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Biomedical subjects

H Korb

Publications and source records attributed to H Korb.

At least 55 records · Page 3Linked to original sources
PubMed1986

Inhibition of thromboxane synthetase by the imidazole derivative 3-(1H-imidazol-1-yl-methyl)-2-methyl-1H-indole-1-propanoic acid as a novel therapeutic approach to experimental myocardial ischemia.

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)

Animals↗
PubMed1985

Effectiveness of nicorandil in the preservation of myocardium stressed by transient ischemia and its influence on cardiac metabolism during coronary artery occlusion with subsequent reperfusion: a comparison with isosorbide dinitrate.

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)

Animals↗
PubMed1985

[Acute cardiac side effects of iodecol, a new nonionic dimer roentgen contrast medium, in intracoronary injection].

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.

Animals↗
PubMed1984

Changes in myocardial substrate utilisation and protection of ischemic stressed myocardium by oxfenicine [(S)-4-hydroxyphenylglycine].

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.

Animals↗
PubMed1984

Estimation of myocardial blood flow heterogeneity by transorgan helium transport functions.

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.

Animals↗
PubMed1984

[Comparison of the acute cardiovascular side effects of iopamidol, metrizamide and amidotrizoate after intracoronary and left ventricular injections].

The acute cardiovascular side effects of iopamidol (osmolality: 0.8 osmol/kg), metrizamide (0.6 osmol/kg), and amidotrizoate (2.1 osmol/kg) during coronary arteriography (n = 30) and left ventriculography (n = 9) have been compared in anesthetized closed-chest dogs (n = 5). The influences of these contrast media on hemodynamics, coronary circulation, ECG and physicochemical properties of coronary sinus blood were evaluated. Following intracoronary injection, iopamidol and metrizamide cause positive inotropism while amidotrizoate initially induces cardiodepression. All contrast solutions lead to marked increase of myocardial blood flow. Electrocardiographic changes are greater after amidotrizoate (P less than 0.05). A fall of cationic content in coronary sinus blood is seen after each contrast medium. Amidotrizoate leads to more decrease of potassium (P less than 0.01) and both ionized and total calcium (P less than 0.001). Increase of osmolality and hydrogen ionic content is greater after amidotrizoate than after iopamidol and metrizamide (P less than 0.01). Following left ventricular injection, marked peripheral vasodilation, as seen after amidotrizoate, does not occur after low osmolality compounds. There are no significant differences between iopamidol and metrizamide in spite of the slightly higher osmolality of the former. Thus, both contrast materials should be equivalent with respect to their acute cardiovascular side effects under clinical conditions. Advantages of low osmolality radiological contrast media are discussed.

Animals↗
PubMed1984

[Central venous injection of large amounts of contrast media--advantages of a low osmolar contrast medium in experimentally-induced pulmonary hypertension].

Intravenous administration of contrast material is a prerequisite for the imaging of the cardiovascular system with computed tomography and digital subtraction techniques. Fatal side effects after intravenous contrast injection, particularly in patients with pulmonary hypertension, have been reported repeatedly. The object of this study was to compare hemodynamic side effects of a conventional, ionic contrast medium (amidotrizoate; 2.1 osmol/kg) and a modern, non-ionic compound (iopamidol; 0.8 osmol/kg) after intravenous bolus injection (1.5 ml/kg). Experiments were carried out in 10 open-chest dogs with pulmonary normotension and hypertension induced by embolisation. Under control conditions (PPA = 19.9 mm Hg) both contrast media produced marked pulmonary and peripheral vasodilation. Major effects were seen after amidotrizoate (RPULM 60.3%, RPERI 32.1% vs 72.5% and 70.4% of controls). In pulmonary hypertension (PPA = 44.2 mmHg), iopamidol had similar hemodynamic effects compared to control conditions. In contrast, amidotrizoate initially led to a significant increase in pulmonary pressure and resistance (PPA = 118.6%; RPULM = 141.7%) followed by a delayed depression of right ventricular function (dP/dt = 65.3%; PRVED = 180.9%). Resuscitation was required in 3 dogs with pulmonary hypertension after amidotrizoate injection. Because of these unfavorable hemodynamic side effects of the conventional high osmolality contrast medium in animal experiments, it can be expected that modern compounds with low osmolality pruduce smaller side effects during diognostic interventions in patients with pulmonary hypertension.

