[show abstract][hide abstract] ABSTRACT: BACKGROUND: Although a decrease in serum potassium level has been suggested to be a fairly common observation in acute coronary syndrome (ACS), there have so far been no definitive reports directly demonstrating the transient potassium decrease (the potassium dip) during ischemic attack of ACS compared to stable phase in individual patients. To understand the pathophysiological significance of the potassium dip, we examined the changes in serum potassium level throughout ischemic attack and evaluated the clinical factors affecting it. METHODS: The degree of the potassium dip during ischemic attack (as indicated by DeltaK, DeltaK = K at discharge - K on admission) was examined in 311 consecutive patients with ACS who required urgent hospitalization in our institution. RESULTS: Serum potassium level during ischemic attack was significantly decreased compared to that during stable phase (P < 0.001). Multiple regression analysis revealed that plasma glucose level during attack was the sole factor which was positively correlated with DeltaK (P < 0.01), while HbA1c level was negatively correlated (P < 0.05). The medication profiles and renal function had no impact on DeltaK. A longer hospitalization period, higher incidence of myocardial infarction and higher peak creatine kinase level were observed in patients with a larger DeltaK. CONCLUSIONS: We have clearly demonstrated that there is a transient decrease in serum potassium level during ischemic attack of ACS compared to stable phase. The degree of the potassium dip was tightly correlated with glucose level, which overwhelmed the diabetic condition, and it also indicates the disease severity. The present study therefore promotes awareness of the significance of monitoring potassium level in parallel with glucose level in patients with ACS.
[show abstract][hide abstract] ABSTRACT: Plasma B-type natriuretic peptide (BNP) is finely regulated by the cardiac function and several extracardiac factors. Therefore, the relationship between the plasma BNP levels and the severity of heart failure sometimes seems inconsistent. The purpose of the present study was to investigate the plasma BNP levels in patients with cardiac tamponade and their changes after pericardial drainage. This study included 14 patients with cardiac tamponade who underwent pericardiocentesis. The cardiac tamponade was due to malignant diseases in 13 patients and uremia in 1 patient. The plasma BNP levels were measured before and 24-48 h after drainage. Although the patients reported severe symptoms of heart failure, their plasma BNP levels were only 71.2 ± 11.1 pg/ml before drainage. After appropriate drainage, the plasma BNP levels increased to 186.0 ± 22.5 pg/ml, which was significantly higher than that before drainage (P = 0.0002). In patients with cardiac tamponade, the plasma BNP levels were low, probably because of impaired ventricular stretching, and the levels significantly increased in response to the primary condition after drainage. This study demonstrates an additional condition that affects the relationship between the plasma BNP levels and cardiac function. If inconsistency is seen in the relationship between the plasma BNP levels and clinical signs of heart failure, the presence of cardiac tamponade should therefore be considered.
[show abstract][hide abstract] ABSTRACT: Both aldosterone and Akt signaling play pivotal roles in the pathogenesis of heart failure. However, little is known about the correlation between them. We herein investigated whether aldosterone interacts with Akt signaling in a coordinated manner in cardiomyocytes. Neonatal rat cardiomyocytes were stimulated with aldosterone for either a short (10-min) or long (24-h) time. The phosphorylation of Akt and its downstream effector, GSK3β, were transiently increased after short-term stimulation, which was blocked by either PI3K or Na+/H+ exchanger inhibitors, but not by the mineralocorticoid receptor antagonist, eplerenone. Long-term stimulation also significantly increased Akt-GSK3β phosphorylation and this effect was reduced by eplerenone. Thus, these results suggest that aldosterone activates Akt signaling via a biphasic reaction that occurs through different cascades. To understand the significance of the rapid action of aldosterone, cardiomyocytes were exposed to hydrogen peroxide for from 10 to 60 min. A short-term aldosterone stimulation (for up to 30 min) significantly protected cardiomyocytes from oxidative stress-induced cellular damage. Eplerenone did not abrogate this beneficial effect, while a PI3K inhibitor did. Therefore, during the early phase, aldosterone has favorable effects on cardiomyocytes, partly by acute activation of a mineralocorticoid receptor-independent cascade through the Na+/H+ exchanger, PI3K, and Akt. In contrast, its persistent activity produces pathological effects partly by chronic Akt activation in a mineralocorticoid receptor-dependent manner.
