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Biomedical subjects

R Rösen

Publications and source records attributed to R Rösen.

At least 37 records · Page 2Linked to original sources
PubMed1991

[Interaction between thrombocytes and the coronary system in the presence of SIN 1 and nitroglycerin after endothelial damage].

For further examination of the interaction of platelets with coronary endothelium in more detail, porcine platelets were infused into the coronary system of isolated, Langendorff-perfused rabbit hearts. The hearts were preincubated with very low activity of collagenase inducing functional endothelial lesion characterized by 50% reduction of EDRF-dependent dilation. Platelet infusions into those hearts were accompanied by a sudden myocardial failure and a significant retention of the platelets infused. When in addition to platelets the hearts were perfused with SIN 1 or GTN the global coronary flow did not fall below critical values. Moreover, the platelet recovery was not any longer diminished. After heart passage the platelets aggregation was more inhibited with SIN 1 than with GTN. SIN 1 and GTN in concentrations applicated to the heart could not inhibit porcine platelet aggregation, thus the aggregation behaviour reflects the different availability for platelets of the liberated NO during coronary passage.

Animals↗
PubMed1990

Effects of nimodipine on infarct size and cerebral acidosis after middle cerebral artery occlusion in the rat.

The objective of this study was to determine the effect of nimodipine on infarct development and local brain pH after middle cerebral artery occlusion in the rat. Female Fischer-344 rats were subjected to permanent occlusion of the left middle cerebral artery by electrocoagulation. After 6, 12, or 24 hours, brains were frozen, and infarct size, degree of edema formation, and local brain pH were quantified by standard histology or the umbelliferone technique, respectively. In control rats, cortical infarct size was increased from 29.5 microliters at 6 hours to 72.5 microliters at 24 hours after vessel occlusion. In striatum only, an insignificant increase from 15.2 to 24.7 microliters in infarct volume was observed during this period. Edema increased from 7% to 22% in cortical and from 4% to 39% in the striatal infarct areas during this time. Nimodipine (0.1 mg/kg s.c.), given 45 minutes before and again 8 and 16 hours after middle cerebral artery occlusion, did not alter infarct size at 6 hours but considerably improved outcome at later times. Edema formation was lower at 12 hours in the group treated with the calcium antagonist (p less than 0.05). By contrast, effects on local brain pH were seen as early as 6 hours after the vessel occlusion. Nimodipine greatly reduced the areas exhibiting the lowest pH values beyond pH 6.0 (p less than 0.05). Similar effects by nimodipine on brain pH were observed in the 12-hour series, whereas at 24 hours after middle cerebral artery occlusion, a shift to more alkalotic values was noted with no overt differences between control and drug-treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗
PubMed1989

Response to histamine of the intact coronary system in an isolated rabbit heart preparation.

In isolated Langendorff-perfused rabbit hearts concentration-response relations for histamine were analysed with and without H2-receptor blocker cimetidine (10(-5) mol l-1). The diameter of large epicardial coronary arteries was determined by video angiometry. Global coronary flow and left ventricular isovolumetric pressure were continuously registered. Histamine concentration (10(-7)-6 X 10(-6) mol l-1) reduced the diameter of large coronary arteries up to -50%, however, this vasoconstriction was maximal after 1 min and was then attenuated within the following 20 min. Coronary flow and left ventricular pressure were not significantly altered. In the presence of cimetidine the histamine-induced vasoconstriction was stabilized and not reversed with time. Moreover, the extent of vessel wall narrowing was intensified (up to -70%) when compared with histamine alone. Furthermore, severe functional myocardial failure was observed (flow reduction to 40% of control).

Animals↗
PubMed1989

The influence of endothelium on glyceryl trinitrate induced relaxation in corresponding arteries and veins of the rabbit.

