Biomedical subjects

I Leusen

Publications and source records attributed to I Leusen.

At least 37 records · Page 2Linked to original sources

PubMed1987

Cerebrovascular reserve in the cat after acute bilateral carotid occlusion.

Cerebral blood flow in the cat was studied before and after acute bilateral common carotid occlusion under normocapnic and hypercapnic conditions and after induced hypotension. Regional blood flow to different brain structures was studied with the microsphere method. Local blood flow in the caudate nucleus, the cerebral cortex and medulla oblongata was studied with H2-polarography. Although the blood flow to the anterior brain regions is significantly decreased after bilateral common carotid occlusion, their blood supply is kept above ischaemic levels by re-distribution of the vertebrobasilar flow. Cerebrovascular reserve in anterior brain regions, however, is lost as indicated by the severe impairment of both the flow response to hypercapnia and to blood pressure decrease. After bilateral common carotid occlusion paradoxical CO2-reactions, indicating intracerebral steal, were seen in the caudate nucleus. In posterior brain regions resting blood flow, flow-reaction to hypercapnia and to hypotension are better preserved under these conditions. Measurement of the CBF responses to induced hypercapnia is a dependable test for appreciation of cerebrovascular reserve after cerebrovascular occlusion but may be potentially hazardous where local flow is close to ischaemic levels.

Adaptation, Physiological↗

PubMed1987

Influence of vascular tolerance to nitroglycerin on endothelium-dependent relaxation.

Many physiological important substances elicit a relaxing effect on blood vessels which is mediated by (a) substance(s) [EDRF(s)] released from the endothelial cells. EDRF(s) stimulate(s) guanylate cyclase, increasing cGMP at the smooth muscle level, resulting in relaxation. Since this mechanism of action is very similar to that of nitrovasodilator substances, we investigated whether EDRF(s) would act via the "organic nitrate receptor", which is thought to be the common site of action for organic nitrovasodilator substances. The relaxation effect of EDRF-mediated substances (histamine and acetylcholine) was investigated on contracted rat aorta preparations in which the affinity of the organic nitrate receptor was lowered by a treatment with high doses of nitroglycerin. The dose-relaxation curve of nitroglycerin on aorta preparations of pre-treated animals showed a highly significant shift to the right compared to preparations of control rats, proving the nitrate-receptor tolerance. However, when the same preparations were tested for their reactivity to acetylcholine or histamine, no differences could be demonstrated. These results indicate that, although it is known that organic nitrates and EDRF relax vascular smooth muscle cells by stimulating guanylate cyclase, this stimulation is mediated by a different mechanism.

Acetylcholine↗

PubMed1986

Local cerebral glucose utilization during intracerebral pH changes.

The effect of ventriculocisternal perfusion with mock CSF with alkaline or acidic pH on the local CMRglu (LCMRglu) in the caudatoputamen was studied in artificially ventilated and relaxed rats. In control rats both lateral cerebral ventricles were perfused with mock CSF at pH 7.4. In the experimental series one cerebral ventricle was infused with normal mock CSF while the other was infused with mock CSF in which the pH was decreased or increased by changing [HCO-3]. LCMRglu was depressed in acidotic brain tissue while it was strongly increased in alkalotic brain tissue. The importance of these alterations in brain glucose metabolism for the homeostatic regulation of brain pH is discussed.

Acidosis↗

PubMed1986

Influence of surface pH on intracellular pH regulation in cardiac and skeletal muscle.

The influence of the surface pH (pHs) on the intracellular pH (pHi) and the recovery of pHi after an imposed intracellular acid load was investigated in isolated sheep cardiac Purkinje fiber, rabbit papillary muscle, and mouse and rat soleus muscle. pHs and pHi, respectively, were continuously measured by use of single- and double-barreled pH-sensitive glass microelectrodes. Surface acidosis, usually obtained by superfusion with solutions of acid pH, was also produced with low buffered (5 mM N-2-hydroxyethylpiperazine-N'-2-ethane-sulfonic acid) solutions at control pH. The pHs decrease (delta pHs) induced by low buffering was smallest (-0.08 pH unit) in Purkinje fiber and largest (-0.31 pH unit) in rat soleus muscle, which already had a more acid surface in control conditions. delta pHs was somewhat dependent on the superfusion rate. Higher superfusion rates decreased but did not abolish delta pHs. Surface acidosis was associated with a small intracellular acidification. Intracellular acid loads were produced by adding and subsequently withdrawing 20 meq/l NH4+ from the superfusate. In all preparations, the rate of recovery of pHi after NH4+ withdrawal was notably decreased at acidified pHs. This effect was amiloride sensitive. It is concluded that, in superfused multi-cellular preparations, pHs and therefore the buffer concentration of a superfusate can considerably influence steady-state pHi and pHi recovery from an imposed intracellular acid load.

