Peripheral vascular disorders. Assessment and intervention.

Peripheral vascular diseases are being seen with increased frequency in the health care setting today. It is imperative that nurses have a clear understanding of arterial, venous, and lymphatic circulatory mechanisms as well as the pathophysiologic changes that accompany common diseases of these systems. Providing the ongoing assessment to obtain a diagnosis, establish the acute versus chronic nature of findings, monitor progression, plan care, and assess the response to treatment is an important role for the nurse in order to preserve function, life, and limb in these patients.

Amitriptyline normalizes tetrabenazine-induced changes in cerebral microcirculation.

The cerebromicrocirculation in the tetrabenzaine (TBZ) model of depression has been found to be abnormal with respect to (1) responsiveness of cerebral blood flow to increases in arterial CO2 content and (2) the effective permeability of the blood-brain barrier to water. Development of these abnormalities temporally paralleled the behavioral disturbances and catecholamine depletion induced by TBZ. These TBZ-induced changes occurred globally throughout the brain, being apparent in the forebrain, cerebellum, and medulla-pons. Pretreatment with the antidepressant amitriptyline prevented both behavioral and physiological effects of TBZ, whereas amitriptyline administered after TBZ was less effective. The results suggest that an important action of tricyclic antidepressants may be cerebromicrocirculatory effects.

Cerebromicrocirculatory defects in animal model of depression.

In the tetrabenazine (TBZ) model of depression, the cerebromicrocirculation was discovered to respond abnormally to metabolic demand as mimicked by the administration of CO2. Altered responsivity of cerebral blood flow and effective permeability of the blood--brain barrier to changes in PaCO2 were found. These physiologic defects coincided temporally with TBZ-induced depletion of central norepinephrine and dopamine and with the development of the behavioral effects of TBZ (the end points used to test the antidepressant potential of experimental drugs). Pretreatment with amitriptyline (a standard antidepressant and amine reuptake inhibitor) prevented the development of these TBZ-induced abnormalities in the cerebromicrocirculation, just as it prevented the behavioral effects.

Role of the central adrenergic system in mediating amitriptyline-induced alteration in the mammalian blood-brain barrier in vivo.

All tricyclic antidepressants increase the degree of equilibration of [3H]water across the cerebral capillary (Ew) as measured by a dual-label radioactive tracer technique. By using amitriptyline (AMI) as a prototype, a series of studies was conducted to determine the mechanism for this drug effect. The AMI-induced increase in Ew was blocked by 6-hydroxydopamine ablation of central aminergic neurons and by pretreatment with phenoxybenzamine, an alpha adrenergic antagonist. Pretreatment with propranolol, a beta adrenergic antagonist, did not block the AMI-induced increase. Central serotonergic ablation by p-chloroamphetamine had no effect on the AMI-induced increase. Treatment with atropine and hydroxyzine separately also did not alter Ew. Based on these results, the AMI-induced increase in Ew appears to be mediated by the effect of the drug on central adrenergic neurons. The serotonergic, anticholinergic and antihistaminergic actions of AMI, by themselves, do not appear to play a role in this phenomenon. The results are compatible with the concept that the central adrenergic system functions, in part, to regulate the cerebromicrocirculation.

A dual label radiotracer technique for the simultaneous measurement of cerebral blood flow and the single-transit cerebral extraction of diffusion-limited compounds in rats.

An inexpensive method is described which permits simultaneous quantification of the cerebrovascular extraction (E) of diffusion-limited compounds and cerebral blood flow (CBF) in rats. This method involves the use of two radioisotopic tracers: (a) a diffusion-limited, test tracer such as [3H]water; and (b) a reference tracer. The reference tracer is also used in the measurement of CBF. In the development and validation of this technique, results using two different types of reference tracers were compared. The reference tracers employed were: (a) [14C]butanol, a flow-limited (i.e. freely diffusible) compound; and (b) [141Ce]microspheres which embolize in the cerebromicrocirculation. Inclusion of [3H]water in the injection bolus permitted simultaneous measurement of Ew using both butanol and microspheres as the reference as well as concomitant measurement of CBF. Both tracers provided estimates of these values which behaved physiologically with respect to increasing arterial CO2 content (paCO2). In addition, the simultaneous measurement of Ew and CBF permitted calculation of the effective permeability of water across the blood-brain barrier (PwS) which was discovered to increased with increasing paCO2.

Medical therapies for mood disorders alter the blood-brain barrier.

The effects of amitriptyline, lithium, and electroconvulsive shock on cerebral permeability and blood flow were tested. These three treatments share in common (i) the ability to influence the functional activity of central adrenergic neurons by way of effects on the release, reuptake, or metabolism of norepinephrine and (ii) therapeutic efficacy in mood disturbances. Under control conditions, cerebral permeability increases linealy with increasing arterial partial pressure of carbon dioxide and hence cerebral blood flow. All three treatments altered this relationship in a manner consistent with their adrenergic effects. Amitriptyline potentiated this increase in cerebral permeability whereas lithium and electroconvulsive shock blunted this phenomenon. These results support the hypothesis that one function of central adrenergic neurons is regulation of the blood-brain barrier and raise the possibility that a related effect may underlie the clinical usefulness of such treatment.