Anesthetic management for cesarean delivery in a parturient with exacerbated hemophagocytic syndrome.

Hemophagocytic syndrome is an uncommon disease characterized by cytokine dysfunction and uncontrolled hemophagocytosis. It arises rarely during pregnancy, in which case maternal and fetal mortality are relatively high. It has some similarities with HELLP syndrome. Poor maternal condition increases the risk of preterm labor and the possibility of emergency cesarean delivery in non-optimal conditions, presenting a great challenge to the anesthesiologists. We report a 28-year-old primigravida with the onset of hemophagocytic syndrome and cyopenia at 23 weeks of gestation. A further exacerbation at 28 weeks of gestation brought on preterm labor. General anesthesia was provided successfully for cesarean delivery. The patient recovered completely after this episode. We suggest that early diagnosis, multi-disciplinary intervention, pre-operative correction of the hematological abnormalities, general anesthesia and close postoperative monitoring are necessary.

Anesthetic management of a pregnant living related liver donor.

Pregnancy is often considered a contraindication to living related liver donation. There are serious medical and ethical considerations if a pregnant woman insists on undergoing partial hepatectomy to save her sick child. Herein we report a case of living related liver donation from a pregnant woman at 18 weeks of gestation to her 1-year-old child with decompensated cirrhosis due to biliary atresia. The left lateral segment of the liver was harvested for donation. Meticulous surgical technique and anesthetic management were mandatory in assuring a successful outcome. While this isolated case demonstrated that living related liver donation can be performed successfully with a pregnant donor, it should be undertaken only when there is absolutely no other donor and the recipient is in urgent need.

Inadvertent knotting of a thoracic epidural catheter.

We report a case of corrosive injury of upper gastrointestinal and respiratory tracts scheduled for feeding jejunostomy under thoracic epidural anesthesia. An epidural catheter was inserted at the T8-T9 intervertebral space and threaded 7 cm beyond the tip of the Tuohy needle in a rostral direction. Resistance was noticed during attempts to inject the local anesthetic. As resistance could not be relieved by changing the position of the patient, kinking of the epidural catheter was suspected. Following informing the patient of the associated risks, the catheter was retrieved successfully by gentle and steady pulling. A tight double-knot of catheter was found. No neurological sequelae to the procedure were noticed.

Bilateral pulmonary edema after endoscopic sympathectomy in a patient with glucose-6-phosphate dehydrogenase deficiency.

Transaxillary endoscopic sympathectomy of thoracic ganglia (T2-T3) has recently gained wider acceptance as the treatment of choice for palmar hyperhidrosis. It requires one-lung ventilation to facilitate the surgery. One-lung ventilation, however, is not without complications, among which acute pulmonary edema has been reported. In this case report, we present a patient with palmar hyperhidrosis complicated by glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, who received bilateral endoscopic sympathectomy under alternate one-lung anesthesia, and developed acute pulmonary edema immediately after recruitment of the successive collapsed lung. The effects of hypoxemia, G-6-PD deficiency and sympathectomy might all add to the development of acute pulmonary edema secondary to reexpansion of each individual lung after alternate one-lung ventilation. The possibilities of the inferred causes are herein discussed.

Bullous eruptions caused by extravasation of mannitol--a case report.

Extravasation is one of the common complications seen with intravenous infusion. We bring forward a case of subcutaneous mannitol extravasation, which caused swelling and multiple cutaneous bullous eruptions in the hand and forearm during craniotomy. Treatment consisting of elevation of the affected extremity and application of silver sulfadiazine ointment twice daily to the injured area was successful. The possible mechanisms relevant to extravasation and its tissue damage are reviewed and discussed. Selecting proper intravenous infusion site, using pliable catheters and frequent inspection are important steps for prevention of extravasation.

Detection of iatrogenic cardiac tamponade by transesophageal echocardiography during vena cava filter procedure.

