Biomedical subjects

K Sawada

Publications and source records attributed to K Sawada.

At least 163 records · Page 9Linked to original sources

PubMed1998

In vitro expansion of CD34+/CD41+ cells from human peripheral blood CD34+/CD41- cells: role of cytokines for in vitro proliferation and differentiation of megakaryocytic progenitors.

The aim of this study is to clarify the transitional change of the proliferation and differentiation of human peripheral blood CD34+ cells to megakaryocytic lineage, focusing on its clinical application. We developed a rapid system to purify human peripheral blood CD34+ cells from healthy volunteers, which produced CD34+ cells with a 90% purity. The purified CD34+ cells predominantly consisted of CD41- cells, and the rate of coexpression of CD41 was 0.6% +/- 0.5%. When the purified cells were cultured in liquid phase for 10 days in the presence of recombinant human stem cell factor (rSCF: a ligand for c-kit), interleukin-3 (rIL-3), and thrombopoietin (rTPO: a ligand for Mpl), the number of CD34+/CD41+ cells increased to 19% +/- 7% of total expanded cells on day 4 (4 days of liquid culture) and then gradually decreased to 2.2% +/- 0.6% on day 10. The absolute number of CD34+/CD41+ cells increased and reached a plateau on day 6, and 1.7 +/- 0.6 x 10(5) CD34+/CD41+ cells were produced by 1 x 10(5) CD34+/CD41- day 0 cells. The CD34-/CD41+ cells appeared on day 6, continuously increased in number until day 10, and constituted the main population of expanded cells on day 10, with a value of 38% +/- 18%. On day 10, 19.5 +/- 10.6 x 10(5) of CD34-/CD41+ cells were produced by 1 x 10(5) CD34+/CD41- day 0 cells. The deletion of rTPO from this cytokine combination decreased the number of CD34+/CD41+ and CD34-/CD41+ cells, after days 6 and 8, respectively. Day 0 cells required rIL-3 for promoting colonies containing megakaryocytes, whereas rTPO alone promoted almost no megakaryocytic colonies from day 0 cells. Thus, a combination of IL-3 and SCF expands CD34+/CD41+ cells from CD34+/CD41- cells, and TPO mainly acts to increase CD34-/CD41+ cells. This study suggests that if the expansion of CD34+/CD41+ is performed in vitro, the 6 days' culture of peripheral blood CD34+/CD41- cells with a combination of IL-3 and SCF with TPO provides the most rapid and stable products of CD34+/CD41+ cells for the rapid recovery of platelets in patients with peripheral blood stem cell transplantation.

Adult↗

PubMed1998

[Evaluation of estimated blood concentration of propofol on wake-up using "ConGrase", a software to control the syringe pump for propofol infusion].

We developed a software to control a Graseby 3500 syringe pump for propofol infusion through the serial port of Apple Macintosh/Power-Macintosh computer. This software, "ConGrase", was developed with Metrowerks CodeWarrior Professional (CWP 1) and PowerPlant framework using C++. ConGrase communicates with the syringe pump at least every three seconds, and calculates the estimated blood concentration (EBC) of propofol based on the amount of propofol actually infused by applying either the Euler or Runge-Kutta method using the three-compartment pharmacokinetic model. The parameter sets reported by Gepts et al. are used. ConGrase was released at the 44 th Annual Meeting of the Japan Society of Anesthesiology, and is distributed freely. The mean and S.D. of the emergence EBC calculated by ConGrase were 1.22 micrograms.ml-1 and 0.16 microgram.ml-1, respectively. These values are almost the same as values already reported outside Japan. The necessary wake-up time can be calculated with this estimated concentration. With this system, anesthetists can control the EBC at the required level and avoid long delays before the patients wake up after anesthesia.

Adolescent↗

PubMed1998

[Experience of cancer home chemotherapy with cooperation between hospital and clinic].

Cancer home chemotherapy has improved through the cooperation between hospital and clinic. We have experienced cancer home chemotherapy in 90 cases of terminal cancer from August 1990 to May 1998. Patients had received Low-dose infusions of 5-FU and CDDP during 6-7 days using an implanted reservoir and balloon-style continuous infusor. This therapy was continued for about several months to 2 years. We chose one method from among central venous infusion, subselective aortal infusion, selective arterial infusion, and combination of these types of infusion. The role of the hospital includes reduction operations and operations involving implant systems. When these are finished, patients are discharged from hospital and introduced to the clinic as quickly as possible. On the other hand, the clinic should care for implanted infusion system, prevent side effects, and care for patient's general condition. Side effects due to drug overdose must especially be prevented. This time, we have examined the respective roles of the hospital and clinic, some mutual problems, along with medical costs and insurance.

