Biomedical subjects

T Shishido

Publications and source records attributed to T Shishido.

At least 19 recordsLinked to original sources

PubMed2005

Myocardial interstitial choline and glutamate levels during acute myocardial ischaemia and local ouabain administration.

AIM: Noradrenaline (NA) uptake transporters are known to reverse their action during acute myocardial ischaemia and to contribute to ischaemia-induced myocardial interstitial NA release. By contrast, functional roles of choline and glutamate transporters during acute myocardial ischaemia remain to be investigated. Because both transporters are driven by the normal Na+ gradient across the plasma membrane in a similar manner to NA transporters, the loss of Na+ gradient would affect the transporter function, which would in turn alter myocardial interstitial choline and glutamate levels. The aim of the present study was to examine the effects of acute myocardial ischaemia and the inhibition of Na+,K+-ATPase on myocardial interstitial glutamate and choline levels. METHODS: In anaesthetized cats, we measured myocardial interstitial glutamate and choline levels while inducing acute myocardial ischaemia or inhibiting Na+,K+-ATPase by local administration of ouabain. RESULTS: The choline level was not changed significantly by ischaemia (from 0.93 +/- 0.06 to 0.82 +/- 0.13 microm, mean +/- SE, n = 6) and was decreased slightly by ouabain (from 1.30 +/- 0.06 to 1.05 +/- 0.07 microm, P < 0.05, n = 6). The glutamate level was significantly increased from 9.5 +/- 1.9 to 34.7 +/- 6.1 microm by ischaemia (P < 0.01, n = 6) and from 8.9 +/- 1.0 to 15.9 +/- 2.3 microm by ouabain (P < 0.05, n = 6). Inhibition of glutamate transport by trans-L-pyrrolidine-2,4-dicarboxylate (t-PDC) suppressed ischaemia- and ouabain-induced glutamate release. CONCLUSION: Myocardial interstitial choline level was not increased by acute myocardial ischaemia or by Na+,K+-ATPase inhibition. By contrast, myocardial interstitial glutamate level was increased by both interventions. The glutamate transporter contributed to glutamate release via retrograde transport.

Acetylcholine↗

PubMed2005

Morphological studies on the ageing and osteoarthritis of the articular cartilage in C57 black mice.

PURPOSE: To study the cause and mechanism of joint degeneration in osteoarthritis, through histopathological and ultrastructural-histochemical experiments on the articular cartilage of the knees of the C57 black mouse. METHODS: 192 C57 black mice and a control group of 64 C57BL/6J mice were used in this study. The left and right knee articular capsules of the joints were removed and stained. Each articular cartilage sample was examined and osteoarthritic changes were assessed using a transmission electron microscope. The severity of osteoarthritis in the knee joint cartilage of C57 black mice was histologically assessed using a classification system described by Okabe, based on Maier's system. RESULTS: The incidence and the severity of osteoarthritis gradually increased with age; the incidence increased from 20% at 2 months to 80% at 16 months. Irreversible changes appeared at an advanced stage, and the process of degeneration was quite similar to that in human osteoarthritis. Through transmission electron microscopy, we observed poorly developed Golgi apparatus, markedly increased intracellular microfilaments, decreased proteoglycan granules, and broken collagen networks in all stages of osteoarthritis. By contrast, Golgi apparatus and other organelles were well developed in histologically normal mice of all ages. Proteoglycan granules, which mainly consisted of keratan sulphate, were observed; collagen networks were maintained. CONCLUSION: Disturbed protein transport and sugar synthesis in chondrocytes, caused by the deficient development of the Golgi apparatus, could result in degenerative changes in articular cartilage. The structure and function of the matrix were maintained mainly because of the continued presence of keratan sulphate.

Aging↗

PubMed2004

Activation of distinct signal transduction pathways in hypertrophied hearts by pressure and volume overload.