Amiloride↗

PubMed1986

Endothelium-dependent and independent relaxation of aortic rings from hypertensive rats.

The relaxation effects of endothelium-dependent (acetylcholine, histamine) and endothelium-independent (nitroprusside, nitrite) relaxing substances were comparatively examined on contracted thoracic aortic rings from normotensive and experimental renal and desoxycorticosterone acetate (DOCA)-salt hypertensive Wistar rats. On the aorta preparations from hypertensive animals a highly significant depression of the maximal relaxation effect of histamine and acetylcholine was observed. This was not seen with nitroprusside and nitrite. By use of a bioassay technique it was demonstrated that the depression of the endothelium-mediated response is not due to a diminished release of endothelium-derived relaxing factor. Impaired coupling between the endothelium and the smooth muscle cells is suggested to be responsible for that depression.

Acetylcholine↗

PubMed1986

Effect of premercurial resetting of intrarenal vascular resistance on HgCl2-induced acute renal failure.

The role of renal hemodynamics in the first hours of HgCl2-induced acute renal failure was examined by studying the influence of resetting the total renal vascular resistance (RT) within the limits of autoregulation before and after the mercury administration. Intravenous HgCl2 alone (3 mg/kg) caused an early fall of glomerular filtration rate (GFR) from 69 +/- 3 to 38 +/- 4 ml/min/100 gm kidney weight (KW) and of renal blood flow (RBF) from 535 +/- 42 to 276 +/- 27 ml/min/100 gm KW, 3 hours after HgCl2 (P less than 0.01). In a second series, the RT was decreased by clamping the aorta before and after HgCl2 so that the mean renal perfusion pressure (MRPP) was lowered to a mean of 87 +/- 5 mm Hg). This maneuver did not prevent the fall in GFR (from 81 +/- 5 to 36 +/- 6 ml/min/100 gm KW) or in RBF (from 510 +/- 79 to 197 +/- 20 ml/min/100 gm KW) after HgCl2 (P less than 0.01). In a third group, the RT was increased by a rise of MRPP to 158 +/- 8 mm Hg by bilateral carotid clamping. Subsequently, 3 hours after HgCl2, the GFR decreased not significantly from 72 +/- 6 to 61 +/- 7 ml/min/100 gm KW, and RBF increased from 405 +/- 66 to 431 +/- 71 ml/min/100 gm KW. Three hours of continued carotid clamping alone caused a rise of GFR from 64 +/- 7 to 83 +/- 7 ml/min/100 gm KW (P less than 0.05) and of RBF from 425 +/- 16 to 581 +/- 28 ml/min/100 gm KW (P less than 0.01). Autoregulation of RBF was studied in a control period and after 3 hours of carotid clamping and found to be lost during prolonged carotid clamping. The autoregulatory capacity remained intact after HgCl2 alone. The renal vasoconstrictive response to norepinephrine was not affected 3 hours after carotid clamping. It is concluded that the fall of GFR and RBF after HgCl2 can be prevented by prolonged carotid clamping. This is related to a loss of the capacity to maintain renal vasoconstriction after carotid clamping because of a concomitant loss of autoregulation of RBF and points at least in part to a pathogenetic role of changes in renal hemodynamics in the first hours after HgCl2. The tubular effects of HgCl2 were, however, maintained, despite the protection of GFR.

Acute Kidney Injury↗

PubMed1985

Intracellular pH and contraction of isolated rabbit and cat papillary muscle: effect of superfusate buffering.

The influence of external buffering on surface pH (pHs), intracellular pH (pHi) and developed twitch tension was investigated in rabbit and cat papillary muscle. pHs and pHi were measured using single and double-barreled microelectrodes respectively. In 20 mM HEPES buffered solution, steady state pHi is close to that in control CO2/HCO-3 (25 mM HCO-3, 5% CO2) solution. pHs and developed tension also do not differ greatly from their control values. Decreasing the HEPES concentration to 5 mM, at constant external pH, lowers pHs considerably. The surface acidosis is associated with a small intracellular acidification; steady state pHi in 5 mM HEPES is always more acid than that in control CO2/HCO-3. A significant decrease in developed tension is also seen in 5 mM HEPES. Alteration of the superfusion velocity influences pHs only slightly. Stimulation of the muscle at high frequency is shown to increase surface acidification, the extent of which is dependent on the buffer concentration. The conclusion from the present experiments is that in papillary muscle external buffering influences intracellular pH and contraction via its effect on pHs.

