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Biomedical subjects

I Gabauer

Publications and source records attributed to I Gabauer.

At least 19 recordsLinked to original sources

Modulation of cAMP level by tedisamil in guinea pig heart.

Tedisamil is antiarrhythmic class III drug with antifibrillating/defibrillating potency linked to enhancement of intermyocyte gap junctional electrical coupling most likely via its sympathomimetic cAMP-related mechanisms. This study was designed to examine the effect of tedisamil on cAMP level in guinea pig hearts in vivo and in vitro in Langendorff preparation. The drug was administered either as a bolus into vena jugularis in dosage 1.0 and 1.5 mg/kg or into the perfusion solution at a concentration of 1.5 x 10(-6) mol/l. In additional experiments, this period was followed by brief 10 min global ischemia, induced by clamping of the aorta or perfusion. After 10 min from the onset of tedisamil administration as well as after 10 min of ischemia the ventricular tissue was immediately frozen for cAMP immunoassay. Tedisamil caused in normal heart small but significant dose-dependent increase of myocardial cAMP (pmol/mg) level in vivo 1.8 and 2.5 vs. 1.4 as well as in vitro 1.1 vs. 0.8 (p < 0.05) conditions. Ischemia itself induced accumulation of cAMP in both, in vivo and in vitro experiments, 2.6 vs. 1.4 and 1.3 vs. 0.8, respectively. The preischemic elevation of cAMP by tedisamil was not potentiated by following ischemia, on the contrary, decline of the cyclic nucleotide was detected comparing to ischemia itself. In conclusion, tedisamil increased cAMP level in normal heart and prevented additional ischemia-related elevation of this nucleotide. The results indicate modulation of myocardial cAMP level by tedisamil, which may account for its protective effect on gap junctional electrical coupling.

Animals↗

Evaluation of ischemia-reperfusion injury by malondialdehyde, glutathione and gamma-glutamyl transpeptidase: lack of specific local effects in diverse parts of the dog heart following acute coronary occlusion.

Alterations in the levels of glutathione, glutathione disulfide, malondialdehyde, and the activity of gamma-glutamyl transpeptidase in nonischemic and ischemic parts of the left ventricle and in the right ventricle were studied in canine hearts after occlusion of the left anterior descending coronary artery for 60 minutes and subsequent reperfusion for 20 minutes. Ischemia caused no significant change in malondialdehyde concentration and gamma-glutamyl transpeptidase activity in ischemic or nonischemic parts of the left ventricle, but it increased the activity of gamma-glutamyl transpeptidase in the continuously perfused right ventricle. Reperfusion of the ischemic areas of the left ventricle was accompanied by accumulation of malondialdehyde and an increase in gamma-glutamyl transpeptidase activity, not only in the reperfused and adjacent areas of the left ventricle, but also in the continuously perfused right ventricle. An increase in the level of glutathione disulfide and decrease in glutathione occurred in all parts of the myocardium during coronary occlusion; these changes were maintained in reperfusion. The findings indicate that the effects of acute occlusion and reperfusion of the left anterior descending coronary artery on myocardial concentrations of glutathione, glutathione disulfide and malondialdehyde or gamma-glutamyl transpeptidase activity are not confined to the local area.

Animals↗

[Initial clinical experience with cardiopulmonary bypass and auto-oxygenation].

Cardiopulmonary bypass has been successfully used in cardiac surgery for more than 39 years. In spite of many technical improvements oxygenators are still damaging to blood. We therefore decided to change the conventional CPB into biventricular bypass without an oxygenator, using the patient's lungs for autooxygenation. A double-pump system without an oxygenator was used in 11 patients undergoing aortocoronary bypass grafting. The cardiopulmonary pulmonary setup consisted of two separate systems with two roller pumps, plastic reservoirs and filters, and one cardiotomy reservoir and heat exchanger. Cannulations were performed through the right atrium and pulmonary artery for right-sided bypass, and through the left atrium and aorta for left-sided bypass. The results confirmed the full reliability of autooxygenation during CPB. All patients were well oxygenated with and inspired oxygen fraction of 30%. Values of arterial and venous O2 saturation as well as pO2 and pCO2 varied within the normal range. Platelet count decreased by 23% between interval I and IV, but only by 12% during biventricular bypass. Fibrinogen concentration decreased by 7% between interval I and IV, but only by 4% during biventricular bypass. No patient developed postperfusion syndrome. In our small series of patients, biventricular bypass was found to be simple to handle and to provide good conditions for the surgical procedure. It appears to be more physiological and less traumatic than conventional CPB. The described approach may further improve results of aortocoronary bypass grafting. (Tab. 2, Fig. 1, Ref. 12.).

