[Side Effects of Acetaminophen and their Management].

Acetaminophen, a para-aminohenol derivative, was first clinically used in 1893. In 1980 s, the relevance of aspirin for Reye's syndrome became a problem, then acetaminophen came into use for various kinds of cases such as children, pregnant women and the elderly for pain management or alleviation of fever. However, because acetaminophen has a very weak COX-1 and COX-2 inhibitory effect it has weak or no anti-inflam- matory effect Therefore physicians do not wish to use acetaminophen for management of pain in which in- flammation is thought to be the main mechanism. But recently acetaminophen has become reevaluated as an indication for patients with chronic pain. In 2011, the maximum daily dose of acetaminophen in Japan was increased from 1,500 ng - day-- to 4,000 mg - day-1 (international dosage). As acetaminophen has few side effects of gastrointestinal and renal systems, its use is recommended for the control of long term pain man- agement The side effects of acetaminophen and their management are discussed.

Influence of oral supplementation with sesamin on longevity of Caenorhabditis elegans and the host defense.

PURPOSE: Nutritional control has been proposed as a potential therapy for slowing the senescence of immune function and decreasing mortality. This study investigated whether sesamin could modify host defense systems and extend the lifespan of the nematode Caenorhabditis elegans. METHODS: Nematodes were fed standard food (the bacterium Escherichia coli strain OP50) supplemented with various doses of sesamin/γ-cyclodextrin inclusion compounds starting from young adulthood. The mean lifespan, muscle function, lipofuscin accumulation, protein carbonyl content, and stress resistance of the worms were examined. Then, C. elegans mutants harboring loss-of-function lesions in longevity- and host defense-related signaling pathways were supplemented with sesamin to identify the genes involved in the longevity effects. RESULTS: Worms supplemented with sesamin displayed higher locomotion and prolongevity and produced offspring at levels similar to unsupplemented control animals. The growth curves of nematodes were similar to those of controls, suggesting that sesamin did not induce prolongevity effects through dietary restriction. Notably, sesamin made the worms more resistant to infection by Legionella pneumophila and more resistant to oxidative stressors such as paraquat and hydrogen peroxide and prolonged the lifespan of a mev-1 mutant that produces abundant superoxide anions. However, the accumulation of protein carbonyls and lipofuscin was similar in sesamin-exposed and control worms, suggesting that sesamin is unlikely to work simply as an antioxidant. Sesamin supplementation failed to extend the lifespan of loss-of-function mutants of daf-2, daf-16, pmk-1, and skn-1. CONCLUSIONS: Sesamin enhances the host defense of C. elegans and increases the average lifespan via activation of both skn-1 (encoding a component of the p38 MAPK pathway) and daf-16 (encoding a component of the IGF-1 pathway).

Mechanism underlying prolongevity induced by bifidobacteria in Caenorhabditis elegans.

Lactobacilli and bifidobacteria are probiotic bacteria that modify host defense systems and have the ability to extend the lifespan of the nematode Caenorhabditis elegans. Here, we attempted to elucidate the mechanism by which bifidobacteria prolong the lifespan of C. elegans. When the nematode was fed Bifidobacterium infantis (BI) mixed at various ratios with the standard food bacterium Escherichia coli strain OP50 (OP), the mean lifespan of worms was extended in a dose-dependent manner. Worms fed BI displayed higher locomotion and produced more offspring than control worms. The growth curves of nematodes were similar regardless of the amount of BI mixed with OP, suggesting that BI did not induce prolongevity effects through caloric restriction. Notably, feeding worms the cell wall fraction of BI alone was sufficient to promote prolongevity. The accumulation of protein carbonyls and lipofuscin, a biochemical marker of aging, was also lower in worms fed BI; however, the worms displayed similar susceptibility to heat, hydrogen peroxide, and paraquat, an inducer of free radicals, as the control worms. As a result of BI feeding, loss-of-function mutants of daf-16, jnk-1, aak-2, tol-1, and tir-1 exhibited a longer lifespan than OP-fed control worms, but BI failed to extend the lifespan of pmk-1, skn-1, and vhp-1 mutants. As skn-1 induces phase 2 detoxification enzymes, our findings suggest that cell wall components of bifidobacteria increase the average lifespan of C. elegans via activation of skn-1, regulated by the p38 MAPK pathway, but not by general activation of the host defense system via DAF-16.

[Low reactive laser therapy].

