Yoshio Hatano

Modifications by stretches of the mechanical response of isolated cerebral and extracerebral arteries to vasoactive agents

SummaryLength-tension relationship was compared in helically cut strips of canine cerebral, coronary, mesenteric, renal, and femoral arteries. Tension developed progressively by increasing the stretch; with the same strain, a greater passive tension developed in cerebral than in extracerebral arteries. The peak active tension developed by serotonin (cerebral, coronary), norepinephrine (mesenteric, renal and femoral) or K+ (coronary) was obtained at a resting tension of 1.5 g (other than coronary) or 2.0 g (coronary). Papaverine (10−4 M) caused a relaxation in cerebral arterial strips contracted with serotonin to a level lower than that prior to the addition of serotonin, the relexation from the initial level of tension being related directly to the stretch applied. The relaxing effect of adenosine was related directly to stretches of cerebral arterial strips. It seems likely that a rise of intra-arterial pressure effects a greater increase in the wall stiffness in cerebral than in extracerebral arteries. The responsiveness to vasoconstricting and vasodilating agents of both cerebral and extracerebral arteries appears to increase when the arteries are distended.

Hemodynamic changes after resection of thoracic duct for en bloc resection of esophageal cancer

An en bloc resection of esophageal cancer is one of the most radical forms of esophagectomy, and includes the resection of the thoracic duct, but a relatively high hospital motality rate has been reported. There is very little knowledge on the pathophysiological changes after resection of the thoracic duct. We examined 24 patients who underwent en bloc resection. Some patients developed severe tachycardia or shock postoperatively which subsided after a massive infusion of plasma. Analysis of the fluid balance revealed that much more fluid was necessary during surgery and the postoperative 24 h than in patients treated by a standard esophagectomy. Postoperative lymphangiography or CT revealed abnormal collateral lymphatics around the kidneys or in the pelvic cavity. This suggests the development of the lymphaticovenous shunts, which differed depending on the anatomy of each patient. One patient with chronic hepatitis developed uncontrollable ascites. These are important findings which can hopefully reduce the high rate of hospital death after this operation.

Responses to barbiturates of isolated dog cerebral and mesenteric arteries contracted with KCl and prostaglandin F2a

In helical strips of dog cerebral and mesenteric arteries previously contracted with KCl or prostaglandin F2a (PGF2a), the addition of pentobarbital (10‐5 to 10‐3 moll‐1‐1) caused dose‐related relaxation, whereas thiamylal and thiopental in a low concentration (10‐5 to 10‐4 moll‐1‐1) caused further contraction and in a high concentration (10‐3 mol‐1‐1) profound relaxation. Thiobarbiturate‐induced contractions were greater in mesenteric than in cerebral arteries previously contracted with PGF2a. In cerebral and mesenteric arteries exposed to Ca++‐free media for 60 min and treated with KCl or PGF2a, reintroduction of Ca ++ produced a transient contraction, a transient relaxation and a persistent contraction. The Ca++ ‐induced persistent contraction was attenuated by pretreatment with pentobarbital (10‐4 to 10‐3 mol‐1‐1) and thiamylal (10‐3 mol‐1‐1); the attenuation was greater in arteries treated with KCl than with PGF2a. The Ca++ ‐induced contractions of mesenteric artery treated with PGF2a were potentiated by 10‐4 mol‐1‐1 thiamylal. It is concluded that pentobarbital possesses only a vasodilator effect, whereas thiamylal and thiopental have both constrictor and dilator effects on vascular smooth muscle. The vasodilator effect of barbiturates is associated in part with inhibition of transmembrane influx of Ca++; the inhibition is more predominant on the influx evoked by KCl‐induced depolarization than by a stimulation of PGF2a receptors. Thiamylal in low concentrations appears to enhance Ca++ influx through a receptor‐operated Ca++ channel for PGF2a.

Suppression of acetylcholine-induced relaxation by local anesthetics and vascular NO-cyclic GMP system.

Background: Local anesthetics have been demonstrated to attenuate acetylcholine‐induced relaxation of vascular smooth muscle, but the mechanism responsible has not been elucidated. The present study was undertaken to ascertain whether this effect of local anesthetics is due to suppression of the vascular nitric oxide (NO)‐cyclic GMP (cGMP) system.

