Mamoru Takeuchi

Right ventricle–pulmonary artery shunt in first-stage palliation of hypoplastic left heart syndrome

OBJECTIVE Pulmonary overcirculation through a systemic-pulmonary shunt has been one of the major causes of early death after the Norwood procedure. To avoid this lethal complication, we constructed a right ventricle-pulmonary shunt in first-stage palliation of hypoplastic left heart syndrome. METHODS Between February 1998 and February 2002, 19 consecutive infants, aged 6 to 57 days (median, 9 days) and weighing 1.6 to 3.9 kg (median, 3.0 kg), underwent a modified Norwood operation with the right ventricle-pulmonary artery shunt. The procedure included aortic reconstruction by direct anastomosis of the proximal main pulmonary artery and a nonvalved polytetrafluoroethylene shunt between a small right ventriculotomy and a distal stump of the main pulmonary artery. The size of the shunt used was 4 mm in 5 patients and 5 mm in 14. RESULTS All patients were managed without any particular manipulation to control pulmonary vascular resistance. There were 17 survivors (89%), including 3 patients weighing less than 2 kg. Two late deaths occurred due to obstruction of the right ventricle-pulmonary artery shunt. Thirteen patients underwent a stage II Glenn procedure after a mean interval of 6 months, with 2 hospital deaths. To date, a stage III Fontan procedure has been completed in 4 patients. Overall survival was 62% (13/19). Right ventricular fractional shortening at the last follow-up (3-48 months after stage I) ranged from 26% to 43% (n = 13, mean, 33%). CONCLUSION Without delicate postoperative management to control pulmonary vascular resistance, the modified Norwood procedure using the right ventricle-pulmonary shunt provides a stable systemic circulation as well as adequate pulmonary blood flow. This novel operation may be particularly beneficial to low-birth-weight infants with hypoplastic left heart syndrome.

Correlation between the Distribution of Contrast Medium and the Extent of Blockade during Epidural Anesthesia

Background: If the epidural spread of contrast medium can be well correlated with the spread of local anesthetics, epidurography can predict the dermatomal distribution of the anesthetic block. The authors evaluated the relation between radiographic and analgesic spread. Methods: An epidural catheter was inserted in 90 patients, and predicted catheter tip position was recorded. The analgesic area was determined by pinprick after a 5-ml injection of 1.5% lidocaine, and epidurography was performed after a 5-ml injection of 240 mg I/ml iotrolan. Patients were assigned to three groups according to catheter tip position (group C: C–T4; group T: T5–T10; group L: T11–L), and patterns of spread were compared. In 16 of 90 subjects, radiographic and analgesic spread was further investigated after an additional 5-ml injection of iotrolan and lidocaine. Results: The total radiographic spread correlated well with analgesic spread (right side: Y = 0.84 X + 0.16, r = 0.92, P < 0.01; left side: Y = 0.78 X + 0.45, r = 0.91, P < 0.01). The mean radiographic spread in the cephalad and caudal directions from the catheter tip also correlated well with mean analgesic spread (r = 0.97, P < 0.01, each direction). The mean distance between the predicted catheter tip and radiographically determined positions was 1.0 ± 0.8 segments: the value in group T was significantly larger than that in groups C (P < 0.05) and L (P < 0.01). Although the correlation of radiographic spread with age was statistically significantly (r = 0.39, P < 0.01), great individual variation in spreading pattern was seen. In 16 subjects, mean radiographic spread correlated well with analgesic spread after 5- and 10-ml injections of iotrolan and lidocaine. Conclusions: Epidurography is useful to indicate epidural catheter position and can help to predict the exact dermatomal distribution of analgesic block.

Heme Arginate Pretreatment Attenuates Pulmonary NF-κB and AP-1 Activation Induced by Hemorrhagic Shock via Heme Oxygenase-1 Induction

Hemorrhagic shock followed by resuscitation (HSR) induces oxidative stress that leads to acute lung injury. Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme catabolism, is induced by oxidative stress and is thought to play an important role in the protection from oxidative tissue injuries. We previously demonstrated that HO-1 induction by heme arginate (HA), a strong inducer of HO-1, ameliorated HSR-induced lung injury and inflammation. Cellular redox state is known to modulate the DNA biding activity of the transcription factors; nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). In the present study, we treated rats with HA (30 mg/kg of hemin) 18 h prior to HSR and examined its effect on the DNA binding activity of NF-kappaB and AP-1 at 1.5 h after HSR. HSR significantly increased the DNA binding activity of NF-kappaB as well as AP-1, while HA pretreatment markedly attenuated the activities of these transcription factors. In contrast, administration of tin mesoporphyrin, a specific competitive inhibitor of HO activity, to HA-pretreated animals abolished the suppressive effect of HA on the activities of NF-kappaB and AP-1, and increased these activities to almost the same level as those in HSR animals. Our findings indicate that HA pretreatment can significantly suppress the increased activity of NF-kappaB and AP-1 induced by HSR by virtue of its ability to induce HO-1. Our findings also suggest that HO-1 induced by HA pretreatment ameliorates HSR-induced lung injury at least in part mediated through the suppression of the activities of these transcription factors.