PURPOSE: To present a patient who developed cardiac tamponade during insertion of an inferior vena cava (IVC) filter. Intraoperative transesophageal echocardiography (TEE) was used as a means to diagnose the cardiac tamponade and to facilitate guiding of pericardiocentesis. CLINICAL FEATURES: A 45-yr-old man with protein S deficiency complicated by repeated attacks of deep vein thrombosis and pulmonary thromboembolism was scheduled for insertion of an IVC filter. He had history of chronic renal insufficiency, heart failure, and cerebral infarction with mild left hemiparesis. Current medication included diltiazem (30 mg, I tab tid ), prednisolone (5 mg, 2 tabs qd ), and warfarin (2.5 mg daily). Preoperative transthoracic echocardiography demonstrated bilateral pleural effusions, moderate mitral regurgitation and tricuspid regurgitation, left atrial appendage thrombus and severe generalized hypokinesia of left ventricle. Nuclear medicine examination by (99)Tc showed ejection fractions of left ventricle and right ventricle as 20% and 22%, respectively. Under the impression of protein S deficiency with multiple attacks of thromboembolism and failure of anticoagulant therapy, he was arranged for the procedure of vena caval filter insertion. Unfortunately, iatrogenic cardiac tamponade occurred during the course of the procedure with rapid hemodynamic deterioration. Because of the expedient of routine monitoring of cardiac condition with TEE, a prompt diagnosis was made. We successfully improved the patient's hemodynamic status after transthoracic echo-guided pericardiocentesis. CONCLUSION: Intraoperative TEE is recommended to be used routinely in patients undergoing vena cava filter procedures. The availability of echocardiographic monitoring in the operation room allows the confirmation of the diagnosis and facilitation pericardiocentesis.

Shortening of cardiac action potentials in endotoxic shock in guinea pigs is caused by an increase in nitric oxide activity and activation of the adenosine triphosphate-sensitive potassium channel.

OBJECTIVE: To investigate the roles of nitric oxide and adenosine triphosphate (ATP)-sensitive potassium channels (KATP) in the shortening of cardiac action potential in endotoxic shock. DESIGN: Prospective animal study with concurrent controls. SETTING: University animal research laboratory. SUBJECTS: Adult Hartley guinea pigs, weighing 300-400 g. INTERVENTIONS: Guinea pigs were anesthetized and mechanically ventilated for 6 hrs. Lipopolysaccharide (LPS) or saline (sham group) were given intravenously. Drug effects were examined at the end of 6 hrs. MEASUREMENTS AND MAIN RESULTS: Plasma nitrate concentration was measured hourly, while guanosine 3',5'-cyclic monophosphate (cGMP) content and action potential duration at 90% of repolarization (APD90) of papillary muscle were examined every 2 hrs in the 6-hr endotoxemia in both the sham and the LPS-treated groups. The basal levels of these three variables showed no difference in the two groups. In the sham group, these variables did not change significantly (n = 14 for plasma nitrate determination; n = 5 for cGMP content measurement; n = 5-14 for APD90 measurement; all p > .05). But in the LPS-treated group, both plasma nitrate concentration and cGMP content of papillary muscle showed time-dependent increases and they were significantly higher than those in the sham group (at the 6th hr, plasma nitrate: 42.6 +/- 7.7 vs. 21.8 +/- 3.1 micromol/L, both n = 14, p < .01; cGMP: 1.52 +/- 0.15 vs. 0.73 +/- 0.08 pmol/mg protein, both n = 5, p < .01). In contrast, APD90 revealed a time-dependent decrease compared with that in the sham group (at the 6th hr, 137.1 +/- 52 vs. 188.2 +/- 4.8 msecs, both n = 14, p < .001). In the following 60-min in vitro recording of action potentials after the end of 6-hr endotoxemia, the shortened APD90 in the LPS-treated group did not recover and remained shorter compared with that in the sham group, in which the APD90 showed no significant changes (at the 60th min, 165.1 +/- 5.7 vs. 200.2 +/- 3.8 msecs, each n = 14, p < .01). However, in the presence of glibenclamide, a specific KATP blocker (100 micromol/L; n = 10), the APD90 could be reversed almost completely to the same value as that in the sham group (n = 14) (196.6 +/- 3.5 vs. 200.2 +/- 3.8 msecs; p > .05), despite glibenclamide having no effect on the APD90 in the sham group. In the LPS-treated group, NG-nitro-L-arginine methyl ester (1 mmol/L; n = 4), methylene blue (10 micromol/L; n = 5), and aminoguanidine (100 micromol/L; n = 4) significantly prolonged the shortened APD90 (192.5 +/- 3.1, 195.0 +/- 3.3, and 176.5 +/- 3.3 msecs, respectively; p < .01, p < .01, and p < .05, respectively, compared with that without these agents, 165.1 +/- 5.7 msecs, n = 14). These agents had negligible effects on the APD90 in the sham group (all p > .05). Furthermore, 8-bromoguanosine-3',5'-cyclic monophosphate (500 micromol/L; n = 5) decreased APD in intact papillary muscle (mean reduction of APD90, 13.5 +/- 3.5%, n = 5; p < .05), an effect abolished by pretreatment with glibenclamide (100 micromol/L; n = 5) that did not have an effect by itself. CONCLUSIONS: In this experimental model, we provide reasonably convincing evidence to suggest that in endotoxic shock, an increase in nitric oxide activity may activate KATP, which plays a major role in the shortening of APD, presumably through a cGMP-dependent pathway.