Comparison of the vasodilator effects of thiopentone and pentobarbitone

The aim of this study was to elucidate the vasodilator mechanisms of barbiturates. In helical strips of dog mesenteric artery, the effects of pretreatment with thiopentone and pentobarbitone on the contractions induced by KCl (2.0 × 10−2 M) and norepinephrine (10−5 M) in normal bathing fluid, and those induced by norepinephrine and caffeine (2.5 × 10−2 M) in Ca++-free fluid were tested, and their effects on caffeine-induced contractions in skinned strips were also examined. Thiopentone, at concentrations over 10−4 M, inhibited the KCl-induced contractions in normal bathing fluid and those induced by caffeine in Ca++-free fluid and, at concentrations over 3 × 10−4 M, inhibited norepinephrine-induced contractions in normal and Ca++-free bathing fluids significantly. Pentobarbitone, at concentrations over 3 × 10−4 M, inhibited KCl- and norepinephrine-induced contractions in normal bathing fluid significantly, whereas contractions in Ca++-free fluid induced by norepinephrine and caffeine were inhibited only by a high concentration (10−3 M) of pentobarbitone. Caffeine-induced contractions of chemically skinned fibres were more susceptible to inhibition by thiopentone than by pentobarbitone. These results suggest that the vasodilator effect of thiopentone is mediated via its intracellular inhibitory effect and that, in contrast, the vasodilator effect of pentobarbitone can be attributed mainly to its Ca++ -channel blocking action.RésuméLe but de cette étude était d’élucider les mécanismes vasodilatateurs des barbituriques. Sur des bandelettes spiralées de l’artère mésentérique du chien, nous avons vérifié les effets d’un traitement préparatoire au moyen de thiopental et de pentobarbital sur les contractions induites par du KCl (2,0 × 10−2 M) et de la norépinéphrine (10−5 M) dans un liquide de bain normal, ainsi que sur celles induites par de la norépinéphrine et de la caféine (2,5 × 10−2 M) dans un liquide ne contenant pas d’ions Ca++. Sur des bandelletes dénudées, nous avons également examiné leurs effets sur les contractions induites par la caféine. Le thiopental, à des concentrations supérieures à 10−4 M, inhibait les contractions induites par le KCl dans un liquide de bain normal et celles induites par la caféine dans le liquide sans Ca++ et, à des concentrations supérieures à 3 × 10−4 M, inhibait significativement les contractions induites par la norépinéphrine dans les liquides de bain normal et sans Ca++. Le pentobarbital, à des concentrations supérieures à 3 × 10−4 M, inhibait significativement les contractions induites par le KCl et la norépinéphrine dans le liquide de bain normal, alors que les contractions induites par la norépinéphrine et la caféine dans le liquide sans Ca++ étaient inhibées seulement par une forte concentration (10−3 M) de pentobarbital. Pour les fibres dénudées chimiquement, les contractions induites par la caféine étaient plus susceptibles à une inhibition par le thiopental que par le pentobarbital. Ces résultats suggèrent que l’effet d’inhibition intracellulaire du thiopental sert de médiateur à son effet vasodilatateur et que, par contraste, l’effet vasodilatateur du pentobarbital peut être attribué principalement à son action de bloqueur des canaux calciques.

Intravenous administration of isosorbide dinitrate attenuates the pressor response to laryngoscopy and tracheal intubation

In order to evaluate the effect of isosorbide dinitrate (ISDN), administered as a bolus intravenous injection, on the circulatory response to tracheal intubation, mean arterial pressure (MAP), and heart rate (HR) in response to laryngoscopy for 30 s followed by tracheal intubation were compared in patients not receiving ISDN (control) and receiving 40 μg/kg or 80 μg/kg of ISDN 45 s before starting laryngoscopy. Each group consisted of 10 patients undergoing elective surgery. Forty–five seconds after starting laryngoscopy, MAP was significantly (P < 0.01) lower in patients receiving 80 μg/kg ISDN than in those receiving no or 40 μg/kg ISDN. HR increased to a similar extent in the three groups. These results indicate that a bolus injection of ISDN (80 μg/kg) is a simple, practical and highly effective means of attenuating the hypertensive response to direct laryngoscopy and tracheal intubation.

Effects of halothane on the efflux of [3H]D asprtate from rat brain slices

The in vitro effects of halothane on the potassium‐stimulation‐induced efflux of [3H]D‐aspartate in rat cerebral cortex slices were studied. The slices were initially incubated with Krebs‐Ringers solution containing [3H]D‐aspartate, a putative excitatory transmitter. The slices were then stimulated with high concentrations of K+ in the presence and absence of halothane, and the efflux was measured using a scintillation counter. Halothane, 1% and 2%, had little effect on the potassium‐stimulation‐induced efflux, but that of 4 and 8% increased the efflux significantly. The spontaneous efflux was unaffected by all concentrations of halothane studied. The control study of pentobarbital, in the concentration of 0.05 to 1.00 mmol/1, reduced the efflux in a dose‐related manner. These findings indicate that the release of an excitatory transmitter, aspartate, may not be involved in the mechanism of halothane anaesthesia.

