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Biomedical subjects

G Hellige

Publications and source records attributed to G Hellige.

At least 73 records · Page 4Linked to original sources

Protective effects of the Hemopump left ventricular assist device in experimental cardiogenic shock.

The efficacy of the new cable-driven rotating left ventricular assist device Hemopump in cardiogenic shock was examined in experiments with adult sheep (n = 14; body weight 50-71 kg). Shock was induced by high frequency ventricular pacing. Aortic, pulmonary, central venous and left ventricular pressures as well as electromagnetic measurements of coronary blood flow were recorded continuously; cardiac output was measured by thermodilution technique. Blood samples for determination of oxygen content, electrolytes and lactate were taken under control conditions, in shock, and during pump intervention at different levels of pump speed. Vascular resistance, total body and myocardial oxygen consumption as well as myocardial uptake and release of lactate were calculated. High frequency pacing led to a significant decrease in cardiac output (from 3.8 +/- 0.8 to 2.2 +/- 1.6 l/min), mean aortic pressure (89.1 +/- 14.4 to 47.6 +/- 7.2 mmHg), and total body oxygen consumption (2.6 +/- 0.3 to 1.4 +/- 0.7 ml/min per kg), as well as myocardial release of lactate (arterial coronary-venous difference of lactate: 0.27 +/- 0.26 to -0.32 +/- 0.72 mmol/l). Hemopump assist in this condition resulted in a significant increase in cardiac output (to 2.8 +/- 0.6 l/min), mean aortic pressure (to 65.6 +/- 13.9 mmHg), and myocardial perfusion pressure (from 25.5 +/- 11.0 to 59.0 +/- 14.7), and led to nearly normal total body oxygen consumption (2.5 +/- 0.7 ml/min per kg), a decrease in myocardial oxygen consumption (from 6.1 +/- 2.1 in shock, to 4.8 +/- 1.7 ml/min per 100 g), and to normal arterial coronary-venous difference of lactate (0.24 +/- 0.26 mmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Calculation of body transport function.

A new model for simulation of recirculation has been developed which describes the measured concentration-time course of a drug in the aorta. It is based on repetitive convolution of the injected input dilution curve with a body transport function plus the input dilution curve. If the basic shape of a body transport function, i.e. such as log-normal distribution, is known, it is possible to calculate the parameters of this function with a non-linear least-squares procedure from measured tracer dilution data. In the present investigation this algorithm is used to estimate the body transport function for experimental data, obtained in two experiments with sheep. Once the body transport function is known, the formula can be used to describe the dispersion of a drug. Intravascular concentration time curves at different places in the body can also be predicted or the blood volume can be estimated.

Algorithms↗

Efficiency of the left ventricle assist device Hemopump in cardiac fibrillation.

We have examined in sheep the efficiency of the Hemopump during ventricular fibrillation. Circulatory arrest was induced by electrical stimulation and maintained for 30 min. Haemodynamic measurements were recorded continuously and blood samples were taken before, during and after fibrillation to determine total body and myocardial metabolic activity. All hearts were defibrillated successfully after 30 min of fibrillation. During fibrillation, the Hemopump sustained a mean arterial pressure of about 60 mm Hg with a blood flow rate of about 2.3 litre min-1. These perfusion conditions were sufficient for maintenance of aerobic myocardial metabolism, but with a borderline circulatory supply to the total organism.

Animals↗

Influence of pH management on hemodynamics and metabolism in moderate hypothermia.

In moderate hypothermia, three different concepts of pH management have been described to date: pH-stat, alpha-stat, and alkalinity. In our study these pH strategies were compared in adult sheep, with animals serving as their own controls for direct comparability. Hemodynamic parameters, such as mean aortic pressure (from 109 +/- 12 to 72 +/- 23 mm Hg), cardiac output (from 5.55 +/- 1.25 to 4.5 +/- 0.82 L/min), and systemic oxygen consumption (from 3.73 +/- 0.8 to 1.81 +/- 0.4 ml/kg/min), decreased significantly with alpha-stat at 28 degrees C from values for normothermia. No marked or even significant differences were found among the three pH strategies in any value, with the exception of body oxygen consumption. The difference of 2% between pH-stat and alpha-stat, at 0.06 ml oxygen/kg/min, was significant (p < or = 0.05), however of no practical relevance because hypothermia itself caused a decrease of nearly 52%. With regard to myocardial parameters, pH-stat impaired myocardial function compared with both alpha-stat and alkalinity. At nearly identical mean aortic pressures and cardiac outputs, myocardial oxygen consumption reached the highest level in pH-stat (7.65 ml oxygen/100 gm/min; alpha-stat, 6.76 ml oxygen/100 gm/min; p < or = 0.05). Myocardial efficiency thus decreased from 21% (alpha-stat) to 17% (pH-stat). No evident changes in hemodynamic and metabolic values were found for alkalinity vs alpha-stat. The best response to continuously infused epinephrine, however, was found with alkalinity. According to our data there was an impairment of myocardial function without any evident further reduction in body metabolism with pH-stat vs alpha-stat. There were, however, no marked metabolic or hemodynamic differences between alkalinity and alpha-stat, with the exception of a better preservation of sensitivity to adrenergic stimuli with alkalinity.

