Kovách Ag

Biomechanical properties of normal and fibrosclerotic human cerebral arteries

Quasi-static passive mechanical properties of histologically fibrosclerotic and normal groups of human anterior cerebral arteries (ACA) and internal carotid arteries (ICA) were studied in vivo. Cylindrical arterial segments were subjected to slow, cyclic inflation by air in the range of 5-250 mm Hg intraluminal pressure at axial isometry. To characterize mechanical properties, incremental elastic modulus, incremental distensibility and strain energy density were computed from the continuously recorded pressure-external diameter curves. Compared to normal arteries, at identical intraluminal pressures, the elastic modulus of fibrosclerotic arteries was found to be 34-45% lower in ACA and 40-56% lower in ICA, and the radius to wall thickness ratio was 25-30% smaller in ACA and 37-38% smaller in ICA. Distensibility of fibrosclerotic arteries was not smaller than that of the normal vessels. There were no significant differences in internal radius and in strain energy density between the fibrosclerotic and normal groups. Results of mathematical modelling suggests that the observed decrease in the elastic modulus of fibrosclerotic arteries was accompanied by different types of structural reorganization in the case of ACA and ICA. It is supposed that changes in mechanical properties of the passive wall elements have a compensatory character to restore some hemodynamically important properties of fibrosclerotic arteries, namely tangential stress, incremental distensibility or characteristic impedance.

Contractile and endothelium-dependent dilatory responses of cerebral arteries at various extracellular magnesium concentrations

To clarify the effect of extracellular magnesium (Mg2+) on the vascular reactivity of feline isolated middle cerebral arteries, the effects of slight alterations in the Mg2+ concentration on the contractile and endothelium-dependent dilatory responses were investigated in vitro. The contractions, induced by 10−8-10−5 M norepinephrine, were significantly potentiated at low Mg2+ (0.8 mM v. the normal, 1.2 mM). High (1.6 and 2.0 mM) Mg2+ exhibited an inhibitory effect on the contractile responses. No significant changes, however, in the EC50 values for norepinephrine were found. The endothelium-dependent relaxations induced by 108–10−5 M acetylcholine were inhibited by high (1.6 and 2.0 mM) Mg2+. Lowering of the Mg2+ concentration to 0.8 mM or total withdrawal of this ion from the medium failed to alter the dilatory potency of acetylcholine. The changes in the dilatory responses also shifted the EC50 values for acetylcholine to the right. The present results show that the contractile responses of the cerebral arteries are extremely susceptible to the changes of Mg2+ concentrations. In response to contractile and endothelium-dependent dilatory agonists, Mg2+ probably affects both the calcium influx into the endothelial and smooth muscle cells as well as the binding of acetylcholine to its endothelial receptor. Since Mg2+ deficiency might facilitate the contractile but not the endothelium-dependent relaxant responses, the present study supports a role for Mg2+ deficiency in the development of the cerebral vasospasm.

Effect of the organic calcium antagonist D-600 on cerebrocortical vascular and redox responses evoked by adenosine, anoxia, and epilepsy.

The purpose of this study was to investigate the role of calcium ions in cerebrocortical vasodilatation and oxidized and reduced nicotinamide adenine dinucleotide (NAD/NADH) redox responses evoked by adenosine, anoxia, and epileptic seizures. The brain cortex of chloralose-anaesthetized cats was treated locally with gallopamil-hydrochloride (D-600) and verapamil (Isoptin®). These organic calcium antagonists decrease the inward movement of calcium ions into vascular smooth muscle cells. Cerebrocortical vascular volume (CVV) and NADH fluorescence were measured in vivo by fluororeflectometry. Adenosine and calcium antagonists were dissolved in artificial cerebrospinal fluid (mock CSF) and applied topically to the brain cortex by superfusion. Adenosine (10−8 to 10−3 M) resulted in concentration-dependent increases in CVV. The NAD/NADH redox state was not altered below adenosine concentrations of 10−5 M. However, in the concentration range of 10−5 to 10−3 M, significant NAD reduction was obtained. Both calcium antagonists increased CVV markedly, but did not bring about significant changes in NAD/NADH ratio and local electrical activity of the exposed brain cortex. D-600 (2 × 10−6 M) increased CVV as much as did 10−4 M adenosine, but it failed to diminish the vascular and metabolic effects of the adenosine. D-600 (2 × 10−4 M) resulted in an increase in CVV approximately 2.5 times greater than that caused by 10−4 M adenosine alone. However, the adenosine-induced CVV response was inhibited by only about 70%, compared with the control response. After pretreating the brain cortex with 2 × 10−3 M D-600, adenosine had no effects on CVV and NAD/NADH redox state; the NAD reduction accompanying anoxia and epileptic seizures was considerably diminished. These results suggest that the inhibition of transmembrane calcium influx could have a minor role in the vasodilatatory mechanism of adenosine. Since the vascular effect of adenosine vanished only at very high concentration of D-600, which might also inhibit the release of calcium from intracellular binding sites, it is presumed that adenosine dilates the cerebrocortical vessels by interacting with intracellular calcium-sequestrating mechanisms. Furthermore, since adenosine had a marked NAD reducing effect and since it is well known that it increases the activity of adenylate cyclase and phosphorylase enzymes, accumulation of 3′,5′-cyclic adenosine monophosphate (cAMP) and substrate mobilization might be involved also in the vasodilatatory mechanism of adenosine. Our results concerning the inhibitory effect of D-600 on epilepsy- and anoxia-induced cerebrocortical NAD reduction unambiguously demonstrate the significance of calcium fluxes in glycogen and glucose metabolism under these conditions.