The type, characteristics and effect of low reactive laser equipment used for pain treatment in Japan are described in this section. Currently, low reactive laser therapy equipments marketed and used in Japan include diode laser therapeutic device with semiconductor as a medium consisting of aluminum, gallium and arsenic. Low reactive laser equipment comes in three models, the first type has a capacity of generating 1,000 mW output, and the second type has a capacity of generating 10 W output. The third type has four channels of output, 60, 100, 140 and 180 mW and we can select one channel out of the four channels. This model is also used as a portable device because of its light weight, and we can carry it to wards and to the outside of the hospital. Semiconductor laser has the capacity of deepest penetration and the effect tends to increase proportionally to the increasing output. Low reactive laser therapy is less invasive and lower incidence of complications. Although low reactive laser therapy might be effective for various pain disorders, the effect is different depending on the type of pain. We should keep in mind that this therapy will not give good pain relief equally in all patients with pain.

A randomized trial to identify optimal precurarizing dose of rocuronium to avoid precurarization-induced neuromuscular block.

PURPOSE: The aim of this study was to examine the safe precurarizing dose of rocuronium required to avoid neuromuscular block after precurarization. METHODS: Twenty-four female patients were randomly allocated into two groups of 12 patients each. General anesthesia was induced and maintained with remifentanil and propofol, and a laryngeal mask was inserted without the aid of a neuromuscular blocking agent. Patients were randomized to receive either 0.03 or 0.06 mg/kg rocuronium as a precurarizing dose. Neuromuscular block was monitored using acceleromyographic train-of-four (TOF) of the adductor pollicis muscle. Three minutes after the precurarization, all patients received suxamethonium 1.5 mg/kg and were graded on severity of fasciculations. RESULTS: The average TOF ratio was kept above 0.9 even 3 min after precurarization with 0.03 mg/kg rocuronium. In contrast, in patients who received 0.06 mg/kg rocuronium, the ratios significantly decreased to 0.72 (0.14) [mean (SD), P < 0.004] and 0.68 (0.18) (P < 0.006) 2 min and 3 min after the precurarization, respectively. No visible muscle movement was observed following suxamethonium injection, except that one patient who received 0.03 mg/kg rocuronium showed very fine muscle movements of the fingertips. CONCLUSION: Rocuronium at 0.06 mg/kg is an overdose for precurarization. The results of the present study demonstrate that a safe and effective precurarizing dose of rocuronium is 0.03 mg/kg.

Onset of rocuronium-induced neuromuscular block evaluated subjectively and accerelomyographically at the masseter muscle.

PURPOSE: The main aim of this study was to compare the onset times of rocuronium evaluated subjectively and by acceleromyography at the masseter muscle (MM). METHODS: Forty female patients were sequentially enrolled in this study. In the first 20 patients, neuromuscular block was evaluated subjectively. After induction of anesthesia with fentanyl and propofol, both the left masseter and ulnar nerves were stimulated in 2-Hz train-of-four (TOF) mode using peripheral nerve stimulators. Contractions of the MM were felt with an anesthesiologist's left hand holding an anesthesia facemask; those of the adductor pollicis (APM) were visually observed. All the patients received a bolus of rocuronium, 0.6 mg/kg. Onset times after rocuronium were defined as the duration until the contractions became impalpable at the MM or invisible at the APM. At the time contraction of the MM had not been felt, intubating conditions were assessed. In the next 20 patients, contractions of the MM and the APM were concurrently quantified using acceleromyography after induction of anesthesia and laryngeal mask insertion. Following 0.6 mg/kg rocuronium, onset of the action was recorded. RESULTS: Onset of the action of rocuronium at the MM evaluated subjectively [mean (SD), 70.3 (17.7) s] was similar to that monitored acceleromyographically [73.3 (27.6) s, P > 0.05], and significantly shorter than that at the APM acceleromyographically [111.0 (34.8) s, P = 0.016]. Intubating conditions of 20 patients were graded either excellent or good. CONCLUSION: Subjective evaluation of contractions of the MM by an anesthesiologist's hand may be reliable to determine faster timing for safe tracheal intubation.

Molecular characterization and expression of the low-density lipoprotein receptor-related protein-10, a new member of the LDLR gene family.

