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Biomedical subjects

A Lochner

Publications and source records attributed to A Lochner.

At least 55 records · Page 3Linked to original sources
PubMed1993

Ro 5-4864 and PK 11195, but not diazepam, depress cardiac function in an isolated working rat heart model.

The present study was designed to investigate the effects of diazepam, a benzodiazepine (BZ) with high affinity to central BZ receptors and moderate affinity to mitochondrial BZ receptors, and of Ro 5-4864 and PK 11195, ligands specific for mitochondrial BZ receptors, on cardiac function in the isolated working rat heart model. Five concentrations of these drugs (10(-9)-10(-5) mol/l) were used, and the chronotropic (heart rate) and inotropic [maximum elastance of the left ventricle at end systole (Emax), maximal first derivative of left ventricular (LV) pressure (dP/dtmax), LV pressure at dP/dtmax (pressure at dP/dtmax), aortic flow, stroke work, and total pressure-volume area] cardiac parameters were measured. Diazepam, Ro 5-4864, and PK 11195 showed no significant chronotropic activity up to 10(-5) mol/l. Diazepam did not alter the inotropic properties of the heart. Ro 5-4864 at 10(-5) mol/l significantly decreased the indices of contractility, namely, Emax, dP/dtmax, and pressure at dP/dtmax. Aortic flow, stroke work, and total pressure-volume area were significantly depressed at the same concentration. The negative inotropism of PK 11195 appeared to be identical, by most indices, to that of Ro 5-4864, both qualitatively (same pattern) and quantitatively (similar maximal variations); however, for some indices a depressant effect was also found at 10(-7) mol/l. These results show that at high concentrations Ro 5-4864 and PK 11195, but not diazepam, have a depressant effect on mechanical function.

Animals↗
PubMed1993

Enflurane and isoflurane reduce reperfusion dysfunction in the isolated rat heart.

We evaluated the possible cardioprotective effects of enflurane (E) and isoflurane (I) in isolated rat hearts subjected to 40 min normothermic arrest. After reperfusion, hearts were stimulated with adrenaline to evaluate their systolic reserves. In hearts not receiving I or E, adenosine triphosphate (ATP) was reduced from 23.0 +/- 0.8 to 9.3 +/- 1.1 mumol/g dry weight (means +/- SEM; P < 0.001) after arrest. This was associated with a significant reduction in ventricular work (Wt) from 13.6 +/- 0.7 to 1.6 +/- 0.7 mW (P < 0.001). Adrenaline partially restored Wt but not the ATP. E and I given only during normothermic arrest (in the cardioplegic solution) resulted in reductions in ATP similar to the hearts not receiving the drugs. However, on reperfusion and subsequent administration of adrenaline, hearts subjected to the anesthetic drugs performed as well as hearts before arrest. For example, in hearts not exposed to I or E, the Wt after the elective arrest was 1.55 +/- 0.05% (mean +/- SEM) of the pre-arrest value. This was significantly less than hearts exposed to either one of the inhalational agents (40.02 +/- 3.49% of the pre-arrest value; P < 0.0001). Adrenaline improved function in hearts which did not receive I or E to 55.02 +/- 12.80% of the pre-arrest value, but this was significantly less than the Wt performed by the hearts exposed to the anesthetic agents (122.67 +/- 7.78% of pre-arrest value; P < 0.001). This beneficial effect of I and E during reperfusion probably is mediated by the effect of the anesthetic agents on Ca2+ slow channels. The effect could not be ascribed to depression of global myocardial contractile function associated with I and E.

Adenosine Triphosphate↗
PubMed1993

Free radical effects on myocardial membrane microviscosity.

