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Biomedical subjects

E Gerlach

Publications and source records attributed to E Gerlach.

At least 73 records · Page 4Linked to original sources
PubMed1979

Functional and metabolic features of an isolated perfused guinea pig heart performing pressure-volume work.

Cardiac performance and some parameters of glycolytic and oxidative metabolism were analyzed in isolated perfused guinea pig hearts performing pressure-volume work. Perfusion medium was an oxygenated Krebs-Henseleit bicarbonate buffer (pH 7.4) which contained glucose and physiological concentrations of pyruvate and insulin. The pressure-flow relationship in the coronary vascular bed indicated autoregulation of coronary flow. Left ventricular function was influenced by aortic pressure (Pa) and venous filling pressure (Pv) in accordance with the Frank-Starling principle, i.e. stroke work increased as a function of Pa or Pv to a certain maximum and then decreased. Myocardial oxygen consumption (MVO2), on the other hand, was linearly correlated with Pa and Pv, respectively, over the entire pressure range. Efficiency of the left ventricle, therefore, increased to an optimum (16%) and decreased at higher pressures. Myocardial contents of glycogen, ATP and creatine phosphate were not markedly influenced by a change in Pa or Pv. L-Noradrenaline (0.08 micrometer, NA) stimulated stroke work and MVO2 at a all Pv tested; efficiencies reached physiologic values (21%) at high volume loads. The increased MVO2 was associated with an acceleration of pyruvate decarboxylation and lactate release up to 10- and 15-fold, respectively, at elevated but physiological NA concentrations (0.2 micrometer). Our results demonstrate that the isolated perfused working guinea pig heart compares favourably with the non-failing Starling heart-lung preparation and hearts in situ, as far as coronary function, left ventricular performance and oxidative metabolism are concerned.

Animals↗
PubMed1978

Radioimmunoassay for adenosine in biological samples.

A sensitive and specific radioimmunoassay for adenosine has been developed. Antibodies directed against adenosine (titer 1:400--1:700) were obtained by immunizing rabbits with adenosine, conjugated via its vicinal hydroxyl groups to bovine serum albumin (periodate oxidation). Interfering adenosine deaminase activity was removed from the antisera by treatment with DEAE-cellulose. Free and antibody bound 3H-adenosine was separated by either the "second antibody" precipitation method or by a simple filtration step. The sensitivity and assay range for adenosine was 1--100 pmoles per assay tube. Structurally related purine compounds (adenine nucleotides, adenine) crossreacted with adenosine binding and were removed by a single chromatographic step. Analysis of the adenosine content in normoxic guinea pig hearts yielded 2.53 nmoles/g, a value which was confirmed by spectrophotometric analysis.

Adenosine↗
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

Adenosine as inhibitor of myocardial effects of catecholamines.

Infusion of adenosine into the coronary arteries of isolated guinea pig hearts produced a dose-dependent inhibition of dP/dtmax caused by bolus injections of isoproterenol (4 X 10(-11) moles). Threshold concentration of adenosine was 10(-7) M and maximal inhibition (90%) occurred at 10(-5) M. Coronary dilation induced by papaverine did not influence the contractile response to catecholamines. In addition to its influence on cardiac performance, adenosine (10(-5) M) effectively inhibited the isoproterenol (10(-7)M) induced initial rise in myocardial levels of cyclic 3'5'-AMP, glucose-1-phosphate and glucose-6-phosphate. Adenosine also antagonized the effect of isoproterenol on adenylate cyclase activity in a crude membrane preparation from guinea pig ventricles; it was without effect on the activity of the membrane phosphodiesterase. Theophylline inhibited the actions of adenosine both on adenylate cyclase activity and on contractile force development. Upon infusion of isoproterenol (3 X 10(-7)M) into the coronary arteries of the isolated heart (perfusion at constant pressure), the adenosine concentration in the effluent perfusate increased within 45 s from 10(-8) M to about 10(-6) M. It thus appears conceivable that in ventricular myocardium endogenously formed adenosine may serve 2 functions: dilation of the coronary arteries and limitation of the inotropic and metabolic effects of catecholamines.

Adenosine↗
PubMed1977

Release of adenosine, inosine and hypoxanthine from the isolated guinea pig heart during hypoxia, flow-autoregulation and reactive hyperemia.

In an attempt to test the hypothesis whether adenosine is involved in the regulation of coronary flow adenosine, inosine and hypoxanthine were measured in the effluent perfusate and in the tissue of isolated guinea pig hearts under various experimental conditions. In addition, the release of 14C-adenosine, 14C-inosine and 14C-hypoxanthine was determined after prelabeling cardiac adenine nucleotides with 14C-adenine. The decrease in coronary resistance induced by hypoxic perfusion (30% and 20% in the gas phase) and during autoregulation was associated with a considerable increase in the release of adenosine and hypoxanthine. Under both conditions the concentrations of adenosine in the effluent perfusate were clearly within the coronary vasodilating range of exogenously administered adenosine. The tissue content of adenosine also increased significantly when the perfusion pressure was reduced. The release of 14C-adenosine closely paralleled the changes in coronary resistance during hypoxic perfusion, autoregulation and during reactive hyperemia. The specific activity of adenosine in the effluent perfusate, however, decreased substantially upon reduction of the oxygen supply to the heart, indicating that the release of 14C-adenosine does not provide an absolute measure of total adenosine release by the heart. Our data indicate that the greater part of the adaptive changes of vascular resistance during hypoxia and autoregulation can be attributed to adenosine which is formed at an enhanced rate under these conditions. However, other factors might be involved as well.

Adenosine↗
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↗
PubMed1976

Compartmentation of cardiac adenine nucleotides and formation of adenosine.

