Yoshikuni Amakata

Comparison of responses of canine pulmonary artery and vein to angiotensin II, bradykinin and vasopressin

Responses to angiotensin II, bradykinin and arginine vasopressin were compared in helical strips of canine pulmonary arteries and veins. Angiotensin II contracted the artery but relaxed the vein strip. The artery contraction was augmented by indomethacin and aspirin and was abolished by losartan. The vein relaxation was not affected by endothelium denudation but was abolished by the cyclooxygenase inhibitors, a prostaglandin I2 synthase inhibitor and losartan. The bradykinin-induced artery relaxation was inhibited by endothelium denudation, NG-nitro-L-arginine (L-NA) or indomethacin and abolished by their combined treatment. The vein relaxation produced by bradykinin was endothelium-independent and was abolished by indomethacin. Vasopressin produced a slight relaxation in the arteries, which was abolished by endothelium denudation and L-NA. The vein relaxation produced by vasopressin was abolished by endothelium denudation and combined treatment with L-NA and indomethacin. It may be concluded that (1) activation of angiotensin AT1 receptor subtype in smooth muscle produces contraction and also relaxation due to prostaglandin I2 release; the former predominates over the latter in the artery, whereas only the latter is operative in the vein, (2) the bradykinin-induced relaxation is due to nitric oxide (NO) from the endothelium and prostaglandin I2 from subendothelial tissues in the artery and solely to prostaglandin I2 in the veins, and (3) the vasopressin-induced relaxation is mediated by endothelial NO in the artery, and NO and prostaglandin I2 in the vein.

Comparative study of the mammalian liver innervation: an immunohistochemical study of protein gene product 9.5, dopamine β-hydroxylase and tyrosine hydroxylase

The liver innervation of eight different mammalian species was examined by immunohistochemical localization of protein gene product (PGP) 9.5 to visualize the general innervation for autonomic nerve fibres. In addition, dopamine beta-hydroxylase (DBH) and tyrosine hydroxylase (TH), two enzymes involved in catecholamine synthesis, were localized immunohistochemically to delineate hepatic sympathetic nerve fibres. We found that: (1) Within the interlobular region of each species, PGP 9.5, DBH and TH-positive nerve fibres were all seen in close association with branches of hepatic arteries, portal veins and bile ducts. (2) Within the parenchyma of the guinea-pig, cat, dog, pig, monkey and human liver, the presence of the three immuno-positive nerve fibres could be unequivocally identified, although the density of these intralobular fibres showed marked species variation. Moreover, immunoelectron microscopic study confirmed that PGP 9.5-positive nerve terminals of the human liver are in close apposition to hepatocytes. (3) In mouse and rat, no parenchymal nerve fibres immunoreactive for PGP 9.5, TH or DBH could be demonstrated.

Selective Actions of Intravenous Anesthetics on Nicotinic- and Muscarinic-receptor-mediated Responses of the Dog Adrenal Medulla

The selective actions of intravenous anesthetics on the cholinergic nicotinic and muscarinic responses of adrenal medullary cells were studied using isolated dog adrenals perfused with modified Lockes solution. Log-probit dose-response curves of the inhibitory effects of the anesthetics on the catecholamine releases induced by acetylcholine, nicotine, and muscarine were determined. Percentage inhibition by the anesthetics at clinically relevant concentrations were 98% of nicotine- and 31% of muscarine-induced releases by alphaxalone 2.6 μM, 76% of nicotine and 13% of muscarine by thiopental 23.9 μM, 86% of nicotine and no inhibition of muscarine by ketamine 17.0 μM, and no inhibition of either response by diazepam 5.0 μM. The ratio of IC50 (concentration for 50% inhibition), which was calculated by dividing IC50 for muscarine by 50 for nicotine, showed a variety of values ranging from 3.9 for diazepam to 38.0 for ketamine. The results suggest that each anesthetic has characteristic selective inhibitory effects on nicotinic and muscarinic cholinergic responses. The differing effects on the muscarinic responses might be one of the factors contributing to the characteristic properties of each anesthetic, whereas the inhibition of nicotinic responses might reflect a common property for many anesthetics

