Effects of sepsis on the neuromuscular blocking actions of d-tubocurarine on rat adductor and abductor laryngeal muscles

Purpose

We evaluated the effects of sepsis on the neuromuscular blocking actions of d-tubocurarine (dTc) in the lateral cricoarytenoid (LCA) and posterior cricoarytenoid (PCA) muscles, an adductor muscle and an abductor muscle of the vocal cords, respectively, in vitro.

Methods

Sepsis was induced in rats by cecal ligation and puncture (CLP) to elicit panperitonitis. Electromyograms (EMGs) and endplate potentials (EPPs) were recorded from the LCA and PCA muscles of CLP-operated septic rats and sham-operated nonseptic rats, using extracellular and intracellular microelectrodes, respectively.

Results

EMG and EPP (amplitude and quantum content) were depressed by dTc, but the dTc-induced neuromuscular blocking effects were attenuated by sepsis. The suppressive effects of dTc on EMG and EPP (amplitude and quantum content) were less intense in the LCA muscle than in the PCA muscle under both sepsis and nonsepsis conditions.

Conclusion

Our study shows that sepsis has a depressive effect on dTc-induced neuromuscular blocking actions at both the adductor and abductor muscles of vocal cords in the larynx.     

Effects of running exercise on the mandible and tibia of ovariectomized rats

To examine the effects of running exercise on the mandible and tibia of ovariectomized (OVX) rats, 26-week-old sham-operated (Sham) and OVX rats 1 week post-ovariectomy were subjected to non-exercise (Sham-Cont and OVX-Cont) and exercise (Sham-Exc and OVX-Exc) for 8 weeks. OVX induced a significant decrease in alkaline phosphatase (ALP) and an increase in tartrate-resistant acid phosphatase (TRAP) activity and a reduction of 17β-estradiol in the serum. In OVX-Cont rats, histology and bone mineral density (BMD) showed bone loss in the proximal tibia, and histology, soft X-ray photographs and bone marrow area (BMA) revealed enlargement of the bone marrow cavity in the neck of the condylar process. In OVX-Exc rats, exercise significantly increased ALP activity, decreased TRAP activity and markedly elevated serum progesterone levels. Histology and BMD in the tibia and histology, X-ray photographs and BMA in the mandible were comparable to those in Sham rats. In Sham-Exc rats, unexpected decreases were observed in serum enzymes and hormones, but the histology and BMD in the tibia and histology, X-ray photographs and BMA in the mandible were very similar to those in Sham-Cont rats, suggesting a decrease of bone turnover with no change of bone mass in the tibia and mandible. We conclude that exercise has a beneficial effect not only on bone loss in the tibia, but also on differential changes in the neck of the condylar process, perhaps by increasing serum levels of progesterone in OVX rats. Received: May 29, 2000 / Accepted: November 6, 2000     

Pharmacokinetics of amikacin in the pediatric surgical field

Amikacin (AMK) was intravenously administered to pediatric surgical patients, and its pharmacokinetics was studied. The results obtained are summarized as follow: 1. The serum levels following administration were similar to those which had been reported by others. Urinary excretion was excellent. 2. The concentration of AMK in pleural effusion of a postoperative premature baby was an effective level higher than MIC's to target organisms. 3. Bile levels of AMK were the highest soon after surgery on patients with biliary atresia, these declined as time passed. The high levels obtained were in the effective range where the levels were higher than MIC's against organisms isolated from bile of patients with biliary tract infections. Biliary excretions were good in cases with good hepato-enteric circulation. 4. Biliary and urinary excretion rates were well correlated.     

Enhancement by bFGF of osteogenesis induced by rhBMP-2 in rats

Subcutaneous implantation of bone morphogenetic protein (BMP) combined with a fibrous glass membrane (FGM) induces cartilage formation in the entire inner area of the membrane within 2 wk. It has been hypothesized that a tight FGM network (1 μm exclusion size) provides immature cells with spaces for penetrating Into the membrane, but not for vascular formation, at least until 2 wk. To test this hypothesis, basic fibroblast growth factor (bFGF), known to be a potent stimulant of capillary formation, was applied to the implant. BMP was combined with FGM in the presence or absence of bFGF. and then implanted subcutaneously into the backs of rats. The bFGF-supplemented implant caused 1.3 times higher alkaline phosphatase activity and 3 times higher calcium contents at 2 wk. whereas type II collagen contents decreased. thus indicating that bFGF enhances bone formation in BMP/FGM implants. These results suggest that bFGF induces faster and stronger invasion of capillaries into the FGM and destroys its tight network, resulting in acceleration of the ossification process.     

