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Biomedical subjects

C M Ferrario

Publications and source records attributed to C M Ferrario.

At least 199 records · Page 11Linked to original sources

Magnetic resonance of brain tumors: considerations of imaging contrast on the basis of relaxation measurements.

Proton spin-lattice and spin-spin relaxation times have been measured in surgically-removed normal CNS tissues and a variety of tumors of the brain. All measurements were made at 20 MHz and 37 degrees C. Between grey and white matter from autopsy human or canine specimens significant differences in T1 or T2 were observed, with greater differences seen in T1. Such discrimination was reduced in samples obtained from live brain-tumor patients due to lengthening in T1 and T2 of white matter near tumorous lesions. Edematous white matter showed T1 and T2 values higher than those of autopsy disease-free white matter. Compared to normal CNS tissues, most brain tumors examined in this study demonstrated elevated T1 and T2 values. Exceptions, however, did exist. No definitive correlation was indicated on a T1 or T2 basis which allowed a distinction to be made between benign and malignant states. Furthermore, considerable variation in relaxation times occurred from tumor to tumor of the same type, suggesting that within a tumor type there are important differences in physiology, biology, and/or pathologic state. Such variation caused partial overlap in relaxation times among certain tumor types and hence may limit the capability of magnetic resonance imaging (MR) alone for the diagnosis of specific disease. Nonetheless, this study predicts that on the basis of T1 or T2 differences most brain tumors are readily detectable by MR via saturation recovery or inversion recovery with appropriate selections of pulse-spacing parameters. In general, tumors can be discriminated against white matter better than grey matter and contrast between glioma and grey matter is usually superior to that between meningioma and grey matter. This work did not consider tissue-associated proton density which should be addressed together with T1 and T2 for a complete treatment of MR contrast.

Adenoma↗

Rat brain angiotensin II receptors: effects of intracerebroventricular angiotensin II infusion.

Angiotensin II (Ang II) was infused into a lateral cerebral ventricle of male Sprague-Dawley rats and its effects on blood pressure, water balance and specific [125I]Ang II binding to brain and adrenal tissues were studied. The infusion was maintained at a rate of 500 ng/microliter/h for 6 days using subcutaneously implanted osmotic minipumps. A control group was infused intracerebroventricularly (i.c.v.) with 0.9% saline at a rate of 1 microliter/h for 6 days. Angiotensin II treated rats showed a four-fold increase in water intake and urine volume and a moderate increase in blood pressure; these effects were not observed in rats given saline i.c.v. There was no significant difference in [125I]Ang II binding site density or binding affinity in either the hypothalamus-thalamus-septum-midbrain (HTSM) or the brainstem between Ang II-treated and saline-treated groups. In addition, [125I]Ang II binding sites in the adrenals were also unaffected by i.c.v. infusion of Ang II. The results suggest that brain Ang II receptors are unresponsive to increased Ang II levels in cerebrospinal fluid.

Adrenal Glands↗

Afferent projections of the cervical vagus and nodose ganglion in the dog.

The distribution within the brain stem of the afferent projections of the cervical vagus and the nodose ganglion was studied with horseradish peroxidase (HRP) and HRP-wheat germ agglutinin conjugate. Two to eight days after application of tracer into the cervical vagosympathetic trunk or the nodose ganglion the brain stems and ganglia were perfused and processed by the tetramethyl benzidine method. Vagal afferent fibers entered the lateral medulla as a distinct bundle spatially separate from the vagal efferent rootlets which were caudal and ventral to the afferents. Labeled axons in the solitary tract began to enter the nucleus tractus solitarii (nTS) 4.5 mm anterior to obex and were seen throughout the ipsilateral nTS as far as 3.5 mm caudal to obex. Label density varied within the nTS, with heaviest labeling in the dorsal and dorsolateral portions. Label was also seen in the ipsilateral area postrema (ap) and dorsal motor nucleus of the vagus. Labeled fibers crossed in the commissural portions of ap and nTS to enter the contralateral ap and nTS.