OBJECTIVE: Two types of hemodynamic overload, pressure and volume overload, result in morphologically distinct types of cardiac remodeling. We explored the possibility that distinct hemodynamic overload may differentially activate the signal transduction pathway. METHODS: Pressure and volume overload were induced by thoracic aortic banding and carotid-jugular shunt formation in rabbits, respectively. Phosphorylation activities of mitogen-activated protein (MAP) kinase families, Akt, and signal transducer and activator of transcription (STAT) 3 in the left ventricular myocardium were determined by Western blotting using phospho-specific antibodies and were compared between hypertrophied hearts by pressure and volume overload. RESULTS: Pressure and volume overload produced concentric and eccentric cardiac hypertrophy in rabbits, respectively. In pressure-overloaded hearts, extracellular signal-regulated kinase (ERK) 1/2, p38 MAP kinase, and STAT3 were transiently activated prior to hypertrophic changes. In contrast, activation of ERK1/2, but not p38 MAP kinase and STAT3, was observed only at 12 weeks after shunt surgery. Pressure overload evoked short and biphasic activation of Akt at 15 min and 1 day after aortic banding. In contrast, volume overload induced sustained activation of Akt from 1 day to 1 week. Concordant phosphorylation of downstream targets of Akt, glycogen synthase kinase-3beta (GSK-3beta) and p70 ribosomal S6 kinase (p70(S6K)), in response to Akt activation was observed at 15 min after pressure overload. However in volume-overloaded hearts, phosphorylation of GSK-3beta and p70(S6K) was observed at 6 weeks and at 6 and 12 weeks, respectively, and was not coincident with Akt activation. These findings suggest that phosphorylation of GSK-3beta and p70(S6K) is regulated by an alternative pathway other than Akt in volume-overloaded hearts. CONCLUSION: Pressure and volume overload-induced cardiac hypertrophy is associated with distinct patterns of activation of signal transduction pathways. These data may suggest that stimulus-specific heterogeneity in the signaling pathway plays a role in determining the type of cardiac hypertrophy.

Animals↗

PubMed2004

Protein kinase C and extracellular signal regulated kinase are involved in cardiac hypertrophy of rats with progressive renal injury.

Increased cardiovascular mortality is an unresolved problem in patients with chronic renal failure. Cardiac hypertrophy is observed in the majority of patients with chronic renal failure undergoing haemodialysis. However, the mechanisms, including signal transduction pathways, responsible for cardiac hypertrophy in renal failure remain unknown. We examined the subcellular localization of protein kinase C (PKC) isoforms and phosphorylation activities of 3 mitogen-activated protein (MAP) kinase families in hypertrophied hearts of progressive renal injury rat model by subtotal nephrectomy (SNx). We also examined the effects of a novel angiotensin II type-1 receptor antagonist, CS-866, on the PKC translocation, MAP kinase activity and cardiac hypertrophy in SNx rats. The left ventricle/body weight ratios were significantly larger in SNx rats than in sham rats at 1, 2, and 4 weeks after surgery. The translocation of PKCalpha and epsilon isoforms to membranous fraction was observed in SNx rat hearts at 1, 2, and 4 weeks after surgery. Activation of extracellular signal regulated kinase (ERK) 1/2, but not p38 MAP kinase and c-Jun N-terminal kinase (JNK), was observed at 1 and 2 weeks after surgery. Angiotensin II receptor blockade with CS-866 (1 mg kg-1 day-1) prevented cardiac hypertrophy, PKC translocation and ERK1/2 activation in SNx rats without significant changes in blood pressure. These data suggest that PKC and ERK1/2 are activated by an angiotensin II receptor-mediated pathway and might play an important role in the progression of cardiac hypertrophy in renal failure.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2004

Fatty acid metabolism assessed by 125I-iodophenyl 9-methylpentadecanoic acid (9MPA) and expression of fatty acid utilization enzymes in volume-overloaded hearts.

