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Biomedical subjects

S Takeo

Publications and source records attributed to S Takeo.

At least 163 records · Page 9Linked to original sources
PubMed1988

Cardioprotective action of alpha-blocking agents, phentolamine and bunazosin, on hypoxic and reoxygenated myocardium.

The present study was undertaken to determine whether alpha-blocking agents, phentolamine and bunazosin, may exert a cardioprotective effect on hypoxic and subsequently reoxygenated hearts. For this purpose, rabbit hearts were perfused for 20 min under hypoxic conditions, followed by a 45 min-reoxygenation. Agents were administered between the 8th and 20th min of hypoxic perfusion. Hypoxic perfusion for 8 min resulted in a decline of cardiac contractile force and myocardial high-energy phosphates and a loss of adenine nucleotide metabolites from the heart, whereas a rise in resting tension was not observed. Neither increase in perfusion pressure, release of creatine kinase from hearts nor increase in tissue calcium was observed. At 20 min-hypoxia, significant changes in resting tension and perfusion pressure of the heart and release of creatine kinase from the heart were observed. Cardiac contractile force after 45 min of reoxygenation was less than 10% of the initial value. Treatment with 83 microM phentolamine or 46 microM of bunazosin resulted in a significant suppression of hypoxia-induced increase in tissue calcium, release of creatine kinase and adenine nucleotide metabolites and rise in perfusion pressure and resting tension. Treatment with either phentolamine or bunazosin resulted in appreciable recovery of cardiac contractile force. Reoxygenation-induced release of creatine kinase was also suppressed significantly. Two possible mechanisms for the protective effect of this treatment are considered; 1) preservation of ATP metabolites which may be utilized as substrates for a salvage synthesis of ATP during reoxygenation and 2) prevention of a nonselective transmembrane flux of cellular constituents due to changes in cell membrane permeability.

Adenosine Triphosphate↗
PubMed1988

Role of ATP metabolites in induction of incomplete recovery of cardiac contractile force after hypoxia.

The present study was designed to elucidate metabolic factors related to reoxygenation-induced recovery of cardiac contractile force after a period of hypoxia, from the view point of energy metabolism in the myocardium. Rabbit hearts were perfused for 20 mins under various degrees of hypoxic conditions, followed by 45 mins of reoxygenation. Hypoxia induced a rise in resting tension, a cessation of cardiac contractile force, a depletion of high energy phosphates, an increase in tissue calcium and an increase in UV absorbance of the perfusate. High performance liquid chromatography analysis of the perfusate indicated that the increase in UV absorbance of the perfusate was attributed to the release of ATP metabolites from the perfused heart. Reoxygenation-induced recovery of cardiac contractile force after 20 mins of hypoxia was predicted by the degree of the rise in resting tension at the final period of hypoxia. The recovery was related to the level of high energy phosphates in the reoxygenated heart as well as the loss of ATP metabolites from the heart but not to the tissue calcium content. The loss of ATP metabolites also correlated with myocardial ATP levels at 45 mins of reoxygenation and a rise in resting tension at 20 mins of hypoxia. The results suggest that loss of ATP metabolites is a vital step in the induction of incomplete recovery of cardiac contractile force after hypoxia.

Adenosine Triphosphate↗
PubMed1987

Antitumor activity of pleural cavity macrophages and its regulation by pleural cavity lymphocytes in patients with lung cancer.

Antitumor activities of pleural cavity macrophages (PCM) and pleural cavity lymphocytes (PCL) in lung cancer patients were examined. The effect of coculture supernatants of PCL and autologous tumor cells on the cytostatic activity of macrophages was also examined. Cytostatic activity of PCM was not affected by an advance of metastasis to regional lymph nodes or increase of tumor size and difference of histological type. However, the cytostatic activity of PCM was markedly augmented when pleural invasion was limited to within the visceral pleura although it was low when pleural invasion was absent or extended beyond the visceral pleura. On the other hand, PCL did not exert any cytolytic activity against various tumor target cells. However, coculture supernatants of PCL and autologous tumor cells exhibited the activity of macrophage-activating factor against guinea pig peritoneal macrophages. Furthermore, the higher the cytostatic activity of PCM, the higher the macrophage-activating factor activity of the coculture supernatant of PCL and autologous tumor cells was. These results suggested that antitumor activity of PCM was controlled by specifically sensitized PCL through lymphokines.

Animals↗
PubMed1987

An analysis of the depressant effect of indomethacin on contractions of isolated and perfused rat hearts.

The depressant effect of indomethacin on contractions of isolated rat hearts was investigated under a constant heart rate. Ca2+ produced dose-dependent increases in myocardial contractile force and coronary perfusion pressure. Indomethacin-infusion significantly decreased myocardial contractile force and depressed increases in myocardial contractile force by Ca2+, but never affected both coronary perfusion pressure and increases in coronary perfusion pressure by Ca2+. Results suggest that indomethacin will depress myocardial contractile force with no involvement of any calcium antagonism.

Animals↗
PubMed1987

Pharmacological actions of dopamine sulfoconjugate on cardiovascular system.