Afferent Pathways↗

New method for the collection of cerebrospinal fluid from the cisterna magna of conscious dogs.

We have developed a catheter system than can be implanted chronically into the cisterna magna of the dog to obtain serial samples of cerebrospinal fluid (CSF) for up to 8 wk. A direct access to the CSF of the cisterna magna provided an opportunity to determine also base-line values of CSF sodium, potassium, norepinephrine, epinephrine, and angiotensin II immunoreactivity and compare relative differences in the concentration of these variables between the central and peripheral compartments.

Angiotensin II↗

Assessment of parasympathetic control of heart rate by a noninvasive method.

The degree of parasympathetic control of heart rate was assessed by the abolition of respiratory sinus arrhythmia with atropine. Peak-to-peak variations in heart periods (VHP) before atropine injection correlated significantly (r = 0.90, P less than 0.001) with parasympathetic control, indicating that VHP alone may be used as a noninvasive indicator of the parasympathetic control of heart rate. Pharmacologic blockade of beta-adrenergic supply in a separate group of normal volunteers did not alter the relationship between VHP and parasympathetic control, indicating that the condition of the experiment (complete rest in a quiet atmosphere) allows the use of VHP alone without pharmacologic interventions to characterize the vagal control of heart rate in humans.

Animals↗

Neurohormonal characteristics of cardiovascular response due to intraventricular hypertonic NaCl.

In morphine-pentobarbital anesthetized dogs (n = 25) we measured the effect of cerebroventricular administration of hypertonic sodium chloride (NaCl) on mean arterial pressure (MAP), heart rate (HR), and integrated renal nerve activity (RNA); in separate experiments (n = 9) we also evaluated the effect of hypertonic NaCl on the osmolarity and electrolyte and catecholamine concentrations of both the blood and the cerebrospinal fluid (CSF); plasma arginine vasopressin (AVP), cortisol, and renin activity were also measured. The intraventricular (ivt) injection of 1.5 M NaCl caused a hypertensive response associated with tachycardia and a significant decrease in RNA (P less than 0.001). Intravenous hexamethonium chloride prevented the changes in HR and RNA, whereas the increases in MAP were markedly reduced but not abolished. The neurohormonal effects of ivt hypertonic NaCl consisted of activation of the sympathoadrenal pituitary axis as reflected by significant increases in the plasma levels of norepinephrine (NE), epinephrine, AVP, and cortisol. On the other hand, there was a significant decrease in plasma renin activity not associated with any significant changes in plasma osmolarity and serum electrolytes. These hormonal changes coincided with an increase in the concentration of CSF NE, CSF Na+, and CSF osmolarity obtained from the cisterna magna. Altogether the results indicate that central administration of hypertonic NaCl in dogs with intact baroreflexes causes a preferential activation of the sympathetic nervous system to vascular systems other than those of the kidneys. In addition, a part of the pressor response may be due to the activation of nonneurogenic mechanisms.

Animals↗

Restricted dietary sodium intake alters peripheral but not central angiotensin II receptors.

Male Sprague-Dawley rats were maintained on either a normal or low-sodium diet for 5 weeks to examine whether dietary sodium restriction alters angiotensin II (Ang II) receptors. The receptor sites in the hypothalamus-thalamus-septum (H-T-S) region of the brain, the adrenal glands and bladder visceral smooth muscle were measured by saturation isotherm binding assays using 125I-Ang II. Compared to control rats, the low-sodium diet group showed a smaller weight gain, reduced water intake, elevated hematocrit, and decreased urinary sodium concentration. In addition, sodium-depleted rats had a 10-fold elevation in plasma renin activity. However, neither binding affinity of 125I-Ang II to the brain H-T-S region nor its density was significantly different between the two groups. In contrast, both the 125I-Ang II binding density and dissociation constant in the adrenal gland were significantly elevated, while the binding density of 125-I-Ang II in the bladder smooth muscle was significantly decreased in the sodium-restricted group. These results suggest that dietary sodium depletion does not alter Ang II receptors in the rat brain areas wherein Ang II exerts the majority of its central actions.