Glyceryl trinitrate (GTN) induced relaxation was investigated in preparations of corresponding femoral arteries and veins from rabbits containing the intact endothelium in comparison to denuded vessels. Either vascular rings (app. 5 mm segments) or helical cut strips were isotonically mounted in organbaths (37 degrees C, Krebs-Henseleit-buffer). Vessels were precontracted with their specific EC-50 of norepinephrine. Cumulative concentration response curves for GTN were evaluated. Arteries and veins were dilated in a concentration dependent manner in the range of 1 nmol/l to 0.1 mmol/l. V.femoralis was the most sensitive vessel with an EC-50 of 10 nmol/l. There was no significant difference in the sensitivity of veins with or without endothelium. In contrast to this, for half-maximal relaxation of A. femoralis 2-3 orders of magnitude higher concentrations were necessary, depending on the presence of endothelium. The concentration ratio artery/vein (A/V) amounted to 800 in normal vessels, 100 in denuded vessels, resp. indicating that for half-maximal relaxation of endothelium containing arteries significant higher concentrations were needed. By preincubation for 60 min with the EC-90 of GTN in arteries, as well as in veins, tolerance could be induced independently of the presence of endothelium. However, veins were more affected than arteries, but tolerant veins were still more sensitive to GTN than tolerant arteries. This was true both for preparations with and without endothelium (A/V = 70 in normal vessels, 20 in denuded vessels, resp.). Moreover, the endothelial dependence of arterial relaxation was attenuated. Treatment of the tolerant vessels with cystein (1 mmol/l) did abolish the GTN-tolerance in veins but not in arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Early vascular alterations in the diabetic rat heart.

The aim of this study was to evaluate whether there are vascular alterations in diabetes prior to atherosclerotic lesions. Four and 12 weeks after induction of diabetes (streptozotocin, 60 mg/kg b.w.) in rats characterized by low plasma insulin, hyperglycaemia, glucosuria, and loss of body weight, however, without morphological alterations of the cardiac vasculature--local myocardial perfusion parameters were estimated in the epicardium of Langendorff perfused hearts using fluorescence indicator (FITC-dextrane, MG 3kD) washout kinetics after bolus injection. The elution profile was characterized by a fast vascular and a slow transendothelial component. In diabetic hearts, vascular as well as transendothelial washout were prolonged. Concomitantly, the vascular perfusion volume and the amount of indicator exchanged with the interstitium was significantly diminished. Vascular response to bradykinin (5 nmol/l) was moderately attenuated and the limitations in transendothelial indicator exchange could not be affected by bradykinin, although vascular perfusion volume was significantly increased. These findings clearly indicate disturbed local myocardial perfusion early in the development of diabetes.

Animals↗
PubMed1987

Platelet induced aggravation of acute ischaemia in an isolated rabbit heart model.

In isolated coronary ligated rabbit hearts the effects of washed human platelets on the size of the epicardial ischaemic area and on recovery from ischaemia during 60 min of reperfusion was evaluated by endogenous NADH-surface-fluorescence photography. Infusion of washed human platelets to non-ischaemic control hearts produced a decrease in left ventricular pressure to 64(3)% of control (n = 4), no change in global coronary flow rate, no retention of platelets (recovery 108(9)%), and no alteration in basal NADH-fluorescence. When platelets were infused into coronary ligated hearts, however, the size of the epicardial ischaemic area was significantly enhanced to 127(8)% (n = 5) of control. Moreover, this increase in size was negatively correlated with the recovery of platelets in the coronary effluent: the lower the recovery rate the larger the ischaemic area (y = 253-1.44x, r = -0.855, n = 15, p less than 0.001). When platelet infusion was stopped after 30 min the enlargement of the ischaemic area seemed to be reversible. When the coronary ligature was released, however, and the ischaemic myocardium reperfused the recovery from ischaemia was retarded in the platelet treated hearts as shown by functional (left ventricular pressure and flow) and metabolic (NADH-fluorescence) indices. Thus it is directly shown for the first time in an isolated in vitro heart preparation that platelets aggravate myocardial ischaemia.

Acute Disease↗
PubMed1987

Different sensitivities of arteries and veins to glyceryltrinitrate-induced relaxation and tolerance: an "in vitro" study on isolated vessels from rabbits.

Glyceryltrinitrate (GTN)-induced relaxation was examined in helical strips of rabbit femoral and mesenteric vessels after precontraction with norepinephrine (EC-50). Concentration-response curves over a wide concentration range (10(-9) to 3 X 10(-4) mol/l) appeared to be biphasic with a plateau at 10(-6) mol/l. Threshold concentrations for relaxation (EC-10) were different in arteries (2 X 10(-8) mol/l) and in veins (2 X 10(-9) mol/l), indicating a higher sensitivity of veins than of arteries to low concentrations of GTN. After induction of GTN-tolerance (60 min preincubation with EC-90) the arterial vessels revealed a monophasic concentration response curve (EC-10: 10(-6); EC-50: 10(-5) mol/l). The relaxation at the lower concentration range was abolished (shift to the right at lower GTN-concentration). On the other hand, in veins the concentration-response curve was completely shifted to higher concentrations (EC-10: 10(-8) mol/l) and the high sensitivity component was diminished to 50%. However, the enhanced sensitivity of veins in comparison to arteries was preserved. 10(-3) mol/l cystein was unable to affect tolerance in arteries, but partially reversed the development of tolerance effects in veins. Moreover, 10(-6) mol/l indomethacin could mimic GTN-tolerance in arteries but not in veins. Thus, relaxation as well as tolerance induced by GTN, seem to be mediated at least by 2 different mechanisms. Only in arteries the prostaglandin system appears to be involved. On the other hand depletion of SH-groups seems to play a major role in veins in agreement with the hypothesis of Ignarro et al. (1981).