Acid-Base Equilibrium↗

Myocardial support and protection during regional myocardial ischemia using the Hemopump assist device.

A study was designed to quantify the influence of the Hemopump on myocardial metabolism in regional myocardial ischemias induced by repetitive balloon-occlusions (3.5 minutes) of the LAD in 12 sheep (b.w. 49-61 kg). In order to make immediate comparisons and obtain paired-couples, ischemias were carried out with and without the Hemopump in operation. An energetic unloading of the left ventricle was achieved by the Hemopump already under preocclusion conditions, reducing myocardial O2-consumption from 7.52 to 5.98 ml/min/100 g LV (= 20%) as well as lowering the LVEDP from 13.3 to 9.8 mmHg (p less than or equal to 0.01). During ischemia a clear increase of LVEDP (13.3 to 21.0 mmHg) occurs, which was prevented in the group with Hemopump-assist (9.8 to 12.1 mmHg). Combined with a sustained higher diastolic aortic pressure, a better myocardial perfusion pressure resulted. Energetic unloading and improvement of perfusion conditions might be the cause of the significantly lowered release of lactate and potassium. Due to theses fibrillation (n = 3) only occurred during occlusions without Hemopump-support. In summary, a significant reduction of the ischemic burden on the myocardium was found. Thus the Hemopump could be of benefit to patients who fail to be weaned from CPB or who are suffering from instable cardiovascular performance.

Animals↗

Application of a CCD linear array camera in the quantification of tissue staining: NBT detection in ischaemic myocardium.

A method was developed to quantify the intensity of tissue staining using a CCD (charge-coupled device) camera. Reflection spectra of NBT-stained (nitro-blue tetrazolium-stained) and unstained myocardium were recorded via fibre optics coupled to a CCD camera, connected to a microcomputer. The calculation of the intensity of staining was based on evaluation of the NBT-related changes of the reflectance spectrum. In each of six anaesthetized sheep, global ischaemia was induced by cross-clamping of the aorta. The hearts were removed and incubated at 35 degrees C. At predetermined times two sections of ventricular myocardium were taken, one of which was then stained with NBT, the other being left unstained. Evaluation of the reflectance spectra from stained sections during the first phase of ischaemia showed a slight loss of NBT colour intensity followed by a more rapid loss of staining until the values of the unstained sections were reached. In contrast to the conventional visual evaluation, the method provides quantitative data on the intensity of staining, and allows use of the NBT technique for statistical evaluation of what happens over time, and the regional distribution of ischaemic injury of tissue. This method may also be applied to other staining techniques.

Animals↗

[The energetics and economics of the cardiac pump function].