Acid-Base Equilibrium↗

PubMed1985

Comparative study between histochemical and biochemical estimation of estrogen receptors in tumors.

Sucrose gradient analysis (SDGC) was compared with histofluoroassay, using 17 beta-Estradiol-6-carboxymethyloxime-bovine serum albumin-fluorescein isothiocyanate (E2-BSA-FITC) as fluorescent ligand, for the estimation of estrogen receptors (ER) in human breast tumors. No correlation was seen between fluorescent ligand binding capacity by the tumoral tissues on the one hand and ER levels estimated by SDGC on the other hand. The fluorescent ligand had a lower affinity for the receptor than estradiol itself and was contaminated with free estradiol. It was concluded that the absence of correlation between both techniques was for the greatest part due to unspecific binding of E2-BSA-FITC.

Breast Neoplasms↗

PubMed1984

Testosterone metabolism by incubated rat testes after chronic LHRH treatment.

Adult male rats were injected 4 or 8 days with LHRH agonist. After sacrifice the testes were incubated in vitro with or without [4-14C]testosterone. After LHRH-administration the endogenously produced amounts of testosterone and of 7 alpha-hydroxytestosterone, the main testosterone metabolite normally found on incubation of adult rat testes, were drastically reduced when compared with controls. hCG, injected to rats 2 h before sacrifice, increased steroid production. In the LHRH-treated rats, however, the amounts of testosterone and of 7 alpha-hydroxytestosterone produced were much less while an important formation of 5 alpha-androstanediol was observed. The testes of LHRH treated rats metabolized [4-14C]testosterone to a large extent to 5 alpha-reduced and unextractable metabolites while the formation of 7 alpha-hydroxylated metabolites was much reduced. It is concluded that prolonged LHRH treatment provokes not only a depression of the testosterone production but has also an influence on the testicular metabolism pattern of testosterone resulting in a proportionally increased production of 5 alpha-reduced steroids and unextractable metabolites while the formation of 7 alpha-hydroxylated steroids is inhibited.

Androgens↗

PubMed1984

Metabolism of [4-14C]testosterone and precursors by homogenates of rat testes after chronic LHRH-treatment.

Adult male rats were injected daily for 8 days with an LHRH agonist. Twenty-four hours after the last injection testes-homogenates were incubated in the presence of a 4-14C-labeled steroid, either progesterone, 17 alpha-hydroxyprogesterone, dehydroepiandrosterone, androstenedione or testosterone. The activity of several enzymes involved in the androgen biosynthetic pathway was inferred from the amount of metabolites produced under these conditions. After LHRH-treatment a significant increase in the 17,20-lyase activity was observed without any significant change in the activity of 17 alpha-hydroxylase, 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase and 17 beta-hydroxysteroid dehydrogenase. The results of the experiments indicate that the decreased testosterone secretion observed in rats after chronic LHRH-administration is not due to an inhibition of the enzyme-systems studied.

Androstenedione↗

PubMed1984

Analysis of Cl- -HCO3(-) exchange during recovery from intracellular acidosis in cardiac Purkinje strands.

The possible role of a Cl- -HCO3(-) exchange mechanism in the recovery from intracellular acidosis of isolated cardiac Purkinje strands was investigated. Intracellular pH (pHi) was measured using double-barreled pH-sensitive microelectrodes. Acidifications were produced by withdrawing 20 meq NH+4 from the superfusate. Experiments were performed in normal CO2-HCO3(-)-buffered, in HCO3(-)free, and in Cl-free solutions and also in the presence of 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS), a blocker of Cl--HCO3(-) exchange. In the absence of external HCO3(-), the apparent rate of acid extrusion following induced acidification was only slightly decreased, but the observed effect does not necessarily imply the intervention of a Cl--HCO3(-) exchange mechanism. SITS had little effect on the response to acidification. In zero-Cl- solutions, recovery of pHi from acidosis was not impaired. These observations suggest that in Purkinje fibers, [Cl-]i-[HCO3(-)]o exchange plays no significant role in recovery from intracellular acidification. Moreover, additional evidence is presented in favor of a passive HCO3(-) efflux at steady-state pHi in the normal superfusate. The apparent membrane permeability to HCO-3 was estimated to be 3.2 X 10(-8) cm X s-1.

Acidosis↗

PubMed1984

Local cerebral glucose utilization in systemic acidosis.