Adult↗

Haemodynamics in the first seconds after coronary artery occlusion.

The changes in cardiac and in total haemodynamics, occurring during the first seconds of occlusion and the subsequent desocclusion of coronary arteries were studied on 28 dogs. The most intensive changes were observed after the trunk occlusion of the left coronary artery. Simultaneously with decreasing blood inflow into the myocardium its contractility and the systolic pressure in the left ventricle and the outflow from the coronary sinus began to fall rapidly. The systolic pressure in the left ventricle decreased within the first 10 s from 24 to 13-15 kPa (180 to 100-110 mm Hg), which means that the systolic pressure fell about 1 kPa (7-8 mm Hg) per second, or 0.5-0.6 kPa (4-5 mm Hg) per systole. At the same time the end-diastolic pressure in the left ventricle also increased from zero to 3-4 kPa (25-30 mm Hg). After the trunk desocclusion of the left coronary artery the systolic pressure in the left ventricle proceeded to fall by about 2-3 kPa (15-22 mm Hg). Only then, 20-25 s after the desocclusion, blood flow in the left coronary artery began to rise intensively and 4-6 s later the myocardial contractility and the systolic pressure in the left ventricle also increased. After unclamping (50-60 s), there was an overshoot of haemodynamic values above preocclusive values and then followed the compensatory phase. This phase lasted 80-90 s and on its peak the pressure and flow parameters increased by about 50-60% above preocclusive values. During the occlusion of ramus interventricularis anterior or ramus circumflexus for 30-60 s the haemodynamic parameters changed only slightly. The same was observed during trunk occlusion of the right coronary artery (30-60 s), but in that case many extrasystoles occurred.

Animals↗

Vulnerability of specialized conductive tissue to ischemia and reperfusion related injury.

The fine structural alteration and histochemical changes of the cardiac conduction system were studied in dogs and rats using various models of ischemic and reperfusion injury. The role of Ca2+ overload and reactive oxygen species (ROS) per se were also investigated. In all models of injury the activity of glycogen phosphorylase (histochemical indicator of the early ischemic changes) was present in nodal and conducting cells, although it was markedly diminished or absent in surrounding contractile muscle. Fine structural ischemic alterations progressed more slowly in conducting cells in comparison with working myocardial cells. Changes induced by Ca2+ paradox or ROS were reversible in conducting tissue in contrast to working myocardial tissue. The observations support the concept that conducting cells are more resistant to ischemia and also to reperfusion related injury than contractile myocardial cells.

Animals↗

[Right-sided mechanical circulatory support in acute right ventricular failure in the dog].

The technique of surgically induced acute progressive right ventricular failure in experimental animals is described. It sumultates the hemodynamic situation of right ventricular failure in some patients after termination of extracorporeal circulation applied for carrying out procedures on the left ventricle. The described technique consists of rightsided longitudinal ventriculotomy, destruction of the tricuspid valve, and ligation of the right coronary artery. Nine control dogs died within two hours after induction of failure due to low stroke volume caused by low pulmonary and left atrial pressure. The use of rightsided support appliance draining blood from the right atrium in systole and pumping it into the trunk of the pulmonary artery in diastole by means of a membrane pump resulted in further 12 dogs in the restoration of left ventricular diastolic pressure, significant increase of aortal pressure (p less than 0.003) and stroke volume (p less than 0.003) and in a decrease of right atrial pressure (p less than 0.003). The study demonstrated that by using the described mechanical support the circulation can be adequately assisted so that the failing right side of the heart can get restored. (Tab.1,Fig.5,Ref.25.).

Acute Disease↗

Bilateral acute heart atrial auriectomy reduced diuresis and natriuresis following hypertonic sodium load in anaesthetized dogs.

Anaesthetized dogs were deprived of a portion of the atrial natriuretic factor producing tissue by bilateral acute heart atrial auriectomy. Their ability to respond by diuresis and natriuresis either to the expansion of extracellular fluid volume with isotonic saline (3% b.w.) or to hyperosmolality induced by hypertonic saline loading (0.13% b.w. of 20% NaCl solution) was subsequently reduced by about 50%. It is thus suggested that atrial natriuretic system may also play a role in osmoregulation by taking part in the promotion of renal sodium excretion.