Hormone and Metabolic Research 07/2012; · 2.15 Impact Factor
[show abstract][hide abstract] ABSTRACT: Obesity has recently been shown to have a favorable effect on the prognosis of patients with congestive heart failure (CHF), but only a few such studies are available in Japan. The purpose of the present study was to investigate whether the obesity paradox is still present after adjusting for CHF characteristics.
A total of 219 patients hospitalized with CHF were reviewed, and the impact of body mass index (BMI) on prognosis was examined. Patients were divided into 4 groups according to BMI quartiles. The endpoint was defined as all-cause death or unplanned CHF hospitalization. According to univariate analysis, a higher BMI was associated with better outcomes. High-BMI patients were younger, likely to be male, and had a higher prevalence of hypertension and diabetes. The plasma B-type natriuretic peptide (BNP) levels and blood urea nitrogen (BUN) levels were lower, while the serum hemoglobin and sodium levels were higher in high-BMI patients. The prevalence of atrial fibrillation was lower in high-BMI patients. Predictors for all-cause death or CHF hospitalization based on univariate analysis were age, prior CHF hospitalization, estimated glomerular filtration rate, plasma BNP levels, BUN levels, and serum hemoglobin and sodium levels. According to multivariate analysis, a high BMI was still associated with better outcomes.
High BMI was associated with better clinical outcomes in Japanese CHF patients.
[show abstract][hide abstract] ABSTRACT: Neural blockades are considered an alternative to pharmacotherapy for neuropathic pain although these blockades elicit limited effects. We encountered a patient with postbrachial plexus avulsion injury pain, which was refractory to conventional treatments but disappeared temporarily with the administration of the local anesthetic lidocaine around the left mandibular molar tooth during dental treatments. This analgesic effect on neuropathic pain by oral local anesthesia was reproducible. Under conditions of neuropathic pain, cerebral somatotopic reorganization in the sensorimotor cortices of the brain has been observed. Either expansion or shrinkage of the somatotopic representation of a deafferentated body part correlates with the degree of neuropathic pain. In our case, administration of an oral local anesthetic shrank the somatotopic representation of the mouth, which is next to the upper limb representation and thereby expanded the upper limb representation in a normal manner. Consequently, oral local anesthesia improved the pain in the upper limb. This case suggests that pain alleviation through neural plasticity within the brain is related to neural blockade.
Anesthesiology Research and Practice 01/2011; 2011:984281.
[show abstract][hide abstract] ABSTRACT: This study evaluated the relationship between the severity of coronary artery disease (CAD) and traditional coronary risk factors, metabolic syndrome, and chronic kidney disease (CKD). Three hundred and forty-three patients (35-90 years of age) with initial diagnosis of CAD were separated into two groups: 165 patients with single-vessel coronary artery disease (SVD group) and 178 patients with multivessel coronary artery disease (MVD group). We compared the risk factors for CAD between the two groups. An adjusted multivariate analysis showed that only CKD was associated with MVD (odds ratio, 2.85; 95% confidence interval [CI], 1.76-4.63; P = 0.00002). Next, the relationship between the severity of CAD, CKD, and the incidence of subsequent major adverse cardiac event (MACE) was investigated in 338 patients during the patient follow-up. The risk of MACE was approximately threefold higher in the group with MVD and CKD stage of 3 or greater than in the group with SVD but without CKD stage of 3 or greater (adjusted hazard ratio, 3.40; 95% CI, 1.26-9.17; P = 0.016). A statistical analysis also suggested that having MVD and advanced CKD was a more powerful risk factor for MACE. The comparison of risk factors between patients with SVD and patients with MVD revealed that CKD was the most important risk factor for MVD. In addition, having MVD and advanced CKD together was a crucial risk factor for subsequent MACE. To reduce the progression of CAD and to improve the prognosis of patients with MVD, the renal status should therefore be carefully assessed during treatment for CAD.