In anesthesiology and intensive care medicine it is often necessary to treat disorders involving cardiac failure or low-output syndrome. However, in patients who are endangered by ischemic heart disease, any pharmacologic therapy with positive inotropic agents should improve cardiac output without increasing myocardial oxygen demand significantly: the heart should perform its task as efficiently as possible. In the present study a mathematical model of myocardial efficiency was developed. The implications of this theoretical concept of myocardial efficiency were evaluated in animal experiments. THEORETICAL MODEL. Cardiac efficiency is predominantly dependent on preload, afterload, and inotropic state. Quantitatively, it can be calculated from end-diastolic volume, left ventricular systolic pressure (Psyst), stroke volume (SV), and ejection time. The implications of the theoretical analysis are: (1) the inotropic state, which leads to optimal myocardial efficiency, is specifically determined by preload and afterload: for each preload and afterload one matched inotropic state is necessary to achieve optimal efficiency; (2) an increase in blood pressure leads to a decrease in myocardial efficiency even if the inotropic state is optimally matched to preload and afterload; and (3) an increase in end-diastolic volume improves the efficiency of myocardial pump work. ANIMAL EXPERIMENTS. The validity of the theoretical model was studied in animal experiments with emphasis on the following items: (1) is theoretically optimal efficiency of myocardial pump work achieved by physiologic regulation of myocardial performance? (2) how does sympathetic stimulation influence myocardial efficiency? and (3) how do cardiodepressive agents such as beta-blockers or volatile anesthetics influence myocardial efficiency? METHODS. Experiments were performed on nine mongrel dogs after induction of piritramide--nitrous oxide anesthesia. Standard hemodynamics: heart rate, Psyst, maximum left ventricular pressure rise (dP/dtmax), and SV (thermodilution) as well as coronary blood flow (pressure difference catheter) and myocardial oxygen consumption (Fick principle) were measured. In order to create a broad range of different hemodynamic settings, blood withdrawal and retransfusion of blood and/or colloid osmotic solutions were used to modify intravascular volume. Additionally, the inotropic state was varied by infusion of catecholamines (isoproterenol 0.4-0.8 microgram.kg-1.min-1 or norepinephrine 1-2 micrograms.kg-1.min-1). Experimental myocardial failure was induced by adding halothane (0.8-1.5 MAC) to the basic anesthesia, beta-blockade with propranolol (125-250 micrograms.kg-1), and combination of beta-blockade with a pressure load imposed on the myocardium (propranolol 125-250 micrograms.kg-1 + norepinephrine 1-2 micrograms.kg-1.min-1). RESULTS. During variation of the intravascular blood volume by normo-, hypo-, and hypervolemia, the myocardial efficiency very closely matched the theoretically predicted values of optimal efficiency: the average observed efficiency was 98.8% of predicted optimal efficiency. Increasing afterload with norepinephrine did not alter this close relationship, although absolute values of efficiency decreased as predicted by the theoretical model. Application of isoproterenol resulted in SVs that exceeded optimal values by 41.5%. In contrast, during experimental myocardial failure SVs were too small to achieve the necessary values for optimal pump work; observed myocardial efficiency was therefore significantly lower than optimal efficiency. CONCLUSIONS. For pharmacological interventions, it can be concluded that maximal efficiency of cardiac pump work requires maximal end-diastolic filling in combination with minimal afterload. (ABSTRACT TRUNCATED AT 400 WORDS)

Anesthesia, Inhalation↗

Transfemoral placement of the left ventricular assist device "Hemopump" during mechanical resuscitation.

The Hemopump is a new left-ventricular assist device (21 F diameter), which provides up to 3.5 L/min output after placement in the left ventricle via the femoral artery. We describe the first case in which the device was inserted during resuscitation. The patient developed untreatable sustained ventricular tachycardias/fibrillation 40 hours after coronary artery bypass grafting. After prolonged mechanical resuscitation (about 3 hours) as a last resort the Hemopump was inserted and rhythm and hemodynamics stabilized. In the following hours a decrease in aortic pressure pulsatility indicated, effective left ventricular support when the Hemopump was running. For short periods the patient had nonpulsatile aortic pressure wave forms, implying complete pump dependence. In this situation cardiac output was about 3.0 L/min, mean aortic pressure reached nearly 50 mmHg using high dosage of catecholamines. The patient remained pump-dependent and died due to untreatable ventricular fibrillation. There was no significant hemolysis during the 20 hours the Hemopump was running. Autopsy revealed no signs of thrombembolism, but intimal lesions of the A. iliaca and of the abdominal aorta with subsequent thrombus formation were demonstrated. In view of the experimentally proven benefit in cardiogenic shock and problems and risks caused by the insertion, future indications for clinical use of this new device are discussed.

Femoral Artery↗

Heterogeneity of myocardial blood flow under normal conditions and its dependence on arterial PO2.

We studied the heterogeneity of myocardial blood flow in nine anesthetized closed-chest dogs using an indicator-dilution technique that allows the stochastic description of transport characteristics for three inert gases (helium, argon, and xenon) from the coronary inflow to outflow. The results show that under normal conditions the transcoronary transport of the tracers is spatially heterogeneous. Heterogeneity is strongly dependent on the arterial oxygen tension over a range of 40-200 Torr. This could be similarly observed with each tracer gas despite different physicochemical properties and was largely independent from the magnitude of coronary blood flow. The results are interpreted to mean that the arteriolar or intratissue PO2 influences myocardial blood flow over a broad range and possibly acts as an important integrating factor in the local regulation of coronary blood flow and flow reserve.

Animals↗

Transport of inert gases in mammalian myocardium: comparison with a convection-diffusion model.