Animals↗

[Assisted circulation for volume relief of the right heart ventricle].

The model of the failure of the right ventricle was formed in dog experiments. The animals were connected with the right mechanically assisted circulation. The blood was pumped synchronously with the heart action from the right atrium directly to the pulmonary artery by temporary bypass of the right ventricle. The right volume relief improved (p less than 0.03) the decisive hemodynamic parameters. The value of assisted circulation in case of the hitherto only difficulty to controlled failure of the right ventricle is proved with that.

Animals↗

Heart atrial auriectomy reduces the diuretic and natriuretic responses to a hypertonic saline load.

Acute bilateral atrial auriectomy in anesthetized dogs reduced diuresis and natriuresis induced by both extracellular fluid volume expansion with isotonic saline and a hypertonic saline load. Since a hypertonic saline load, in contrast to isotonic saline infusion, was not accompanied by a significant increase in central venous pressure it is proposed that either increased plasma osmolality or plasma sodium concentration (or both) participate in the modulation of the atrial natriuretic mechanism.

Animals↗

Diminution of "reperfusion injury" in reperfused ischemic myocardium by phenothiazines. A quantitative morphological study.

The effect of pretreatment by phenothiazines--Chlorpromazine (CPR) /Spofa/ and Trifluoperazine (TFP) /Smith Kline and French/ on reperfusion injury of ischemic myocardium were studied. Reperfusion of ischemic myocardium following an ischemic period exceeding 40 min resulted in morphological, physiological and biochemical changes identical with those induced by enhanced cytosolic Ca2+ concentration. Left descending coronary ligation was performed on 70 dogs divided into four group. Group I: permanent occlusion (5 dogs--60 min, 5 dogs--120 min, 5 dogs--180 min); group II: 15 dogs (60 min occlusion + 120 min reperfusion); group III: 20 dogs (60 min occlusion, 15 mg CPR, reperfusion 120 min); group IV: 20 dogs (60 min occlusion, 2 mg TFP + 120 min reperfusion). CPR or TFP were administered 30 min after the ligation. The effect of drugs was quantified on tetrazolium stained gross sections and studied from physiological, biochemical and ultrastructural points of view. Treatment of animals with phenothiazines, known as calmodulin inhibitors, considerably improved the ultrastructure of myocytes in area at risk, and allowed for the recovery of at least 60 per cent of injured myocytes after reflow restoration. Ultrastructural findings tightly correlate with physiological and biochemical results.

Adenine Nucleotides↗

Diminution of injury in reperfused ischemic myocardium by phenothiazines. A quantitative morphological study.

Left descending coronary ligation was performed on 70 dogs and divided into four groups. I. group - permanent occlusion (5 dogs 60 min, 5 dogs 120 min, 5 dogs 180 min), II. group - 15 dogs (60 min occlusion + 120 min reperfusion), III. group - 20 dogs (60 min occlusion, 15 mg Chlorpromazine [CPR], reperfusion 120 min), IV. group - 20 dogs (60 min occlusion, 2 mg Trifluoperazine [TFP] + 120 min reperfusion). CPR or TFP were administered 30 min after the ligation. Effect of drugs was quantified on tetrazolium stained gross sections and studied from physiological, biochemical and ultrastructural points of view. Results reveal that treatment of animals with phenothiazines revealing calmodulin inhibitory action, considerably improved the ultrastructure of myocytes in area at risk and allowed for recovery at least 60 per cent of injured myocytes after restoration of reflow. Ultrastructural findings tightly correlate with physiological and biochemical results.

Animals↗

[Etimizol absorption from the small intestine in dogs: the dependence on dosage].

As etimizol has been previously reported to be of low bioavailability, the kinetics of its absorption from the dog intestinal loop was investigated in chronic experiments. After administration of etimizol at doses of 10 or 1 mg/loop mean residence time of etimizol in the loop was 20.1 and 7.6 min, respectively, with mean standard deviation being 3.1 and 0.8, respectively. It was concluded that overall etimizol absorption from small intestine was high and its low bioavailability resulted from presystemic drug metabolism, as well as that the absorption kinetics was dose-dependent, with saturation reached at higher drug doses.

Animals↗