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Biomedical subjects

D Kling

Publications and source records attributed to D Kling.

At least 19 recordsLinked to original sources
PubMed1992

Inhibition of leukocyte extravasation with a monoclonal antibody to CD18 during formation of experimental intimal thickening in rabbit carotid arteries.

In the rabbit model of electrically induced intimal thickening, the adherence processes of different leukocyte subsets as well as the functional significance of leukocyte invasion in the initial migration of smooth muscle cells (SMCs) into the intima were studied by using monoclonal antibody (MAb) 60.3 (directed to the leukocyte adherence glycoprotein CD18), a known potent inhibitor of leukocyte adhesive functions. In control carotid arteries exposed to two periods of electrical stimulation within 36 hours, leukocytes, including all granulocyte subsets, monocytes, and lymphocytes, invaded the cell-free subendothelium. Concomitantly, SMCs were observed to migrate from the media into the intima. In the MAb 60.3-treated rabbits, however, neutrophil emigration into the stimulated arteries was abolished, whereas mononuclear leukocyte accumulation in the intima was only partially inhibited, indicating a complete CD18-dependent mechanism for neutrophil extravasation and additional receptor-ligand systems for the emigration of mononuclear leukocytes. SMCs moved into the intima despite complete blockage of neutrophils and the reduced accumulation of mononuclear cells within the subendothelium after MAb administration. These results preclude neutrophils as initiators of SMC migration into the intima. The influence of mononuclear cells on the migratory behavior of SMCs in intimal thickening formation, however, needs further elucidation.

Animals↗
PubMed1990

The new phosphodiesterase inhibitor enoximone in patients following cardiac surgery--pharmacokinetics and influence on parameters of coagulation.

Enoximone is a selective inhibitor of the phosphodiesterase-III enzyme (PDE-III) and possesses positive inotropic and vasodilatory properties. The PDE-inhibitor amrinone has been associated with adverse effects on coagulation by decreasing platelets. To investigate the influence of enoximone on hemostasis, 18 patients undergoing elective aorto-coronary bypass grafting and receiving enoximone were compared to a control group (n = 18). In addition, the plasma levels of enoximone and its major metabolite (enoximone-sulfoxide) were studied following a single injection (0.5 mg/kg) and during a continuous infusion (5 and 10 micrograms/kg.min) before, during and after extracorporeal circulation (ECC). No difference between study and control groups was found for the parameters of coagulation during the investigation period; in particular there were no differences in platelet count and platelet function (thrombelastography). Following the single bolus, peak plasma levels decreased during ECC to ineffective levels. Continuous infusion, however, maintained effective plasma levels of enoximone; sulfoxide levels were twice as high as enoximone concentrations up until the end of the investigation period. It is concluded that enoximone can be judged to be safe in respect to its effects on coagulation even following ECC and at relatively high doses. The use of continuous infusion results in plasma levels which remain at an effective concentration through to the time that the patient is transferred to the intensive care unit.

Aged↗
PubMed1990

Comparative effects of enoximone and theophylline on plasma catecholamines and haemodynamics in cardiosurgical patients.

The release of endogenous catecholamines in aorto-coronary bypass graft patients receiving either 0.5 mg/kg enoximone (n = 10), 4.0 mg/kg theophylline (n = 10) or saline solution (control, n = 10) has been studied, as well as certain haemodynamic parameters. Adrenaline (A) and noradrenaline (NA) concentrations were not significantly changed by the administration of enoximone. Theophylline caused a small increase in NA (+40% in the 1st min) and a marked increase in A (approximately +7000% in the 1st min), which still remained elevated at the end of the investigation period (+220% in the 30th min). The major haemodynamic effects of enoximone were a significant increase in cardiac index (CI; +35%) and a decrease in pulmonary capillary wedge pressure (PCWP; -27%), pulmonary artery pressure (PAP; -21%), RVEDV and RVESV, while the heart rate (HR) remained almost unchanged. The dominant haemodynamic effects of theophylline were an increase in HR (+26%; arrhythmia in 3 patients), PAP (+22%), and RVEDV (+19%), while RVESV (+26%), MAP (-16%), CI (-14%), and RVEF (-15%) fell significantly. It is concluded that the haemodynamic actions of enoximone are not mediated by catecholamine release, whereas the adverse cardiovascular effects of theophylline might partly be explained by the significant increase in plasma adrenaline.

Cardiac Catheterization↗
PubMed1990

RETRACTED: Acute preoperative plasmapheresis and established blood conservation techniques.