Previous studies have shown that myocardial membranes, isolated from ischemic myocardial tissue, showed marked changes in microviscosity. To evaluate the contribution of free radical production and concomitant lipid peroxidation to these changes in microviscosity, the in vitro effects of two radical producing systems (H2O2/FeCl2 and xanthine oxidase/hypoxanthine/FeCl3) were investigated separately on the microviscosity of sarcolemmal, mitochondrial and sarcoplasmic reticulum membranes. In all three membranes both these free radical producing systems caused formation of malondialdehyde as quantitated by the thiobarbituric acid test. The sensitivity of the membranes to free radical damage differed: the sarcolemma was more sensitive to H2O2 damage, while mitochondrial malondialdehyde production was highest with xanthine oxidase. H2O2/FeCl2 caused a reduction in microviscosity (i.e. increased fluidity) of all three membranes, whereas the xanthine oxidase system increased mitochondrial and sarcolemmal microviscosity and reduced that of the sarcoplasmic reticulum. The similarity between ischemia-induced membrane microviscosity changes and those induced in vitro by xanthine oxidase, indicate a possible causal role for superoxide and hydroxyl free radicals produced during ischemia.

Animals↗
PubMed1993

Effect of captopril on changes in rats' hearts induced by long-term irradiation.

The aim of this study was to test the efficacy of captopril, an angiotensin-converting enzyme inhibitor and a known suppressor of fibrosis, in preventing late radiation-induced cardiac pathology. Myocardial functional, histochemical and ultrastructural-morphometric studies were done on perfused hearts of rats isolated 3 and 6 months after 60Co gamma irradiation with 20 Gy and age-matched controls. At each time the animals were divided into the following groups: nonirradiated controls; irradiated once with 20 Gy; irradiated as above and given daily doses of captopril; daily doses of captopril without irradiation. The results showed that captopril, while ameliorating the decrease in the indices of capillary function, increase in mast cells, fibrosis, number of atrial granules, and changes in nerve terminals, failed to prevent the progressive functional deterioration of the hearts after irradiation. These findings suggest that an intramyofiber derangement may be involved in the long-term myocardial complications of irradiation.

Animals↗
PubMed1993

[Osteomalacia caused by malabsorption].

Reports on sickness osteomalacia are relatively rare in Europe. Distinction from other painful illnesses of the locomotor system is difficult. A case of osteomalacia has been reported which was caused by a primarily biliary cirrhosis of the liver as well as by chronic cholecystitis and pancreatitis.

Cholecystitis↗
PubMed1992

The effect of ischaemia-reperfusion on [3H]inositol phosphates and ins(1,4,5)P3 levels in cardiac atria and ventricles--a comparative study.

In this study incorporation of [3H]inositol into inositol phosphates and phosphoinositides as well as tissue Ins(1,4,5)P3 levels of the atria and ventricles of isolated, perfused rat hearts were compared. Although the incorporation of [3H]inositol into the phosphoinositides of atria and ventricles was similar, significantly higher (2-3 fold) incorporation rates into inositol phosphates were observed in atrial tissue. Using a D-myo-[3H]Ins(1,4,5)P3 assay system, the Ins(1,4,5)P3 levels observed in atria from perfused rat hearts were also significantly higher than those obtained under the same experimental circumstances in the ventricles. Since previous studies on whole hearts showed inhibition of the phosphatidylinositol (PI) pathway during ischaemia with an immediate significant stimulation upon reperfusion [12, 20], the effects of ischaemia and 1 min postischaemic reperfusion were also examined separately in atria and ventricles. The results showed that 20 min of global ischaemia significantly depressed Ins(1,4,5)P3 levels as well as incorporation of [3H]inositol into ventricular InsP2 and InsP3. Reperfusion caused an immediate (within 1 min) increase in Ins(1,4,5)P3 levels and also [3H]inositol incorporation into all three cytosolic inositol phosphates in the ventricles. However, the effect of ischaemia and reperfusion on Ins(1,4,5)P3 levels as well as the incorporation of [3H]inositol into the inositol phosphates were less prominent in the atria. It therefore appears that the differential responses of the atria and the ventricles to an oxygen deficiency [41] are also reflected in the differences in PI metabolism during ischaemia-reperfusion.