Mechanism of the Effect of Droperidol to Induce Catecholamine Efflux from the Adrenal Medulla

The study was undertaken to determine whether droperidol had an effect to induce catecholamine efflux from the adrenal medulla as a mechanism for the possible pressor effect of droperidol in patients with pheochromocytoma and, if so, to ascertain the site of action of this compound. The efflux of catecholamines from perfused dog adrenals was increased from control level, 0.15 μg/min, to 0.66 μg/min by the administration of droperidol 6.6 μm. This effect of droperidol was not dependent on extracellular Ca++, in contrast to acetylcholine. The concomitant secretion of catecholamines and dopamine-β-hydroxylase was observed in response to acetylcholine and caffeine. However, droperidol-, histamine-, and reserpine-induced catecholamine efflux was not accompanied by dopamine-ß-hydroxylase release. In additional studies, chromaffin granules were isolated with a Millipore· filter technique from the bovine adrenal medulla and were incubated for 10 min in an isotonic medium to examine the direct effects of droperidol. Droperidol did not enhance the efflux of catecholamines from the granules in contrast to histamine. The upake of 14C-norepinephrine into the granules was inhibited by droperidol in a manner comparable to reserpine. The results suggest that droperidol induces catecholamine efflux from adrenal medullary cells and the efflux probably is caused by a nonexocytotic mechanism. A contributing mechanism was an inhibition of catecholamine uptake into chromaffin granules, resulting in an increased diffusion of catecholamines out of the cell.

Pituitary apoplexy following cholecystectomy

A case of pituitary apoplexy, which presented with hyperaesthesia in the distribution of the ophthalmic division of the left trigeminal nerve and a left sixth nerve palsy following cholecystectomy, is reported. Computed tomography and magnetic‐resonance imaging revealed a large intrasellar mass which extended laterally into the left cavernous sinus and showed evidence of old and recent haemorrhage within the tumour. This case demonstrates that patients who present with unusual neurological symptoms involving the cranial nerves after general anaesthesia, should undergo neurological and radiological investigations.

Mechanism of the differential effects of halothane on nicotinic- and muscarinic-receptor-mediated responses of the dog adrenal medulla.

The mechanism of the differential effects of halothane on the cholinergic nicotinic and muscarinic responses of adrenal medullary cells was studied using isolated dog adrenals perfused with modified Lockes solution. The concentrations of halothane exhibiting 50% inhibition of catecholamine release induced by nearly equipotent agonists were 0.8% for nicotine, 1.9% for acetylcholine, and 2.8% for muscarine, respectively. Per cent inhibition by halothane (1.5%) of nicotine-induced catecholamine release was 98.5%, and those of veratridine-, acetylcholine-, CaCl2−, Na+-deprivation and muscarine-induced catecholamine release were 89.7, 32.5, 21.4, 10.1, and 9.5%, respectively. Halothane showed an inhibitory effect on the agonist-induced catecholamine release in Na+-free solution to the same extent as in Na+ -containing solution. Tetrodotoxin abolished veratridine-induced catecholamine release completely and decreased nicotine-induced release slightly, whereas it had no effect on either muscarine- or acetylcholine-induced catecholamine release. Verapamil inhibited acetylcholine-induced catecholamine release by 65%, and nicotine- and muscarine-induced release by 79% and 26%, respectively. The results suggest that halothane at clinical concentrations selectively inhibits the nicotinic-receptor-mediated responses of the dog adrenal medulla. The mechanism involved might be the susceptibility to halothane of the Ca++ channels that are linked to the respective nicotinic and muscarinic receptors. An inhibition of exocytosis might be also indicated as part of the effect of halothane.

Effect of halothane, fentanyl, and ketamine on the threshold for transpulmonary passage of venous air emboli in dogs.

