Peritumoral brain edema associated with meningioma--histological study of the tumor margin and surrounding brain.

Thirty-nine cases of intracranial meningiomas were analyzed to identify factors causing brain edema. Edema was significantly correlated with tumor size and the destruction of the leptomeninges and cortex. Meningotheliomatous meningioma tended to have more peritumoral edema. There was no correlation between the presence of edema and location of the tumor or histological features including lymphocytic infiltration and the presence of glial fibrillary acidic protein-positive cells in the tumor tissue. Larger tumors destroy the leptomeninges and cerebral cortex, allowing direct transmission of humoral edema-promoting factor or edema fluid into the white matter, resulting in vasogenic edema.     

Causal relationship between conformational change and inhibition of domain functions of glycoxidative fibronectin

Glycoxidative modification of various body proteins, including fibronectin (FN), has been shown to change their structural and functional properties, and be implicated in pathogenesis of diabetic complications. Little is known about the role of secondary structure of glycoxidative FN (gFN) in its domain functions. gFN was prepared by incubation with 25 and 200 mM glucose in 0.2 M sodium phosphate buffer at 37 degrees C on a shaking plate under aerobic and sterile conditions for various time intervals up to 49 days, being defined as gFN25 and gFN200, respectively. Unmodified FN (uFN) was prepared by incubation in 0.2 M sodium phosphate buffer without any glucose at 4 degrees C for 49 days. The extent of glycoxidative modification was examined using a noncompetitive enzyme-linked immunosorbent assay with an antibody against N(epsilon) -(carboxymethyl)lysine (CML), one of the major glycoxidation products. The binding activities of uFN and gFN to collagen, gelatin and heparin were determined by a solid phase enzyme immunoassay or heparin-affinity HPLC. Cell attachment was estimated by the extent of adhesion of FITC-labeled smooth muscle cells to uFN or gFN. Conformational change in gFN was detected by SDS-polyacrylamide gel electrophoresis and spectroscopy (circular dichroism). CML was detected in gFN25 and gFN200 after 49 and 21 days of incubation, respectively. Levels of CML were about six-fold higher in gFN200 than in gFN25 after 49 days. Both gFN25 and gFN200 showed a significant decrease in the ability of binding to collagen and gelatin after 7 days of incubation. The binding activity for heparin was significantly decreased in both gFN25 and gFN200 after one day. Cell attachment activity was reduced to 89% and 76% of the unmodified form in both gFN25 and gFN200 after 49 days, respectively. High molecular weight materials were found in gFN25 and gFN200 after 21 and 7 days, respectively. CD spectrum showed that gFN25 had lost its native conformation after 3 days of incubation, depending upon the concentration and incubation interval of the applied glucose. These in vitro results suggest that the loss of native conformation may reduce the domain functions of gFN, including binding activity to macromolecular ligands and cell attachment, and may play a major role in the pathogenesis of diabetic complications.     

The Protective effect ofd-sotalol against hypoxia-induced myocardial uncoupling

Summary The effects ofd-sotalol on intercellular electrical coupling and ultrastructure under hypoxic conditions were investigated in myocardial samples from eight young (1–2 months) and four older (10–12 months) guinea pigs. A right ventricular muscle strip was kept simultaneously in two divided chambers and superfused with normoxic and/or hypoxic (97% N₂+ 3% C_O2) Krebs solution. Hypoxia caused shortening of action potential duration (APD) and electrical cellto-cell uncoupling. If the uncoupling appeared after short-term hypoxia (less than 30 min), administration of 3.10^–7M ofd-sotalol to the hypoxic perfusate led to a recovery of electrical coupling. Transmission electron microscopy revealed moderate reversible ultrastructural alterations of the cardiomyocytes. No apparent changes in intercellular junctions were observed. The recoupling effect of sotalol decreased with the time of hypoxia as the ultrastructural damage progressed. After prolonged hypoxia (more than 30min), cardiomyocytes were markedly injured, intercellular junctions were severely affected, and gap junctions occurred less frequently. In these cases, administration ofd-sotalol caused only transient recoupling. After 1h of hypoxia, no recoupling was observed. Pretreatment withd-sotalol prevented hypoxia-induced electrical uncoupling and markedly attenuated ultrastructural damage, although shortening of APD still persisted. Our results indicate that the cardioprotective effect ofd-sotalol on electrical intercellular coupling is closely associated with sotalol-induced prevention of the ultrastructural damage. Considering previous results, we suggest that this protective effect ofd-sotalol may be related to its ability to increase intracellular cyclic adenosine monophosphate and, thereby, to decrease cytosolic free Ca. These effects can explain the antiarrhythmic and defibrillating properties ofd-sotalol.     

Does intravenous landiolol, a β1-adrenergic blocker, affect stroke volume variation?

