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Murakami, Manabu ; Nemoto, Takayuki ; Niwa, Hidetoshi ; Kushikata, Tetsuya ; Ono, Kyoichi ; Watanabe, Hiroyuki ; Hirota, Kazuyoshi ; Ohba, Takayoshi
概要:
Aims: The purpose of the current study was to evaluate the significance of the endothelin system in catecholamine release and synthesis in the adrenal gland.Main Methods: Primary cultures of isolated bovine adrenal medullary cells
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were prepared. Gene expression, intracellular calcium changes, epinephrine release, and other factors were investigated.Key findings: Expression of endothelin receptors in the rat adrenal gland was confirmed. Intravenous infusion of endothelin-1 (1.0 nmol) increased blood pressure (systolic and diastolic). Endothelin-1 stimulated intracellular calcium changes, resulting in increased nuclear factor of T cell (NFAT) activity and epinephrine release from cultured adrenal medullary cells. Furthermore, endothelin-1 increased catecholamine synthesis and caused hypertrophic changes in the cell size.Significance: Our findings indicate involvement of the endothelin system in the sympathetic regulation of the adrenalmedulla.
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Shintaku, Tomohiro ; Ohba, Takayoshi ; Niwa, Hidetoshi ; Kushikata, Tetsuya ; Hirota, Kazuyoshi ; Ono, Kyoichi ; Mariya, Yasushi ; Imaizumi, Tadaatsu ; Sawamura, Daisuke ; Murakami, Manabu
概要:
General anesthesia is important for pharmacological studies in laboratory animals. Although a number of transgenic anima
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ls have been reported, basic analyses concerning mouse ECG and heart rate variability（ HRV） have not been rigorously examined.
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| 3.
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Shintaku, Tomohiro ; Ohba, Takayoshi ; Niwa, Hidetoshi ; Kushikata, Tetsuya ; Hirota, Kazuyoshi ; Ono, Kyoichi ; Mariya, Yasushi ; Imaizumi, Tadaatsu ; Sawamura, Daisuke ; Murakami, Manabu
概要:
We compared the effects of inhalation anesthesia（ 2% isoflurane）, intraperitoneal injection of pentobarbital anesthesia
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（50 mg/kg）, and a combination anesthetic consisting of medetomidine, midazolam and butorphanol （MMB） on electrocardiograms in mice. Using either isoflurane inhalation anesthesia or pentobarbital anesthesia, heart rate （HR） was in the acceptable range （ca. 450-500 bpm）. In contrast, MMB anesthesia decreased HR significantly. Importantly, MMB anesthesia responded minimally to propranolol （β-blocker）, suggesting that MMB anesthesia affects sympathetic tonus and is not suitable for evaluation of the cardiovascular or sympathetic system. We confirmed that modified MMB, with a decreased dose of medetomidine from the original protocol（ an α2 agonist）, was associated with a HR of 400 bpm and a diminished response to propranolol. Our present results illustrate the importance of using an appropriate form of anesthesia suitable for experimental pharmacological studies.
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| 4.
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Chong, Han ; Ogata, Yoshiki ; Niwa, Hidetoshi ; Kushikata, Tetsuya ; Watanabe, Hiroyuki ; Imaizumi, Tadaatsu ; Hirota, Kazuyoshi ; Ono, Kyoichi ; Ohba, Takayoshi ; Murakami, Manabu
概要:
Transgenic mice experiments have become increasingly popular to research human inherited disease.However, a number of Ja
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panese researchers have difficulty with the selection of anesthesia, after the classificationof ketamine, probably the most used anesthesia, as a narcotic drug in 2006. Therefore, we compared the effects ofinhalation anesthesia （2% of isoflurane, sevoflurane and enflurane） and intraperitoneal pentobarbital anesthesia （50mg/kg） on the electrocardiogram（ ECG） and blood oxygen saturation（ SPO2） of mice. With inhalation anesthesia, theheart rate（ HR） and SPO2 were within an acceptable range. In contrast, the HR significantly decreased after initiationof pentobarbital anesthesia, and gradually returned to a low rate. Importantly, pentobarbital anesthesia significantlylowered SPO2, and heart rate variability analysis showed unstable beat-to-beat intervals during pentobarbitalanesthesia, suggesting that inhalation anesthesia is more suitable for evaluation of cardiorespiratory responsesthan pentobarbital anesthesia. During anesthesia, propranolol, a ????-adrenergic blocker, significantly decreased heartrate. Atropine, a parasympathetic blocker, also significantly increased heart rate. Our data suggest that inhalation anesthesia is suitable for cardiorespiratory analysis in mice.