BACKGROUND: The peroxisome proliferator-activated receptor (PPAR) alpha is a member of the nuclear receptor superfamily and regulates gene expression of fatty acid utilization enzymes. In cardiac hypertrophy and heart failure by pressure-overload, myocardial energy utilization reverts to the fetal pattern, and metabolic substrate switches from fatty acid to glucose. However, myocardial metabolism in volume-overloaded hearts has not been rigorously studied. The aim of the present study was to examine fatty acid metabolism and protein expressions of PPARalpha and fatty acid oxidation enzymes in volume-overloaded rabbit hearts. METHODS: Volume-overload was induced by carotid-jugular shunt formation. Sham-operated rabbits were used as control. Chronic volume-overload increased left ventricular weight and ventricular cavity size, and relative wall thickness was decreased, indicating eccentric cardiac hypertrophy. (125)I-iodophenyl 9-methylpentadecanoic acid (9MPA) was intravenously administered, and animals were sacrificed at 5 min after injection. The 9MPA was rapidly metabolized to iodophenyl-3-methylnonanoic acid (3MNA) by beta-oxidation. Lipid extraction from the myocardium was performed by the Folch method, and radioactivity distribution of metabolites was assayed by thin-layer chromatography. The protein was extracted from the left ventricular myocardium, and levels of PPARalpha and fatty acid oxidation enzymes were examined by Western blotting. RESULTS: Myocardial distribution of 9MPA tended to be more heterogeneous in shunt than in sham rabbits (P = 0.06). In volume-overloaded hearts by shunt, the conversion from 9MPA to 3MNA by beta-oxidation was faster than the sham-control hearts (P < 0.05). However, protein levels of PPARalpha and fatty acid utilization enzymes were unchanged in shunt rabbits compared with sham rabbits. CONCLUSIONS: These data suggest that myocardial fatty acid metabolism is enhanced in eccentric cardiac hypertrophy by volume-overload without changes in protein expressions of PPARalpha and fatty acid utilization enzymes. Our data may provide a novel insight into the subcellular mechanisms for the pathological process of cardiac remodelling in response to mechanical stimuli.

Animals↗

PubMed2004

Effects of ethane-1-hydroxy-1,1-diphosphonate on ossification of the posterior longitudinal ligament in Zucker fatty rats.

PURPOSE: Using Zucker fatty rats as an animal model, we evaluate the effectiveness of ethane-1-hydroxy-1,1-diphosphonate on ossification of the posterior longitudinal ligament by histopathologically investigating the prodromal, early, and advanced stages of ossification of the spinal ligaments. METHODS: 73 Zucker fatty rats were allocated to the ethane-1-hydroxy-1,1-diphosphonate group (n=33) and the control group (n=40). The former group was fed ethane-1-hydroxy-1,1-diphosphonate daily. The feed was given starting 2 months after birth and continued until the rats were killed at 3 to 18 months later. Chemical analysis of the blood, radiographic tests, and histopathological examination were then conducted for both groups. RESULTS: The results showed that ossification of the spinal ligaments involved excessive cartilage cell proliferation around areas affected by enthesitis; enlargement of the fibrocartilage tissue layer; ligament thickening; calcification of the matrix around the cartilage cells; and ossification of the spinal ligaments through enchondral ossification. Radiographic examinations showed that osteoproliferation in vertebral bodies in rats receiving ethane-1-hydroxy-1,1-diphosphonate was generally suppressed compared with controls, whereas histopathological examinations found no clear difference in cartilage cell proliferation in areas affected by enthesitis between the two groups, indicating the absence of calcification or osteo-proliferation in areas affected by enthesitis for the rats receiving ethane-1-hydroxy-1,1-diphosphonate. CONCLUSION: Ethane-1-hydroxy-1,1-diphosphonate is effective in suppressing progressive ligament ossification.

Animals↗

PubMed2004

Traumatic anterior dislocation of the hip associated with ipsilateral femoral shaft fracture in a child: a case report.

