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Biomedical subjects

H Akiho

Publications and source records attributed to H Akiho.

At least 19 recordsLinked to original sources

Two endothelin receptors (ETA and ETB) expressed on circular smooth muscle cells of guinea pig cecum.

BACKGROUND/AIMS: The functional receptors for endothelin (ET) in colonic smooth muscle are still unknown. This study investigated the expression of ET receptors in isolated circular smooth muscle cells of guinea pig cecum. METHODS: Inhibition of 125I-ET-1 binding was examined using unlabeled ET-1, ET-2, ET-3, sarafotoxin 6c (S6c), and ETA antagonists. Expression of the ET-receptor message was investigated using reverse-transcription polymerase chain reaction. The contractile potency of the ET family and the inhibitory effect of ETA antagonists on ET-1-induced contraction were also investigated. RESULTS: Unlabeled ET-1, ET-2, and ET-3 inhibited the specific binding of 125I-ET-1 in a concentration-dependent manner, but the inhibitory effect of ET-3 was smaller than those of ET-1 and ET-2. At a 10(-6) mol/L concentration of S6c, the specific binding of 125I-ET-1 was 24.7%. S6c had clearly reached maximal inhibition. Abundant polymerase chain reaction products for both the ETA and the ETB message were observed. ET-1 and ET-2 showed similar contractile potency, but ET-3-induced and S6c-induced contractions were significantly less potent than the ET-1-induced contraction. A significant response to S6c was obtained at a concentration as low as 10(-10) mol/L. The ETA antagonists BQ-123 and FR 139317 significantly inhibited ET-1-induced contraction. CONCLUSIONS: The results show a direct contractile effect of ETs on circular smooth muscle of guinea pig cecum and the presence of both ETA- and ETB-receptor subtypes.

Animals

Interaction between atrial natriuretic peptide and vasoactive intestinal peptide in guinea pig cecal smooth muscle.

BACKGROUNDS & AIMS: The role of atrial natriuretic peptide (ANP) in gastrointestinal motility is still unclear. The aim of this study was to investigate the relationship between ANP and vasoactive intestinal peptide (VIP) in guinea pig cecal circular smooth muscle cells. METHODS: The inhibition of 125I-ANP binding or 125I-VIP binding to cecal smooth muscle cells was assessed using unlabeled peptides (i.e., ANP, ANP fragments, VIP, secretin, and peptide histidine isoleucine); the effect of ANP, ANP fragments, and VIP on muscle contraction stimulated by 1 mumol/L carbachol was assessed; and the inhibitory effects of ANP 1-11 on VIP-induced relaxation, ANP 1-11 and VIP 10-28 (a VIP antagonist) on ANP-induced relaxation, and nitric oxide production inhibitors on ANP-induced relaxation were assessed. RESULTS: The specific binding of 125I-ANP was inhibited completely by unlabeled ANP and VIP in a dose-dependent manner but only slightly inhibited by secretin and peptide histidine isoleucine. ANP 1-11 and C-atrial natriuretic factor inhibited the binding of 125I-ANP with a lower affinity than ANP. ANP only partly inhibited 125I-VIP binding. ANP and VIP inhibited 1 mumol/L carbachol-induced contraction in a dose-dependent manner. ANP 1-11 significantly inhibited VIP-induced relaxation. ANP 1-11, VIP 10-28, and NO production inhibitors completely inhibited ANP-induced relaxation. CONCLUSIONS: The results of the study showed that ANP 1-11 antagonized ANP-induced relaxation and that ANP stimulated NO production and subsequently induced relaxation via a receptor to which VIP binds.

Animals

Functional endothelin A receptor on gastric smooth muscle cells.

Smooth muscle cells isolated from the gastric muscle layers of the guinea pig were used to examine the functional endothelin receptor subtype responsible for gastric smooth muscle contraction by endothelin. Endothelin-1 induced the contraction of these cells in a dose-dependent manner, with an ED50 value of 0.2 nM. Endothelin-3-induced contraction was significantly less than that of endothelin-1. Sarafotoxin 6c (10(-11)-10(-7) M), endothelinB highly selective agonist, did not elicit the contraction of gastric smooth muscle cells. BQ-123, endothelinA selective antagonist, inhibited the contractile response produced by 10(-7) M endothelin-1 in a dose-dependent manner, with an IC50 value of 5 nM. These results strongly suggest that endothelin elicited the contraction of gastric smooth muscle cells via functional endothelinA receptor subtype.

Animals

Chaotic behavior of hemodynamics with ventricular assist system.