Animals↗
PubMed1992

The role of alpha 1-adrenergic stimulation in inositol phosphate metabolism during post-ischaemic reperfusion.

The aim of this study was to elucidate the mechanism of enhanced inositol phosphate metabolism during reperfusion. Inositol phosphate stores were prelabelled by perfusing isolated rat hearts for 1 h with [3H]inositol (1.5 microCi/ml). LiCl (10 mM) and prazosin (0.3 microM) were subsequently added 15 min before (i) 20 min control perfusion; (ii) 20 min normothermic ischaemic cardiac arrest (NICA); (iii) 20 min NICA followed by 1 min reperfusion. The ventricles were freeze-clamped before determination of isotopical incorporation of [3H]inositol into the inositol phosphates (Dowex anion exchange chromatography) and InsP3 levels (Amersham InsP3 assay system). In addition, noradrenaline release into the perfusate was also assessed (HPLC and electrochemical detection). The results showed: (i) increased noradrenaline release into the perfusate immediately after the onset of reperfusion; (ii) significant depression of [3H]inositol incorporation into inositol phosphates and InsP3 levels after 20 min NICA; (iii) reperfusion caused an immediate significant increase in isotopical incorporation of [3H]inositol into inositol phosphates as well as InsP3 levels; (iv) the alpha 1-adrenergic blocker, prazosin (0.3 microM), completely inhibited the reperfusion-induced increase in inositol phosphate metabolism. These observations suggested that increased alpha 1-adrenergic receptor stimulation by noradrenaline might be responsible for the stimulation of ventricular inositol phosphate metabolism during postischaemic reperfusion.

Animals↗
PubMed1991

The effect of ischaemia and reperfusion on sarcolemmal inositol phospholipid and cytosolic inositol phosphate metabolism in the isolated perfused rat heart.

In this study the mass of polyphosphoinositides as well as the turnover of [3H]inositol phospholipids and [3H]inositol phosphates during ischaemia and short periods of reperfusion were studied in the isolated perfused rat heart. Since the phosphoinositides located within the sarcolemma are precursors for release of inositoltrisphosphate (InsP3) and diacylglycerol, sarcolemmal membranes (rather than whole tissue) isolated at the end of the experimental procedure, were used. Hearts were prelabelled with [3H]inositol and subsequently perfused with 10 mM LiCl to block the phosphatidylinositol (PI) pathway. The results showed that 20 min of global ischaemia depressed the amount of [3H]inositol present in both sarcolemmal phosphatidylinositol-4-phosphate (PI-4-P) and phsophatidylinositol-4,5-bisphosphate (PI-4,5-P2), as well as in the cytosolic [3H]inositol phosphates, [3H]InsP2 and [3H]InsP3. The mass of the sarcolemmal inositol phospholipids remained unchanged during ischaemia. Reperfusion caused an immediate (within 30 sec) increase in the amount of [3H]inositol in sarcolemmal PI, PI-4-P and PI-4,5-P2. PI-4-P levels showed a transient increase after 30 seconds postischaemic reperfusion, while the mass of the other sarcolemmal inositol phospholipids, PI and PI-4,5-P2, remained unchanged. [3H]InsP, [3H]InsP2 and [3H]InsP3 also increased significantly in comparison to ischaemic hearts after only 30 sec postischaemic reperfusion. In summary, the results obtained indicate inhibition of the PI pathway during ischaemia with an immediate significant stimulation upon reperfusion. In view of the capacity of InsP3 to mobilize Ca2+, the possibility exists that stimulation of this pathway during reperfusion may play a role in the intracellular Ca2+ overload, characteristic of postischaemic reperfusion.

Animals↗
PubMed1991

Testosterone and cyproterone acetate modulate peripheral but not central benzodiazepine receptors in rats.

