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Biomedical subjects

H G Zimmer

Publications and source records attributed to H G Zimmer.

At least 19 recordsLinked to original sources
PubMed1992

Effects of ribose on exercise-induced ischaemia in stable coronary artery disease.

There is no established treatment specifically aimed at protecting or restoring cardiac energy metabolism, which is greatly impaired by ischaemia. Even after reperfusion, myocardial content of ATP remains low for more than 72 h. Long-term post-ischaemic dysfunction and irreversibility of ischaemic damage have been associated with low ATP content. Evidence that the pentose sugar ribose stimulates ATP synthesis and improves cardiac function led us to test the possibility that ribose increases tolerance to myocardial ischaemia in patients with coronary artery disease (CAD). 20 men with documented severe CAD underwent two symptom-limited treadmill exercise tests on 2 consecutive days; we postulated that the ischaemia induced might bring about changes in ATP metabolism lasting for several days. Patients whose baseline tests showed reproducibility were randomly allocated 3 days of treatment with placebo or ribose 60 g daily in four doses by mouth. Exercise testing was repeated after treatment on day 5. At that time mean (95% confidence interval) treadmill walking time until 1 mm ST-segment depression was significantly greater in the ribose than in the placebo group (276 [220-331] vs 223 [188-259] s; p = 0.002). The groups did not differ significantly in time to moderate angina. In the ribose-treated group the changes from baseline to day 5 in both time to ST depression and time to moderate angina were significant (p less than 0.005), but these changes were not significant in the placebo group. In patients with CAD, administration of ribose by mouth for 3 days improved the heart's tolerance to ischaemia. The presumed effects on cardiac energy metabolism offer new possibilities for adjunctive medical treatment of myocardial ischaemia.

Aged↗
PubMed1992

Nuclear DNA content and nucleation patterns in rat cardiac myocytes from different models of cardiac hypertrophy.

Nuclear DNA content and number of nuclei were examined in cardiac myocytes isolated from controls and rats with volume and pressure overload hypertrophy to determine if haemodynamic overload alters these nuclear parameters. The experimental groups were comprised of normotensive (WKY) and Spontaneously Hypertensive rats (SHR). Additionally, Sprague-Dawley rats with aortic constriction (AC), pulmonary stenosis (PS), myocardial infarction (MI), and 5 month arteriovenous fistulas (F) were studied along with appropriate shams for each of these groups. Nuclear DNA content was measured from DAPI-stained nuclei using an image analysis microdensitometry system. Myocyte volume was measured with a Coulter Channelyzer system. Approximately 83% of the left ventricular myocytes from the SHR and WKY groups contained a diploid DNA content with the remainder being tetraploid. The remaining experimental and sham groups, all female Sprague-Dawley rats (SD), were approximately 93% diploid. The nucleation patterns differed slightly between rat strains with the SHR/WKY expressing approximately 85% binucleation, 14% mononucleation and 5% tri- or tetranucleation. All SD groups, control and hypertrophied, showed approximately 89% binucleation, and 10% mononucleation with the remainder being tri- or tetranucleated. In summary: (1) cardiac myocytes from SHR/WKY strains are predominantly diploid but to a lesser degree than myocytes from SD; (2) nuclear number follows the same pattern with SHR/WKY showing a smaller percentage of binucleated myocytes than SD myocytes; (3) neither the duration, severity, or type of overload caused a significant change in the extent of polyploidy in overloaded hearts from SD rats; and (4) the extent of polyploidy in cardiac myocytes from both the right and left ventricles of SHR and WKY animals does not differ statistically.

Animals↗
PubMed1992

Effects of norepinephrine on the oxidative pentose phosphate pathway in the rat heart.

