Circulatory Catecholamines Research Articles

Anesthetics Affect the Cerebral Metabolic Response to Circulatory Catecholamines

This study examined whether the effect of intravenous infusions of either epinephrine or norepinephrine on cerebral metabolic rate for oxygen (CMRO2) in the dog was modified by different anesthetics. Infusions of either epinephrine or norepinephrine at rates of 0.1-0.25 mu.kg-1.min-1 reversibly increased the CMRO2 by 17-23% during anesthesia with cyclopropane 20% and nitrous oxide 50% in oxygen, whereas infusions at rates of 0.1-25.0 micrograms.kg-1.min-1 had no effect in dogs anesthetized with other inhalational or intravenous agents. Cyclopropane/nitrous oxide also increased permeability of the blood-brain barrier to Evan's blue dye whereas the other anesthetics tested did not. It is concluded that epinephrine and norepinephrine crossed the blood-brain barrier during cyclopropane anesthesia, accounting for the increase in CMRO2. The authors speculate that cyclopropane may have increased blood-brain barrier permeability by a direct effect on endothelial cells or by affecting central adrenergic systems and that epinephrine or norepinephrine may increase CMRO2 either by a direct action on neuronal receptors or via metabolically coupled synaptic events.

Plasma catecholamines following low and high doses of ouabain in anesthetized dogs with or without cervical vagotomy.

Circulating catecholamine (CA) levels in the aortic blood did not change significantly in anesthetized dogs during a period of 60 min following the rapid intravenous injection of ouabain at a dose of 10 microgram/kg, but they did increase significantly after administration of a dose of 75 microgram/kg. After bilateral cervical vagotomy, the high dose of ouabain caused a greater and earlier elevation in circulating CA levels than in intact animals along with an increased cardiac index and a lower peripheral resistance. These findings suggest the existence of a vagal inhibitory mechanism upon liberation of CA following the administration of ouabain. Although ventricular arrhythmias did occur before the increase in circulating CA, preinjection CA levels were significantly higher in animals presenting ventricular fibrillation, suggesting that a high background adrenergic tone facilitates the production of ventricular arrhythmias by ouabain. Moreover, ventricular tachycardia occurred earlier in vagotomized dogs, in which the immediate elevation of circulating CA could have been a precipitating factor for this type of arrhythmia.

Evidences supporting an increased sympathetic tone and reactivity in a subgroup of patients with essential hypertension.

Several experimental evidences have shown that, under standarized conditions, circulating catecholamines (CA) or norepinephrine (NE) levels can be used as a valid index of the sympatho-adrenal activity in animal and man. This approach in the study of hypertensive patients has permitted to uncover that about 50% of patients with labile hypertension and about 30% of patients with stable hypertension had elevated CA levels at rest for 20 minutes in the supine position. The increased CA levels were mainly due to a rise in NE in stable hypertension and to a rise in epinephrine (E) in labile hypertension. On the basis of circulating CA levels, the hypertensive patients were divided into hyperadrenergic (CA levels above normal range) and normoadrenergic (CA levels within the normal range) subgroups. The hyperadrenergic labile or stable hypertensive subgroups were found to be also characterized by an enhanced CA or NE increase in response to change in position from supine to standing, by a faster heart rate and by an increased myocardial contractility, while these parameters were normal in the normoadrenergic subgroups. These findings support therefore the existence of an increased sympathetic tone and reactivity in association with hyperkinetic cardiac functions in an important population of hypertensive patients. In response to two weeks treatment with beta-blockers (either propranolol or metoprolol) hyperadrenergic stable hypertensive patients were found to be more responsive to this therapy than normoadrenergic patients although both groups had the same initial blood pressure. Moreover, this treatment lowered basal NE or CA levels and restored the enhanced CA or NE response to change in position toward normal in hyperadrenergic patients while it did not modify significantly circulating supine or standing CA and NE in normoadrenergic patients. These findings strongly support a participation of the sympathetic system in the maintenance of an elevated blood pressure in hyperadrenergic patients and raise the possibility of using a more rational approach in the therapy of hypertension.

