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Biomedical subjects

R E Beamish

Publications and source records attributed to R E Beamish.

At least 73 records · Page 4Linked to original sources
PubMed1981

Protective effect of sulfinpyrazone against catecholamine metabolite adrenochrome-induced arrhythmias.

Single intravenous injection of adrenochrome (10 to 50 mg/kg body weight), an oxidation product of catecholamines, has been shown to induce arrhythmias and cause death in anesthetized rats in a dose-dependent manner. Sulfinpyrazone, which is an inhibitor of platelet aggregation, was found to protect animals from these adrenochrome effects. It is suggested that sudden death due to arrhythmias in patients following the first attack of myocardial infarction of during other stressful situations may be linked to the formation of adrenochrome from abnormally high catecholamine levels in blood. Furthermore, results presented here also suggest that the reduction in the mortality rate of patients on sulfinpyrazone therapy may involve an antiarrhythmic property of the drug.

Adrenochrome↗
PubMed1981

Ventricular dysfunction and necrosis produced by adrenochrome metabolite of epinephrine: relation to pathogenesis of catecholamine cardiomyopathy.

We have examined the effects of adrenochrome and other metabolites of epinephrine on the ultrastructure and contractile activity of isolated rat hearts perfused under conditions in which the heart rate and coronary flow were controlled. Perfusion of hearts with epinephrine or metanephrine significantly increased contractile force; vanillylmandelic acid and dihydroxymandelic acid did not alter contractile force development, whereas adrenochrome (50 mg/L) declined contractile force with epinephrine (50 mg/L) was associated with increased resting tension and maximum rates of force development and relaxation, and decreased time for peak tension development and 1/2 relaxation. On the other hand, hearts perfused with adrenochrome showed early decline followed by steady increase in resting tension; maximum rates of force development and relaxation were reduced and times for peak tension development and 1/2 relaxation were increased. Hearts perfused or 10 minutes or more with adrenochrome (50 mg/L), but not epinephrine, metanephrine, dihydroxymandelic acid or vanillylmandelic aicd, showed ultrastructural damage. Adrenochrome concentrations of 10 or 25 mg/L altered the appearance of mitochondria after 30 minutes of perfusion. Infusion of epinephrine (1 mg/L) during perfusion with adrenochrome partially maintained contractile force during the first 15 minutes of perfusion but did not alter the severity of ultrastructural changes due to adrenochrome. These results are consistent with the concept that oxidation products of catecholamines such as adrenochrome are partly responsible for inducing myocardial necrosis and failure following massive catecholamine injections in intact animals.

Adrenochrome↗
PubMed1981

Adrenochrome-induced coronary artery constriction in the rat heart.

Adrenochrome, an oxidation product of epinephrine, has been demonstrated to produce cardiotoxic effects. In this study, we have investigated whether this agent can alter coronary resistance in isolated rat hearts. Concentrations of adrenochrome from 1 to 1000 ng/ml increased coronary pressure in a dose- and time-dependent manner. The highest concentration produced a 3-fold elevation in pressure after a 1-hr perfusion. Myocardial contractile force decreased only with either 100 or 1000 ng/ml of adrenochrome and this effect was evident after substantial elevations in coronary pressure. The elevation in coronary pressure was significantly reduced by two calcium antagonists, verapamil and D-600. Furthermore, the degree of constriction by adrenochrome was dependent on the CaCl2 concentration in the perfusion medium. High concentrations of indomethacin or propranolol attenuated the degree of coronary pressure elevation, whereas acetylsalicylic acid and phenoxybenzamine were without effect. Sulfinpyrazone, which has been shown to reduce the arrhythmogenic action of adrenochrome in vivo, significantly reduced the coronary pressure increases. These results suggest that adrenochrome is a potent coronary constricting agent in the rat heart and its action is seemingly dependent on external Ca++ availability.

Adrenochrome↗
PubMed1981

Influence of reducing agents on adrenochrome-induced changes in the heart.

To elucidate the role of oxidation products of catecholamines play in myocardial necrosis, we examined the effects that adrenochrome in the presence of some reducing agents and that autoxidized solution of adrenochrome have on the ultrastructure and force of contraction in the isolated rat heart. Addition of ascorbic acid (1 mM) or cysteine (0.5 mM) into a perfusion medium containing 25 mg/L of adrenochrome produced ultrastructural damage greater than that seen with adrenochrome alone, whereas addition of dithiothreitol (0.5 mM) did not. The rate of failure of the heart due to adrenochrome was accelerated by use of ascorbic acid and dithiothreitol. Reduction of adrenochrome into other oxidation products of catecholamines by these reducing agents was indicated by the results of spectral analysis studies. Myocardial damage or contractile failure did not occur if the adrenochrome solution was allowed to autoxidize for 24 hours before perfusion. These data indicate that oxidation products of epinephrine other than adrenochrome are involved in the genesis of catecholamine-induced cardiotoxicity. This effect may occur through the formation of cardiotoxic free radicals, as well as through interaction of these oxidation products with sulfhydryl groups.

Adrenochrome↗
PubMed1980

Effects of adrenochrome on calcium accumulating and adenosine triphosphatase activities of the rat heart microsomes.

