Three cases of suspected sugammadex-induced hypersensitivity reactions.

Neuromuscular blocking agents have been implicated in 60-70% of anaphylactic events associated with anaesthesia. We report two cases of probable hypersensitivity reaction to sugammadex and an additional suspected but less supported case of possible immune-mediated reaction or other adverse reaction. The patients were given a bolus of sugammadex 100 mg immediately before extubation. In all three patients, a possible allergic reaction was suspected within 4 min of sugammadex administration, but with different degrees of severity. Skin testing was positive in two of these patients. Hypersensitivity to sugammadex unaccompanied by cardiovascular or respiratory symptoms might be missed during the course of anaesthesia. Careful monitoring for possible allergic responses is required in patients who have received sugammadex.

Measurement of microsomal ATPase activities: a comparison between the inorganic phosphate-release assay and the NADH-coupled enzyme assay.

The specific activity of the Mg2+-ATPase and the (Ca2+ + Mg2+)-ATPase has been measured in a microsomal fraction from pig antral smooth muscle with the phosphate-release assay and the NADH-coupled enzyme assay, and the release of inorganic phosphate as a function of time is compared with the concomitant production of ADP. Both assays are found to overestimate the true Mg2+-ATPase activity. The adenylate kinase inhibitor P1,P5-di(adenosine-5'-)pentaphosphate (Ap5A) reduces the specific activity of the Mg2+-ATPase measured in the NADH-coupled enzyme assay to about half of its original value; however, it does not affect the specific activity of the Mg2+-ATPase in the Pi-release assay. The considerable overestimation of the Mg2+-ATPase activity in the NADH-coupled enzyme assay results from a combined action of an ATP pyrophosphatase (ATP in equilibrium AMP + PPi) and adenylate kinase activity contaminating the microsomes. The adenylate kinase activity in the microsomes catalyses the conversion of AMP formed by the ATP pyrophosphatase together with ATP into two ADP's. Also the phosphate-release assay is prone to an overestimation artefact because an inorganic pyrophosphatase will degrade the pyrophosphate and thus lead to additional Pi-production. Measurements of AMP and NAD+ production by HPLC confirmed our proposed reaction scheme. The same (Ca2+ + Mg2+)-ATPase activity is found in both assays, because the (Ca2+ + Mg2+)-ATPase activity is calculated from the difference in ATPase activity in the presence and absence of Ca2+, so that as a consequence the interfering activities are automatically subtracted.

Effects of doxorubicin and ruthenium red on intracellular Ca2+ stores in skinned rabbit mesenteric smooth-muscle fibres.

Several agents are known to influence the contraction of skeletal and cardiac muscle via a modification of the Ca2+ release mechanism of the sarcoplasmic reticulum, e.g. caffeine, ryanodine, ruthenium red and doxorubicin. Of these substances, only the effects of caffeine and ryanodine have been described in smooth muscle. In this paper we describe the action of ruthenium red and doxorubicin on saponin-skinned mesenteric arteries of the rabbit. A high concentration (20 microM) of ruthenium red inhibited the Ca2+ release induced by low concentrations of caffeine, but had little effect on Ca2+ release induced by high concentrations (20 mM) of caffeine. This result indicates that the Ca2+ release channel of the internal Ca2+ store of smooth muscle cells is less sensitive to inhibition by ruthenium red than that of striated muscle. Doxorubicin in the micromolar range elicited a Ca2+ release and a concomitant contraction, essentially similar to its effect on skinned skeletal muscle cells. This work reveals further similarities between the Ca2+ release mechanisms of smooth and striated muscle, but the results also indicate that important differences between both systems may exist.

Properties of intracellular calcium stores in pregnant rat myometrium.

1. The properties of the Ca2+ stores in myometrium of 21-day pregnant rats were studied by recording the contractile responses of saponin-treated skinned muscles. 2. After accumulation of Ca2+ into the stores in the presence of 5 mM NaN3, inositol 1,4,5-trisphosphate (InsP3) at concentrations exceeding 3 microM produced a contraction. The amplitude of this contraction was maximal at about 20 microM. A second application of 20 microM InsP3 produced a smaller contraction than the first one. However after reloading the stores with Ca2+, 20 microM InsP3 produced a contraction of the same amplitude as the initial one. 3. After application of 20 microM InsP3, 1 microM A23187 still evoked a large contraction. If A23187 was applied first, the subsequent application of InsP3 or A23187 no longer induced a contraction, even after Ca2+ loading. 4. Guanosine triphosphate (GTP) or arachidonic acid, both 100 microM neither evoked a contraction nor enhanced the subsequent contraction elicited by 20 microM InsP3. 5. Caffeine 25 mM did not induce a contraction nor did it affect the contraction elicited by 20 microM InsP3. 6. The results indicate that in pregnant rat myometrium InsP3 releases Ca2+ from intracellular stores as has been proposed in vascular smooth muscles.

