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ABSTRACT: Atrial electrical remodeling is thought to be the cause of the maintenance of atrial fibrillation (AF). Although the initiation and maintenance of AF is partially associated with autonomic nervous tone, vagally mediated AF does not tend to become permanent. Therefore, the effects of preceding vagal stimulation (VS) on the atrial effective refractory period (ERP) under electrical remodeling conditions were investigated in anesthetized dogs. Atrial ERPs were measured at 5 sites before and after a 7-h period of atrial rapid pacing in the control group. In the VS group, the vagus nerve was stimulated for 20 min before a period of atrial rapid pacing. Atrial rapid pacing shortened the ERP at each site in the control group (electrical remodeling). On the other hand, atrial rapid pacing after VS did not shorten the ERP at any site in the VS group. Tetrodotoxin, which was administered into the fatty tissue overlying the right atrial side of the right pulmonary vein junctions, blocked the protective effect of VS against the shortening of the ERP induced by atrial rapid pacing. In contrast, atropine did not interfere with such protective effects. These results suggest that VS prior to atrial rapid pacing protects the atrium from atrial electrical remodeling.
Japanese Circulation Journal 01/2002; 65(12):1077-81.
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Echocardiography 05/2001; 18(3):203-4. · 1.24 Impact Factor
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ABSTRACT: Some parasympathetic ganglionic cells are located in the epicardial fat pad between the medial superior vena cava and the aortic root (SVC-Ao fat pad) of the dog. We investigated whether the ganglionic cells in the SVC-Ao fat pad control the right atrial contractile force, sinus cycle length (SCL), and atrioventricular (AV) conduction in the autonomically decentralized heart of the anesthetized dog. Stimulation of both sides of the cervical vagal complexes (CVS) decreased right atrial contractile force, increased SCL, and prolonged AV interval. Stimulation of the rate-related parasympathetic nerves to the sinoatrial (SA) node (SAPS) increased SCL and decreased atrial contractile force. Stimulation of the AV conduction-related parasympathetic nerves to the AV node prolonged AV interval. Trimethaphan, a ganglionic nicotinic receptor blocker, injected into the SVC-Ao fat pad attenuated the negative inotropic, chronotropic, and dromotropic responses to CVS by 33 approximately 37%. On the other hand, lidocaine, a sodium channel blocker, injected into the SVC-Ao fat pad almost totally inhibited the inotropic and chronotropic responses to CVS and partly inhibited the dromotropic one. Lidocaine or trimethaphan injected into the SAPS locus abolished the inotropic responses to SAPS, but it partly attenuated those to CVS, although these treatments abolished the chronotropic responses to SAPS or CVS. These results suggest that parasympathetic ganglionic cells in the SVC-Ao fat pad, differing from those in SA and AV fat pads, nonselectively control the atrial contractile force, SCL, and AV conduction partially in the dog heart.
AJP Heart and Circulatory Physiology 10/2000; 279(3):H1201-7. · 3.71 Impact Factor
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ABSTRACT: Effects of a Na+/Ca2+ exchanger inhibitor, KB-R7943 (2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl] isothiourea methanesulfonate), on the sinoatrial nodal pacemaker activity, atrial contractility and ventricular contractility were investigated in the isolated and blood-perfused right atrium and left ventricle of the dog. KB-R7943 (0.03- 3 micromol) induced negative inotropic effects and negative followed by positive chronotropic effects in the right atrium and negative inotropic effects in the left ventricle. Neither atropine nor hexamethonium affected the cardiac responses to KB-R7943. Propranolol attenuated the positive chronotropic response to KB-R7943 but imipramine did not. Tetrodotoxin potentiated the positive chronotropic response to KB-R7943 in 6 of 11 isolated atria. When NaCl infusion increased atrial contractile force and atrial rate, KB-R7943-induced negative inotropic and chronotropic responses were attenuated in a dose-dependent manner. CaCl2 infusion potentiated the negative chronotropic response to KB-R7943 but did not affect the inotropic response significantly. On the other hand, ouabain (17 nmol) attenuated the negative inotropic response, but not chronotropic response, to KB-R7943. These results suggest that KB-R7943-induced cardiac effects relate to the Na+ activity, probably mediated through the Na+/Ca2+ exchanger, and the Na+/Ca2+ exchanger modifies the pacemaker activity and myocardial contractility in the dog heart.
