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Biomedical subjects

A Sugiyama

Publications and source records attributed to A Sugiyama.

At least 19 recordsLinked to original sources
PubMed2002

Activation of human gingival epithelial cells by cell-surface components of black-pigmented bacteria: augmentation of production of interleukin-8, granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor and expression of intercellular adhesion molecule 1.

Black-pigmented anaerobic bacteria, such as Porphyromonas gingivalis and Prevotella intermedia, are amongst the predominant bacteria in periodontal pockets and have been implicated in periodontal diseases. To elucidate the roles of gingival keratinocytes, which are the first cells encountered by oral bacteria in periodontal diseases, human gingival keratinocytes in primary culture were stimulated with cell-surface components of P gingivalis and Pr. intermedia. A glycoprotein fraction from Pr. intermedia (PGP) clearly augmented the release of interleukin-8, granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor, as determined by enzyme-linked immunosorbent assay. This PGP also induced expression of intercellular adhesion molecule-1 (ICAM-1), as determined by flow cytometry. The augmentation of mRNA expression for these molecules was also confirmed by reverse transcription PCR. In contrast, lipopolysaccharide (LPS) from Pr. intermedia and Escherichia coli was completely inactive in these assays. LPS fraction and purified fimbriae from P gingivalis exhibited weak activities. Cytokine production and ICAM-1 expression by gingival keratinocytes might cause accumulation and activation of neutrophils in the epithelium and, therefore, may be involved in the initiation and development of inflammation in periodontal tissues.

Cells, Cultured↗
PubMed2001

Neutrophil proteinase 3-mediated induction of bioactive IL-18 secretion by human oral epithelial cells.

IL-18, a potent IFN-gamma-inducing cytokine, is expressed by various nonimmune cells as well as macrophages, suggesting that it has important physiological and immunological roles. The present study focused on the mechanism of active IL-18 induction from human oral epithelial cells. The epithelial cells and the cell lines constitutively express IL-18 mRNA and the 24-kDa precursor form of IL-18. Bioactive IL-18 exhibiting IFN-gamma-inducing activity was detected in the supernatant of the cells on costimulation with neutrophil proteinase 3 (PR3) and LPS for 24 h after IFN-gamma-priming for 3 days. An active 18-kDa form of IL-18 was detected in lysate and supernatant of the cells only after the above treatment and the induction was inhibited by cycloheximide and by serine proteinase inhibitors. After the treatment, lactate dehydrogenase activity was not detected in the cell culture supernatant, and PR3 was detected only in the membrane and not in cytoplasm fractions of the cells. Caspase-1 was not detected in the cells even after the treatment and the IL-18 induction was not inhibited by a caspase-1 inhibitor. These results suggest that the PR3-mediated induction of bioactive IL-18 secretion from oral epithelial cells in combination with LPS after IFN-gamma-priming occurred via a caspase-1-independent pathway, and provide new insight into the possible involvement of a neutrophil proteinase in the induction of bioactive IL-18 in oral inflammation such as periodontitis.

Adult↗
PubMed2001

In vivo canine model comparison of cardiohemodynamic and electrophysiological effects of a new antipsychotic drug aripiprazole (OPC-14597) to haloperidol.

The cardiovascular effects of aripiprazole were assessed in comparison with those of haloperidol using a halothane-anesthetized canine model with monophasic action potential monitoring. Aripiprazole (n = 6) or haloperidol (n = 6) was infused over 10 min at escalating doses of 0.03, 0.3, and 3.0 mg/kg with intervals of 20 min between doses. Clinically relevant plasma concentrations were obtained after 0.03-0.3 mg/kg of aripiprazole as well as haloperidol. After 0.03-0.3 mg/kg of aripiprazole, positive chronotropic, inotropic, and dromotropic effects, shortening of the ventricular effective refractory period (ERP) and repolarization phase, and decrease of total peripheral resistance were observed in a dose-related manner. However, in the presence of a beta-blocking dose of esmolol (0.1 mg/kg/min), these changes were not induced. After 3.0 mg/kg of aripiprazole administration, cardiac effects induced by the lower doses were attenuated or disappeared, while the negative chronotropic, dromotropic, and hypotensive actions and prolongation of ERP and repolarization phase were induced. After 0.03 mg/kg of haloperidol, no significant change was observed, except for the decrease of the peripheral resistance. After 0.3-3.0 mg/kg of haloperidol, negative chronotropic, inotropic, and hypotensive actions, intraventricular conduction delay, and prolongation of ventricular ERP and repolarization phase were observed in a dose-related manner accompanied by further decrease of the peripheral resistance. The inhibitory effects of aripiprazole on cardiovascular parameters in dogs were less potent than those of haloperidol at clinically relevant exposures, moreover, aripiprazole, unlike haloperidol, neither induced early afterdepolarization nor prolonged the ventricular electrical vulnerable period. Therefore, aripiprazole can be considered safer to use than haloperidol.