Heart and Vessels 12/2010; 26(4):370-8. · 2.13 Impact Factor
[show abstract][hide abstract] ABSTRACT: In this study, we investigated the effects of processed Aconiti tuber (PAT), an oriental herbal medicine, at analgesic doses on acute morphine antinociception in morphine-naïve mice and morphine tolerance in morphine-tolerant mice.
In acute experiments, mice received subcutaneous (s.c.) morphine (2, 5, or 10 mg/kg) and oral distilled water or PAT (0.3, 1.0, or 3.0 g/kg). The mechanical nociceptive threshold (MNT) and thermal nociceptive latency (TNL) were measured with the tail pressure test and tail flick test, respectively, before, and at 30, 60, 90, and 120 min after s.c. morphine injection. In chronic experiments, mice received s.c. morphine (10 mg/kg) and oral distilled water or PAT (0.3, 1.0, or 3.0 g/kg) once daily for 11 days. MNT was measured before, and at 60 min after, and TNL was measured before, and at 30 min after, daily morphine injections on days 1-11.
PAT at analgesic doses inhibited the acute antinociceptive effect of morphine dose-dependently in morphine-naïve mice. In contrast, PAT at analgesic doses potentiated the chronic antinociceptive effect of morphine dose-dependently by inhibiting the development of morphine tolerance dose-dependently. These effects of PAT on acute and chronic morphine antinociception were mediated through activation of kappa-opioid receptors.
These results indicated that chronic co-administration of PAT at analgesic doses with morphine could provide better-maintained morphine analgesia in a long-term morphine treatment after initial inhibition of acute morphine antinociception for a brief period of time.
Journal of Ethnopharmacology 08/2008; 119(2):276-83. · 2.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: Clonidine can effectively reduce pain and/or hypersensitivity. However, the antihypersensitivity effects of clonidine topically applied in cream (CC) have not been investigated. The authors evaluated effects of topical application of CC on pain behaviors and spinal Fos-like immunoreactivity in rats with hypersensitivity.
Clonidine (30, 100, and 300 microg/g) was prepared in a cream base. In rat models of neuropathic pain, inflammatory pain, and postoperative pain, the authors evaluated effects of CC (0.1 g), topically applied onto the plantar surface of the injured or uninjured paw, on thermal hyperalgesia and mechanical allodynia to von Frey filaments. The authors also evaluated effects of CC on lumbar spinal Fos-like immunoreactivity.
In neuropathic rats, CC applied onto the injured paw reduced thermal hyperalgesia and mechanical allodynia dose dependently, whereas CC applied onto the uninjured paw had no effect. The antihypersensitivity effects of CC were antagonized by intraperitoneal yohimbine (10 mg/kg). Further, CC reduced Fos-like immunoreactivity in neuropathic rats. In contrast, CC in a single dose had no effects on hyperalgesia, allodynia, or Fos-like immunoreactivity in rats with inflammatory or postoperative pain. In rats with postoperative pain, CC repeatedly applied for 6 days reduced thermal hyperalgesia, but not mechanical allodynia, in the postoperative days, whereas it had no effects on hyperalgesia or allodynia in those with inflammatory pain.
Topical CC in concentrations examined significantly reduced hypersensitivity and lumbar spinal Fos-like immunoreactivity in rats with neuropathic pain, probably through activation of peripherally located alpha2 adrenoceptors. However, CC was only partially effective and totally ineffective in rats with postoperative pain and inflammatory pain, respectively.
[show abstract][hide abstract] ABSTRACT: In the previous studies, we demonstrated that an oriental herbal medicine processed Aconiti tuber (PAT) at subanalgesic doses could inhibit the development of mechanical antinociceptive tolerance to morphine using the tail pressure test. In the present study, we evaluated whether PAT could inhibit thermal antinociceptive tolerance to morphine using the high temperature (55 degrees C) hot plate test. Mice received subcutaneous morphine (10mg/kg), and oral PAT at doses that did not inhibit the hot plate response (0.3, 0.5, 1.0, and 2.0 g/kg), once daily for 14 days. The thermal nociceptive latency was measured at 30 min after daily morphine injections. Compared with placebo, oral PAT partially and dose-dependently inhibited the development of morphine tolerance in morphine-naïve mice, and reversed already-developed morphine tolerance in morphine-tolerant mice. These data suggested that PAT at subanalgesic doses could dose-dependently inhibit and reverse thermal antinociceptive tolerance to morphine.