In vivo cell tracking by bioluminescence imaging after transplantation of bioengineered cell sheets to the knee joint

In our previous studies, we have demonstrated effective regeneration of cartilage through the creation and application of layered cell sheets that combine both chondrocytes and synovial cells. In this study, we were able to demonstrate that cells derived from cell sheets can survive for long periods after transplantation into rat knee joints having osteochondral defects. We established a method for generating cell sheets from firefly luciferase-expressing chondrocytes obtained from transgenic Lewis rats, and carried out allogenic transplantation of these cell sheets into wild-type Lewis rats. We then administered luciferin and monitored the survival of the transplanted cells by using bioluminescence imaging (BLI). Our data showed that the transplanted cells survived and could be detected for more than 21 months, which was longer than expected. Furthermore, the BLI data showed that the transplanted cells remained in the knee joint and did not migrate to other parts of the body, thus confirming the safety of the cell sheets. In this study, we monitored the duration of survival of cell sheets composed of only chondrocytes, only synovial cells, or both chondrocytes and synovial cells, and found that all three types of cell sheets survived for an extended period of time.

Complete Heart Block during Anesthetic Management in a Patient with Mucopolysaccharidosis Type VII

IT is believed that complete heart block is unlikely to occur in patients without preexisting left bundle branch block. We describe the occurrence of complete heart block during attempted placement of a central venous catheter in a child with mucopolysaccharidosis (MPS) type VII (Sly syndrome) without preexisting left bundle branch block. Numerous reports of anesthesia in patients with MPS have described airway management and respiratory complications. However, cardiac problems during anesthesia in patients with MPS should he considered important because of the possibility of preexisting cardiomyopathy or coronary stenosis.

Comparison of the analgesic effects of continuous extrapleural block and continuous epidural block after video-assisted thoracoscopic surgery.

DESIGN A prospective, randomized, open study. The regional technique used was not blinded. SETTING A university teaching hospital. PARTICIPANTS Forty-eight patients undergoing video-assisted thoracoscopic surgery (VATS) for tumor resection. INTERVENTIONS Patients received either continuous extrapleural block or continuous epidural block using ropivacaine for a period of 60 hours after surgery. MEASUREMENTS AND MAIN RESULTS To evaluate postoperative pain control, the primary and secondary endpoints were the visual analog scale (VAS) on movement and the amount of rescue analgesia, respectively. There were no significant differences between the extrapleural and epidural block groups with regard to VAS at rest and during movement assessed at 4, 12, 24, 36, and 48 hours after surgery, dosage of intravenous morphine (extrapleural: 12.9 ± 11.3, epidural: 10.2 ± 6.9 mg), supplemental nonsteroidal anti-inflammatory drugs, incidence of postoperative nausea and vomiting (extrapleural: 12/20, epidural: 11/20), postoperative ambulation (extrapleural: 18 at postoperative day [POD] 1 and 20 at POD 2, epidural: 19 at POD 1 and 20 at POD 2) and hospital stay after surgery (extrapleural: 12.7 ± 6.3, epidural: 12.6 ± 4.7 days). CONCLUSIONS Although this study did not show the superiority of continuous extrapleural block relative to continuous epidural in VATS patients, the results suggest that both methods provided effective analgesia with a relatively small dose of rescue morphine. Although the analgesic effects of these techniques were comparable, extrapleural block has the advantage of safety and precise placement of the catheter and can be considered an alternative to epidural block in VATS patients.

Electroencephalographic changes and their regional differences during pediatric cardiovascular surgery with hypothermia