After prelabeling the adenine nucleotides (ATP, ADP, AMP) of isolated perfused guinea pig hearts with either 14C-adenine or 14C-adenosine for 35 min, labeled adenosine, inosine, hypoxanthine and cyclic 3'5'-AMP (cAMP) were continuously released into the cardiac perfusate. Determination of the specific activities (SA) of the adenine nucleotides, cAMP, and their breakdown products (adenosine, inosine, hypoxanthine) in tissue and perfusate revealed: Under steady state conditions the SA of adenosine and cAMP in the perfusate were of the same order of magnitude and proved to be many times higher than the SA of the respective precursor adenine nucleotides. This difference was observed regardless whether adenine or adenosine was used as prelabeling substances. The SA of inosine and hypoxanthine in the perfusate were constantly lower than the SA of adenosine. Cardiac ischemia of 6 min, which resulted in a markedly increased formation of adenosine, led to a pronounced decrease in the SA of adenosine released from the heart. Our findings provide evidence that at least two different adenine nucleotide compartments of the heart severe as precursors for the formation of adenosine and cAMP, one characterized by a high, the other by a lower SA. Under normoxic conditions adenosine and cAMP released into the cardiac perfusate are derived mainly from a nucleotide fraction of high SA, which appears to be rather small. During ischemia a second compartment of much lower SA in addition contributes to the formation of adenosine.

Adenine Nucleotides↗
PubMed1976

Studies on potassium induced coronary dilation in the isolated guinea pig heart.

Changes of coronary flow in the isolated perfused spontaneously beating guinea pig heart were induced by elevation of potassium concentration in the perfusion medium (4-16 meq/l). Potassium caused a dose-dependent transient increase of diastolic coronary inflow. The response was inhibited by ouabain (1.4 X 10(-7) M) or reduced temperature. Rubidium ions elicited almost identical vasodilator effects which were also inhibited by ouabain. Autoregulation of coronary flow, reactive hyperemia, and hypoxic coronary dilation were not significantly altered in the presence of ouabain. The results support the hypothesis that potassium as well as rubidium cause vasodilation by activating a Na+, K+-ATPase. On the other hand, they do not favour the view of an essential involvement of potassium ions in local regulation of coronary flow under the conditions studied.

Animals↗
PubMed1976

[Studies on the frequency and diagnostic value of hepatomegaly].

In 4 groups of patients (I = 1 621 internistic in-patients, II = 2 073 donors with increased SGPT-values, III = 2 619 after-examined patients with hepatitis, IV = 514 patients of a sanatorium for liver diseases) frequency and diagnostic validity of the symptom enlargement of the liver are tested. The most frequent cause of hepatomegalia is in group I an insufficiency of the right heart. The highest percentage, however, is to be found in liver diseases, then come heart insufficiency, diseases of stomach and gall-bladder, diabetes, rheumatic diseases. In these diseases liver biopsy detects additional changes in many cases. The validity test in the 4 groups yields very different results, dependent on the number of patients and the diagnostic questioning. The symptom hepatomegalia cannot be used as a screening test, but it is of high diagnostic value in the clinical diagnostics.

Blood Donors↗
PubMed1975

Coronary responses to dilating substances and competitive inhibition by theophylline in the isolated perfused guinea pig heart.

Coronary dilation induced by infusion of adenosine, adenine nucleotides, dipyridamole, and papaverine was quantitated in the spontaneously beating isolated perfused guinea pig heart. Theophylline antagonized the effects of all the substances tested. The inhibition proved to be reversible and of a competititve type. Single injections of ADP and ATP induced flow increases which were more rapid in onset and of greater magnitude than those due to equimolar amounts of adenosine. Lowering the perfusate temperature prolonged coronary responses to ADP and ATP more than those to adenosine. Papaverine produced greater maximal dilation than adenosine. Theophylline inhibited papaverine-induced dilation less effectively than dilating responses to adenosine and other compounds. In the potassium arrested heart, the dilation caused by compound D 600 and papaverine was sensitive to the perfusate calcium concentration but that due to adenosine was unaffected. Dipyridamole, which was equipotent to adenosine in the non-arrested hear, became less potent than adenosine in the arrested heart. The results favour the view that all of the substances tested induce coronary dilation per se and that their effects are not mediated by adenosine. The dilator response to papaverine is assumed to be the result of two effects, one of which is inhibited by theophylline, the other by high extracellular calcium.

Adenine Nucleotides↗
PubMed1975

An isolated guinea pig heart preparation with in vivo like features.

Hemodynamic and metabolic characteristics of an isolated guinea pig heart preparation perfused with a pyruvate fortified Krebs-Ringer-bicarbonate solution are described. The preparation is stable for more than 90 min with respect to coronary flow, heart rate, left ventricular pressure, dP/dt, oxygen consumption, and myocardial high energy phosphate levels. The changes in coronary flow induced by alterations of perfusion pressure, ischemia, and hypoxia resemble those seen under in vivo conditions. The preparation also exhibits concentration dependent and reproducible changes in coronary resistance upon administration of adenosine and papaverine. The in vivo like features of this preparation can be mainly attributed to the use of pyruvate as additional and preferentially utilized substrate. The preparation appears to be suitable for quantitative studies of myocardial metabolism and heart function as well as for investigations of the coronary system.

Adenine Nucleotides↗
PubMed1975

Release of (14C) adenosine from the guinea pig heart during autoregulation.

The radioisotope method applied in the studies presented appears to be of particular advantage for the sensitive measurement of changes in adenosine release from the myocardium. The data obtained provide evidence that conditions which alter the oxygen supply to the heart such as lowering the perfusion pressure, temporary interruption of coronary inflow, and reducing oxygen content in the perfusion medium are accompanied by an enhanced release of adenosine. These results further support the concept that adenosine is a mediator in the regulation of coronary flow.

Adenosine↗