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Biomedical subjects

E Röth

Publications and source records attributed to E Röth.

At least 19 recordsLinked to original sources

Laparoscopic azygoportal disconnection procedure with a bipolar feedback controlled sealing system in a porcine model.

BACKGROUND: To examine the feasibility of a new, minimally invasive procedure for the devascularization of the proximal stomach and distal esophagus to prevent recurrent variceal bleeding in portal hypertension in a new animal model. MATERIAL AND METHODS: Portal hypertension was created by laparoscopic clip ligation of the portal vein on 20 pigs. After 2 weeks the azygoportal disconnection procedure was performed with the LigaSure-ATLAS instrument. RESULTS: There were 16 pigs out of 20 that survived both operations. Two died during introduction of anesthesia, one because of a cardiac arrest (second operation). One pig died resulting from necrosis of the gastric and esophageal wall. Autopsy (2 weeks later) showed that there was a complete arterial devascularization. At autopsy, none of the remaining 16 pigs had esophageal varices or necrosis of the stomach or esophagus. CONCLUSION: Laparoscopic azygoportal disconnection is a less invasive method for the prevention of rebleeding and seems to be safely performed with the LigaSure-ATLAS instrument.

Animals↗

Angiotensin-converting enzyme inhibition enhances a subthreshold stimulus to elicit delayed preconditioning in pig myocardium.

OBJECTIVES: We assessed the effect of angiotensin-converting enzyme (ACE) inhibition in combination with a subthreshold preconditioning (PC) stimulus to elicit delayed preconditioning against infarction in pig myocardium. BACKGROUND: Bradykinin triggers early PC. Angiotensin-converting enzyme inhibitors increase local bradykinin levels via inhibition of kinin breakdown and have been shown in experimental studies to augment early protection afforded by PC. A role for bradykinin in eliciting delayed PC has not so far been identified. METHODS: We used a two-day protocol. On day 1 (closed chest), pigs were either sham-operated (group 1) or preconditioned, using balloon catheter inflation of the left anterior descending (LAD) coronary artery, with either a full (4 x 5 min PC, group 2) or subthreshold PC stimulus (2 x 2 min PC, group 3). Additional groups were pre-treated with perindoprilat (0.06 mg/kg i.v.) before sham (group 4) or subthreshold PC (group 5). On day 2 (open chest), all pigs were subjected to 40 min occlusion of the LAD followed by 3 h of reperfusion. Infarct size was determined by tetrazolium staining. RESULTS: Group 1 had a mean infarct size of 42.8+/-3.2% of the risk zone. Preconditioning with 4 x 5 min reduced the infarct size to 19.5+/-3.9% (p < 0.05). Groups 3 and 4 had infarct sizes not statistically different from group 1. However, combining perindoprilat with subthreshold PC resulted in a significant limitation of the infarction (18.4+/-3.1% p < 0.05), comparable with group 2. CONCLUSIONS: This is the first study to show that ACE inhibition can augment a mild ischemic stimulus to induce a protected state 24 h later.

Angiotensin-Converting Enzyme Inhibitors↗

[Monitoring of oxidative stress after experimental small bowel autotransplantation].

The difficulty at transplanting the small bowel mainly is caused by the biology of the intestine. It is highly immunogenic, is one of the most sensitive tissues to ischemia-reperfusion injury. Our aims were to investigate changes of oxygen free radical mediated reactions after autotransplantation at different preservation times and perfusion fluids. Our results prove that this model is feasible to examine ischemia-reperfusion injury in the small intestine. Euro Collins (EC) is a suitable preserving solution for small bowel transplantation. There was no significant lipid peroxidation within the first 6 hours of graft preservation. However superoxide dismutase (SOD) activity was dramatically reduced during reperfusion in the tissues samples. Significant increase of reduced glutathione at the same time can be explained by compensatory mechanism to neutralize increased free radical production.

Animals↗

[Partial replacement of the trachea with jejunal autograft in the dog].

Extensive lesions of the cervical trachea can occur as a result of malformation, inflammation, tumor disease or trauma. If a short segment of the trachea is resected primary anastomosis may be possible. The problem of how to treat lesions longer than 50% of total tracheal length is still unresolved. The aim of our study was to clarify the possible use and limitations of small bowel interposition for tracheal replacement in veterinary model. We resected 6 cm of the cervical trachea of 5 adult mongrel dogs. Autolog jejunum free flap was used for replacement. The wall of the implant was supported with 5 polytetrafluoroethylene rings placed on the outer surface of the bowel perpendicular to its axis. We performed the surgery in two stages. Intraoperative tracheostomy was necessary in every case. The tracheal tube extended through the whole length of the implant. The survivals, the viability of the graft and complications were examined. The length of survival ranged between 18 h and 72 h. In one case obstruction of the tracheal tube occurred, in 3 cases the micro vessel anastomosis of the graft thrombosed, in one case both complications developed. In our experience use of the small bowel flap was complicated with fatal technical difficulties. The micro vessel anastomosis proved to be highly risky. Further investigations are needed to improve the results with this method.