We report the characterization of a new member of the low-density lipoprotein receptor (LDLR) gene family designated LRP10. Human LRP10 cDNA encodes a 1905 amino acid type I membrane protein consisting of five functional domains characteristic of the LDLR gene family. CHO-ldlA7 cells transfected with human LRP10 cDNA bound LDLR-associated protein, but not beta-VLDL and HDL. Human LRP10 transcripts were primarily found in the brain, muscle and heart. In situ hybridization of the rat brain showed that the transcripts were intensely present in the cerebral cortex, hippocampus, choroid plexus, ependyma and granular layer. In the developing rat brain, transcript levels gradually increased from postnatal day 1 to 20. Immunofluorescence analysis indicated that LRP10 was observed in the ventricular zone of the embryonic day 14.5 mouse cerebral cortex. The present studies suggest that LRP10 may play a significant role in the brain physiology other than lipoprotein metabolism.

The low-density lipoprotein receptor-related protein 10 is a negative regulator of the canonical Wnt/beta-catenin signaling pathway.

Wnt signaling pathways play fundamental roles in the differentiation, proliferation and functions of many cells as well as developmental, growth, and homeostatic processes in animals. Low-density lipoprotein receptor (LDLR)-related protein (LRP) 5 and LRP6 serve as coreceptors of Wnt proteins together with Frizzled receptors, triggering activation of canonical Wnt/beta-catenin signaling. Here, we found that LRP10, a new member of the LDLR gene family, inhibits the canonical Wnt/beta-catenin signaling pathway. The beta-catenin/T cell factor (TCF) transcriptional activity in HEK293 cells was activated by transfection with Wnt3a or LRP6, which was then inhibited by co-transfection with LRP10. Deletion of the extracellular domain of LRP10 negated its inhibitory effect. The inhibitory effect of LRP10 was consistently conserved in HEK293 cells even when GSK3beta phosphorylation was inhibited by incubation with lithium chloride and co-transfection with constitutively active S33Y-mutated beta-catenin. Nuclear beta-catenin accumulation was unaffected by LRP10. The present studies suggest that LRP10 may interfere with the formation of the beta-catenin/TCF complex and/or its binding to target DNA in the nucleus, and that the extracellular domain of LRP10 is critical for inhibition of the canonical Wnt/beta-catenin signaling pathway.

Polymorphisms in the human apolipoprotein E receptor 2 gene in Japanese sporadic Alzheimer's disease patients.

Apolipoprotein E (apoE) polymorphism is associated with onset of Alzheimer's disease (AD). We found seven polymorphisms in apoE receptor 2 (ApoER2), an apoE-binding receptor, in Japanese sporadic AD patients, but no association of ApoER2 polymorphisms with AD. We consider that the functions of ApoER2 in the brain may be compensated for by those of other apoE-binding receptors such as VLDL receptor.

Monitoring masseter muscle evoked responses enables faster tracheal intubation.

PURPOSE: The aim of this study was to investigate whether monitoring neuromuscular block at the masseter muscle (MM) would allow faster tracheal intubation when compared with that at the adductor pollicis muscle (APM). METHODS: Twenty female patients undergoing gynecological surgery were enrolled into this study. Immediately after inducing anesthesia with fentanyl and propofol, both the left masseter and ulnar nerves were stimulated in a 2 Hz train-of-four (TOF) mode using peripheral nerve stimulators. Contractions of the MM were felt with the anesthesiologist's left hand lifting the patient's jaw and holding an anesthesia facemask, while those of the APM were visually observed. Immediately after the contracting responses of the muscles were confirmed, all of the patients received an iv bolus of vecuronium 0.1 mg kg(-1). Onset times after vecuronium were defined as the duration until the contractions became impalpable at the MM or invisible at the APM. When the contraction of the MM could no longer be felt, the conditions for laryngoscopy and tracheal intubation were assessed. RESULTS: Onset time evaluated tactually at the MM (mean +/- SD, 108.4 +/- 27.7 s) was significantly shorter than that evaluated visually at the APM (181.2 +/- 32.1 s, P < 0.0001). The intubating conditions for all patients were graded as either excellent or good. CONCLUSION: Tactual evaluation of muscle paralysis of the MM during induction of anesthesia is clinically useful since it leads to faster tracheal intubation.

Effectiveness of the timing principle with high-dose rocuronium during rapid sequence induction with lidocaine, remifentanil and propofol.

