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Biomedical subjects

A Kitabatake

Publications and source records attributed to A Kitabatake.

At least 37 records · Page 2Linked to original sources
PubMed1995

[Pathophysiology and treatment of congestive heart failure--recently advanced strategy for heart failure].

The principle functions of the heart are to accept blood from the systemic and the pulmonary circulatory system, pump and deliver it to the whole body tissues and lungs. The term "heart failure" is used to describe the pathophysiological state in which an abnormality of cardiac function is responsible for failure of the heart to pump blood at a rate commensurate with the requirements of the metabolizing tissues, or to do so only from an elevated filling pressure. Thus, for a long period, heart failure has been thought of as a mechanical disorder of the heart and vessels, and its treatment has been based on improving impaired cardiac function and hemodynamic disorder. Recently multi-center, randomized placebo-controlled survival trials revealed that pure inotropic agents such as phosphodiesterase inhibitors succeeded in mechanical improvement, yet not only failed to prolong the patient's life, but also increased mortality. A number of neurohumoral mechanisms, which are activated in heart failure, were thought to be compensatory ones. However, survival trials demonstrated that two types of drug interfering with the renin-angiotensin system and the sympathetic nervous system reduced mortality. Those drugs are angiotensin-converting enzyme (ACE) inhibitors and beta blockers. ACE inhibitors reduce the direct effects of angiotensin II on myocardial cells, which may lead to cell necrosis, imbalanced remodeling through fibrosis, and attenuate the progressive ventricular dilatation. Local tissue renin-angiotensin system may be potentially important in regulating the angiotensin II production in both heart and vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1995

Effects of BQ-485, a selective ETA antagonist, on endothelin-mediated vasomotion in rat coronary vascular beds.

The effects of BQ-485, a selective endothelin (ET)-A receptor antagonist, on the vasomotion induced by a low dose of ET were investigated. In the isolated rat heart perfused with Krebs-Henseleit solution at a constant flow, intracoronary bolus injection of ET-1 or ET-3 (10 pmol) elicited a rapid transient decrease, followed by a slight sustained increase, in the coronary perfusion pressure (CPP). The decrease in CPP induced by ET-1 was similar in magnitude to (approximately 30%) but shorter in duration than that induced by ET-3. Pretreatment of the heart with saponin (30 micrograms/ml) to denude the coronary endothelium abolished the decrease and markedly enhanced the increase in CPP induced by ETs, indicating that the vasorelaxing action of ETs is endothelium-dependent. The selective ETA receptor antagonist BQ-485 (1 microM) significantly prolonged the duration of the ET-1-induced decrease in CPP, made the vasodilatation by ET-1 indistinguishable from that by ET-3, and eliminated the subsequent increase in CPP. In the saponin-treated heart, BQ-485 also eliminated the ET-1-mediated increase in CPP. These findings suggest that, in rat coronary vascular beds, a low dose of ET-1 elicits vasoconstriction and endothelium-dependent vasodilatation through the ETA receptor on the vascular smooth muscle and presumably the ETB receptor on the endothelium, respectively. Furthermore, it is expected that selective ETA receptor antagonists, including BQ-485, may be able to protect the heart against ET-1-induced coronary spasm in situations, such as hyperlipidemia or artherosclerosis, in which the release and/or function of endothelium-derived vasorelaxing substances is impaired.

Animals↗
PubMed1994

Distribution of angiotensinogen in diseased human hearts.

