[Separator membranes for blood gas mass spectrometry: gas permeability with reference to measuring indicator gases for the determination of organ blood flow].
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Biomedical subjects
Publications and source records attributed to G Hellige.
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This study evaluates the routine mathematic approach (monoexponential extrapolation) for analysis of transpulmonary thermal-dye dilution curves and estimates the effects of systemic-indicator recirculation by use of a deconvolution technique. Fifteen dogs anesthetized with N2O-piritramid were studied before and after induction of pulmonary edema by oleic acid. After introduction of central venous indicator (10 ml of a mixture of cold blood and indocyanine green dye), dilution data were recorded from the pulmonary artery and the ascending aorta. The conclusions were: (1) monoexponential extrapolation yields reasonably good estimates of the mean transit times of dye; (2) mean transit times of heat are usually overestimated by monoexponential extrapolation; (3) extravascular lung thermal volume assessed by monoexponential extrapolation is overestimated by 2.03 ml/kg of body mass under baseline conditions; and (4) the prepulmonary volume of distribution of heat exceeds that of dye by 1.4 ml/kg of body mass, thus increasing the overestimation of pulmonary extravascular heat-accessible space by the conventional technique.
UNLABELLED: In patients undergoing thoracic surgery central blood volume is subject to large variations and extravascular lung water may change critically due to fluid shifts. Therefore, an accurate monitoring of these parameters, in particular under perioperative conditions, seems to be desirable. This study describes an improved method for the measurement of intrathoracic volumes. Experiments were carried our in 9 mongrel dogs under piritramide-N2O anesthesia. In order to produce low cardiac output in combination with uneven distribution of perfusion, measurements were performed under base line conditions and after postural changes. Indicators (cold and indocyanine green dye) were injected into the v. cava and indicator kinetics were recorded from the pulmonary artery and aorta using thermistor-fiberoptic catheters. The transport functions of cold and dye were computed from the corresponding pairs of dilution curves. From the transport functions, the mean transit times of the intravascular (dye) and diffusible (cold) indicator were determined. Central blood volume and extravascular lung thermal volume were calculated from the mean transit times and a thermodilution cardiac output. RESULTS: Under base line conditions, central blood volume was 15.3 +/- 2.5 ml/kg body weight. In orthostasis, a significant and reversible reduction to 11.6 +/- 2.4 ml/kg body weight was found. Cardiac output fell significantly from 3.3 +/- 0.5 to 2.4 +/- 1.1. l/min. In contrast, the slight decrease of extravascular lung thermal volume was not statistically significant. It is concluded that the method presented is sensitive enough to detect even small changes of central blood volume.(ABSTRACT TRUNCATED AT 250 WORDS)
The haemodynamic side-effects of ionic (amidotrizoate) and non-ionic (iopamidol) contrast media after injection into the right atrium were compared in experimental and clinical studies. Pulmonary hypertension was induced in 10 dogs by embolization of the pulmonary vascular bed with agar-agar solution (mean pulmonary artery pressure = 44.2 mmHg). Iopamidol (1.5 ml kg-1) caused a moderate decrease in pulmonary and systemic vascular resistance, slight increases in right ventricular end-diastolic pressure and a marked rise in right ventricular contractility (dP/dtmax). Amidotrizoate (1.5 ml kg-1) caused considerable systemic vasodilation and initial increases in pulmonary vascular resistance and pressure followed by a substantial increase in right ventricular end-diastolic pressure and a decrease in contractility. Central and peripheral haemodynamics were measured in 20 patients with pulmonary hypertension (mean pulmonary artery pressure = 38.1 mmHg) due to valvular heart disease before and following injections with 40 ml of both types of contrast medium in randomized order. Heart rate, cardiac output and right atrial pressure rose significantly more after amidotrizoate and this contrast medium caused more extensive systemic vasodilation and a larger decrease in aortic pressure as compared to iopamidol. Pulmonary artery pressure went up moderately with both contrast media. It is concluded that non-ionic low-osmolality contrast media like iopamidol induce less pronounced haemodynamic alterations, in particular less increase in right ventricular filling pressure. This may be beneficial to patients with pulmonary hypertension undergoing angiocardiography or digital subtraction angiography.
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Validation studies of inert gas techniques are limited in number and usually have not included circumstances with marked heterogeneity of flow. This study was intended to investigate the validity of the method in experimental animals under various hemodynamic conditions by parallel application of helium, argon, krypton and xenon as indicators and by comparison with direct flow measurements. Gases were applied by single breath inhalation. In order to avoid the limitations of conventional methods arising from the systemic recirculation of tracer and from shortened measuring periods we used continuous mass spectrometric recording and numeric deconvolution of the dilution curves in arterial and coronary venous blood. When the transit times are evaluated by "stochastic" analysis and commonly used tissue/blood partition-coefficients (lambda He = 0.95, lambda Ar = 1.1) the helium and argon values are found in reasonable agreement with reference flows. The effects of a shortening of measurements that are based on single integrated samples (Argon method) are shown under control conditions, adenosin infusion and elevated ventricular filling pressure. With xenon (lambda Xe = 0.7) coronary blood flow above 100 ml/min X 100 g is underestimated by the "stochastic" and by the "initial slope technique"; parallel measurements with argon suggest that in the initial slope technique a lambda Xe between 0.8 and 0.9 might be more adequate.