Animals↗
PubMed1984

Reduced transcoronary exchange and prostaglandin synthesis in diabetic rat heart.

In perfused hearts of streptozotocin-diabetic rats the kinetics of a fluoresce indicator transit was measured after pulse injection of FITC-dextran 3. The fluorescence changes on the left ventricle could be described by two pseudo first-order processes with half times in the range of seconds (t/2) corresponding to the intravascular washout and a slow process (T/2) corresponding to the exchange between the extra- and the intravascular space. In diabetes both half times became prolonged, and the amount of FITC-dextran 3 exchanged between the two compartments was reduced, indicating an impaired transcoronary transport in diabetic hearts. There was a time-dependent reduction in the basal release of prostacyclin in hearts of control and diabetic rats. However, studied hearts of diabetic rats released less 6-keto-prostaglandin F1 alpha (PGF1 alpha) than controls. This impaired release of 6-oxo-PGF1 alpha could be prevented partly by adrenalectomy. Because diabetic hearts release more 6-oxo-PGF1 alpha than controls after application of arachidonic acid, these data suggest that the supply of arachidonic acid for the synthesis of prostaglandins is impaired in diabetes, but not the cyclooxygenase pathway itself. The reduced transcoronary transport and the impaired synthesis of prostacyclin might be early steps in the development of microangiopathic myocardial alterations in diabetes.

6-Ketoprostaglandin F1 alpha↗
PubMed1981

Prostacyclin prevents ischemia-induced increase of lactate and cyclic AMP in ischemic myocardium.

The effect of prostacyclin (PGI2, 0.5 nmol . kg-1 . min-1,i.v.) on myocardial metabolism was studied in cats subjected to 5 h of myocardial ischemia (MI) and compared to vehicle-treated MI cats. MI was followed by a 52% decrease in ATP and a concomitant increase (2-3 fold) in lactate and lactate/pyruvate ratio in the severely ischemic area. PGI2 prevented this increase in lactate with an unchanged ATP and lactate/pyruvate ratio. Moreover, PGI2 abolished the ischemia-induced in myocardial cAMP. It is concluded, the PGI2 exerts its beneficial actions on ischemic myocardium partly via cAMP-linked mechanisms.

Animals↗
PubMed1980

Prostacyclin-induced coronary vasodilation. Interactions with adenosine, cyclic AMP and energy charge in the rat heart in vitro.

The action of prostacyclin (PGI2) on several biochemical and physiological parameters of myocardial function and coronary perfusion was studied in the rat heart in vitro, perfused according to Langendorff either at constant pressure (65 mmm Hg) or at constant volume (8 ml/min). PGI2 dose-dependently decreased coronary vascular resistance, the ED50, being 5--10 nM, whereas that of adenosine was 550--650 nM. PGI2 (30 nM) did not alter the myocardial energy-rich phosphate content but diminished myocardial cAMP by 23% and adenosine release by 61%. In contrast to adenosine, the coronary dilating activity of PGI2 was not inhibited by isobutyl-methyl-xanthine (MIX; 0.4 microM). There were no direct effects of PGI2 on myocardial contractile force, oxygen consumption or heart rate. The results provide evidence for (1) a direct powerful coronary dilating activity of PGI2 which appears to be independent of adenosine, (2) the absence of any direct activity of the compound on myocardial contraction and energy charge.

1-Methyl-3-isobutylxanthine↗
PubMed1980

Different sensitivities of prostaglandin-cyclooxygenases in blood platelets and coronary arteries against non-steroidal antiinflammatory drugs.