Thoracic epidural analgesia with morphine does not prevent postthoracotomy pain syndrome: a survey of 159 patients.

BACKGROUND: This retrospective study sought to determine the incidence of postthoracotomy pain syndrome (PTPS), and whether epidural morphine for the postoperative analgesia could prevent the development of PTPS. METHODS: We reviewed the charts of 372 patients who had undergone thoracotomy. The majority underwent general anesthesia (GA) combined with thoracic epidural analgesia (TEA). Of the 372 patients, only 159 (42%) were available for interview. Patients were divided into two groups based on the duration of pain, i.e., pain group (pain > 3 months, n = 65) and pain-free group (pain < 3 months, n = 94). RESULTS: Both groups were comparable regarding sex, age, weight, height, smoking, alcohol ingestion, education, marital status, duration of surgery, and the number of patients either receiving GA plus TEA or GA alone. About 41% of the patients experienced PTPS that persisted for 21 +/- 12 mon (follow-up: 28 +/- 12 mon). Most pain was mild or moderate and was usually described as being only a discomfort. Only 6.2% suffered severe pain with shooting, aching, burning or numbness. Patients with PTPS suffered more depression and insomnia. The incidence of PTPS was not different in patients who received GA alone or GA plus TEA (39% vs. 42%). CONCLUSIONS: Epidural morphine for postoperative analgesia that continued for 3 days appeared to have no effect in the prevention of PTPS.

Reduction in lipopolysaccharide-induced thrombocytopenia by triflavin in a rat model of septicemia.

BACKGROUND: Thrombocytopenia frequently occurs early in the course of Gram-negative bacterial infections. Triflavin, an Arg-Gly-Asp-containing disintegrin, has been suggested to interfere with the interaction of fibrinogen with the glycoprotein IIb/IIIa complex. The present study was undertaken to determine whether triflavin could prevent thrombocytopenia in lipopolysaccharide (LPS)-treated rats. METHODS AND RESULTS: In this study, 51Cr-labeled platelets were used to assess blood and tissue platelet accumulation after LPS challenge. The administration of LPS (4 mg/kg IV bolus) for 4 hours induced a reduction in radiolabeled platelets in blood and an obvious accumulation of platelets in liver. Triflavin (500 microg/kg) but not GRGDS (20 mg/kg) significantly prevented the alteration of radiolabeled platelet distribution in blood and liver when induced by LPS. Furthermore, triflavin but not GRGDS markedly suppressed the elevation in plasma thromboxane B2 concentration within the 4-hour period of LPS administration. In LPS-treated rats, the 5-hydroxytryptamine level was lower in the blood and higher in the liver compared with levels in normal saline-treated rats. Pretreatment with triflavin (500 microg/kg) significantly reversed the 5-hydroxytryptamine concentration in blood and liver of LPS-treated rats. In histological examinations and platelet adhesion assay, triflavin markedly inhibited the adhesion of platelets to subendothelial matrixes in vivo and in vitro. CONCLUSIONS: The results indicate that triflavin effectively prevents thrombocytopenia, possibly through the following 2 mechanisms: (1) Triflavin markedly inhibits platelet aggregation, resulting in decreased thromboxane A2 formation. (2) It inhibits the adhesion of platelets to subendothelial matrixes, thereby leading to a reversal in the distribution of platelets in blood and liver in LPS-treated rats.