Traumatic anterior dislocation of the hip joint in children is rare, and only one case with ipsilateral femoral fracture has been reported in Japan. We report a case of such dislocation and a review of the literature. The patient was a 31-month-old girl who was injured in a car accident while asleep on a tilted front passenger seat. Radiographic examination showed dislocation of the right obturator foramen and transverse fracture of the ipsilateral femoral shaft. The dislocation of the right hip was easily reduced without anaesthesia during radiography. We applied Bryant traction after reduction for 4 weeks, followed by cast application for 3 weeks. Walking with support and full weightbearing were permitted 14 weeks and 16 weeks after the injury, respectively. Radiography at 4.5 years after the injury showed a mildly enlarged right femoral head and femur overgrowth of approximately 8 mm. Magnetic resonance imaging showed no evidence of suspected avascular necrosis of the femoral head. The patient has no subjective or objective symptoms, and is able to engage in all usual activities. The detailed mechanism of the injury is unknown. We assume that the lower leg was dislocated through abduction during flexion, or abducent, external flexion, considering that the child was sleeping at the time of the accident. Since she was hurled to the back seat, it was assumed that strong external force was vertically added to the femur, which caused the abducent force.

Accidents, Traffic↗

PubMed2003

Clinical and simulator wear study of alumina ceramic THR to 17 years and beyond.

Three THAs with cementless monolithic alumina ceramic sockets and cementless Co-alloy stems were retrieved because of aseptic loosening after 17 and 24 years. At revision heads and cups were marked for orientation. Maps were drawn of wear patterns with the use of light microscopy and surveyed by SEM. In a simulator experiment 28-mm-diameter alumina heads and liners were used. The cups were mounted inverted in a hip simulator and run with calf serum as the lubricant. The hip loads were 2 kN maximum and a 1-Hz frequency for 20 million cycles. Wear severity was classified into five grades. In retrieved implants, SEM analysis showed that the main wear zones (MWZ) had Grade 4 wear. The peripheral wear zones (PWZ) showed grain pull-out regions (Grade 5 wear). These corresponded to neck-socket impingement and head-acetabular cup separation. Gray was due to transferred CoCr particles from the stem. In the simulator study, the MWZ had only localized areas of grain pull out surrounded by polished surface regions (Grade 4 wear) at 20 million cycles; stripe wear was not seen. The alumina ceramic bearings proved excellent up to 22 years in simulator studies and clinical studies. However, microseparation kinematics would be necessary in the simulator to duplicate the more peripheral wear zones.

Adult↗

PubMed2001

Heart rate-independent vagal effect on end-systolic elastance of the canine left ventricle under various levels of sympathetic tone.

BACKGROUND: Although we have shown that in rabbits the direct (heart rate [HR]-independent) vagal effect on left ventricular end-systolic elastance (E(es)) was negligible under minimal sympathetic tone, how underlying sympathetic tone modulates the inotropic response to vagal stimulation remains unknown. METHODS AND RESULTS: We used an isolated canine heart preparation with functioning autonomic nerves. We examined the direct vagal inotropic effect by measuring E(es) under fixed-rate atrial pacing with or without concomitant sympathetic nerve stimulation. Right and left vagal stimulation at 20 Hz decreased HR by 27+/-3% and 14+/-2%, respectively, and decreased E(es) by 11+/-2% and 6+/-2%, respectively. When we fixed HR by atrial pacing, right and left vagal stimulation at 20 Hz did not decrease E(es) (0.01+/-0.3% and 0.3+/-0.4%; NS). Concomitant left sympathetic nerve stimulation at 4 Hz enhanced direct vagal negative inotropism to -19+/-3% and -34+/-5% for 20-Hz right and left vagal stimulation (interaction, P<0.01). CONCLUSIONS: Direct vagal negative inotropism was unobservable with minimal sympathetic tone in dogs but was enhanced with concomitant sympathetic stimulation.

Animals↗

PubMed2001

Liver metastatic model for human gastric cancer established by orthotopic tumor cell implantation.