Journal of Ethnopharmacology 10/2007; 113(3):560-3. · 2.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: The effect of linear polarized light irradiation around the lumbar sympathetic ganglion area upon the skin temperature of legs may be similar to that of irradiation of near stellate ganglion area upon arms.
Linear polarized light irradiation was induced with SUPER LIZER (Tokyo Iken, Tokyo, Japan). The C probe of SUPER LIZER was placed on the left side of the supine at the level of L2.
Seven-minute irradiation around the lumbar sympathetic ganglion area increased significantly the skin temperature of the irradiated side leg.
These results suggest that linear polarized light irradiation around the lumbar sympathetic ganglion area might be useful and beneficial for clinical application.
Masui. The Japanese journal of anesthesiology 07/2007; 56(6):706-7.
[show abstract][hide abstract] ABSTRACT: No systematic study has been conducted to investigate effects of deep hypothermic circulatory arrest (DHCA) on electroencephalographic bispectral index (BIS) and suppression ratio (SR). Thus, the effects of DHCA were evaluated on BIS and SR.
A prospective clinical study.
University hospital (single institute).
Twenty consecutive patients undergoing thoracic aortic surgery using DHCA under narcotics-sevoflurane anesthesia.
BIS and SR were monitored during cardiopulmonary bypass, simultaneously with nasopharyngeal temperature (NPT).
BIS decreased to 0 with induction of deep hypothermia and rose again with rewarming, although rates of BIS changes in response to cooling and rewarming varied widely among patients. Typically, BIS decreased slowly until NPT reached 26 degrees C during cooling and then it began to decrease rapidly and reached 0 at 17 degrees C, in inverse proportion to SR, which increased rapidly with deep hypothermia and reached 100% at 17 degrees C. When SR was 50% or more, BIS was determined by SR according to the expression: BIS = 50-SR/2. With rewarming, BIS rose again and returned to precooling baseline levels. Time to the beginning of the BIS recovery significantly correlated with duration of DHCA.
With induction of deep hypothermia, BIS decreased in a biphasic manner to 0 at rates varying among patients. With rewarming, BIS rose again at rates extremely widely varying among patients. The rate of BIS recovery was related to duration of DHCA. BIS may be capable of conveniently tracing suppression and recovery of a part of cerebral electrical activity before, during, and after DHCA.
Journal of Cardiothoracic and Vascular Anesthesia 03/2007; 21(1):61-7. · 1.45 Impact Factor
[show abstract][hide abstract] ABSTRACT: Previously, we found that processed Aconiti tuber (PAT) could inhibit morphine tolerance in mice. In the present study, we investigated mechanisms underlying this effect. Mice received subcutaneous (s.c.) morphine (10 mg/kg) and oral PAT at a subanalgesic dose (0.3 g/kg), once a day for 12 days. Additional PAT-treated groups received morphine and PAT, at 120 min after pretreatment with s.c. clocinnamox mesylate (C-CAM) (0.5 mg/kg), or nor-binaltorphimine (nor-BNI) (5 mg/kg). The antinociceptive effect was assessed with the tail pressure test, at 60 min after the daily s.c. morphine injections were given. In the placebo-treated group, repeated morphine injections caused morphine tolerance, and morphine antinociception was abolished by day 6, whereas in PAT-treated groups, significant antinociception was maintained until day 12, suggesting that PAT inhibited morphine tolerance, thereby sustaining morphine antinociception. C-CAM, a selective mu-opioid receptor (MOR) antagonist, blocked morphine antinociception whereas nor-BNI, a selective kappa-opioid receptor (KOR) antagonist, did not. However, both C-CAM and nor-BNI could block the antinociception maintained by the morphine-PAT combination. Results of the study suggested that chronic treatment with PAT at a subanalgesic dose maintained MOR-mediated morphine antinociception by attenuating development of morphine tolerance, and that this tolerance-attenuating effect of PAT was mediated by KOR.
