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PubMed1979

[Effect of 1-[(1-pyrrolidynylcarbonyl) methyl]-4-(3, 4, 5-trimethoxycinnamoyl)piperazine maleate (cinepazide) on cerebral and peripheral circulation in cats (author's transl)].

Effects of cinepazide, a vasoactive agent, on regional circulations in various sites of brain and other organs in curarized, artificially respirated cats were studied using a thermoelectrical method. The mechanism of the vascular effect was also investigated. Cinepazide produced a marked increase in blood flow in the cerebellar cortex and an apparent increase in blood flow in the cerebral cortex. Effects of the drug on blood flow in the thalamus, hypothalamus and amygdala were inconsistent. Cinepazide produced the most significant increase in myocardial blood flow and also an apparent increase in muscular blood flow, whereas the drug did not consistently alter hepatic blood flow, and decreased renal and dermal blood flow. Cinepazide produced a mild and sustained fall in blood pressure, however, a transient slight rise in blood pressure was noted when the drug was given into the vertebral artery. It seems possible that the action of cinepazide might involve a mild stimulation of beta adrenergic receptors and slight stimulation of alpha adrenergic receptors but not cholinergic receptors, in the cerebral and peripheral vascular systems. Increase in blood flow induced by cinepazide seems to be mainly due to the smooth muscle relaxant effect and may be mediated via a metabolic mechanism.

Amygdala↗
PubMed1987

[Pharmacological study of TJ-8007 (Tsumura-Zokumeito) (I): Protective effects of TJ-8007 against anoxic brain damage].

The protective effects of TJ-8007 (Tsumura-Zokumeito, Traditional chinese medicine) against cerebral anoxia were investigated with various experimental models in mice and rats. 1) In histotoxic anoxia, TJ-8007 (0.3-3.0 g/kg, p.o.) dose-dependently demonstrated a protective effect on coma induced by a sublethal dose of KCN (1.8 mg/kg, i.v.) in mice. Ifenprodil (30 mg/kg, p.o.) tended to reduce the coma time, but papaverine (100 mg/kg, p.o.) showed a negative effect. 2) TJ-8007 (0.3-3.0 g/kg, p.o.) dose-dependently tended to prolong the survival time of mice subjected to a lethal dose of KCN (3.0 mg/kg, i.v.), TJ-8007 also improved the survival rate at the dose of 3.0 g/kg. Ifenprodil (30 mg/kg, p.o.) or papaverine (100 mg/kg, p.o.) exerted a similar effect on the survival time, but did not affect the mortality. 3) In the normobaric hypoxia with a gas mixture of 96% N2 and 4% O2, TJ-8007 (0.3-3.0 g/kg, p.o.) did not affect the survival time of mice. On the other hand, papaverine (100 mg/kg, p.o.) prolonged the survival time, and phenytoin (100 mg/kg, p.o.) showed a marked protective effect, but ifenprodil (30 mg/kg, p.o.) produced an adverse effect. 4) In the asphyxic anoxia induced by stopping artificial respiration of immovable rats, TJ-8007 (1.0, 3.0 g/kg, p.o.) showed a protective effect on the fall of systemic blood pressure and on the decline of heart rate; furthermore, it dose-dependently prolonged the disappearance time of cortical activity. Also, phenytoin (100 mg/kg, p.o.) tended to protect against the fall of blood pressure and prolonged the cortical resistance time.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1978

New method for evaluating bronchomotor and bronchosecretory activities: Effects of prostaglandins and antigen.