Animals↗
PubMed1983

A new model for testing therapeutic interventions during myocardial ischemia.

An open-chest dog heart model is presented which shows highly reproducible hemodynamic, electrophysiologic, and metabolic changes during and after short-term coronary occlusions. We repeatedly performed 3-min coronary ligations of the proximal ramus interventricularis anterior followed by reperfusion periods of 45 min. Thus, hemodynamic, metabolic, and electrophysiologic parameters of myocardial damage were fully reversible. The experimental model presented seems well suited to evaluate interventions which aim at influencing the extent and damage of myocardial ischemia without needing a large number of separate experiments.

Animals↗
PubMed1983

Improvement of the metabolic and energetic situation of ischemically stressed myocardium by verapamil after experimental coronary artery occlusion.

On anaesthetized open-chest mongrel dogs (n = 7) short-time (3 min), repeated ischemia of relatively large parts of the myocardium was produced by proximal, intermittent occlusion of the LAD artery in intervals of 45 min. Usually, 2-3 control occlusions and 2-3 occlusions under therapy were performed. From hemodynamic data, coronary blood flow and AVD-O2 myocardial oxygen consumption (MVO2) and energy demand (Et) were continuously recorded by use of a micro-computer. The occurring difference between MVO2 and Et (dO2) allowed to calculate during the occlusion period the O2-debt (DO2) and during the reperfusion period the O2-repayment (RO2). Furthermore, the releases of the metabolic ischemia parameters lactate, inorganic phosphate and potassium were determined in the first minute of postischemic reperfusion. Compared to control occlusions, premedication with verapamil (Isoptin) 0.12--0.2 mg/kg b.w.) led intra- and interindividually to a significantly reduced O2-debt (p less than 0.001) during the occlusion period combined with a significantly reduced amount of oxygen, additionally taken up in the early reperfusion period (p less than 0.001). Under verapamil the amounts of metabolic parameters released in the first minute of reperfusion decreased significantly: lactate: -36% (p less than 0.001), inorganic phosphate: -32% (p less than 0.001), potassium: -30% (p less than 0.001). The improvement of the metabolic and energetic situation of ischemic myocardium indicates that verapamil may be of importance in reducing the extent and severity of acute myocardial ischemic injury.

Animals↗
PubMed1982

[Effects of radiographic contrast media on cellular electrophysiology in the beating heart (author's transl)].

Electrophysiological effects of intracoronarily administered contrast media have been documented in 12 thoracotomized dogs at the cellular level by use of a modified microelectrode technique. Injections (n = 63) of 4 different contrast media uniformly led to a temporary cellular hyperpolarisation of the resting potential and prolongation of the action potential. Additional experiments with intracoronary injections of several electrolyte solutions indicate that the observed effects can be explained by contrast-induced changes in the extracellular electrolyte concentrations, mainly by a local deficiency of potassium ions and an excess of sodium ions. The significance of the findings for mechanisms underlying ECG-changes and ventricular arrhythmia by radiographic contrast media will be discussed.

Animals↗
PubMed1981

Basic physiological studies on cardiac pacing with special reference to the optimal mode and rate after cardiac surgery.

Temporary cardiac pacing (CP) is frequently applied postoperatively in the management of low cardiac output (CO) and rhythm instability. However, uncertainty exists about the "optimal" pacing rate, range and mode due to incomplete information on myocardial oxygen consumption (MVO2), related to its hemodynamic determinants, and on myocardial pumping efficiency (eta) at CP. In 10 intact dogs atrial pacing (AP) (90 to 210 beats/min) and ventricular pacing (VP) (70 to 330 beats/min) were investigated in normal and failing hearts. AP and VP were compared at identical rates. MVO2 (4 to 20 ml/min . 100 gr) was measured directly according to the Fick principle. Cardiac efficiency was calculated as the ratio of oxygen equivalent of external cardiac work to MVO2. Rates with maximum CO and a maximal eta occurred only in heart failure. However, maximal CO and eta were obtained at different heart rates (HR). MVO2 was significantly higher (p less than 0.001) under VP as compared to AP at identical rates with a mean increase of 26.5% +/- 6% over AP, although hemodynamics were significantly lower under VP (p less than 0.001). Myocardial pumping efficiency was markedly better under AP with a mean increase of 63% +/- 4.5% over VP even in normal heart. Adjustment of HR at maximal response in CO may become dangerous, particularly under VP, in heart failure. AP, if applicable, may be regarded as the optimal pacing technique due to an optimal relation of improved hemodynamics to MVO2. It may be helpful in correcting an imbalance between oxygen supply and demand in cases of low output syndrome. The pathophysiologic mechanisms and further clinical implications are discussed.

