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Biomedical subjects

D Kling

Publications and source records attributed to D Kling.

At least 37 records · Page 2Linked to original sources
PubMed1990

Suppression of tumor-forming ability and related traits in MCF-7 human breast cancer cells by fusion with immortal mammary epithelial cells.

Somatic cell hybrids between MCF-7 human breast cancer cells and normal immortalized human mammary epithelial cells have been obtained by polyethylene glycol-mediated cell fusion. The hybrid cells are suppressed in their ability to form tumors in nude mice, as well as in traits specific to the tumorigenic MCF-7 parent: growth factor independence, tumor necrosis factor sensitivity, and pS2 gene expression. In addition, they display other characteristics of the "normal" parent, including increased expression relative to the MCF-7 cells of the genes for the extracellular matrix component fibronectin, the intermediate filament keratin 5, and the angiogenesis inhibitor thrombospondin. The levels of keratins 8 and 18 also resemble those of the nontumorigenic parent. These results provide evidence for the existence of tumor suppressor gene products in immortal mammary epithelial cells. We propose a characteristic "suppressed" tumor cell phenotype, which encompasses altered cytoarchitecture, angiogenesis capabilities, and growth factor requirements.

Animals↗
PubMed1990

Haemodynamic effects of the phosphodiesterase inhibitor enoximone in comparison with dobutamine in esmolol-treated cardiac surgery patients.

In a randomized study, the haemodynamic effects of the new phosphodiesterase-III-inhibitor, enoximone, were compared with dobutamine in acutely beta-adrenoceptor blocked patients. Twenty patients scheduled for aorto-coronary bypass grafting suffering from tachycardia (heart rate (HR) greater than 100 beat min-1) were treated by infusion of esmolol, an ultra-short acting, selective beta 1-blocker. Twenty minutes after the start of esmolol, either enoximone 0.5 mg kg-1 as a bolus (n = 10) or dobutamine 5 micrograms kg-1 min-1 was administered. Haemodynamic effects were monitored for 40 min, including measurement of left ventricular haemodynamics. Esmolol reduced HR (-27%) and dP/dtmax (-38%) significantly in both groups. Cardiac index (CI) was decreased also. Enoximone increased Cl (+35%) and dP/dtmax (+39%) significantly, while no change in dobutamine-treated patients was observed. Systemic vascular resistance increased only in the dobutamine group (+44%).

Adrenergic beta-Antagonists↗
PubMed1990

Preoperative plasmapheresis in patients undergoing cardiac surgery procedures.

Donor plasmapheresis that is carried out weeks before the operation has proven to be of benefit in elective orthopedic patients with regard to reducing homologous blood consumption and preserving coagulation. In this study acute preoperatively performed plasmapheresis (APP) was investigated in cardiac surgery patients. Forty-five patients scheduled for elective aortocoronary bypass surgery were randomly divided into three groups of 15 patients each: 1) removal of platelet-poor plasma (PPP), 2) removal of platelet-rich plasma (PRP), and 3) no plasmapheresis (control group). Plasma volume removed was 10 ml/kg in all APP patients, and plasma was replaced by the same amount of low-molecular weight hydroxyethylstarch solution (6% HES 200/0.5). Various laboratory data were investigated before, during, and after extracorporeal circulation (ECC). Blood loss in control patients was more pronounced than in the two APP groups; two of the control patients needed packed red cells. APP itself did not affect coagulation variables, free hemoglobin, or polymorphonuclear (PMN) elastase. At the end of the operation, 5 h after ECC, and at the first postoperative day the number of platelets was significantly lower in the control group; PRP patients showed the highest values. Fibrinogen and AT-III levels were less compromised in APP patients than in the control group. Global coagulation parameters did not differ between the groups within the whole investigation period. PMN elastase increased significantly during ECC in all groups with the greatest increase in the control group (722%) and the smallest increase in PRP patients (280%), possibly due to the removal of cellular elements in this group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Volume therapy with hypertonic saline hydroxyethyl starch solution in cardiac surgery.