We devised a new method for measuring responses of canine airway musculature, bronchosecretion and bronchial vasculature simultaneously, in situ, and investigated the effects of prostaglandins F2alpha and E2 and antigen-antibody reaction by using this model. The right bronchial artery was perfused with blood at a constant flow under artificial respiration. Airway musculature response was measured as a change in ventilation overflow with a modification of the Konzett-Rössler method; the airway secretory activity was measured with our stopper method for secretion volume and with the glass plate method for viscosity. Close intraarterial injections of prostaglandin (PG) F2alpha, 0.01--10 microgram, into the right bronchial artery produced bronchomuscular and vascular constrictions, while those of PGE2, 0.01--3 microgram, produced dilatation in a dose dependent manner. A close intraarterial injection of 1 mg protein of ascaris suum antigen to dogs with positive skin reaction produced bronchoconstriction and vascular dilatation. Thirty min intraarterial infusions of PGF2alpha, 0.3--3 microgram/min, and ascaris antigen, 0.03--0.3 mg protein/min, resulted in a dose-dependent increase in the volume of airway secretions, while those of PGE2, 0.1--1.0 microgram/min, did not alter the secretory activity. These findings indicate that prostaglandin F2alpha in relatively high doses increases both bronchomotor tone and bronchosecretory activity, as does antigen-antibody reaction with ascaris antigen, and that the present method is useful for evaluating effect of drugs on the respiratory tract.

Animals↗
PubMed1982

Analysis of efferent discharges of the phrenic nerve during the cough reflex.

The response of the phrenic nerve activities during the cough reflex was investigated in anesthetized dogs. The phrenic nerve activities were recorded from the central cut end of the nerve. Changes in phrenic nerve activities were evaluated by means of computer analysis using the programs for power spectrum, amplitude histogram, pulse density variation, and autocorrelation. The cough reflex was induced by mechanical stimulation of the tracheal mucosa. The cough reflex evoked was accompanied by an increase in the number of spike potentials and shortening of the respiratory burst period of the phrenic nerve activities. There was a significant correlation between the intensity of expiration and the multiplication product of the mean amplitude of spike potentials and spike numbers of the phrenic nerve activities during the cough reflex. Total activity of the discharge, amplitude of spike potentials, and pulse density of the phrenic nerve activities also increased during the cough reflex, while the autocorrelation coefficient decreased. These changes were inhibited by codeine. The responses of the phrenic nerve activity during the cough reflex were also observed under artificial respiration as well as under spontaneous respiration. These findings indicate that the phrenic nerve activity can be an indicator of the cough reflex, and it is useful for the indicator to investigate the central mechanisms of the cough reflex.

Animals↗
PubMed1982

Influence of tolerance to and physical dependence on opioid analgesics on cortical evoked potential in rats.

The influence of single and repeated doses of morphine, pentazocine, and chlorpromazine on the latent time of cortical evoked potentials was observed in rats. The evoked potentials were induced by electrical stimulation of the sciatic nerve under the condition of curarization and artificial respiration. The evoked potential consisted of 4 phases. The latent time of the N2 component was prolonged by single dose administration of morphine at 5 mg/kg, s.c., pentazocine at 15 mg/kg, s.c., or chlorpromazine at 2 mg/kg, s.c. The effects of morphine and pentazocine were antagonized by naloxone but that of chlorpromazine was not. By repeated administration of morphine at 5 mg/kg or pentazocine at 15 mg/kg twice daily for 4 weeks, the prolongation of latent time tended to disappear gradually. Further, in these rats the latent time became shorter than that of normal rats after naloxone administration or natural withdrawal for 18 hr. Thus the development of tolerance to and physical dependence on these drugs were demonstrated by recovering and shortening of the latent time, even when withdrawal signs were not apparently observed in the rats' gross behavior. On the other hand, repeated administration of chlorpromazine at 2 mg/kg twice daily for 4 weeks did not produce such shortening of the latent time as was observed with morphine and pentazocine. These results indicate that the evoked potential can serve as a sensitive parameter for observation of the development of tolerance to and physical dependence on opioid analgesics in rats.

Analgesics, Opioid↗
PubMed1987

Inhalation of carbon dioxide enhances the coronary vasodilating action of isosorbide dinitrate in the dog.

Two kinds of inspiratory gases, 100% O2 and 81% O2 + 19% CO2, were used for the artificial respiration. Elevating the inspiratory CO2 tension enhanced the decrease in coronary vascular resistance caused by isosorbide dinitrate (100 micrograms/kg), without any change in heart rate and systemic arterial pressure. Such a change in coronary vascular resistance was prevented by indomethacin. The results suggested an interaction between isosorbide dinitrate and CO2, which was mediated by prostaglandins.

