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Biomedical subjects

H G Zimmer

Publications and source records attributed to H G Zimmer.

At least 73 records · Page 4Linked to original sources
PubMed1989

[The effect of allopurinol on the synthesis of adenine nucleotides and ribonucleic acid from inosine via a salvage pathway in the brain of rats].

The authors investigated in experiments on rats the action of allopurinol and isoproterenol on the metabolism of adenine nucleotides and the total fraction of ribonucleic acids in the brain, liver heart and kidneys. It was revealed that allopurinol enhances the synthesis of adenine nucleotides from administered inosine in the brain and liver of rats. In the heart and kidneys allopurinol did not affect the synthesis of these compounds. Isoproterenol has a more marked effect on the metabolism of adenine nucleotides in the heart only: it reduced the amount of adenine nucleotides and enhanced their synthesis from inosine. It is assumed that the protective effect of allopurinol on the restoration of the reduced amount of these substances in brain and liver after their ischaemization could take place also by their increased resynthetization from accumulated inosine.

Adenine Nucleotides↗
PubMed1987

Combination of ribose with calcium antagonist and beta-blocker treatment in closed-chest rats.

In previous studies ribose has been recognized as a substrate that has beneficial effects on myocardial metabolism. It leads to an elevation of the available 5-phosphoribosyl-1-pyrophosphate pool and stimulates adenine nucleotide de novo synthesis in the rat heart under control and various pathophysiological conditions (Zimmer and Gerlach, 1978; Zimmer and Ibel, 1983, 1984). When the clinical application of ribose in patients with heart disease is envisaged, it is understood that conventional cardiac therapy must be continued. It is therefore necessary to demonstrate in animal experiments that ribose retains its stimulating metabolic effect when administered in conjunction with therapeutically used drugs. In this study we have selected representatives of two pharmacological principles, the calcium antagonist verapamil and the beta 1-specific adrenoceptor blocker metoprolol. Measurements of functional parameters in closed-chest rats revealed that i.v. administration of ribose alone for 24 h (200 mg/kg/h) had no hemodynamic or vasoactive influence, whereas verapamil and metoprolol (i.v. infusion of 2 mg/kg/h each for 24 h) induced negative chronotropic and negative inotropic effects. Cardiac output was reduced by metoprolol, but not by verapamil. Ribose did not affect these drug-induced hemodynamic alterations, and verapamil as well as metoprolol did not interfere with the characteristic metabolic effect of ribose, the stimulation of cardiac adenine nucleotide de novo synthesis. Administration of ribose in combination with these pharmacological agents is therefore compatible.

Adenine Nucleotides↗
PubMed1986

Metabolic aspects of the development of experimental cardiac hypertrophy.

In three models of cardiac hypertrophy the significance of catecholamines and the adenylate cyclase-cyclic AMP-system was examined. Two approaches were utilized: 1. The time course of cyclic AMP alterations was correlated with the changes in adenine nucleotide and protein biosynthesis. 2. The effect of beta-receptor blockade on the obligatory increase in adenine nucleotide and protein synthesis was evaluated. In isoproterenol-elicited cardiac hypertrophy, the elevation of the cyclic AMP content was one of the earliest metabolic alterations preceding the enhancement of the biosynthesis of adenine nucleotides and proteins. beta-Receptor blockade with propranolol abolished the increase in adenine nucleotide synthesis. In pressure-induced cardiac hypertrophy due to constriction of the abdominal aorta, catecholamines and the adenylate cyclase-cyclic AMP-system were found not to play a significant role. In triiodothyronine-elicited hypertrophy, the cyclic AMP level was increased very early, but beta-receptor blockade did not prevent hypertrophy nor the enhancement of cardiac adenine nucleotide biosynthesis, although the positive chronotropic and inotropic effects of triiodothyronine were abolished. This result can best be interpreted to indicate a direct effect of triiodothyronine on myocardial carbohydrate metabolism including the pentose phosphate pathway.

Adenine Nucleotides↗
PubMed1986

Metabolic recovery following temporary regional myocardial ischemia in the rat.

The restoration of the cardiac ATP content after an ischemic insult takes a long period of time. Ribose, via stimulation of adenine nucleotide biosynthesis, accelerated the replenishment of the adenine nucleotide pool in the heart, in the kidney, however, it had no effect. In the myocardium, the ribose-mediated restoration of the adenine nucleotide content was dependent on the duration of the previous ischemic period and was not influenced by the beta-receptor blocker atenolol.

Acute Disease↗
PubMed1985

Effects of inosine on cardiac adenine nucleotide metabolism in rats.

