Search PubMed⌕ Search

Biomedical subjects

G Hellige

Publications and source records attributed to G Hellige.

At least 145 records · Page 8Linked to original sources
PubMedDate not supplied

Investigation of cardiac metabolism using stable isotopes and mass spectrometry.

The technique described in this communication enables detailed investigations of cardiac metabolism using 13C-labeled substrates and mass spectrometric measurements of 13CO2 in the coronary effluent. To validate this technique for further studies isolated working rat hearts were perfused with 13C-labeled substrates in a bicarbonate-free perfusion fluid. The fraction of CO2 produced by oxidation of labeled substrate was calculated by the 13CO2/CO2 ratio in the coronary perfusate. The oxidation of 13C-acetate showed a linear correlation with 13C-acetate concentrations between 0.015 and 0.16 mmol/l. An inhibitor of acylcarnitine translocase, 2-(3-methylcinnamylhydrazono)-propionate (BM42.304) decreased CO2 production from 13C-palmitate from 48% +/- 4% to 31% +/- 3% (n = 11, SEM). Taking into account considerations of tracer kinetic theory rapidly accessible intracellular palmitate stores were estimated to be less than 900 nmol/g ww. This technique allows specific investigations of the oxidation of labeled substrates in the heart and may be useful for basic research and/or clinical diagnosis, thus avoiding the hazards of radiolabeled substrates.

Acetates↗
PubMedDate not supplied

[Recording of ventricular pressure by conventional catheter manometer systems. I. Minimal requirements of blood pressure recording systems and estimation of frequency response characteristics].

Parallel recordings of pressure pulses by conventional catheter manometer systems and catheter tip manometer demonstrate severe errors in the peak velocity of pressure rise estimated by conventional systems. This fact is due to inadequate dynamic response characteristics of conventional systems in relation to the frequency content of pressure curves. During cardiac rest the error in dp/dt max is less than 10% if the frequency response of the recording system is uniform up to 10 Hz, the corresponding value under maximal cardiac stimulation is about 40 Hz. This is equal to the first 10 harmonics of heart rate. The examination of left and right ventricular pressure curves leads to similar results. The experimental determination of dynamic response characteristics of cathermanometer systems requires a test system producing suitable sinus or step functions, parallel high fidelity recording of pressure functions to be recommended. A simple test station is described. Examinations of temperature influence on catheter material and resulting changes in dynamic response characteristics were carried out. The incubation of catheters at the temperature of 37 degrees C is indispensable. A new diagram for simplifying the interpretation of results is described. Other publications are discussed in viewpoint of employed techniques and representation of results.

Blood Pressure Determination↗
PubMedDate not supplied

Experimental validation of methods for the measurement of coronary sinus blood flow in man.

The measurement accuracy of clinically applicable methods for blood flow measurement in coronary sinus -- continuous local thermodilution (LTD), differential pressure (DP), ultrasonic Doppler (US) and the electromagnetic flow measurement method (EMF) -- was examined in 15 anaesthetized closed chest dogs with left ventricle weights between 150 and 200 g. The LTD, DP, US and the EMF were examined in each experiment in the two following arrangements. 1. In coronary sinus -- left jugular vein by-pass: This arrangement allowed four reference methods for measurement of coronary sinus blood flow (CBF). 2. In "clinical" position, without by-pass, which allowed two reference methods for CBF measurements. The results on the measurement accuracy of the LTD, DP and US are, depending on the measurement arrangement, contradictory. In the by-pass arrangement 1 there was observed a good agreement of the LTD, DP and US CBF values with the reference values. In the "clinical" position, without by-pass 2 the measurement accuracy of LTD was not sufficient for exact measurement of CBF and derived parameters. The examined velocity tip flow probes (US, DP) gave no correlation with the reference methods. US and DP are even for semiquantitative estimation of CBF unsuitable. The EMF tip flow probe was for the CBF measurement unsuitable, because of disturbance by the electrical activity of myocardium.

Animals↗
PubMedDate not supplied

Unfavorable effects of ventricular pacing on myocardial energetics.

The effects of ventricular pacing (90-330 beats/min) and atrial pacing (120-210 beats/min) on myocardial oxygen consumption (MVO2) and its hemodynamic determinants and on myocardial pumping efficiency were studied systematically on intact dogs. In six closed-chest experiments 158 steady states were analyzed. Myocardial blood flow was measured with a differential pressure sinus catheter, oxygen consumption (5-30 ml/min . 100g) was determined simultaneously by the Fick principle and the additive hemodynamic parameter Et. Ventricular and atrial pacing were compared with both methods at identical heart rates. Additionally, the coincidence between both methods of determining MVO2 was examined at sinus rhythm with sympathetic stimulation (norepinephrine, atropine) within each experiment. Ventricular pacing increased MVO2 overproportionally up to 50% in relation to the hemodynamic determinants. Consequently, myocardial pumping efficiency markedly decreased with increasing ventricular rate. The close relation between directly measured MVO2 and Et, found in previous studies, was maintained under sympathetic stimulation. Atrial pacing, as compared to ventricular pacing at identical rates, resulted in a decrease of MVO2 up to 25% although the expected mVO2 according to its hemodynamic determinants rather increased. The hemodynamic and metabolic mechanisms probably responsible for the energetic difference between ventricular and atrial pacing at equal heart rates are discussed.