Monitoring brain function by EEG is an important means of preventing cerebral insults in pediatric cardiovascular surgery. We studied intraoperative EEG changes and their regional differences associated with hypothermia and brain ischemia. The subjects of this study consisted of 13 children ranging in age from 4 months to 4 years and 6 months. Multi-channel EEGs were recorded using a portable digital EEG system, and the EEG changes were examined by visual inspection and computerized analyses. The results were as follows. (1) During cooling, a discontinuous EEG pattern was transiently observed in four patients, and this phenomenon indicated rapid suppression of cerebral function and subsequent adaptation. (2) Regarding the patterns of change in equivalent potentials induced by hypothermia, there were two different patterns depending on the degree of hypothermia, and the borderline rectal temperature was found to be around 32 degrees C. (3) During cooling, regional differences in the changes in equivalent potentials were observed in nine patients. A decrease in slow waves was marked in the occipital head area, and a decrease in fast waves was prominent in the anterior head area. (4) Arterial hypotension caused transient EEG abnormalities. Of them, bilaterally synchronous rhythmic high voltage slow waves were remarkable and exhibited bifrontal or bicentral dominance. (5) The EEG changes induced by hypothermia were influenced not only by the rectal temperature itself, but also by the rate of change in rectal temperature, and we speculated that this phenomenon was a result of adaptation. In intraoperative EEG monitoring, these findings constitute the basis for early detection of a cerebral hypoxic-ischemic state during pediatric cardiovascular surgery.

Increased Pulmonary Heme Oxygenase-1 and δ-Aminolevulinate Synthase Expression in Monocrotaline-Induced Pulmonary Hypertension

Monocrotaline (MCT), a pyrrolizidine alkaloid plant toxin, is known to cause pulmonary hypertension (PH) in rats. Recent findings suggest that pulmonary inflammation may play a significant role in the pathogenesis in MCT-induced PH. Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme catabolism, is known to be induced by various oxidative stresses, including inflammation and free heme, and its induction is thought essential in the protection against oxidative tissue injuries. In this study, we examined expression of HO-1 as well as non-specific delta-aminolevulinate synthase (ALAS1), the rate-limiting enzyme in heme catabolism and biosynthesis, respectively, in a rat model of PH produced by subcutaneous injection of MCT (60 mg/kg). MCT treatment caused infiltration of inflammatory cells, fibrosis of the interstitium, and pulmonary arterial wall thickening with marked elevation of right ventricular (RV) pressure, which are characteristics of MCT-induced PH. Gene expression of tumor necrosis factor-alpha (TNF-alpha) as well as DNA binding activity of nuclear factor-kappaB (NF-kappaB) increased at 1 week after MCT treatment, reached a maximum at 2 weeks, and then decreased to the pretreatment level at 3 weeks. HO-1 expression was markedly increased at 1 week, and continued to increase by 3 weeks following MCT treatment, both at transcriptional and protein levels in the mononuclear cells in the lung. ALAS1 mRNA levels in the lung also significantly increased at 2 weeks after MCT treatment. These findings suggest that pulmonary HO-1 expression was presumably induced by proinflammatory cytokine(s) in MCT-treated rats, resulting in the derepression of heme-repressible ALAS1 expression, and that HO-1 induction plays a significant role as an inflammatory factor in this condition.

Kisspeptin-10 potentiates miniature excitatory postsynaptic currents in the rat supraoptic nucleus.

Kisspeptin is the natural ligand of the G protein-coupled receptor -54 and plays a major role in gonadotropin-releasing hormone secretion in the hypothalamus. Kisspeptin-10 is an endogenous derivative of kisspeptin and has 10 -amino acids. Previous studies have demonstrated that central administration of kisspeptin-10 stimulates the secretion of arginine vasopressin (AVP) in male rats. We examined the effects of kisspeptin-10 on- excitatory synaptic inputs to magnocellular neurosecretory cells (MNCs) including AVP neurons in the supraoptic nucleus (SON) by obtaining in vitro whole-cell patch-clamp recordings from slice preparations of the rat brain. The application of kisspeptin-10 (100 nM-1 μM) significantly increased the frequency of miniature excitatory postsynaptic currents (mEPSCs) in a dose-related manner without affecting the amplitude. The kisspeptin-10-induced potentiation of the mEPSCs was significantly attenuated by previous exposure to the kisspeptin receptor antagonist kisspeptin-234 (100 nM) and to the protein kinase C inhibitor bisindolylmaleimide I (20 nM). These results suggest that kisspeptin-10 participates in the regulation of synaptic inputs to the MNCs in the SON by interacting with the kisspeptin receptor.

Right ventricle of patients undergoing congenital cardiac surgery differentially expresses Haem oxygenase-1 and heat shock protein 70 genes

Reactive oxygen species are implicated in the pathogenesis of cardiac hypertrophy. Haem oxygenase-1 (HO-1), the rate-limiting enzyme in haem catabolism, is induced by oxidative stress and confers protection against oxidative tissue injuries. We used Northern blotting to examine expression of HO-1 and heat shock protein 70 (HSP70) in the hypertrophic cardiac muscle of eight patients (one infant and seven children) who underwent surgery for congenital heart disease. Levels of HO-1 and HSP70 mRNA were significantly increased in all specimens, but the orders of magnitude of the increases were different, suggesting that the genes expressing HO-1 and HSP70 are regulated separately.