Cerebral glucose metabolism (CMRglu) is decreased during acute and prolonged hypercapnic acidosis and during prolonged metabolic (HCl) acidosis; it is increased in acute (hypocapnic) metabolic acidosis and is not changed in acute isocapnic metabolic acidosis. The alteration in CMRglu can be explained by the changes occurring in intracerebral pH under these experimental conditions. In pontine gray matter, n. tractus solitarii, and n. ambiguus, three structures participating in the neuronal regulation of ventilation, local CMRglu is increased in all acidotic groups, suggesting coupling of function and metabolism at the local level during acidosis-induced hyperventilation.

Acidosis↗

PubMed1984

Effects of acetazolamide on ionic composition of cisternal fluid during acute respiratory acidosis.

We studied the effects of intravenous acetazolamide (50-200 mg/kg) on cerebrospinal fluid (CSF) electrolytes and pH regulation in 10 anesthetized and nephrectomized dogs (group II): acetazolamide was injected at -1 h, and respiratory acidosis was induced at zero time for 6 h. A control group of 10 animals (group I) was treated similarly except that an equal volume of 0.45% saline was injected intravenously instead of acetazolamide. The mean CSF PCO2 values in group I were 49.7 +/- 3.4 (SD), 50.2 +/- 3.6, 92.3 +/- 7.0, 100.3 +/- 8.1, and 97.8 +/- 7.3 Torr, respectively, at -1, 0, 3, 4.5, and 6 h; respective values in group II were 49.8 +/- 2.0, 55.2 +/- 5.2, 95.8 +/- 6.4, 103.1 +/- 16.7, and 104.9 +/- 14.1 Torr. During acute respiratory acidosis CSF [HCO3-] rose progressively with time in group I, and the mean values were 28.1 +/- 1.4 (SD), 29.2 +/- 1.7 and 30.1 +/- 1.9 mmol/l, respectively, 3, 4.5, and 6 h after induction of acidosis; respective values in group II were 28.2 +/- 1.1, 28.3 +/- 0.9, and 28.5 +/- 1.4 mmol/l. Acetazolamide at various doses administered inhibited any further rise in CSF [HCO3-] beyond the 3rd h of acidosis. The lower rise in CSF [HCO3-] in group II could not be ascribed to differences in CSF lactate concentration which changed similarly in both groups. Increments in CSF K+ and phosphate concentrations were significantly higher in the acetazolamide group than in the control group, the former presumably reflecting efflux of K+ from intracellular to extracellular fluid compartment. We conclude that in nephrectomized dogs during acute respiratory acidosis intravenously administered acetazolamide diminishes the rise in CSF [HCO3-], impairs CSF H+ regulation, and increases CSF K+ and phosphate concentrations.

Acetazolamide↗

PubMed1984

Effects of SITS, an anion transport blocker, on CSF ionic composition in metabolic alkalosis.

Disulfonic stilbenes combine with the carrier protein involved in anion transport and inhibit the exchange of Cl- for HCO3- in a variety of biomembranes. Our aim was to determine whether such a mechanism is operative in the regulation of cerebrospinal fluid (CSF) [HCO3-] in metabolic alkalosis. In anesthetized, curarized, and artificially ventilated dogs either mock CSF (group I, 9 dogs) or mock CSF containing SITS, 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (group II, 7 dogs) was periodically injected into both lateral cerebral ventricles. During 6 h of isocapnic metabolic alkalosis, produced by intravenous infusion of Na2CO3 solution, plasma [HCO3-] was increased by approximately 14 meq/l in both groups. In SITS-treated animals the mean cisternal CSF [HCO3-] increased by 7.7 meq/l after 6 h, and this was significantly higher than the respective increment, 3.5 meq/l, noted in the control group. Increments in CSF [HCO3-] in both groups were reciprocated by decrements in CSF [Cl-] with CSF [Na+] remaining unchanged. Cisternal CSF PCO2 and lactate concentrations showed similar increments in both groups. It is hypothesized that in metabolic alkalosis a carrier transports HCO3- out of cerebral fluid in exchange for Cl- and that SITS inhibits this mechanism. The efflux of HCO3- out of CSF in metabolic alkalosis would minimize the rise in CSF [HCO3-] brought about by HCO3-] influx from blood into CSF and therefore contributes to the CSF [H+] homeostasis.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗

PubMed1984

Single-unit pH-sensitive double-barreled microelectrodes for extracellular use.