Animals↗
PubMedDate not supplied

The influence of myocardial edema formation on the energy consumption of the heart during aerobiosis and hypoxia.

Isolated rat and guinea pig hearts show, during perfusion with aequeous salt solutions, myocardial edema formation of different degree. The extent of tissue fluid accumulation is dependent on the species, the osmolality, and the oxygen partial pressure of the perfusion medium. With increasing edema formation there is, in both species, an increasing energy requirement for the same hemodynamic state. Addition of 50 mM mannitol to the perfusion medium can diminish edema of the hypoxic perfused rat heart and improves the myocardial function during hypoxia. The beneficial effect of hyperosmolality in the isolated hypoxic rat heart is discussed in terms of an improvement of myocardial energy balance and coronary microcirculation.

Aerobiosis↗
PubMedDate not supplied

Increase of myocardial oxygen consumption due to active diastolic wall tension.

A marked increase in left ventricular diastolic pressure ( PLVD ) relative to volume is regularly observed during angina pectoris and may contribute to further deteriorations of myocardial perfusion in the ischemic myocardium and to pulmonary congestion as well. A possible simultaneous increase in myocardial oxygen consumption (MVO2) due to a reversible diastolic tone during transient ischemia has not been taken into consideration in previous studies on alterations in ventricular diastolic properties. 13 closed-chest experiments were carried out in clinical catheterization technique with situations of high PLVD (18-50 mm Hg) relative to volume induced by right ventricular pacing (n = 19; 172 +/- 5 beats/min) and catecholamine-induced reversible diastolic tone (n = 17) in moderate hypothermia (31 degrees C). MVO2 was directly measured and indirectly calculated from its hemodynamic determinants using Bretschneider's equation (Et) that does not consider ventricular diastolic pressure. In addition, an energy demand for maintenance of active diastolic wall tension (E5) was calculated from PLVD , mean ventricular diastolic volume estimated from endsystolic and stroke volume, diastolic time and heart rate in ml O2/min X 100 g. During pacing tachycardia with high PLVD (27.4 +/- 1.8 mm Hg) the MVO2 (12.49 +/- 0.50 ml O2/min X 100 g) exceeds Et (10.11 +/- 0.25 ml O2/min X 100 g) (p less than 0.001), partly due to neglect of E5 (1.39 +/- 0.11 ml O2/min X 100 g). During catecholamine-induced high PLVD (31.1 +/- 2.5 mm Hg) the MVO2 (12.29 +/- 0.83 ml O2/min X 100 g) increases significantly (p less than 0.001) over Et (10.43 +/- 0.81 ml O2/min X 100 g). Addition of E5 (1.76 +/- 0.14 ml O2/min X 100g) to Et abolishes the differences between MVO2 and Et yielding non-significantly different values. Results indicate by means of indirect energetic evidence the occurrence of a diastolic tone of the heart under unphysiologic conditions. Acute increases in PLVD during angina pectoris are supposed to increase MVO2 markedly due to an additional energy demand for maintenance of reversible active diastolic wall tension.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

[Recording of ventricular pressure by conventional catheter manometer systems. Efficiency of several combinations of conventional catheters, modern transducers and catheter-flush systems (author's transl)].

The experimentally in vitro determined dynamic response characteristics of 38 catheter manometer systems were uniform in the worst case to 5 c.p.s. and optimally to 26 c.p.s. Accordingly, some systems are only satisfactory for ordinary pressure recording in cardiac rest, while better systems record dp/dt correct up to moderate inotropic stimulation of the heart. In the frequency range of uniform response (amplitude error less +/- 5%) the phase distortion is also negligible. In clinical application the investigator is often restricted to special type of cardiac catheter. In this case a low compliant transducer yields superior results. In all examined systems the combination with MSD 10 transducers is best, whereas the combination with P 23 Db transducers leads to minimal results. An inadequate system for recording ventricular pressure pulses leads in most cases to overestimations of dp/dtmax. The use of low frequency pass filters to attenuate higher frequency artefacts is, under clinical conditions, not suitable for extending the range of uniform frequency response. The dynamic response of 14 catheter manometer systems with two types of continuous self flush units was determined. The use of the P 37 flush unit in combination with small internal diameter catheters leads to serious error in ordinary pressure recording, due to amplitude distortion of the lower harmonics. The frequency response characteristics of the combination of an Intraflow flush system and MSD 10 transducer was similar to the non-flushing P 23 Db transducer feature.

