PubMed Health⌕ Search

Biomedical subjects

H Brasch

Publications and source records attributed to H Brasch.

At least 19 recordsLinked to original sources
PubMed2006

Parotid metastasis--an independent prognostic factor for head and neck cutaneous squamous cell carcinoma.

BACKGROUND: Metastatic parotid cutaneous squamous cell carcinoma (SCC) is the most common parotid gland malignancy in New Zealand and Australia. The current AJCC TNM staging system does not account for the extent of nodal metastasis. A staging system that separates parotid (P stage) from neck disease (N stage) has been proposed recently. AIM: To review the outcome of patients with metastatic head and neck cutaneous SCC treated at our multidisciplinary Head and Neck Service using the proposed staging system. METHOD: Consecutive patients were culled from our Head and Neck/Skull Base Database, 1990-2004. These patients were restaged according to the proposed staging system: P stage: P0 = no disease in the parotid (i.e., neck disease only); P1 = metastatic node < or = 3 cm; P2=metastatic node > 3 cm and < or =6 cm, or multiple nodes; and P3 = metastatic node > 6 cm, or disease involving the facial nerve or skull base. N stage: N0=no disease in the neck (i.e., parotid disease only); N1 = single ipsilateral metastatic node < or = 3 cm; and N2 = multiple metastatic nodes, or any node > 3 cm, or contralateral neck involvement. Loco-regional recurrence and disease-specific survival were calculated using the Kaplan-Meier method and comparison of graphs made with the log-rank test. Multivariate analysis using the Cox regression model was carried out to assess the impact of various parameters. RESULTS: Sixty-seven patients with metastatic head and neck cutaneous SCC were identified. Thirty-seven patients had parotid metastasis (of whom 13 also had neck disease) while 21 had neck metastasis alone. Nine patients had dermal or soft tissue metastasis. These nine patients were excluded from this series, and data analysis was carried out on the remaining 58 (46 men, 12 women, mean age 71 years) patients. Sixty-seven percent of the patients underwent post-operative adjuvant radiotherapy. The five-year disease-specific survival rate was 54%. Among 56 patients followed up to disease recurrence or for a minimum period of 18 months, the loco-regional recurrence rate was 52%. The presence of parotid disease was an independent prognostic factor on survival (p < 0.01), and P3 fared significantly worse than P1 and P2. Those patients who had both parotid and neck disease fared worse than those who had parotid or neck disease alone (p = 0.01). N2 had a significantly poorer outcome compared with N1 (p < 0.01). Immunosuppression (p = 0.01) and a positive surgical margin (p < 0.01) were significant adverse prognostic factors for survival. Adjuvant radiotherapy, extracapsular spread, and perineural and vascular invasion did not influence survival. Our study demonstrates that the extent of parotid disease is an independent prognostic factor for metastatic head and neck cutaneous SCC.

Aged↗
PubMed2006

Malignant peripheral nerve sheath tumour of the cervical vagus nerve in a neurofibromatosis type 1 patient.

One serious complication of neurofibromatosis type 1 (NF1) is the development of malignant peripheral nerve sheath tumours (MPNSTs). These malignancies often develop within pre-existing plexiform neurofibromas and their development is now thought to be associated with both tumour suppressor gene mutations and dysregulated growth factor signalling. Recent work demonstrates that the lifetime risk of malignant transformation is significantly greater than previously thought. Ionising radiation, a long-standing disease, particularly the presence of a large number of plexiform neurofibromas from an early age, are suggested risk factors. We present an NF1 patient who developed an MPNST of the cervical vagus nerve which was successfully treated with surgery. Close monitoring of patients with NF and a high level of suspicion towards rapidly enlarging and painful swellings is merited as these features may signify malignant transformation. Whether a positive history of MPNST in other affected family members predisposes the individual to a higher risk of malignant transformation is unclear.

Adult↗
PubMed2001

A meta-analysis comparing eradication, healing and relapse rates in patients with Helicobacter pylori-associated gastric or duodenal ulcer.