Circulating catecholamines and systolic time intervals in normotensive and hypertensive patients with and without left ventricular hypertrophy

Circulating catecholamine (CA) levels were measured in normotensive and hypertensive patients with or without left ventricular hypertrophy (LVH) and were related with systolic time intervals, heart rate, and blood pressure. The pre-ejection period (PEP) and the ratio PEP LVET were correlated with circulating CA in normotensive and hypertensive patients. For a given circulating CA level, the PEP was higher in hypertensive patients with LVH than in those without LVH. This is probably secondary to a diminished myocardial contractility in these patients. Heart rate was related with circulating CA in hypertensive patients without LVH. When hypertensive patients without LVH were divided into normoadrenergic (circulating CA levels within normotensive range) and hyperadrenergic (circulating CA above normal range) groups, the hyperadrenergic group was found to have significantly higher heart rate than normotensive patients while the heart rate of the normoadrenergic group was similar to that of the normotensive group. PEP and PEP LVET were significantly elevated in the normoadrenergic group when compared with normotensive subjects but were not different in the hyperadrenergic group. These differences in chronotropic and inotropic myocardial activity between these two groups of hypertensive patients with normal and high levels of circulating CA suggest that they are separate entities.

Cardiac arrhythmias in experimental subarachnoid hemorrhage.

Experimental subarachnoid hemorrhage (SAH) in dogs was produced by introducing blood into the subarachnoid space through a catheter connected to an artery of the animal. The intact animals and those with preserved vagi and heart sympathetic innervation, developed arrhythmias with short latencies which correlated with the sudden increase in the intracranial pressure. The animals with sections of both vagi and heart sympathetic innervation, but with an intact spinal cord, developed arrhythmias that were delayed and did not correlate with the changes in intracranial pressure. These arrhythmias were preceded by changes in the QT interval, T wave and ST segment. It was concluded that the arrhythmias could be produced either by direct autonomic discharges to the heart or by increased circulating and tissue catecholamines. The clinical implications of these findings are discussed.

Effects of the sympathetic nervous system and the adrenal medullary hormones on dog hind limb blood flow after haemorrhage.

The contributions of the sympathetic nervous system and the adrenal medullary catecholamines to the response of dog hind limb resistance vessels to haemorrhage were examined. Anaesthetized dogs were bled either 30% or 45% of blood volume. There was little difference between the vascular conductance response in untreated hind limbs and sympathectomized limbs. Conductance in limbs that had been both sympathectomized and alpha-adrenergically blocked with phenoxybenzamine was markedly above that of untreated limbs. Blood flow in both the untreated limbs and the sympathectomized limbs was closely similar to that predicted from the pressure-flow curve for the hind limbs obtained in non-bled dogs. Flow was higher than predicted in the limbs with combined sympathectomy and alpha-adrenergic blockade. It is concluded that the sympathetic nervous system exerted little vasoconstrictive influence after haemorrhage, but that circulatory catecholamines exerted a strong vasoconstrictive influence that was opposed in the normal limbs by an almost equally powerful vasodilatory force of undetermined origin.

Physical and adrenergic factors affecting systemic vascular resistance in the rainbow trout: a comparison with branchial vascular resistance.

The passive distensibility and adrenergic reactivity of the systemic vascular resistance (Rs) in Salmogairdneri have been studied using perfused trunk preparations, and the data compared with previous results on the branchial resistance (Rg). At normal levels of efferent blood pressure, Rs is relatively more distensible than Rg in response to afferent pressure increases, but this difference may not be important in vivo. alpha-adrenegic constrictory receptors predominate in Rs, in contrast to beta-adrenergic dilatory receptors in Rg; a significant alpha-adrenergic tone in Rs is lost during perfusion. Rs is far less sensitive than Rg to circulatory catecholamine levels. It is suggested that the sympathetic nervous system, rather than plasma catecholamines, provides the effective adrenergic control of Rs in vivo.

Role of cardiac output and the autonomic nervous system in the antinatriuretic response to acute constriction of the thoracic superior vena cava.