Journal of Ethnopharmacology 07/2006; 106(2):263-71. · 2.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: Drug challenge test (DCT) is performed to evaluate chronic pain pharmacologically and determine its medical treatment. One test drug is administered in one day for DCT and characterization of the test drug. Four patients developed side effects of the test drugs for DCT in whom other drug tests were postponed or canceled. A 58-year-old man with multiple arthritis of rheumatic arthritis and fibromyalgia had headache, nausea, and vomiting all day after ketamine test. A 76-year-old man with chronic general pain and failed back surgery syndrome had vomiting and abdominal discomfort two hours after morphine test and had redness and itching on his bilateral forearms the following day. A 78-year-old man with chronic lumbar and right lower limb pain due to L 4-5 lumbar disc herniation and postherpetic neuralgia felt dizzy, fell down and bruised on his lower back and left knee twelve hours after morphine test. A 32-year-old woman with chronic pelvic pain had skin eruption on her thigh the day after phentolamine test. Although the amount of the test drug in DCT is small and its half-life is short, long-term side effects might occur. We should decrease the amounts or frequencies of ketamine and morphine, and administer them taking long intervals before other tests.
Masui. The Japanese journal of anesthesiology 03/2006; 55(2):169-73.
[show abstract][hide abstract] ABSTRACT: Processed Aconiti tuber (PAT) is a herbal medicine that has been widely used as an analgesic since ancient times. We investigated effects of subanalgesic doses of PAT on morphine tolerance in mice. Mice received subcutaneous morphine (10 mg/kg) and oral PAT at subanalgesic doses (0.1 or 0.3 g/kg), once a day for 7 days. Mechanical nociceptive thresholds were measured using the tail pressure test, at 60 min after the daily s.c. morphine injections. In the placebo-treated group, repeated administration of s.c. morphine resulted in development of analgesic tolerance. In the PAT-treated groups, oral PAT attenuated morphine tolerance, dose-dependently. The main ingredient alkaloid of PAT causing its tolerance-attenuating activity was mesaconitine, but other ingredient alkaloids, such as aconitine and hypaconitine, also contributed to this activity. In addition, repeated treatment with PAT could reverse already-developed morphine tolerance. Subanalgesic doses of oral PAT thus can attenuate and reverse morphine tolerance in mice.
Journal of Ethnopharmacology 03/2006; 103(3):398-405. · 2.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: Neuropathic pain is often refractory to conventional pain therapies and thus requires exploration of effective drugs. We evaluated if processed Aconiti tuber (PAT), a traditional oriental herbal medicine that has been used as an analgesic, relieves neuropathic pain in the rat chronic constriction injury (CCI) model. Ten to 14 days after CCI in the right hind paw, six groups of rats received oral placebo, or PAT at 0.5, 1, 2, 3, or 5 g/kg. Additional groups received oral PAT, 2 g/kg, after pretreatment with intraperitoneal naloxone; intraperitoneal nor-binaltorphimine (norBNI); or intrathecal norBNI. As indicators of mechanical allodynia and thermal hyperalgesia, the pressure threshold of paw withdrawal (PWT) in response to linearly increasing pressure, and latency to paw withdrawal (PWL) in response to radiant heat, were measured before and after drug administration. Oral PAT dose-dependently increased PWT and PWL, which had been decreased due to CCI. The increases in PWT and PWL by oral PAT were inhibited by intraperitoneal and intrathecal norBNI: a selective kappa-opioid receptor antagonist, but not by intraperitoneal naloxone. These results indicate that oral PAT can alleviate mechanical allodynia and thermal hyperalgesia, dose-dependently, via spinal kappa-opioid receptor mechanisms in a rat CCI neuropathic pain model.
Journal of Ethnopharmacology 03/2006; 103(3):392-7. · 2.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: Lines of evidence have indicated that cyclooxygenase 2 plays a role in the pathophysiology of neuropathic pain. However, the site and mechanism of its action are still unclear. Spinal glia has also been reported to mediate pathologic pain states. The authors evaluated the effect of continuous intrathecal or systemic cyclooxygenase-2 inhibitor on the development and maintenance of neuropathic pain and glial activation in a spinal nerve ligation model of rats.