AIM: To compare the effectiveness of Helicobacter pylori eradication in curing peptic ulcer disease in trials involving both gastric ulcer and duodenal ulcer. METHODS: Twenty-four relevant randomized controlled trials and randomized comparative trials met the predefined selection criteria. Only proton pump inhibitor-based eradication trials were considered for the evaluation of eradication efficacy and ulcer healing. For the determination of relapse rates, all trials independent of the eradication therapy regimen were considered. RESULTS: Data from 2102 patients were analysed comparing gastric ulcer with duodenal ulcer. No statistical differences between gastric ulcer and duodenal ulcer patients were found with regard to eradication rates (summarized odds ratio, 1.23; 95% confidence interval, 0.98-1.55) or ulcer relapse rates, whether in successfully H. pylori eradicated patients (summarized odds ratio, 0.69; 95% confidence interval, 0.26-1.84) or unsuccessfully H. pylori eradicated patients (summarized odds ratio, 1.48; 95% confidence interval, 0.85-2.56). Owing to heterogeneity, healing rates were not comparable. CONCLUSIONS: The eradication of H. pylori infection cures both gastric and duodenal ulcer, and the cure rates are similar. This suggests that H. pylori is the key factor in peptic ulcer disease independent of the ulcer site.

Anti-Bacterial Agents↗
PubMed1998

[Paracetamol-induced tubulointerstitial nephritis in a chronic alcoholic patient].

Hepatic and renal toxicity of paracetamol overdosage is well known like the fact that ethanol enhances the toxicity of the drug. Scanty data report on reversible hepatic and renal failure appearing after therapeutic dose of paracetamol in alcohol-abusers. Renal damage might also occur without gross hepatocellular damage in alcoholics. We report the case of a young alcoholic male whose first renal biopsy disclosed mesangiocapillary glomerulonephritis. One month later he took 1.5 g paracetamol to control the fever caused by upper respiratory tract infection. Soon he got hospitalised due to fever, toxicoderma, elevated liver and renal function test. While liver enzymes returned to normal, macroscopic haematuria, nephrotic range proteinuria oliguria, uraemia developed. A repeated renal biopsy revealed severe interstitial inflammation, tubular atrophy, progression of the vascular changes seen in the first biopsy. Haemodialysis was started and he got steroids (1 mg/kg body-weight) besides aggressive antihypertensive medication. He showed considerable recovery of renal function in some weeks. The case points to the possibility that paracetamol--even in therapeutic dosage--might result in hepatic and renal damage in alcoholics. The sudden deterioration in renal function was due to the acute tubulointerstitial nephritis superimposed on mesangiocapillary glomerulonephritis, provoked by paracetamol. Early diagnosis, immediate withdrawal of the toxic drug, steroid treatment might have kidney and life saving effect.

Acetaminophen↗
PubMed1998

Guidelines for the treatment of acidaemia with THAM.

THAM (trometamol; tris-hydroxymethyl aminomethane) is a biologically inert amino alcohol of low toxicity, which buffers carbon dioxide and acids in vitro and in vivo. At 37 degrees C, the pK (the pH at which the weak conjugate acid or base in the solution is 50% ionised) of THAM is 7.8, making it a more effective buffer than bicarbonate in the physiological range of blood pH. THAM is a proton acceptor with a stoichiometric equivalence of titrating 1 proton per molecule. In vivo, THAM supplements the buffering capacity of the blood bicarbonate system, accepting a proton, generating bicarbonate and decreasing the partial pressure of carbon dioxide in arterial blood (paCO2). It rapidly distributes through the extracellular space and slowly penetrates the intracellular space, except for erythrocytes and hepatocytes, and it is excreted by the kidney in its protonated form at a rate that slightly exceeds creatinine clearance. Unlike bicarbonate, which requires an open system for carbon dioxide elimination in order to exert its buffering effect, THAM is effective in a closed or semiclosed system, and maintains its buffering power in the presence of hypothermia. THAM rapidly restores pH and acid-base regulation in acidaemia caused by carbon dioxide retention or metabolic acid accumulation, which have the potential to impair organ function. Tissue irritation and venous thrombosis at the site of administration occurs with THAM base (pH 10.4) administered through a peripheral or umbilical vein: THAM acetate 0.3 mol/L (pH 8.6) is well tolerated, does not cause tissue or venous irritation and is the only formulation available in the US. In large doses, THAM may induce respiratory depression and hypoglycaemia, which will require ventilatory assistance and glucose administration. The initial loading dose of THAM acetate 0.3 mol/L in the treatment of acidaemia may be estimated as follows: THAM (ml of 0.3 mol/L solution) = lean body-weight (kg) x base deficit (mmol/L). The maximum daily dose is 15 mmol/kg for an adult (3.5L of a 0.3 mol/L solution in a 70kg patient). When disturbances result in severe hypercapnic or metabolic acidaemia, which overwhelms the capacity of normal pH homeostatic mechanisms (pH < or = 7.20), the use of THAM within a 'therapeutic window' is an effective therapy. It may restore the pH of the internal milieu, thus permitting the homeostatic mechanisms of acid-base regulation to assume their normal function. In the treatment of respiratory failure, THAM has been used in conjunction with hypothermia and controlled hypercapnia. Other indications are diabetic or renal acidosis, salicylate or barbiturate intoxication, and increased intracranial pressure associated with cerebral trauma. THAM is also used in cardioplegic solutions, during liver transplantation and for chemolysis of renal calculi. THAM administration must follow established guidelines, along with concurrent monitoring of acid-base status (blood gas analysis), ventilation, and plasma electrolytes and glucose.