Acidosis↗
PubMed1987

Effects of mast cell stabilizers on a new bronchial asthma model using compound 48/80 in dogs.

Development of a nonimmunologically induced experimental asthma model using compound 48/80 was attempted. Male mongrel dogs anesthetized with pentobarbital-Na were immobilized with decamethonium bromide under artificial respiration. Airway resistance was measured with a modified Konzett-Rössler method and expressed as a change in ventilation overflow (VO). Inhalation of compound 48/80 caused no change in VO even in high concentrations up to a 1% solution. Infusion of compound 48/80 into the bronchial artery at a dose of 0.2 mg/min for 10 min by using the right bronchial perfusion method caused a marked increase in VO accompanied by decreases in perfusion pressure and systemic blood pressure. The compound 48/80-induced bronchoconstriction was inhibited 58% by surgical vagotomy and was almost abolished by chlorpheniramine (10 mg/kg, intraduodenally (i.d.)). Disodium cromoglycate (inhalation of 1% solution along with 5 mg/kg, i.v.), tranilast (300 mg/kg, i.d.) and NCO-650, a new antiallergic drug (100 mg/kg, i.d.) significantly inhibited the compound 48/80-induced bronchoconstriction. These results indicate that compound 48/80 infusion into the bronchial artery produces an asthma-like bronchoconstriction, the main chemical mediator involved in this response would be histamine acting through H1-receptors, and effects of mast cell stabilizers can be evaluated with this model.

Airway Resistance↗
PubMed1987

Isosorbide dinitrate blocks thromboxane synthesis caused by CO2 in dog heart-lung preparation.

Effects of isosorbide dinitrate (ISDN) on coronary flow and arterial prostaglandin (PG) concentrations were investigated, using dog heart-lung preparations. Two kinds of gases (low and high CO2 gases) were used for the artificial respiration. Low CO2 gas contained 55% O2 and 0.2% CO2, whereas high CO2 gas contained 55% O2 and 8% CO2. Administration of ISDN into a blood reservoir at high CO2 caused an increase in coronary sinus blood flow, which was blocked by indomethacin, but not at low CO2. In the absence of ISDN, the arterial concentration of thromboxane (TX) B2 was larger at high CO2 than at low CO2. ISDN attenuated such an increase in TXB2 concentration caused by CO2. The arterial concentration of 6-keto PGF1 alpha was altered by neither CO2 nor ISDN, but slightly increased with time. Indomethacin lowered the concentrations of 6-keto PGF1 alpha and TXB2. These results suggested that the arterial CO2 tension enhanced the TXA2 synthesis and that ISDN inhibited such a relation between CO2 and TXA2 synthesis. Additionally, the vasodilatory effects of PGI2 was enhanced by elevating the arterial CO2 tension. Thus, the increase in canine coronary flow at high CO2 in the presence of ISDN may be related to the inhibitory effects of ISDN on the TXA2 synthesis enhanced by the high arterial CO2 tension and the facilitatory effects of CO2 on the PGI2-induced vasodilation.

Animals↗
PubMed1988

A new rhinitis model using chemical mediators in rats.

No good experimental model for studying rhinitis, has been hitherto available. In the present study, development of a new rhinitis model using chemical mediators was attempted, especially to establish an index of nasal congestion. Male Wistar rats were anesthetized with pentobarbital-Na. Nasal cavities were ventilated between both cannulae inserted into the nasopharynx and bilateral nostrils, with an artificial respirator. Intranasal resistance was recorded with a modification of a Konzett-Rössler apparatus as a change in ventilation overflow (VO). To provoke rhinitis, some mediators were inhaled into the nasal cavities with an ultrasonic nebulizer for 5 min. To assess the capillary permeability of the nasal mucosa, exudation of Evans blue was determined by injecting the dye before inhalations of mediators. Inhalation of histamine (0.01, 0.1, 0.3%), bradykinin (0.01, 0.1%) and ACh (0.3%) markedly increased VO, while inhalation of serotonin (0.01, 0.1, 0.3%) did not increase VO. Histamine, bradykinin and high concentration of ACh significantly increased the dye exudation in the nasal cavities, although serotonin did not. From the above results, it is concluded that 1) a new rhinitis model in which symptoms of nasal blockage and increased capillary permeability in nasal mucosa are quantitatively determined, was established, and 2) histamine- and bradykinin-inhalations can cause rhinitis-like symptoms, although serotonin-inhalation can not.