The ideal solution for volume therapy remains controversial. In cardiac surgery, haemodynamic efficacy as well as the influence of extracorporeal oxygenation are of major interest when administering volume. The present study examines the effects of a new hypertonic saline hydroxyethyl starch solution in comparison to a 6% hydroxyethyl starch solution on haemodynamics and laboratory variables. Patients scheduled for elective aortocoronary bypass grafting received hypertonic saline hydroxyethyl starch (n = 10) or hydroxyethyl starch (n = 10) after induction of anaesthesia in order to double baseline pulmonary capillary wedge pressure. Ten patients without volume therapy served as a control group. Significantly less hypertonic solution than standard solution was effective in doubling pulmonary capillary wedge pressure. Fluid requirements in the patients who received the hypertonic solution were significantly less during, as well as after, cardiopulmonary bypas in comparison to those in the other groups. Cardiac index increased most in the patients who received the hypertonic solution (+34.8%), as did right ventricular end-diastolic volume. Patients in that group showed the highest decrease in total systemic resistance (-29.8%), whereas arterial pressure and right ventricular ejection fraction remained almost unchanged in all groups. No negative alteration in coagulation or organ function was demonstrated within the investigation period. It can be concluded that hypertonic saline hydroxyethyl starch solution seems to be a valuable alternative to conventional volume therapy in cardiac surgery.

Blood Volume↗
PubMed1990

RETRACTED: Efficacy of the phosphodiesterase inhibitor enoximone in complicated cardiac surgery.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the request of the editor. In 2018, CHEST published a notice1 that all articles authored by Joachim Boldt be read with caution due to expressions of concern about falsified data. In 2020, CHEST received additional evidence of research misconduct and breaches of scientific integrity that were discovered following an investigation by the author's former institution, the University of Giessen2. In light of this new evidence, this article has been retracted by CHEST. 1. Irwin, R.S., MD, Master FCCP. Notice From the Editor in Chief. CHEST 153(3), p. 767. 2. Mukherjee, J. Statement on the scientific credibility of articles published by Joachim Boldt, formerly professor at Justus Liebig University (JLU), Giessen, Germany. https://ars.els-cdn.com/content/image/1-s2.0-S000709122030163X-mmc3.pdf.

Aged↗
PubMed1990

Drug interactions: the new phosphodiesterase inhibitor enoximone and the calcium channel blocker nifedipine in coronary surgery patients--influence on hemodynamics and plasma concentrations.

The calcium channel blocker nifedipine and the new phosphodiesterase (PDE) inhibitor enoximone are used in the treatment of cardiovascular diseases. Since both substances are acting on slow calcium channels and because systemic elimination of these two agents is dependent on oxidative drug metabolizing enzyme activity, this study was performed in order to investigate hemodynamic changes and effects on plasma levels when both substances are given simultaneously. Forty-five patients undergoing aortocoronary bypass grafting were randomly subdivided into three groups: (a) group (n = 15) received 0.3 micrograms/kg/min of nifedipine as an infusion (N patients); (b) group (n = 15) received 0.5 mg/kg of enoximone as a bolus (E patients); and (c) group (n = 15) received nifedipine and enoximone in the same dosages (E + N patients). In addition to various hemodynamic variables, plasma levels of nifedipine, enoximone, and enoximone sulfoxide were measured until the end of the operation. Injection of enoximone was followed by an increase in cardiac index and right ventricular ejection fraction, decrease in pulmonary artery pressure, pulmonary capillary pressure, and systemic vascular resistance, whereas heart rate and mean arterial pressure remained almost unchanged. These changes were comparable for E and E + N patients. Plasma concentrations of enoximone and enoximone sulfoxide were not affected by nifedipine infusion and showed a comparable course in E and E + N patients. Nifedipine plasma level dropped to values less than 15 ng/ml at the end of extracorporeal circulation in N and E + N patients. It can be concluded that enoximone improved hemodynamics even in patients pretreated with nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

[The hemodynamic effects of various hydroxyethyl starch solutions in heart surgery patients].