To examine whether stimulation of alpha-adrenergic receptors may affect the oxidative pentose phosphate pathway (PPP) in the rat heart, norepinephrine (NE) and the alpha-adrenergic agonist norfenephrine were used. NE was administered as a continuous intravenous infusion in awake rats for 3 days. It stimulated the activity of cardiac glucose-6-phosphate dehydrogenase (G-6-PD), the first and regulating enzyme of the oxidative PPP, in a dose-dependent manner. With the highest dose (0.2 mg.kg-1.hr-1), there was also a time-dependent enhancement. The increase observed after 48 hours was attenuated partially by the beta-receptor blocker metoprolol and the alpha-receptor blocker prazosin. It was entirely abolished when both drugs were administered. Carvedilol, a beta-adrenergic blocker and vasodilator with alpha 1-blocking activity (0.5 mg.kg-1.hr-1), prevented the NE-induced increase in cardiac G-6-PD activity, in functional parameters (heart rate, left ventricular systolic pressure, and left ventricular dP/dtmax), and in the heart weight/body weight ratio. The alpha-adrenergic stimulator norfenephrine increased myocardial G-6-PD activity; prazosin prevented this stimulation. NE and norfenephrine also elevated the available pool of cardiac 5-phosphoribosyl-1-pyrophosphate. G-6-PD activity was enhanced in cardiac myocytes freshly isolated from the left ventricle of rats that had received NE infusion for 3 days (12.3 +/- 1.4 units/g protein) compared with control rats (1.5 +/- 0.4 units/g protein). The activity of 6-phosphogluconate dehydrogenase, one of the enzymes in the oxidative PPP, was elevated only moderately from 12.7 +/- 0.7 to 19.1 +/- 1.4 units/g protein. Combined alpha- and beta-receptor blockade with carvedilol attenuated these effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1992

Development and modulation of experimental right ventricular hypertrophy in rats.

Two models of right ventricular (RV) hypertrophy in rats have been created and characterized: chronic myocardial infarction and pulmonary artery stenosis. A Millar ultraminiature catheter pressure transducer designed specifically for right heart catheterization was used for the measurement of RV function in closed-chest, anesthetized rats. Four weeks after coronary artery ligation, left ventricular (LV) function was depressed as evidenced by the reduction of LV systolic pressure (LVSP), the maximal rate of rise in LV pressure (LV dp/dtmax), cardiac output, and by the elevation of LV end-diastolic pressure (LVEDP). There was an increase in RVSP and an elevation in RV dp/dtmax as well as an increase in the RV weight/body weight ratio. Myocytes isolated from the RV 4 weeks after coronary artery ligation had a greater volume and cross-sectional area. In addition, 14 days after pulmonary artery stenosis, there also was an elevation in RVSP and in RV dp/dtmax. In this model, the effect of angiotensin-converting enzyme (ACE) inhibition with ramipril (1 mg/kg daily) was examined. The increase in RVSP from 35 +/- 2 to 61 +/- 4 mm Hg after pulmonary artery stenosis was not influenced by ramipril (63 +/- 4 mm Hg), neither was the elevation of RV weight. However, the increase in cell volume and cross-sectional area of myocytes isolated from the RV was less pronounced in the ramipril-treated group (+27% compared with +58% in untreated animals). Thus, ACE inhibition with ramipril altered the hypertrophic response at the cellular level.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Energy metabolism of the hypertrophied heart studied by 31P nuclear magnetic resonance.

We report studies on the isolated hearts of rats treated with triiodothyronine (0.2 mg/kg daily) for 14 days, on spontaneously hypertensive rats (12 and 21 weeks old, Lyon strain) and on their respective controls. A 30% increase in cardiac weight was developed with triiodothyronine and a 40% increase in heart weight in the presence of spontaneous hypertension. The hearts were perfused in the presence of 2 mM pyruvate and the intracellular content of phosphocreatine, inorganic phosphate and ATP measured by nuclear magnetic resonance spectroscopy with 31P. The left ventricular developed pressure was measured with an intraventricular balloon. Changes in contractile strength were induced by stepwise modifications of the extracellular concentration of calcium from 0.5 mM to 1.0, 1.5 and 2.0 mM. In all experimental groups, each increase in the extracellular calcium induced an increase in the developed pressure, together with a decrease in phosphocreatine and an increase in inorganic phosphate; the ATP level remained unchanged. These metabolic changes increased progressively with the increase in developed pressure. In the hearts of animals treated with triiodothyronine and of the 21 weeks old hypertensive rats, the extent of changes in phosphocreatine and inorganic phosphate was the same as in the controls; but, in the hearts of 12 weeks old hypertensive rats, the changes were significantly greater than in their controls. These observations suggest that, during the development of cardiac hypertrophy from spontaneous hypertension, there is a transitory deficiency in the capacity for aerobic ATP production relative to the rate of hydrolysis of ATP induced by an inotropic effect.