Airway Resistance↗
PubMed2004

Functional hypophysectomy simply by neck-strangulation in the rat: applications for ACTH and LH assays.

The classical methods for hypophysectomy require a long training-period and at the end of each experiment, it is required to check any undue remnant of the hypophyseal tissue in the sella turcica, and there must be exclusion of such datum with the remnant from the experimental group. The present method for functional hypophysectomy by neck-strangulation in the rat is very simple to perform so that even an experimenter with little experience can become easily accustomed to the technique and obtain a number of functionally hypophysectomized preparations at any time he intends, with no need to check the remnant. The cerebral blood circulation of vertebrally dislocated rats was immediately intercepted by means of neck-strangulation and artificially respired. Fifteen minutes after intravenous injection of ACTH (0.1 - 3.2 mU/rat) or LH (312.5 - 2500 ng/rat), blood was sampled from the vena cava, and sera were examined for corticosterone or testosterone by radioimmunoassay. A linear dose-response relationship was obtained within a dose range of 0.2 - 1.6 mU/rat of ACTH and 312.5 - 1250 ng/rat of LH. In the ACTH assay, parapharyngeally hypophysectomized rats were compared. It was found that the sensitivity of functionally hypophysectomized preparations was 2.72 times higher than that of the parapharyngeally hypophysectomized rats.

Adrenocorticotropic Hormone↗
PubMed1978

Renal transplantation in the rabbit: a model for preservation studies.

Transplantation is necessary for evaluation of kidney preservation procedures, and a model using a small laboratory animal is desirable. The rabbit was found to be a suitable animal for this purpose. Even long periods of anaesthesia without artificial respiration were safely achieved. Hydration and serum electrolytes could be maintained within normal ranges with intravenous injections of isotonic saline and dextrose during and after the operation. The kidneys were implanted by anastomosing the artery and vein end-to-side to the abdominal aorta and the posterior vena cava respectively. The ureter was implanted into the bladder over a nylon stent. In a recent 100 transplantations the incidence of vascular thrombosis was low (4%), but rather more (10%) mainly late ureteral complications were encountered. Transplanted kidneys showed good function with mean peak serum creatinines of 285 mumol/l and normal macroscopic and histological appearance at autopsy.

Anesthesia↗
PubMed1988

Four methods for general anaesthesia in the rabbit: a comparative study.

The efficacy and safety of pentobarbitone, ketamine/xylazine, fentanyl/fluanisone/diazepam, and halothane/nitrous oxide anaesthesia were compared in 4 groups of six New Zealand White rabbits. Heart and respiratory rates, body temperature, reflexes, blood pressure and blood gases were measured. Pentobarbitone appeared to be unsuitable for anaesthesia in rabbits, as 5 of the 6 rabbits to whom it was administered, required artificial respiration or died. The combinations of ketamine/xylazine and fentanyl-fluanisone/diazepam both produced unpredictable levels of anaesthesia together with a substantial decline in arterial blood pressure and PO2. Despite a severe drop in blood pressure (up to 37.5%), anaesthesia with halothane and nitrous oxide was found to be superior to the other anaesthetic agents.

Anesthesia, General↗
PubMed2003

Laparoscopic gastric bypass for morbid obesity with linear gastroenterostomy.

