Cardiac effects of clinically available Kampo medicine assessed with canine isolated, blood-perfused heart preparations.

Cardiac effects of 10 kinds of clinically available Kampo medicines were investigated: Kakkon-to (TJ-1), Dai-saiko-to (TJ-8), Boi-ogi-to (TJ-20), Chorei-to (TJ-40), Rokumi-gan (TJ-87), Tsu-do-san (TJ-105), Gosha-jinki-gan (TJ-107), San'o-shashin-to (TJ-113), Sairei-to (TJ-114) and Inchin-gorei-san (TJ-117). Chronotropic and inotropic effects were studied using canine isolated, blood-perfused heart preparations, while subcellular mechanisms were analyzed by measuring the drug-induced changes of the adenylate cyclase activity in the canine ventricular membrane preparation. Intracoronary injections of TJ-1, TJ-20, TJ-105 and TJ-113 increased the sinoatrial rate and developed tension of papillary muscle in a dose-related manner, which was significantly attenuated by the pretreatment of the preparations with beta-blocker propranolol. Meanwhile, the other extracts hardly affected these parameters. TJ-1, TJ-20 and TJ-113 increased the adenylate cyclase activity in a dose-related manner, but their potency was significantly less compared with that by an equivalent concentration of isoproterenol. Moreover, TJ-105 did not increase the adenylate cyclase activity. These results suggest that the positive chronotropic and inotropic effects of TJ-1, TJ-20, TJ- 105 and TJ-113 may be exerted through the direct stimulation of the beta-adrenoceptor and/or the norepinephrine release from the postganglionic nerve terminals in the heart.

Sistema extracorpóreo para soporte de la falla hepática fulminante como puente al trasplante de hígado (xenohemodiafiltración): informe del primer caso clínico con un procedimiento desarrollado en el Hospital Italiano de Buenos Aires / Extracorporeal system for fulminant hepatic failure support as a bridge to liver transplantation (xenohemodiafiltration): case report of a procedure developed at Hospital Italiano in Buenos Aires

Antecedentes: La falla hepática es una causa importante de morbilidad y mortalidad en Unidades de Terapia Intensiva. Las terapias convencionales no son lo suficientemente efectivas. El trasplante hepático es el tratamiento definitivo para esta entidad, pero debido a la falta de donantes se hacía necesario desarrollar una "terapia puente" o de sostén de la vida hasta que aquél se realizara. La xenohemodiafiltración hepática extracorpórea pretende ser el soporte transitorio de un paciente con falla hepática fulminante. Objetivo: Presentamos el primer caso de xenohemodiafiltración hepática extracorpórea. Lugar de aplicación: Hospital Italiano de Buenos Aires. Diseño: Descripción del primer caso clínico de xenohemodialfiltración. Población: Mujer de 42 años portadora de falla hepática fulminante, con grave alteración de la coagulación, déficit de factor V y severa hipertensión intracraneana. Método: El sistema consiste en una circulación cruzada entre un hígado porcino y un paciente con falla hepática fulminante a través de una membrana de poliacrilonitril. Resultados: El procedimiento duró 5 horas y alcanzó mejoras hemodinámicas, bioquímicas y metabólicas. La presión intracraneana disminuyó de 34 a 5 cm H2O, el amoníaco sérico cayó de 673 a 370 ng/dl, ácido láctico de 11 a 5.3 mmol/L y la bilirrubina de 7.4 a 2.5 mg/dl. Los valores hemodinámicos se mantuvieron estables durante el procedimiento. La paciente pudo recibir el trasplante y continúa viva 11 meses después. Conclusiones: La xenohemodiafiltración hepática extracorpórea es un método clínico experimental que puede constituir una terapia clínica alternativa para soporte de pacientes con falla hepática fulminante hasta que se obtenga un órgano apto para trasplante. (AU)

Sistema extracorpóreo para soporte de la falla hepática fulminante como puente al trasplante de hígado (xenohemodiafiltración): informe del primer caso clínico con un procedimiento desarrollado en el Hospital Italiano de Buenos Aires / Extracorporeal system for fulminant hepatic failure support as a bridge to liver transplantation (xenohemodiafiltration): case report of a procedure developed at Hospital Italiano in Buenos Aires