Inhibitory mechanisms of naloxone on human platelets.

1. In the present study, naloxone was tested for its antiplatelet activities in human platelet-rich plasma (PRP). In human PRP, naloxone (0.1-0.5 mmol/L) inhibited aggregation stimulated by a variety of agonists (i.e. collagen, adenosine diphosphate (ADP), U46619 and adrenaline). 2. Naloxone (0.1-0.5 mmol/L) did not significantly affect cyclic adenosine monophosphate and cGMP levels in human washed platelets, whereas naloxone (0.5 mmol/L) significantly inhibited thromboxane B2 formation stimulated by collagen (5 micrograms/mL) in human washed platelets. 3. Naloxone (0.5 mmol/L) significantly inhibited [3H]-inositol monophosphate formation of [3H]-myoinositol-loaded platelets stimulated by collagen and U46619. Moreover, naloxone did not influence the binding of 125I-triflavin to platelet membranes. Triflavin is an Arg-Gly-Asp-containing specific fibrinogen receptor antagonist. 4. Addition of naloxone (0.5 mmol/L) to platelet preparations tagged with diphenylhexatriene (DPH) resulted in a considerable decrease in relative fluorescence intensity. 5. It is suggested that the anti-platelet effects of naloxone may be caused, at least partly, by the induction of conformational changes in the platelet membrane initially, followed by the inhibition of thromboxane A2 formation and phosphoinositide breakdown of platelets stimulated by agonists.

Inhibition of angiogenesis in vitro and in vivo: comparison of the relative activities of triflavin, an Arg-Gly-Asp-containing peptide and anti-alpha(v)beta3 integrin monoclonal antibody.

Disintegrin which contains the amino acid sequence Arg-Gly-Asp (RGD), has been implicated as a recognition site in interactions between extracellular matrix (ECM) and cell membrane receptors. Triflavin, a 7.5 kDa cysteine-rich polypeptide purified from Trimeresurus flavoviridis snake venom, belongs to a family of disintegrins. Integrin alpha(v)beta3 has recently been identified as a marker of angiogenic blood vessels and therefore anti-alpha(v)beta3 mAb may significantly inhibit angiogenesis. Therefore, this study was designed to compare the relative activity of triflavin and anti-alpha(v)beta3 mAb in human umbilical vein endothelial cell (HUVEC) adhesion and migration in vitro, and on angiogenesis induced by TNF(alpha) in chicken chorioallantoic membrane (CAM). In this study, it was shown that triflavin (0.1 to 0.4 microM) dose-dependently inhibited the adhesion of HUVECs to ECMs (i.e., vitronectin, fibronectin, laminin and collagen type IV). At a concentration of 10 microM, anti-alpha(v)beta3 mAb almost completely inhibited the adhesion of cells to vitronectin, had a moderate inhibitory effect on fibronectin and laminin, but only a slight inhibitory effect on collagen type IV. On the other hand, vitronectin and fibronectin promote a significantly greater extent of cell adhesion and migration than laminin or collagen type IV over a wide range of concentrations (5 to 15 microg/ml). In cell migration studies, triflavin (0.4 microM) inhibited more markedly vitronectin- and fibronectin-mediated migration than that mediated by laminin- and collagen type IV. Comparison of the relative effectiveness of triflavin with anti-alpha(v)beta3 mAb, showed that triflavin was at least twenty to thirty times more potent than anti-alpha(v)beta3 mAb at inhibiting cell adhesion and migration. Furthermore, we used TNF(alpha) as an inducer of angiogenesis in the CAM assay. Close examination of the effects of triflavin and anti-alpha(v)beta3 mAb on TNF(alpha)-induced angiogenesis revealed the presence of discontinuous and disrupted blood vessels. However, anti-alpha(v)beta3 mAb showed a significant effect only at a higher concentration (10 microM). These results suggest that the inhibition of angiogenesis may have been due to interference with the adhesion and migration of endothelial cells to ECMs. The results also indicate that triflavin has a more powerful inhibitory effect than anti-alpha(v)beta3 mAb on angiogenesis, suggesting that triflavin could theoretically be used as a reasonable therapeutic adjuvant for therapy or prevention of angiogenesis-induced diseases.