The influence of adrenochrome (1-100 microgram/ml or 5.6 x 10(-6)-5.4 x 10(-4) M) on microsomal calcium binding, calcium uptake and Ca++-stimulated Mg++-dependent adenosine triphosphatase (ATPase) activities was studied in vitro. Adrenochrome decreased microsomal calcium binding, calcium uptake and Ca++-stimulated Mg++-dependent ATPase activities. The inhibitory effect of adrenochrome on microsomal calcium uptake activity of the isolated membrane was independent of pH (6.0-8.0), calcium concentrations (10-200 muM), protein concentration (0.02-0.10 mg/ml), temperature (25-37 degrees C) and incubation time (2-30 min). Kinetic study of calcium uptake activity in different concentrations of ATP showed that the inhibition was of a mixed type. Perfusion of hearts with adrenochrome resulted in marked depression in contractile force and the microsomal fraction obtained from these hearts showed depressed calcium binding, calcium uptake and Ca++-stimulated Mg++-dependent ATPase activities. The depression in microsomal The influence of adrenochrome (1-100 microgram/ml or 5.6 x 10(-6)-an irreversible nature. It is proposed that cardiodepressant action of adrenochrome may partly be explained on the basis of its inhibitory effect on the calcium transporting ability of the sarcoplasmic reticulum.

Adrenochrome↗
PubMed1980

Protection against adrenochrome-induced myocardial damage by various pharmacological interventions.

Perfusion of the isolated rat heart with Krebs-Henseleit solution containing adrenochrome (25 or 50 mg/l), and oxidation product of catechalmines, resulted in contractile failure and myocardial necrosis. Various pharmacological agents known to protect the myocardium against catecholamine-induced necrosis were also found to be effective against adrenochrome-induced changes in the ultrastructure of the isolated perfused rat heart. The alpha-receptor-blocking drugs tolazoline and Dibenamine (dibenzylchlorethamine), and the adrenergic neurone-blocking agents guanethidine and bretylium did not alter the development of contractile failure and necrosis due to adrenochrome. The beta-receptor-blocking compounds propranolol and practolol effectively protected the heart from adrenochrome-induced necrotic damage, and partially prevented contractile failure. The hydrazine-type monoamine oxidase inhibitor iproniazid completely prevented ultrastructural damage and partially maintained contractile-force development in adrenochrome perfused hearts. The non-hydrazine-type monoamine oxidase inhibitor tranylcypromine partially protected the isolated rat heart against adrenochrome necrosis, but disruption of mitochondrial structure was still seen. Tranylcypromine did not significantly improve contractile force development during adrenochrome perfusion. The calcium antagonist D-600 reduced the severity of adrenochrome-induced ultrastructural damage. These results provide strong support for the view that catecholamine-induced cardiotoxicity is mediated through the formation of adrenochrome.

Adrenochrome↗
PubMed1980

Modification of adrenochrome-induced cardiac contractile failure and cell damage by changes in cation concentrations.

Adrenochrome has been shown to produce cardiac necrosis as well as failure in the isolated rat hearts. These effects of adrenochrome were influenced by alterations in the Ca2+, Na+, K+, and Mg2+ concentrations of the perfusion medium. Increasing the Ca2+ or K+ concentration or decreasing the Na+ concentration of the adrenochrome-containing perfusion medium partially maintained contractile force but increased the severity of ultrastructural damage. Reducing the K+ concentration of the medium did not alter the failure of contractile force development but increased the severity of ultrastructural damage due to adrenochrome. Reducing the Ca2+ or increasing the Mg2+ concentration of the perfusion medium completely prevented myocardial necrosis due to adrenochrome. Omission of Mg2+ from the perfusion medium neither altered the time course of contractile failure nor effected the severity of necrosis due to adrenochrome. These results for the most part parallel the influence of similar ionic interventions on the severity of necrosis produced by excessive amount of catecholamines.

Adrenochrome↗
PubMed1977

Ambulant management of patients with recent myocardial infarction.

Thirty-two patients who had remained ambulant and active after suffering an acute myocardial infarction were observed for 6 months. Complications were present initially in 11 but proved transient. One patient died of a new coronary thrombosis 15 weeks after the initial episode. There were no recurrences among the 31 surviving patients. After the 6 months all but two patients were as well as before the attack; 21 were free of symptoms and there was no undue incidence of objective findings that could be attributed to failure to rest after the attack. It is therefore concluded that, for patients who suffer an acute myocardial infarction, immediate diagnosis and admission to a coronary care unit need not be equated invariably with immobilization in bed. Our experience suggests that selected patients can be allowed moderate activity without ill effects and thus avoid the undesirable consequences of enforced bed rest.

Acute Disease↗
PubMed1965

Heart affairs.

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Canada↗
PubMedDate not supplied

Sarcolemmal Na+-Ca2+ exchange and Ca2+-pump activities in cardiomyopathies due to intracellular Ca2+-overload.

In order to identify defects in Na+-Ca2+ exchange and Ca2+-pump systems in cardiomyopathic hearts, the activities of sarcolemmal Na+-dependent Ca2+ uptake, Na+-induced Ca2+ release, ATP-dependent Ca2+ uptake and Ca2+-stimulated ATPase were examined by employing cardiomyopathic hamsters (UM-X7.1) and catecholamine-induced cardiomyopathy produced by injecting isoproterenol into rats. The rates of Na+-dependent Ca2+ uptake, ATP-dependent Ca2+ uptake and Ca2+-stimulated ATPase activities of sarcolemmal vesicles from genetically-linked cardiomyopathic as well as catecholamine-induced cardiomyopathic hearts were decreased without any changes in Na+-induced Ca2+-release. Similar results were obtained in Ca2+-paradox when isolated rat hearts were perfused for 5 min with a medium containing 1.25 mM Ca2+ following a 5 min perfusion with Ca2+-free medium. Although a 2 min reperfusion of the Ca2+-free perfused hearts depressed sarcolemmal Ca2+-pump activities without any changes in Na+-induced Ca2+-release, Na+-dependent Ca2+ uptake was increased. These results indicate that alterations in the sarcolemmal Ca2+-efflux mechanisms may play an important role in cardiomyopathies associated with the development of intracellular Ca2+ overload.

Adenosine Triphosphatases↗