Continuous intrathecal infusion of meloxicam (32 or 320 mug . kg . day) or saline was started immediately after L5-L6 spinal nerve ligation. Mechanical allodynia and thermal hyperalgesia were evaluated on days 4 and 7 postoperatively. Spinal astrocytic activation was evaluated with glial fibrially acidic protein immunoreactivity on day 7. In other groups of rats, continuous intrathecal meloxicam was started 7 days after spinal nerve ligation, and effects on established neuropathic pain and glial activation were evaluated. Last, effects of continuous systemic meloxicam (16 mg . kg . day) on existing neuropathic pain and glial activation were examined.
Intrathecal meloxicam prevented the development of mechanical allodynia and thermal hyperalgesia induced by spinal nerve ligation. It also inhibited spinal glial activation responses. In contrast, when started 7 days after the nerve ligation, intrathecal meloxicam did not reverse established neuropathic pain and glial activation. Systemic meloxicam started 7 days after ligation partially reversed neuropathic behaviors but not glial activation.
Spinal cyclooxygenase 2 mediates the development but not the maintenance of neuropathic pain and glial activation in rats. Peripheral cyclooxygenase 2 plays a part in the maintenance of neuropathic pain.
[show abstract][hide abstract] ABSTRACT: Children frequently suffer transient cerebral ischaemia during cardiac surgery. We measured cerebral ischaemia in children during cardiac surgery by combining two methods of monitoring.
We studied 65 children aged between 5 months and 17 yr having surgery to correct non-cyanotic heart disease using hypothermic cardiopulmonary bypass (CPB). During surgery, we measured the Bispectral Index (BIS) and regional cerebral haemoglobin oxygen saturation (SrO2) with near-infrared spectroscopy (NIRS). Cerebral ischaemia was diagnosed if both SrO2 and BIS decreased abruptly when acute hypotension occurred. In each patient, the relationship between SrO2 and arterial blood pressure (AP) was indicated by a plot of mean SrO2 against simultaneous mean AP.
We noted 72 episodes of cerebral ischaemia in 38 patients. Sixty-three ischaemic events were during CPB. Cerebral ischaemia was less frequent in older patients. Cerebral ischaemia was more common and more frequent in children under 4 yr old. Haematocrit during CPB was lower and SrO2 was more dependent on AP in children under 4 yr.
Children less than 4 yr of age are more likely to have cerebral ischaemia caused by hypotension during cardiac surgery. Ineffective cerebral autoregulation and haemodilution during CPB may be responsible.
BJA British Journal of Anaesthesia 06/2004; 92(5):662-9. · 4.24 Impact Factor
[show abstract][hide abstract] ABSTRACT: Basic data are lacking regarding the efficacy and mechanisms of action of corticosteroids in neuropathic pain. Because recent studies indicate that spinal glial activation mediates the pathologic pain states, the authors sought to determine the effects of systemic and intrathecal methylprednisolone on the development and maintenance of neuropathic pain and spinal glial activation in a rat model.
Rats were anesthetized, and L5 and L6 spinal nerves were tightly ligated. Then, continuous infusion of systemic (4 mg x kg(-1) x day(-1)) or intrathecal (80 microg x kg(-1) x day(-1)) methylprednisolone or saline was started. Mechanical allodynia and thermal hyperalgesia were evaluated on days 4 and 7 postoperatively with von Frey and Hargreaves tests, respectively. Spinal astrocytic activation was evaluated with glial fibrillary acidic protein immunoreactivity on day 7. In other groups of rats, continuous 3-day treatment with intrathecal methylprednisolone or saline was started 7 days after spinal nerve ligation, when neuropathic pain had already developed. Behavioral tests and immunostaining were performed up to 3 weeks after the treatment.
Spinal nerve ligation induced mechanical allodynia and thermal hyperalgesia on days 4 and 7 postoperatively. Glial fibrillary acidic protein immunoreactivity was remarkably enhanced on day 7. Both systemic and intrathecal methylprednisolone inhibited the development of neuropathic pain states and glial activation. Three-day treatment with intrathecal methylprednisolone reversed existing neuropathic pain state and glial activation up to 3 weeks after the treatment.
: Systemic and intrathecal methylprednisolone inhibited spinal glial activation and the development and maintenance of a neuropathic pain state in a rat model of spinal nerve ligation.