BACKGROUND: Laparoscopic gastric bypass (LGBP) is a well-established procedure for the surgical management of morbid obesity. Most surgeons create the gastroenteral anastomosis by using the circular EEA stapler. We describe an alternative laparoscopic anastomotic technique using the EndoGIA linear stapling device. METHODS: The stomach was proximally transected with a linear stapler (45 mm, Endo-GIA) to create a 15 to 20 ml pouch. Next, an antecolic Roux-en-Y gastroenterostomy was performed, using the 45 mm Endo-GIA. The proximal loop of the intestine was then separated from the anastomotic site by the Endo-GIA. Finally, the Endo-GIA was used for the intraabdominal creation of a side-to-side enteroenterostomy. RESULTS: Between June and August 2001, 5 patients with mean BMI 56.7 kg/m(2)+/-7.3 underwent LGBP. All patients were seen 6 months post-surgery. Operating time was 7.5 and 6.5 hours for the first 2 operations, but was under 4.5 h for the next 3 cases. 1 patient suffered from perioperative hypoxia leading to long-term artificial respiration. 6 weeks after surgery, 1 patient developed obstruction due to torsion of the enteroenterostomy and required open revision. The 3 remaining patients made an uneventful recovery. All patients lost considerable weight (mean 36.5 kg; [range 32 to 45] after 6 months). No stenosis or anastomotic leakage was noted. CONCLUSIONS: A linear stapled anastomosis is an alternative to the use of the circular stapler.

Adult↗
PubMed2007

Rapid microglial activation induced by traumatic brain injury is independent of blood brain barrier disruption.

Following CNS injury, microglia respond and transform into reactive species exhibiting characteristic morphological changes that have been termed "activated" or "ameboid" microglia. In an attempt to establish that microglial reactions induced immediately after injury are caused by intrinsic mechanisms rather than infiltration of blood and its constituents, oxygenized Ringer's solution was perfused into the cerebral circulation of rats so that the circulating blood could be eliminated prior to injury induction. Under artificial respiration, a catheter was inserted from the cardiac apex into the ascending aorta, and oxygenized Ringer's solution was immediately perfused with a pulsatile blood pump, resulting in wash out of the circulating blood from the brain within 1 min. Subsequently, a cortical contusion was induced in the unilateral parietal cortex using a controlled cortical impact (CCI) device. At 5 min following the injury, the brain was fixed by perfusion of fixative through the catheter and removed. Coronal vibratome sections were then processed for CR3 immunohistochemistry to examine the microglial activation. It appeared that microglial activation with both morphological transformation and an increase in CR3 immunoreactivity was induced throughout the hemisphere ipsilateral to the injury side exclusively, even in rats with elimination of circulating blood. The microglial reactions did not differ substantially from those observed in the control rats with extensive BBB disruption. The present results thus provide direct evidence that the microglial activation induced immediately after injury is independent of infiltration of circulating blood induced by concurrent BBB disruption.

Animals↗
PubMed1996

A study on the mediators of antidromic vasodilatation elicited by sciatic nerve stimulation in cats.

This study was undertaken to ascertain whether a purinergic substance, histamine, dopamine or prostaglandins are mediators involved in antidromic vasodilatation. This type of vasodilatation was elicited by stimulation of the distal end of sectioned sciatic nerve at 40 V with 2 msec pulses for 30 sec in autoperfused hindlimb of reserpine-pretreated and anesthetized cats. Artificial respiration was applied because of curarization that was done to abolish the vascular responses due to contractions of striated muscle. Stimulation of sciatic nerve caused a sustained vasodilatation which was more marked at a frequency of 30 pps. The responsiveness of the perfused vessels to vasodilator stimuli tended to increase by increasing the duration of perfusion as controlled by papaverine administration at certain intervals. Both mepyramine and subsequent administration of metiamide did not produce any change in the vasodilator response to nerve stimulation though they blocked the vasodilator response to histamine. Dopamine injected intra-arterially elicited a pressor response which was reversed into a vasodilator one by phentolamine. This vasodilator response to dopamine tended to be reduced by haloperidol which produced either no change or a slight increase in antidromic vasodilatation. Pretreatment with theophylline to antagonize the likely purinergic mediators or with indomethacin to inhibit the synthesis of prostaglandins had no effect on antidromic vasodilatation elicited by sciatic nerve stimulation. These results suggest that the above-mentioned compounds might not be involved in antidromic vasodilatation.

