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Biomedical subjects

A Sawamura

Publications and source records attributed to A Sawamura.

At least 55 records · Page 3Linked to original sources
PubMed1988

Mechanism of the protective action of taurine against isoprenaline induced myocardial damage.

The effect of the sulphur amino acid, taurine, on the biochemical changes induced by a toxic dose of isoprenaline was examined in chick hearts. Isoprenaline treatment (80 and 240 mg.kg-1 subcutaneously twice a day for four days) caused a dose dependent increase in heart to body weight ratio. Isoprenaline administration induced a substantial accumulation of calcium and caused a profound decrease of adenosine triphosphate content and creatine phosphokinase activity in the myocardium. A pronounced increase in lipoperoxide and decrease in phospholipid and reduced glutathione concentrations were also seen. Oral administration of taurine (200 mg.kg-1 for seven days) partially protected against these changes induced by isoprenaline. It is suggested that the beneficial effect of taurine may be due in part to inhibition of lipoperoxide formation and calcium accumulation and to protection against the deterioration of membrane phospholipids.

Adenosine Triphosphate↗
PubMed1987

Mechanism of direct cardiostimulating actions of hydralazine.

The vasodilator, hydralazine, was reported to also exert a direct positive inotropic effect on the myocardium at high concentrations. In the present study we investigated the mechanism of this positive inotropic action by using the ventricular myocardium of isolated perfused chick hearts. Hydralazine (10(-3) M) enhanced contractile force and heart rate, and elevated the myocardial cyclic AMP level. To study the Ca2+-dependent slow action potentials, the fast N+ channels were voltage-inactivated with elevated K+ (25 mM), resulting in a loss of electrical excitability. Hydralazine (10(-4) M) rapidly (less than 3 min) allowed the generation of slow action potentials and accompanying contractions by electrical stimulation. These effects of hydralazine were only partially prevented by propranolol. The results suggest that the increase of myocardial contractility produced by hydralazine is the result, at least in part, of a direct effect on the myocardium to increase Ca2+ inflow. The increased Ca2+ influx and inward slow current is due partly to activation of beta-adrenoceptors, with resultant elevation of cyclic AMP, and partly to another mechanism.

Action Potentials↗
PubMed1987

Acute haemodynamic effect of taurine on hearts in vivo with normal and depressed myocardial function.

The acute haemodynamic effects of taurine were studied in normal and in beta blocker (propranolol) or calcium antagonist (diltiazem) treated rabbits and in rabbits with experimentally produced chronic aortic regurgitation. The administration of taurine (25 mg.kg-1) did not affect heart rate and left ventricular end diastolic pressure but produced significant increases in left ventricular dP/dtmax, cardiac output, and left ventricular systolic pressure in control hearts, indicating that intravascularly administered taurine substantially increased cardiac performance. In propranolol (1 mg.kg-1) treated rabbits taurine significantly improved left ventricular dP/dtmax and cardiac output, which were previously depressed by propranolol. Taurine had the same effect on diltiazem (1 mg.kg-1) treated rabbits. In rabbits with aortic regurgitation a bolus injection of taurine improved cardiac performance. Continuous infusion of taurine (100 mg.h-1) also produced a significant increase in left ventricular dP/dtmax. These results suggest that taurine has a unique action as an inotropic agent and that it may be useful in the treatment of patients with congestive heart failure.

Animals↗
PubMed1986

Protective effect of taurine against decline of cardiac slow action potentials during hypoxia.

The effect of taurine on cardiac slow action potentials (APs) during hypoxic superfusion was studied in isolated guinea-pig papillary muscles. Ca2+-dependent slow APs were induced by isoproterenol (10(-6) M) in preparations which were voltage-inactivated by high (25 mM) K+. Although taurine had no effect on the slow AP parameters during normoxia, taurine (10 mM) superfusion significantly protected against the decline of slow APs produced by hypoxia. Taurine also restored slow APs that had been previously abolished by hypoxia. Therefore, taurine exposure may protect the Ca2+ slow channels which are inhibited or blocked by hypoxic conditions.