Different effects of halothane, isoflurane and sevoflurane on sarcoplasmic reticulum of vascular smooth muscle in dog mesenteric artery

Background: The direct effect of halothane on vascular smooth muscle is mediated in part via its effects on the sarcoplasmic reticulum (SR). Little information is available concerning the effects of other volatile anesthetics including isoflurane and sevoflurane, whose vascular effects differ from those of halothane. The aim of the present study was to compare the effects of halothane, isoflurane and sevoflurane on the SR by testing the contraction induced by caffeine in vascular smooth muscle.

Halothane and isoflurane preferentially inhibit prostanoid-induced vasoconstriction of rat aorta

In a previous study, we demonstrated that halothane and isoflurane inhibit binding of thromboxane A2 to its receptors on human platelets and thus inhibit prostanoid-induced aggregation strongly. The aim of this study was to determine whether volatile anaesthetics inhibit prostanoid-induced vasoconstriction preferentially. Rat isolated aortic rings were mounted in organ baths and their isometric tension was measured. They were contracted with STA2 (a stable thromboxane A2 analogue), prostaglandin F2α (PGF2α), phenylephrine, and 20 mM KCl, and then exposed to halothane (0.5–3%), isoflurane (0.5–3%), and sodium nitroprusside (SNP, 10−9−3 × 10−7 M). Halothane (2–3%) and isoflurane (2–3%) induced greater relaxation of aortic rings precontracted with STA2 and PGF2α than of those precontracted with phenylephrine (P < 0.01). Halothane induced greater relaxation of rings precontracted with KCl than phenylephrine only at 3%, whereas isoflurance relaxed rings precontracted with KCl more than those with phenylephrine at 0.5, 2 and 3% (P < 0.05). In contrast, SNP relaxed rings precontracted with PGF2α, KCl and phenylephrine equally, but induced smaller relaxations of those precontracted with STA2 (P < 0.05). We conclude that halothane and isoflurane inhibit prostanoid-induced vasoconstriction preferentially, possibly by interacting with prostanoid receptors.RésuméLors d’une étude antérieure, nous avons démontré que l’halothane et l’isoflurane inhibaient la liaison de la thomboxane A2 avec ses récepteurs situés sur les plaquettes humaines et inhibaient fortement ainsi l’agrégation induite par les prostanoïdes. Cette étude vise à déterminer si les anesthésiques volatils inhibent la vasoconstriction induite par les prostanoïdes de façon préférentielle. Des anneaux isolés d’aorte de rat sont introduits dans des bains organiques et leur tension isométrique est mesurée. On les fait a’abord contracter avec du STA2 (un analogue stable de la thomboxane A2), de la prostaglandine F2α (PGF2α), de la phényléphrine, et 20 mM de KCl, et on les expose ensuite à l’halothane (0,5% à 3,0%), l’isoflurane (0,5%–0,3%) et au nitroprussiate de soude (SNP, 10−9−3 × 10−7 M). Vhalothane (2–3%) et l’isoflurane (2–3%) produisent une plus grande relaxation des anneaux aortiques précontractés avec la phényléphrine (P < 0,01). L’halothane produit, mais seulement à 3%, te plus grande relaxation des anneaux précontractés avec le KCL qu’avec la phényléphrine, alors que l’isoflurane aux concentrations de 0,5 2 et 3% relaxe les anneaux précontractés avec le KCl plus que ceux contractés avec la phényléphrine (P < 0,05). Par contre, le SNP relaxe également les anneaux précontractés avec la PGF2α, le KCl et la phényléphrine, mais produit une relaxation moins grande sur ceux qui ont été précontractés avec du STA2 (P < 0,05). Nous concluons que lhalothane et l’isoflurane inhibent la vasoconstriction induite par les prostanoïdes de façon préférentielle, possiblement par interaction avec les récepteurs prostanoïdes.

The relaxing effects of barbiturates in vascular smooth muscle of rat aorta.

The effects of thiamylal and pentobarbital on contractions mediated through the influx of extracellular Ca++ and the release of intracellularly stored Ca++ were compared in rat aortic strips. Thiamylal (3×10−5M to 10−3M) and pentobarbital (10−4 to 10−3M) significantly attenuated the contraction induced by KCl (20 mM), and shifted the dose-response curve for Ca++ of KCl (20 mM)-treated strips downwards and to the right. Caffeine (l0−2M)-induced contraction was significantly attenuated by thiamylal at concentrations greater than 10−4M and by pentobarbital at 3×10−4M. Only a high concentration (l0−3M) of these barbiturates significantly inhibited the contractions induced by norepinephrine (NE, 10−6M) in Ca++-free medium. Contraction of strips without endothelium by a Ca++ ionophore, A23187 (5×10−6M), in the presence of a Ca channel blocker, was relaxed by high concentrations of thiamylal (3×10−4M to 10−3M) and pentobarbital (l0−3M). It is concluded that thiamylal inhibits contraction through an intracellular action as well as a Ca channel-blocking action in vascular smooth muscle of rat aorta. However, the intracellular action of pentobarbital is less potent than that of thiamylal.