Propofol inhibits medullary pressor mechanisms in cats.

PURPOSE: Propofol may cause hypotension and the mechanism is complex. The present study was designed to determine the direct actions of propofol in medulla of cats. METHODS: Mean systematic arterial pressure (MSAP), heart rate (HR) and cardiac contractility (dp/dt) were compared before and after administration of propofol the femoral vein (2, 3, or 4 mg.kg-1), vertebral artery (1 mg.kg-1) or the lateral cerebral ventricle (0.5 mg.kg-1) in eight anaesthetized cats. To study the direct effect of propofol in medulla, pressor areas of the dorsomedial medulla (DM) and rostral ventrolateral medulla (RVLM), or the depressor area of the caudal ventrolateral medulla (CVLM) were first identified with electrical stimuli and then confirmed by pressure microinjection of glutamate (Glu, 0.25M, 30 nl) via a multibarrel-micropipette in 28 cats. One hour later, propofol (0.001%, 50 nl) was microinjected at the same site. Electrical stimulation and Glu were applied again to compare changes of SAP, HR and dp/dt with that of the control. RESULTS: Propofol dose-dependently decreased SAP, HR and cardiac contractility. The percent increase of MSAP induced by Glu were reduced by propofol in DM (59 +/- 3% vs 13 +/- 2%, n = 11, P < 0.01) or in RVLM (56 +/- 4% vs 18 +/- 2%, n = 9, P < 0.01). In CVLM, propofol slightly but not significantly increased depressor responses elicited by Glu (-27 +/- 2% vs -33 +/- 3%, n = 5, P > 0.05). CONCLUSION: Our results show that propofol principally inhibits the vasomotor mechanism in the dorsomedial and ventrolateral medulla to effect its hypotensive actions.

Genistein directly induces cardiac CFTR chloride current by a tyrosine kinase-independent and protein kinase A-independent pathway in guinea pig ventricular myocytes.

With one-suction electrode voltage-clamp technique, we demonstrated that genistein, a tyrosine kinase (TK) inhibitor, could directly activate cystic fibrosis transmembrane regulator (CFTR) chloride current in guinea pig ventricular myocytes. The activation showed concentration-dependent effect with the estimated IC50 of 39.7 microM. Tyrphostin 51, another TK inhibitor, had no effect, suggesting that genistein's effect might be unrelated to TK inhibition. After the chloride current had been activated by the maximally elevated intracellular cAMP content by saturating concentration of isoproterenol, forskolin and IBMX, genistein could further enhance the current. Pre-treatment with saturating concentration of a specific protein kinase A (PKA) inhibitor, H-89, or other protein kinase inhibitors H-8 and H-9 in the perfusate or intracellularly could not prevent the activation of the current by genistein, suggesting a PKA-independent activity. Furthermore, saturating concentration of calyculin A, a specific inhibitor of phosphotase 1 and 2A, in the perfusate or intracellularly could not block genistein's action. It is possible that genistein opens the channels directly or inhibits the dephosphorylation process of CFTR, which is not sensitive calyculin A.

Genistein directly inhibits L-type calcium currents but potentiates cAMP-dependent chloride currents in cardiomyocytes.

We have examined the possible modulatory effects of genistein, a specific tyrosine kinase inhibitor, on cardiac L-type calcium currents and cAMP-dependent chloride currents in guinea pig ventricular myocytes. With one-suction electrode voltage-clamp technique, genistein dose-dependently and reversibly inhibited L-type calcium currents in cardiomyocytes (Km = 17.5 microM). Neither threshold potential nor the peak potential of current-voltage relationship was affected. Interestingly, daidzein (an inactive analogue of genistein) also depressed L-type calcium currents. When L-type calcium currents were directly activated by Bay K 8644, genistein was able to exert an inhibitory action. In contrast, genistein potentiated cardiac cAMP-dependent chloride currents activated by either isoproterenol or 3-isobutyl-1-methylxanthine. These results suggest that genistein may directly inhibit L-type calcium currents but may potentiate cAMP-dependent chloride currents in the heart.