Effect of cilostazol, a phosphodiesterase type III inhibitor, on histamine-induced increase in [Ca2+]i and force in middle cerebral artery of the rabbit.

1. The effect of cilostazol, an inhibitor of phosphodiesterase type III (PDE III), on the contraction induced by histamine was studied by making simultaneous measurements of isometric force and the intracellular concentration of Ca2+ ([Ca2+]i) in endothelium-denuded muscle strips from the peripheral part of the middle cerebral artery of the rabbit. 2. High K+ (80 mM) produced a phasic, followed by a tonic increase in both [Ca2+]i and force. Cilostazol (10 microM) did not modify the resting [Ca2+]i, but it did significantly decrease the tonic contraction induced by high K+ without a corresponding change in the [Ca2+]i response. 3. Histamine (3 microM) produced a phasic, followed by a tonic increase in both [Ca2+]i and force. Cilostazol (3 and 10 microM) significantly reduced both the phasic and tonic increases in [Ca2+]i and force induced by histamine, in a concentration-dependent manner. 4. Rp-adenosine-3':5'-cyclic monophosphorothioate (Rp-cAMPS, 0.1 mM), a PDE-resistant inhibitor of protein kinase A (and as such a cyclic AMP antagonist), did not modify the increases in [Ca2+]i and force induced by histamine alone, but it did significantly decrease the cilostazol-induced inhibition of the histamine-induced responses. 5. In Ca2+-free solution containing 2 mM EGTA, both histamine (3 microM) and caffeine (10 mM) transiently increased [Ca2+]i and force. Cilostazol (1-10 microM) (i) significantly reduced the increases in [Ca2+]i and force induced by histamine, and (ii) significantly reduced the increase in force but not the increase in [Ca2+]i induced by caffeine. 6. In ryanodine-treated strips, which had functionally lost the histamine-sensitive Ca2+ storage sites, histamine (3 microM) slowly increased [Ca2+]i and force. Cilostazol (3 and 10 microM) lowered the resting [Ca2+]i, but did not modify the histamine-induced increase in [Ca2+]i, suggesting that functional Ca2+ storage sites are required for the cilostazol-induced inhibition of histamine-induced Ca2+ mobilization. 7. The [Ca2+]i-force relationship was obtained in ryanodine-treated strips by applying ascending concentrations of Ca2+ (0.16-2.6 mM) in Ca2+-free solution containing 100 mM K+. Histamine (3 microM) shifted the [Ca2+]i-force relationship to the left and increased the maximum Ca2+-induced force. Under the same conditions, whether in the presence or absence of 3 microM histamine, cilostazol (3-10 microM) shifted the [Ca2+]i-force relationship to the right without producing a change in the maximum Ca2+-induced force. 8. It is concluded that, in smooth muscle of the peripheral part of the rabbit middle cerebral artery, cilostazol attenuates the histamine-induced contraction both by inhibiting histamine-induced Ca2+ mobilization and by reducing the myofilament Ca2+ sensitivity. It is suggested that the increase in the cellular concentration of cyclic AMP that will follow the inhibition of PDE III may play an important role in the cilostazol-induced inhibition of the histamine-contraction.

Ketamine-induced relaxation in intact and skinned smooth muscles of the rabbit ear artery.