Sixteen days of testosterone acetate (TA) treatment in male rats induced an increase in the densities of peripheral benzodiazepine receptors (PBR) in the adrenal and Cowper's glands and a decrease in PBR density in the testis. TA did not alter PBR density in the heart, cerebral cortex, or pituitary, or central benzodiazepine receptor (CBR) density in the cerebral cortex or hypothalamus. The antiandrogenic agent cyproterone acetate induced a decrease in PBR density in the testis, adrenal, and pituitary, but did not affect PBR density in Cowper's glands, heart, or cerebral cortex, or CBR density in the cerebral cortex or hypothalamus. In all of the above organs, affinity values did not change following the treatment with both agents. The receptoral changes may be relevant to the physiological and neurobehavioral effects of the chronic exogenous androgenic and antiandrogenic treatment.

Androgen Antagonists↗
PubMed1991

Oxygenation of cardioplegic solutions: a note of caution.

The merits of oxygenated crystalloid cardioplegic solutions have been well established in experimental animals. The positive effects of oxygenation of Plasmalyte B (Sabax Ltd) and St. Thomas Hospital solution (Plegisol) were achieved by gassing with 95% O2/5% CO2 and 100% O2, respectively. In view of the marked pH differences induced by these gas mixtures, we evaluated the effect of mode of oxygenation on myocardial recovery during reperfusion after hypothermic cardioplegic arrest. Oxygenation with 100% O2 of Plasmalyte B containing high K+ levels caused marked deterioration in myocardial recovery, whereas the mode of oxygenation did not affect recovery after arrest with St. Thomas Hospital solution. Because the major differences between these solutions reside in their respective K+, Mg2+, and HCO3- contents, the effects of variations in the levels of these ions were investigated. The results showed that oxygenation with 100% O2 was deleterious only in the presence of high K+ (29 mmol/L), low Mg2+ (3 mmol/L), and high NaHCO3 (28 mmol/L) levels. The marked decline in mechanical recovery during reperfusion was associated with significant changes in myocardial adenosine triphosphate and intracellular Ca2+ levels. Although an explanation for these findings is not readily available, it is suggested that complex ionic interactions and possibly oxygen free radical generation may lead to intracellular Ca2+ overload, depression in mitochondrial adenosine triphosphate generation, and, hence, deterioration in mechanical recovery.

Acid-Base Equilibrium↗
PubMed1991

Myocardial membrane cholesterol: effects of ischaemia.

Evidence has recently been presented that myocardial ischaemia is associated with a significant increased mitochondrial cholesterol content, suggesting a redistribution of cholesterol within the ischaemic cell (Rouslin et al. 1980, 1982). The aim of this study was therefore to determine the effects of different periods of ischaemia and reperfusion on the cholesterol content of myocardial mitochondria, sarcoplasmic reticulum and sarcolemma. Using the isolated perfused rat heart as experimental model, it was demonstrated that increasing periods of ischaemia (15-60 min) caused a progressive loss of cholesterol from the tissue as well as from the sarcolemma and sarcoplasmic reticulum, concomitant with a significant increase in mitochondrial cholesterol content. These compositional changes were associated with a marked increase in sarcolemmal and mitochondrial microviscosity, while that of the sarcoplasmic reticulum was reduced. To gain more insight into the mechanisms controlling intracellular cholesterol distribution, control and ischaemic hearts were perfused with either exogenous cholesterol or its precursor [U-14C]acetate as an indicator of endogenous cholesterol synthesis. Perfusion with exogenous cholesterol resulted in significant increases in the membrane cholesterol content of control hearts. However, hypoxic, low flow perfusion prevented cholesterol enrichment of the sarcolemmal and sarcoplasmic reticulum membranes, while the cholesterol content of the mitochondria was increased from 99.48 +/- 12.75 to 127.61 +/- 1.84 nmols/mg protein, indicating specific incorporation into this membrane system. Incorporation of [U-14C]acetate into cholesterol in the sarcoplasmic reticulum was increased by 120% in ischaemic conditions. However, a marked redistribution of newly synthesized cholesterol was observed within the ischaemic cell: under control conditions most of the labelled cholesterol was transferred to the sarcolemma and least to the mitochondria, while this distribution pattern was reversed in ischaemia. In view of the fact that exchange of cholesterol between membranes is affected by both phospholipid polar head-group composition and acyl chain length and saturation, it is suggested that prior ischaemia-induced membrane compositional changes might lead to intracellular cholesterol redistribution. Finally, to determine whether cholesterol loss affects sarcolemmal permeability, hearts enriched in sarcolemmal cholesterol were subjected to 15 or 30 min global ischaemia followed by reperfusion and the rate of enzyme release determined. However, enzyme release was similar in treated and untreated hearts, indicating that sarcolemmal cholesterol loss probably does not affect its permeability.