Comparative effects of chloralose anesthesia and Sernylan analgesia on cerebral blood flow, CO2 responsiveness, and brain metabolism in the baboon.

A comparison was made between the effects of two different anesthetics, alpha-D-gluco-chloralose and 1-1-phenylcyclohexyl piperidine hydrochloride (Sernylan8), on cerebral blood flow (CBF), brain metabolism and cerebrovascular CO, responsiveness in primates. The experiments were carried out on immobilized and artificially ventilated baboons. Anesthesia was induced either with 100/mg/kg chloralose (i.p.) or with 1 mg/kg Sernylan (i.m.). CBF in 8 different brain regions was measured by the intra-arterial luXe clearance technique. The CO] responsiveness of the cerebrovascular bed was tested by a gas mixture containing 5% CO,. Chloralose depressed total as well as regional CBF compared to the effect of Sernylan. A significant shift occurred toward lower CBF values in the grey matter while white matter flow was identical in the two groups. Brain Oa consumption was significantly higher during Sernylan analgesia (3.35 ± 0.34 ml/100 g/min) than during chloralose anesthesia (2.42 ± 0.22 ml/100 g/min). There were no differences in glucose uptake, lactate and pyruvate production, or in arterial and cerebral venous blood gases in the two types of anesthesia. The cerebrovascular CO2 sensitivity of the Sernylan-treated baboons was higher than that of the chloralose-anesthetized animals, in both the grey and white matter.

Endothelium-dependent influence of small changes in extracellular magnesium concentration on the tone of feline middle cerebral arteries.

The aim of this study was to investigate the effect of small alterations in the extracellular magnesium concentration on the tone of feline middle cerebral arteries and to examine the role of the endothelium in these responses. We measured the isometric tension of isolated arterial rings placed between two stainless steel wires in a tissue chamber containing Krebs-Henseleit solution aerated with a gas mixture containing 95% O2 and 5% CO2 at 37 degrees C. After precontraction with noradrenaline, a decrease of the extracellular magnesium concentration from 1.2 mM to 1.0 and 0.8 mM resulted in sustained relaxations, whereas elevation of the extracellular magnesium concentration from 0.8 mM to 1.2 mM caused an increase in vascular tone when the endothelium was intact. The magnesium deficiency-related dilations were absent in endothelium-denuded vessels and were inhibited by 5 x 10(-6) M oxyhemoglobin and 10(-5) M methylene blue, suggesting the involvement of an endothelium-derived relaxing factor in this vascular response. However, 5 x 10(-7) M nifedipine or 3 x 10(-5) M dichlorobenzamil did not affect the magnesium deficiency-related relaxations. Therefore, nifedipine-sensitive calcium channels or the sodium/calcium antiport system are not involved in this vascular action of magnesium. We conclude that small alterations in the extracellular magnesium concentration, possibly within the physiological range, are able to modify the basal formation and release of endothelium-derived relaxing factor and thus alter arterial smooth muscle tone in this vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of endothelium in the response of the vein wall to magnesium withdrawal

Complete absence of magnesium has a two-fold effect on the arterial tone: direct smooth muscle contraction and relaxation via endothelium-derived relaxing factor (EDRF) release. In the present study performed on a systemic vein we investigated (1) which of these effects dominates following reduction of magnesium concentration from 1.2 mM to 0.8 and 0.4 mM and (2) whether the vessel segments asymmetrically respond when the magnesium concentration is reduced on either the intra- or extraluminal side. The effects of reducing magnesium concentration on both the isometric tension of isolated ring preparations and the diameter of isolated, perfused and superfused feline femoral veins were investigated. In nor-adrenaline-precontracted rings, rapid decreases in the extracellular magnesium concentration from 1.2 mM to 0.8 and 0.4 mM caused relaxation, whereas total omission of magnesium returned the tone to the level of the initial tone induced by noradrenaline. Both in the presence of haemoglobin (5×10−6M), and in vessels without endothelium, lowering the magnesium concentration caused a dose-dependent elevation of the noradrenaline-induced tone. In perfused and superfused noradrenaline-contracted vein segments, each reduction of extraluminal magnesium concentration caused contraction of the vessels, regardless of whether the endothelium was intact or not. A decrease in intraluminal magnesium concentration did not alter the diameter of the vessel when the endothelium was intact, but caused contraction when the endothelium was disrupted. The results of the present study demonstrate that both the reduction of magnesium concentration or its complete absence cause an EDRF-mediated relaxation and a directly mediated smooth muscle contraction in the femoral vein of the cat. Within the physiological range of extracellular magnesium concentrations, however, the EDRF-mediated relaxation seems to dominate.