Animals↗
PubMed1978

Biogenesis of cytochrome c in Neurospora crassa. Synthesis of apocytochrome c, transfer to mitochondria and conversion to Holocytochrome c.

1. Precipitating antibodies specific for apocytochrome c and holocytochrome c, respectively, were employed to study synthesis and intracellular transport of cytochrome c in Neurospora in vitro. 2. Apocytochrome c as well as holocytochrome c were found to be synthesized in a cell-free homogenate. A precursor product relationship between the two components is suggested by kinetic experiments. 3. Apocytochrome c synthesized in vitro was found in the post-ribosomal fraction and not in the mitochondrial fraction, whereas holocytochrome c synthesized in vitro was mainly detected in the mitochondrial fraction. A precursor product relationship between postribosomal apocytochrome c and mitochondrial holocytochrome c is indicated by the labelling data. In the microsomal fraction both apocytochrome c and holocytochrome c were found in low amounts. Their labeling kinetics do not subbest a precursor role of microsomal apocytochrome c or holocytochrome c. 4. Formation of holocytochrome c from apocytochrome c was observed when postribosomal supernatant containing apocytochrome c synthesized in vitro was incubated with isolated mitochondria, but not when incubated in the absence of mitochondria. The cytochrome c formed under these conditions was detected in the mitochondria. 5. Conversion of labelled apocytochrome c synthesized in vitro to holocytochrome c during incubation of a postribosomal supernatant with isolated mitochondria was inhibited when excess isolated apocytochrome c, but not when holocytochrome c was added. 6. The data presented are interpreted to show that apocytochrome c is synthesized on cytoplasmic ribosomes and released into the supernatant. It is suggested that apocytochrome c migrates to the inner mitochondrial membrane, where the heme group is covalently linked to the apoprotein. The hypothesis is put forward that the concomitant change in conformation leads to trapping of holocytochrome c in the membrane. The problems of permeability of the outer mitochondrial membrane to apocytochrome c and the site and nature of the reaction by which the heme group is linked to the apoprotein are discussed.

Apoenzymes↗
PubMed1977

Transport of cytoplasmically synthesized proteins into the mitochondria in a cell free system from Neurospora crassa.

Synthesis and transport of mitochondrial proteins were followed in a cell-free homogenate of Neurospora crassa in which mitochondrial translation was inhibited. Proteins synthesized on cytoplasmic ribosomes are transferred into the mitochondrial fraction. The relative amounts of proteins which are transferred in vitro are comparable to those transferred in whole cells. Cycloheximide and puromycin inhibit the synthesis of mitochondrial proteins but not their transfer into mitochondria. The transfer of immunoprecipitable mitochondrial proteins was demonstrated for matrix proteins, carboxyatractyloside-binding protein and cytochrome c. Import of proteins into mitochondria exhibits a degree of specificity. The transport mechanism differentiates between newly synthesized proteins and preexistent mitochondrial proteins, at least in the case of matrix proteins. In the cell-free homogenate membrane-bound ribosomes are more active in the synthesis of mitochondrial proteins than are free ribosomes. The finished translation products appear to be released from the membrane-bound ribosomes into the cytosol rather than into the membrane vesicles. The results suggest that the transport of cytoplasmically synthesized mitochondrial proteins is essentially independent of cytoplasmic translation; that cytoplasmically synthesized mitochondrial proteins exist in an extramitochondrial pool prior to import; that the site of this pool is the cytosol for at least some of the mitochondrial proteins; and that the precursors in the extramitochondrial pool differ in structure or conformation from the functional proteins in the mitochondria.

Biological Transport↗
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

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↗