We have established an orthotopic implantation model that is highly metastatic to the liver. A human gastric carcinoma cell line, AZ521, with low capacity for liver metastasis was implanted as a single-cell suspension in the stomach of nude mice. The tumor cells derived from a few liver metastatic foci were subsequently implanted orthotopically, and we established a cell line, AZH5G, by repeating the in vivo stepwise selection method. This metastasizing line (AZH5G) developed liver metastasis in seven of eight (87.5%) cases, whereas parental AZ521 developed in 3 of 20 (15.0%). The in vitro growth activities of AZH5G were lower than that of AZ521, although the in vivo tumorigenicity of AZH5G was clearly higher than that of AZ521. Motility assays demonstrated higher motility of AZH5G than of AZ521. Flow cytometric analysis demonstrated that the expression of alpha 6-integrin significantly decreased in AZH5G (4.9% +/- 4.1%) compared to in AZ521 (17.7% +/- 8.1%) (p < 0.05). The adhesive activity of AZH5G cells to laminin was lower than that of AZ521 cells. In contrast, the adhesive activity of AZH5G cells to fibronectin was clearly higher than that of AZ521 cells. These findings suggested that changes in the expression of integrins on the cell surface might play an important role in metastatic ability. This well characterized line and its in vivo experimental model should be useful to investigate the mechanisms of liver metastasis and to develop a new therapeutic approach for human gastric cancer.

Adenocarcinoma↗

PubMed2001

Glycine reduces novelty- and methamphetamine-induced locomotor activity in neonatal ventral hippocampal damaged rats.

The use of neonatal ventral hippocampal nVH lesioned rats is well established in animal models of schizophrenia. Moreover, the dysfunction of N-methyl-D-aspartate (NMDA) neurotransmission may play a crucial role in the pathophysiology of schizophrenia. To examine the effect of glycine (GLY) in this animal model, we compared the effects of GLY (0.8 and 1.6 g/kg, IP) on locomotor activity induced by a novel environment (NOVEL) and methamphetamine (MAP, 1.5 mg/kg, IP) in lesioned and sham-operated rats. Compared with sham rats, GLY significantly reduced NOVEL- and MAP-induced locomotor activity in lesioned rats (p <.001 and p <.05, respectively). It is suggested that GLY attenuated nVH-induced hyperactivity, and that this effect was evident both in the presence and absence of MAP. The nVH lesions may result in a form of hyperactivity that differs from normal locomotion in the degree to which it is highly sensitive to regulation by GLY.

Animals↗

PubMed2001

Crk family adaptor proteins trans-activate c-Abl kinase.

BACKGROUND: c-Abl kinase is activated in response to a variety of biological stimuli. Crk family adaptor proteins can interact physically with c-Abl and be involved in the activation of c-Abl kinase. RESULTS: We report that the Crk family of adaptor proteins act as trans-acting activators of c-Abl kinase. The interaction of the amino-terminal Src-homology (SH) 3 domain of c-Crk and the proline-rich motifs of c-Abl is an essential step for the phosphorylation of c-Crk by c-Abl, as well as the activation of c-Abl by c-Crk. The activation of c-Abl by c-Crk is negatively regulated by phosphorylation of the tyrosine 221 of c-Crk. Our data suggest that, in the absence of phosphorylation of the tyrosine Y221, the SH2 domain of c-Crk becomes free to bind to target molecules while the carboxyl-terminal SH3 domain of c-Crk binds to the proline-rich region of c-Abl, inducing the activation of c-Abl by c-Crk. CONCLUSION: This study suggests that the Crk family functions as trans-acting activators of c-Abl kinase. The phosphorylation of c-Crk may regulate c-Abl kinase.

Animals↗

PubMed2001

Histopathological and immunohistochemical studies on arteritis induced by fenoldopam, a vasodilator, in rats.

Fenoldopam, a dopaminergic (DA1) agonist, has been reported to induce medial necrosis and adventitial inflammatory response in the splanchnic arteries in rats. This study was carried out to clarify the detailed time course of the inflammatory responses, using antibodies for the inflammatory cell markers, CD3 (T cell), CD20 (B cell) and ED-1 (macrophage), and inflammatory serum factors, IgG, IgM and C3. Rats were administered fenoldopam for 24 hours by intravenous infusion. Histopathologically, medial necrosis with hemorrhage was observed at the end of infusion, but it almost disappeared on day 7 post-infusion. Adventitial inflammatory responses with ED-1-, CD3- and CD20-positive cells were very slight at the end of infusion, became prominent with marked fibrosis on days 3 and 5, decreased on day 7, and subsided on day 14. The serum factors were first present in the area of medial necrosis, then shifted to the subendothelial space or cytoplasm of smooth muscle cells, and disappeared on day 14 post-infusion. Gaps in the external elastic lamina were observed on days 3 and 5 post-infusion, and IgG and IgM were present outside the gaps in the adventitia. These results provided us with more detailed information on the inflammatory responses following medial damage induced by vasodilators.