Propofol inhibits cardiac L-type calcium current in guinea pig ventricular myocytes.

BACKGROUND: Propofol may exert negative inotropic and chronotropic actions in the heart. Single-channel studies show that propofol affects the kinetics of opening and closing of cardiac L-type calcium channels (ICa(L)) without altering channel conductance. The aim of this study was to investigate the mechanisms of depressant effects of propofol on cardiac whole-cell ICa(L). METHODS: Single ventricular myocytes were freshly dissciated from guinea pig hearts using enzymatic isolation. One-suction electrode voltage-clamp technique (whole-cell mode) was used. LCa(L) was separated from other contaminated ionic currents. Propofol was applied in the commercial 10% Intralipid emulsion formula (Zeneca, UK). RESULTS: In isolated cardiomyocytes, propofol significantly inhibited whole-cell ICa(L) in a concentration-dependent manner (K D = 52.0 microM; Hill coefficient = 1.3). The solvent (Intralipid) did not affect ICa(L). Propofol decreased ICa(L) at all potentials tested along the voltage axis and reduced the slope conductance. The threshold potential for activation and the peak potential of the current-voltage relationship were not changed by propofol. The steady-state activation curves overlapped in the absence and the presence of 56 microM propofol. In contrast, the steady-state inactivation curve was shifted in the hyperpolarizing direction. The time course of the recovery from inactivation was delayed by 56 microM propofol. The blocking action on ICa(L) of propofol shows marked resting block and use-dependent block. Propofol caused more pronounced inhibition at a higher stimulation frequency. The effect of propofol on the inactivation process was even more clear on ICa(L). CONCLUSIONS: The authors conclude tha propofol, at supratherapeutic concentrations, inhibits cardiac ICa(L). This inhibition is mainly due to a shift of inactivation curve and a reduction in slope conductance.

Effects of NMDA receptor antagonists on inhibition of morphine tolerance in rats: binding at mu-opioid receptors.

Past studies have shown antagonists of excitatory amino acid receptors, both N-methyl-D-aspartate (NMDA) and non-NMDA, to produce an antinociceptive effect in vitro and in vivo. Additionally, NMDA receptor antagonists have been demonstrated to prevent morphine tolerance. We had found that one NMDA receptor antagonist, ketamine, potentiates morphine's analgesic effect in post-operative patients. Our latest experiment was performed to examine the modulatory effect of competitive and non-competitive NMDA receptor antagonists on morphine antinociception and tolerance. A PE10 catheter was intrathecally (i.t.) implanted in male Sprague-Dawley rats for drug administration. The antinociceptive effect of morphine, D-(-)-2-amino-5-phosphonovaleric acid (D-AP5) and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine maleate (MK-801) was measured using the hot-water tail immersion test. Neither competitive nor non-competitive NMDA receptor antagonists had an antinociceptive effect by themselves, but they did potentiate the antinociceptive effect of morphine. Both D-AP5 (AD50 = 0.18 micrograms) and MK-801 (AD50 = 0.57 micrograms) shifted the antinociceptive dose-response curve of morphine (AD50 = 4.2 micrograms) to the left. Both D-AP5 (4 micrograms/h) and MK-801 (10 micrograms/h) when co-administered with i.t. morphine infusions (10 micrograms/h) also inhibited the development of tolerance. In [3H][D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin ([3H]DAMGO) binding assays, MK-801 (Bmax = 32.90 +/- 3.33 fmol/mg) treatment prevented the down-regulation of mu-opioid receptor high-affinity sites induced by continuous morphine infusions alone (Bmax = 13.97 +/- 1.47 fmol/mg). D-AP5 (Bmax = 20.78 +/- 3.36 fmol/mg) did not prevent the reduction of mu-opioid receptor high-affinity sites. However, high-affinity sites in rats treated with D-AP5 and morphine displayed a higher affinity (KD = 0.45 +/- 0.09 nM) than those of control animals (KD = 0.95 +/- 0.08 nM). Results of this study indicate that competitive as well as non-competitive NMDA receptor antagonists enhance morphine's antinociceptive effect, and prevent the development of morphine tolerance. Thus, in our opinion, there opens a new frontier in clinical pain management, especially for those patients who require long-term opioid treatment for pain relief.