A new device for pediatric one-lung anesthesia

We were using an L type connector with single side port with a Fogarty catheter in pediatric one-lung anesthesia. This method was not as good as roported, because modification of catheter position was rather too difficult during operation. We have made a new device with two side ports to improve weak points of the old device. We used this device for pediatric one-lung anesthesia, and obtained good results.     

Changes in Response Properties and Receptive Fields of Spinal Dorsal Horn Neurons in Rats after Surgical Incision in Hairy Skin

Background: Mechanical hyperalgesia and allodynia associated with chemical irritant application are mediated by spinal high-threshold (HT) as well as wide-dynamic-range neurons as a result of "central sensitization." Because the pathophysiology of pain is thought to differ depending on the type of injury and may vary between hairy and glabrous skin, the authors examined changes in properties of spinal dorsal horn neurons after surgical incisions in hairy skin of rats to obtain insights into the mechanisms of postoperative pain.

Methods: Withdrawal responses to punctate mechanical stimulation and gentle brushing were measured in awake rats in an area adjacent to the injured site (primary area) and in an area 2 cm from the injured site (secondary area) after 1-cm longitudinal incisions through the hairy skin, fascia, and muscle had been made in the hindquarters. In a separate study, responses of spinal wide-dynamic-range, HT, and low-threshold neurons to nonnoxious and noxious stimuli were recorded before and after similar incisions had been made in the centers of their receptive fields. Effects of spinal application of the [gamma]-aminobutyric acid A receptor antagonist bicuculline (15 [mu]g) on responses of HT neurons were then studied.

Results: Awake rats showed primary and secondary hyperalgesia to punctate mechanical stimulation 30 min after the incision and thereafter for 4 days and 1 day, respectively. Mechanical allodynia associated with brush stimulation was only seen in the primary area 30 min after the incision and thereafter for 1 day. The incision resulted in increases in activity of wide-dynamic-range neurons (receptive field sizes and responses to both innocuous and noxious stimuli). HT neurons did not respond to innocuous stimulation and showed very small increases or no changes in receptive field size and responses to noxious stimuli after the incision. However, the majority of HT neurons began to respond to innocuous stimuli after application of bicuculline (15 [mu]g/50 [mu]l) to the spinal cord.     

Substance P and vasoactive intestinal peptide in rat small-bowel isografts

BACKGROUND: It is established that substance P (SP) is released by stimulation of nonadrenergic noncholinergic (NANC) excitatory nerves and vasoactive intestinal peptide (VIP) by stimulation of NANC inhibitory nerves. To evaluate the function of peptidergic nerves such as SP and VIP in small-bowel isografts, we examined the enteric nerve responses to SP and VIP in the isografted rat jejunum, using the normal rat jejunum as a control. METHODS: Orthotopic entire small bowel transplantation (SBT) with portocaval drainage was performed from Lewis rats to Lewis rats. Grafted tissue specimens were obtained 130 days after SBT (n = 9). As controls, normal segments of the jejunum were obtained from untransplanted Lewis rats (n = 22). A mechanograph was used to evaluate in vitro jejunal responses to electrical field stimulation of the enteric nervous system before and after treatments with various autonomic nerve blockers and neuropeptides (SP and VIP). RESULTS: SP concentration-dependently mediated the contraction reaction of NANC excitatory nerve in the isografted jejunum and to a lesser extent in the normal jejunum. In addition, there were significant diferences in the percentages showing contraction at 1 x 10(-8) and 1 x 10(-6)g/mL SP between the normal and isografted jejunal muscle strips (P < .05, respectively). VIP concentration dependently mediated the relaxation reaction of NANC inhibitory nerve in the normal jejunum and to a lesser extent in the isografted jejunum. In addition, there was a significant difference between the relaxation frequencies of the normal and those of isografted jejunal muscle strips at 1 x 10(-6) g/mL SP (P < .01). CONCLUSIONS: Contraction reactions of SP were observed in both the normal and isografted jejunum but were increased in the isografted jejunum. Relaxation reactions of VIP were also observed in both the normal and isografted jejunum but were decreased in the isografted jejunum. The increase of the effects of SP via NANC excitatory nerves and the decrease of the effects of VIP in mediating NANC inhibitory nerves may be largely related to the peristaltic abnormalities seen in the isografted LEW rat jejunum.     