Studies were performed on anesthetized saline-loaded dogs to delineate the afferent and efferent mechanisms involved in the antinatriuretic response to acute constriction of the thoracic vena cava. The kidneys of the animals were denervated prior to study, and renal perfusion pressure was controlled throughout the experiment. To differentiate between the potential afferent stimuli, increased hepatic venous pressure and decreased cardiac output, the thoracic superior vena cava (TSVC) was acutely constricted to lower cardiac output without increasing hepatic venous pressure. Acute TSVC constriction caused a decrease in sodium excretion qualitatively similar to that resulting from an acute constriction of the thoracic inferior vena cava (TIVC) which generated a comparable decrease in cardiac output. This finding suggests that the afferent limb of the antinatriuretic response to acute constriction of the thoracic vena cava, either TSVC or TIVC, involves diminution in cardiac output, or some consequence thereof, rather than increased hepatic venous pressure. Additional experiments were then performed in animals with pharmacologically-induced autonomic blockade. Autonomic blockade with hexamethonium or phenoxybenzamine abolished the antinatriuretic response to constriction of either the TIVC or TSVC. This finding suggests that the efferent limb of the antinatriuretic response to thoracic vena cava constriction involves sympathetic efferent pathways, either by an intrarenal effect of circulatory catecholamines or by controlling the release of an extrarenal factor influencing sodium reabsorption.

CIRCULATING SEROTONIN AND CATECHOLAMINES FOLLOWING OCCLUSION OF THE SUPERIOR MESENTERIC ARTERY.

CIRCULATING SEROTONIN AND CATECHOLAMINES FOLLOWING OCCLUSION OF THE SUPERIOR MESENTERIC ARTERY.

THE EFFECTS OF CYCLOPROPANE ON THE PERIPHERAL CIRCULATION IN MAN

Cyclopropane decreases forearm blood flow and, as the mean arterial pressure is little altered, vascular resistance is increased. The extent of the increase in vascular resistance is directly proportional to the concentration of cyclopropane. The vasoconstriction appears to be due to the direct action of cyclopropane on the blood vessel walls or associated nerve endings, possibly in conjunction with an enhanced effect of noradrenaline, and an increase in circulatory catecholamines. The earlier reports state that cyclopropane increases forearm blood flow but the data which are presented indicate that surgery, and not cyclopropane per se, may be the cause of this increased flow.

ALTERATIONS IN RESPONSE TO SOMATIC PAIN ASSOCIATED WITH ANAESTHESIA: XIV: EFFECTS OF SUBNARCOTIC CONCENTRATIONS OF METHOXYFLURANE

Analgesimetry readings failed to reveal an increase in pain threshold readings following the inhalation of subnarcotic concentrations (0.25 to 0.5 per cent) of methoxyflnrane. There may be a connection between the lack of analgesia and the absence of an increase in circulating catechol amines during methoxyflurane anaesthesia.

Effects of Acute Cardiac Tamponade on Circulatory Dynamics and Catecholamine Plasma Levels

Effects of Acute Cardiac Tamponade on Circulatory Dynamics and Catecholamine Plasma Levels

Retention of injected catechol amines by the mouse.

The importance of tissue storage as a method of inactivation of circulating catechol amines has been assessed by measuring the amount of unchanged hormone remaining in the mouse 30 min after the injection of various doses of [(3)H]-adrenaline or [(3)H]-noradrenaline. The results show that this method of inactivation is quantitatively more important for noradrenaline than for adrenaline at all dose levels studied, and that for both hormones storage is relatively more important at physiological dose levels (3 to 30 mug/kg) than at higher dose levels (150 to 300 mug/kg). The results obtained after the simultaneous injection of various doses of [(3)H]-adrenaline and [(14)C]-noradrenaline show that under certain conditions the two hormones compete for entry into the tissue storage sites. The possible nature of the mechanisms by which circulating catechol amines enter the tissue stores is discussed in the light of previous findings on the uptake of catechol amines by tissues in vitro.

Myocardial extraction and production of catechol amines.