Blood conservation is gaining more and more interest because of the increasing risks involved in homologous blood transfusions. Acute normovolemic hemodilution (ANH) is becoming an established technique even in cardiac surgery patients. The "optimal" kind of volume replacement, however, is still controversial. Thus, this study was carried out to investigate the hemodynamic response of 6 different hydroxyethyl starch (HES) solutions as volume replacement. METHODS. In 60 patients undergoing elective aortocoronary bypass surgery, acute, preoperative hemodilution was performed (10 ml/kg) and HES with different concentrations, molecular weight, and substitution was infused according to a randomized sequence: 1. 6% HES 450,000/0.7; 2. 10% HES 200,000/0.5; 3. 3% HES 200,000/0.5%; 4. 6% HES 40,000/0.5; 5. 6% HES 200,000/0.5; 6. 6% HES 200,000/0.62. All patients were monitored using a new pulmonary artery catheter that allows measurement of the right ventricular ejection fraction (RVEF), right ventricular enddiastolic volume (RVEDV), and right ventricular end systolic volume (RVESV) in addition to standard hemodynamic parameters. RESULTS. Immediately after finishing ANH the typical hemodynamic changes of hemodilution (HD) were apparent (decrease in peripheral resistance and increase in cardiac index (CI]. All 6 solutions investigated were effective in hemodynamic stabilization (no changes in mean arterial pressure (MAP), filling pressures (PCP, RAP), or heart rate (HR]. Forty min after ANH, however (before beginning extracorporeal circulation (ECC], there were significant differences between the groups: in groups 3 and 4 the increase in CI had already disappeared, and SVI in group 3 was even lower than the baseline values (-8%). In the other groups, a higher CI level remained even 40 min after ANH, which was most pronounced in groups 2 (+40%) and 5 (+43%). Right ventricular performance was not changed by ANH (RVEF unchanged in all groups). Forty min after hemodilution RVEDVI (-8%) and RVESVI (-16%) decreased significantly only in group 4, whereas in the other groups these parameters were still elevated. The most pronounced positive fluid balance after the end of ECC was found in group 4 (+850 ml); in these patients paO2 decreased significantly (-150 mmHg). CONCLUSIONS. The guarantee of stable hemodynamic conditions is a prerequisite when performing ANH in coronary surgery patients. The different physiochemical attributes of various HES solutions seem to be important, thus influencing their hemodynamic response. In this study, low-concentration (3% HES 200/0.5) and low-molecular (6% HES 40/0.5) HES solutions were less effective in stabilizing hemodynamics until the beginning of ECC. Additionally, their negative influence on fluid balance during ECC, followed by a deterioration in pulmonary function led to the conclusion that other solutions are preferable; in particular, 10% HES seems to be of advantage in these situations.

Coronary Artery Bypass↗
PubMed1990

[The hemodynamic effects of a treatment with beta-receptor blockers during coronary surgery. A comparison between acebutolol and esmolol].

UNLABELLED: Patients undergoing coronary artery bypass grafting are at risk for perioperative myocardial ischemia. Most such ischemic episodes occur without obvious hemodynamic changes. Tachycardia as a predictor for increased myocardial oxygen consumption doubles the incidence of myocardial ischemia when heart rate increases to over 110 beats/min. During the operative procedure for coronary revascularization, some maneuvers, e.g. intubation, sternotomy and mediastinal preparation, may be associated with tachycardia and increases in blood pressure despite an adequate level of anesthesia, so that the administration of beta-receptor blocking agents seems to be indicated. METHODS: The study included 20 patients undergoing elective aortocoronary bypass grafting. All patients developed tachycardia (heart rate greater than 100 beats/min) before the start of extracorporeal circulation. The hemodynamic effects of 0.1 mg/kg acebutolol given i.v. as a bolus over 30 s and hemodynamic effects of the ultrashort-acting esmolol by continuous infusion (loading dose 500 micrograms/kg over 1 min followed by a dose of 100 micrograms/kg per min) were randomly investigated. Anesthesia was maintained with fentanyl, midazolam and pancuronium bromide. All patients were invasively monitored by means of a pulmonary artery catheter. In addition, left ventricular pressure (LVP), left ventricular end diastolic pressure (LVEDP) and dp/dtmax were measured. RESULTS: Both acebutolol and esmolol, decreased the heart rate significantly (-24%, -27.5%), while the mean arterial pressure remained nearly unchanged. The cardiac index was diminished following acebutolol (-15.4%) and esmolol (-27.4%), while no significant change in stroke volume index was observed; systemic vascular resistance rose in all patients. Pulmonary artery pressure, PCP, PRA, LVP and LVEDP were unchanged, whereas dp/dtmax decreased both with acebutolol (-23.5%) and with esmolol (-36.5%). CONCLUSION: Both beta-receptor blockers--acebutolol and the ultrashort-acting esmolol--diminish heart rate sufficiently when tachycardia occurs during coronary artery bypass grafting. Reduction of heart rate is associated with a decrease of cardiac output and an impairment of myocardial contractility. From the hemodynamic point of view there is no major difference between the two beta-receptor blockers investigated, but esmolol may have an advantage over acebutolol because of its short elimination half-life.