The Japanese Journal of Pharmacology 03/2000; 82(2):155-63.
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ABSTRACT: The site of impulse origin in the right atrium generally is considered to be a single static locus within the sinoatrial (SA) node. Previous investigators showed that the pacemaker site may shift due to changes in sympathetic or parasympathetic neural activity. We investigated the interactions between sympathetic and parasympathetic influences on the site of impulse initiation in the right atrium in anesthetized dogs.
We determined the site of impulse initiation and the spread of excitation over the anterior and posterior regions of the right atrium by a matrix of 48 unipolar recording electrodes. We assessed the spread of excitation at 3-msec intervals by constructing isochronal activation sequence maps. Sympathetic stimulation increased the frequency of atrial excitation (i.e., the heart rate), but also shifted the earliest activation region (EAR) from a locus in the SA node to a locus in the superior vena cava (the superior pacemaker site). Vagus stimulation decreased the heart rate and shifted the EAR to a lower site in the SA node or a site in the inferior right atrium along the sulcus terminalis (the inferior pacemaker site). A short period of vagus stimulation during a more prolonged sympathetic stimulation elicited a larger decrease in rate than did vagus stimulation alone and shifted the EAR from the superior site to the SA node or to the inferior site. After atropine, combined stimulation shifted the EAR to the superior site, but propranolol did not change EAR location.
Our results suggest that parasympathetic activity predominates over sympathetic activity not only on heart rate, but also on the location of the EAR in the anesthetized dog.
Journal of Cardiovascular Electrophysiology 09/1999; 10(8):1066-76. · 3.06 Impact Factor
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ABSTRACT: To investigate whether slow inward Ca2+ current (ICa), hyperpolarization-activated inward current (If), and a rapid type of delayed rectifier K+ current (IKr) similarly act on the pacemaker location, sinoatrial node region, and subsidiary superior and inferior pacemaker regions, we studied the effects of verapamil, zatebradine, and E-4031 on the atrial rate and the 3-ms earliest activation region (EAR) determined from the isochronal activation sequence map in the autonomically decentralized heart of the anesthetized dog. Three blockers decreased atrial rate similarly. Verapamil shifted the EAR from the SA node region to the inferior pacemaker region. The EAR induced by zatebradine was variable, but the EAR induced by E-4031 tended to shift to the inferior pacemaker region. Sympathetic nerve stimulation increased atrial rate and shifted the EAR to the superior pacemaker region. Verapamil attenuated the increased atrial rate by 28%, and it shifted the EAR to the lower pacemaker regions consistently. Zatebradine also attenuated the increased rate by 53% and shifted the EAR from the anterior to the posterior-superior right atrium. On the other hand, E-4031 affected neither the rate nor the EAR in response to sympathetic stimulation. These results suggest that ICa, If, and IKr inhibitors differentially influence the pacemaker activity among three pacemaker regions when sympathetic tone is absent or present and that the role of ICa, If, and IKr of the pacemaker cells distributed in the atrial pacemaker complex is different in the dog heart in situ.
Journal of Pharmacology and Experimental Therapeutics 07/1999; 289(3):1334-42. · 3.83 Impact Factor
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ABSTRACT: Parenchymal manifestations of pulmonary sarcoidosis include a diffuse, symmetric, reticulonodular interstitial pattern, a fibrotic pattern, and an acinar pattern. Large pulmonary nodules in sarcoidosis are rare, and their frequency (> 1 cm in diameter) has been estimated at 2-4%. We report a rare case of sarcoidosis associated with large bilateral pulmonary nodules. These nodules reached up to 7 cm in diameter, which is larger than any others reported previously. Furthermore, these nodular lesions developed within only 6 months of normal chest X-ray results and were not found to accompany bilateral hilar lymph adenopathy, which is observed in the usual course of sarcoidosis. As described above, this case of pulmonary sarcoidosis was significant not only in terms of the large size of the nodules but also the unique chest X-ray course.