Inosine was administered as a continuous intravenous infusion (100 mg/kg per hr) in rats treated with isoproterenol (25 mg/kg, s.c.). After 24 hr, the isoproterenol-induced decline in myocardial ATP and total adenine nucleotides was attenuated by inosine. Infusion of ribose (100 mg/kg per hr) had a similar cardioprotective influence. The effect of inosine may have been due to the incorporation into cardiac adenine nucleotides of the degradation products of inosine, either of the ribose moiety via the de novo synthesis pathway or of hypoxanthine via the salvage pathway utilizing 5-phosphoribosyl-1-pyrophosphate. To decide this, [8-(14)C]inosine was injected intravenously 4 hr after administration of isoproterenol. Its incorporation into myocardial adenine nucleotides was enhanced. Furthermore, the effect of inosine on the de novo synthesis of adenine nucleotides in normal and isoproterenol-stimulated hearts was studied and compared to that of ribose. The normal rate was attenuated and the isoproterenol-elicited increase was reduced by inosine. In contrast, ribose stimulated adenine nucleotide biosynthesis in the control rat heart and potentiated the isoproterenol-induced enhancement. These results indicate that the effect of inosine is not due to the metabolism of ribose-1-phosphate via the pentose phosphate and the de novo synthesis pathways, but rather to the 5-phosphoribosyl-1-pyrophosphate-dependent salvage of hypoxanthine. Obviously, this pathway is of such a magnitude that the isoproterenol-evoked decline in myocardial adenine nucleotide levels is attenuated.

Adenine Nucleotides↗
PubMed1984

Ribose intervention in the cardiac pentose phosphate pathway is not species-specific.

Ribose is cardioprotective in the rat in a variety of pathophysiological conditions. The metabolic basis for this effect is the low capacity of the oxidative pentose phosphate pathway in the myocardium. Ribose bypasses this pathway, elevates the available pool of 5-phosphoribosyl-l-pyrophosphate, and thus stimulates the biosynthesis of adenine nucleotides. In this study reported here the activity of glucose-6-phosphate dehydrogenase, the first and rate-limiting enzyme of the oxidative pentose phosphate shunt, was very low in the human heart and was of the same order of magnitude in the myocardium of various animal species. Furthermore, ribose had a similar stimulating effect on myocardial adenine nucleotide biosynthesis in the guinea pig, in which hemodynamic parameters are different from those in the rat. It is concluded that the metabolic basis for the effectiveness of ribose is similar in all species investigated.

Adenine Nucleotides↗
PubMed1984

Ribose accelerates the repletion of the ATP pool during recovery from reversible ischemia of the rat myocardium.

It is a characteristic feature of the myocardium that the derangement in function [6] and the depletion of the ATP pool [1, 2, 9] that occur subsequent to oxygen deficiency persist when blood flow is restored. Of renewed interest is the inability of the heart to replenish rapidly its adenine nucleotide pool once it has been diminished during a brief period of regional ischemia [2, 9]. A hypothesis that could explain this metabolic insufficiency of the myocardium is that the biosynthesis of adenine nucleotides is very slow in the normal heart and is increased only moderately during postischemic recovery [15] so that the replenishment of adenine nucleotides is not affected appreciably. To substantiate such a hypothesis it is necessary to provide evidence that the restitution of the ATP pool can be accelerated by stimulation of this biosynthetic process. In previous studies ribose has been recognized as a substrate that enhances markedly adenine nucleotide biosynthesis in the rat heart [11, 12]. We now demonstrate that continuous i.v. infusion of ribose during recovery from a 15-min period of myocardial ischemia in rats leads to restoration of the cardiac ATP pool within 12 h, whereas 72 h are needed for ATP normalization without any intervention.

Adenosine Triphosphate↗
PubMed1984

Correlation between haemodynamic and metabolic changes in three models of experimental cardiac hypertrophy.

Three models of cardiac hypertrophy (aortic constriction, application of isoproterenol, daily injections of triiodothyronine) were characterized in haemodynamic and in metabolic terms. Heart function was evaluated in closed-chest rats after catheterization of the left ventricle with an ultraminiature catheter pressure transducer. Heart rate (HR), left ventricular systolic pressure (LVSP), and the maximal rate of rise of left ventricular pressure (LV dP/dtmax) were measured. The metabolic parameters determined included the levels of cardiac cyclic AMP and the rates of the biosynthesis of myocardial adenine nucleotides. During the first 72 h after aortic constriction, HR was decreased, whereas LVSP and LV dP/dtmax were both elevated. Within 12 h after administration of isoproterenol, HR and LV dP/dtmax were markedly increased, while LVSP was depressed. In triiodothyronine-treated animals, all haemodynamic parameters were elevated during the first 72 h. Comparison with the time course of changes in metabolic parameters revealed that the rise in cardiac contractility measured as LV dP/dtmax occurred at about the same time as the increase in the content of myocardial cyclic AMP in the isoproterenol- and triiodothyronine-models. In hypertrophy due to aortic constriction, cardiac cyclic AMP was elevated only moderately, and this elevation did not correlate with the enhancement of contractility. Beta-receptor-blockade with propranolol prevented entirely the increase of myocardial adenine nucleotide biosynthesis in the isoproterenol- and triiodothyronine- but not in pressure-induced hypertrophy.