Acebutolol↗
PubMed1990

Myocardial temperature during cardiac operations: influence on right ventricular function.

Maintenance of right heart integrity is frequently neglected during coronary operations. Right ventricular dysfunction sometimes limits the success of the surgical procedure, however. In addition to the use of cardioplegic solutions, myocardial hypothermia during ischemic cardiac arrest seems to be an important factor for guaranteeing right ventricular performance thereafter. This study was designed to measure myocardial temperature in patients with coronary artery disease who have significant stenosis of the right coronary artery in comparison with those who do not have stenosis of the right coronary artery and to evaluate the influence of myocardial temperature on right ventricular hemodynamics after cardiopulmonary bypass. Right ventricular function was assessed by thermodilution technique, which allows measurement of right ventricular ejection fraction, right ventricular end-diastolic volume, and right ventricular end-systolic volume. Right ventricular temperature differed significantly between the two groups, with the lowest value of 15.1 degrees +/- 1.8 degrees C in the group without stenosis of the right coronary artery and a value of 22.2 degrees +/- 2.1 degrees C in the group with stenosis of the right coronary artery. Left ventricular and septal temperatures were without group differences within the investigation period. Right ventricular hemodynamics were impaired only in the group with stenosis of the right coronary artery with a decrease in right ventricular ejection fraction from 44.2% to 34.1% immediately after termination of bypass and an increase in right ventricular end-diastolic volume index (+38%) and right ventricular end-systolic volume index (+70%). Cardiac index decreased only in this group, too (-22.5%). Analysis of covariance revealed a significant correlation only between changes in right ventricular ejection fraction, right ventricular end-diastolic volume, and right ventricular end-systolic volume and the course of right myocardial temperature. It is concluded that right ventricular hypothermia is more difficult to achieve in patients with a diseased right coronary artery. Constant myocardial hypothermia, however, seems to be important in guaranteeing right ventricular function, which easily can be evaluated by the thermodilution technique.

Body Temperature↗
PubMed1989

Intimal thickenings of jugular veins after application of a stimulus known to be sclerogenic in arteries.

The present study examined the intimal reactions of rabbit jugular veins to a stimulus known to elicit arteriosclerotic alteration in the artery wall. Repeated transmural electrical stimulation was applied to external jugular veins of both normo- and hypercholesterolaemic rabbits. Endothelial permeability, as well as changes in intimal architecture, were investigated by electron microscopy. Initially, the veins responded to electrical stimulation with an increased transendothelial transport of horseradish peroxidase (40,000 daltons). After application of the stimulation program for 4 weeks, intimal fibrous thickening (33%), cellular fibrous proliferation (50%), and organized mural thrombi were observed. The fibrous thickening was characterized by an abundance of connective tissue matrix and paucity of subendothelial cells. The cellular fibrous proliferate predominantly consisted of myocytes with few interspersed monocytes/macrophages and granulocytes. It resembled intimal plaques induced in carotid arteries by the same method. However, the venous thickenings showed limited size and a more pronounced fibrous response when compared with the arteriosclerotic lesions. The morphological similarities between the observed venous intimal thickenings and the different types of phlebosclerotic manifestations described in the literature, especially intimal proliferations in vein grafts, render the model of electrical stimulation suitable for the elucidation of underlying pathogenic mechanisms.