Adrenal Glands↗

Contribution of vasopressin to hypertension after solitary tract lesioning in the dog.

The relative contributions of vasopressin and sympathetic outflow to the acute hypertension that followed central baroreceptor deafferentation at the level of the rostral solitary tract (TS) were examined. In nine dogs (TS lesion group) baroreflex control of heart rate was abolished, confirmed histologically with bilateral interruption of the solitary tracts. Baroreflex tests were positive and one solitary tract was spared in three dogs (incomplete lesion group). Blood pressure rose rapidly after discontinuation of anaesthesia in the animals of the TS lesion group. Administration of an antagonist of the vascular effects of vasopressin 2 1/2 h after lesioning produced a significant decrease in mean arterial pressure and tachycardia in the TS lesion animals, but did not alter blood pressure in the incomplete lesion group. Subsequent ganglionic blockade with hexamethonium produced comparable falls in mean arterial pressure in both groups of dogs. We conclude that vasopressin contributes significantly to the elevated blood pressure only in animals with complete interruption of the baroreceptor afferents in the rostral TS.

Acute Disease↗

Participation of the area postrema in cardiovascular control in the dog.

Investigations have demonstrated that the pressor effects of low-dose intravertebral angiotensin II (Ang II) in the dog are mediated by the area postrema (AP). Chronic ablation of the AP has been shown to produce both mild hypotension and blunting of the pressor effects of peripherally administered Ang II, which suggests a tonic influence by this structure on the regulation of blood pressure. These findings motivated a correlated series of neurophysiological and anatomical studies to characterize further the AP pressor pathway. The pressor response to electrical stimulation of the AP was shown to be mediated by increased central sympathetic outflow, as shown previously for the response to intravertebral Ang II, and unopposed by the central nervous system baroreflex pathways. Neuroanatomical investigations demonstrated a three-layer structure in the dog's AP, with efferent projections into the medial nucleus tractus solitarii bilaterally. These studies have provided new evidence about the functional and structural mechanisms by which the AP participates in cardiovascular regulation.

Angiotensin II↗

Hypotensive actions of microinjections of angiotensin II into the dorsal motor nucleus of the vagus.

Angiotensin II (ANG II) was injected via double-barrelled micropipettes into brain stem nuclei of 83 chloralose anaesthetized rats at doses between 8 fmol and 250 pmol. Femtomole injections of ANG II confined to the dorsal motor nucleus of the vagus (dmnX) and the ventral portion of the medial nucleus tractus solitarius (NTS) produced falls in blood pressure (BP) and heart rate (HR) of 28 and 12%, respectively, which were significantly greater than those produced by vehicle injections at these same sites (9 and 6% for BP and HR, respectively). ANG II injections into either the medial NTS or the hypoglossal nucleus were not different from vehicle. Prior administration of methylatropine (intraperitoneally) or bilateral cervical vagotomy significantly attenuated the bradycardia without affecting the fall in blood pressure. These data provide the first evidence for a direct action of low doses of ANG II within discrete nuclei of the dorsal medulla. The findings suggest that activation of the parasympathetic nervous system primarily accounts for the bradycardia. However, inhibition of sympathetic nervous system activity may contribute to the hypotension. Additionally, these data are consistent with a neurotransmitter or neuromodulator role for ANG II in the brain stem of rats.

Angiotensin II↗

Brainstem distribution of neurons with efferent projections in the cervical vagus of the dog.

The distribution within the brainstem of cell bodies and efferent fibers projecting in the cervical vagus was studied with retrograde transport of horseradish peroxidase (HRP). Five to eight days after multiple microinjections of HRP into either the cervical vagosympathetic trunk or the nodose ganglion the brainstems and nodose ganglia were perfused and processed by the tetramethyl benzidine method. HRP-positive neurons were found in three brainstem regions: a dorsal cell column comprising the dorsal motor nucleus of the vagus (dmnX), a ventrolateral group in the region of nucleus ambiguus (nA), and scattered cells along a line between these columns. The density of labeled neurons was greatest within dmnX. Axons from cells of the ventrolateral column projected dorsomedially; just ventral to dmnX they turned laterally to exit the medulla in multiple rootlets. Within nA labelled neurons were distributed according to size, with larger cells more medial and smaller ones more lateral. Caudal to nA in nucleus retroambigualis and nucleus dorsalis medialis cell bodies appeared segregated into clusters.

