Effects of nicardipine on the circulatory responses to tracheal intubation in normotensive and hypertensive patients

This study was undertaken to examine the effects of nicardipine on circulatory responses to laryngoscopy and tracheal intubation in normotensive (n = 39) and hypertensive (n = 36) patients. Laryngoscopy and tracheal intubation were performed after induction of anaesthesia with thiamylal, followed by administration of intravenous saline or nicardipine 20 or 30 micrograms.kg-1 and suxamethonium. Blood pressure and heart rate were recorded, and rate-pressure product was calculated. Nicardipine 20 and 30 micrograms.kg-1 prevented the increase in mean arterial pressure after intubation in normotensive and hypertensive patients (p less than 0.01 compared with saline). The changes in heart rate after intubation were significantly greater in normotensive patients than in hypertensive patients when 20 or 30 micrograms.kg-1 of nicardipine was given (p less than 0.05 and p less than 0.01 respectively). Rate-pressure product increased significantly (p less than 0.01) after intubation in normotensive patients whether nicardipine was administered or not, but the increase was suppressed completely by nicardipine 20 or 30 micrograms.kg-1 in hypertensive patients. We conclude that nicardipine is effective in preventing the circulatory responses to laryngoscopy and tracheal intubation in hypertensive patients.     

Plasma cyclic nucleotide responses to insulin-induced hypoglycaemia and methacholine in patients with hyperthyroidism

The effect of insulin-induced hypoglycaemia and methacholine on plasma cAMP and cGMP levels was studied in normal volunteers, hyperthyroid and hypothyroid patients. A significant positive correlation existed between the maximal increase in plasma cAMP and the maximal decrease in plasma glucose in normals during insulin-induced hypoglycaemia. Therefore, the plasma cAMP response is considered to be dependent on the degree of hypoglycaemia, rather than the dose of insulin. The cAMP response to hypoglycaemia was significantly higher in hyperthyroid patient, and was lower in patients with hypothyroidism than in normals. The cAMP response of the hyperthyroid patients was normalized when their hyperthyroidism was controlled after 3 months of treatment. The plasma level of cGMP was slightly elevated during hypoglycaemia, but there was no significant difference between controls and hyperthyroid patients. The cGMP response to methacholine, which is probably mediated by cholinergic receptors, was significantly potentiated in hyperthyroid patients. The cAMP response, which is presumably dependent on endogenous catecholamines secreted during methacholine-induced hypotension, was also enhanced in hyperthyroid patients. It is likely that beta-adrenergic receptor responses and cholinergic receptor responses are both enhanced in hyperthyroidism.     

Effects of morphine on neuronal and behavioural responses to visceral and somatic nociception at the level of sinal cord

This study was undertaken to examine the role of morphine in modulation of nociception in visceral and somatic pain tests at the level of the spinal cord, using neurophysiological and behavioural reflex assays. In the neurophysiological study, we recorded extracellularly the activity of the single viscero–somatic convergent neurons of the spinal dorsal horn, which was evoked by the colorectal distension (80 mmHg) of noxious visceral stimulation and the radiant heat (51C) of noxious somatic stimulation, in decerebrated, spinally transected cats. Spinally administered morphine (200 μg) produced significant suppression of noxiously evoked activity by both stimuli in a time–dependent manner. In addition, intravenously administered naloxone reversed the suppressive effects of morphine. In the behavioral reflex study, colorectal distension threshold and tail–flick latency were measured in rats chronically implanted with lumbar intrathecal catheter. Intrathecally administered morphine significantly elevated the colorectal distension threshold and prolonged the tail–flick latency in a time– and dose–dependent manner. The results of the present study demonstrated that spinal morphine was capable of suppressing the evoked activity of the viscero–somatic convergent neurons, resulting in suppression visceral and somatic pain behavioural reflexes.     