Animals↗
PubMed2001

Cardiovascular action of a cardioselective Ca(2+)channel blocker AH-1058 in conscious dogs assessed by telemetry.

AH-1058, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-[(E)-3-(3-methoxy-2-nitro)phenyl-2-propenyl]piperidine hydrochloride, is a novel Ca(2+)channel blocker exerting cardioselective action in isolated or anesthetized canine heart preparations. To clarify the cardiac and hemodynamic action of AH-1058 in conscious dogs, we assessed the effects of the drug on the hemodynamic parameters continuously recorded by telemetry in conscious unrestrained beagle dogs, and its cardiovascular effects were compared with those of verapamil, disopyramide and atenolol. Oral administration of AH-1058 (0.15, 0.3 and 0.6 mg/kg) reduced the systolic blood pressure and maximal upstroke velocity of the left ventricular pressure (LVdP/dt(max)), increased heart rate and prolonged the QA interval in a dose-dependent manner whereas the drug did not affect diastolic blood pressure. Verapamil at 10 mg/kg reduced systolic and diastolic blood pressure with little effect on heart rate, LVdP/dt(max) and QA interval. Disopyramide at 20 mg/kg increased systolic and diastolic blood pressure, decreased LVdP/dt(max) and prolonged the QA interval with little changes in heart rate. Atenolol at 10 mg/kg decreased LVdP/dt(max) and prolonged the QA interval with little changes in systolic blood pressure, diastolic blood pressure and heart rate. The time course of the cardiohemodynamic action of AH-1058 was longer than those of the other drugs. These results suggest that AH-1058 is a long-acting cardiodepressive drug, and its hemodynamic profile is obviously different from that of disopyramide and atenolol. This unique cardiovascular profile may be beneficial for the treatment of certain pathological processes in which selective inhibition of the ventricular Ca(2+)channels would be the target of drug therapy.

Animals↗
PubMed2001

Antinociceptive effect of spinally injected L-NAME on the acute nociceptive response induced by low concentrations of formalin.

The formalin test has been proposed as an animal model of pain produced by tissue injury. Although biphasic nociceptive responses to formalin injection have been well documented, low concentrations (0.125 and 0.5%) of formalin injected into the mouse hindpaw produced only the phasic (acute) paw-licking response, lasting the first 5 min after the formalin injection. To explore the involvement of nitric oxide (NO) in the spinal cord and peripheral system during the acute phase of the formalin test, we examined the effect of intrathecal (i.t.) or intraplantar (i.pl.) injection of L-N(G)-nitro arginine methyl ester (L-NAME), a NO synthase inhibitor in mice. Pretreatment with L-NAME (160 nmol), injected i.t., resulted in a significant inhibition of the paw-licking response induced by 0.125 and 0.5% of formalin. L-Arginine (600 mg/kg, i.p.) but not D-arginine (600 mg/kg, i.p.) reversed the antinociceptive effect of L-NAME on the acute nociceptive response induced by low concentrations of formalin. The i.pl. injection of L-NAME (160 nmol) produced a significant decrease of the late (tonic) phase response evoked by 2.0% formalin without affecting the early (acute) phase response. Similar results have been reported in the case of i.t. injected L-NAME as assayed by the 2.0% formalin test. L-NAME (160 nmol), injected into the plantar paw, gave no significant effect on the acute nociceptive response induced by a low concentration of formalin (0.125%). These results suggest that NO in the spinal cord may be involved in not only the late phase response of the formalin (2.0%)-induced paw-licking, but also at least the acute phase response induced by low concentrations (0.125 and 0.5%) of formalin, while peripheral NO has little effect on the early (acute) phase nociceptive response evoked by formalin (0.125--2.0%) injection.