Animals↗
PubMed1989

Effects of thiopentone and etomidate on median nerve somatosensory evoked responses.

Somatosensory evoked potentials (SEP) after median nerve stimulation were recorded in 40 patients during infusion of either 15 mg/kg bw thiopentone or 1 mg/kg bw etomidate (n = 10) within 15 min and after 0.3 mg/kg bw etomidate (n = 20). Marked alterations of SEP waveforms and changes in latencies were observed in all patients. Central conduction time (CCT) was significantly correlated to plasma thiopentone concentration. Infusion of high doses of thiopentone and etomidate was followed by a complete loss of middle and long latency components. Amplitude of the primary cortical SEP N20 was found to be unchanged after thiopentone and to be increased after etomidate, indicating the synchronizing properties of this drug. A pronounced increase in SEP latencies and CCT and waveform alterations have to be considered during hypnotic drug administration in intensive care medicine and intraoperatively.

Adult↗
PubMed1989

Influence of acute volume loading on right ventricular function after cardiopulmonary bypass.

The influence of acute volume loading on right ventricular function immediately after extracorporeal circulation (ECC) was investigated in 25 patients undergoing elective aortocoronary bypass grafting. In addition to commonly monitored hemodynamic variables, right ventricular (RV) ejection fraction (EF) was measured by thermodilution technique using a new fast-response thermodilution catheter. In eight patients with concomitant severe stenosis (greater than 89%) of the right coronary artery (RCA), volume loading was followed by a decreased RVEF and cardiac output. In contrast, RVEF in the 17 patients without diseased RCA increased significantly, with an increase in cardiac output. Duration of aortic cross-clamping (i.e., ischemia) was more pronounced in the group with decreased RVEF due to RCA grafting. Increased end-diastolic volume and decreased RV contractility index indicated that patients with myocardial ischemia during cardiac surgery procedures sometimes were unable to make the adaptations required. We conclude that cardiocirculatory dysfunction associated with ECC may be caused by depressed RV function. Acute volume loading in this situation may lead to further deterioration of myocardial function due to RV failure, a condition which cannot be diagnosed readily at the bedside with the usual monitoring techniques.

Aged↗
PubMed1989

Hemodynamic effects of enoximone in cardiac surgery patients.

Enoximone belongs to a new class of inotropic drugs that are not related either to digitalis or to catecholamines. It acts primarily through selective inhibition of phosphodiesterase III (PDE-III) and has additional vasodilating properties. Hemodynamic effects of intravenously administered enoximone (0.5 mg/kg) were investigated in patients undergoing aortocoronary bypass grafting before and during anesthesia as well as during extracorporeal circulation (ECC). Patients who were impossible to be weaned off ECC without pharmacological support were investigated also. A significant increase in cardiac index and dp/dtmax, a decrease in pulmonary capillary pressure, and a small decrease in mean arterial pressure were the major hemodynamic effects. Heart rate was not changed and no signs of arrhythmia were seen during the entire investigation period. Interactions with the anesthetics used could not be observed in this study. In patients with impaired myocardial performance during weaning from ECC, enoximone seems to be helpful in stabilizing cardiac output and decreasing filling pressure. The mechanism for improvement appears to be enhanced contractility due to its positive inotropic effects, as well as a decrease in left ventricular outflow resistance resulting from peripheral vasodilation.

Cardiac Surgical Procedures↗
PubMed1989

[Hemodynamic effects of the new phosphodiesterase inhibitor enoximone in heart surgery patients].