Extrahepatic synthesis and localization of angiotensinogen (ATN) have been described in animals, thus establishing the tissue renin-angiotensin (RA) system. However, there had been no reports of tissue RA systems in human organs, including the heart. In earlier, we have reported the possibility of ATN synthesis in the human heart using ribonuclease protection assay system. ATN mRNA was detected not only in the liver, but also in both the atrial and ventricular heart tissues, suggesting that ATN is synthesized in the human heart. In this report, we looked for the distribution of ATN in diseased human heart. Northern blot hybridization of cDNA with total RNA extracted from human liver, brain, kidney, atrial and ventricular tissues revealed that ATN mRNA exists in cardiac ventricule. Immunohistochemical studies using a specific antibody to ATN revealed a stronger reaction in the endocardial layer of the human left ventricle, than in the epicardial layer, and intense immunoreactivity in the conduction system and right atrium. This distribution pattern was similar to that of human atrial natriuretic peptide (hANP), which functions a smooth muscle relaxant. Double immunostaining of ATN and hANP demonstrated that all myocytes in the right atrium had immunopositive reactions to ATN, hANP or both of ATN and hANP. Double immunoelectron staining enabled us to show more detailed localization of ATN and hANP; hANP only existed in the specific granules and ATN existed in the myofibril, but not in the granule. Furthermore, our experiments provide evidence of ATN in healthy human hearts and also reveal a widespread immunopositive reaction for ATN in the left ventricle of diseased hearts.

Angiotensinogen↗
PubMed1994

Microdynamics of the phospholipid bilayer in cardiomyopathic hamster heart cell membrane.

To investigate the microdynamics and the structural architecture of the membrane phospholipid bilayer during the course of cardiomyopathy, membrane fractions were prepared from hearts of cardiomyopathic Syrian hamsters (BIO 14.6) aged 4, 18 and 31 weeks and compared with age-matched control hamsters (F1b). Membrane cholesterol, phospholipids and phospholipid fatty acids were measured by thin-layer chromatography, gas-liquid chromatography and high performance liquid chromatography. Microdynamics of the phospholipid bilayer were determined by a nanosecond fluorometer using pulsed excitation of a fluorescent probe, diphenyl-hexatriene. At the age of 4 weeks, there was no difference in lipid compositions and microdynamics between the BIO 14.6 and F1b. At the age of 18 weeks, saturated fatty acids, 18:0 and 22:0 increased and 20:0, 20:2 and 32:4 decreased in the BIO 14.6. At the age of 31 weeks, adding to the above changes in phospholipid fatty acids, unsaturated fatty acids 20:4 and 22:6 decreased, moreover membrane phospholipids, especially phosphatidylinositol and phosphatidylethanolamine significantly decreased. The viscosity and the wobbling angle of phospholipid molecules were decreased significantly. We have previously demonstrated that intracellular Ca2+ accumulation might be responsible for the pathogenesis of cardiomyopathy. Thus, we conclude that cardiomyopathic membrane may alter its structure and function with age. These alterations in cell membranes might be involved in the cardiac hypertrophy and dysfunction through impaired Ca2+ handling in cardiomyopathic hamsters.

Animals↗
PubMed1994

Transforming growth factor beta-1 modulates the number of beta-adrenergic receptors in cardiac fibroblasts.

The effects of transforming growth factor beta-1 on concentration of intracellular Ca2+ changes in the presence of isoproterenol were studied in cardiac fibroblasts. Transforming growth factor beta-1 effect on cyclic-AMP production and ligand assay of beta-adrenergic receptors were also examined. Production of cyclic-AMP in fibroblasts preincubated with transforming growth factor beta-1 decreased compared with non-transforming growth factor beta-1-treated fibroblasts in the presence of isoproterenol. An increase of intracellular Ca2+ concentration in the presence of isoproterenol was also inhibited in transforming growth factor beta-1-treated fibroblasts. Islet-activating protein did not restore these reactions of transforming growth factor beta-1. Concentration change of intracellular calcium under the treatment of transforming growth factor beta-1 was unaffected by forskolin addition. Binding of [3H]CGP-12177 was decreased to 47% of control preincubated for 24 h with transforming growth factor beta-1 in fibroblasts. Scatchard plots suggested a decrease in beta-adrenergic receptor number without specific change in receptor affinity. These results suggested that transforming growth factor beta-1 modulates the signal transduction through beta-adrenergic receptor and intracellular Ca2+ concentration by regulating the number of receptor in fibroblasts.

Animals↗
PubMed1994

Depressed responsiveness to angiotensin II in ventricular myocytes of hypertrophic cardiomyopathic Syrian hamster.