Acidosis↗
PubMed1995

Activators of sodium, calcium and potassium channels modulate the cardiac effects of quinidine in vitro.

Quinidine (25.5 mumol/l) reduced the beating frequency of isolated right guinea-pig atria, caused a negative inotropic effect in papillary muscles and slightly raised the contractile force of left atria. The functional refractory period of both tissues was prolonged. A 20% increase of the extracellular sodium concentration did not reverse the effects of quinidine. The Na-channel activator BDF 9148 (1 mumol/l) and the Ca-channel agonist Bay-K-8644 (0.5 mumol/l) further increased the contractile force and caused an additional prolongation of the functional refractory period in quinidine-pretreated atria. Only Bay-K-8644 was able to reverse the negative inotropic effect of quinidine in papillary muscles. The influence of Bay-K-8644 on the contractile force in quinidine-pretreated muscles was not attenuated by lemacalim (3 mumol/l), an activator of ATP-dependent potassium channels, but the duration of the functional refractory period was significantly reduced. These results suggest that a combination of a calcium channel activator and a potassium channel opener might be able to improve the treatment of quinidine intoxications.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1993

Cardiotoxic effects of nitrofurantoin and tertiary butylhydroperoxide in vitro: are oxygen radicals involved?

Langendorff rat hearts were perfused for 15, 30 or 75 min. with the oxygen radical generators nitrofurantoin (0.25 or 0.5 mmol/l) or tertiary butylhydroperoxide (0.25 mmol/l). Both agents reduced the force of contraction and increased the release of glutathione, oxidized glutathione, lactate dehydrogenase and creatine phosphokinase into the perfusion fluid. The tissue concentration of glutathione was reduced. While there were no signs of an increased production of conjugated dienes, the tissue concentration of malondialdehyde was greater than in control experiments. The variability of the latter effect was large, however, and in most cases the increase was not statistically significant. Addition of catalase (100 mU/ml) or catechin (0.5 mmol/l) to the perfusion medium abolished the nitrofurantoin induced release of oxidized glutathione but did not not prevent or attenuate enzyme leakage from the cells and the development of a negative inotropic effect. These results suggest that the cardiotoxic effects of nitrofurantoin and tertiary butylhydroperoxide cannot be explained by the appearance of oxygen radicals alone and that an increased lipid peroxidation is not the mechanism which is primarily responsible for cell death.

Animals↗
PubMed1993

Angiotensin II increases norepinephrine release from atria by acting on angiotensin subtype 1 receptors.

Norepinephrine stores in electrically driven guinea pig isolated atria were loaded with [3H]norepinephrine, and norepinephrine release was deduced from the radioactivity efflux. Electrical field stimulation of sympathetic nerve endings was applied during the refractory period of atrial contractions. The stimulation-induced release of norepinephrine was increased by angiotensin II (Ang II) (10(-8) to 10(-6) mol/L) in a concentration-dependent manner. The maximum observed effect was a 55% augmentation. The effects of 10(-7) and 10(-6) mol/L Ang II were abolished by 10(-6) and 10(-5) mol/L of the subtype 1 Ang II receptor antagonist losartan, respectively. Losartan by itself (10(-6) mol/L) caused a 14% reduction of norepinephrine release. The subtype 2 Ang II receptor ligand PD 123319 (1-[[4-(dimethylamino)-3-methylphenyl]methyl]-5-(diphenylacetyl)- 4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid ditrifluoroacetate) in a concentration of 10(-4) mol/L had no detectable influence on transmitter release and did not antagonize the effect of Ang II. Angiotensin I (10(-6) and 10(-5) mol/L) increased norepinephrine release maximally by 23%. This effect was antagonized by 10(-5) mol/L losartan and did not appear in the presence of 10(-6) mol/L of the converting enzyme inhibitor ramiprilat. These results suggest that Ang II increases norepinephrine release by an activation of subtype 1 receptors, whereas angiotensin I is converted to Ang II to become effective.