Action Potentials↗
PubMed1986

Beneficial effect of taurine in rabbits with chronic congestive heart failure.

To examine the effect of daily treatment with taurine on improving the status of congestive heart failure (CHF), we used rabbits with artificially induced aortic regurgitation. Ten rabbits were treated daily with taurine (100 mg/kg by mouth) and eight with guanidinoethyl sulfonate (GES) (100 mg/kg by mouth) immediately after induction of aortic regurgitation. The cumulative mortality rate at 8 weeks in the taurine-treated CHF group was 10% (1 of 10) compared with 53% (16 of 30) in the nontreated CHF group and 75% (6 of 8) in the GES-treated CHF group (p less than 0.05). Although cardiac function (max dP/dt) in CHF rabbits was significantly decreased (p less than 0.001), taurine-treated CHF rabbits maintained the same values as control rabbits. Taurine content of the left ventricular tissue of the CHF rabbits was significantly increased (p less than 0.01). Administration of taurine and GES to control rabbits for 8 weeks affected neither the hemodynamics nor the taurine content of the heart. It was concluded that taurine slowed the rapid progression of heart failure and consequently prolonged life expectancy.

Animals↗
PubMed1986

Effects of taurine on the electrical and mechanical activities of embryonic chick heart.

The effect of taurine (2-aminoethanesulphonic acid) on myocardial slow action potentials (APs) and accompanying contractions was examined in isolated perfused chick hearts and reaggregated cultured cells. Isoproterenol (ISO), histamine (HIS), or tetraethylammonium (TEA) induced slow APs and contractions in hearts whose fast Na+ channels had been inactivated by elevated K+. Taurine (10 mM) not only failed to induce slow APs, but actually decreased ISO (10(-8) M), HIS (10(-4) M), or TEA (10 mM) induced slow APs and contractions transiently (about 30s-2 min after the addition of taurine). The properties of the slow APs recovered to control levels by 7-13 min after the addition of the taurine; at this time, there was an increase in developed tension of the contraction accompanying the slow APs. These results suggest that the positive inotropic action of taurine is not mediated through an increase in the slow inward Ca2+ current. However, the transient depression of Ca2+-dependent slow APs by taurine probably explains the transient negative inotropic effect of taurine.

Action Potentials↗
PubMed1986

Stimulation of cardiac slow Ca++ current by high concentration of cimetidine.

Electrophysiological studies on the cardiac effects of a H2-antagonist, cimetidine, were examined in three kinds of preparations: guinea-pig papillary muscles, rat left atria and perfused chick hearts. Cimetidine (10(-5) to 10(-4) M) depressed or abolished the slow action potentials (APs) induced by histamine (10(-5) to 10(-4) M) in hearts whose fast Na+ channels had been inactivated by 25 mM K+. Higher concentrations of cimetidine (10(-3) to 5 X 10(-3) M) increased myocardial cyclic AMP level and allowed the generation of slow APs in such inexcitable tissues. These cimetidine-induced slow APs were not prevented by propranolol (10(-6) to 10(-5) M) or pretreatment with 6-hydroxydopamine (50 mg/kg). These results suggest that cimetidine, in doses higher than that required to block cardiac H2-receptors, may have a cardio-stimulating action mediated through increase of inward Ca++ current.

Action Potentials↗
PubMed1985

Taurine's possible protective role in age-dependent response to calcium paradox.

When hearts were reperfused with Ca++ after a short period of Ca++-free perfusion, irreversible loss of electrical and mechanical activity was observed. This phenomenon, first described by Zimmerman and Hulsmann, was termed the "calcium paradox". Chizzonite and Zak recently reported that rat hearts exhibited an age-dependent response in a calcium paradox model. The taurine (2-aminoethanesulfonic acid) content of hearts in the newborn animal is high, and decreases rapidly during the first few days of life. The present experiments were performed to test whether the myocardial taurine content was closely linked to an age-dependent response in the calcium paradox model, using post-hatched chicks. The mechanical dysfunction of the heart was much more severe in 9-day-old post-hatched chicks than in 2-day-old chicks when the hearts were subjected to the calcium paradox. Myocardial taurine content was lower in the 9-day-old chicks than in the 2-day-old chicks. The age-related response to the calcium paradox was partially protected by oral pretreatment with taurine, and there was a small increase in myocardial taurine level. It is proposed that myocardial taurine is one factor in the protection against the calcium paradox phenomenon.