Electromechanical responsiveness to angiotensin II (Ang II) receptor stimulation in ventricular myocardium and myocytes of hypertrophic cardiomyopathic Syrian hamsters (BIO 14.6) was examined and compared with that in preparations of normal hamsters (F1B) using conventional microelectrode and patch clamp techniques. Action potential duration (APD) and developed tension (DT) corrected for the cross-sectional area of the papillary muscles of 14-20 week-old BIO 14.6 hamsters were significantly smaller than those in preparations of age-matched normal hamsters. An Ang II (1 microM)-induced increase in DT in BIO 14.6 papillary muscles (24.7 +/- 11.0%) was significantly smaller than that in F1B papillary muscles (53.8 +/- 8.5%), which was associated with a smaller increase in APD in BIO 14.6 papillary muscles. In ventricular myocytes of both BIO 14.6 and F1B hamsters. Ang II increased the calcium current (ICa) following a transient decrease in ICa. However, the magnitude of the Ang II-induced increase in ICa in BIO 14.6 myocytes (35.5 +/- 7.5%) was significantly smaller than that in F1B myocytes (86.0 +/- 19.7%), suggesting a causal relationship between ICa and mechanical response to Ang II in these hamsters. The depressed responsiveness to Ang II receptor stimulation in hypertrophic cardiomyopathic hamster is in a marked contrast with the enhanced responsiveness to alpha 1-adrenergic stimulation, which was demonstrated by previous studies, and may be one of adaptational changes to the activated renin-angiotensin system in the cardiomyopathy.

Action Potentials↗
PubMed1994

Involvement of muscarinic M1 receptor in the central pathway of the serotonin-induced Bezold-Jarisch reflex in rats.

The involvement of central muscarinic receptors in mediating the Bezold-Jarisch reflex elicited by injection of 5-hydroxytryptamine (5-HT) was studied in urethane/chloralose-anesthetized rats. Intravenous bolus injection of 5-HT (3.1 to 50 micrograms/kg) evoked a short-lasting dose-related bradycardia and hypotension, the Bezold-Jarisch reflex, accompanied with bursts of the efferent cervical vagus nerve. Systemic administration of atropine (0.1 and 1 mg/kg) blocked not only the cardiac responses but also the efferent cervical vagus nerve activity changes. Although the afferent cervical vagus nerve was also activated by an intravenous bolus injection of 5-HT, these responses were not altered by the systemic administration of even a high dose of atropine (1 mg/kg). Intracerebroventricular (i.c.v.) administration of pirenzepine (1 and 10 micrograms/10 microliters), a selective M1 receptor antagonist, caused a rightward shift of the 5-HT dose-response curve for efferent vagus nerve activity. In contrast, i.c.v. administration of muscarinic type 2 receptor antagonist, gallamine, and type 3 receptor antagonist, p-fluorohexahydrosiladifenidol, failed to alter the response in nerve activity to 5-HT. These results suggest that the activation of central nervous muscarinic receptors might be involved in mediating the Bezold-Jarisch reflex and that the subtype might belong to type 1.

Animals↗
PubMed1994

Lysophosphatidylcholine, a component of stromal phospholipids, as a candidate vasoconstrictive factor in stroma-free hemoglobin.

Stroma-free hemoglobin (SFH) contains a trace amount of phospholipids, which has been implicated in the toxic reactions associated with SFH. We analyzed stromal phospholipids by high-performance liquid chromatography and found that SFH contained small quantities of lysophosphatidylcholine (LPC), which is known to be capable of producing a defect in endothelium-dependent arterial relaxation, in addition to major classes of constituent phospholipids in red cell membrane. LPC content was determined to be 1.65 nmol/ml (hemoglobin 8.1 g/dl). To evaluate the role of these stromal phospholipids in SFH-induced vasoconstriction, we next examined the effect of lipids on vascular tone in rabbit aortic strips. Preincubation with the crude lipid extract or the LPC purified from SFH significantly inhibited acetylcholine-induced relaxation in phenylephrine-precontracted tissues. The LPC-induced inhibition was reversed by incubation of the tissues in the absence of lipids, indicating the functional integrity of endothelium. From these results, we propose a possibility that LPC, a component of stromal phospholipids, is a candidate for vasoconstrictive factors present in SFH.