Adenine Nucleotides↗
PubMed1984

A "high-performance" 2D gel scanner.

We describe the design principles of a photometric flatbed scanner with a scan area of 250 X 250 mm2, a dynamic range of 4000 gray levels, a signal/noise ratio of 2000/1, a step size of 0.1 mm, and a step frequency of 2000 steps per second. It is controlled by a microcomputer and used to acquire data for quantitative evaluation of gels or chromatograms. The performance of the instrument is demonstrated by the data obtained by scanning gratings, gray step filters, and high-resolution electropherograms.

Electronic Data Processing↗
PubMed1984

Spot identification in two-dimensional patterns by a least-squares template matching.

The coordinates of the center of measured spots are nonlinearly transformed to get an optimal match between the transformed coordinates and the given coordinates of a reference pattern. The parameters of the transformation are determined by the minimum of a function of squared distances between all spots of the sample and of the reference pattern. The algorithm requires a priori defined correspondences between some pivot points in the sample and the reference and treats their distances differently from the others. The parameters of the transformation are the solutions of a system of nonlinear equations; their numerical values are obtained by iteration.

Amino Acids↗
PubMed1983

Normalization of depressed heart function in rats by ribose.

Severe constriction of the abdominal aorta and simultaneous injection of isoproterenol in rats induced depression in heart function and reductions in cardiac adenosine triphosphate and total adenine nucleotides. When ribose was continuously infused for 24 hours, biosynthesis of cardiac adenine nucleotides was stimulated to such an extent that the reductions in adenosine triphosphate and total adenine nucleotides were prevented and left ventricular hemodynamic parameters were normal. These results support the hypothesis that adenosine triphosphate is primarily responsible for depression in myocardial contractility and that ribose is cardioprotective through its pronounced effects on adenine nucleotide metabolism in heart muscle.

Adenine Nucleotides↗
PubMed1983

Effects of ribose on cardiac metabolism and function in isoproterenol-treated rats.

Continuous iv infusion of ribose for 5 h in unanesthetized and unrestrained rats treated with isoproterenol (25 mg/kg sc) further enhanced the available pool of 5-phosphoribosyl-1-pyrophosphate and the biosynthesis of adenine nucleotides in the myocardium. The increase in adenine nucleotide biosynthesis was of such an extent that the isoproterenol-induced decline of the ATP level (mumol/g) was attenuated after 5 h (isoproterenol + ribose infusion 4.0 +/- 0.2, n = 10; isoproterenol + NaCl infusion 3.5 +/- 0.1, n = 23; control 4.5 + 0.1, n = 38) and prevented after 24 h (isoproterenol + ribose infusion 4.6 +/- 0.3, n = 5; isoproterenol + NaCl infusion 3.2 +/- 0.1, n = 9). Ribose, however, did not affect the isoproterenol-elicited elevation of the adenosine 3',5'-cyclic monophosphate (cAMP) and glucose 6-phosphate content nor did it influence the decline in glycogen. Thus ribose acts primarily via elevation of the cardiac 5-phosphoribosyl-1-pyrophosphate pool. Measurements of hemodynamic parameters with an ultraminiature catheter pressure transducer in intact rats anesthetized with thiobutabarbital sodium revealed that ribose infusion for at least 3 h further enhanced the isoproterenol-elicited increase in left ventricular dP/dtmax by about 20% but did not influence appreciably the rise in heart rate and the fall in left ventricular systolic pressure. Since ribose did not affect the immediate hemodynamic alterations induced by isoproterenol, it appears that it exerts its hemodynamic effects via the pronounced influence on cardiac adenine nucleotide metabolism.

Adenine Nucleotides↗
PubMed1982

Possible role of oxidized glutathione for the regulation of the myocardial hexose monophosphate shunt.

Infusion of the isolated perfused Langendorff rat heart with tert-butyl hydroperoxide (3 X 10(-4) M) resulted in a marked enhancement of the concentration of oxidized glutathione, in an increase of the NADP+/NADPH ratio, and in an elevation of the available pool of 5-phosphoribosyl-1-pyrophosphate, which is one of the end products of the hexose monophosphate shunt. Since it has been shown that oxidized glutathione overcomes the inhibition of glucose-6-phosphate dehydrogenase exerted by NADPH, these results suggest that the myocardial hexose monophosphate shunt can be stimulated rapidly and markedly through this control mechanism.

Animals↗