Ambulatory Care Facilities↗

PubMed1997

Subunit interactions of Escherichia coli F1-ATPase: mutants of the gamma subunits defective in interaction with the epsilon subunit isolated by the yeast two-hybrid system.

Previously, we established a method to detect subunit interactions of F1-ATPase by the yeast two-hybrid system (Moritani, C., et al. Biochim. Biophys. Acta 1274, 67-72, 1996). Here, we isolated mutants of the gamma subunits defective in interaction with the epsilon subunit by this new procedure to study the molecular basis of coupling mechanisms of the F1F0-ATPase. Based on the intensities of the reporter gene expression in this system, five mutants of the gamma subunit with different levels of gamma-epsilon interactions were isolated and their single base substitutions were determined. Mutants with a substitution of Pro-55 for Leu, Thr-102 for Met, Val-141 for Asp, or Gln-235 for Leu exhibited decreased reporter gene expression, suggesting decreased levels of interaction, while Asp-85 for Gly mutation caused a higher level of expression, suggesting increased interaction. Among these point mutations, G85D, M102T, or D141V mutations were introduced into the gamma subunit gene in the plasmid carrying whole unc operon. Transformants carrying a deletion mutant of the whole unc operon with these expression plasmids were analyzed. Mutations M102T and D141V with decreased gamma-epsilon interaction caused increases of membrane-bound F1-ATPase activity and proton pumping activity, while G85D with increased gamma-epsilon interaction exhibited lower levels of F1-ATPase activity in the membranes. Molecular assembly of the F1 subunits on the mutant membranes detected by Western blotting exhibited no defect for all three mutants. These results suggested that the correlation between the ATPase activity and gamma-epsilon interaction is reciprocal and this interaction may regulate the ATPase activity. The topological and functional importance of Gly-85, Met-102, and Asp-141 together with Leu-55 and Leu-235 in gamma-epsilon interaction is discussed.

Amino Acid Substitution↗

PubMed1997

Interaction of the delta and b subunits contributes to F1 and F0 interaction in the Escherichia coli F1F0-ATPase.

Interactions of the F1F0-ATPase subunits between the cytoplasmic domain of the b subunit (residues 26-156, bcyt) and other membrane peripheral subunits including alpha, beta, gamma, delta, epsilon, and putative cytoplasmic domains of the a subunit were analyzed with the yeast two-hybrid system and in vitro reconstitution of ATPase from the purified subunits as well. Only the combination of bcyt fused to the activation domain of the yeast GAL-4, and delta subunit fused to the DNA binding domain resulted in the strong expression of the beta-galactosidase reporter gene, suggesting a specific interaction of these subunits. Expression of bcyt fused to glutathione S-transferase (GST) together with the delta subunit in Escherichia coli resulted in the overproduction of these subunits in soluble form, whereas expression of the GST-bcyt fusion alone had no such effect, indicating that GST-bcyt was protected by the co-expressed delta subunit from proteolytic attack in the cell. These results indicated that the membrane peripheral domain of b subunit stably interacted with the delta subunit in the cell. The affinity purified GST-bcyt did not contain significant amounts of delta, suggesting that the interaction of these subunits was relatively weak. Binding of these subunits observed in a direct binding assay significantly supported the capability of binding of the subunits. The ATPase activity was reconstituted from the purified bcyt together with alpha, beta, gamma, delta, and epsilon, or with the same combination except epsilon. Specific elution of the ATPase activity from glutathione affinity column with the addition of glutathione after reconstitution demonstrated that the reconstituted ATPase formed a complex. The result indicated that interaction of b and delta was stabilized by F1 subunits other than epsilon and also suggested that b-delta interaction was important for F1-F0 interaction.

Bacterial Proteins↗

PubMed1997

FR146687, a novel steroid 5 alpha-reductase inhibitor: in vitro and in vivo effects on prostates.