The action of the non-steroidal antiinflammatory drugs indomethacin, tiaprofenic acid, diclofenac and meclofenamate on vascular and platelet-cyclooxygenases was studied by measuring the arachidonic acid-induced thromboxane A2 (TXA2)-formation of washed human platelets and prostacyclin (PGI2)-formation of bovine coronary artery rings. TXA2 was bioassayed as RCS on rabbit aorta strips, PGI2 in terms of its antiaggregatory activity on ADP-induced aggregation of human platelet-rich plasma. All of the substances studied produced concentration-dependent inhibition of PGI2- and RCS-release. The IC50 [micrometer] in inhibition of RCS-formation was 0.019 for indomethacin, 0.070 for tiaprofenic acid but 44.9 for meclofenamate and 63.2 for diclofenac. The IC50 [micrometer] in inhibition of PGI2-release was 0.42 for diclofenac, 0.63 for indomethacin and 0.99 for tiaprofenic acid. The data suggest (1) high sensitivity of human platelet-cyclooxygenase against indomethacin and tiaprofenic acid, (2) different sequence of the substances studied in inhibiting arachidonic acid-induced TXA2- and PGI2-formation. The possible therapeutic value of selective inhibition of platelets and vascular cyclooxygenases is discussed.

Animals↗
PubMed1976

Interaction of digitoxigenin with lecithin membranes.

The binding of digitoxigenin to lecithin model membranes was investigated by application of electron spin- and nuclear magnetic resonance methods. A digitoxigenin spin-label derivative was found to bind specifically to the pseudohexagonal rigid lattice of lecithin membranes. The binding is accomplished by some of the structural features which are required for the biological activity of cardiac glycosides. Digitoxigenin has a procooperative effect on dipalmitoyl-lecithin membranes. The induction of lipid phase separation is discussed as a hypothetic molecular mechanism of action of cardiac glycosides on biological membranes.

Adenosine Triphosphatases↗
PubMedDate not supplied

Nitric oxide (EDRF) enhances the vasorelaxing effect of nitrendipine in various isolated arteries.

Recent studies suggest endothelium to be involved in the vasorelaxation of calcium antagonists of the 1,4-dihydropyridine type, which may at least in part be mediated by endothelium-derived relaxing factor (EDRF = NO). To study this effect further, the influence of L-NG-nitro arginine (L-NNA), a specific inhibitor of EDRF-synthesis, on nitrendipine-induced vasorelaxation was examined in different isolated porcine arteries. Coronary, basilary, and tail arteries were bathed in Krebs-Henseleit solution and endothelial function was verified by means of substance P, an EDRF releasing neuropeptide. Vasorelaxation of nitrendipine in PGF2 alpha-precontracted arteries was studied in the presence and absence of L-NNA. Nitrendipine-induced vasorelaxation was markedly reduced by the addition of L-NNA in all vessels studied. Tachyphylactic effects of nitrendipine could be excluded. The obtained results may be explained by an enhancement of nitrendipine action by basally released EDRF, alternatively, by an increased EDRF-release induced by this calcium antagonist. Therefore, in a second series of experiments the release of EDRF was studied in isolated coronary arteries under cumulative application of nitrendipine. Using the nitric oxide scavenging properties of oxyhemoglobin, EDRF release was measured spectrophotometrically by means of methemoglobin formation. The application of nitrendipine resulted in a concentration-dependent increase in the extinction rate, indicating an increased release of NO which could be inhibited by preincubation with L-NNA. It may be concluded that, in functionally intact vessels, vasorelaxation induced by nitrendipine may additionally be mediated by an increased release of EDRF.

Animals↗
PubMedDate not supplied

Local myocardial perfusion and epicardial NADH-fluorescence after coronary artery ligation in the isolated guinea pig heart.

In Langendorff-perfused guinea pig hearts, local myocardial perfusion was evaluated by analysis of FITC-dextran-150 elution kinetics after bolus injection. Locally estimated half-times of the monoexponential elution curves showed good correlation with global undisturbed coronary flow. After ligation of the left anterior descending coronary artery indicator transit kinetics in the ischemic area were only slightly affected (increase of t/2 by 30 +/- 19%), indicating a residual flow of 80% to the ligated area. The moderate increase (40 +/- 20%) of NADH-surface fluorescence in the same area confirms a high degree of residual flow. Indicator partition volume (signal peak height after bolus injections) was additionally enhanced. Moreover, indicator transit kinetics changed from monoexponential to composed kinetics. On reperfusion these effects were partially reversible. Ligation of the left coronary artery at its aortic root produced only moderate ischemia, indicating very effective mechanisms in the isolated guinea pig heart from the right coronary artery to support the left ventricle. Severe ischemia as evidenced from NADH-surface fluorescence could be observed only after "stopped flow" ischemia.

Animals↗