PURPOSE: The main purpose of this study was to examine the effectiveness of the timing principle with 1 mg kg(-1) rocuronium for rapid sequence intubation. As secondary outcomes, propofol and lidocaine with or without remifentanil were examined to note their effects on the cardiovascular responses to laryngoscopy and intubation. METHODS: Thirty patients were randomly allocated to one of two groups of 15 patients each: a lidocaine-treated group (L) and a lidocaine/remifentanil-treated group (LR). Thirty seconds after lidocaine 1 mg kg(-1) with or without infusion of remifentanil 1 microg kg(-1) min(-1), all patients received a bolus of rocuronium 1 mg kg(-1). Shortly afterwards, patients were given propofol 2-2.5 mg kg(-1). Intubating conditions and cardiovascular responses were observed 60 s after rocuronium. The time to spontaneous recovery of visible train-of-four (TOF) counts of 4 was observed at the thumb during 1.0-1.5% end-tidal sevoflurane and remifentanil anesthesia. RESULTS: All patients had excellent or good intubating conditions. Hypertension and tachycardia during laryngoscopy were well prevented in group LR, whereas they were significantly observed in group L. The times to reappearance of TOF counts of 4 were comparable in all groups [mean (SD); 63.6 (8.6) min in group L and 63.5 (11.6) min in group LR]. CONCLUSION: Application of the timing principle with 1 mg kg(-1) rocuronium is beneficial for rapid tracheal intubation. Co-administered lidocaine, remifentanil and propofol can definitely suppress cardiovascular responses during laryngoscopy and intubation.

[Optimum intubating dose of rocuronium for short duration surgery in adult patients].

BACKGROUND: The aim of this study was to examine optimum intubating dose of rocuronium in adult patients who had been scheduled for short duration surgery. METHODS: Thirty patients were randomly assigned to receive rocuronium 0.4 mg x kg(-1), 0.5 mg x kg(-1) or 0.6 mg x kg(-1) during induction with propofol and fentanyl. Immediately after the adduction of thumb to the ulnar nerve stimulation could not be visually observed, the patients were intubated tracheally and the intubating conditions were evaluated. Thereafter, time to recover to train-of-four (TOF) counts of 4 was recorded during sevoflurane and nitrous oxide anesthesia. RESULTS: Intubating conditions after rocuronium 0.5 and 0.6 mg x kg(-1) were all graded either excellent or good. In contrast, inadequate conditions for safe and easy tracheal intubation were observed in 60% of the patients receiving 0.4 mg x kg(-1). Time to spontaneous recover to the TOF counts of 4 correlated with the intubating doses of rocuronium. CONCLUSIONS: For short duration surgeries, rocuronium 0.5 mg x kg(-1) was appropriate to perform safe tracheal intubation and minimize duration of action of rocuronium.

Loss of nuclear receptor SHP impairs but does not eliminate negative feedback regulation of bile acid synthesis.

The in vivo role of the nuclear receptor SHP in feedback regulation of bile acid synthesis was examined. Loss of SHP in mice caused abnormal accumulation and increased synthesis of bile acids due to derepression of rate-limiting CYP7A1 and CYP8B1 hydroxylase enzymes in the biosynthetic pathway. Dietary bile acids induced liver damage and restored feedback regulation. A synthetic agonist of the nuclear receptor FXR was not hepatotoxic and had no regulatory effects. Reduction of the bile acid pool with cholestyramine enhanced CYP7A1 and CYP8B1 expression. We conclude that input from three negative regulatory pathways controls bile acid synthesis. One is mediated by SHP, and two are SHP independent and invoked by liver damage and changes in bile acid pool size.

A randomized pilot trial of oral branched-chain amino acids in early cirrhosis: validation using prognostic markers for pre-liver transplant status.