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This study was performed to examine potential protective effects of UK 38.485, an inhibitor of thromboxane synthetase, in canine myocardium stressed by transient ischemia. On anesthetized open-chest mongrel-dogs (n = 9) repeated ischemia (3 min) was produced by proximal, intermittent occlusion of the left anterior descending artery. A total of 18 occlusions after 3 mg UK 38.485/kg body wt. and 12 occlusions after 5 mg UK 38.485/kg body wt. were compared to a total of 24 occlusions under control conditions. In each experiment, 2-3 control occlusions and 3-4 therapy occlusions were performed. The drug was applied i.v. in a dose of 3 or 5 mg/body wt. 30 min before the first therapy occlusion. In both groups, hemodynamics and energetics did not significantly change as compared to control. The efficiency of the drug in protecting ischemically stressed myocardium was examined by (a) quantification of oxygen debt and oxygen repayment in the occlusion and reperfusion periods and (b) the amounts of inorganic phosphate, lactate, and potassium released in the first minute of reperfusion. Compared to control occlusions, premedication with either 3 or 5 mg UK 38.485 led to a significantly reduced oxygen debt combined with a significant decrease of the release of inorganic phosphate, lactate, and potassium. The protective effect is suggested to be mainly due to enhanced flow to ischemic areas. Data obtained in this study suggest protective effects of the compound in the preservation of myocardium in transient ischemia and attest to the concept that thromboxane A2 may aggravate the metabolic and energetic situation of myocardium in circumstances with reduced oxygen supply.
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3-(1H-imidazol-1-yl-methyl)-2-methyl-1H-indole-1-propanoic acid (UK 38.485), a novel imidazole derivative, was employed to study potential protective effects of thromboxane synthetase inhibition on ischemically stressed canine myocardium. In anaesthetized open-chest mongrel dogs (n = 5) repeated ischemia (3 min) was produced by proximal, intermittent occlusion of the left anterior descending artery. A total of 18 occlusions after therapy was analysed and compared to a total of 15 occlusions under control conditions. In each experiment 2-3 control occlusions and 3-4 occlusions under therapy were performed. The drug was applicated intravenously at a dose of 5 mg/kg body weight 30 min before the first therapy occlusion. Hemodynamics and energetics did not significantly change. The efficiency of the drug in protecting ischemically stressed myocardium was examined by the amounts of potassium, inorganic phosphate and lactate released in the first minute of reperfusion and by quantification of 02-debt and 02-repayment in the occlusion and reperfusion periods. Compared to control occlusions, premedication with UK 38.485 led to a reduced 02-debt (-39.1%; p less than 0.01) combined with a significant decrease of 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). The protective effect is suggested to be mainly due to enhanced flow to ischemic areas regarding a significant lesser reduction of myocardial blood flow and an improved oxygen uptake during ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
This study was designed to investigate the effects of nicorandil in comparison to isosorbide dinitrate (ISDN) on hemodynamics, on myocardial metabolism and on effectiveness in the preservation of ischemically stressed myocardium. Repeated ischemia (3 min) was produced in anaesthetized open-chest mongrel dogs by proximal, intermittent left anterior descending artery occlusion with subsequent reperfusion. In each experiment 2--3 control occlusions were compared to 2--3 occlusions under nicorandil or ISDN. Application of both nicorandil (0.64 mumol X kg-1 body weight, i.v.) and ISDN (1.27 mumol X kg-1 body weight, i.v.) led to a significant afterload reduction and to a decrease of the coronary vascular resistance. The efficiency of the compounds in the protection of ischemic myocardium was examined by quantification of oxygen-debt and oxygen-repayment in the occlusion and reperfusion periods. Compared to control, premedication with nicorandil led to a significant increase of oxygen-debt, whereas ISDN reduced it significantly. Oxygen-repayment remained unchanged. The influence of the drugs on the metabolism of glucose, lactate and free fatty acids (FFA) was examined under basic conditions, in ischemia and during reperfusion. For all substrates, extraction, extraction ratio and oxygen extraction ratio were calculated. Under basic conditions, glucose metabolism was significantly enhanced in both groups but FFA metabolism was inhibited only by ISDN. In ischemia, FFA metabolism was enhanced by nicorandil and depressed by ISDN.(ABSTRACT TRUNCATED AT 250 WORDS)
The effects of intracoronary injections of Iodecol, a nonionic-dimeric contrast medium (iodine content 350 mg/ml, osmolality 0.34 osmol/kg, viscosity 13.8 mPa X s) on haemodynamics, coronary blood flow, ECG, and cationic content as well as osmolality of coronary sinus blood have been evaluated and compared to those of Iopamidol and Amidotrizoate. Experiments were carried out in 9 closed-chest dogs using heart catheterisation techniques. After Iodecol and Iopamidol only positive inotropism was seen while Amidotrizoate initially had cardiodepressive effects. Iodecol caused less increase of peak velocity of pressure rise and systolic blood pressure than Iopamidol. All contrast media led to an increase in coronary blood flow of the same extent. ECG changes were most marked following Amidotrizoate and only slight after Iodecol. Decrease of cationic content and increase of osmolality in coronary sinus blood were seen after each compound. Changes were only small after Iodecol and always greater after Amidotrizoate. Moreover, an overproportional decrease of coronary sinus calcium content was seen after Amidotrizoate due to calcium binding. Thus, based on these animal experiments, a further slight reduction of acute cardiac side effects during coronary arteriography could be expected from the use of nonionic dimeric compounds, compared to ionic and currently used nonionic contrast media.
