D. F. Peterson

Intrapulmonary receptor response to changes in airway-gas composition in Gallus domesticus

1. A unidirectional, artificial ventilating system was used to observe respiratory and neural responses to changes in CO2 concentration in pulmonary airways of the chicken.

Receptors Sensitive to Carbon Dioxide in Lungs of Chicken

Receptors responsive to the removal of carbon dioxide from ventilatory gas were demonstrated in the lungs of the chicken. Apnea was induced in 0.64 second after rapid lowering of respired carbon dioxide in the absence of blood flow through the lungs. Afferent impulses from the receptors are conducted centrally in the vagi.

Identification of vagal sensory receptors in the rat lung: are there subtypes of slowly adapting receptors?

1. We studied the characteristics of pulmonary sensory receptors whose afferent fibres are in the left vagus nerve of opened‐chest rats. The activity of these receptors was recorded during mechanical ventilation approximating eupnoea, as well as during deflation, stepwise inflations and constant‐pressure inflations of the lungs. Data were also collected from closed‐chest rats and analysed separately. 2. Ninety‐four per cent of receptors were located in the ipsilateral lung or airways with the remainder in the contralateral lung. 3. Not only were slowly adapting receptors (SARs) the most abundant pulmonary receptors but 21% of them were either exclusively or predominantly active during the deflationary phase of the ventilatory cycle. Deflationary units were found in opened‐ and closed‐chest rats. The average conduction velocity for all fibres innervating SARs averaged 29.7 m s‐1. 4. We found rapidly adapting receptors (RARs) to be extremely rare in the rat. Their activity was sparse and irregular. The conduction velocities of fibres innervating RARs averaged 12.3 m s‐1. 5. Far more abundant than RARs in the remaining population of pulmonary fibres were C fibres. They were observed to have an average conduction velocity of 2.1 m s‐1, base‐level activity which was irregular and a high pressure threshold of activation and were stimulated by intravenous capsaicin injection. 6. Notable differences exist between pulmonary receptors in rats and those reported in other species. The variations include the abundant existence of intrapulmonary SARs with exclusively deflationary modulation and the rarity of RARs. We also encountered C fibres which have not previously been described systematically in the rat.

INHIBITION OF SYMPATHETIC ACTIVITY BY STIMULATING IN THE RAPHE NUCLEI AND THE ROLE OF 5-HYDROXYTRYPTAMINE IN THIS EFFECT

The possibility that the putative transmitter 5-hydroxytryptamine (5-HT) is involved in the mediation of long latency to onset raphe-spinal inhibition of sympathetic preganglionic neurones was investigated in anaesthetized cats by stimulating sites located in nucleus raphe pallidus and obscurus and recording sympathetic discharge in T3 or T10 white rami evoked either reflexively or by intraspinal stimulation at cervical level. Several putative 5-HT antagonists were administered intravenously (i.v.) or topically to the spinal cord. In 7 cats lysergic acid diethylamide (LSD) in a dose range 25-50 microgram/kg i.v. or 0.6 microgram topically, reversibly reduced the raphe spinal inhibition by 40-100%. Topical application was more effective than i.v. administration. In 5 cats stimulating within the ventromedial reticular formation at sites unlikely to involved 5-HT neurones produced a short latency to onset inhibition which was unaffected by LSD. Methysergide, cinanserin and cyproheptadine depressed sympathetic discharge in the absence of brain stimulation in cats with CNS intact and in unanaesthetized decerebrate spinal cats. The results are discussed in the light of the known actions of the putative 5-HT antagonists.

Some characteristics of sympathetic preganglionic Neurones in the rat

In anaesthetized rats sympathetic preganglionic neurones (SPN) were identified by their antidromic response to stimulation of the ipsilateral cervical sympathetic trunk (CST). Units were recorded at a depth of 0.75-1.1 mm from the dorsal surface of the spinal cord. The majority of SPN had axonal conduction velocities less than 1 m/s. Units could be routinely held for periods of up to 1 h. Spontaneously active SPN had discharge rates within the range 0.3-8.0 Hz. Application of horseradish peroxidase (HRP) to the central cut end of the CST resulted in the labelling of neurones only on the ipsilateral side, mainly in the intermediolateral cell column (IML) and the lateral funiculus and between the first and third thoracic (T) segments.

The circulatory influences of vagal afferents at rest and during coronary occlusion in conscious dogs.

We studied the role of cardiopulmonary vagal afferents in the cardiovascular responses to coronary artery occlusion in conscious dogs with intact carotid sinuses and following functional denervation of the arterial baroreceptors. The contributions of vagal afferents were determined by cold blocking the vagi. In dogs with intact carotid sinuses, coronary artery occlusion produced small decreases in mean cardiac output and arterial pressure, whereas heart rate increased by 35 beats/min. In dogs with intact carotid sinuses, vagal cold block increased mean arterial pressure by 22 ± 2 (mean ± SE) mm Hg and heart rate by 90 ± 6 beats/min. Mean cardiac output increased by 505 ± 90 ml/min. With the exception of heart rate, responses to coronary occlusion during vagal cold block were similar to the occlusion response prior to vagal cold block. Furthermore, prior occlusion of the coronary artery did not significantly influence the responses to vagal cold block. After arterial baroreceptor denervation, coronary artery occlusion resulted in a substantially greater fall in systemic arterial pressure (-52 mm Hg as compared to −8 mm Hg, with intact carotid sinuses) and peripheral resistance decreased by −0.49 peripheral resistance units (PRU). Vagal cold block following denervation increased the arterial pressure by 49 ± 10 mm Hg and peripheral resistance by 0.59 ± 0.13 PRU. Both values were significantly greater than those observed during vagal cold block prior to denervation. In arterial baroreceptor-denervated dogs, vagal blockade significantly attenuated the response to coronary occlusion. Therefore, in conscious dogs, vagal afferents from cardiopulmonary receptors exert a significant inhibitory influence on the peripheral vascular tone. When the carotid sinuses are intact, this inhibitory influence appears to be marked during myocardial ischemia. In the absence of functional arterial baroreflexes, vagal afferent activity contributes to the depressor responses observed during ischemia.