BACKGROUND: Steroid 5 alpha-reductase is implicated in the pathogenesis of benign prostatic hyperplasia (BPH). We studied the in vitro and in vivo effects of FR146687, a new inhibitor of 5 alpha-reductase. METHODS: Two isozymes of rat and human 5 alpha-reductases were expressed in 293 cells. In vivo effects of drugs were evaluated on rat and dog prostates. Castrated immature rats were injected with testosterone propionate (TP) or 5 alpha-dihydrotestosterone propionate (DHTP) to induce growth of the ventral prostates. Testosterone and 5 alpha-dihydrotestosterone (DHT) contents in rat and dog prostates were measured by gas chromatography-mass spectrophotometry (GC-MS). RESULTS: FR146687 showed noncompetitive inhibition in both isozymes and no inhibitory effects on other steroid oxidoreductases. In mature rats and castrated immature rats treated with TP, FR146687 dose-dependently reduced ventral prostate and seminal vesicle weight at doses above 0.1 mg/kg, while castrated immature rats treated with DHTP were not affected by FR146687. FR146687 showed more potent reduction of rat prostates than finasteride. DHT concentration in the prostates was significantly reduced when FR146687 was administered to rats and beagles. CONCLUSIONS: FR146687 is a dual inhibitor for 5 alpha-reductase isozymes and significantly reduced the growth and DHT content in the prostate.

Animals↗

PubMed1997

A novel type of calcium channel sensitive to omega-agatoxin-TK in cultured rat cerebral cortical neurons.

We characterized the electrophysiological properties of calcium channels in cultured rat cerebral cortical neurons using omega-agatoxin-TK (omega-Aga-TK) by a patch-clamp technique. Two types of slowly inactivating calcium channels sensitive to omega-Aga-TK were detected. The first type showed high sensitivity to omega-Aga-TK and low recovery from the omega-Aga-TK-induced blockade during washout, corresponding to the P-type channel. The second type showed low sensitivity to omega-Aga-TK and high recovery, resembling the Q-type channel, although it was distinct from the Q-type in terms of slower inactivation kinetics. We designate this channel as Q(L)-type (long-lasting Q channel). The omega-Aga-TK-sensitive calcium channels involved in the glutamatergic synaptic transmission were also divided into two types based on the sensitivity to omega-Aga-TK and reversibility of omega-Aga-TK-induced blockade. We conclude that the Q(L)-type is a novel type of channel, and that both P-type and Q(L)-type channels play a significant role in the cerebral cortical synaptic transmission.

Agatoxins↗

PubMed1997

Selective expression of the receptor tyrosine kinase, HTK, on human erythroid progenitor cells.

HTK is a receptor tyrosine kinase of the Eph family. To characterize the involvement of HTK in hematopoiesis, we generated monoclonal antibodies against HTK and investigated its expression on human bone marrow cells. About 5% of the bone marrow cells were HTK+, which were also c-Kit+, CD34(low), and glycophorin A(-/low). Assays of progenitors showed that HTK+ c-Kit+ cells consisted exclusively of erythroid progenitors, whereas HTK- c-Kit+ cells contained progenitors of granulocytes and macrophages as well as those of erythroid cells. Most of the HTK+ erythroid progenitors were stem cell factor-dependent for proliferation, indicating that they represent mainly erythroid burst-forming units (BFU-E). During the erythroid differentiation of cultured peripheral CD34+ cells, HTK expression was upregulated on immature erythroid cells that corresponded to BFU-E and erythroid colony-forming units and downregulated on erythroblasts with high levels of glycophorin expression. These findings suggest that HTK is selectively expressed on the restricted stage of erythroid progenitors, particularly BFU-E, and that HTK is the first marker antigen that allows the purification of erythroid progenitors. Furthermore, HTKL, the ligand for HTK, was expressed in the bone marrow stromal cells. Our findings provide a novel regulatory system of erythropoiesis mediated by the HTKL-HTK signaling pathway.

Antibodies, Monoclonal↗

PubMed1997

Escherichia coli F1-ATPase subunit interactions: beta and gamma subunit peptides inhibit in vitro reconstitution of the active alpha beta gamma complex.