Respirology 12/1998; 3(4):273-6. · 2.42 Impact Factor
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ABSTRACT: No data are available for the direct effect of C-type natriuretic peptide (CNP) on atrioventricular (AV) conduction in mammalian hearts. Thus we studied the dromotropic effects of CNP-22 injected into the AV node artery in autonomically decentralized hearts in open-chest, anesthetized dogs. CNP decreased AV interval (AV conduction time) in a dose-dependent manner with increase in coronary artery blood flow rate in six anesthetized dogs. Isosorbide dinitrate did not affect AV interval, but it increased coronary artery blood flow rate. A guanylyl cyclase-linked natriuretic peptide receptor antagonist, HS-142-1, inhibited the decreases in AV interval and the increases in coronary blood flow rate in response to CNP, whereas propranolol did not affect the positive dromotropic response to CNP. These results demonstrate that CNP decreases AV interval and increases coronary artery blood flow rate mediated by a guanylyl cyclase-linked natriuretic peptide receptor, but not beta-adrenoceptor, in the dog heart.
The American journal of physiology 09/1998; 275(2 Pt 2):H717-20.
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ABSTRACT: There are no available data on the direct effect of C-type natriuretic peptide (CNP) and brain natriuretic peptide (BNP) on the myocardial contractility in mammalian hearts. Thus we studied the inotropic and chronotropic effects of CNP-22 and BNP-32 compared with those of atrial natriuretic peptide (ANP)-28 using the isolated, blood-perfused canine right atrial or left ventricular preparations. CNP increased the atrial contractile force in a dose-dependent manner with a small increase in sinus rate in isolated atria, whereas neither ANP nor BNP changed atrial force and rate. CNP but not BNP also increased the ventricular contractile force in isolated ventricles. Pretreatment with a high dose (3 nmol) of CNP attenuated the positive inotropic response to CNP at a low dose (1 nmol) but not to norepinephrine. A guanylyl cyclase-linked natriuretic peptide receptor antagonist, HS-142-1, inhibited the increases in atrial contractile force and sinus rate in response to CNP, but it did not affect the positive cardiac responses to norepinephrine. Propranolol did not block the positive cardiac responses to CNP. 3-Isobutyl-1-methylxanthine in rates of 0.6 to 1.3 mumol/ min attenuated the CNP-induced positive inotropic responses, when it potentiated the positive inotropic response to norepinephrine. On the other hand, parasympathetic nerve stimulation attenuated the positive cardiac responses to CNP and norepinephrine. These results demonstrate that CNP increases myocardial contractile force with a small increase in sinus rate mediated by guanylyl cyclase-linked natriuretic peptide receptors, probably type B receptors in the dog heart, and suggest that the positive inotropic response to CNP is influenced by the cyclic adenosine 3',5'-monophosphate-dependent signal transduction.
Journal of Pharmacology and Experimental Therapeutics 08/1998; 286(1):70-6. · 3.83 Impact Factor
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ABSTRACT: A 27-year-old female with short stature and mild hearing loss was diagnosed as having focal-segmental glomerulosclerosis by renal biopsy at our hospital. One year later she developed progressive renal dysfunction and cardiac failure and was admitted again to our hospital for evaluation. Though her only neurological disorder was mild hearing loss, her short stature and elevated lactate and pyruvate values in cerebrospinal fluid suggested mitochondrial cytopathy. A muscle biopsy specimen of the left biceps brachii, using modified Gomori trichrome stain, showed a typical image of ragged-red fibers, and an increased number of giant mitochondria with paracrystalline inclusions were visible by electron microscopy. Mitochondrial DNA from the skeletal muscle showed an A-to-G transition at 3243 of transfer RNALeu(UUR), the common point mutation for mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes. These data confirmed the diagnosis of atypical mitochondrial cytopathy with renal and heart involvement. Mitochondrial cytopathies are often associated with hypertrophic cardiomyopathy but rarely with renal disease. Among the few reported cases with associated renal disease, most included renal tubular disorders; few cases with focal glomerular sclerosis are known. The present case of atypical mitochondrial cytopathy was characterized by a unique clinical course and rare complications with focal-segmental glomerulosclerosis.
American Journal of Nephrology 02/1998; 18(6):551-6. · 2.54 Impact Factor