Acetylcholine↗
PubMed1994

Contribution of chamber compliance and left ventricular minimum pressure to abnormal left ventricular filling dynamics.

This study was designed to clarify whether changes in transmitral flow velocity patterns in left ventricular (LV) dysfunction are determined primarily by changes in left atrial (LA) pressure and LV relaxation, and, if not, to determine the contribution of changes in other parameters. Two levels of acute LV dysfunction were produced in 11 dogs by coronary microembolization, and pulsed Doppler transmitral flow velocity patterns and hemodynamic parameters were recorded. The mean ratio of peak early diastolic filling velocity (E) to peak late diastolic filling velocity decreased with mild LV dysfunction (LV end-diastolic pressure of between 12 and 17 mmHg), and redistribution of diastolic filling to early diastole was observed with severe LV dysfunction (LV end-diastolic pressure of > or = 18 mmHg). Changes in E correlated best with those in the LA-LV pressure gradient integral. Multiple linear regression analysis of the changes in possible determinants of the pressure gradient integral, i.e., LA to LV crossover pressure, LV time constant, LV minimum pressure, and LA and LV chamber compliance, yielded a highly significant correlation with the changes in E. However, analysis of only the changes in the crossover pressure and the time constant showed a very poor correlation. Thus, changes in chamber compliance and LV minimum pressure, in addition to the changes in LA pressure and LV relaxation, may significantly affect the changes in E that are associated with LV dysfunction.

Animals↗
PubMed1994

The quality control of stroma-free hemoglobin: lysophosphatidylcholine, a component of stromal phospholipids, as candidate vasoconstrictive factor.

We characterized stromal phospholipids in stroma-free hemoglobin (SFH) by normal-phase and cation-exchange HPLCs, and found that SFH contained not only four phospholipids which were the major constituent classes in membrane, but also several peaks which were not yet identified. The residual amounts of these lipids in SFH were changed with storage of red cell concentrates. The four major phospholipids decreased concomitantly with storage, whereas the unidentified peaks increased after 21 days and then decreased after 48 days. We also found that SFH contained lysophosphatidylcholine (LPC) at 5.71 micrograms/ml, which was the deacylated metabolite of phosphatidylcholine (PC). These results suggest that stromal phospholipids are degradable. Since LPC is known to be capable of producing a defect in endothelium-dependent arterial relaxation, we next examined the effect of stromal lipids on vascular tone in rabbit thoracic aortic strips. Preincubation with the crude lipid extract or the LPC purified from SFH by TLC significantly inhibited acetylcholine (ACh)-induced relaxation in phenylephrine (PhE)-precontracted tissues. These observations have led to the proposal that LPC, a component of stromal phospholipids, induces vasoconstriction as a result of inhibition of endothelium-dependent vasorelaxation.

Animals↗
PubMed1994

[Image diagnosis of vasculitis--ultrasound].

Ultrasound is widely used for the diagnosis and follow-up of patients with many kinds of vasculitis. Transcutaneous or transesophageal two-dimensional ultrasound images can depict vascular wall lesions associated with vasculitis such as stenosis, aneurysm or wall thickening. Pulsed Doppler and color Doppler are useful for the assessment of stenoses and changes in blood flow. Recent progress in intravascular ultrasound apparatus made it possible to more precisely assess morphological changes in vascular wall. Intravascular ultrasound of a 27-year old male patient suffering from inferior myocardial infarction with right coronary aneurysms revealed calcification and fibrosis of the intima and early development of atherosclerosis in both right and left coronary arteries suggestive of the sequelae of Kawasaki disease.

Adult↗
PubMed1994

Pertussis toxin pretreatment alters agonist binding to beta-adrenoceptors in rabbit ventricular myocardium.