For biochemical analysis of subunit interactions in the proton-translocating ATPase, a new approach with in vitro reconstitution of the Escherichia coli alpha beta gamma complex and the peptides derived from the subunits was established. Various portions of the beta or gamma subunits were used for in vitro reconstitution of the alpha beta gamma complex from the purified subunits. For the beta subunits, peptides corresponding to residues 226-459, 254-459, and 226-365 inhibited reconstitution, while those corresponding to residues 1-105, 1-146, and 295-459 did not. For the gamma subunits, peptides corresponding to residues 1-192 and 74-286 exhibited inhibitory effect on reconstitution, but the peptide containing residues 191-286 did not. Only inhibitory peptides blocked the assembly of the alpha beta gamma complex which was detected by nondenaturing polyacrylamide gel electrophoresis. These inhibitory peptides bound to the alpha or beta subunit on the filter, but the noninhibitory peptides did not. These results suggested that regions beta 254-294 and gamma 74-190 have sequences important for subunit interactions which interfered with those in the reconstitution mixtures. Based on comparison between X-ray crystallographic data of bovine alpha beta gamma complex and the present results, we discussed here the significance of the biochemical approach adopted in this study.

Circular Dichroism↗

PubMed1997

Exacerbated autoimmune hepatitis successfully treated with leukocytapheresis and bilirubin adsorption therapy.

A 58-year-old man with subacute fulminant onset of autoimmune hepatitis (AIH) was treated by leukocytapheresis (LCAP) and bilirubin adsorption therapy (BAT), rather than by administration of high-dose corticosteroids as he had mild glucose intolerance, and a definitive diagnosis of AIH was not obtained on admission; further, there was a risk of viral infection. After initiation of the therapies, serum transaminases and bilirubin, immunoglobulins, anti-nuclear antibodies, and rheumatoid factor decreased rapidly, as did the initially high levels of activated cells and several pro-inflammatory cytokines. Liver inflammation observed on liver biopsy settled during the course of the therapies, with no adverse side effects. A pause in the therapies was associated with deterioration; however, restoration of apheresis was followed by normalization. Remission was sustained throughout the period monitored, except for a recurrence 14 months after discharge, which was successfully resolved by two additional LCAP sessions. These results suggest that LCAP influences the causal mechanism(s) of exacerbation of AIH.

Adsorption↗

PubMed1997

A rapid nylon-fiber syringe system to deplete CD14+ cells for positive selection of human blood CD34+ cells. Use of immunomagnetic microspheres.

To achieve a rapid and an efficient purification of CD34+ cells, we devised a nylon-fiber syringe (NF-S) and we manipulated it to deplete adherent cells from normal human blood mononuclear cells (MN cells). The cells processed by NF-S were further purified as the CD34+ fraction, using CD34 monoclonal antibody, immunomagnetic microspheres and chymopapain treatment to detach the microspheres. When steady-state human peripheral blood MN cells were processed by NF-S at 24 degrees C for 5 min, the frequency of monocytes (CD14+ cells) significantly decreased from 22.0 +/- 5.2% to 2.5 +/- 0.4%, with a 73% recovery of CD34+ cells. The subsequent immunomagnetic positive selection achieved preparations of 91 +/- 8% pure CD34+ cells with a 86 +/- 23% yield. The overall yield of CD34+ cells was 44 +/- 11%, and the time required for all procedures was 5 h. There was a tight and an inverse correlation (P < 0.0001) between the frequency of CD14+ cells in the initial cell population and the purity of CD34+ cells in the final preparation. A recommended frequency of CD14+ cells for achieving preparations of over 90% pure CD34+ cells was less than 4.4%. When combining NF-S and immunomagnetic microspheres, efficient bench-top separation of CD34+ cells in steady-state peripheral blood can be done in any laboratory, and fluorescence-activated cell-sorting is not required.

Antigens, CD34↗

PubMed1997

Effective high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation in a patient with the aggressive form of cytophagic histiocytic panniculitis.

A 20-year-old Japanese man developed generalized, subcutaneous, painless nodules, fever, abnormal liver function, serosal effusions, hepatosplenomegaly, lymphadenopathy and anemia. Skin biopsies revealed lobular panniculitis with a morphologically benign histiocytic infiltration and prominent phagocytosis. Atypical T lymphocytes were also present in the skin and liver. The diagnosis given was aggressive cytophagic histiocytic panniculitis (CHP) or aggressive subcutaneous panniculitic T cell lymphoma (SPTCL). He received cyclophosphamide, doxorubicin, and vincristine on day 1, prednisolone on days 1-5, and etoposide on days 1, 3 and 5 (CHOP-E), with the support of granulocyte colony-stimulating factor. This regimen was repeated every 2 weeks and complete clinical remission (CCR) was attained after three cycles of CHOP-E. As the clinical course of aggressive CHP is recurrent and often fatal, he was given high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (APBSCT), after five cycles of CHOP-E. He has remained in CCR for 12 months after APBSCT. High-dose chemotherapy followed by APBSCT is considered to be one of the most beneficial therapies for patients with aggressive CHP and aggressive phase SPTCL.