1. The effects of ketamine, an intravenous anaesthetic, on the rabbit ear artery were investigated by measuring the tension in intact and saponin-treated skinned smooth-muscle fibres. 2. Ketamine dose-dependently inhibited contractions of intact smooth-muscle fibres induced by high K+ solution and by noradrenaline (NA) or histamine in Krebs solution. This drug similarly attenuated both phasic and tonic contractions induced by high K+ solution. 3. Ketamine also inhibited NA- or histamine-induced contractions in Ca2+-free solution containing 2mM EGTA, but it did not affect the caffeine-induced contraction in this solution. 4. Because the pCa-tension relationship of saponin-treated skinned smooth-muscle fibres was not affected, it can be proposed that ketamine does not have an effect on the contractile proteins. 5. In the presence of 5mM NaN3, 20 microM inositol 1,4,5-trisphosphate (InsP3) or 25mM caffeine produced a contraction in skinned smooth-muscle fibres after accumulation of Ca2+ by intracellular stores. Analysis of the InsP3- or caffeine-induced contractions indicates that ketamine does not have an effect on the Ca2+ accumulation into and Ca2+ release from the intracellular stores. 6. These results indicate that the relaxant effects produced by ketamine in the rabbit ear artery are not likely to be due to an intracellular action. The inhibitory effects of ketamine could be caused by a decrease of the Ca2+ influx through the plasma membrane or interference with the process of signal transduction between receptors on the plasma membrane and intracellular stores.

Nitroglycerine- and isoprenaline-induced vasodilatation: assessment from the actions of cyclic nucleotides.

To investigate the vasodilator actions of nitroglycerine and isoprenaline, the effects of these agents, dibutyryl cyclic AMP (db cyclic AMP) and 8-bromo cyclic GMP (8-Br cyclic GMP) on intact muscle tissue, and cyclic AMP and cyclic GMP on skinned muscle of the rabbit mesenteric artery were investigated. In porcine coronary artery, nitroglycerine (greater than 0.1 microM) increased the production of cyclic GMP with no change in the amount of cyclic AMP, while isoprenaline (greater than 0.1 microM) significantly increased the production of cyclic AMP with no change in the amount of cyclic GMP. In the rabbit mesenteric artery, nitroglycerine or isoprenaline inhibited the tonic component of the 39 mM [K]o-induced contraction to a greater extent than the phasic component. Nitroglycerine and 8-Br cyclic GMP showed a stronger inhibitory action on the K-induced contraction than did isoprenaline and db cyclic AMP. The sources of Ca utilized for the generation of contraction by noradrenaline and caffeine were estimated to be the same as those determined from the amplitudes of contractions evoked in Ca-free solution by various concentrations of noradrenaline or caffeine. In intact muscle tissues, the effects of nitroglycerine or 8-Br cyclic GMP on the amount of Ca stored in cells were estimated from the caffeine-induced contraction in Ca-free solution. Both agents inhibited the contractions due to a reduction in the amount of Ca in the cells. When the effects of isoprenaline or db cyclic AMP were observed, both agents inhibited the caffeine-induced contraction but the accumulation of Ca into cells was greater than the control. In saponin skinned muscles, the pCa-tension relationship in the presence of cyclic AMP and cyclic AMP-dependent protein kinase (cyclic AMP-PK) shifted to the right and to a lower level in comparison with the control. Applications of cyclic GMP with cyclic GMP-dependent protein kinase (cyclic GMP PK) also inhibited the contraction induced by low concentrations of Ca. In skinned muscles, cyclic AMP exhibited dual actions on Ca store sites, i.e. in the presence of high concentrations of Ca or prolonged superfusion of Ca, cyclic AMP reduced the amount of Ca due to activation of the Ca-induced Ca release mechanism by excess accumulation of Ca. On the other hand, cyclic GMP consistently inhibited the amplitude of the caffeine-induced contraction due to a reduction in the amount of Ca in the store sites. 8 These results indicate that nitroglycerine and isoprenaline increase the amount of cyclic GMP and cyclic AMP, respectively. The main effect of cyclic GMP is activation of Ca extrusion, thus reducing the amount of Ca stored in the cell, while the main effect of cyclic AMP is to increase the amount of Ca stored in the cell. Both cyclic AMP with cyclic AMP-PK and cyclic GMP with cyclic GMP-PK inhibit the phosphorylation of myosin. Consequently both cyclic nucleotides reduce the free Ca in the myoplasm and promote relaxation, but by different mechanisms.

Nisoldipine-induced relaxation in intact and skinned smooth muscles of rabbit coronary arteries.