Analgesics↗
PubMed2001

Development and characterization of a hybrid bioartificial liver using primary hepatocytes entrapped in a basement membrane matrix.

For the development of a bioartificial liver (BAL) support device, it is most important to establish highly differentiated liver cells cultured at high density. When rat hepatocytes were cultured on a basement membrane matrix, Engelbreth-Holm-Swarm (EHS) gel, their rates of albumin secretion were very high, as measured by ELISA, and these high rates were maintained for more than three weeks of culturing. This level of activity greatly exceeded that of hepatocytes cultured on a plastic substratum, poly-N-p-vinylbenzyl-D-lactonamide (PVLA), on a single layer of collagen, or in a collagen sandwich culture. In an in vitro perfusion experiment, rat hepatocytes rapidly and completely removed ammonia from Eagle's MEM supplemented with 0.2 mM NH4Cl, although ammonia levels of the medium serially increased in modules containing HepG2 cells. A hybrid liver support system was developed and consisted of plasma perfusion through porous hollow fiber modules inoculated with 10 billion porcine hepatocytes entrapped in EHS gel. This system was applied to pigs with ischemic liver failure 8 hr after creation of a portocaval shunt and hepatic devascularization. In animals treated with the BAL support system, blood bicarbonate levels were increased immediately after treatment, and hemodynamic stability was improved. In control pigs, on the other hand, blood bicarbonate levels and blood pressure remained low. Plasma levels of ammonia and lactate decreased in pigs treated with the BAL device, but not in control animals. These results indicate that primary hepatocytes outperform HepG2 cells as a source of biotransformation functions in a BAL system and that the use of a BAL support device in combination with a hollow fiber module and hepatocytes entrapped in EHS gel has potential advantages for clinical use in patients with fulminant hepatic failure.

Ammonia↗
PubMed2001

Paradoxical role of Helicobacter pylori infection: protective effect against ethanol-induced gastric mucosal injury in Mongolian gerbils.

We investigated the effect of ethanol (a representative necrotizing agent) on gastritis induced by Helicobacter pylori infection in Mongolian gerbils. Seventy-eight gerbils were used. Four and 12 weeks after H. pylori inoculation, 30% ethanol was administered into the stomach. The stomachs were removed after 30 min, the intramucosal prostaglandin (PG) E2 concentration was measured, and histopathology was recorded. H. pylori infection caused chronic active gastritis, gastric erosion, hypersecretion of mucin from gland mucus cells, and a rise in the activity of intramucosal PGE2. After ethanol administration, gastric erosion was significantly less in animals infected with H. pylori than in uninfected animals. In conclusion, in the early stage of H. pylori infection, accentuation of intramucosal PGE2 and hypersecretion of mucin from gland mucus cells have a protective effect against gastric mucosal injury induced by necrotizing agents.

Animals↗
PubMed2001

Proliferation of alpha-smooth muscle actin-containing stromal cells (myofibroblasts) in the lamina propria subjacent to intraepithelial carcinoma of the esophagus.

BACKGROUND: The lamina propria of the digestive tract is the space containing vessels, myofibroblasts, and other interstitial components. The present study was undertaken to elucidate the relationships between the proliferation of myofibroblasts within this space and other histological features such as inflammatory cell infiltration and proliferation of blood vessels. METHODS: Thirty-eight cases in total-comprising 19 cases of early and 19 cases of advanced esophageal squamous cell carcinoma with intraepithelial extension (the former including 10 lesions of carcinoma in situ and 15 lesions of carcinoma with invasion only into the lamina propria)-were examined using H&E staining, Azan Mallory staining, and immunostaining for the characterization of mesenchymal cells in the lamina propria against alpha-smooth muscle actin (alphaSMA), desmin, vimentin, factor VIII, collagen type IV, laminin, or inflammatory cells (L26, UCHL1, Kp1, and c-kit). The proliferative potential of myofibroblasts was evaluated by measuring the total length of the bundles of myofibroblasts per case. RESULTS: Proliferation of alphaSMA-containing stromal cells: i) occurred in the lamina propria subjacent either to intraepithelial carcinomas (64%) or to the intraepithelial extension of carcinoma tissue (47%), and ii) showed a significant correlation with both the degree of mononuclear cell infiltration (mostly UCHL1-positive T cells) and the total length of the carcinoma tissue in each case. CONCLUSIONS: Proliferation of alphaSMA-containing stromal cells in the lamina propria may be involved in altering the endoscopic features of the esophagus in cases with intraepithelial carcinoma or an intraepithelial extension of carcinoma tissue.