Stimulation of the cardiac sympathetic efferent nerves is accompanied by a release of catechol amines in coronary blood. This release is a function of stimulation intensity and occurs even when stroke volume and coronary outflow are maintained constant. Comparison between the ethylenediamine and the trihydroxyindole methods for the analysis of plasma catechol amines shows both quantitative and qualitative differences, with only the results with the latter method showing a consistent relationship to the hemodynamic changes observed during cardiac sympathetic stimulation. The acutely synipatheetomized heart extracts catechol amines from coronary blood in the absence of nervous stimulation. The patterns of extraction observed indicate that the quantity of catechol amines in the myocardium can modify the extent of extraction in the unstimulated state as well as the extent of release during stimulation. Continued stimulation of the cardiac sympathetics is accompanied by at least a partial depletion of the myoeardial catechol amine stores. These stores appear to be repleted by circulating catechol amines, since the response to any given intensity of stimulation can be potentiated by a prior norepinephrine infusion. Dichloroisoproterenol prevents neither the myocardial extraction of catechol amines in the unstimulated state nor the release of catechol amines during sympathetic stimulation; it does lessen or abolish the cardiody-namic effects of sympathetic stimulation. Data are presented which indicate that a direct coronary vasoconstriction is one of the consequences of cardiac sympathetic nerve stimulation, the vasodilatation usually observed being due, at least in part, to overriding metabolic factors.

Reflex circulatory effects elicited by hypertonic and hypotonic solutions injected into femoral and brachial arteries of dogs.

Rapid injection of 40 ml. of 5 per cent saline into the femoral or brachial arteries of 24 dogs resulted in an average elevation of arterial blood pressure of +42/+20 mm. Hg, an increase in the heart rate of +20 beats/min., and an acceleration of the respiratory rate of +140 per cent. The response began 6 to 10 seconds after the onset of injection and lasted for 5 to 30 minutes. It occurred with the injection of hypertonic solution of saline, dextrose, and urea. The magnitude of the response was related to the degree of hypertonicity. Responses could be provoked by 10 ml. of 1.25 per cent saline. Rapid intra-arterial injection of isotonic saline, dextrose, and urea solutions, and of whole blood in volumes up to 80 ml. had no circulatory effect. Rapid injection of distilled water, 0.225 per cent and 0.45 per cent saline into the femoral or brachial arteries resulted in a slight degree of hypotension and a rise in the respiratory rate. The appearance of circulating catechol amines following the response to intra-arterial injection of hypertonic solutions was suggested by the demonstration of hypotensive response to intravenous injection of phentolamine. These responses to injection of hypertonic and hypotonic solutions in the femoral artery were abolished by section of the sciatic nerve in animals with an ipsilateral partially-transected hind limb, a preparation which left intact only the femoral artery, femoral vein, and femur. Sciatic section in the intact limb reduced but did not abolish the response. Removal of the sympathetic chain from the eleventh thoracic through the third lumbar ganglia had no apparent effect. It is concluded that the response to femoral aud brachial intra-arterial injection of hypertonic and hypotonic solutions is initiated by peripherally located "osmoreceptors" in the distribution of these arteries and is mediated via a reflex whose afferent fibers travel in the peripheral somatic nerves and enter the spinal cord without passing through the sympathetic chain. The efferent are is the sympathetic nervous system.

Mechanism of the protective action of magnesium in mechanical trauma involving epinephrine and norepinephrine.

Pretreatment of animals subjected to tumbling trauma with MgSO4·7H2O injected intraperitoneally brings about a significant decrease in the mortality and a concomitant decrease in the concentration of the circulating epinephrine and norepinephrine. The pretreatment also prevents as large a decrease in blood volume as is seen in the untreated animals. In the treated animals, the small decrease that is seen soon returns to normal. It is proposed that the protective action of the Mg++ lies in its ability to maintain the blood volume and thereby prevent the increase in circulating catechol amines seen in the untreated animals.

The catechol amine content of various organs of the cat after injections and infusions of adrenaline and Noradrenaline.

Infusions of 2.5-7.8 µg. noradrenaline/Kg./min. over 30 min. and intraperitoneal injections of noradrenaline and adrenaline up to 2000 µg/Kg, in the cat had no effect on the catechol amine content of the heart, spleen, liver, kidney and skeletal muscle, except for a slight increase in the adrenaline content. It is concluded that these organs lack the ability to accumulate circulating catechol amines administered in physiologic dosage.