The new phosphodiesterase-III inhibitor (PDI) enoximone is a non-catecholamine, non-glycoside cardiotonic agent with concomitant vasodilating properties. It has proved beneficial in patients with severe chronic heart failure. The influence of enoximone i.v. on hemodynamics was investigated during cardiac surgery under various conditions. METHODS. A randomized series of 60 patients undergoing elective aorto-coronary bypass grafting were studied. The hemodynamic effects of 0.5 mg/kg enoximone given i.v. as a bolus (30 s) were investigated before anesthesia (n = 10), during anesthesia (n = 10), and during extracorporeal circulation (ECC, n = 10) and compared with those observed in corresponding control groups (n = 10 in each control) of patients who had received saline solution as placebo. Anesthesia was maintained with weight-dependent dosages of fentanyl, midazolam and pancuronium bromide. All patients were invasively monitored by means of a pulmonary artery catheter. Additionally, left ventricular pressure (LVP), left ventricular end-diastolic pressure (LVEDP) and dp/dtmax were measured before the initiation of ECC. During ECC direct vascular effects were investigated with measurement of perfusion pressure and the volume of the oxygenator. RESULTS. Before the induction of anesthesia no significant change in MAP and HR could be observed, whereas CI increased (+20%) and TSR decreased (-24%) significantly. During anesthesia, the injection of enoximone was followed by a significant decrease in MAP only in the 1st min (-17%); baseline level was reached again after 6 min; and HR was slightly increased (+8%). TSR (-31%) and LVEDP (-38%) decreased, whereas CI (+17%) and dp/dtmax (+45%) were increased significantly. During ECC perfusion pressure (-37%) and the volume of the oxygenator (-17%) were significantly decreased, demonstrating direct vasodilating effects on both the arteries and the vein. CONCLUSION. Arterial and venous vasodilation with an increase in myocardial performance (dp/dtmax) resulting in an increase in CI were the predominant hemodynamic effects of enoximone i.v. No arrhythmogenic effects or interactions with the anesthetics used were observed in this study.

Anesthesia↗
PubMed1989

[Homologous fresh frozen plasma in heart surgery. Myth or necessity].

Routine administration of homologous fresh frozen plasma (FFP) is widely carried out in cardiac surgery although the risks of blood transfusion can never be excluded. The effect of two units of FFP (430 +/- 11 ml) given after the end of extracorporeal circulation (ECC) (group 1, n = 20) was compared to a control group (n = 20) without FFP in elective aorto coronary bypass patients. Various laboratory parameters, including coagulation data, were measured before and after the end of ECC up to the 1st postoperative day. The patients were comparable with regard to biometric data, anesthesia, and surgical procedure. The major result of this study shows, that routine administration of FFP has no beneficial effect with respect to hemostatic balance. In comparison to a control group, the increase in elastase and decrease in paO2 was even more pronounced in the FFP group. Both blood loss and the need for blood transfusion did not differ between the groups. It can be concluded that a bleeding tendency in cardiac surgery may be caused by ECC itself and by perioperative plasma loss. The routine administration of a relatively small amount of FFP has no positive influence on hemostasis. Substitution therapy in this situation should be guided by the results of coagulation studies.

Aged↗
PubMed1989

[Preoperative normvolemic hemodilution in heart surgery. Pulmonary changes with the use of new technics].

Interest in preoperative hemodilution (HD) has intensified perceptibly again, because of the increasing risk of adverse reactions to donor blood. However, in coronary surgery patients the use of HD is still the subject of controversy, as it may possibly influence organ function and especially lung water content. New techniques, including membrane oxygenation, extracorporeal circulation (ECC) with only "partial" bypass due to 2-stage cannulation, and hemoconcentration with cell separators, have significantly modified patient management in the field of cardiac surgery. Therefore, the influence of moderate hemodilution (12 ml/kg) on extravascular lung water (EVLW) was investigated under these conditions in 45 patients with coronary artery disease. Volume replacement was performed either with hydroxyethyl starch solution (HD-HES group, n = 15, ratio of replacement 1:1) or with Ringer's lactate (HD-RL-group, n = 15, ratio 2.5:1); 15 patients not subjected to HD served as controls. ECC was carried out with membrane oxygenators only in partial bypass. Both during and after ECC, blood was concentrated by means of a cell-saving system allowing separation and reinfusion of the red cells while the plasma is discarded. EVLW was measured using a double-indicator dilution technique with indocyanine green. Starting from comparable baseline values, EVLW was not significantly changed by hemodilution. After ECC, however, the HD-RL group showed a significant increase in lung water content (means: +2.49 ml/kg equal 42.6%), whereas this was not significantly changed in the other groups. By 5 h after ECC, the lung water content had returned to baseline values and no more differences could be observed between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Water↗