Administration, Oral↗
PubMed1985

Therapeutic effect of taurine in congestive heart failure: a double-blind crossover trial.

In a double-blind, randomized, crossover, placebo-controlled study, we investigated the effects of adding taurine to the conventional treatment in 14 patients with congestive heart failure for a 4-week period. Compared with placebo, taurine significantly improved the New York Heart Association functional class (p less than 0.02), pulmonary crackles (p less than 0.02), and chest film abnormalities (p less than 0.01). A benefit of taurine over placebo was demonstrated when an overall treatment response for each patient was evaluated on the basis of clinical examination (p less than 0.05). No patient worsened during taurine administration, but four patients did during placebo. Pre-ejection period (corrected for heart rate) decreased from 148 +/- 14 ms before taurine treatment to 137 +/- 12 ms after taurine (p less than 0.001), and the quotient pre-ejection period/left ventricular ejection time decreased from 47 +/- 9 to 42 +/- 8% (p less than 0.001). Side effects did not occur in the patients during taurine. The results indicate that addition of taurine to conventional therapy is safe and effective for the treatment of patients with congestive heart failure.

Administration, Oral↗
PubMed1985

Effects of methyl linoleate hydroperoxide and hydrogen peroxide on N-nitrosation of dimethylamine.

The effects of methyl linoleate hydroperoxide and hydrogen peroxide on the N-nitrosation of dimethylamine were investigated. Hydrogen peroxide inhibited the formation of N-nitrosodimethylamine by the reaction of dimethylamine and nitrite in citrate buffer (pH 3-5). The inhibitory effect was due to the loss of available nitrite by quantitative conversion into nitrate. The formation of N-nitrosodimethylamine from the reaction of dimethylamine and nitrous acid in chloroform was effectively inhibited by methyl linoleate hydroperoxide. The inhibitory effect of the hydroperoxide was much greater than that of methyl linoleate. The loss of nitrous acid from the reaction mixture was due to the conversion of nitrous acid into nitric acid and the formation of two adducts, both of which contained nitrogen and had peroxide and carbonyl or carbonyl-liberating functions. It is suggested that unsaturated fatty acids and lipid hydroperoxides are effective inhibitors of nitrosamine formation.

Chromatography, Thin Layer↗
PubMed1984

Enhanced suppression of myocardial slow action potentials during hypoxia by free fatty acids.

Effects of free fatty acids (palmitate and linoleate) on myocardial contractility and slow action potentials (APs) were examined in Langendorff-perfused chick hearts. To study the slow APs exclusively, the fast Na+ channels were voltage-inactivated in elevated K+ (25 mM), and the concentration of Ca2+ ion was increased to 5.4 mM in order to induce slow APs. Palmitate (0.18, 0.54 or 0.72 mM) along with albumin (0.12 mM) was added to the perfusate. Albumin by itself did not affect contractility or the slow APs during normoxia and hypoxia. Under well oxygenated conditions, palmitate had no effect on contractility or the slow APs. However, palmitate accelerated the decline of contractility during hypoxia in a dose-dependent fashion. Hypoxia suppressed the slow APs, and palmitate and linoleate further exacerbated the suppression of slow APs produced by hypoxia. Nevertheless, palmitate and linoleate did not enhance the hypoxic reduction of the tissue high energy phosphate level. The present results suggest that free fatty acids elicit cardio-depressant effects on hearts through their direct action on the myocardial cell membrane (slow channels) rather than through any metabolic effects.

Adenosine Triphosphate↗
PubMed1984

Beneficial effect of taurine on congestive heart failure induced by chronic aortic regurgitation in rabbits.