Animals↗

[Effect of chronic anemia on the endothelium-dependent dilatation of the brachial artery].

UNLABELLED: The effect of changes in main determinants of whole blood viscosity after red blood cell transfusion on endethel dependent dilatation of brachial artery was studied in patients treated with transfusion because of symptoms of chronic anaemia. PATIENTS AND METHODS: 10 patients were involved, 8 females 2 males, mean age 50.9 +/- 16.6 years. Following blood tests were performed at hospital admission: hemoglobin, red blood cell count, heamatocrit, white blood cell count, platelet count, plasma total protein, fibrinogen, plasma viscosity, blood urea nitrogen, creatinine, cholesterol, triglicerides. Flow mediated dilatation of brachial artery was determined, too. Blood tests and flow mediated dilatation study were repeated after transfusion. RESULTS: The main determinants of whole blood viscosity increased after transfusion. The increase of hemoglobin, red blood cell count, hematocrit were highly significant. The central flow velocity in brachial artery decreased at rest and during hyperemia as well. The flow mediated dilatation of brachial artery wasn't significantly changed by transfusion. CONCLUSIONS: Change of determinants of whole blood viscosity caused by transfusion didn't change the flow mediated dilatation of brachial artery. The probable reason for this that the increase of whole blood viscosity in associated with the decrease of central flow velocity. These two counteracting changes probably equal each other.

Aged↗

[Surgical trauma induced by laparoscopic cholecystectomy].

The objective demonstration of improved postoperative recovery suggests that surgical injury induced by the laparoscopic approach is less intense than that after open surgery. Forty-two patients diagnosed as having noncomplicated gallstones were studied prospectively. They were operated on by laparoscopy (LC, n = 21) or open surgery (OC, n = 21). Both surgical procedures induced significant changes of investigated parameters (acute-phase response, free radical mediated reactions, neutrophil functions). Comparison of the results of the two cholecystectomy techniques showed that laparoscopic cholecystectomy induced a significantly less intense acute-phase response, a more attenuated oxidative stress characterising by free radical mediated reactions and that is less disruptive to neutrophil function. The results and the data from the literature suggest that surgical injury causing by the laparoscopic cholecystectomy is less intense than that after open cholecystectomy, which can explain partially the better clinical outcome following laparoscopic versus open procedure.

Cholecystectomy↗

Bisaramil and antiarrhythmics as inhibitors of free radical generation.

The aim of this study was to investigate the effect of bisaramil--an antiarrhythmic drug under clinical trials-on free radical generation of isolated polymorph neutrophil granulocytes (PMN) and furthermore to compare its activity to that of well-known antiarrhythmics which have different modes of action. PMNs were isolated from healthy beagle dogs, and superoxide radical generation was induced by phorbol-myristate-acetate. Stimulated free radical generation capacity of PMNs and the time lag necessary for the initiation of free radical production were measured. All compounds were used at the concentrations of 10, 25, 50, 75, 100 micrograms ml-1. None of the antiarrhythmics stimulated by itself the free radical generation. Bisaramil exerted concentration dependent inhibitory effect on PMA-stimulated free radical generation and prolonged the time lag concentration dependently. At the investigated concentration range of antiarrhythmics only propafenon, mexiletine and diltiazem showed similar activity to bisaramil, but clear concentration dependency could not be seen in any of the cases. According to the results of this study inhibition of the stimulated free radical production of isolated PMNs cannot be closely connected merely to either membrane stabilizing or Ca-antagonistic activity of drugs. In vitro and earlier measured in vivo inhibitory action of bisaramil on free radical generation indicate a possible cardioprotective effect existing independently from its antiarrhythmic one. This observation may be important in outlining of the clinical indication field of bisaramil, and may be useful in the treatment of reperfusional damage.

Animals↗

Haemarthros induced articular cartilage degradation.