Antecedentes: La falla hepática es una causa importante de morbilidad y mortalidad en Unidades de Terapia Intensiva. Las terapias convencionales no son lo suficientemente efectivas. El trasplante hepático es el tratamiento definitivo para esta entidad, pero debido a la falta de donantes se hacía necesario desarrollar una "terapia puente" o de sostén de la vida hasta que aquél se realizara. La xenohemodiafiltración hepática extracorpórea pretende ser el soporte transitorio de un paciente con falla hepática fulminante. Objetivo: Presentamos el primer caso de xenohemodiafiltración hepática extracorpórea. Lugar de aplicación: Hospital Italiano de Buenos Aires. Diseño: Descripción del primer caso clínico de xenohemodialfiltración. Población: Mujer de 42 años portadora de falla hepática fulminante, con grave alteración de la coagulación, déficit de factor V y severa hipertensión intracraneana. Método: El sistema consiste en una circulación cruzada entre un hígado porcino y un paciente con falla hepática fulminante a través de una membrana de poliacrilonitril. Resultados: El procedimiento duró 5 horas y alcanzó mejoras hemodinámicas, bioquímicas y metabólicas. La presión intracraneana disminuyó de 34 a 5 cm H2O, el amoníaco sérico cayó de 673 a 370 ng/dl, ácido láctico de 11 a 5.3 mmol/L y la bilirrubina de 7.4 a 2.5 mg/dl. Los valores hemodinámicos se mantuvieron estables durante el procedimiento. La paciente pudo recibir el trasplante y continúa viva 11 meses después. Conclusiones: La xenohemodiafiltración hepática extracorpórea es un método clínico experimental que puede constituir una terapia clínica alternativa para soporte de pacientes con falla hepática fulminante hasta que se obtenga un órgano apto para trasplante.

Utilization of an isolated, blood-perfused canine papillary muscle preparation as a model to assess efficacy and adversity of class I antiarrhythmic drugs.

To develop a model to predict the efficacy and adversity of class I antiarrhythmic drugs, intraventricular conduction time (IVCT), coronary blood flow (CBF), developed tension of papillary muscle (DT) and idioventricular automaticity rate (VR) were measured following drug administration in an isolated canine papillary muscle preparation cross-circulated with the heparinized blood of a donor dog. Tetrodotoxin, the prototypic fast Na+ channel blocker, and class I drugs increased IVCT and CBF, but decreased DT and VR, in a dose-dependent manner. The profiles of known class I drugs, procainamide, disopyramide, lidocaine, mexiletine and flecainide were similar, but the potencies of each drug were different. Two new class I drugs, ME3202 and AN-132, were also tested and found to have effects that were similar to that of tetrodotoxin. There was a good correlation between the doses of drugs prolonging IVCT by 50% and the canine antiarrhythmic plasma concentrations in our previous study. This model can also be used to estimate the use-dependency and the kinetics of use-dependent sodium channel block; however, it is not suitable for extensive investigation of cellular and molecular mechanisms. Thus, the use of this model facilitates the comparison of multiple cardiac effects of class I drugs and may be an effective way to better assess new antiarrhythmic drugs.

[Humoral factors in the modulation of sustained discharges of polymodal nociceptors].

By using a model of sustained discharges of polymodal nociceptors (PMN) due to injection of a compound algogenic substance into the skin in anesthetized rats, it was found that stimulation of the sciatic nerve inhibited or facilitated at first and then inhibited the PMN sustained discharges markedly. In a crossperfused preparation, stimulation of the sciatic nerve of donor rat caused the similar effects on sustained discharges of PMN of the recipient rat. Injection of the animal serum after stimulation of the sciatic nerve affected PMN activity obviously. The inhibitory course of most units could not be reversed by naloxone. In the animal tolerance to morphine, the effects of stimulation of the sciatic nerve could still be obtained. Preadministration of reserpine almost completely abolished the facilitatory effect. The results indicate that sustained activity of PMN could be modulated by some humoral factors due to somatic afferents. The inhibitory substances in the humoral factor seem to be both opioid and nonopioid in nature. The facilitatory substance seem to be a catecholamine.

The effect of antihypertensive treatment on the circulating hypertensive factor in the spontaneously hypertensive rat.