Analysis of Variance↗
PubMed1992

Beta-adrenoceptor blocking effects of two bopindolol metabolites in isolated guinea-pig atria.

The beta-adrenoceptor blocking effects of the bopindolol (Wandonorm, CAS 62658-63-3) metabolites 18-502 (indole-2,4- methylaminopropoxy(N-tert.butyl)-tartrate) and 20-785 (indole-2,4-carboxyaminopropoxy(N-tert.butyl] were studied in electrically stimulated guinea-pig left atria and in spontaneously beating guinea-pig atria in vitro. Both compounds shifted the concentration-response curve of isoprenaline to the right, but did not reduce the maximum effect of this drug. For compound 20-785, pA2 values of 7.44 (left atrium, inotropic effect) and 7.58 (right atrium, chronotropic effect) were calculated. The metabolite 18-502 had a much greater beta-adrenoceptor blocking potency, as judged from its pA2 values of 9.53 and 9.48, resp., and in the concentration of 10(-8) mol/l it caused a significant flattening of the concentration-response curve of isoprenaline. From these results, compound 20-785 can be classified as a competitive beta-adrenoceptor antagonist, while for higher concentrations of the metabolite 18-502 additional noncompetitive mechanisms of action cannot be excluded.

Adrenergic beta-Antagonists↗
PubMed1991

Pre- and postjunctional effects of phorbol 12-myristate-13-acetate in the mouse vas deferens.

The protein kinase C stimulator phorbol 12-myristate-13-acetate (PMA) increased the release of noradrenaline from field-stimulated mouse vasa deferentia and antagonized the inhibitory effect of xylazine and FK 33-824. The mechanical response to field stimulation was not modified by PMA in unpretreated vasa, but the contractility was partly restored when the stimulation-response curve had been depressed by xylazine or FK 33-824. In contrast, PMA decreased the contractile response to exogenous noradrenaline and bethanechol. A similar but smaller reduction was obtained with 1,2-dioctanoyl-sn-glycerol. In vasa depolarized by KCl, PMA and verapamil reduced the amplitude of contractions elicited by CaCl2. Only the effect of verapamil could be reversed by the calcium ionophore A 23187, while the effect of PMA was greatly attenuated in muscles pretreated with ouabain. Phorbol 12-myristate-13-acetate-4-O-methylether was ineffective in all experiments. These results suggest that PMA increases noradrenaline release (prejunctional effect) and decreases vasal contractility (postjunctional effect) by activation of protein kinase C.

Animals↗
PubMed1991

Negative chronotropic but no antiarrhythmic effect of (+)- and (-)-naloxone in rats and guinea pigs.

STUDY OBJECTIVE: The aim was to investigate the antiarrhythmic effects of (+)- and (-)-naloxone in various arrhythmia models in vivo. DESIGN: Naloxone (1-40 mg.kg-1), naltrexone (20-40 mg.kg-1), or standard antiarrhythmic drugs (quinidine, lignocaine, phenytoin, (+)-sotalol) were injected intravenously. Ventricular extrasystoles were then elicited by infusion of either ouabain (guinea pigs) or aconitine (rats), or by electrical stimulation (guinea pigs). EXPERIMENTAL MATERIAL: Male Wistar rats and guinea pigs (n = 6-10) were used. Arterial blood pressure and ECG were recorded continuously. MEASUREMENTS AND MAIN RESULTS: Naloxone and naltrexone decreased the heart rate. The effect of naloxone was not stereospecific and is apparently not mediated by opioid receptors. Naloxone had no influence on ouabain induced arrhythmias or fibrillation threshold in guinea pigs. The appearance of aconitine induced extrasystoles was accelerated by 20 mg.kg-1 (-)-naloxone but delayed by 40 mg.kg-1. No effects were seen with (+)-naloxone or (-)-naltrexone. CONCLUSIONS: The results show that naloxone does not possess prominent antiarrhythmic properties.

Aconitine↗
PubMed1991

No influence of prejunctional alpha 2-adrenoceptors on the effects of nicotine and tyramine in guinea-pig atria.