Effects of stress on growth of transplanted hepatic tumours and immune responses

Growth of transplanted hepatic tumours (T-9) was enhanced in immune rats under stress, compared with immune rats in an unstressed condition. Compared with unstressed immune rats, killer activity of mononuclear cells infiltrating the tumours against T-9 cells was significantly reduced in stressed immune rats. In contrast, killer activity of splenocytes obtained from stressed immune rats against T-9 cells was elevated compared with that from unstressed immune rats. In addition, natural killer cell activity of mononuclear cells infiltrating the tumours obtained from stressed immune rats was significantly reduced compared with that from unstressed immune rats. Cell populations infiltrating tumour tissues were identified by flow cytometric analysis. The percentage of CD8+ cells in mononuclear cells isolated from tumour tissues of stressed immune rats was reduced compared with that of unstressed immune rats. Furthermore, interleukin-2 responsiveness of splenocytes was suppressed in stressed immune rats, whereas T cell function as reflected by phytohaemagglutinin- or Concanavalin A-reactivity was unaffected by stress. Collectively, it is likely that stress suppressed the generation of cytotoxic cells from the spleen cells of immune rats.     

TESTICULAR FOLLICLE STIMULATING HORMONE RECEPTORS AND EFFECTIVENESS OF HUMAN MENOPAUSAL GONADOTROPHIN-HUMAN CHORIONIC GONADOTROPHIN TREATMENT IN INFERTILE MEN

In order to investigate the relationship between testicular FSH receptors and the effectiveness of hMG-hCG treatment in idiopathic male infertility, 36 infertile men were examined. None of the 13 patients without detectable testicular high affinity FSH receptors showed any increase in motile sperm count after the hMG-hCG treatment, whereas 11 of the 23 patients with FSH receptors responded to the treatment. In patients with FSH receptors, patients with a middle or high Johnsen's score count responded more than those with a low score count did. From the above results, it seems that both the presence or absence of testicular FSH receptors and the histological appearance of spermatogenesis predict responsiveness to hMG-hCG treatment in infertile men.     

Interrelationship of Cardiovascular Effects,Plasma Levels of Nicorandil,and Vascular cGMP Formation in Conscious Rats

The relationship between the dual activity of nicorandil (K_ATP channel-opening activity and nitrate-like action), plasma levels, and changes in vascular cGMP levels and cardiovascular parameters was investigated in conscious rats. Nicorandil (3 mg kg^?1, p.o.) was rapidly absorbed and caused a significant reduction in blood pressure, lasting for at least 1 h, increases in heart rate and femoral blood flow, and decreases in femoral vascular resistance. These were entirely abolished by intravenous glibenclamide (20 mg kg^?1). The plasma concentration of nicorandil reached a maximum 30 min after dosing. After administration of nicorandil, a correlation was observed between blood pressure and plasma nicorandil level or femoral vascular resistance. A significant increase (P < 0.05) in the cGMP content of the thoracic aorta occurred 15 min after administration of nicorandil, and persisted for at least 2 h. These results imply that nicorandil induces vasodilatation by opening K_ATP channels in peripheral resistance vessels, leading to overt reduction of blood pressure, but acts on conductance vessels mainly through nitrate-like activity.     

Clinical Application of Left Ventricular Assist Devices

In Japan, 32 patients have had application of monoventricular and biventricular assist devices during the past three years. Five of the 32 patients treated by the Fall of 1986 have successfully achieved long-term survival. In this paper we describe our experience with the Tomasu and Pierce VAD in a total of four and two patients, respectively. Four of the six patients could be successfully weaned from the VAD and two of them were long-term survivors. Nonsynchronizing pumping of the VADs was effective, as well as synchronizing pumping. Anticoagulant therapy is highly recommended during the use of the VAD although there was no significant incidence of thromboembolism or thrombus in the devices in this clinical series.     

Induction and the possible mechanism of ventricular tachycardia after catheter ablation with direct current shocks in dogs