Bone loss in survival motor neuron (Smn−/− SMN2) genetic mouse model of spinal muscular atrophy

Spinal muscular atrophy (SMA) is characterized by degenerating lower motor neurons and an increased incidence of congenital bone fractures. Survival motor neuron (SMN) levels are significantly reduced due to deletions/mutations in the telomeric SMN1 gene in these patients. We utilized the Smn^?/? SMN2 mouse model of SMA to determine the functional role for SMN in bone remodelling. µCT analysis of lumber vertebrae, tibia and femur bones from SMA mice revealed an osteoporotic bone phenotype. Histological analysis demonstrated a thin porous cortex of cortical bone and thin trabeculae at the proximal end of the growth plate in the vertebrae of SMA mice compared to wild‐type mice. Histochemical staining of the vertebrae showed the presence of abundant activated osteoclasts on the sparse trabeculae and on the endosteal surface of the thin cortex in SMA mice. Histomorphometric analysis of vertebrae from SMA mice showed an increased number of osteoclasts. Serum TRAcP5b and urinary NTx levels were elevated, consistent with increased bone resorption in these mice. SMA mice showed a significant decrease in the levels of osteoblast differentiation markers, osteocalcin, osteopontin and osterix mRNA expression; however, there were no change in the levels of alkaline phosphatase expression compared to WT mice. SMA mouse bone marrow cultures revealed an increased rate of osteoclast formation (54%) and bone resorption capacity (46%) compared to WT mice. Pre‐osteoclast cells from SMA mice showed constitutive up‐regulation of RANK receptor signalling molecules critical for osteoclast differentiation. Our results implicate SMN function in bone remodelling and skeletal pathogenesis in SMA. Understanding basic mechanisms of SMN action in bone remodelling may uncover new therapeutic targets for preventing bone loss/fracture risk in SMA. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Computer assisted design for the implantable left ventricular assist device (LVAD) blood pump using computational fluid dynamics (CFD) and computer-aided design and manufacturing (CAD/CAM)

Thrombus formation and hemolysis are critical issues in the design of a long-term implantable LVAS (left ventricular assist system). The fluid dynamic characteristics of the blood flow are one of the main factors that cause thrombus formation and hemolysis. In this study, we optimized blood chamber geometry, port design, and fluid dynamics in our implantable LVAS to ensure minimization of shear-stress-related blood damage. A blood pump chamber (stroke volume, 65 ml) and an inflow and outflow port were designed with three-dimensional CAD (computer-aided-design) software (Pro-Engineering version 20) and estimated by FEM (fine-element method) computational fluid dynamic (CFD) analysis (Ansys version 5.5). We adopted three-dimensional distribution of CFD results for qualitative evaluation, and we also tried to estimate the normalized index of hemolysis (NIH) and time-series change of hematocrit from the results of CFD analysis as quantitative index of optimization for geometry of the blood pump chamber. With the use of this design, the blood pump geometry was optimized as the decrease of NIH from 2.72 g/1001 in the first model to 0.098 g/1001 in the second model, corresponding to the decrease in shear stress. The hematocrit also improved from 0.7% in the first model to 11.5% in the second model 2 years after implantation of the pump. Areas where flow stagnation was observed in the first model were free of stagnation in the second model. The results show that computer-aided design of the blood pump contributes to optimizing a blood pump chamber for reducing thrombus formation and hemolysis, and also contributes to reducing cost and time in developing the implantable LVAS.