Actins↗
PubMed2001

Role of N-methyl-N-nitrosourea in the induction of intestinal metaplasia and gastric adenocarcinoma in Mongolian gerbils infected with Helicobacter pylori.

BACKGROUND: Progression from intestinal metaplasia to neoplasia has not been demonstrated experimentally. The hypothesis that gastric adenocarcinoma arises from intestinal metaplasia was tested in a Mongolian gerbil model of Helicobacter pylori (H. pylori) infection. METHODS: One hundred and fourteen specific pathogen-free gerbils were divided in five groups. A and D: infected with H. pylori and administered the carcinogen N-methyl-N-nitrosourea (MNU); C and E: received MNU; B: H. pylori, but no MNU. Animals were killed at 41 weeks, stomachs were mapped, and the relationship between metaplasia and cancer was assessed. RESULTS: Intestinal metaplasia occurred more frequently in the H. pylori-infected, MNU-treated gerbils than in those receiving H. pylori inoculation only (P < 0.01). Carcinomas arose only in H. pylori-infected animals receiving MNU (8 well differentiated, 2 poorly differentiated, and 10 signet ring). Intestinal metaplasia occurred more frequently in association with intestinal-type carcinoma. CONCLUSIONS: Intestinal metaplasia and adenocarcinoma arise in stomachs subjected to the same injuries (in this study, H. pylori and MNU). Only two intestinal-type carcinomas were contiguous to intestinal metaplasia; all other tumors developed most commonly at non-metaplastic sites. This suggests that in this animal model H. pylori and MNU induce several phenotypes of gastric cancer, but intestinal metaplasia may be a direct precursor only in a subset of the intestinal-type tumors.

Adenocarcinoma↗
PubMed2001

Electropharmacologic effects of a new phosphodiesterase III inhibitor, toborinone (OPC-18790), assessed in an in vivo canine model.

Electropharmacologic effects of a new phosphodiesterase (PDE) III inhibitor toborinone (OPC-18790) were assessed in a halothane-anesthetized, closed-chest canine model. Toborinone, 0.03 mg/kg, increased ventricular contractility, decreased total peripheral resistance, and inhibited intraventricular conduction without changing other cardiovascular parameters. A clinically relevant dose of 0.3 mg/kg increased heart rate, systolic blood pressure, and cardiac output, decreased preload to the left ventricle, enhanced atrioventricular nodal conduction, and shortened repolarization and the vulnerable period of the ventricle, in addition to enhancing the effects observed after the low dose. A high dose of 3 mg/kg of toborinone decreased systolic, mean, and diastolic pressures and prolonged the effective refractory period (ERP) in addition to the effects observed after the middle dose. No further change was detected in ventricular repolarization. Most of the cardiohemodynamic effects can be explained by the PDE III inhibition by toborinone. With regard to electrophysiologic properties, the prolongation of intraventricular conduction time and ERP by toborinone suggests sodium channel inhibition. The lack of the prolongation of ventricular repolarization suggests that previously demonstrated inhibition of I(Kr) and I(K1) and increased I(Ca-L) by toborinone might be counteracted by factors such as the cyclic AMP-dependent outward currents, I(Ks) and I(C1).

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2001

Cardiac electrophysiologic and hemodynamic effects of sildenafil, a PDE5 inhibitor, in anesthetized dogs.

A recent in vitro study demonstrated that supratherapeutic concentrations of sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, blocked I(Kr) and prolonged cardiac repolarization. This study assessed the in vivo cardiohemodynamic and electrophysiologic effects of sildenafil using a halothane-anesthetized, closed-chest canine model (n = 5) to bridge the gap between basic observation and clinical experience. Intravenous administration of sildenafil citrate in doses of 0.03, 0.3, and 3.0 mg/kg for 10 min, which provided sub-to supratherapeutic plasma drug concentrations, did not affect the monophasic action potential duration or effective refractory period of the right ventricle during the sinus rhythm as well as the ventricular pacing at the cycle length of 400 and 300 ms. However, sildenafil decreased the total peripheral resistance, simultaneously inducing positive chronotropic and inotropic effects at the top dose, which gave plasma concentrations at least 10 times higher than the therapeutic range. This cardiohemodynamic profile of sildenafil can be largely explained by reflex sympathetic activation associated with its vasodilator effect. Meanwhile, the lack of prolongation of the ventricular repolarization phase at the therapeutically relevant to moderately supratherapeutic sildenafil concentrations supports the earlier clinical studies that indicate that sildenafil has no effect on electrocardiogram.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2001

AH-1058: a novel cardioselective Ca2+ channel blocker.