Animals↗
PubMed1991

Increased myocardial inositol trisphosphate levels during alpha 1-adrenergic stimulation and reperfusion of ischaemic rat heart.

Although stimulated [3H] inositol phosphate turnover has been demonstrated in isolated, perfused [3H] inositol prelabelled rat hearts, there is still no information regarding Ins (1,4,5)P3 levels in intact cardiac muscle. Using a D-myo-Ins(1,4,5)P3 assay system, Ins(1,4,5)P3 levels were determined in isolated perfused rats hearts during ischaemia, reperfusion and alpha 1-adrenergic stimulation via noradrenaline (3 x 10(-5) M). Control hearts contained +/- 674 pmols Ins(1,4,5)P3/g dry heart weight. Myocardial Ins(1,4,5)P3 levels were significantly decreased (+/- 389 pmols/g dry heart weight) after exposure to 20 mins of normothermic ischaemic cardiac arrest (NICA). Reperfusion produced a marked increase in Ins(1,4,5,)P3 levels (+/- 1,115 pmols/g dry heart weight) after only 30 s. Noradrenaline caused a 3-4 fold increase in tissue Ins(1,4,5)P3 levels within 30 s. After 20 mins stimulation with noradrenaline, the Ins(1,4,5)P3 levels were still significantly elevated. The rise in tissue Ins(1,4,5)P3 levels during reperfusion as well as during noradrenaline administration was counteracted by neomycin (0.5 x 10(-3) M), an inhibitor of phosphoinositidase specific phospholipase C. In both events neomycin restored the Ins(1,4,5)P3 levels to control values. For correlation of tissue Ins(1,4,5)P3 levels with mechanical events, noradrenaline (3 x 10(-5) M), in the presence of 10 mM LiCl, 10(-7) M propranolol and 10(-7) M atropine, was administered to isolated perfused rat hearts and the mechanical performance recorded over a period of 20 mins. Noradrenaline caused a significant increase in peak systolic pressure and work performance which was maintained for at least 10 mins, suggesting that the positive inotropic effects of noradrenaline may be provoked by Ins(1,4,5)P3. Furthermore, the finding that 20 min NICA followed by 30 s reperfusion causes an immediate significant increase in Ins(1,4,5)P3 content suggests a role for the phosphatidylinositol pathway in the intracellular Ca2+ overloading, characteristic of ischaemia-reperfusion.

Adrenergic Fibers↗
PubMed1991

Halothane does have protective properties in the isolated ischemic rat heart.

To determine whether halothane has protective effects on the ischemic heart, the influence of various concentrations (0.5%-1.5%) of halothane on metabolic and functional recovery during reperfusion after 60-min hypothermic (20 degrees C) and 40-min normothermic cardioplegic arrest was determined in the isolated rat heart. Halothane was administered either before and after arrest or intermittently during arrest. Hearts not receiving halothane demonstrated a reduction in adenosine triphosphate (ATP) content from a control value of 20.35 +/- 1.66 mumol/g dry wt (mean +/- SEM) (before arrest) to 9.34 +/- 1.12 mumol/g dry wt at the end of arrest (P less than 0.001). The myocardial ATP content, when measured 20 min after arrest and during reperfusion, remained decreased (9.57 +/- 0.62 mumol/g dry wt). Under these experimental conditions, aortic flow was reduced from 43.62 +/- 2.40 mL/min before arrest to 1.80 +/- 1.80 mL/min 20 min after arrest and during reperfusion (P less than 0.001). The administration of adrenaline after 20 min of reperfusion resulted in partial recovery to 22.01 +/- 8.36 mL/min. Administration of halothane (0.5%) before the cardioplegic period was associated with a reduction of ATP at the end of the normothermic arrest (4.02 +/- 0.38 mumol/g dry wt; P less than 0.01), but the ATP increased significantly (13.45 +/- 0.32 mumol/g dry wt) when measured after the arrest and after 20 min of reperfusion and stimulation with adrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1991