We studied the effects of different metabolic interventions, which stimulate oxidative myocardial carbohydrate metabolism, on ischemic stress during repeated coronary occlusions of three minutes in open-chest dog hearts. Increase of glucose concentration in plasma and decrease of peripheral lipolysis by glucose-insulin-potassium (n = 6) had no substantial beneficial effects on myocardial damage indicated by hemodynamic, electrocardiographic, and metabolic parameters. Infusion of lactate and pyruvate (10 mM, n = 6) was detrimental. Only activation of pyruvate dehydrogenase by dichloroacetate (n = 6) without influence on plasma osmolality reduced epicardial ST-segment elevations (-42%) and myocardial release of potassium (-36%), phosphate (-58%), and lactate (-39%). Elevations of plasma osmolalities by 10 and 20 mOsm with the metabolically inert mannitol increased ECG changes, functional loss and release of potassium, phosphate, and lactate during ischemia in our model. It is suggested, that the oxygen-saving potency of metabolic interventions can exert univocal beneficial effects in experimental and in clinical conditions only when systemic hyperosmolality and hypervolemia are avoided.
Potential protective effects of oxfenicine [(S)-4-hydoxyphenylglycine] in ischemic stressed canine myocardium have been studied. This compound is characterized as a drug leading to metabolic inhibition of free fatty acid (FFA) metabolism. The drug (0.06 mmol . kg-1 body weight) caused no changes in hemodynamics or energy demand (Et) but depressed myocardial oxygen consumption (MVO2) by 11% (P less than 0.02). Significant changes in FFA and lactate metabolism were observed: lactate extraction (EX) increased from 22.5-37.1 mumol/Min, extraction ratio (EXR) from 16.5-30% and oxygen extraction ratio (OER) from 24.8-38%; EX of FFA decreased from 6900-5000 nmol/min, EXR from 48.2-31.4% and OER from 59.7-46.6%. Arterial concentrations of FFA and lactate remained unchanged. EX, EXR and OER of glucose were not affected under basic conditions. In the same collective, repeated ischemia (3 min) was produced by proximal occlusion of the left anterior descending artery (LAD). The efficiency of the drug was examined by (a) the amounts of ischemia metabolites released in the early reperfusion and (b) quantification of O2-debt and O2-repayment in the occlusion- and reperfusion periods. Compared to control occlusions, premedication led to a reduced O2-debt (P less than 0.01) combined with a reduced amount of oxygen additionally taken up in the early reperfusion (P less than 0.05). Furthermore, release of potassium increased (+7.1%; P less than 0.05); release of lactate (-32%, P less than 0.001) and inorganic phosphate (-34%, P less than 0.01) decreased. These data give support to the concept that a pharmacologically induced shift of cardiac metabolism with reduction of FFA utilisation may be favourable in circumstances with limited oxygen supply.
Following single breath inhalations of helium 49 simultaneous inlet-outlet pairs of helium dilution curves were recorded in seven dog experiments from the aortic and coronary sinus blood by use of mass spectrometric technique. After numeric deconvolution of the dilution curves the weighting function of tracer transit times was used for calculation of the mean myocardial blood flow per unit of tissue, which closely correlated with directly measured flow. Secondly, the degree of blood flow heterogeneity was estimated from the first moments of the weighting function of transit times and by compartmental analysis based on an inverse Laplace transform. In the intact heart the results suggest a rather constant dispersion of flows relative to the mean flow F in the order of sigma/F = 0.3. The apparent dispersion of flows is increased by alpha-adrenergic stimulation with pressure and volume load, particularly in a state of beta-blockade, a finding, which may be attributed to variations of intercapillary distances and to a heterogeneity of blood flow per unit of tissue.