The influence of pretreatment with pertussis toxin (PTX) on characteristics of beta-adrenoceptor bindings was examined in myocardial ventricular membranes prepared from rabbits which received an intravenous injection of PTX (10 micrograms/kg) or its vehicle. The density and affinity of beta-adrenoceptors assessed by (-)-[125I]iodocyanopindolol were not significantly altered by PTX pretreatment. However, a fraction of agonist binding sites with high affinity significantly increased in PTX-pretreated myocardial membranes. In the presence of 100 microM 5'-guanylyl imidodiphosphate, all agonist binding sites were converted to low-affinity sites in both control and PTX-pretreated membranes. The results suggest that Gi might regulate negatively coupling of beta-adrenoceptors to Gs.

Animals↗
PubMed1993

Increased calcium release from sarcoplasmic reticulum stimulated by inositol trisphosphate in spontaneously hypertensive rat heart cells.

It is known that inositol (1, 4, 5)-trisphosphate (IP3) stimulates Ca2+ release from sarcoplasmic reticulum (SR) in several tissues, but in cardiac myocytes this phenomenon has not been confirmed. The purpose of the present study was to confirm the effect of (1, 4, 5)-IP3 on Ca2+ release from SR in cardiac myocytes. The effect of IP3 on Ca2+ release from SR in hypertrophic cardiac cells was also determined. We examined the effects of IP3 on Ca2+ release from cardiac myocyte SR by the digital-image method in a single cell. We also determined the effect of IP3 on calcium release from isolated SR. SR was prepared from spontaneous hypertensive rat hearts and Wistar kyoto rat hearts. The SR was prelabeled with 45Ca2+, and then incubated with the indicated concentrations of IP3 for 1 min at 37 degrees C. In cardiac myocytes treated with saponin, Ca2+ release stimulated by 10 microM (1, 4, 5)-IP3 was detected by fura-2. In 45Ca2+ prelabeled SR, the maximal Ca2+ release was achieved at 10 microM IP3 incubated for 1 min. The release of Ca2+ was higher in SR of SHR than in the SR of WKY. IP3 stimulates Ca2-release from cardiac SR, and this release is greater in SHR than in WKY. However, it is uncertain whether this phenomenon plays a role in cardiac hypertrophy.

Animals↗
PubMed1993

Effects of thiol protease inhibitors on fodrin degradation during hypoxia in cultured myocytes.

The effects of thiol protease inhibitors on fodrin (a cell membrane nonerythroid spectrum-like protein) degradation were studied during hypoxia in cultured myocytes. Cardiac myocytes, isolated from neonatal rat hearts, were incubated under hypoxic conditions for 6 h. Cell membrane proteins, including fodrin, prepared from hypoxic myocytes were examined with electroblots stained for fodrin by the peroxidase method. Cell death during hypoxia rose to 80% after 6 h. Intracellular protease activity was also elevated in hypoxia. This intracellular protease activity was markedly inhibited by the cysteine protease inhibitor E-64 and calpain inhibitor 1. Hypoxic cell death was also suppressed by E-64 and calpain inhibitor 1. A 125 kDa immunoreactive degradation product of fodrin was found in hypoxic conditions. Treatment with E-64 and calpain inhibitor 1 decreased both the appearance of this band and the degradation of fodrin. These observations indicate that intracellular thiol proteases, including calpains, are activated during hypoxia and that these are related to cell membrane protein degradation, especially of fodrin. The data also suggest that protease inhibitor E-64 treatment may be beneficial in protection against hypoxic myocyte injury.

Animals↗
PubMed1993

Effects of heart rate on left ventricular filling dynamics: assessment from simultaneous recordings of pulsed Doppler transmitral flow velocity pattern and haemodynamic variables.