Purpose

There are no reports about the effect of bradycardia on stroke volume variation (SVV), and we hypothesized that induced bradycardia alters the value of SVV. Landiolol, an ultra-short-acting adrenergic β₁-receptor blocking agent, was reported to induce bradycardia without decreasing blood pressure. The initial aim of this prospective study was to investigate changes in SVV values by induced bradycardia in patients with good cardiac function.

Methods

At 30 min after anesthesia induction, if heart rate (HR) was >80 bpm, the patient was chosen as a subject. Ten ASA physical status I–II patients aged 38–75 years who were scheduled for elective abdominal surgery were included in this study. Baseline values were recorded, and then administration of landiolol was started at 125 μg/kg/min for 1 min and then continued at 40 μg/kg/min. SVV and other parameters were recorded at baseline and 3 min after continuous landiolol injection.

Results

Landiolol significantly decreased systolic arterial pressure, and diastolic arterial pressure, contrary to our expectations, and also HR, SVV, cardiac output, stroke volume index, and pressure of end-tidal CO₂, whereas systemic vascular resistance values increased significantly.

Conclusions

SVV decreased after continuous administration of a β₁-adrenergic blocker, probably because of a decrease in the difference of maximum stroke volume (SV) and minimum SV, or the downward shift of the Frank–Starling curve that occurred after landiolol administration. We believe that SVV values might be overestimated or misinterpreted when HR is decreased by landiolol and might not necessarily indicate that the patient is hypervolemic or normovolemic.     

Cell membrane-derived lysophosphatidylcholine activates cardiac ryanodine receptor channels

Lysophosphatidylcholine (LPC) is metabolized from a membrane phospholipid and modulates a variety of channels in the plasma membrane (PM). We examined LPC modulation of cardiac ryanodine receptor (RyR) channels in the sarcoplasmic reticulum (SR) using the planar lipid bilayer method to measure the single-channel currents. Micromolar concentrations of LPC increased the open probability of the reconstituted RyR channels irrespective of whether LPC was added to the cis or trans chamber. LPC also increased the membrane capacitance of the bilayer. The effects of LPC contrasted well with those of sphingosylphosphorylcholine (SPC). Taken together, these results suggest that amphipathic lipid LPC does not bind directly to the RyR channel protein, but rather, is incorporated into the bilayer membrane and activates the channel. Thus, we consider cell membrane-derived LPC to be a putative endogenous mediator that activates not only plasma membrane channels but also RyR channels and induces arrhythmogenic Ca²⁺ mobilization in cardiomyocytes.     

Phosphorylation of connexin in functional regulation of the cardiac gap junction

In cardiac muscle, the gap junction contributes to electrical cell-to-cell coupling. This physiological function of the gap junction depends on the phosphorylation state of the connexin molecule, which comprises the gap junction channel. The effects of intracellular Ca²⁺ overload, acidosis, activation of protein kinase (PK) A, PKC and PKG on the phosphorylation and expression of connexin 43 (Cx43) were examined in animal hearts with reference to physiological function. Activation of PKA promotes cell-to-cell coupling due to augmentation of the PKA-mediated phosphorylation of Cx43, with a rise in the quantity of and an increase in the expression of Cx43. A rise in the ionic strength of Ca²⁺ and H⁺ impaired cell communication, with the inhibition of PKA-mediated Cx43 phosphorylation. Activation of PKC reduces the quantity and expression of Cx43 despite augmentation of PKC-mediated phosphorylation of the protein. The effects of PKG activation are similar to those of PKC activation. It is suggested that PKA activation upregulates and PKC activation downregulates Cx43. The role of connexin phosphorylation in the regulation of gap junction function is discussed.     

The effects of diltiazem on hemodynamics and seizure duration during electroconvulsive therapy

Electroconvulsive therapy (ECT) is often associated with acute hyperdynamic responses, and we hypothesize that diltiazem can blunt this response. We measured the effect of a 10-mg dose of diltiazem on heart rate and mean arterial pressure during ECT. Furthermore, we assessed seizure duration by using both the cuff method and two-lead electroencephalogram. We studied 18 patients with a randomized, double-blinded, placebo-controlled cross-over study design. Diltiazem significantly reduced heart rate and mean arterial pressure just after medication, and it also significantly reduced the increases in these variables after ECT, as compared with the placebo. The use of diltiazem was, however, associated with a shortened seizure duration, possibly making ECT less effective. Because of the reduction in seizure duration, the routine administration of diltiazem may not be advisable because it can possibly interfere with the psychotherapeutic efficacy of ECT. However, diltiazem medication for ECT is potentially useful for reducing tachycardia and hypertension in high-risk patients. IMPLICATIONS: Diltiazem can blunt acute hyperdynamic responses after electroconvulsive therapy, but seizure duration is also significantly reduced, possibly making this therapy less effective.