The statement that blood in the articular cavity is cause of cartilage degradation is widely accepted as an axiom. Although the causes of the different articular diseases were explained in numerous studies, none of them has clarified the pathomechanism of haemarthrosis. Our aims were: 1/ to give a morphological description of the blood induced changes in the cartilage, 2/ to verify that the haemarthros is the cause of the cartilage degradation. 10 white rabbits were used in our experimental model. Artificial haemarthros was produced in their left hind knees by intraarticular injection of their own blood. The right hind served as control. The rabbits were divided into to five groups based on the time of the haemarthros (22-50 days). Samples of the condylar cartilage were taken for light, polarization, transmission and scanning electron microscopy examinations. Signs of the disorganization of the matrix structure were showed by polarisation microscope and serious lesions were detected in the perichondrium by scanning electron microscope. Similarity have been suggested amongst the pathomechanism of haemarthrosis and other degenerative cartilage diseases (e. g.: osteoarthrosis, rheumatoid arthritis), so we made the same comparison. In many cases similar morphological changes were observed, as described by other authors in case of degenerative diseases.

Animals↗

The values of detection of free radical mediated reactions in patients.

The peroxidative processes and individual antioxidant protection were measured in patients with different cardiovascular diseases. We concluded that monitoring of this system we were able to detect not only the actual changes of lipid peroxidation and antioxidant defence mechanisms, but additionally the therapeutic efficacy of the treatment.

Adrenergic beta-Antagonists↗

The effects of bisaramil and antiarrhythmics on free radical generation of isolated neutrophil granulocytes.

The aim of this study was to investigate the effect of bisaramil--an antiarrhythmic drug under clinical trials--on free radical generation of isolated polymorph neutrophil granulocytes (PMN) and to compare its activity with well-known antiarrhythmics. PMNs were isolated from healthy beagle dogs, and superoxide radical generation was induced by phorbol-myristate-acetate. Free radical generation capacity of stimulated PMNs were measured. Bisaramil exerted a concentration dependent inhibitory effect on stimulated free radical generation. At the investigated concentration range of the antiarrhythmics only propafenon, mexiletine and diltiazem showed similar activity as bisaramil, but clear concentration dependency could not be seen in any of the cases. According to the results of this study inhibition of stimulated free radical production by isolated PMNs can not be closely related merely to either membrane stabilizing or Ca-antagonistic activity of drugs. In vitro inhibitory action of bisaramil on free radical generation indicates a possible cardioprotective effect existing independently of its antiarrhythmic one. This observation may be important in outlining the range of clinical indications of bisaramil as it may also be useful in the treatment of reperfusion injury.

Animals↗

Monitoring of plasma total antioxidant status in different diseases.

The pathological increase of oxygen free radical generation has already been recognised in more than one hundred diseases. To gain information about the consequences of oxidative stress the investigation of plasma antioxidants seems to be plausible. In our study we used a new kit (RANDOX, England) for measurement of total antioxidant status (TAS) to determine whether it has diagnostic value in comparison with our earlier results of measuring other parameters of oxidative stress in the following diseases: i./In the group of patients with ischemic heart disease (n = 19) the TAS elevated from 1.08 +/- 0.13 to 1.16 +/- 0.11 mM after 2 weeks of cardioprotective drug administration showing the beneficial effect of drug treatment. ii./In the group of patients with essential hypertension (n = 47) its values were below the normal range (1.11 +/- 0.15 mM) at the time of the first investigation and increased gradually following antihypertensive treatment. iii./The changes of TAS values of patients who underwent open (n = 21) or laparoscopic (n = 21) cholecystectomy indicated the less surgical trauma following laparoscopic procedures. Our results suggest that determination of TAS is a valuable and reproducible method to detect the actual antioxidant status in patients.

Antihypertensive Agents↗

Influence of the beta-blocker therapy on neutrophil superoxide generation and platelet aggregation in experimental myocardial ischemia and reflow.

