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Biomedical subjects

S M Mueller

Publications and source records attributed to S M Mueller.

36 records · Page 2Linked to original sources
PubMed1982

The blood-brain barrier in young spontaneously hypertensive rats.

It has been shown that the blood-brain barrier (BBB) of chronically hypertensive adult spontaneously hypertensive rats (SHR) is less susceptible to disruption during acute superimposed hypertension than normotensive controls. The purpose of this study was to determine if the BBB of young SHR, not yet markedly hypertensive, was similarly protected during super-imposed acute hypertension. Spontaneously hypertensive rats (n = 22) and normotensive Wistar-Kyoto rats (WKY) (n = 23) 4-5 weeks of age were anesthetized with secobarbital sodium (50 mg/kg) intraperitoneally and acute hypertension was produced by an intravenous injection of norepinephrine (75 micrograms). Permeability of the BBB was studied with radioactive iodine serum albumin (RISA) injected intravenously. The ratio of brain-to-blood RISA X 100 was used as an index of permeability of the BBB expressed as % protein transfer. In WKY exposed to acute hypertension mean arterial pressure increased by 52 +/- 2 mmHg and in SHR the increase was 49 +/- 3 mmHg. The protein transfer of the cerebral hemispheres was 1.17 +/- 0.30% in WKY and 0.90 +/- 0.20% in SHR (P less than 0.40). These data indicate that BBB protein transfer during acute superimposed hypertension does not differ between young SHR and WKY. Thus, the reduced susceptibility to BBB disruption in chronically hypertensive adult SHR is not present in young SHR, making them as susceptible as WKY to cerebral complications related to protein transfer during acute hypertension.

Animals↗
PubMed1980

Enlarged cerebral ventricular system in infant achondroplastic dwarf.

The cause of the enlarged head found in achondroplastic dwarfs has been disputed. We studied an infant achondroplastic dwarf who had an enlarged (90%) head at age 2 months without enlarged cerebral ventricles. At age 10 months, her head size further enlarged (95%) and the cerebral ventricles were dilated. Megalencephaly may be the major factor contributing to the enlarged head in newborn achondroplastic dwarfs. Later, enlarged cerebral ventricles also contribute.

Achondroplasia↗
PubMed1980

Reversal of emissary vein blood flow in achondroplastic dwarfs.

We used a noninvasive technique--the directional Doppler examination--to determine the direction of flow in an emissary vein of achondroplastic dwarfs. Normally, the direction of flow in this emissary vein is into the orbit. The direction of flow in all 10 achondroplastic dwarfs whom we studied was away from the orbit. This indicates that ophthalmic vein blood flow is reversed in achondroplastic dwarfs, perhaps because there is a pressure gradient between the intracranial and extracranial venous systems.

Achondroplasia↗
PubMed1979

Effect of sympathetic nerves on cerebral vessels during seizures.

The purpose of this study was to determine the effect of activation of sympathetic pathways during seizures on cerebral blood flow and integrity of the blood-brain barrier. We measured cerebral blood flow with microspheres and disruption of the blood-brain barrier with labeled albumin in cats. One cerebral hemisphere was denervated by cutting the superior cervical sympathetic trunk on one side. During bicuculline-induced seizures, superior cervical sympathetic nerve activity increased about threefold. Blood flow to the innervated hemibrain was significantly lower than flow to denervated hemibrain. However, in relation to the total increase in flow, this effect of nerves was minor. Blood-brain barrier permeability increased about sixfold during seizures, but there was no difference between the innervated and denervated sides of the brain. We conclude that sympathetic nerves attenuate the increase in cerebral blood flow during seizures, despite the increase in metabolism, but this effect is small. Activation of sympathetic nerves does not reduce disruption of the blood-brain barrier during seizures.

Animals↗
PubMed1977

Achondroplasia and hydrocephalus. A computerized tomographic, roentgenographic, and psychometric study.

Nine achondroplastic dwafts were studied with computerized tomography, skull and cervical spine films, and psychometric testing. All had large ventricles that ranged from the top limits of normal to severe hydrocephalus. Three had enlarged cortical sulci. Skull and cervical spine films were typical for achondroplasia, but in addition significant asymmetry of the petrous ridge was noted. Psychometric testing disclosed generally average intelligence quotients which fell below the expected performance level in each case. These findings may be explained on the basis of the abnormal endochondral bone formation found in achondroplasia.