Animals↗

PubMed2001

Reverse redistribution of 99m Tc-sestamibi after direct percutaneous transluminal coronary angioplasty in acute myocardial infarction: relationship with wall motion and functional response to dobutamine stimulation.

Reverse redistribution (RR) of 99mTc-sestamibi is observed after direct percutaneous transluminal coronary angioplasty (PTCA) in acute myocardial infarction (AMI). The purpose of this study was to clarify the functional characteristics of myocardial segments with RR after direct PTCA in AMI. Thirty patients with AMI who had undergone direct PTCA were examined. Myocardial perfusion tomography with 99mTc-sestamibi and low dose dobutamine echocardiography were performed within 2 weeks of the onset. The 99mTc-sestamibi images were obtained 1 and 3 h after tracer administration. The left ventricle was divided into nine segments, and regional 99mTc-sestamibi uptake and clearance were quantitatively evaluated in each segment. RR was defined as a decrease in 99mTc-sestamibi uptake of >10% on 3 h delayed images compared with the 1 h early images. The left ventricle in the echocardiographic images was also divided into nine segments corresponding to the scintigraphic images, and regional wall motion was assessed in the resting condition as the baseline and during dobutamine administration (5-10 microg x kg(-1) x min(-1)). Out of a total of 270 myocardial segments, 111 segments were perfused by the culprit coronary artery and were defined as ischaemic segments. There were 25 segments with RR and 86 segments without RR in the ischaemic myocardium. Enhanced clearance of 99mTc-sestamibi was observed in ischaemic segments with RR (P<0.001). Echocardiography demonstrated that 24 out of 25 segments with RR and 61 out of 86 segments without RR had wall motion abnormalities. Dobutamine infusion improved wall motion in 20 (83%) of the 24 dysfunctional segments with RR and 33 (54%) of the 61 dysfunctional segments without RR (P<0.02). These findings suggest that RR indicates reversible functional abnormalities associated with preserved contractile reserve in response to dobutamine. The early and delayed imaging of 99mTc-sestamibi provides useful information regarding the residual viability of the dysfunctional myocardium in AMI patients.

Acute Disease↗

PubMed2001

A new peritoneal dissemination model established from the human pancreatic cancer cell line.

We established a new cell line, HPC-3P4a, with high peritoneal disseminated potential in nude mice. HPC-3P4a was derived from a human pancreatic carcinoma cell line (HPC-3) that had low capacity for peritoneal dissemination. HPC-3P4a developed peritoneal dissemination in 10 of 11 (90.9%) cases, whereas parental HPC-3 developed peritoneal dissemination in one of six (16.7%) cases. The metastatic foci in the peritoneum showed essentially the same histologic appearance of parental involvement. The tumorigenicity, motility, and adhesive activity of HPC-3P4a to the extracellular matrix were stronger than were those of the HPC-3. In FACS analysis, HPC-3P4a significantly increased the expression of alpha6 and alpha(v)beta5 integrins, while it decreased alpha2 integrin, hCD44H, and hCD44v 10, as compared with HPC-3. The VEGF production of HPC-3P4a was significantly lower than that of HPC-3. Analysis of gene macroarrays showed a variety of cytokines, interleukin, and other immunomodulatory, and their receptors were up-regulated and down-regulated on an mRNA level in HPC-3P4a cells, compared with HPC-3 cells. Intrasplenic injection of HPC-3P4a produced no liver metastasis. We named our original highly liver metastatic cell line HPC-3H4 (previously reported). This HPC-3H4 cell was established by repeated intrasplenic injection from parental cell HPC-3; thus, it developed high liver metastasis. Moreover, HPC-3H4 developed peritoneal dissemination by intra-abdominal injection. In contrast, HPC-3P4a did not develop liver metastasis by intrasplenic injection. These findings are very interesting and might suggest that the process of hematogenous metastasis differed from that of peritoneal dissemination. Thus, this cell line may be useful for investigating the mechanism of peritoneal dissemination in human pancreatic cancer.