Adenosine Triphosphate↗
PubMed1979

Long-term effects of ribose on adenine nucleotide metabolism in isoproterenol-stimulated hearts.

1. Among the precursor substances tested 1-14C-glycine is the most suitable for measuring rates of AN biosynthesis in rat hearts in vivo. 2. Continuous i.v. infusion of ribose for 24 hours stimulates AN biosynthesis in normal hearts and amplifies the enhancement of this process in hearts of isoproterenol-treated rats. The isoproterenol-induced decline of myocardial ATP is prevented by long-term application of ribose. 3. Elevation of the available PRPP pool mainly mediated by ribose and release of feedback inhibition of PRPP amidotransferase activity by the isoproterenol-induced ATP decline appear to be the optimal conditions required for maximal stimulation of myocardial AN biosynthesis.

Adenine Nucleotides↗
PubMed1979

Digital picture analysis in microphotometry of biological materials.

Automatic evaluation of two-dimensional thin-layer-chromatograms exemplarily demonstrates the applicability of signal processing, image analysis, and pattern recognition to microphotometry by an enlarged dynamic range of the photometer, improved reproducibility by noise reduction, discrimination between objects and background, feature extraction and automatic classification of the results. Emphasis is put on simple procedures which are tested in routine work and can be implemented on minicomputers.

Analog-Digital Conversion↗
PubMed1979

The fluorescence scanning of microgels stained for glycoproteins with fluorescein isothiocyanate-labelled concanavalin A.

A technique is presented which allows one to label and quantitate glycoproteins. Small amounts of protein from biological samples (0.5-2.5 microgram for mixtures and less for individual proteins) are separated by sodium dodecyl sulfate gel electrophoresis on 1-30% polyacrylamide gradient microgels. The gels are stained with Co-omassie Brillant Blue R250 to evaluate relative migration or fixed in 2-propanol/acetic acid and stained with fluorescein isothiocyanate-labelled concanavalin A. The microgels are then scanned using a fluorescence microscope controlled by a computer, although simpler configurations are possible. Standards of known carbohydrate composition (e.g., glucose oxidase) are used for comparative purposes. Glycoproteins in the order of 5-30 ng protein (or 1-5 ng carbohydrate) can be detected without difficulty. This technique may prove valuable in evaluating glycoproteins when the available material is limited.

Animals↗
PubMed1979

A simple, versatile, sensitive and volume-independent method for quantitative protein determination which is independent of other external influences.

A method is described which in principle is a quantitative "spot analysis". 0.5-5 microliter of a protein solution in the concentration range between 0.01-10 mg/ml is used for one determination. The sample is taken up by capillary attraction in a 0.5-, 1-, 2- or 5-microliters capillary and transferred to a cellulose acetate strip. The protein is fixed and stained simultaneously by dipping the cellulose acetate strip into a solution of Amido Black or a benzoxanthene derivative (Hoechst 2495) dissolved in in methanol/acetic acid. After elution of the excess of dye (3 x 5 min) the quantitative evaluation can be performed in different ways: 1) The sample is fixed and made transpartent by incubation in dioxane/1-butanol and evaluated densitometrically (Amido Black 10B) or 2) the evaluation is performed in situ by spot fluorometry (Hoechst 2495). 3 The sample can be dissolved together with the acetate layer completely in dioxane, dimethylsulfoxide or N,N-dimethylformamide and evaluated photometrically or 4) fluorometrically. 5) Highest sensitivity is reached if the fluorochrome (Hoechst 2495) bound to the protein is eluted with 15% NH4OH and measured fluorometrically. There is a linear correlation with a correlation coefficient of 0.999 between the fluorescence and a protein amount of 10 ng-20 micrograms. In addition to its simplicity, the method has the advantage of being independent of or well-defined against other external influences, e.g., sodium dodecyl sulfate, mercaptoethanol, Triton X-100, etc. The stainability of a protein with Amido Black is influenced stoichiometrically by sodium dodecyl sulfate (not by mercaptoethanol) whilst the staining with Hoechst 2495 is not at all affected. As there is linear correlation between the area of a spot on an acetate layer and the volume applied in the range between 0.5 and 5 microliters, (only influenced stoichiometrically by the protein concentration in that volume, which in turn is measured by staining with Amido Black), then with a simple iterative calculation on the basis of suitable calibration curves, it is easily possible to determine a protein concentration in mg/ml even in an unknown volume between 0.5 and 5 microliters.