Contribution of Adenosine to the Regulation of Cerebral Blood Flow: The Role of Calcium Ions in the Adenosine-Induced Cerebrocortical Vasodilatation

It is well established that cerebral blood flow (CBF) and adenosine concentration in the brain can be elevated severalfold during arterial hypoxia and epileptic seizures (Winn et al., 1981). Since perivascularly administered adenosine dilatates pial arteries (Wahl and Kuschinsky, 1976) and the stable analog of adenosine, chloroadenosine, is an even more efficient dilatator of cerebrocortical vessels (Winn et al., 1981), it was suggested that adenosine plays a central role in the regulation of CBF (Winn et al., 1981). However, since the adenosine concentration of the normal brain is very low (Winn et al., 1981: around 10−7 mol l−1), this assumption is valid only if adenosine is present exclusively in the extracellular fluid. Besides this, it is also not yet clear whether the vasodilatator action of adenosine involves changes in calcium availability of the vascular smooth muscle (Dutta et al., 1980; Fenton et al., 1982), or adenosine dilates the vessels by some other mechanism (Kukovetz et al., 1978). In the present study the following questions were addressed: a) How efficient is topically administered adenosine when compared with arterial hypoxia and epileptic seizures in altering cerebrocortical vascular volume (CVV) ? b) Is there a possible role of adenosine-induced cortical metabolic changes in the vasodilatatory mechanism? c) What is the importance of calcium availability in the vascular action of adenosine? To answer these questions the brain cortex was superfused with various concentrations of adenosine.

Correlation between the Redox State, Electrical Activity and Blood Flow in Cat Brain CORTEX During Hemorrhagic Shock

Owing to its well developed autoregulatory mechanisms, total cerebral blood flow is stable over a wide range of mean arterial blood pressures and decreases significantly only when the perfusion pressure is below 50 mmHg.

Relationship Between Steady Redox State and Brain Activation-Induced NAD/NADH Redox Responses

It is well recognized that activation of the brain leads to an overwhelming increase in cerebral blood flow (CBF), oxygen, and glucose consumption (Siesjo, 1978; Sokoloff, 1981). Because ATP usage is augmented, the ratio of ATP/ADP decreases, and according to the in vitro data of Chance and Williams (1955), the rate of mitochondrial electron transport and ADP phosphorylation will be accelerated. Consequently, mitochondrial NADH should be oxidized (Chance and Williams, 1955). The increased need of mitochondrial electron transport for reducing equivalents is matched by the increased production of pyruvate via stimulation of glycogenolysis and glycolysis (Siesjo, 1978; Sokoloff, 1981). Though it is unlikely that brain suffers from hypoxia under augmented electrical activity (Siesjo, 1978), a considerable amount of pyruvate is converted into lactate, and NADH accumulates in the cytosol (Howse and Duffy, 1975; Siesjo, 1978). This NADH reduction is explained as being due to the restriced capability of the so-called “H-shuttle” mechanisms to transfer H+ from cytosolic NADH to mitochondrial NAD (Howse and Duffy, 1975; Siesjo, 1978). Interestingly, when the mitochondrial NAD/NADH ratio has been determined with the oxidized-reduced substrate ratio method during epileptic seizures, discernible NADH oxidation was not obtained (Siesjo, 1978).

Effect of two week lymphatic occlusion on the mechanical properties of dog femoral arteries.

In order to study the long-term effect of impaired lymphatic drainage on the mechanical properties of the arterial wall, cylindrical femoral artery segments from 10 mongrel dogs after 2 weeks of hindlimb lymphatic occlusion were subjected to in vitro mechanical test and compared with the contralateral, sham-operated segments. Smooth muscle contraction was induced by norepinephrine (7.4 X 10(-6) M) and smooth muscle relaxation by papaverine (1.6 X 10(-4) M). As a result of 2 weeks of lymphatic occlusion, wall thickness increased from 243 +/- 18 to 343 +/- 35 microns (P less than 0.02), inner radius decreased from 1.69 +/- 0.11 to 1.42 +/- 0.12 mm (P less than 0.01) and elastic modulus decreased from 1.23 X 10(6) to 0.55 X 10(6) N/m2 (P less than 0.01), when determined at 100 mm Hg (13.3 kPa) intraluminal pressure and with relaxed smooth muscle. The contractile apparatus was able to produce active strain in the vessels with lymphostasis and at physiological pressures not significantly different from the controls (0.89 +/- 0.02 vs. 0.91 +/- 0.02), but at significantly lower levels of tangential stress. Active stress decreased significantly. This study shows that a reorganization of the vessel wall mechanical force-bearing elements occurs in lymphostasis, which, in some respects, resembles the mechanical alterations found in different forms of atherosclerosis.