Taurine (2-aminoethanesulfonic acid) is known to have a cardiotonic action. The present study was designed to see whether oral treatment with taurine could improve the status of congestive heart failure induced by aortic regurgitation. Nine rabbits were treated daily with taurine (100 mg/kg) after producing aortic regurgitation. Cumulative mortality at 8 weeks in the non-treated group was 52% compared with 11% in the taurine-treated group (p less than 0.05). Cardiac function (max dP/dt) was significantly decreased in rabbits with aortic regurgitation, whereas in taurine-treated rabbits, cardiac function was maintained the same as control. The present data suggest that taurine prevented the rapid progress of heart failure, and consequently prolonged the life expectancy.

Animals↗
PubMed1983

Concentration-dependent effect of trapidil on slow action potentials in cardiac muscle.

Trapidil, a coronary vasodilator and positive inotropic agent, was tested for its ability to affect the normal "fast" action potentials and the "slow" action potentials and contractions of isolated perfused chick hearts, and to affect the tissue cyclic AMP level. At 5 X 10(-3) M, trapidil completely blocked the fast Na+ channels in hearts perfused with normal Tyrode solution, since this dose abolished the action potential when verapamil (2 X 10(-6) M) was present to eliminate the inward slow current. To study effects on the slow channels, the fast Na+ channels were voltage-inactivated by partial depolarization to about -40 mV with an elevated (25 mM) K+-Tyrode solution, resulting in loss of excitability. At low concentrations (1 X 10(-4) - 1 X 10(-3) M), trapidil induced slow action potentials accompanied by contractions, even in the presence of a beta-adrenergic blocker. In contrast, at high concentrations (3 X 10(-3) - 1 X 10(-2) M), trapidil markedly depressed or blocked the isoproterenol-induced slow action potentials. Consistent with this dual action, in hearts perfused with normal Tyrode solution, trapidil exerted a small positive inotropic action at low doses and a considerable negative inotropic action at high doses, even though the intracellular cyclic AMP level was substantially elevated. That is, trapidil has actions similar to those of papaverine. It is concluded that trapidil blocks both fast Na+ channels and slow channels in cardiac muscle, the fast Na+ channels being more sensitive, and that low concentrations of trapidil induce slow channels by elevating the cyclic AMP level because of phosphodiesterase inhibition.

Action Potentials↗
PubMed1983

Protection by oral pretreatment with taurine against the negative inotropic effects of low-calcium medium on isolated perfused chick heart.

Chicks were given taurine by mouth using a cannula pushed down into the oesophagus. This treatment had protected the heart, when subsequently removed, against the decline of contractile force in the perfused heart brought about by low-calcium media. A small but statistically significant increase in taurine concentration occurred in the ventricular tissue of such pretreated hearts. In contrast, pretreatment with taurine did not affect ventricular calcium level. Addition of taurine (3 to 100 mmol . litre-1) into the perfusing solution did not alter the cyclic AMP level in the control perfused hearts, and failed to induce slow channel action potentials in hearts whose fast Na+ channels had been inactivated by high K+ (25 mmol . litre-1). However, taurine perfusion produced a significant positive inotropic action which became stable after 5 to 10 min of exposure.

Administration, Oral↗
PubMed1983

Therapy of congestive heart failure with orally administered taurine.

The clinical efficacy of 2 gm BID of oral taurine (2-aminoethane sulfonic acid) was studied in 24 patients with congestive heart failure (CHF). We expressed the severity of CHF by a score based on clinical signs and symptoms and on roentgenographic data. The maximum possible score, corresponding to the worst CHF, was 23 points. How much the 24 patients improved after receiving taurine for four or eight weeks was estimated by the difference between their pretreatment and posttreatment scores. In 19 of the 24 patients, taurine was effective. In the group as a whole, mean (+/- SEM) scores fell significantly, from 7.3 +/- 0.6 before treatment to 4.4 +/- 0.5 after treatment. Thirteen of the 15 patients who were designated as New York Heart Association (NYHA) functional class III or IV before receiving taurine could be designated as class II after they completed the study. This pilot study should prompt further investigation into the possible use of taurine in the treatment of patients with CHF.

Administration, Oral↗