Achondroplasia↗
PubMedDate not supplied

Quantitative importance of the 25-hydroxylation pathway for bile acid biosynthesis in the rat.

During biosynthesis of bile acid, carbons 25-26-27 are removed from the cholesterol side chain. Side-chain oxidation begins either with hydroxylation at the 26-position, in which case the three-carbon fragment is released as propionic acid, or with hydroxylation at the 25-position, in which case the three-carbon fragment is released as acetone. In the present study, we have quantitated the relative importance of these two pathways in vivo by measuring production of [14C] acetone from [14C]-26-cholesterol. Four days after intraperitoneal injection of 20 to 40 muCi [14C]-26-cholesterol and 1 day after beginning a constant intravenous infusion of unlabeled acetone at 25 mumoles per kg per min, 6 male and 2 female Sprague-Dawley rats underwent breath collections. Expired acetone was trapped and purified as the 2,4-dinitrophenylhydrazine derivative. 14CO2 was trapped quantitatively using phenethylamine. Specific activity of breath acetone was multiplied times the acetone infusion rate to calculate production of [14C]acetone. [14C] Acetone production averaged 1.7% of total release of 14C from [14C]-26-cholesterol, estimated by 14CO2 output. The method was validated by showing that [14C] acetone production from [14C]isopropanol averaged 111% of the [14C]isopropanol infusion rate. We conclude that, in the normal rat, the 25-hydroxylation pathway accounts for less than 2% of bile acid synthesis.

1-Propanol↗
PubMedDate not supplied

Effect of chronic hypertension on the blood-brain barrier.

Disruption of the blood-brain barrier (BBB) during acute hypertension may contribute to hypertensive encephalopathy. In this study we tested the hypothesis that, in chronic hypertension, vascular changes might influence the susceptibility of the BBB to disruption. Spontaneously hypertensive rats (SHR) and normotensive rats (WKY), 3-4 months of age, were anesthetized and acute hypertension was produced by infusing phenylephrine intravenously (i.v.). Permeability of the BBB was studied with radioactive iodine serum albumin (RISA) injected i.v. The ratio of brain-to-blood RISA was used as an index of permeability of the BBB expressed as protein transfer. In both SHR and WKY at resting arterial pressure, the protein transfer was less than 0.10%. In WKY exposed to acute hypertension (mean arterial pressure increased by 87 +/- 7 mm Hg), the protein transfer was 2.77 +/- 0.60%. In SHR with acute hypertension superimposed on chronic hypertension (arterial pressure increased by 80 +/- 7 mm Hg), the protein transfer was 1.16 +/- 0.45% (p less than 0.05, SHR vs WKY). These data suggest that cerebral vessels are less susceptible to disruption of the BBB by acute hypertension in SHR than in WKY. We speculate that the finding of reduced susceptibility to BBB disruption in chronic hypertension may explain, in part, the apparent susceptibility of previously normotensive patients to acute hypertensive encephalopathy.

Animals↗
PubMedDate not supplied

Longitudinal study of the hindquarter vasculature during development in spontaneously hypertensive and Dahl salt-sensitive rats.

The purpose of this study was to examine vascular structural alterations longitudinally in spontaneous and Dahl genetic hypertension. Hypertensive and control animals were studied at 5,9-11, and 17-19 weeks of age to permit analysis of prehypertensive, early and established hypertensive stages. Minimal and maximal resistance of the hindquarter vasculature was used as a functional assessment of structural alterations. At 5 weeks of age, the minimal vascular resistance of the spontaneously hypertensive rats (SHR) was elevated over Wistar-Kyoto (WKY) (p less than 0.02) but there was no difference between Dahl salt-sensitive (S) and resistant (R) rats. In both sets of animals, the minimal vascular resistance of the hypertensive group was significantly elevated over controls with age: p less than 0.001 in SHR; p less than 0.001 in Dahl S. The maximal vasoconstrictor response was significantly greater with age in SHR than in WKY, (p less than 0.001), but was not different in Dahl S compared to R. Thus, structural alterations, determined by assessing minimal vascular resistance, are present in both spontaneous and Dahl salt-sensitive hypertension, but the origin of the two differ. An increase in smooth muscle mass, assessed by maximal constriction, contributes importantly to the structural alterations in spontaneous hypertension; in Dahl S, other factors appear to contribute to structural alterations. Further, structural alterations precede frank hypertension in SHR but not in Dahl S hypertension.