Animals↗

Lack of interaction between a hypertonic NaCl stimulus and the brain renin-angiotensin system.

Sodium and the renin-angiotensin system (RAS) participate in the regulation of cardiovascular function, in part via activation of central nervous system (CNS) mechanisms. Because intraventricular (IVT) administration of either hypertonic sodium chloride (NaCl) or angiotensin II (ANG II) elicits similar effects (i.e., natriuresis, hypertension, increased drinking, and enhanced vasopressin release) a common and final pathway may be involved. With this in mind, we measured the effect of an IVT injection (third or lateral ventricle) of 0.6 M NaCl on postganglionic renal nerve activity (RNA) and blood pressure in morphine-pentobarbital-anesthetized dogs before and after blockade of the brain RAS with either captopril or [Sar1,Ile8]ANG II. Both vagus and carotid sinus nerves were cut to avoid impingement of the baroreceptor reflex on the measured variables. IVT injection of 0.6 M NaCl produced a prominent hypertensive response and tachycardia associated with a 59 +/- 9% increase in RNA. These changes were statistically significant (P less than 0.001), correlated with each other, and were abolished by administration of hexamethonium chloride (10 mg/kg iv). Blockade of central ANG II receptors with [Sar1,Ile8]ANG II was without effect. However, in dogs given IVT SQ 14,225, there was a slight increase in baseline RNA before injection of 0.6 M NaCl; in addition, both the pressor and heart rate responses to the stimulus of hypertonic NaCl were further augmented. These results demonstrate that central administration of hypertonic NaCl in baroreceptor-denervated dogs produces marked activation of sympathetic nerve activity via mechanisms other than activation of the brain RAS.

Animals↗

Evidence for the existence of a family of biologically active angiotensin I-like peptides in the dog central nervous system.

A family of angiotensin I-like peptides has been derived from endogenous precursors present in dog cerebrospinal fluid after incubation with species homologous renin. These peptides are immunologically and pharmacologically similar to [Ile5]angiotensin I, and have molecular weights ranging between 1300 and 2200 daltons. The presence of precursors in the cerebrospinal fluid able to generate various biologically active angiotensin I-like peptides dissimilar to plasma angiotensin I supports the concept of a local angiotensin I-forming system in the brain.

Angiotensin I↗

Hierarchy of blood pressure control mechanisms after spinal sympathectomy.

We have investigated the relative importance of angiotensin and vasopressin in the regulation of arterial pressure following permanent interruption of supraspinal sympathetic influences. To accomplish this aim, the spinal cord of 12 dogs was transected just above the intervertebral foramen of C-6; several days later, we gave first a potent blocker of the vasculotropic actions of vasopressin and 40 min later captopril. The same experiment was performed in other dogs with the drug order reversed. Mean arterial pressure and heart rate were recorded continuously and blood samples were taken to measure plasma renin activity and plasma catecholamines. All studies were carried out at three levels of hydration: normal, after 36 h water deprivation and following an overnight infusion of 0.9% saline. Conscious dogs with complete surgical sympathectomy by spinal cord section had normal mean arterial pressure, heart rate and plasma renin activity but undetectable levels of catecholamines. Captopril produced significant falls in mean arterial pressure that were greatest in water deprivation and least in volume loading, whether the drug was given before or after treatment with the vasopressin antagonist. On the other hand, the vasopressin antagonist modified mean arterial pressure only in the water deprived state. In spinal dogs the renin angiotensin system assumes a primary role in maintaining normal mean arterial pressure at various extremes of body fluid volumes. Vasopressin plays a role only after removal of the two dominant systems.

Animals↗