Capillary Action↗
PubMed1979

Improved microphotometry by compensating for fluctuations in the illumination.

Behind a beam-splitter in the illuminator, the irradiation of an area conjugated to the object plane is measured by a silicon photodiode and used as a reference signal. Analog division of the photomulitplier signal by this reference acts like stabilizing the light source by a factor greater than 25. A technical realization of the optical and electronical components as well as experimental results are described.

Microscopy, Fluorescence↗
PubMed1978

Stimulation of myocardial adenine nucleotide biosynthesis by pentoses and pentitols.

In rats, pentoses and pentitols, intravenously injected in a single dose of 100 mg/kg, induced a considerable enhancement of the available pool of 5-phosphoribosyl-1-pyrophosphate and of the rate of adenine nucleotide biosynthesis in the heart, but not in liver and kidney. De novo synthesis of adenine nucleotides not detectable in skeletal muscle of normal rats became measurable after application of ribose. The stimulatory effect of isoproterenol on myocardial adenine nucleotide biosynthesis could be further potentiated by ribose and xylitol, but not by glucose. The isoproterenol-induced decrease of cardiac adenine nucleotide concentrations could be almost completely prevented by repeated administrations of ribose. Thus, pentoses and pentitols in combination with beta-receptor stimulation markedly and quite specifically enhance adenine nucleotide biosynthesis in the rat heart. The results indicate that the increase in the available pool of 5-phosphoribosyl-1-pyrophosphate is an important factor for the enhancement of cardiac adenine nucleotide biosynthesis. Moreover, the availability of 5-phosphoribosyl-1-pyrophosphate and the rate of de novo synthesis of adenine nucleotides in the heart seem to be limited by the flow through the hexose monophosphate shunt.

Adenine Nucleotides↗
PubMed1977

Studies on the regulation of the biosynthesis of myocardial adenine nucleotides.

1) Changes in the rates of biosynthesis of adenine nucleotides in rat hearts under various experimental conditions are paralleled by corresponding alterations in the concentration of cyclic AMP. 2) Pentoses and pentitols cause an acceleration of the de novo synthesis of adenine nucleotides in the normal heart and a further amplification of the increase of adenine nucleotide synthesis in isoproterenol-stimulated hearts. 3) The enhancement of de novo synthesis of adenine and nucleotides induced by isoproterenol as well as by pentoses and pentitols appears to be causally related to a greater availability of 5-phos-phoribosyl-1-pyrophosphate.

Adenine↗
PubMed1977

Effect of triiodothyronine on the biosynthesis of adenine nucleotides and proteins in the rat heart.

1) During the development of myocardial hypertrophy induced by 3,3',5-triiodo-L-thyronine the enhancement of de novo synthesis of adenine nucleotides occurs very early and precedes the increase of protein synthesis. In this respect there is a striking parallelism with other types of cardiac hypertrophy. 2) The acceleration of adenine nucleotide synthesis under these experimental conditions seems to be due to a greater availability of cardiac 5-phosphoribosyl-1-pyrophosphate. 3) The triiodothyronine-induced enhancement of adenine nucleotide synthesis can be attenuated by beta-receptor-blocking agents.

Adenine↗