We assumed that the capacity of the lungs to filter gas bubbles would vary as a function of anesthetic management. The effects of halothane (1% inspired concentration [group 1, n = 8]), fentanyl (100 micrograms/kg IV, followed by 1 micrograms.kg-1.min-1 [group 2, n = 7]), and ketamine (10 mg/kg IV, followed by 0.2 mg.kg-1.min-1 [group 3, n = 6]) on the passage of bolus injections of air across the pulmonary circulation were studied in dogs by using transesophageal echocardiography to detect air in the left atrium or the aorta, or both. The thresholds for bolus air detection during halothane, fentanyl, and ketamine administration were 0.05 mL/kg (range 0.01-0.1), 0.5 mL/kg (range 0.2-1.0), and 0.35 mL/kg (range 0.1-0.5), respectively. We conclude that the threshold during fentanyl- or ketamine-induced anesthesia was significantly higher than during halothane-induced anesthesia. Therefore, halothane interferes with the capacity of the lungs to filter air from the pulmonary circulation.

Localization of [D-Ala2]deltorphin I-like immunoreactivity in perinatal rat respiratory system

SummaryThe localization of [D-Ala2]deltorphin I, a δ-opioid receptor ligand, was studied in the lower respiratory tract of developing rats using an immunohistochemical method. [D-Ala2]-like immunoreactive cells were detected first in the principal bronchus as early as embryonic day 16. As embryos grew, positive cells became gradually visible everywhere from principal bronchi to respiratory bronchioles. The density of positive cells reached the highest level on embryonic day 21, but decreased gradually after birth. Positive cells were no longer seen on postnatal day 30 in any region of the airways. No positive cells were ever found in the trachea or alveoli of rats at any age studied. Ultrastructural examination indicated that the immunoreactive cells possessed a similar morphology to serous or Clara cells of the respiratory epithelium. Immunoreaction products tended to locate at the apical cytoplasm of positive cells. The result suggests that [D-Ala2]-like molecule(s) may be expressed transiently in serous cells or Clara cells, or both, of the rat bronchopulmonary tract. Such a molecule may act as a pulmonary growth-promoting or a differentiation-initiating factor in an early period of lung development.

A new leak test for specifying malfunctions in the exhalation and inhalation check valve.

problem exists that there is fractional extraction of epinephrine in forearm tissues in the range of 25%-50% (1,2). Measurement of norepinephrine concentrations from the antecubital vein is also subject to the influence of local factors that both add and remove norepinephrine from forearm tissues. Accordingly, we acknowledge that the pulmonary artery is the best sampling site for measuring epinephrine concentrations.and that arterial measurements provide a good alternative. However, the medical condition of our patient population did not ethically justify the use of either pulmonary or radial arterial catheters, so antecubital venous sampling was used instead. In taking this limitation into consideration, we wish to emphasize that we evaluated the percentage of change of both epinephrine and norepinephrine concentrations in response to a standardized stimulus (tracheal intubation) and measured the within-patient serial changes of both catecholamines over a very short period ( 4 0 min). We observed that the changes in catecholamine concentrations paralleled the cardiovascular response in both the control and experimental groups, suggesting a reasonably reliable reflection of the body‘s response to stress. Reflecting on our study design, we concur with the recently expressed opinion of Dr. Herd that “epinephrine is not secreted from organs other than the adrenal medulla. Accordingly, few assumptions need to be made concerning the pattern of epinephrine levels in the forearm venous blood” (1). Donald R. Miller, MD Raymond J. Martineau, MD Kathryn Hull, RN Department of Anaesthesia

Catecholamine Uptake and Release in Isolated Chromaffin Granules Exposed to Halothane

The effects of halothane on the catecholamine release from chromaffin granules and the uptake of 14C-epinephrine into the granules were studied using isolated bovine adrenal medullary chromaffin granules. The granules were isolated with a Millipore filter, and were incubated for 10 min in an isotonic medium containing adenosine triphosphate (ATP)-Mg++. At halothane concentrations of 0.4 mM or greater, the uptake of 14C-epinephrine into the granules was inhibited in a dose-related manner. At 0.7 mM halothane, epinephrine uptake was reduced to 56 per cent of control. The inhibition was completely reversible after removal of halothane from the medium. The inhibitory effect of halothane was not affected by high-osmolar medium. Catecholamine release from isolated chromaffin granules was enhanced by halothane at concentrations of more than 1.3 mM, but was not affected when the concentration was 0.7 mM or less. The results suggest the possibility that halothane might alter the intracellular storage -turnover process and the subsequent release pattern of catecholamines. The possible mechanisms of this action are discussed.