Adenocarcinoma↗

PubMed2001

Vagosympathetic interactions in ischemia-induced myocardial norepinephrine and acetylcholine release.

To elucidate the pathophysiological roles of vagosympathetic interactions in ischemia-induced myocardial norepinephrine (NE) and acetylcholine (ACh) release, we measured myocardial interstitial NE and ACh levels in response to a left anterior descending coronary occlusion in the following groups of anesthetized cats: intact autonomic innervation (INT, n = 7); vagotomy (VX, n = 6); local administration of atropine (Atro, n = 6); transection of the stellate ganglia (TSG, n = 5); local administration of phentolamine (Phen, n = 6); and combined vagotomy and transection of the stellate ganglia (VX+TSG, n = 5). The maximum NE release was enhanced in the VX group (141 +/- 30 nmol/l, means +/- SE, P < 0.05) compared with the INT group (61 +/- 12 nmol/l). Neither the Atro (50 +/- 24 nmol/l) nor VX+TSG groups (84 +/- 25 nmol/l) showed enhanced NE release. The maximum ACh release was unaltered in the TSG and Phen groups compared with the INT group (19 +/- 4, 18 +/- 4, and 13 +/- 3 nmol/l, respectively). These findings indicate that the cardiac vagal afferent but not efferent activity reduced the ischemia-induced myocardial NE release. In contrast, the cardiac sympathetic afferent and efferent activities played little role in the ischemia-induced myocardial ACh release.

Acetylcholine↗

PubMed2001

Differential dynamic baroreflex regulation of cardiac and renal sympathetic nerve activities.

Although regional difference in sympathetic efferent nerve activity has been well investigated, whether this regional difference exists in the dynamic baroreflex regulation of sympathetic nerve activity remains uncertain. In anesthetized, vagotomized, and aortic-denervated rabbits, we isolated carotid sinuses and randomly perturbed intracarotid sinus pressure (CSP) while simultaneously recording cardiac (CSNA) and renal sympathetic nerve activities (RSNA). The neural arc transfer function from CSP to CSNA and that from CSP to RSNA revealed high-pass characteristics. The increasing slope of the transfer gain in the frequencies between 0.03 and 0.3 Hz was significantly greater for CSNA than for RSNA (2.96 +/- 0.72 vs. 1.64 +/- 0.73 dB/octave, P < 0.01, n = 9). The difference was hardly explained by the difference in static nonlinear characteristics of CSP-CSNA and CSP-RSNA relationships or by the difference in conduction velocities in the multifiber recording. These results indicate that the central processing in the brain stem differs between CSNA and RSNA. The neural arc of the baroreflex may exert differential effects on the heart and kidney in response to dynamic baroreflex activation.

Animals↗

PubMed2001

Dynamic sympathetic control of atrioventricular conduction time and heart period.

Although power spectra of R-R and P-R intervals in response to random respiration show similar frequency distributions, the way in which dynamic sympathetic regulation contributes to such similarity remains unknown. We estimated the transfer function from sympathetic stimulation to the atrioventricular interval (AV conduction time; T(AV)) with and without constant atrial pacing in seven anesthetized cats. The transfer function from sympathetic stimulation to T(AV), except for absolute gain values, approximated a low-pass filter similar to that from sympathetic stimulation to the A-A interval (heart period; T(AA)). The 90%-rise times did not differ between the T(AA) and T(AV) step responses (32.3 +/- 1.8 vs. 29.6 +/- 3.2 s). Constant pacing augmented the T(AV) step response (-0.58 +/- 0.10 vs. -0.86 +/- 0.12 ms/Hz, P < 0.05) without affecting the 90%-rise time. These findings suggest that the dynamic characteristics of sympathetic control are similar between T(AA) and T(AV) despite the different electrophysiological mechanisms determining T(AA) and T(AV). A numerical simulation indicated that if the dynamic characteristics of the sympathetic control do not match between T(AA) and T(AV), a critical condition for initiation of reentrant tachycardia would be encountered.

Animals↗