The pharmacologic profile of a cyproheptadine-related compound, 4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-[(E)-3-(3-methoxy-2-nitro)phenyl-2-propenyl]piperidine hydrochloride (AH-1058), was assessed in various in vivo and in vitro models. In guinea pig cardiomyocytes, AH-1058 effectively suppressed L-type Ca2+ channel currents without affecting other ion channel or ion exchange currents. In rat cerebral cortical membranes AH-1058 appears to bind preferentially to L-type Ca2+ channels at phenylalkylamine- and benzothiazepine-binding sites. In canine isolated, blood-perfused heart preparations, AH-1058 exerted negative inotropic, dromotropic, and chronotropic and weak coronary vasodilator effects. In halothane-anesthetized dogs, AH-1058 suppressed ventricular contractility and decreased blood pressure and cardiac output. Total peripheral vascular resistance was hardly affected by the drug, suggesting that in vivo AH-1058 can selectively suppress cardiac, as compared to peripheral vascular, function. In conscious dogs, by intravenous administration AH-1058 reduced systolic blood pressure and maximal upstroke velocity of the left ventricular pressure, while it increased heart rate in a dose-dependent manner. The drug did not affect diastolic blood pressure, which is quite different from cardiovascular properties of well-known Ca2+ channel blockers, verapamil and diltiazem. This unique cardiovascular profile of AH-1058 is expected to be useful in the treatment of certain pathological processes such as the obstructive hypertrophic cardiomyopathy, vasovagal syncope, dissecting aortic aneurysm, and ventricular arrhythmias, in which selective inhibition of the ventricular Ca2+ channels is essential for drug therapy.

Animals↗
PubMed2001

Serum immunoglobulin G immune response to Helicobacter pylori antigens in Mongolian gerbils.

The Mongolian gerbil model for Helicobacter pylori infection is an animal model that mimics human disease. We examined the serum immune response to H. pylori infection in gerbils by enzyme-linked immunosorbent assay (ELISA) and Western blotting, both with whole-cell (H. pylori) extracts. A total of 66 7-week-old specific-pathogen-free male gerbils were inoculated orogastrically with H. pylori strain ATCC 43504. Sera were collected 1, 2, 4, 8, 12, 26, 38, and 52 weeks after H. pylori inoculation. Sixty-nine noninfected gerbils and their sera were used as controls. The specificity of the ELISA was 95.7%. The frequency of seropositivity increased over time: 2 of 10 (20%), 7 of 10 (70%), and 7 of 7 (100%) samples of sera from inoculated gerbils were positive for H. pylori at 2, 4, and 8 weeks postinoculation, respectively. Western blot assays showed that the primary immunoglobulin G (IgG) response against low-molecular-mass (25-, 30-, and 20-kDa) proteins appeared after a lag period of 2 to 8 weeks after inoculation. Antibodies against 160-, 150-, 110-, 120-, 80-, 66-, and 63-kDa proteins were observed 12 weeks after inoculation. The early reactive 30-kDa protein was identified as a urease alpha subunit by N-terminal amino acid sequencing. After 26 weeks, two groups of animals could be distinguished: one group developed ulcers (n = 5), and the other developed hyperplastic polyps without ulcers (n = 19). Gerbils in the gastric ulcer group showed significantly higher serum anti-H. pylori IgG levels than did gerbils in the hyperplastic group (P = 0.001) as measured by ELISA. Furthermore, a higher proportion of animals developed antibodies to H. pylori proteins of 26, 25, and 20 kDa in the ulcer group than those animals with hyperplastic polyps (75 to 100% versus 17 to 50%) in Western blot assays. These results highlight the importance of the immune response of the host in the development of H. pylori-related gastric lesions.

Animals↗
PubMed2001

In vivo complex formation of oxidized alpha(1)-antitrypsin and LDL.