Electropharmacological actions of propofol on calcium current in guinea-pig ventricular myocytes.

Propofol, a widely-used intravenous anesthetic, causes bradycardia, depression in contractility and hypotension. The cellular mechanisms responsible for these cardiac toxicity remain unclear. In this study, we examined the cellular electropharmacological actions of propofol on calcium current in guinea-pig heart. Single ventricular myocytes were freshly isolated from guinea-pig using modified enzymatic method. Whole-cell voltage-clamp technique was applied with one suction pipette. Transmembrane L-type calcium current (ICa(L)) was separated from other ionic currents by voltage-control, ionic channel blockers and ion substitution methods. Our results show that propofol decreased ICa(L) in a concentration-dependent manner (KD = 54.2 microM). Slope conductance of current-voltage relation was decreased by 56 microM propofol. Propofol did not affect the steady-state activation curve, but shifted the inactivation curve to hyperpolarizing direction. Recovery from inactivation was slowed down by propofol. Marked resting block and use-dependent block were noted. In conclusion, our results indicate that propofol inhibits cardiac L-type calcium current mainly by shifting inactivation curve and retarding the recovery from inactivation.

Depressant Effects of Prostacyclin in Human Atrial Fibers and Cardiomyocytes.

The aim of this study was to characterize the electropharmacological effects of prostacyclin (PGI(2)) in human atrial fibers and cardiomyocytes. Atrial tissues obtained from the hearts of 28 patients undergoing corrective cardiac surgery were used. Transmembrane action potentials were recorded using a conventional microelectrode technique, and twitch force by a transducer. Effects of PGI(2) (1 nM-10 &mgr;M) on action potential characteristics and contraction of atrial fibers were evaluated in normal [K](o) (4 mM) and high [K](o) (27 mM) in the absence and presence of cardiotonic agents. In addition, atrial and ventricular myocytes were isolated enzymatically from atrial tissues and hearts of 4 patients undergoing cardiac transplant. The effects of PGI(2) on Na- and Ca-dependent inward currents (I(Na) and I(Ca)) of cardiomyocytes were tested. In 9 human atrial fibers showing fast-response action potentials (mean dV/dt(max) = 101 +/- 15 Vs(-1)) in 4 mM [K](o), PGI(2) did not influence dV/dt(max) of phase 0 depolarization even at 1 &mgr;M. However, at a concentration as low as 10 nM, PGI(2) depressed spontaneous rhythms or slow-response action potentials in high-K-depolarized fibers. PGI(2) also depressed delayed afterdepolarizations and aftercontractions induced by cardiotonic agents. In isolated cardiomyocytes, PGI(2) reduced I(Ca) but not I(Na). The present findings show that, in human atrial fibers and cardiomyocytes, PGI(2) induces greater depressant effects on the slow-response action potential, I(Ca) and triggered activity than on the fast-response action potential. It is suggested that PGI(2) may act through a selective reduction of transmembrane Ca influx. Copyright 1994 S. Karger AG, Basel

Na(+)-activated K+ current in cardiac cells: rectification, open probability, block and role in digitalis toxicity.

The Na(+)-activated K+ current was studied in inside-out patches and in whole cells isolated from the guinea-pig cardiac ventricle. The single channel conductance showed inward rectification for K+i less than K+e, but outward rectification for K+i greater than K+e. The open probability was dependent on Na+i and Na+,K(+)-pump activity. In the presence of pump blockade the channel remained active at low Na+i. Similar results were obtained in whole cells. These results suggest the existence of Na+ gradients depending on Na+,K(+)-pump activity and passive inward leak of Na+. The channel and whole cell current were blocked by R56865. The drug did not change the single channel conductance but markedly reduced open probability by shortening burst duration. The current may play an important role in action potential shortening during pump blockade.