Because of the chronic shortage of liver donors, hepatologists are required to prolong the liver transplant waiting period by preserving the hepatic reserve of scheduled recipients. This study examined the effectiveness of oral branched-chain amino acids (BCAAs), using outcome markers indicating pretransplant hepatic reserve. Fifty-six consecutive eligible patients with Child class A cirrhosis without major complications were randomly assigned to receive oral BCAA granules (12.45 g/day) for least 1 year or no BCAAs. Differences between groups in the Model for End-Stage Liver Disease (MELD) score, Child-Turcotte-Pugh (CTP) score, asialoscintigraphic clearance index (CI), and complications were examined. Of 50 remaining patients, 27 received BCAAs, and 23 received no BCAAs (mean duration, 3.2 years). The mean annual changes in the MELD score, CTP score, and asialoscintigraphic CI were smaller in the BCAA group than in the control group (-0.06 +/- 0.23 versus 0.10 +/- 0.40, P = 0.024, 0.06 +/- 0.30 versus 0.30 +/- 0.48, P = 0.037, and 0.00 +/- 0.02 versus 0.02 +/- 0.04, P = 0.040, respectively). The mean annual changes in the serum total bilirubin and the serum albumin in the BCAA group were better preserved than those in the control group (-0.07 +/- 0.20 versus 0.12 +/- 0.18 mg/dL, P < 0.001, and 0.07 +/- 0.13 versus -0.02 +/- 0.19 g/dL, P = 0.005, respectively); other laboratory variables were not significant. The incidence of overall major cirrhotic complications was lower in the BCAA group than in the control group [14.8% (4 of 27 patients) versus 30.4% (7 of 23 patients) at 3 years, P = 0.043]; only ascites was significant individually. In conclusion, early interventional oral BCAAs might prolong the liver transplant waiting period by preserving hepatic reserve in cirrhosis.

Effect of landiolol hydrochloride on suxamethonium-induced neuromuscular block.

PURPOSE: The aim of this study was to examine the effect of landiolol hydrochloride, an ultrashort-acting beta(1)-blocker, on suxamethonium-induced neuromuscular block. METHODS: Thirty patients were randomly allocated to receive a loading dose of landiolol, 0.125 mg x kg(-1) x min(-1) for 1 min, followed by an infusion at 0.04 mg x kg(-1) x min(-1), or placebo. Twenty minutes after the infusion of landiolol or placebo, suxamethonium 1 mg x kg(-1) was administered during propofolfentanyl-nitrous oxide anesthesia. Neuromuscular block was monitored by train-of-four (TOF) responses of the adductor pollicis muscle, applying acceleromyographic stimuli to the ulnar nerve. RESULTS: The onset of neuromuscular block did not differ between the groups. The time from administration of suxamethonium to spontaneous recovery to the first twitch of TOF (T1) of control was significantly longer in the landiolol group (mean [SD]; 12.2 [2.5] min), when compared with the control group (9.8 [2.6] min). However, the TOF ratios measured when the T1 had spontaneously recovered to 10%, 25%, 50%, 75%, 90%, and 100% of control was comparable between the groups. CONCLUSION: Landiolol delayed recovery from suxamethonium-induced paralysis. However, the interaction between the drugs seemed to be small in the clinical setting.

[Crisis management during regional anesthesia including peripheral nerve block, epidural anesthesia and spinal anesthesia].

Crisis management during regional anesthesia including peripheral nerve block, epidural anesthesia and spinal anesthesia was reviewed. Common crisis which is encountered during regional anesthesia includes toxic reaction to local anesthetic drugs, allergic reaction induced by local anesthetic drugs, reaction induced by epinephrine, nerve injury, hematoma etc. Concerning peripheral nerve block, crisis encountered during brachial plexus block, interscalene block and supraclavicular block used for surgical operation of upper extremity was discussed. On the other hands, there are various common crises encountered during epidural anesthesia and spinal anesthesia. These crises include hypotension, bradycardia, total spinal anesthesia, postspinal headache and infection, and hematoma in the spinal canal. Especially, epidural hematoma and epidural abcess have possibility to cause nerve defect symptoms such as motor paralysis and sensory disturbance if appropriate treatment was not started in early stage. Moreover crisis such as cauda equina syndrome and anterior spinal cord syndrome have possibility to remain permanent and hard to cure. We anesthesiologists should make efforts to prevent crisis, to detect crisis in early stage, and to treat it in early stage.

[Investigations into neostigmine-induced inhibition of neuromuscular transmission].