Aging↗
PubMedDate not supplied

Association between sympathetic nerve activity and cerebrovascular protection in young spontaneously hypertensive rats.

The purpose of this study was to determine resting and maximal superior cervical sympathetic nerve activity in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) at five and ten weeks of age as hypertension was developing. Basal cervical sympathetic nerve activity (SNA) of five week SHR was 58 +/- 3 muv* which was significantly elevated over age-matched WKY (SNA = 30 +/- 4 muv, *p less than 0.001) and ten week SHR (SNA = 30 +/- 4 muv, *p less than 0.001) as well as ten week WKY (SNA = 24 +/- 4 muv, *p less than 0.001). Thus, during basal conditions five week SHR nerve traffic was approximately two times that found in age-matched WKY as well as in ten week SHR and WKY. The peak sympathetic nerve activity in response to rapid hemorrhage in five week SHR (215 +/- 16 muv*) was significantly elevated over the maximal response of WKY (140 +/- 23 muv) (*p less than 0.02). Ten week SHR also reached a maximal sympathetic nerve activity (187 +/- 28 muv*) that was significantly elevated over WKY (100 +/- 15 muv) (*p less than 0.02). Thus, both five and ten week SHR had a greater capacity for elevated nerve activity following rapid hemorrhage than age-matched WKY. The elevation in resting cervical sympathetic activity in five week SHR, and the elevated capacity for sympathetic neural response in both five as well as ten week SHR, are consistent with a central nervous system abnormality in SHR that could relate to the previously described protective influence of sympathetic nerves on SHR cerebral blood vessels as hypertension is developing.

Adrenergic Fibers↗
PubMedDate not supplied

The chronic influence of sympathetic nerves on cerebral vessels is age-related.

The purpose of this study was to determine the effect of chronic sympathetic denervation on cerebral vessels of the spontaneously hypertensive rat when superior cervical ganglionectomy was performed in adulthood. In a previous study, we have demonstrated increased protein transfer across the cerebral vessels of the chronically denervated hemisphere when superior cervical ganglionectomy was performed in adolescent spontaneously hypertensive rats. After four weeks of sympathetic denervation, the adult rats in this study did not demonstrate increased protein transfer in the denervated compared to the innervated cerebral hemisphere. Thus, the "trophic" effect of sympathetic nerves on cerebral vessels appears to be age-related.

Aging↗
PubMedDate not supplied

Cerebral hemorrhage associated with phenylpropanolamine in combination with caffeine.

Phenylpropanolamine (PPA) is a drug that has been associated with serious side effects including stroke. It is often combined with caffeine in diet preparations and "look-alike" pills. In order to determine if PPA/caffeine can lead to stroke in normotensive and/or hypertensive rats, we administered the combination in six times the allowed human dose calculated on a per weight basis for the rats two times per day for five days. Subarachnoid and cerebral hemorrhage was noted in 18% of the hypertensive rats. A single PPA/caffeine administration (same dose) lead to acute hypertension in both the normotensive and hypertensive animals. These results suggest that PPA/caffeine can lead to cerebral hemorrhage in previously hypertensive animals when administered in greater than the allowed dosage. An acute elevation in blood pressure may be a contributing factor.

Animals↗
PubMedDate not supplied

Sympathetic nerve activity: a link to stroke?

Spontaneously hypertensive rats (SHR) have been shown to have an increased capacity for superior cervical sympathetic nerve activity which may protect against stroke (Mueller et al: Stroke 13: 115, 1982). Sympathetic nerve activity has never been examined in the stroke-prone substrain of SHR (SP). In this study we measured superior cervical sympathetic nerve activity during rest and during a maximal sympathetic response in SHR, SP, and their normotensive controls, Wistar-Kyoto (WKY). The resting superior cervical sympathetic nerve activity of SP was significantly less than SHR (p less than 0.02) but not different from WKY. During central ischemia, used to induce maximal sympathetic response, the increase in SP sympathetic nerve activity was significantly less than SHR (p less than 0.001) but was not different from WKY. This diminished capacity for elevated superior cervical sympathetic nerve activity in stroke-prone SHR may relate to their increased predisposition to stroke because sympathetic hyperactivity cannot protect cerebral vessels during acute hypertension.

Adrenergic Fibers↗