In smooth muscles of the rabbit coronary artery, nisoldipine inhibited the phasic and tonic responses of the contraction induced by 128 mM K (the IC50 values were 4 X 10(-8) M and 1 X 10(-13) M, respectively). This agent also inhibited the tonic response of the acetylcholine (ACh) (10(-5) M)-induced contraction (the IC50 value was 3 X 10(-10) M), but only slightly inhibited the phasic response (in 10(-7) M, 0.86 times the control). Nisoldipine (less than 10(-7) M) had no effect on the K-induced depolarization of the membrane at any given concentration. This drug (5 X 10(-8) M) did inhibit the oscillatory potential changes and spike potential evoked on the ACh-induced slow depolarization. After depletion of stored Ca from the polarized muscles (5.9 mM K), muscle cells accumulated Ca by application of 2.6 mM Ca without generation of contraction, i.e. a subsequently applied 20 mM caffeine produced the contraction in Ca-free solution. Nisoldipine (less than 10(-7) M) had little effect on this accumulation of Ca. The rate of rise and time to reach the maximum amplitude of the 128 mM K- or ACh-induced contraction (in 2.6 mM Ca) depended on the amount of stored Ca in cells. Nisoldipine (10(-8) M) consistently inhibited the Ca-induced contraction evoked in depolarized muscles (128 mM K), regardless of the amount of stored Ca. However, this agent (10(-8) M) did not inhibit the Ca release from storage sites evoked by activation of the muscarinic receptor. After prolonged superfusion (over 120 min) with Na- and Ca-free solution (guanethidine and atropine were present), application of 2.6 mM Ca produced contraction which was inhibited by 10(-8) M nisoldipine, while the depolarization induced by application of these solutions was not inhibited by nisoldipine. In saponin-skinned muscles, nisoldipine had no effect on the contractile proteins, as estimated from the pCa-tension relationship, or on the Ca accumulation into the Ca release from the Ca storage sites, as estimated from the caffeine-induced contraction. It is concluded that nisoldipine possesses a selective inhibitory action on voltage-dependent Ca influx, when the Ca channel is activated by depolarization.

Possible mechanisms underlying the midazolam-induced relaxation of the noradrenaline-contraction in rabbit mesenteric resistance artery.

1. The mechanisms underlying the midazolam-induced relaxation of the noradrenaline (NA)-contraction were studied by measuring membrane potential, isometric force and intracellular concentration of Ca2+ ([Ca2+]i) in endothelium-denuded muscle strips from the rabbit mesenteric resistance artery. The actions of midazolam were compared with those of nicardipine, an L-type Ca2+-channel blocker. 2. Midazolam (30 and 100 microM) did not modify either the resting membrane potential or the membrane depolarization induced by 10 microM NA. 3. NA (10 microM) produced a phasic, followed by a tonic increase in both [Ca2+]i and force. Midazolam (10-100 microM) did not modify the resting [Ca2+]i, but attenuated the NA-induced phasic and tonic increases in [Ca2+]i and force, in a concentration-dependent manner. In contrast, nicardipine (0.3 microM) attenuated the NA-induced tonic, but not phasic, increases in [Ca2+]i and force. 4. In Ca2+-free solution containing 2 mM EGTA, NA (10 microM) transiently increased [Ca2+]i and force. Midazolam (10-100 microM), but not nicardipine (0.3 microM), attenuated this NA-induced increase in [Ca2+]i and force, in a concentration-dependent manner. However, midazolam (10 and 30 microM), had no effect on the increases in [Ca2+]i and force induced by 10 mM caffeine. 5. In ryanodine-treated strips, which have functionally lost the NA-sensitive Ca2+ storage sites, NA slowly increased [Ca2+]i and force. Nicardipine (0.3 microM) did not modify the resting [Ca2+]i but partly attenuated the NA-induced increases in [Ca2+]i and force. In the presence of nicardipine, midazolam (100 microM) lowered the resting [Ca2+]i and further attenuated the remaining NA-induced increases in [Ca2+]i and force. 6. The [Ca2+]i-force relationship was obtained in ryanodine-treated strips by the application of ascending concentrations of Ca2+ (0.16-2.6 mM) in Ca2+-free solution containing 100 mM K+. NA (10 microM) shifted the [Ca2+]i-force relationship to the left and enhanced the maximum Ca2+-induced force. Under these conditions, whether in the presence or absence of 10 microM NA, midazolam (10 and 30 microM) attenuated the increases in [Ca2+]i and force induced by Ca2+ without changing the [Ca2+]i-force relationship. 7. It was concluded that, in smooth muscle of the rabbit mesenteric resistance artery, midazolam inhibits the NA-induced contraction through its inhibitory action on NA-induced Ca2+ mobilization. Midazolam attenuates NA-induced Ca2+ influx via its inhibition of both nicardipine-sensitive and -insensitive pathways. Furthermore, midazolam attenuates the NA-induced release of Ca2+ from the storage sites. This effect contributes to the midazolam-induced inhibition of the NA-induced phasic contraction.