Plasmapheresis performed weeks before an operation producing autologous plasma has proved to be of benefit in elective operations. First experiences in acute plasmapheresis, which is performed immediately before the operation, have been reported recently. When acute plasmapheresis is used in cardiac operations, however, it must be viewed in connection with other techniques for reducing blood consumption such as the Cell Saver (CS) and ultrafiltration devices. In 60 patients undergoing elective aortocoronary bypass grafting, acute plasmapheresis was performed, producing either platelet-poor plasma or platelet-rich plasma, in combination with either the Cell Saver or hemofiltration. Fluid balance during cardiopulmonary bypass was significantly lower in the hemofiltration patients. Postoperatively, none of these patients received donor blood, whereas 4 patients of the Cell-Saver groups needed packed red blood cells. AT-III, fibrinogen, the number of platelets, albumin, total protein, and colloid osmotic pressure were less compromised when hemofiltration was used in combination with acute plasmapheresis in contrast to combination with the Cell-Saver technique. Plasma hemoglobin was without differences during the investigation period, and polymorphonuclear elastase was less increased when platelet-rich plasma was produced preoperatively. On the first postoperative day, most of the differences between the groups had already disappeared. We conclude that when acute plasmapheresis is used in cardiac operations, discarding of plasma by the Cell Saver should be avoided and ultrafiltration devices should replace centrifugation techniques for blood conservation.

Blood Coagulation Factors↗
PubMed1990

Enoximone treatment of impaired myocardial function during cardiac surgery: combined effects with epinephrine.

Enoximone belongs to a new class of noncatecholamine-positive inotropes, which selectively inhibit phosphodiesterase type III and increase cyclic AMP (cAMP). This study was performed in 30 coronary artery surgery patients with impaired myocardial function (ejection fraction [EF] less than 50%). The study's two purposes were to investigate the hemodynamic effects of enoximone, 0.5 mg/kg, administered following induction of anesthesia (phase I), and to assess whether enoximone can potentiate the actions of sympathomimetic agents during weaning from cardiopulmonary bypass (CPB) (phase II). Starting with already reduced hemodynamics, induction of anesthesia led to a further deterioration of blood pressure and cardiac output (CO). Administration of enoximone produced a significant increase in cardiac index (CI) (+47%), whereas pulmonary capillary wedge pressure (PCWP) (-37%), pulmonary artery pressure (PAP) (-17%), and systemic vascular resistance (SVR) (-17%) were significantly reduced. Heart rate (HR) was not increased, and no dysrhythmias occurred during the investigation. The hemodynamic effects were maintained for 30 minutes until the start of the operation. In phase II, where weaning from CPB was not possible without pharmacological support, either enoximone (0.5 mg/kg) + epinephrine (0.1 micrograms/kg/min) or only epinephrine (same dosage) was randomly selected. Weaning was successful in both groups, but the combined therapy produced a larger increase in cl and a more pronounced decrease of the elevated filling pressure (PCWP). PAP was not changed in the combined therapy group, but increased in the patients receiving epinephrine alone. It is concluded that enoximone has beneficial hemodynamic effects in the perioperative period, and that potentiation of the effects of epinephrine in severe heart failure may be one of the drug's most useful features.

Aged↗
PubMed1990

Acute plasmapheresis during cardiac surgery: volume replacement by crystalloids versus colloids.

Acute plasmapheresis (APP) is an additional tool for blood conservation during cardiac surgery. In a randomized study of 60 aortocoronary bypass patients undergoing APP, the influence of replacement of the withdrawn autologous plasma (10 mL/kg) by either colloids (low molecular weight hydroxyethyl starch solution [6% HES 200/0.5]) or crystalloids (Ringer's solution) was investigated. APP was performed by means of a centrifugation technique producing platelet-poor plasma. During and after cardiopulmonary bypass (CPB), either a cell saver (CS) or a hemofiltration (HF) device was also used for blood concentration. Almost three times as much crystalloid as HES solution was necessary for replacement of autologous plasma. Fluid balance during CPB was significantly more positive in the crystalloid patients, particularly when a CS was used. Blood loss was highest in the crystalloid patients in whom a CS was used in addition to APP, and these were the only patients who needed packed red cells. The platelet count, AT-III and fibrinogen plasma concentrations, colloid osmotic pressure, albumin, and total protein were significantly less compromised in the patients with colloid volume replacement. These parameters were closest to control values in patients receiving colloid replacement and HF. It is concluded that colloid is preferred for replacement of autologous plasma withdrawn by APP, and HF is superior to the CS when the combined technique for blood conservation is used.

Coronary Artery Bypass↗
PubMed1990

Effects of nitrous oxide on endocrine stress response and haemodynamic parameters during coronary artery surgery.

To compare simultaneously the influence of nitrous oxide on haemodynamic parameters and on surgical stress response, 20 patients scheduled for coronary artery bypass graft were investigated during standardized modified neurolept anaesthesia. Before onset of cardiopulmonary bypass, one group received nitrous oxide and oxygen (2:1), whereas in the other group air with oxygen (F10(2) 0.33) was used. Increases in adrenaline, noradrenaline, ADH, and cortisol were slightly less and mean arterial pressure and cardiac output reached markedly lower levels in the nitrous oxide group. When nitrous oxide is not acceptable for a cardiac surgery patient during modified neurolept anaesthesia due to haemodynamic side effects enhancing intravenous application of anaesthetics to compensate the analgetic properties of the substance should be considered.

Adrenocorticotropic Hormone↗
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↗