Adolescent↗

PubMed1997

Protection by alpha2-macroglobulin of tissue plasminogen activator against inhibition by plasminogen activator inhibitor-1.

Tissue plasminogen activator (tPA) is widely used in the treatment of acute myocardial infarction (MI). However, its thrombolytic efficacy does not correlate with the dose administered. The interactions between tPA, alpha2-macroglobulin (alpha2-M), and plasminogen activator inhibitor-1 (PAI-1) were investigated both in vitro and in patients undergoing tPA therapy for MI in an attempt to identify variables that might affect the clinical efficacy of tPA. Purified alpha2-M (5.4 mg/ml) protected 16.0% or 22.4% of tPA (12.5 IU/ml) activity from inhibition by PAI-1 at 4 or 8 IU/ml in vitro. Of nine patients treated with 5-20 mega IU of tPA for MI, the plasma activity of tPA remained increased for 15-30 min after the cessation of infusion in eight; the patient who failed to exhibit a persistent increase in tPA activity had a low plasma concentration of alpha2-M. Total tPA activity, derived from the area under the activity-versus-time curve (AUC), showed a significant inverse correlation with the ratio of the plasma PAI-1 activity to the plasma alpha2-M concentration. Total tPA activity did not correlate with plasma PAI-1 activity or plasma alpha2-M concentration alone. Results suggest that alpha2-M, by binding to tPA, protects the latter against inhibition by PAI-1.

Aged↗

PubMed1997

A germ cell-specific nuclear antigen recognized by a monoclonal antibody raised against mouse testicular germ cells.

A monoclonal antibody (mAb TRA 104) raised against mouse testicular germ cells was able to recognize the nuclei of testicular germ cells at all the stages of differentiation from embryonic gonocytes to spermatids and did not react with any somatic cells. The antigen recognized by mAb TRA 104 was exclusively present in testicular extracts. The molecular weights and isoelectric point (pI) of the antigens determined by Western blotting analysis were 60-110 kDa and 7.2, respectively. This antigen(s) is referred to as a germ cell-specific nuclear antigen(s) (GENA) since GENA was first detected specifically in the genital ridge at around 12 days of gestation by Western blotting analysis. In the testis, the expression increased gradually until adulthood whereas it was lost in the ovary by postpartum day 5. Thus, GENA is a molecule(s) exclusively present in the nuclei of germ cells and may be a useful marker with which to study the mechanism of germ cell development and differentiation at the molecular level.

Animals↗

PubMed1997

Recovery of heart rate variability profile in patients after coronary artery surgery.

UNLABELLED: We examined the different characteristics of heart rate variability (HRV) to define the time course of HRV profile after coronary artery surgery (CAS). Spectral analysis of HRV was performed on a 512-s segment of R-R intervals of the electrocardiogram on the preoperative day and on Postoperative Days 1, 2, 3, 4, 5, 6, 7, 14, 21, and 28. Power spectral area was divided into low (0.04-0.15 Hz; LF)- and high (0.15-0.5 Hz; HF)-frequency components. Fractal slope and sympathovagal slope of 1/f characteristics of HRV were determined in two different frequency ranges (from 0.01 to 0.15 Hz and from 0.01 to 0.5 Hz, respectively). Three recovery profiles of HRV were identified. Early HRV recovery profiles (Postoperative Days 1-6) included reduction in LF, HF, and sympathovagal slope, as well as an increase in fractal slope. Subsequent HRV recovery profiles (Postoperative Days 7-21) revealed reductions in LF, HF, and sympathovagal slope. Fractal slope became normal. Later HRV recovery profiles (Postoperative Day 28) demonstrated that all spectral components of HRV remained reduced, but sympathovagal and fractal slopes became normal. These changes in the HRV profile after CAS suggest significant postoperative alterations in cardiovascular homeostasis with significant but incomplete recovery during the first 28 postoperative days. IMPLICATIONS: Heart rate variability reflects normal neural regulation of cardiac function. This variability remains depressed as long as 28 days after coronary artery bypass surgery, but can recover as early as 1 wk postoperatively. Despite implied loss of normal neural regulation of cardiac function, a specific correlation between depressed heart rate variability and outcomes was not performed.