Actions of isosorbide dinitrate on smooth muscle cells of rabbit vascular tissues.

To investigate the mechanism of the anti-anginal actions of isosorbide dinitrate (ISDN), the effects of this agent on smooth muscle cells of intact and skinned preparations of the rabbit mesenteric artery and vein, and of the coronary artery were studied. ISDN (less than 10(-5) M) had no effect on the membrane potential or resistance of smooth muscle cells of the mesenteric artery and vein under resting conditions, nor when the membrane was depolarized by the presence of various concentrations of [K]o or noradrenaline (NA). The amplitude of spike evoked by outward current pulse after pretreatment with 10 mM tetraethylammonium (TEA) in the mesenteric artery was slightly inhibited by application of 10(-5) M ISDN. The K-induced and NA-induced contractions in the mesenteric artery were not affected by 10(-5) M ISDN, while those evoked in the mesenteric vein were inhibited in concentrations above 10(-6) M. The amplitude and facilitation of excitatory junction potentials evoked by perivascular nerve stimulation in the mesenteric artery were not affected by 10(-5) M ISDN. In skinned muscles, the free calcium concentration (pCa)-tension relationships observed in the mesenteric artery and vein were not affected by 10(-5) M ISDN. This agent had no effect on Ca accumulation into and Ca release from the stores in muscle cells of the mesenteric artery and vein, in skinned preparations. In the rabbit coronary artery, the membrane potential, resistance and spike evoked in the presence of 10 mM TEA were not affected by application of 10(-5) M ISDN. The contraction evoked by excess concentrations of [K]o was not affected. The contraction evoked by a low concentration of acetylcholine (3 X 10(-7) M) but by high concentrations (greater than 10(-6) M) was slightly inhibited by 10(-5) M ISDN. A tonic contraction induced in 39 mM [K]o was reduced by 10(-5) M nitroglycerine but not by 10(-5) M ISDN. Thus in rabbit vascular tissues, ISDN mainly acts on the venous system in vitro. The induced vasodilatation may lead to a reduction in the venous return and hence, reduce oxygen consumption in the cardiac muscles. This effect of ISDN may relate to the anti-anginal actions.

Effects of nifedipine derivatives on smooth muscle cells and neuromuscular transmission in the rabbit mesenteric artery.

The effects of nifedipine and its derivatives, nisoldipine, nimodipine and nitrendipine, on smooth muscle cells and neuromuscular transmission were investigated in the rabbit mesenteric artery. These agents in concentrations of up to 2 X 10(-7) M modified neither the membrane potential nor the membrane resistance, yet did inhibit the spike potential evoked by direct muscle stimulation in the presence of TTX or by perivascular nerve stimulation. The inhibitory action of nitrendipine was weaker than that of the other derivatives. These agents had no effect on the miniature excitatory junction potentials (m.e.j.ps) and e.j.ps evoked by the first stimuli and after completion of the facilitation in a train stimulation. Nifedipine and its derivatives had no effect on the K-induced depolarization but did have a marked effect on the K-induced contraction. Nisoldipine showed the highest inhibitory potency for the K-induced contraction [IC50 was 1.2 X 10(-9) M for the 128 mM (K)o-induced contraction]. Noradrenaline depolarized the membrane (greater than 5 X 10(-7 M) and produced contraction (greater than 3 X 10(-7) M). The contraction evoked by high concentrations of noradrenaline was inhibited by these agents to a greater extent than that evoked by low concentrations. The contraction evoked by perivascular nerve or direct muscle stimulation was partly inhibited by nifedipine and its derivatives. The contraction elicited by Na-free solution was inhibited by these agents but the noradrenaline- or caffeine-induced contraction in Ca-free solution was not. These results indicate that in smooth muscle cells of the rabbit mesenteric artery, nifedipine and its derivatives inhibit the voltage dependent Ca-influx which occurs during the spike potential and in response to K-, electrically- or noradrenaline-induced depolarization. These derivatives appear to have no effect on the adrenoceptor operated Ca increase in myoplasm which occurs in the absence of depolarization at low noradrenaline concentrations. The derivatives act as Ca antagonists with a quantitative difference in potency, i.e. the strongest action was observed with nisoldipine and the weakest with nitrendipine.