BACKGROUND: Fade of the muscle contraction evoked by indirect tetanic nerve stimulation shows residual neuromuscular block. Anticholinesterases can reverse the partial block; however, they may also inhibit normal neuromuscular transmission and can cause fading responses by misuse of these drugs. The aim of this study is to investigate how neostigmine acts on normal neuromuscular function. METHODS: In cats, we observed a series of 8 consecutive muscular compound action potentials (mCAPs; M1-8) of the gastrocnemius muscle evoked by repetitive sciatic nerve stimulation at 100 Hz and calculated the M8/M1 amplitude ratio as an index of fading phenomenon. Neostigmine 0.05 mg x kg(-1) repetitively every 5 minutes before neuromuscular blocking agent had been administered, or after the complete recovery from vecuronium-induced block had been obtained. RESULTS: Neostigmine caused dose-dependent fade in the mCAPs. The mean doses (SD) of neostigmine for depressing M8/M1 ratio to 50% of baseline were 0.087 (0.029) mg x kg(-1) before use of neuromuscular blocking agent and 0.161 (0.070) mg x kg(-1) after the recovery from neuromuscular block. The fading responses induced by neostigmine were paradoxically reversed by small doses of vecuronium. CONCLUSIONS: Therapeutic doses of neostigmine administered during normal neuromuscular function cause fade of the repetitive muscle contractions. Neuromuscular monitoring should be used before the reversal with neostigmine.

[Indication and usage of opioids except morphine for chronic non-malignant intractable pain].

Indication and usage of opioids except morphine for chronic non-malignant intractable pain were reviewed. In Japan, other than morphine, we can use only two opioids, codeine phosphate (codeine), and dihydrocodeine phosphate (dihydrocodeine) for non-malignant pain management according to medical insurance system. But in western countries sustained-release opioids such as MS contine, transdermal fentanyl, oxycontin were used for the management of non-malignant chronic pain. The WHO ladder for cancer management should also be used for the management of non-malignant pain. Initial dose of codeine is 60 mg x day(-1) and the dosage should be increased or decreased according to pain intensity, patients' general condition and age. In most cases pain is controlled at the dose of 80-310 mg x day(-1). If pain intensity does not decrease or change, codeine should be changed to morphine. In our clinic, starting dose of codeine was 40-480 mg x day(-1) (average dose: 107.8 mg x day(-1)), maximum dose was 60-1280 mg x day (average dose: 310 mg x day(-1)). Average period for administration of codeine was 294.4 days. Dihydrocodeine has twice analgesic efficacy compared to codeine. The initial dose is the same as codeine. We hope that sustained release opioids such as transdermal fentanyl, oxycontin, tramadol etc will be used in Japan for management of non-malignant chronic pain in the near future.

Reflex sympathetic activity after intravenous administration of midazolam in anesthetized cats.

BACKGROUND: Although intrathecal midazolam has been reported to produce antinociceptive effects mediated by gamma-aminobutyric acid type A-benzodiazepine receptor complexes in the spinal cord, the effects of systemic midazolam on nociception remain unclear. We performed this study to examine the effects of IV-administered midazolam on somatosympathetic Adelta and C reflex discharges in brain-intact cats and decerebrate cats (with transection at midbrain level). METHODS: Somatosympathetic Adelta and C reflexes were elicited in the inferior cardiac sympathetic nerve by electrical stimulation of myelinated (Adelta) and unmyelinated (C) afferent fibers of the superficial peroneal nerve in 28 mature cats. After control somatosympathetic reflex responses were obtained, midazolam was administered IV to four groups of randomly allocated cats as follows: brain-intact cats at a dose of 0.03 mg/kg, brain-intact cats at a dose of 0.1 mg/kg, brain-intact cats at a dose of 0.5 mg/kg, and decerebrate cats at a dose of 0.1 mg/kg. RESULTS: C reflex discharges were significantly augmented at the dose of 0.03 mg/kg and significantly depressed at the dose of 0.1 and 0.5 mg/kg in brain-intact cats. C reflex discharges were also significantly depressed at the dose of 0.1 mg/kg in decerebrate cats. CONCLUSIONS: We have demonstrated that IV midazolam produces dose-related effects on somatosympathetic reflex discharges. The clinical implication of these findings is that the effect of midazolam on nociception depends on its dosage. It also appears that the infra-midbrain region plays a major role in mediating the depressive effects of midazolam on somatosympathetic C reflex discharges.

Anesthesia for repair of ventricular septal rupture after acute myocardial infarction.

A surgical patient with ventricular septal rupture after acute myocardial infarction is presented. The primary concern of general anesthesia was in the maintenance of systemic arterial pressure and reduction of afterload. General anesthesia was induced with a combination of fentanyl, ketamine, and propofol, which successfully suppressed fluctuations of hemodynamic variables associated with induction of anesthesia and tracheal intubation. Intravenous milrinone was used for inotropic support and reduction of systemic vascular resistance. The ventricular septal rupture was successfully repaired.