1. Guinea-pig left atria were stimulated at a rate of 0.5 Hz and preloaded with 10 microCi 7-[3H]noradrenaline. In the presence of cocaine, 3 x 10(-6) mol l-1, and atropine, 10(-7) mol l-1, noradrenaline release was stimulated twice in each atrium, either by electrical field stimulation (one pulse, 0.2 ms 30 V, during each refractory period for 5 min) or by addition of either nicotine, 3 x 10(-5) mol l-1, or tyramine 10(-5) mol l-1. 2. The release of radioactivity caused by field stimulation and the associated positive inotropic effect were almost abolished by 3 x 10(-8) mol l-1 tetrodotoxin. Pretreatment with 3 x 10(-7) mol l-1 idazoxan increased the effects of field stimulation, while they were attenuated in the presence of clonidine, 3 x 10(-7) mol l-1. 3. The inotropic effect and the release of radioactivity caused by nicotine were greatly attenuated by tetrodotoxin, but were not significantly influenced by idazoxan or clonidine. 4. The release of radioactivity caused by tyramine and the inotropic effect of this drug were resistant to tetrodotoxin pretreatment and were not modified by idazoxan or clonidine. 5. It is concluded that nicotine releases noradrenaline by initiating a propagated action potential. But activation of prejunctional alpha 2-adrenoceptors does not seem to attenuate the transmitter release by limiting the spread of the action potential in the prejunctional sympathetic neuronal network.

Action Potentials↗
PubMed1991

Inotropic and electrophysiological effects of BDF 9148, a congener of DPI 201-106, in guinea-pig atria and papillary muscles.

1. BDF 9148 is a newly synthesized congener of DPI 201-106 in which the piperazidinyl moiety has been replaced by an azetidine-3-oxy-moiety. The inotropic effect of both drugs was studied as well as their influence on the action potential, by use of standard microelectrode techniques. 2. BDF 9148 increased the contractile force of guinea-pig atria and papillary muscles. The EC50 was 1.32 X 10(-7) mol l-1 and 0.7 X 10(-6) mol l-1 respectively. DPI 201-106 was effective in a similar concentration-range, the EC50 being 2.6 X 10(-7) mol l-1 for atria and 2.8 X 10(-7) mol l-1 for papillary muscles. 3. Both drugs caused a concentration-dependent prolongation of the relaxation time of the isometric contraction curve. With 10(-6) mol l-1 BDF 9148, the mean increase was 39.1 +/- 4.4 ms in atria and 39.4 +/- 7.5 ms in papillary muscles while 10(-6) mol l-1 DPI 201-106 caused increases of 56.7 +/- 2.5 ms and 79.3 +/- 11.7 ms, respectively. The effect of BDF 9148 was not prevented by propranolol, but was reversed by 3 X 10(-6) mol l-1 tetrodotoxin. Pretreatment of atria with 3 X 10(-8) mol l-1 BDF shifted the concentration-response curve of ouabain to the left and reduced the EC50 of the glycoside from 3.21 X 10(-7) mol l-1 to 2 X 10(-7) mol l-1. 4. BDF 9148 and DPI 201-106 concentration-dependently increased the action potential duration of papillary muscles and their functional refractory period. The drugs did not modify the resting potential, the action potential amplitude or the maximum depolarization velocity.5. All effects of BDF 9148 persisted after washout. The lipophilic drug accumulated in the tissues and the tissue drug concentration was little reduced by washout of BDF 9148 from the organ bath.6. In contrast to DPI 201-106, which had a prominent negative chronotropic effect in right atria, BDF 9148 caused only a slight reduction of the beating frequency with the largest (3 x 10 5mol 11) concentration.7. The results are consistent with BDF 9148 being a sodium channel activator with much weaker influence on the beating frequency than the parent compound DPI 201-106.

Action Potentials↗
PubMed1990

Pre- and postjunctional effects of N-ethylmaleimide in the isolated mouse vas deferens.