Animals↗
PubMed1976

The prolongation of QRS-duration resulting from delayed recovery of ventricular excitability. A new mechanism for intraventricular conduction disturbance. A preliminary note.

Chlorpromazine (1, 5, and 20 mg/Kg) was injected intravenously to anesthetized and open-chest dogs under artificial respiration. Using right atrial pacing, the heart rate was increased stepwise from intrinsic sinus rate to higher rate where the A-V block first developed. ECG (II) was recorded simultaneously with arterial blood pressure, ventricular monophasic action potentials and left atrial electrogram. In the control, QRS-duration was constant (46.9 +/- 0.8 msec) irrespective of heart rate. After the drug injection, however, the duration increased significantly with increasing heart rate, the effect depending on the injected dosage (r==0.283, P less than 0.1 in 1 mg/Kg; r==0.406, P less than 0.01 in t mg/Kg; r==0.631, P less than 0.001 in 20 mg/Kg). During the drug action, QRS-duration of atrial premature beats was also longer than that of sinus beats, and the lengthening increased with shortening of preceding cycle length. The observed QRS-prolongations were due to neither incomplete ventricular repolarization nor bundle branch block. The mechanism of prolongation was attributed to delayed or time-dependent recovery of ventricular excitability, i.e., slowed removal of inactivation in rapid sodium system in the ventricular muscle fibers.

Animals↗
PubMed1993

In vivo profile of myocardial energy metabolism of pressure-overloaded rat.

Cardiac energy metabolism of pressure-overloaded rat hearts was examined under in vivo and in vitro conditions. Two, 4 and 6 weeks after constriction of the abdominal artery, the hemodynamic and metabolic profiles of hearts in vivo and of perfused hearts were determined. Significant increases in left ventricular weight/body weight (30 to 45% increase relative to the sham group), systolic and diastolic blood pressure (22 to 33% increase) and pressure-rate product (31 to 33% increase) were observed 2, 4 and 6 weeks after the operation, and a slight but significant decrease in heart rate was observed at 2 weeks after the operation. Tissue hydroxyproline content increased (17 to 93%) with time after pressure-overload. These findings are indicators of pressure-overloaded cardiac hypertrophy. The total high-energy phosphates of the in vivo rat myocardium under artificial respiration were lower than those of sham-operated rat myocardium 2 (23%) and 4 weeks (21%), but not 6 weeks after aortic constriction. The maximal oxygen consumption rates of mitochondria, when determined in the skinned cardiac fibers, also decreased 2 (47%) and 4 weeks (36%), but reversed 6 weeks after pressure-overload. However, the myocardial ATP, a utilizing form of high-energy phosphate, of pressure-overloaded rat myocardium remained normal at all times after cardiac hypertrophy. This suggests that alterations in hemodynamic variables of in vivo pressure-overloaded rats may not be attributable to a reduction in the myocardial energy production. In the perfused hearts isolated from pressure-overloaded rats, tissue ATP levels were similar to those of sham-operated rats, although the tissue creatine phosphate tended to be reduced in the pressure-overloaded animals at all stages of cardiac hypertrophy examined. Only a marginal decrease in the tissue high-energy phosphate (13%) was observed 4 weeks after the operation relative to that of sham-operated rats. In contrast, the developed tension of the perfused pressure-overloaded rat hearts was consistently lower (27 to 36%) than that of the sham-operated rat hearts. The results suggest that the high-energy phosphate levels of pressure-overloaded rat myocardium in vitro are unlikely to account for the observed decline in cardiac contractile function. The reduction of myocardial high-energy phosphates of pressure overloaded rats may be due to an adaptative change rather than a causal events.

Adenosine Triphosphate↗