OBJECTIVE: The effects of heart rate on transmitral flow velocity pattern are still controversial. The aim of this study was to examine the relations between the changes in Doppler echocardiographic variables and those in haemodynamic variables in association with altering heart rate. METHODS: Pulsed Doppler transmitral flow velocity pattern and left atrial and left ventricular pressures were simultaneously recorded at various heart rates (from 80 to 120 beats.min-1) in 14 dogs. RESULTS: As heart rate increased, peak late diastolic filling velocity increased, the time-velocity integral of the early diastolic filling wave decreased, and the deceleration time of early diastolic flow shortened without significant changes in mean values of peak early diastolic filling velocity and acceleration time of early diastolic flow. Peak early diastolic filling velocity increased with heart rate, however, in five dogs and decreased in the other nine dogs. The shortening of the time constant of left ventricular isovolumic relaxation was greater in the five dogs in which peak early diastolic filling velocity increased with heart rate than in the other nine dogs. Results of multiple stepwise linear regression analysis showed that the changes in peak early diastolic filling velocity correlated with the changes in the crossover pressure and peak+dP/dt in addition to the time constant, and that diastolic filling period was not selected as an affecting factor. Changes in the other Doppler echocardiographic variables did not correlate solely with changes in heart rate, or diastolic filling period, but correlated in a complex fashion with the combined changes in haemodynamic variables associated with altering heart rate. CONCLUSIONS: Although transmitral flow velocity pattern changes with altering heart rate, this change is not considered to be a direct effect of alteration in heart rate, but an indirect one through the associated haemodynamic changes including left atrial pressure and left ventricular relaxation and contractility.

Animals↗
PubMed1993

Possible contribution of potassium channels to the endothelin-induced dilatation of rat coronary vascular beds.

The mechanism for the endothelin (ET)-induced vasodilatation of the endothelium-intact rat coronary vascular bed was investigated. Continuous infusion (0.1-1 nM) or bolus injection (1-100 pmol) of ET-1 or ET-3 elicited a dose-related transient decrease, followed by a slight sustained increase, in the coronary perfusion pressure (CPP). The decrease in CPP induced by an injection (10 pmol) of ET-1 or ET-3 was not modified by indomethacin (5 microM). However, oxyhemoglobin (5 mM) shortened the duration of the ET-induced decrease in CPP, although it did not affect the magnitude. The ET-induced decrease in CPP was abolished by raising K+ in the perfusing solution from 5.9 to 16.9 mM. These findings suggest that the ET-induced dilatation of the rat coronary vascular beds may not be mediated by cyclooxygenase products. The ET-induced vasorelaxation may be mediated, at least in part, by endothelium-derived relaxing factor and may be related to opening of K+ channels.

Animals↗
PubMed1993

Time course of functional improvement in stunned myocardium in risk area in patients with reperfused anterior infarction.

BACKGROUND: The beneficial effect of coronary reflow on myocardial salvage may be assessed more accurately than in previous studies if the size of risk area is taken into account, particularly because the size of risk area varies significantly among patients. In this study, the risk area was determined with myocardial contrast echocardiography to investigate the time course of functional recovery of postischemic myocardium within the risk area in patients with reperfused anterior myocardial infarction. METHODS AND RESULTS: The study population consisted of 21 patients with anterior myocardial infarction who achieved coronary reflow within 6 hours of onset by means of thrombolysis or coronary angioplasty. Myocardial contrast echocardiography was performed with the injection of hand-agitated Haemaccel (5 ml) into the right and left coronary arteries before coronary reflow, and the risk area was defined as the area of contrast perfusion defect in the apical long-axis view. The ratio of the endocardial length of abnormal contraction (dyskinesis/akinesis) segment to that of contrast defect segment (AS/CD) was determined at days 1, 2, 3, 7, 14, and 28 of reflow. Before reflow, the length of contrast defect correlated well with the segment length of dyskinesis/akinesis. The values for AS/CD in patients with successful reperfusion significantly and progressively decreased until day 14; 1.00 +/- 0.02 at day 1, 0.93 +/- 0.11 at day 2 (p < 0.05 versus day 1), 0.84 +/- 0.16 at day 3 (p < 0.05 versus day 2), 0.80 +/- 0.13 at day 7 (p < 0.01 versus day 2), 0.73 +/- 0.10 at day 14, and 0.72 +/- 0.10 at day 28. Greater improvement in function was obtained in patients reperfused within 4 hours than in those reperfused at > or = 4 hours (AS/CD at day 28, 0.64 +/- 0.12 versus 0.75 +/- 0.09, p < 0.05). CONCLUSIONS: Thus, a significant amount of myocardium, an average of 28% in segment length of the risk area, is salvaged in patients with reperfused anterior myocardial infarction. Major functional improvement seems to be achieved within 14 days of reflow.

Adult↗