In order to analyze hemodynamic parameters during left ventricular assistance as an entity and not as decomposed parts, non-linear mathematical techniques were utilized. Pneumatically actuated ventricular assist systems (VAS) were implanted as left heart bypasses in acute animal experiments, using healthy adult mongrel dogs. By the use of the non-linear mathematical technique, the arterial blood pressure waveform (AP) was embedded into the four-dimensional phase space and projected into the three-dimensional phase space. The Lyapunov numerical method was used as an adjunct to the graphical analysis of the state space. The phase portrait of the attractor showed a complex structure; a three dimensional solid torus with a screw type structure as a part, suggesting deterministic chaos in the AP without left ventricular assistance. Positive lyapunov exponents confirmed the existence of chaos. During counterpulsation mode left ventricular assistance, the phase portrait of the attractor showed a more complex structure, and positive Lyapunov exponents suggested a greater dimensional deterministic chaos. However, non-structured patterns were seen in the phase space during internal mode VAS driving, suggesting the possibility of dissipative dynamics in the four dimensional phase space. These results suggest that the cardiovascular system with counterpulsation mode VAS driving is in a homeochaotic state, which is thought to be a flexible and intelligent control system. And there is greater dimensional complex dynamics in the circulatory regulatory system with VAD during internal mode assistance.

Animals

Direct inhibitory effect of atrial natriuretic peptide on isolated caecal circular smooth muscle cells via soluble guanylate cyclase.

Atrial natriuretic peptide (ANP) relaxes the vascular smooth muscle via particulate guanylate cyclase. Smooth muscle cells isolated from the caecal circular muscle layer of the guinea pig were used to examine the direct inhibitory effect of ANP on those cells. The role of adenylate cyclase, particulate guanylate cyclase, and soluble guanylate cyclase in the direct inhibitory effect of ANP on contraction of this muscle cell induced by carbachol was investigated. ANP inhibited the contractile response produced by 10(6)M carbachol in a concentration-dependent manner, with an IC50 value of 8nM. An inhibitor of adenylate cyclase (2',5'-dideoxyadenosine) and two inhibitors of particulate guanylate cyclase (HS-142-1, and PMA) had no significant effect on the relaxation produced by ANP. In contrast, an inhibitor of soluble guanylate cyclase (LY83583) significantly and completely inhibited the relaxation produced by ANP. This is the first report demonstrating the direct inhibitory action of ANP on the isolated caecal smooth muscle cells via soluble guanylate cyclase, which differs from the intracellular mechanism responsible for the relaxation of vascular smooth muscle produced by ANP.

Aminoquinolines

Fluctuations of the sympathetic nerve discharges in animals without natural heartbeat.

To assess the effect of artificial circulation on the circulatory regulatory system, rhythmical fluctuations in the cardiovascular system and autonomic nerve discharges were analyzed in animal experiments using adult mongrel dogs. Two pneumatically actuated ventricular assist devices were implanted as total biventricular bypass (BVB) under general anesthesia; then, the natural heart was electrically fibrillated to constitute the BVB part of the complete prosthetic circulation model. All hemodynamic data and sympathetic nerve discharges were recorded and calculated in the computer system by the use of spectral analyzing methods. In the power spectrum of the arterial blood pressure waveform during prosthetic circulation, the Mayer wave peak was significantly decreased though the respiratory wave peak was not significantly changed. However, the Mayer wave peak in sympathetic nerve discharges was significantly increased though the respiratory wave peak was not significantly changed. These results suggest that rhythmical fluctuations are a necessary response of the circulatory regulatory system including the autonomic nervous system. However, sympathetic nerve discharges respond to the artificial heart without rhythmical fluctuations.

Animals

Decrease in coupling of Gs in v-src-transformed NIH-3T3 fibroblasts: possible involvement of tyrosine phosphorylation of Gs by pp60v-src.

In Rous sarcoma virus (RSV)-transformed NIH-3T3 fibroblasts expressing pp60v-src as tyrosine protein kinase, isoproterenol-stimulated cAMP accumulation was much lower than in normal cells. The reduction in v-src-transformed cells seemed to be mainly due to a decrease in the number of beta 2-adrenoceptors. When the membranes were phosphorylated with ATP, however, the binding affinity of isoproterenol to beta 2-adrenoceptors was reduced in transformed cell membranes by 34% compared to that in normal cell membranes. The reduction in transformed cell membranes was restored to the level of normal cell membranes by treatment of membranes with anti-pp60v-src antibody. GTP gamma S- and cholera toxin-stimulated adenylyl cyclase activities were reduced with no change in forskolin-stimulated adenylyl cyclase activity in transformed cell membranes. The reduced effect of GTP gamma S was also restored by treatment with anti-pp60v-src antibody or by adding staurosporine, which inhibits a variety of protein kinases, including tyrosine protein kinase. One of the 32P-phosphoproteins phosphorylated with [gamma-32P]ATP in v-src-transformed cell membranes was bound to GTP-agarose, and was a 46-kDa molecule on a sodium dodecyl sulfate-polyacrylamide gel. This 46-kDa 32P-labeled phosphoprotein was immunoprecipitated with anti-phosphotyrosine antibody or anti-stimulatory GTP-binding protein (anti-Gs) antibody. These results suggest that pp60v-src phosphorylates the alpha-subunit of Gs and consequently causes a decrease in the coupling of beta 2-receptors to Gs and in the coupling of Gs to adenylyl cyclase.

