Edward W. Lowman

Regulatory Dysfunction of Microvasculature and Catecholamine Metabolism in Spinal Cord Injury

Since 1917 when Head and Riddoch (4) first described autonomic hyperreflexia in spinal cord injury, its attending neurophysiological symptoms have been well documented by other investigators. It is well known that the triggering mechanism may well be any noxious stimuli but most often autonomic hyperreflexia is caused by hyperirritability of the bladder due to formation of stones of calcium salts or infection of the urinary bladder; the common denominator being distension of the vesicular wall leading to increased intracystic pressure. The major symptoms during the so-called hyperreflexia are: pallor of the skin below in contrast to a histamine-like flush above the level of the lesion, vasodilatation in the head and neck accompanied by engorging pulsating corotid arteries. Moreover, the peak of hyperreflexia coincides with the height of intracystic and brachial blood pressures, headache, and piloerection. Guttmann and Whitteridge (3) were the first to observe that the hypertensive crises could be produced only in those subjects with lesions above the sixth thoracic dermatome (T6). The purpose of this communication is to shed more light on the etiology of these hypertensive episodes which occur spontaneously in human subjects with high level spinal cord injury and which are frequently the cause of cerebrovascular accidents.

Increased serum dopamine-β-hydroxylase activity during neurogenic hypertension in quadriplegia

Publisher Summary This chapter describes the increased serum dopamines-β-hydroxylase (DBH) activity during neurogenic hypertension in quadriplegia. A group of eight quadriplegic patients were self-compared before and after expansion of the urinary bladder by means of water intake. All patients were during the chronic phase, 6 months or longer after the onset of the injury, and had suffered a complete physiologic transverse lesion at the level of the fifth and seventh cervical dermatomes. Autonomic response in quadriplegia is manifested by headache, piloerection, a red flush and profuse diaphoresis above the level of transection. In contrast to the vasodilatation cephalad to the lesion, there is a marked vasoconstriction of peripheral blood vessels, and pallor of the skin below the level of transection. The hypertension, brought about spontaneously, or by means of water intake, is caused by increased elaboration of catecholamines. The concentration of homovanillic acid, the major metabolite of dopamine, was enhanced significantly concomitant with that of other catecholamine metabolites, and with enhanced activity of serum DBH.

Catecholamine Metabolism and Digital Circulation after Histamine and Its Analogue

In 1959 (1) we reported the paradoxical effects on the digital circulation of histamine administered parenterally and of an orally ingested histamine analogue* (2). Both histamine and its analogue produced vasodilatation of the capillaries as manifested by flushing contrasted with vasoconstriction of the arteriovenous anastomoses (AVAS). It was postulated at that time that the AVA constricted in response to heat loss produced by histamine-mediated precapillary sphincter and hence capillary vasodilatation. The question as to whether the AVA constriction was a neural reflex or produced by some other mechanism such as the release of catecholamines (CM) from nerve endings and/or chrcmaff in tissues remained unanswered (3).

EFFECT OF HYPERTENSIVE STRESS ON PLASMA DOPAMINE-β-HYDROXYLASE ACTIVITY AND PROSTAGLANDINS IN QUADRIPLEGIA

Publisher Summary Quadriplegic subjects are afflicted with “autonomic hyperreflexia” or “autonomic dysreflexia,” a term describing several events that are manifested by cardiovascular symptoms. Autonomic dysreflexia occurs in the subjects with lesion above the sympathetic outflow from the spinal cord. The condition can be elicited by the distension of the hollow viscera or by chemical, tactile, or pressure stimuli applied to the body below the level of the spinal cord transection. The syndrome is characterized by paroxysmal hypertension, including pallor of the skin below and profuse flushing and diaphoresis above the level of the lesion Hypertensive episodes are accompanied by an extreme rise in arterial blood pressure, bradycardia, severe headache, and chest pain. It has been reported that peripheral circulation and catecholamine metabolism in quadriplegic subjects is abnormal in the resting state. It has been shown that the release of dopamine-β-hydroxylase (DβH), the enzyme responsible for the synthesis of the neurotransmitter norepinephrine (NE) from dopamine (DA) was enhanced during hyperreflexia in quadriplegia. It was reported that infusion of prostaglandins causes headache and they have been associated with carcinoid disease in which severe headache, concomitant with a flushing episode is a prominent feature.

EFFECT OF TRAUMATIC STRESS ON CATECHOLAMINE AND METABOLISM IN THE SPINAL CORD SYNTHESIS

Publisher Summary Elevated norepinephrine (NE) levels in traumatized spinal cords were implicated in the formation of the hemorrhagic necrosis or were thought to reflect the ingress of circulating amines as a result of disruption of the blood-spinal cord barrier rather than release from descending adrenergic fibers. The present study was undertaken to resolve the controversy concerning the role of catecholamines in traumatized spinal cord. Analysis of monoamine oxidase (MAO) activity in vitro demonstrates that one hour after impact activity of the enzyme is significantly reduced. The reduction in specific activity of DA after contusion of the spinal cord also indicates that the activity of tyrosine hydroxylase, the rate-limiting enzyme in the biosynthesis of NE, is reduced. Since the incorporation of radioactivity into 3H-DA is reduced using the precursors 3H-tyrosine and -3H -dopa it follows that the activity of L-amino acid decarboxylase (L-AAD) is also impaired. In vitro provided with all co-factors including oxygen, dopamine β-hydroxylase (DβH) activity in the spinal cord after impact remains unchanged; within the time interval of the experiment little protein denaturation has taken place.

INCREASED SERUM DOPAMINES-β-HYDROXYLASE ACTIVITY DURING NEUROGENIC HYPERTENSION IN QUADRIPLEGIA

Publisher Summary This chapter describes the increased serum dopamines-β-hydroxylase (DBH) activity during neurogenic hypertension in quadriplegia. A group of eight quadriplegic patients were self-compared before and after expansion of the urinary bladder by means of water intake. All patients were during the chronic phase, 6 months or longer after the onset of the injury, and had suffered a complete physiologic transverse lesion at the level of the fifth and seventh cervical dermatomes. Autonomic response in quadriplegia is manifested by headache, piloerection, a red flush and profuse diaphoresis above the level of transection. In contrast to the vasodilatation cephalad to the lesion, there is a marked vasoconstriction of peripheral blood vessels, and pallor of the skin below the level of transection. The hypertension, brought about spontaneously, or by means of water intake, is caused by increased elaboration of catecholamines. The concentration of homovanillic acid, the major metabolite of dopamine, was enhanced significantly concomitant with that of other catecholamine metabolites, and with enhanced activity of serum DBH.