An inactivated form of alpha(1)-antitrypsin (AT) and LDL coelutes in gel permeation chromatography. To characterize and to quantify the amount of this fraction of AT, a monoclonal antibody was established against chloramine T-oxidized AT and named OxAT-4. OxAT-4 recognized the oxidatively modified AT, including hexylaldehyde- or 4-hydroxy-2-nonenal-modified AT, but neither normal active AT nor trypsin/AT complex. Comigration of apoB and oxidized AT was demonstrated by Western blotting analysis of AT-LDL by means of anti-apoB monoclonal antibody and OxAT-4. A complex of oxidized AT and LDL (AT-LDL) was isolated from human plasma LDL by affinity column with an OxAT-4 antibody-coated carrier. AT-LDL was degraded 4 times more effectively by mouse peritoneal macrophages, but this was not mediated by scavenger receptor class A type I. Localization of AT-LDL was detected in human atherosclerotic lesions of the coronary artery, but distribution of it was not completely identical to that of macrophages. In situ hybridization revealed AT expression by macrophages, which were present in intimal layers of the coronary artery. From these findings, we concluded that AT is produced and oxidized by macrophages, then attached to LDL in the intimal layer of the arterial wall. Although AT-LDL that escapes into the blood stream can be cleared by hepatocytes, the remaining AT-LDL may be taken up by macrophages and contribute to the lipid accumulation in arterial wall cells as the early stage of atherogenesis.

Animals↗
PubMed2001

Utilization of telemetry system to assess the cardiovascular profile of AH-1058, a new cardioselective Ca2+ channel blocker, in conscious dogs.

Cardiovascular effects of a new Ca2+ channel blocker AH-1058, 4-(5H-dibenzo[a,d]cyclo-hepten-5-ylidene)-1-[(E)-3-(3-methoxy-2-nitro)phenyl-2-propenyl]piperidine hydrochloride, were assessed in conscious dogs using a new telemetry system. AH-1058 (0.03, 0.1 and 0.3 mg/kg, i.v.) reduced systolic blood pressure and the maximal upstroke velocity of the left ventricular pressure and increased the heart rate in a dose-dependent manner without affecting the diastolic blood pressure; each of these responses lasted for several hours. These results support the previous knowledge that AH-1058 is a long-lasting cardiodepressive drug. The telemetry system provided important information for predicting favorable clinical effects of AH-1058.

Animals↗
PubMed2001

In vivo antiarrhythmic profile of AP-792 assessed in different canine arrhythmia models.

The antiarrhythmic effects of a novel antiarrhythmic drug AP-792, 4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-[4-cyclohexylbutyl]piperidine hydrochloride, were analyzed using the epinephrine-, digitalis- and two-stage coronary ligation-induced canine ventricular arrhythmia models. Intravenous administration of AP-792 (0.3 or 1.0 mg/kg) effectively suppressed each of the ventricular arrhythmias, an action that resembles that of a typical cardioselective Ca2+ channel blocker, AH-1058. The antiarrhythmic action of AP-792 was slow in onset and longer-lasting than those in our previous studies using more than 50 antiarrhythmic drugs, including Na+ and Ca2+ channel blockers. These results suggest that AP-792 can become a unique long-acting antiarrhythmic drug.

Animals↗
PubMed2001

Acute electropharmacological effects of intravenously administered amiodarone assessed in the in vivo canine model.

Acute hemodynamic and electrophysiological effects of amiodarone were assessed simultaneously, using the halothane-anesthetized, closed-chest in vivo canine model in comparison with those of solvent ethanol alone. Intravenous administration of the solvent (n = 8) induced no significant change in any of the cardiovascular parameters. On the other hand, intravenous amiodarone in the canine antiarrhythmic dose of 3.0 mg/kg (n = 6) exerted negative chronotropic, inotropic and dromotropic effects in addition to the transient hypotensive action followed by an increase of the total peripheral vascular resistance. Amiodarone also prolonged both the ventricular repolarization phase and the effective refractory period, where the increment was greater in the latter than in the former, indicating the shortening of the electrical vulnerable period of the ventricle. More importantly, appearance of the electrophysiological effect on repolarization took more time and higher dose compared with the effect on refractoriness, which could be detected at a one tenth the dose. These results support the previous knowledge that intravenously administered amiodarone possesses class I, III and IV actions and suggest that shortening of the electrical vulnerable period may be one of the unique antiarrhythmic properties of intravenous amiodarone against re-entry type arrhythmias.

Action Potentials↗