[Pulmonary roentgen findings in interstitial pneumonia after bone marrow transplantation].

In 10-40% of the patients interstitial pneumonias develop after bone marrow transplantation. The identification of causative agents is often problematic, so that particularly clinical but also blood gas-analytic findings allow the making of a diagnosis. The typical X-ray-morphological changes of the lung (particularly symmetrical, fine-reticular, interstitial multiplications of markings and fine-patchy, striated, partly confluent shadows), which are represented with the help of three instances of cases, confirm the diagnosis, are, however, often found only relatively late. Further diagnostic methods such as the computer tomography or the bronchoscopy, connected with lung biopsy and bronchoalveolar lavage, at present do not play an essential role at least in the early phase after the transplantation of the bone marrow.

Adult↗
PubMed1990

Lanthanum probing of cell membrane permeability in the rat heart: pathological versus artefactual alterations.

The influence of fixation on membrane permeability has been examined in the isolated rat heart using lanthanum as a permeability probe. Normal and ischaemic hearts were probed at various stages during a conventional fixation programme with either ionic or colloidal lanthanum and compared with lanthanum saline administered prior to fixation. Fixation of the myocardium coincident with or followed by lanthanum probing resulted in an influx of the probe into most myocytes in normal tissue. Alterations in permeability after ischaemic episodes could not be distinguished from the artefact. However, lanthanum saline prior to fixation showed exclusion of the probe from normal tissue, while the increased permeability demonstrated after ischaemia was associated with declining myocardial performance during subsequent reperfusion. These results illustrate the need for caution in the application and evaluation of methods determining permeability in fixed tissue. Probes of differing size and charge permeated fixed tissue to varying degrees thereby implicating the formation of specific lesions during chemical fixation.

Animals↗
PubMed1990

Preservation of myocardial function and biochemistry after blood and oxygenated crystalloid cardioplegia during cardiac arrest.

We compared the ability of blood cardioplegia and oxygenated crystalloid cardioplegic solutions to maintain regional left ventricle contractility and adenosine triphosphate levels after cardiopulmonary bypass. Ten baboons were subjected to 90-minute cardiopulmonary bypass conducted at 28 degrees C. Hemodynamic measurements were made before and after the bypass procedure, and biopsies for high-energy phosphate determinations were performed at different time intervals during and after bypass. The results showed improved maintenance of myocardial contractility (measured with the regional end-systolic pressure-length relationship) with the oxygenated crystalloid solution. Expressed as a percentage of values before bypass, contractility after bypass averaged 81.69% +/- 4.81% and 80.47% +/- 10.05%, respectively, after 10 and 20 minutes using the oxygenated crystalloid cardioplegia. For blood cardioplegia, the corresponding values were 71.9% +/- 8.73% and 64.99% +/- 8.60% (mean +/- standard error of the mean). The 10- and 20-minute postbypass values between the two groups differed significantly (t test, Welch modification: p = 0.0464 and p = 0.0342). Myocardial adenosine triphosphate level was higher immediately after induction of cardiac arrest when blood cardioplegia was used (blood cardioplegia, 6.82 mol.g wet wt-1; crystalloid cardioplegia, 4.95 mol.g wet wt-1; p = 0.0314), but values subsequently equalized.

Adenosine Triphosphate↗