minutes post treatment, respectively. Cerebral O2 consumption was reduced from 2.5 +/- 0.3 ml/100 g X min to 1.5 +/- 0.3 ml/100 g X min 20 minutes following treatment of hemorrhaged piglets with indomethacin and to 1.1 +/- 0.3 ml/100 g X min 40 minutes after treatment. Six of 8 piglets for whom the data were recorded that were administered indomethacin following hemorrhage became comatose with cerebral O2 consumption of 0.4 +/- 0.1 ml O2/100 g X min by 40 minutes after treatment. These data are consistent with the hypothesis that the prostanoid system contributes to the maintenance of cerebral blood flow and cerebral metabolic rate during hypotension in the newborn.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Gastroduodenal ulceration in rabbits producing antibodies to prostaglandins.

The consistent occurrence of gastric and duodenal ulcers was observed in laboratory rabbits used for production of high-titer plasma antibody to 6-keto PGF1 alpha and PGE2. Perforations developed in 7 of 10 animals, usually just distal to the pyloroduodenal junction. The remaining rabbits showed gross and/or microscopic evidence of imperforate ulcers and erosions. These lesions appeared to be direct pathologic complications of an immune response directed against prostaglandins since animals immunized against met-enkephalin with similar methods had no ulcers.

6-Ketoprostaglandin F1 alpha↗