Regional differences in the actions of verapamil and isosorbide dinitrate on rabbit and dog vascular smooth muscle.

The effects of verapamil and isosorbide dinitrate (ISDN) alone or together on mechanical responses of the rabbit coronary artery and mesenteric vein, and the dog coronary artery have been investigated. Verapamil, in concentrations exceeding 10 nM consistently inhibited and at 10 microM, blocked the contraction evoked by excess concentrations of K in these tissues, but agonist-induced contraction was not modified by the presence or absence of Ca. In concentrations greater than 1 microM, verapamil depolarized the membrane by inhibiting the K-conductance of the membrane. ISDN had little effect on the rabbit coronary artery in concentrations below 10 microM. In contrast, in the rabbit mesenteric vein and dog coronary artery, ISDN in concentrations over 1 microM inhibited the contraction evoked by excess concentrations of K or by agonists. Species differences were apparent in the actions of ISDN on vascular tissues. When verapamil and ISDN were simultaneously applied to the rabbit mesenteric vein and dog coronary artery, the K-induced contraction was markedly inhibited by an amount exceeding that produced by the sum of the contractions evoked by the individual application of both agents. An enhanced vasodilating action induced by simultaneous applications of both agents indicates a possible clinical benefit for anti-anginal treatment.

New calculation of internal Ca(2+) recirculation fraction from alternans decay of postextrasystolic potentiation.

In our previous studies, we calculated the internal Ca(2+) recirculation fraction (RF) after obtaining the beat decay constant (tau(e)) of the monoexponential component in the postextrasystolic potentiation (PESP) of the alternans decay by curve fitting. However, this method sometimes suffers from the sensitive variation of tau(e) with small noises in the measured contractilities of the 5th and 6th postextrasystolic (PES) beats in the tail of the exponential component. We now succeeded in preventing this problem by a new method to calculate RF without obtaining tau(e). The equation for the calculation in the new method expresses an alternans decay of PESP as a recurrence formula of PESP. It can calculate RF directly from the contractilities of the 1st through the 4th PES beats without any fitting procedure. To evaluate the reliability of the new method, we calculated RF from the alternans decay of PESP of the left ventricle (LV) of the canine excised cross-circulated heart preparation by both the original fitting and the new method. Although there was no significant difference in the mean value of the obtained RF between these two methods, the variance of RF was smaller with the new method than with the original method. Thus the new method proved useful and more reliable than the original fitting method.

Arterial and left ventricular pressures illude transient alternans of contractility during postextrasystolic potentiation.

We have previously found that the postextrasystolic (PES) potentiation (PESP) of the left ventricular (LV) contractility (Emax) decays typically in transient alternans even in the normally ejecting canine heart. This contradicted the general expectation that arterial pressure (AP) and LV pressure (LVP) usually decay exponentially during PESP. We hypothesized this contradiction to be due to the different cardiodynamic behaviors of AP and LVP from LV Emax during PESP. We tested this hypothesis by measuring AP, LVP, LV volume, Emax, effective arterial elastance (Ea) as an index of afterload, and pulse pressure (PP) during PESP in eight anesthetized open-chest dogs by using the conductance catheter system. We changed Ea by changing the total peripheral resistance (TPR) with methoxamine hydrochloride (iv) and repeated the measurements. Although the Emax alternans patterns during PESP were comparable between the normal and high afterloads, LVP and PP were slightly potentiated and alternated under the normal afterload, whereas LVP and PP were obviously potentiated and alternated under the high afterload. We also simulated the effects of Ea/Emax on the transient alternans of AP and LVP on a computer. Despite the same alternans pattern of Emax, a higher Ea/Emax, which is typical in heart failure, caused a larger PP alternans, whereas a lower Ea/Emax, which is typical in normal hearts, almost eliminated it. These results suggest that a transient alternans of LV contractility during PESP could be overlooked when AP and LVP are monitored in in situ normal hearts.