To elucidate the role of circulating hypertensive factors in the spontaneously hypertensive rat and the effects of antihypertensive treatment on the circulating hypertensive factor, cross circulation was performed in 54 couples of spontaneously hypertensive and normotensive rats. In normotensive rats cross-circulated with untreated spontaneously hypertensive rats mean arterial pressure increased by 20.9 +/- 12.2 mm Hg (p less than 0.01). Increases in mean arterial pressure were also obtained by cross-circulation with spontaneously hypertensive rats pretreated with propranolol, furosemide, and nifedipine. Mean arterial pressure was not changed by cross circulation after pretreatment of the spontaneously hypertensive rats with alpha methyldopa. It is concluded that in this strain of spontaneously hypertensive rats a circulating hypertensive factor exists, the secretion of which can be suppressed by the centrally acting drug, alpha methyldopa. Therefore either the central nervous system may take part in the regulation of the factor or the factor may be synthetized in the central nervous system.

A circulating hypertensive factor in primary hypertension: effect of antihypertensive therapy.

In this study the role of a humoral hypertensive factor in spontaneously hypertensive rats (SHR) of the Münster strain was examined by cross-circulation. It was demonstrated that hypertension of the SHR could be transmitted to cross-circulation normotensive Wistar-Kyoto rats. The results led to the following conclusion: primary hypertension is caused by a circulating factor which is produced by kidneys and adrenals and suppressed by acute volume depletion and chronic dietary salt restriction. The antihypertensive effect of nifedipine probably leads to a compensatory stimulation of the hypertensive factor in SHR.

A reliable cross-circulation model: its use in studying humoral agents.

The purpose of this study was to develop an expeditious and reliable system to examine early alterations in proliferating liver tissue in vivo, uncomplicated by the haemodynamic changes associated with partial hepatectomy. We describe an improved, dependable, massive blood-exchange system, involving aortic blood transposition between two rats, which meets these criteria. The use of heparinized, silicone-rubber tubing and postoperative recirculation obviate the need for supplemental anticoagulants and minimizes haemorrhage. The procedure is rapid, and survival is > 95% for up to 48 h. We cite both the advantages of using this model generally to study humoral agents, and specific advantages associated with studies relating to a humoral hepatic mitogen. As an example in this regard, we present results obtained using this system to examine chromatin protein methylation in the intact liver of rats coupled to partially hepatectomized partners. Labelling with a mixture of 3H-methyl-L-methionine and 2-14C-DL-methionine, we demonstrate an enhancement of methylation in crude chromatin protein fractions obtained from intact liver tissue responding to humoral agents provided by blood exchanged from partially hepatectomized rats. This substituent enhancement appears to correlate with the degree of stimulation of DNA replication in this organ.

Further study of the neurohumoral factor, endorphin, in the mechanism of acupuncture analgesia.

Cross circulation was performed between the femoral arteries and veins of paired rabbits that were entirely conscious. Jaw opening reflex by dental pulp stimulation was used as pain index. When acupuncture was applied to the donor rabbit the pain thresholds of both the donor and recipient were elevated from 30 minutes to one hour after acupuncture stimulation and lasted for another 30 minutes after withdrawal of acupuncture. The analgesic effect in both the donor and recipient was abolished by the pretreatment of naloxone. The increase in the pain threshold of the non-acupunctured recipient was due to an opiate-like, humoral substance generated from the acupuncture donor. The possible role of endorphins in the mechanism of acupuncture analgesia is discussed.

Evaluation in dogs of cross-circulation in the treatment of acute hepatic necrosis induced by yellow phosphorus.

The efficacy of cross-circulation in the treatment of acute liver failure has been evaluated in dogs. Four of 5 dogs administered a dose of yellow phosphorus that is lethal 90% of the time survived after treatment by cross-circulation of whole blood for between 1 and 8 hr with a normal dog. In 2 normal unmatched dogs plasma cross-circulations were performed over a period of 31 days without any clinical or laboratory manifestation of hypersensitivity except for lymphocytotoxic antibody titer rise. The results suggest that whole blood cross-circulation is effective and imply that a single donor could be utilized for prolonged periods of plasma cross-circulation with avoidance of immunological consequences of whole blood exchange.