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Nozaki, Shuhei ; Ogata, Yoshiki ; Yonekura, Manabu ; Han, Chong ; Niwa, Hidetoshi ; Kushikata, Tetsuya ; Hirota, Kazuyoshi ; Matsuzaki, Yasushi ; Tomita, Hirofumi ; Imaizumi, Tadaatsu ; Itagaki, Shirou ; Sawamura, Daisuke ; Murakami, Manabu
概要:
We analyzed the effects of halothane as an inhalational anesthetic agent on electrocardiogram （ECG）parameters in C57/BL6
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mice. Following induction of anesthesia using 2% halothane, the ECGs showed a regularpattern and the heart rate （HR） was within an acceptable range （~500 bpm）. The HR decreased with increasinghalothane concentration in a concentration-dependent fashion. The frequency domain analysis showed that the high-frequency （HF） component decreased and the lowfrequency（LF） component increased in a concentration-dependent fashion. Therefore, the LF/HF ratio increasedwith increasing halothane concentration, suggesting effects on the autonomic nervous system. We analyzed the pharmacological response to sympathetic blockade with propranolol, a typical adrenergicβ-blocker, under halothane anesthesia. Propranolol administration resulted in a decreased HR; interestingly,intraperitoneal injection of propranolol （120 μg/kg body weight） resulted in arrhythmia （sick sinus syndrome）during anesthesia with 3% halothane. Our results indicate the importance of selecting a suitable anesthetic agent for C57/BL6 mice in pharmacological studies
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| 6.
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Ogata, Yoshiki ; Yonekura, Manabu ; Yamaki, Rouichi ; Han, Chong ; Fujiwara, Tomonori ; Seya, Kazuhiko ; Niwa, Hidetoshi ; Kushikata, Tetsuya ; Imaizumi, Tadaatsu ; Hirota, Kazuyoshi ; Tomita, Hirofumi ; Murakami, Manabu
概要:
We examined the effects of enflurane anesthesia on the mouse cardiac autonomic nervous system usingelectrocardiogram（ EC
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G） analysis. Enflurane had a lower effect on heart rate（ HR） compared to isoflurane, which ismore widely used in small animal studies. Under anesthesia with 3 or 4% of enflurane, administration of propranololhad a significant effect on HR. Enflurane increased R-R interval length in a dose-dependent fashion, and the R-Rinterval became unstable at high concentrations. Although HR decreased with high doses of enflurane, we observednormal sinus rhythm and no arrhythmia. These results suggest that the effect of enflurane anesthesia is acceptableeven though the drug can lead to cardiac instability. No remarkable changes were observed in HR frequency. These results suggest that enflurane anesthesia may be suitable for cardiac autonomic nervous system analysis.
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Han, Chong ; Inaba, Wataru ; Yonekura, Manabu ; Ogata, Yoshiki ; Ohba, Takayoshi ; Kushikata, Tetsuya ; Niwa, Hidetoshi ; Yanagisawa, Teruyuki ; Tomita, Hirofumi ; Itagaki, Shirou ; Hirota, Kazuyoshi ; Akai, Hiroaki ; Mizukami, Hiroki ; Murakami, Manabu
概要:
Persistent hyperglycemia is implicated in the pathogenesis of chronic diabetic complications, such asneuropathy. Theref
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ore, we investigated Electrocardiogram（ ECG）-related changes, including various ECG parametersand heart rate variability, and neuropathic changes in diabetic Goto-Kakizaki （GK） rats, a spontaneous model fortype 2 diabetes. GK rats （50 weeks old） showed increased plasma glucose and decreased R-R interval variability,which was likely due to diabetic polyneuropathy in the autonomic nervous system. Interestingly, GK rats showed adecreased baroreflex compared with control Wistar rats. Furthermore, GK rats showed limited fluctuation changesin beat-to-beat dynamics. In the frequency domain analysis, the low-frequency component was similar but the highfrequencycomponent was significantly decreased in GK rats, suggesting decreased parasympathetic nerve regulationand conserved sympathetic nerve regulation. In addition, GK rats showed a limited response to high-dose atropine, amuscarinic receptor antagonist, indicating modified parasympathetic nerve regulation in GK rats. Our data stronglysuggests that GK rat could be a nice animal model for chronic cardiovascular disease related to diabetic neuropathy.
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| 8.
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Matsumoto, Anna ; Kushikata, Tetsuya ; Hirota, Kazuyoshi
概要:
In kidney transplantation, stable hemodynamics is essential to preserve graft function. We used ketamine as an anestheti
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c because of its sympathomimetic properties. On the other hand, ketamine has several adverse effects, such as prolonged emergence from anesthesia or psychological reactions. Altered ketamine pharmacokinetics was previously reported in rabbits with renal nsufficiency, but no study has examined human living kidney transplantation, which has the potential to cause renal nsufficiency in the donor and recipient. Therefore, we evaluated ketamine pharmacokinetics in the donor and recipient of living kidney transplantation in various situation including ABO blood type-compatible and -incompatible transplantation.Materials and Methods: We examined the ketamine pharmacokinetics in donors （n=8）, and ABO blood type -compatible （n=8） and -incompatible （n=8） recipients of living kidney transplantation. We also measured the estimated glomerular filtration ratio（ eGFR）, blood urea nitrogen（ BUN）, and serum creatinine in these patients.Results: The time course of changes in the ketamine level after stopping ketamine administration did not differ between the donors and recipients. We also found that the eGFR in recipients gradually improved 48 h after the kidney transplantation. No patient developed ketamine-related adverse effects or allograft rejection.Conclusion: We conclude that ketamine can be safely applied as an adjuvant with intravenous anesthesia during ABO blood type-compatible and -incompatible living kidney transplantation.
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