Adult↗

PubMed1997

An immunohistochemical study of radial glial cells in the mouse brain prenatally exposed to gamma-irradiation.

The features of a glial cell population in the developing brain of mice prenatally exposed to 60Co gamma-irradiation at the most radiosensitive stage were studied with immunohistochemistry for anti-midkine (MK), anti-vimentin (Vim), and anti-GFAP antibodies. Anti-MK- and anti-Vim-positive radial glial fibers distributed in a similar radial fashion; these fibers were observed primarily in the embryonic period and disappeared after birth. Anti-MK- and anti-Vim-stained radial fibers ran perpendicular to the pial surface in controls, whereas such fibers were disorganized 6 hours (h) after irradiation. This finding provided new evidence that the migratory pathways of young neurons were interrupted beginning a few hours after irradiation. By E17 the ectopic cell masses formed so as to replace the parts of the ventricular zone where no anti-MK immunoreactive radial fibers were present, but where anti-GFAP-stained fibrillary astrocytes emerged in the ectopic cell masses from the early postnatal period. The results suggested a twofold source of the generated astrocytes: either directly from a separate precursor of the astrocytes, or due to the transformation of the classic radial glial cells. In the newborn, numerous protoplasmic transitional forms displaced by astrocytes in irradiated brains indicated that reactive gliosis was a powerful response of a brain exposed to irradiation.

Animals↗

PubMed1997

Leukocytapheresis with leukocyte removal filter as new therapy for ulcerative colitis.

Leukocytapheresis (LCAP) with a leukocyte removal filter column was administered for 45 patients with ulcerative colitis (UC). We evaluated changes in the leukocyte count and the differential percentages during LCAP. Cytokine production was assessed from each patient's peripheral mononuclear cells or monocytes. Flow cytometry was performed to assess the removal rates of activated cells and adhesion molecule positive cells by LCAP. Clinical improvement was recognized in 35 of 45 patients during intensive LCAP therapy, and it continued throughout maintenance therapy in 32 patients (71.1%). The leukocyte count was decreased to about 40% during the first 30 min, but it increased to approximately 170% at 20 min after the completion of LCAP. The concentration of tumor necrosis factor (TNF)alpha before LCAP in the effective group was higher than it was in either the ineffective group or the control group. Its level decreased to near normal range after LCAP. In the effective group, the concentrations of interleukin (IL)-1beta, IL-2, interferon (IFN)gamma, and IL-8 were near the normal upper limits before LCAP; however, they had decreased after LCAP. The concentration of IL-4 increased after LCAP. In the ineffective group, in contrast, the concentrations had been at or near normal before the initial LCAP treatment. Flow cytometry study revealed that LCAP could remove the activated cells and adhesion molecule positive cells more effectively. The clinical improvement and the changes observed before and after LCAP therapy suggest that LCAP is able to intervene in the causal mechanism(s) of UC.

Blood Cell Count↗

PubMed1997

Distribution and neuropeptide content of nitric oxide synthase-containing nerve fibers in arteries and conduction system of the rat heart.

The rat heart receives its blood supply not only from the coronary arteries but also from the accessory coronary arteries that supply mainly the atria. The distribution and chemical nature of nitric oxide synthase-containing nerve fibers in the conduction system as well as the coronary and accessory coronary arteries were investigated using immunohistochemistry and NADPH diaphorase (NADPH-d) histochemistry. A few NADPH-d-positive nerve fibers were observed mainly around the main trunk of the coronary arteries, while NADPH-d-positive fibers were found along the entire course of the accessory coronary arteries from their main branches to the arteriolar level. A double-staining method demonstrated that NADPH-d-positive fibers innervating both the coronary and accessory coronary arteries contained vasoactive intestinal polypeptide or neuropeptide Y. NADPH-d-positive fibers were relatively abundant in the sinus node and penetrating bundle but were very sparse in the atrioventricular node and right bundle branch. No NADPH-d-positive fibers were detected in the left bundle branch. Some of the NADPH-d-positive fibers innervating the penetrating bundle exhibited distinct immunoreactivity to calcitonin gene-related peptide. These results suggest that nitric oxide may play a role as a neurotransmitter and/or neuromodulator in the neural control of the cardiac blood flow and impulse conduction.

Animals↗