The influence of N-ethylmaleimide (NEM) on contractions due to exogenously applied noradrenaline and bethanechol and on the inhibitory effects of clonidine, of the enkephalin derivative, FK 33-824, and 2-chloroadenosine (2-CLA) on field stimulation-response curves and [3H]noradrenaline [( 3H]NA) release was studied in the isolated mouse vas deferens. Exposure to NEM (60 microM: 10 min) caused a 30% reduction of the maximal contraction due to NA but nearly abolished the response to bethanechol. NEM partially reversed the depression of the pulse width-response curves by clonidine and FK 33-824 but was without effect with 2-CLA. The contractions evoked by stimulation frequencies above 20 Hz were depressed by NEM both in presence and absence of the agonists. NEM diminished the inhibition of the stimulation-evoked release of [3H]NA by the three agonists. The prejunctional effect of NEM was markedly influenced by the stimulation parameters. These findings support the suggestion that the inhibition mediated by alpha 2-adrenoceptors, mu- and P1-receptors in the mouse vas deferens is NEM-sensitive and possibly transmitted by a pertussis toxin-sensitive G-protein.

2-Chloroadenosine↗
PubMed1990

Combined peritoneal and haemodialysis therapy for chronic renal insufficiency.

Twenty-three patients with chronic uraemia were treated for an average of 8.5 months with intermittent peritoneal dialysis. When hypervolaemia developed and/or the volume of low-molecular weight substances increased, the therapy was complemented by one or two sessions of haemodialysis per week. The combined treatment was carried on for 4.1 months on average, in consequence of which the general condition improved, body weight reached the optimum, blood pressure diminished, turned normal and could be controlled by drugs. In the wake of the therapy carbamide nitrogen and creatinine levels dropped significantly, serum total protein and albumin values increased. At the close of the observation period 3 patients remained under combined therapy, 2 had undergone cadaveric kidney transplantation, 18 were transferred to chronic haemodialysis. Thoughts are evolved about the advisability of intermittent peritoneal dialysis and combined therapy in the care for uraemic patients.

Adult↗
PubMed1990

Cephalosporins increase the renal clearance of methotrexate and 7-hydroxymethotrexate in rabbits.

Anaesthetized rabbits were infused with methotrexate (MTX; 30 micrograms x kg-1 x min-1) for 4 h. Constant plasma concentrations of MTX and its main metabolite 7-hydroxymethotrexate (7-OH-MTX) were achieved 40-60 min after the start of the infusion. In all, 50% of the infused MTX was eliminated by the kidney; another 15%-30% was hydroxylated and excreted as 7-OH-MTX in the urine. A concomitant infusion of penicillin G (3.96 mg x kg-1 x min-1) decreased the renal clearance of MTX and 7-OH-MTX, probably by competitive antagonism at the common tubular secretion site. In contrast, the four cephalosporins ceftriaxone, ceftazidime, ceftizoxime and cefoperazone all increased the renal clearance of MTX and 7-OH-MTX. At similar plasma concentrations, ceftriaxone and ceftazidime were almost equipotent, ceftizoxime was less effective and cefoperazone seemed to have a biphasic effect, depressing the clearance of MTX and 7-OH-MTX at higher drug concentrations. The effects are best explained by an inhibition of the tubular reabsorption of the cytostatic and its metabolite. The results suggest that cephalosporins are a better choice than penicillin for antibiotic treatment during MTX therapy.

Animals↗
PubMed1990

Influence of N-ethylmaleimide on action potential and force of contraction of guinea-pig papillary muscles.

1. Standard microelectrode techniques were used to investigate the influence of N-ethylmaleimide on the action potential, slow response action potential and force of contraction of guinea-pig papillary muscles. 2. N-ethylmaleimide, 3 x 10(-5) to 10(-4) mol l-1, concentration-dependently increased the force of contraction. The positive inotropic effect developed quickly and, with the largest drug concentration, was followed by a progressive decline of the contractile force. The action potential duration was progressively shortened by N-ethylmaleimide. 3. The effects of N-ethylmaleimide were not prevented in the presence of tetrodotoxin 3 x 10(-8) mol l-1 and propranolol 4 x 10(-6) mol l-1 or by a reduction of the Na(+)-concentration to 70 mmol l-1. 4. Verapamil, 10(-6) mol l-1, reduced the positive inotropic, but not the action potential shortening effect of N-ethylmaleimide. 5. In K(+)-depolarized muscles in the presence of propranolol and tetrodotoxin, N-ethylmaleimide 10(-4) mol l-1 increased the maximum depolarization velocity and the duration of the slow response action potential. The latter effect was transient and was followed by a progressive reduction of the action potential duration. 6. The most likely explanation for the action potential shortening effect of N-ethylmaleimide seems to be an increase of an outward potassium current while the transient inotropic effect of the drug may be caused, at least in part, by an increase of the slow inward calcium current.

Action Potentials↗