The beneficial effect of beta-blockade has been reported in acute myocardial ischemia as well as in the postinfarction period. Recent interest focused on the special effect of beta-blocking agents regarding the changes of lipid metabolism, free radical mediated reactions and arachidonic acid cascade. In previous experiments on dogs we have shown that ultrashort-acting beta-blocker (Brevibloc) could modify production of prostacyclin and thromboxane in ischemic heart tissue. The purpose of this study was to investigate the effect of Brevibloc on the function of isolated neutrophils and platelets during myocardial ischemia and reperfusion. In mongrel dogs the left descending coronary artery (LAD) was ligated for 1 or 2 hours followed by one hour reperfusion. Animals were divided into two groups: Group I control dogs (n = 21) no drugs were given; in Group II. (n = 20) short half-life beta-blocker esmolol HCl (Brevibloc) was administered intravenously. Polymorphonuclear leukocytes (PMN) were isolated from venous blood before and after LAD ligature and following reperfusion. Spontaneous and phorbol myrystate acetate (PMA) stimulated superoxide radical generation of isolated PMN was measured. Platelets were separated at the same periods and maximal aggregation was determined in platelet rich plasma (PRP) after stimulation with collagen, adrenaline and ADP. There was no spontaneous radical production of PMN neither in the control, nor in the Brevibloc treated animals. Neutrophil superoxide production after activation in Group I was 9.54 +/- 0.3 O2-/min/1.5 x 10(6) before LAD ligature, and significant elevation was present following one hour reperfusion (14.8 +/- 0.8 O2-/min/1.5 x 10(6)). Increased production of neutrophils was inhibited by beta-blocker therapy (9.32 +/- 1.05, 8.25 +/- 0.82 respectively). Collagen and ADP stimulated platelet aggregation increased more than 20% during ischemia in Group I, which elevated further after reperfusion. Administration of Brevibloc diminished maximal aggregation in both cases, after 1-2 hours of LAD ligature and after reperfusion, compared to the initial value. Our findings suggested that ultrashort-acting beta-blocker has in vivo inhibitory action on neutrophil superoxide generation and platelet aggregation influencing the pathological cellular interactions.

Adrenergic beta-Antagonists↗

Myocardial protection by antioxidant during permanent and temporary coronary occlusion in dogs.

In an ischaemic heart model the lipid peroxidation, scavenger state and ultrastructure were studied, to determine the action of a new antioxidant of dihydroquinoline type (MTDQ-DA). In dog experiments, the left descending coronary artery (LAD) was ligated permanently (30 minutes, 1, 2 or 3 hours) or temporarily (30 minutes, 1 or 2 hours of ischaemia followed by 1 hour of recirculation). The experimental protocol involved two groups: control animals without antioxidant treatment and animals treated with antioxidant infusion during the ischaemic and reperfusion period. In both groups, the thiobarbituric acid reactive product, the malondialdehyde (MDA), reduced glutathione (GSH) and superoxide dismutase (SOD) were measured, to illustrate the injured or scavenged state of the membrane system. In nontreated animals the permanent and temporary LAD increased the MDA content, decreased GSH concentration (mainly during reperfusion) and reduced SOD activity. Treatment with MTDQ-DA diminishes the characteristic biochemical changes. According to ultrastructural investigations, irreversible alterations (Ca deposits in the mitochondria, disruption of intramitochondrial membranes, hypercontraction bands) occurred only in the control group. Anti-oxidant therapy is able to reduce the myocardial damages both quantitatively and qualitatively.

Animals↗

Promising reduction of ventricular fibrillation in experimentally induced heart infarction by antioxidant therapy.

Studies were undertaken using a synthetic free radical scavenger (MTDQ-DA) on regional ischaemic dog hearts; it was found that the rate of malignant ventricular arrhythmias and fibrillation after coronary ligature unexpectedly decreased. According to experiments on 22 dogs, the intravenous MTDQ-DA therapy decreases the unfavourable ECG consequences of left anterior descending branch ligature: already 5 to 10 minutes after drug administration the ST segment elevation, the QT interval lengthening and the occurrence of ventricular extrasystoles and salvos are diminishing. The so-called epicardial ST map ameliorates rapidly. MTDQ-DA as a blocking agent of free radicals is able to prevent the irritative stimuli around and in the border zone of an infarct, has a vigorous anti-arrhythmogenous effect and greatly reduces the electric heterogeneity. These unexpected results may lead to a promising therapy for the acute heart infarction.

Animals↗

Orientation dependence and motional properties of spin labels in cardiac and skeletal muscle fibres.

Orientation dependence and rotational motion of maleimide spin labels attached to the fast reacting thiol sites of myosin were studied in glycerinated cardiac and skeletal muscle fibres in rigor and in relaxing medium. The probe order in skeletal muscle was shown to be about one order of magnitude higher than that in cardiac muscle. In skeletal muscle in rigor the orientational order is static on the time scale of the saturation transfer electron paramagnetic resonance measurement (ST EPR, rotational correlation time of the label is greater than 1 ms), but in cardiac muscle fibres, a disorder was observed which was at least partly dynamical, the rotational correlation time being about 100 microseconds. In relaxing solution the degree of order of probe molecules in both types of muscle was strongly reduced at and above the resting length. The disorder was at least partly dynamical on the ST EPR time scale, the apparent rotational correlation times being 200 microseconds for skeletal muscle and 60 microseconds for cardiac muscle, respectively. According to the results of ST EPR the rotational behavior of cross-bridges was identical in cardiac and skeletal muscle in relaxing medium.

Adenosine Triphosphatases↗