3T3 Cells

[Two cases of blind pouch syndrome].

Case 1. A 39-yr-old male was presented with anemia. Initial blood examination showed remarkable iron deficiency anemia. Small bowel X-ray and abdominal CT examination revealed a dilated tract at the end of the ileum. Surgical operation was done. The surgical specimen showed side to side anastomosis which was reconstructed at the operation for rt. inguinal herniation 46 days after his birth. The oral side of the tract was remarkably dilated. Case 2. A 50-yr-old male was presented with dizziness. He had anemia and clubbed fingers. A small bowel X-ray examination was done and it showed side to side anastomosis in the middle of the small intestine. Surgical operation was performed. The surgical specimen showed side to side anastomosis about 2 m 20 cm from the Treitz' ligament, which was reconstructed during the operation for ileus when he was 10 years old. The blind portion was remarkably dilated. In both case, the anemia was improved after the operation.

Adult

Estimation of the following cardiac output using sympathetic tone and hemodynamics for the control of a total artificial heart.

A sympathetic neurogram is potentially useful for the development of a real time total artificial heart (TAH) control system. We used sympathetic tone and hemodynamic derivatives to estimate the following cardiac output in acute animal experiments using adult mongrel dogs. Moving averages of the mean left atrial pressure and mean aortic pressure were used as parameters of the preload and afterload, respectively. Renal sympathetic nerve activity (RSNA) was employed as a parameter of sympathetic tone. Equations for the following cardiac output were calculated using multiple linear regression analysis of the time series data. A significant correlation was observed between the estimated and following measured cardiac output. These results suggest the potential usefulness of the sympathetic neurogram for the real time TAH automatic control system.

Animals

Cardiac-related sympathetic nerve activity during circulation with only the left ventricular assist device.

Circulatory maintenance with a left ventricular assist device (LVAD) alone during cardiac arrest until heart transplantation has been evaluated. To assess the effect on the autonomic nervous system, the sympathetic neurogram was analyzed by power spectrum and coherence function. LVAD were inserted between the left atrium and the descending aorta in seven adult mongrel dogs and ventricular fibrillation was induced electrically. Renal sympathetic nerve activity (RSNA) was detected by bipolar electrodes attached to the left renal sympathetic nerve. Values of squared coherence between the arterial pulse wave and RSNA were calculated. Under the condition of circulatory maintenance with only LVAD, coherence at the cardiac rhythm frequency was decreased, and coherence at the LVAD pumping rhythm frequency was increased. These results indicate that the arterial pulse wave observed during maintenance of the circulation with only LVAD contributed to the sympathetic neurogram.

Animals

Postganglionic sympathetic nerve activity with correlation to heart rhythm during left ventricular assistance.

In order to evaluate the effect of ventricular assist device (VAD) driving on the autonomic nervous system, sympathetic neurograms during left ventricular (LV) assistance were analyzed by power spectrum and coherence function. Our TH-7B pneumatically-driven sac-type VAD was used in seven adult mongrel dogs. VADs were inserted between the left atrium and the descending aorta. Renal sympathetic nerve activity (RSNA) was detected by use of bipolar electrodes attached to the left renal sympathetic nerve via a retroperitoneal approach. Values of squared coherence between the arterial pulse wave and RSNA were measured at the same frequency of cardiac and VAD pumping rhythms. During LV assistance, coherence at the cardiac rhythm frequency was decreased, and coherence at the VAD pumping rhythm frequency was increased. These results indicate that the arterial pulse wave, which was produced by the VAD assistance, contributed to postganglionic sympathetic nerve activity.

Animals

Silent obstruction of the coronary stenosis between diagnostic angiography and later percutaneous transluminal coronary angioplasty without myocardial infarction.

Among 204 patients with severe coronary artery stenosis amenable to percutaneous transluminal coronary angioplasty (PTCA), 5 (2.5%) developed new silent total coronary occlusion of the vessel to be dilated without any chest symptom during the period between diagnostic coronary angiography and repeat coronary angiography at the time of the operation. We evaluated the clinical and angiographical characteristics of the patients with silent obstruction of the coronary artery in a short time, compared with the patients with unstable angina pectoris, who is considered to be suffering from acute myocardial infarction with severe chest symptom. None of the clinical variables studied showed a significant difference between the two groups. Among the angiographic variables, the degree of collateral was higher and impaired coronary perfusion distal to the lesion was more frequently found in unstable angina group. These results suggest that unstable angina is in a later stage of the ischemic heart disease compared with the time of the diagnostic angiography in patients with silent obstruction. Silent obstruction of high degree coronary stenosis is presumably due to the development of collateral circulation.