The stabilization of vascular smooth muscle by procaine.

Procaine acts on the cell membrane as a depolarizing agent. It inhibits K-conductance; as a consequence, the membrane is depolarized and the spike potential is readily generated by outward current pulses. This inhibition of the K-conductance of membrane induced by procaine is discussed in relation to the K channel classified by the patch clamp procedure. The authors' observations indicate that procaine acts as a stimulant rather than as a stabilizer of the membrane. Furthermore, procaine inhibits the release of Ca from the store site, with no effect on the contractile protein. This local anaesthetic agent acts not only on the surface membrane but also on the internal membrane, the sarcoplasmic reticulum. Procaine reduces mechanical activity and stabilization of vascular smooth muscles occurs.

Decreased perfusion of the bilateral thalami in patients with chronic pain detected by Tc-99m-ECD SPECT with statistical parametric mapping.

The purpose of this study was to examine whether the Tc-99m-ECD SPECT can detect any difference between the brain perfusion in patients with chronic pain and normal controls by means of the Statistical Parametric Mapping (SPM96). The subjects were twelve patients with chronic pain (CP group) and twelve normal controls (NC group). After informed consent was obtained, 720 MBq of Tc-99m-ECD was intravenously injected as a bolus. The SPECT data were acquired once for 20 mins from 5 mins after i.v. injection of Tc-99m-ECD, with a triple-head rotating gamma camera. The SPECT data were transformed into a standard stereotactic space, and group comparisons between CP and NC groups were performed on a voxel-by-voxel basis. The subset of voxels exceeding a threshold of p < 0.001 in omnibus comparisons and remaining significant after correction for multiple comparison (p < 0.05) was displayed as a volume image rendered in three orthogonal projections. There was a significant decrease in perfusion in the bilateral thalami in the CP group, suggesting that perfusion in the thalamus generally decreases in patients with chronic pain. Tc-99m-ECD SPECT with SPM96 may be useful for studies of the mechanisms of chronic pain.

[Effects of dopamine and dobutamine on vascular smooth muscles].

The effects of dopamine and dobutamine on mechanical responses of the mesenteric artery and ear artery of the rabbit were investigated. Dopamine elicited no contraction in the mesenteric artery, but inhibited contractions evoked by excess concentrations of K+ or norepinephrine. In contrast, in the ear artery, dopamine induced contractions in concentrations exceeding 0.7 microM. Dobutamine did not induce contractions either in the mesenteric artery or ear artery, but inhibited contractions evoked by excess concentrations of K+ or norepinephrine in both tissues. Moreover, dobutamine in concentrations over 10 nM inhibited contractions induced by dopamine in the ear artery. These results indicated that regional differences were apparent in the effects of dopamine on vascular tissues and that dobutamine possessed vasodilating effects. The inhibitory effects of dobutamine on contractions induced by dopamine in the rabbit ear artery suggested a possible clinical benefit of dobutamine for maintaining peripheral circulation during combined use of dopamine and dobutamine.

[Anesthetic management of cesarean section in a patient with dilated cardiomyopathy].

We report the anesthetic management of Cesarean section in a pregnant (31 weeks) woman with dilated cardiomyopathy. She had dyspnea and chest pain which were signs of congestive heart failure. The left ventricular ejection fraction was 38%. Anesthesia was induced and maintained with fentanyl, midazolam and vecuronium. There was no significant cardiovascular changes in the mother during the operation. The baby was apneic and showed no movement at birth, but he was immediately intubated and his condition became almost normal on the following day. In the anesthesiological management of Cesarean sections with cardiac disease, general anesthesia with fentanyl can be used to minimize cardiovascular changes in the mother as long as the baby is immediately resuscitated after delivery.

[Anesthetic management of a patient with congenital cystic adenomatoid malformation].

Congenital cystic adenomatoid malformation (CCAM) is a rare disease that is diagnosed by severe respiratory dysfunction from birth. A 5-day-old-boy with CCAM underwent removal of a large cyst which was present at lower lobe of right lung. Anesthesia was induced slowly and maintained with oxygen and sevoflurane. Severe airway obstruction occurred transiently by the secretion from the lung cyst. Thereafter, the surgery was completed safely and his postoperative course was uneventful. Perioperative anesthetic management of the patient with CCAM is also discussed.