Reflex Heart Rate Control Via Specific Aortic Nerve Afferents in the Rabbit

Reflex bradycardia was elicited in rabbits via repetitive electrical stimulation of the central end of the sectioned left aortic nerve. Supramaximal stimulation produced a 16.9 ±1.3% (SE) increase in the R-R interval when vagal and sympathetic efferent pathways were intact. Reducing the stimulation voltage allowed selective stimulation of the myelinated (A) fibers, and polarizing electrodes placed central to the stimulus site permitted A fiber blockade and selective stimulation of the unmyelinated (C) fibers. When afferent A fibers were selectively stimulated, 64% of the maximum response was obtained; selective C fiber activation elicited 63% of the maximum observed response. Selective stimulation of A or C fibers after either vagotomy or stellectomy indicated that A fiber afferents elicit heart rate responses via both vagal and sympathetic efferents, whereas C fiber afferent information is mediated predominantly via vagal efferents. This afferent-efferent specificity of the aortic baroreceptor pathways suggests baroreceptor mechanisms normally used to modulate heart rate. Small increments in blood pressure would activate low-threshold A fibers and result in reciprocal changes in vagal and sympathetic efferent activity. More substantial increases in blood pressure would activate afferent C fibers and produce additional heart rate effects via vagal efferents.

Fibrosis of extrahepatic biliary system after continuous hepatic artery infusion of floxuridine through an implantable pump (infusaid pump)

A case of severe fibrosis of the extrahepatic biliary system after hepatic artery infusion of floxuridine is described. The clinical and pathologic features are presentedand its pathogenesis discussed. The authors suggest investigation of an alternate drug schedule and/or dosage of floxuridine to eliminate or minimize this serious complication.

Reduction in baroreflex cardiovascular responses due to venous infusion in the rabbit.

We studied reflex bradycardia and depression of mean arterial blood pressure (MAP) during left aortic nerve (LAN) stimulation before and after volume infusion in the anesthetized rabbit. Step increases in mean right atrial pressure (MRAP) to 10 mm Hg did not result in a significant change in heart rate or MAP. After volume loading, responses to LAN stimulation were not as great and the degree of attenuation was proportional to the level of increased MRAP. A change in responsiveness was observed after elevation of MRAP by only 1 nun Hg, corresponding to less than a 10% increase in average calculated blood volume. After an increase in MRAP of 10 mm Hg, peak responses were attenuated by 44% (heart rate) and 52% (MAP), and the initial slopes (rate of change) were reduced by 46% (heart rate) and 66% (MAP). Comparison of the responses after infusion with blood and dextran solutions indicated that hemodilotion was an unlikely explanation for the attenuation of the reflex responses. Total arterial baroreceptor denervation (ABD) abolished the volume-related attenuation of the cardiovascular responses, whereas attenuation was still present following bilateral aortic nerve section or vagotomy. It thus appears that the carotid sinus responds to changes in blood volume and influences the reflex cardiovascular responses to afferent stimulation of the LAN. On the other hand, cardiopuhnonary receptors subserved by vagal afferents do not appear to be involved.

Naloxone does not affect muscle blood flow during low intensity exercise in rats.

The purpose of this study was to determine whether endogenous opioids are involved in the control of skeletal muscle blood flow during locomotory exercise in rats. The radiolabeled miscrosphere technique was used to measure total and regional muscle blood flow. We first determined whether methionine enkephalin (1,000 micrograms.kg-1 I.V.) would produce vasodilation in muscle vascular beds. We found that methionine enkephalin produced a 36 mm Hg (range of 20-50 mm Hg) drop in mean arterial pressure (Pa), which was associated with decreases in calculated skeletal muscle vascular resistance in anesthetized rats, and that these effects on arterial pressure and skeletal muscle vascular resistance were blocked by the infusion of naloxone (10 micrograms.kg-1). Measurements were then made at 5 min of treadmill exercise at 15 m.min-1 (0 degree incline) and following exercise in both saline-treated (controls) and naloxone (10 micrograms.kg-1)-treated conscious rats. There were no differences between the heart rates, blood pressures, or total muscle blood flows of the two groups. There were also no significant differences between the blood flows to 32 hind limb muscle samples composed of various muscle fiber types. Since naloxone blockade did not affect total or regional muscle blood flow during low intensity exercise, it appears that the endogenous opioids are not required for the normal exercise hyperemia of skeletal muscles.