Aged

Spectral analysis of the renal sympathetic neurogram during left ventricular assistance.

To assess the effect of left ventricular assistance on cardiac-related sympathetic nerve activity, renal sympathetic nerve activity was analysed using power spectrum and coherence function. Our TH-7B pneumatically driven sac type Ventricular Assist Device (VAD) was used in the acute experiment of 7 adult mongrel dogs. VAD were inserted between the left atrium and the descending aorta as left heart bypass. RSNA was detected by use of the bipolar electrodes attached to the left renal sympathetic nerve. Values of squared coherence between the arterial pulse wave and RSNA were measured at the cardiac rhythm and VAD pumping rhythm. Before the left ventricular assistance, coherence at the cardiac rhythm and the pumping rhythm were 0.62 +/- 0.15, 0.23 +/- 0.18 (mean +/- SD), respectively. With the VAD pumping, these values became 0.09 +/- 0.05, 0.53 +/- 0.20, respectively. These results indicate that arterial pressure wave which was created by the VAD assistance contributed to the post ganglionic sympathetic activity.

Animals

Development and evaluation of the vibrating electromagnetically-driven artificial heart.

An vibrating electromagnetically driven univalved artificial heart was newly developed in our team. The fluid mechanical, hematological, and hemodynamical properties of this pump was evaluated in the moc circulation and animal experiments using adult goats. This vibrating electromagnetic (VEM) pump could generate more than 101/min with 10 Hz vibration, and could obtain the 2 kinds of flow and pressure patterns, such as constant peak and periodical peak patterns. The values of free Hb showed within acceptable values. We concluded that this pump is useful for totally implantable artificial heart.

Animals

TH-7B pneumatically driven sac-type ventricular assist device and drive system.

TH-7B pneumatically driven sac-type ventricular assist device and drive system including automatic control system were developed and evaluated in the chronic animal experiments. The blood-contacting surfaces of the blood pump are coated with either Cardiothane or Cardiomat. In the chronic experiments using adult goats, only one of fifteen goats showed sudden thrombus formation after 34 pumping days. No gross findings of thrombus formation were observed in any of the cases, except for a thin circular thrombus at the junction of the connectors and the sac of the blood pump. These results suggest that antithrombogenicity of this system was satisfactory for clinical use.

Animals

Development of the total artificial heart control system.

Sympathetic neurogram is potentially useful for the real time total artificial heart (TAH) control system. In this study, we used sympathetic tone and hemodynamic derivatives to prospect the following cardiac output in acute animal experiments using adult mongrel dogs. Moving averages of the mean left atrial pressure and mean aortic pressure were used as the parameters of the preload and afterload, respectively. Renal sympathetic nerve activity (RSNA) was also utilized as the parameter of the sympathetic tone. Equation which prospect the following cardiac output was calculated using the multiple linear regression analysis of the time series data in adult mongrel dogs. A significant correlation was observed between the prospective and following measured cardiac output. These results suggest the potential usefulness of the sympathetic neurogram for the real time TAH automatic control system.

Animals

Coherence function between sympathetic neurogram and arterial pulse wave in animal with total artificial heart.

To assess the influence of the total artificial heart replacement on autonomic nervous system, sympathetic neurogram was analyzed by power spectrum and coherence function. Two pneumatically driven sac-type ventricular assist devices were implanted as biventricular bypass (BVB) in adult mongrel dogs. After the BVB pumping, natural heart was electrically fibrillated to constitute the BVB type TAH model. Renal sympathetic nerve activity (RSNA) was recorded using the bipolar electrode attached to the left renal sympathetic nerve. RSNA was amplified and integrated by the use of R-C integrator. Power spectra of the RSNA and the values of squared coherence between the arterial pressure waveform and the RSNA were calculated by the computer system. In animal with TAH, coherence at the cardiac rhythm frequency was decreased, and coherence at the TAH pumping rhythm frequency was increased. These results indicate that the arterial pulse wave which was observed in TAH animal contributed to sympathetic neurogram.

Animals

Clinical application of the ventricular assist devices in Japan.

From 1980 to March in 1989, there were 177 clinical application of ventricular assist device in Japan. Original diseases were 50% ischemic heart disease and 37% valvular disease. Duration of assistance ranged from one hour to 70 days. Thirty-one cases weaned from ventricular assistance and 11 cases became long-time survivors.

Cause of Death