Blood Pressure Determination↗
PubMedDate not supplied

Quantification of ischemic stress during repeated coronary artery occlusion in the dog. A method for validation of therapeutic effects. I. Estimation of O2-debt and O2-repayment.

In 9 open-chest mongrel dogs 4-6 intermittent 3-min occlusions of the LAD artery were performed with time intervals of about 45 min. Using a mu-computer, the following variables were calculated online: energy demand according to the Bretschneider equation (Et) from digitized hemodynamic data; myocardial oxygen consumption (MVO2) from fiberoptically measured coronary sinus oxygen saturation and coronary sinus blood flow. Coronary occlusion led to a decrease in MVO2 in comparison to Et. The integral of the difference between MVO2 and Et over the entire occlusion time yielded a total O2-deficiency (DO2) of 76 (+/- 12%) microliter O2/g ischemic tissue and a correlation coefficient with the weights of the intravitally stained ischemic areas of r = 0.96. Additional O2-uptake in relation to Et during the early perfusion period yielded a correlation to the size of the ischemic area of r = 0.95 and an average O2-repayment (RO2) of 32 (+/- 14%) microliter O2/g ischemic tissue. The determination of total myocardial O2-deficiency during ischemic stress as well as determination of O2-repayment during the early reperfusion period could be used to estimate the extent of ischemic stressed myocardium. Subsequently, the evaluation of pharmacological effects on myocardial ischemia should be possible.

Animals↗
PubMedDate not supplied

Quantification of ischemic stress during repeated coronary artery occlusion in the dog. A method for validation of therapeutic effects. II. Reproducibility of the release and uptake of electrolytes and substrates.

As criterion for the degree of ischemic stress on myocardium during repeated coronary artery occlusion, the reproducibility of the release of potassium, lactate and inorganic phosphate in the early reperfusion period was examined. On 20 anaesthetized open-chest mongrel-dogs, local ischemia was induced by intermittent occlusion of the LAD artery. In each experiment the artery was occluded for 3 min 4 to 6 times with intervals of 45 min. Just before beginning, at the end of occlusion and after 5 min of reperfusion, arterial and coronary venous blood was collected simultaneously. Additionally, 3 ml of blood were withdrawn by syringe-pumps during the first minute of reperfusion. Intra-individually, the following standard-deviations were found in a representative experiment with 5 occlusions: potassium +/- 7% (22.62 +/- 1.6 mumol/min); inorganic phosphate +/- 9% (19.82 +/- 2.06 mumol/min); lactate +/- 11% (55.38 +/- 5.93 mumol/min). Interindividually, the correlation between the release of these markers and the perfusion bed of the ligated artery led to coefficients of about r approximately 0.88. On an average, per gram ischemic tissue/wet weight 0.74 mumol potassium, 0.6 mumol inorganic phosphate and 1.98 mumol lactate were released. The ratios between the releases remained constant independent of the size of ischemic area. An even closer correlation with coefficients of about r approximately 0.97 was found between the O2-debt in the occlusion period. Based on a synoptic assessment of metabolic and energetic parameters, this experimental model may render more detailed information on pharmacological interventions during ischemic stress.

Animals↗
PubMedDate not supplied

The effect of ion composition on cellular membrane potentials during selective coronary arteriography.

An animal experimental study on seven thoracotomized dogs was designed to investigate the effects of intracoronarily injected sodium meglumine diatrizoate on myocardial electrophysiology and to evaluate the contribution of the corresponding changes of electrolyte levels in coronary blood. For this purpose the effects of alterations in the Na+-, K+- and Ca++-concentrations in coronary blood were studied separately by intracoronarily injected model solutions. Membrane potentials were recorded from the left ventricular myocardium by a modified microelectrode technique which is applicable to the beating and blood perfused heart in situ. Following selective coronary arteriography there was a temporary hyperpolarization of resting potentials and a prolongation of action potentials which may be explained by a contrast-induced local deficiency of potassium and calcium ions and by a relative prevalence of sodium ions in coronary blood. In selective coronary arteriography the synchronicity of cardiac excitation is disturbed by the regional prolongation of action potentials, which may induce ventricular arrhythmias.

Action Potentials↗
PubMedDate not supplied

Simulation of arterial drug concentration after intravenous application.

The aim of this study was to develop a widely applicable model for circulatory indicator dispersion which could describe the pharmacokinetics of early drug distribution. The model assumes that the substance is injected into the right atrium and measured in the aorta. The dilution curve results from the dispersion and recirculation of the indicator in the body. The concentration time curve in the aorta, r, can be described as r = c0 + g* r, where g is the transport function of the body and c0 is the concentration time course, which is measured for the first time in the aorta. If the body transport function is known, then the aortic dilution curve of a drug can be predicted for different elimination rates and injection times. The site of interest can be chosen arbitrarily, i.e. the concentration of inflow into the kidney or any other organ can be described.

Animals↗