Because tracer techniques are gaining an increasing importance for imaging flow (and metabolism) in the heart, experimental evidence is needed on the role of convection and diffusion in the transcoronary transport of solutes. In the present work, the transport of four different inert gases through the coronary system is studied in five closed-chest dog experiments and is compared with a digital multicapillary convection-diffusion model. Transport may be defined as flow dependent, as judged by the gross similarity of shape of the time-normalized dilution curves. However, the results show that the transcoronary transport of helium and xenon is more dispersed than that of argon and krypton, probably because of differences in diffusibility and solubility. A comparison of the animal and model experiments emphasizes the importance of diffusive transport of the gases. It is suggested that there is a diffusion shunt that is mainly located within the capillary network itself rather than between conduit vessels. Only for helium (which has the highest diffusivity) was a small arteriovenous shunt fraction seen that is thought to bypass the capillary exchange region. The conclusion is that although there is evidence of diffusional shunting at a capillary level, the inert gas kinetics in the heart are compatible with a basically flow-limited transport.

Animals↗

Evaluation of methods for indirect calorimetry with a ventilated lung model.

A combined lung and ventilator model was built, validated and used to test commercial systems for indirect calorimetry. It simulates O2 uptake and CO2 excretion under ventilator treatment conditions. In the model inspiratory gases are diluted with N2 and CO2 to give the desired expiratory concentrations. Minute volume, FIO2, ventilatory pressure, VO2, VCO2 and consequently RQ can be altered to simulate the adult clinical situation. A selected respiratory pattern is maintained by the lung model. Equipment for indirect calorimetry can then be connected to it and the results compared. Reference values are derived from measurements with a mass spectrometer and a Godart spirometer. Three commercially available instruments (Beckman MMC, Horizon MMC and Engström MC) were evaluated with this system. The limits of agreement with the reference values under different conditions (FIO2 0.4-0.7, ventilatory pressure 0-50 cmH2O) were determined. Differences as high as 15% from the true values of VO2 and V CO2 were observed. The pattern of mechanical ventilation and the intrinsic properties of the analyzers in the equipment used for indirect calorimetry influence measurements to a significant extent.

Calorimetry↗

Characteristics of the pulmonary transport functions for heat and dye in pulmonary edema and orthostasis.

The aim of this study was to investigate whether changes in the distribution of pulmonary blood flow and disturbances of the pulmonary microcirculation can be detected by use of inflow-outflow indicator-dilution measurements. In 18 anesthetized (N2O-piritramide) mongrel dogs 221 thermal-indocyanine green dye indicator dilution kinetics were recorded in the pulmonary artery and aorta after central venous indicator injection. The lagged normal density function was used as a model for the pulmonary transport functions for heat and dye. The parameters of the lagged normal density function were computed by a non-linear least squares procedure by iterative convolution. After baseline measurements, in nine dogs, pulmonary edema was induced by central venous application of oleic acid. In nine other dogs, measurements were performed before and after postural changes. Our data show that both the microvascular injury caused by oleic acid edema and the perfusion heterogeneity caused by orthostasis can be detected by the indicator dilution technique since the both relative dispersion and skewness of the transport functions for heat and dye were significantly increased after these interventions.

Animals↗

Interference with the prostaglandin system as a therapeutical concept to protect the myocardium during ischemic stress: experimental studies with inhibition of thromboxane synthesis.

The characterization of thromboxane A2 as vasoconstrictor and potent stimulus of platelet aggregation has led to attempts to overcome these effects obviously unfavourable in ischemia. As an attractive approach, we examined potentially protective results of thromboxane synthetase inhibition on canine myocardium stressed by transient ischemia, using as inhibitor the imidazole derivative UK 38.485. On anaesthetized open-chest mongrel-dogs (n = 5) repeated ischemia (3 min) was produced by proximal, intermittent occlusion of the LAD artery. In each experiment 3-4 control occlusions were compared to 3-4 occlusions under therapy. The efficiency of the drug (5 mg/kg body weight, i.v., 30 min before therapy occlusion) was examined (a) by quantification of the energy deficit occurring as the difference between oxygen demand and uptake during occlusion, (b) by the amounts of potassium, inorganic phosphate, and lactate released in the postischemic reperfusion and (c) by changes of the regional myocardial wall function in the central- and peripheral ischemic zone. Compared to control, premedication with UK 38.485 led to a reduced energy deficit (-39.1%; p less than 0.01) combined with a significant decrease in the release of potassium (-15.7%; p less than 0.001), inorganic phosphate (-20.2%; p less than 0.002), and lactate (-20.7%; p less than 0.01). Regional myocardial wall function was improved in the central and peripheral ischemic region as demonstrated by a significantly reduced systolic bulging. The protective effects seem to be mainly due to enhanced flow to ischemic areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

No pulmonary edema or congestion after central venous injection of conventional and newer contrast media in dogs.