The purpose of this study is to systematically describe the construction of pH-sensitive double-barreled microelectrodes for extracellular use. The most important advantages of these microelectrodes are as follows: the reference and the pH barrels are next to each other, and therefore the measured pH is not affected by asymmetric or slowly spreading direct current potential. The diameter of the tip of the microelectrodes is between 7 and 35 micron. These pH-sensitive microelectrodes are generally stable and Nernstian. They can be used repeatedly both in vivo and in vitro to measure tissue extracellular fluid pH. Some applications are described.

Animals↗

PubMed1984

Comparison between mannitol and saline infusion in HgCl2-induced acute renal failure.

The effect of isotonic mannitol and saline in the early phase of mercuric chloride-(HgCl2-)induced acute renal failure (ARF) in the dog was evaluated. During the first 3 h after HgCl2 alone, glomerular filtration rate (GFR) fell from 1.94 +/- 0.14 to 1.04 +/- 0.11 and renal blood flow (RBF) from 13.99 +/- 1.18 to 7.28 +/- 0.77 ml/min X kg BW. Isotonic mannitol alone resulted in a fall of GFR by 22% (p less than 0.05 vs. control), but the subsequent administration of HgCl2 could not induce a further fall in GFR and RBF. A similar, if somewhat less pronounced, protective effect was observed when mannitol was started simultaneously with or 2 h after the HgCl2 injection. Infusion of isotonic saline at the same rate as mannitol did not prevent a fall of GFR and RBF from a premercury value of 2.33 +/- 0.31 to 1.36 +/- 0.26 and 16.83 +/- 3.06 to 9.30 +/- 2.65 ml/min X kg BW, respectively. In contrast, massive doses of isotonic saline, provoking urinary volume and solute losses comparable to those observed with mannitol, stabilized GFR after HgCl2 at the normal level (delta GFR = -3%). No relationship between delta GFR and urinary Hg excretion or renal tissue Hg content could be established. In summary, isotonic mannitol prevented the fall of GFR normally observed in the early phase of HgCl2-induced ARF. This effect was not volume mediated and not due to a higher Hg excretion. The protection was correlated with its osmotic diuretic effect.

Acute Kidney Injury↗

PubMed1984

Role of prejunctional alpha 2-adrenergic receptors in the regulation of myocardial performance during exercise in conscious dogs.

We examined, in conscious dogs, the potential role of prejunctional alpha 2-adrenergic receptors for the regulation of heart rate and contractility response to exercise through modulation of the neurotransmitter release. Changes in heart rate and left ventricular pressure with time during comparable exercise levels, together with changes in norepinephrine concentration in the coronary sinus, were compared before and after the intravenous administration of: prazosin (0.5 mg/kg), a preferential postjunctional alpha 1-adrenergic receptor blocking agent; phentolamine (1 mg/kg), a nonselective alpha-adrenergic blocking agent; and yohimbine (0.3 mg/kg), a preferential prejunctional alpha 2-adrenergic receptor blocking agent. During exercise after phentolamine or yohimbine, changes in heart rate and left ventricular dP/dt were markedly potentiated compared to the control exercise, as well as to exercise after prazosin, whereas the norepinephrine concentration in the coronary sinus was substantially elevated. After intracoronary administration of phentolamine (0.1 mg/kg) or yohimbine (0.03 mg/kg), heart rate and contractility response to exercise were also potentiated, compared to the control exercise. These observations indicate that, in the intact conscious animal, prejunctional alpha 2-adrenoreceptors are stimulated during exercise, thereby modulating the norepinephrine release through a negative feedback inhibitory mechanism. Blocking these receptors by phentolamine or yohimbine results in an uncontrolled norepinephrine release during exercise associated with an augmented beta-adrenergic receptor-mediated end organ response, i.e., a potentiation in heart rate and contractility response.

Adrenergic alpha-Antagonists↗

PubMed1984

Effect of histamine on aorta preparations of different species.

The effect of histamine (10(-8) to 10(-3)M) on aorta preparations of 5 different species was studied. In aortic ring segments, precontracted by norepinephrine, three types of dose-response curves were found: relaxation (rat), contraction (guinea-pig, cat, mouse) and relaxation followed by contraction at higher doses (rabbit). In relaxed preparations, histamine either had no effect (rat) or elicited a contraction (rabbit, guinea-pig). All the contraction effects proved to be H1-mediated as they were antagonized by mepyramine. These contraction effects were maintained or even increased after rubbing the endothelial surface of the vessel, which suggests a direct action on muscular structures. The differences between the species in the dose-response curves to histamine appeared to be determined by the role of the endothelial structures, which can induce an H1-mediated (rat) or an H2-mediated (rabbit) relaxation or may have no influence (guinea-pig).

Acetylcholine↗