Cathodal DC shocks (150-J) were administered via the His bundleto 20 closed-chest dogs, and in a further three dogs 25-J cathodalshocks were given via the left ventricular endocardium. In 18dogs, including three that underwent left ventricular ablation,Holter electrocardiograms were recorded from 1 to 7 days afterablation, and 4 weeks after ablation. There were frequent episodesof sustained ventricular tachycardia (VT) from the first fewhours after ablation to 4 days after ablation in all dogs, butboth the rate and the coupling interval of VT were variable.In five conscious dogs stimulated 1 day after ablation, it wasdifficult to induce and terminate VT repeatedly. There was adirect relationship between the paced cycle length and the intervalof the last paced beat to the initiating VT beat in three outof four dogs. In the fourth dog there was an inverse relationship.There was no transient entrainment with ventricular burst pacingduring VT in any of the four dogs tested. The effects of lidocaine(2–3 mg.kg^–1), verapamil (0.2–0.4 mg.kg^–1),and propranolol (0.2 mg.kg^–1) on VT were tested within2 days of ablation in 10 conscious dogs. In general, both lidocaineand verapamil terminated VT, and propranolol slowed VT. In conclusion,VT soon after ablation possibly results from triggered activity,although abnormal automaticity cannot be ruled out.     

Effects of Alpha Adrenergic Stimulation and Blockade on Early Afterdepolarizations Induced by Cesium in Canine Cardiac Purkinje Fibers

Alpha Adrenergic Stimulation and EADs. The effects of alpha adrenergic stimulation and three alpha adrenoceptor blockers on early afterdepolarizations (EADs) were examined in canine card diac Purkinje fibers. In the first group of 18 preparations, EADs were induced by superfusion with 7.5 mM cesium (Cs) dissolved in low potassium (2.7 mM KCl) Tyrode's solution. During alpha adrenoceptor stimulation (norepinephrine 1 μM and propranolol 1 μM) to enhance EADs, the effects of phentotamine and two new alpha 1 adrenoceptor antagonists, benoxathian and WB 4101 (1, 3, and 10 μM), were examined. WB 4101 (1 μM) suppressed EADs in all six preparations. Benoxathian required 3 μM in five preparations and 10 μM in one to suppress EADs. Phentolamine (10 μM) suppressed EADs in two of six preparations. In the second group of 21 preparations, the effects on cesium-induced EADs of the three alpha adrenoceptor hlockers (10 μM) were examined without alpha adrenoceptor stimulation. WB 4101 (10 μM) suppressed EADs in seven of seven preparations, while benoxathian (10 μM) suppressed EADs in five of seven. Phentolamine (10 μM) enhanced EADs in six of seven preparations. In the third group of 24 Purkinje fibers, the direct effects (without alpha adrenoceptor stimulation) of these three antagonists on the characteristics of normal Purkinje fiber action potentials superfused with normal Tyrode's solution were examined. Phentolamine (1, 3, and 10 μM, n = 8) prolonged action potential duration at 90% repolarization (APD90) by 5.3%± 1.3%, 10.0%± 1.8%, and 14.3%± 2.7%, respectively. Benoxathian (n = 8) and WB 4101 (n = 8) shortened APD90 equally: 6.8%± 1.1% vs 7.7%± 1.3% at 1 μM, 13.6%± 1.0% vs 14.5%± 1.6% at 3 μM, and 21.1%± 1.2% vs 20.8%± 2.1% at 10 μM, respectively. We conclude that in cesium treated Purkinje fibers: (1) Alpha adrenoceptor stimulation enhanced EADs; (2) Phentolamine was least effective in suppressing EADs, probably because of a direct effect that prolonged MM)90,: and (3) Although benoxathian and WB 4101 had similar etTects on APD90, WB 4101 was more effective in suppressing EADs at lower concentrations than henoxathian.     

Immunohistochemistry of collagen types II and X, and enzyme-histochemistry of alkaline phosphatase in the developing condylar cartilage of the fetal mouse mandible

We investigated the immunohistochemical localisation of types II and X collagen as well as the cytochemical localisation of alkaline phosphatase in the developing condylar cartilage of the fetal mouse mandible on d 14–16 of pregnancy. On d 14 of pregnancy, although no immunostaining for types II and X collagen was observed, alkaline phosphatase activity was detected in all cells in the anlage of the future condylar process. On d 15 of pregnancy, immunostaining for both collagen types was simultaneously detected in the primarily formed condylar cartilage. Alkaline phosphatase activity was also detected in chondrocytes at this stage. By d 16 of pregnancy, the hypertrophic cell zone rapidly increased in size. These findings strongly support a periosteal origin for the condylar cartilage of the fetal mouse mandible, and show that progenitor cells for condylar cartilage rapidly or directly differentiate into hypertrophic chondrocytes.