Our aim was to determine whether large central venous doses of ionic diatrizoate, nonionic iopromide, or nonionic iotrolane produce pulmonary edema or pulmonary congestion in dogs. Eighteen dogs (six per group) anesthetized with piritramide and N2O received three sequential doses (1.5 mL/kg body weight) of one contrast medium in less than 20 seconds. Before the first injection, and again 1, 5, 10, 20, and 30 minutes after each contrast injection, extravascular lung water, pulmonary blood volume, and cardiac output were determined by thermal-dye dilution. Neither extravascular lung water nor pulmonary blood volume increased after any contrast medium. Pulmonary blood volume and cardiac output decreased slightly but not significantly after all contrast media during the course of the study. We conclude that diatrizoate, iopromide, or iotrolane do not produce pulmonary edema or congestion in dogs.

Animals↗

Comparison of the effects of right atrial, right ventricular apex and atrioventricular sequential pacing on myocardial oxygen consumption and cardiac efficiency: a laboratory investigation.

As the impact of cardiac pacing on myocardial energetics has not yet been established, this laboratory investigation was undertaken to evaluate the effects of right atrial (AP), right ventricular apex (VP) and atrioventricular sequential pacing (AVP) on cardiac energetics in a closed-chest model. Ninety-two pacing interventions were performed in ten anesthetized mongrel dogs with normal loading conditions and contractile states. The energetic effects of pacing were assessed in terms of myocardial oxygen consumption (MVO2), its hemodynamic determinants and cardiac efficiency. Efficiency was calculated as the ratio of O2-equivalent of external cardiac work to MVO2, using standard definitions. In the first series of experiments 36 intra-individual comparisons were made between AP and VP at identical rates (95-210 beats/min). In the second series AVP was compared to VP in 10 intra-individual comparisons at identical rates (109-190 beats/min). MVO2 was lower (p less than 0.001) during AP (8.30 +/- 2.14 ml O2/min.100 g) compared to VP (10.16 +/- 3.15 ml O2/min.100 g) at the same rate (158 +/- 32 beats/min). Efficiency (p less than 0.001) was considerably higher during AP (21.6 +/- 5.7%) compared to VP (12.8 +/- 5.9%). During AVP, MVO2 (10.85 +/- 1.76 ml O2/min.100 g) was not significantly different from VP (10.57 +/- 1.34 ml O2/min.100 g) at the same rate (146 +/- 25 beats/min). Hemodynamics were superior with AVP compared to VP. Efficiency was significantly higher (p less than 0.01) with sequential (15.4 +/- 3.9%) as compared to ventricular pacing (12.0 +/- 3.2%). In conclusion, this study indicated that VP exerts disadvantageous effects on MVO2 and cardiac efficiency. AP has beneficial effects on cardiac energetics because it improves the relationship between mechanical performance of the heart and its energy requirements. AVP results in a higher efficiency than VP due to superior hemodynamics, despite MVO2 levels comparable to those of VP. The mechanism of energy waste with right ventricular apex pacing is probably related to an asynchronous contraction in the ventricular myocardium due to a nonphysiological spread of excitation.

Animals↗

Thermal recovery after passage of the pulmonary circulation assessed by deconvolution.

For indicator-dilution studies, complete thermal recovery after passage of heat through the pulmonary circulation would be desirable. However, the results in the literature obtained by extrapolation techniques are inconsistent. To overcome problems of the extrapolation approach, transport functions of the pulmonary circulation (including the left heart) were computed by deconvolution of pulmonary arterial and aortic pairs of thermodilution curves after central venous indicator injection (10 ml of an ice-cold blood indocyanine green dye mixture). Thermal recovery was determined as the finite integral of the transport function. Thirteen mongrel dogs under piritramid-N2O anesthesia were examined under base-line conditions, in orthostasis to alter the distribution of pulmonary blood flow (9 dogs), and in oleic acid edema (8 dogs). Using the deconvolution approach, thermal recovery was 0.97 +/- 0.04 under base-line conditions, 0.96 +/- 0.03 in orthostasis, and 0.96 +/- 0.05 in pulmonary edema. Thermal recovery determined from extrapolated dilution curves was greater than 100% in all groups, a physically impossible finding. It is concluded that thermal recovery is incomplete but insensitive with respect to the distribution of blood flow and to the size of the extravascular compartment. Monoexponential extrapolation is unsuited for the determination of thermal recovery.

Animals↗