Pharmacological actions of dopamine 4-sulfate on the cardiovascular systems were examined and compared with those of dopamine. Dopamine 4-sulfate, used in the present study, was minimally contaminated with dopamine (less than 0.02%). Dopamine 4-sulfate at doses ranging from 0.1 to 1 mumol/kg did not elicit any appreciable changes in systemic blood pressure and heart rate of anesthetized rabbits. Contractile activity and heart rate of isolated perfused rat heart were also unaffected by the agent. Dopamine 4-sulfate at concentrations of 1 and 0.3 mM, reduced a significant contraction of isolated rabbit renal and femoral arteries, respectively, but not in the aorta. The extent of the increase in tension development induced by 1 mM dopamine 4-sulfate in the femoral artery, was almost similar to that induced by 3 microM dopamine. The maximal tension development induced by 1 mM dopamine 4-sulfate in the femoral artery occurred more slowly than that induced by 3 microM dopamine. Furthermore, dopamine 4-sulfate-induced increase in tension development, like that of dopamine itself, was inhibited by 0.3 microM phentolamine and 0.1 microM haloperidol. Any appreciable conversion of dopamine 4-sulfate into dopamine was not seen in the medium of the organ bath in vitro during the experiment. The results suggest that dopamine sulfoconjugate exerts little effect on the cardiovascular system and, if any, induces a constriction of some vascular beds without conversion into dopamine.

Animals↗
PubMed1987

Possible mechanism by which coenzyme Q10 improves reoxygenation-induced recovery of cardiac contractile force after hypoxia.

To elucidate possible mechanisms by which coenzyme Q10 enhances reoxygenation-induced recovery of cardiac contractile force after hypoxia, rabbit hearts were subjected to hypoxic perfusion for 20 min, followed by 45 min-reoxygenation with or without pretreatment with coenzyme Q10. Hypoxia induced a decline in cardiac contractile force, a decrease in myocardial high-energy phosphates and a release of ATP metabolites and creatine phosphokinase from the perfused heart. Upon reoxygenation the rate of release of ATP metabolites subsided, but no appreciable recovery of the loss of contractile force and the reduction of myocardial ATP content was seen, and the release of creatine phosphokinase was increased further. Pretreatment of rabbits with coenzyme Q10 resulted in an appreciable recovery of cardiac contractile force and of myocardial ATP content upon reoxygenation. The release of creatine phosphokinase from hearts during hypoxia and reoxygenation was inhibited completely by the pretreatment. Changes in the UV absorbance of the perfusate suggested that coenzyme Q10 reduced the loss of ATP metabolites from hypoxic hearts. Furthermore, high-performance liquid chromatographic analysis indicated that coenzyme Q10 attenuated the release of inosine and hypoxanthine from the hearts and decreased myocardial inosine and adenosine content of the hypoxic heart, suggesting that coenzyme Q10 retards the breakdown of ATP metabolites which are possible substrates for a salvage synthesis of ATP, when oxygen is replenished. This could account for an appreciable restoration of ATP, and eventually provide a significant recovery of cardiac contractile force upon reoxygenation.

Adenosine↗
PubMed1986

Effects of habu (Trimeresurus flavoviridis) venom on isolated and perfused hearts of rats.

Crude habu venom decreased coronary perfusion pressure and produced a small increase in myocardial tension of isolated and perfused rat hearts. Indomethacin infusion depressed the fall in perfusion pressure caused by the venom, without affecting the increase in tension. Heated venom decreased perfusion pressure, but did not increase myocardial tension. These results suggest that crude habu venom has coronary vasodilating and positive inotropic effects, possibly through actions of a phospholipase A2 and a heat-labile component, respectively.

Animals↗
PubMed1986

Acute effects of bunazosin on aortic, vertebral, coronary and renal blood flows of anesthetized dogs.

Effects of 4-amino-2-(4-butyrylhexahydro-1H-1,4-diazepin-1-yl)-6,7-dime thoxy-quinazoline (bunazosin, E-643, Detantol) on aortic, vertebral, coronary and renal blood flows were investigated in anesthetized open-chest dogs. Bunazosin 1, 10 and 100 micrograms/kg i.v. dose-dependently decreased aortic blood pressure (AoP) and inhibited the increase in AoP by phenylephrine 5 micrograms/kg i.v. However, the increase in AoP by norepinephrine 0.5 microgram/kg i.v. remained even after bunazosin 100 micrograms/kg i.v. and was almost undetectable after additional administration of yohimbine 1000 micrograms/kg i.v. A hypotension by bunazosin persisted more than 15 min, but dose-dependent increases in heart rate (HR) induced by bunazosin 1, 10 and 100 micrograms/kg i.v. restored within 2 min. Bunazosin 100 micrograms/kg i.v. significantly but transiently increased aortic blood flow and decreased renal blood flow. Vertebral and coronary blood flows were not significantly changed. Left ventricular dP/dt was transiently increased. Calculated total peripheral vascular resistance and coronary vascular resistance were transiently but significantly decreased. No significant changes were observed in both vertebral vascular resistance and renal vascular resistance. The results indicate that bunazosin maintains the blood flows to brain, heart and kidney, and is continuously lowering AoP without significant changes in HR.

Adrenergic alpha-Antagonists↗
PubMed1986

The role of surgical resection in the management of small cell carcinoma of the lung.

To assess the role of surgical resection in the management of small cell carcinoma of the lung, experience with 118 patients who were treated between 1973 and 1985 was reviewed. Twenty-five patients underwent surgical resection followed by combination chemotherapy in all except one. The remaining 93 patients were treated by combined chemotherapy and radiation therapy. The 5-year survival rate for patients with stage I disease undergoing surgical resection was 50.8%. For all 25 patients operated on, the 5-year survival rate was 30.7%. In the patients not operated on, only those with complete response had long-term survival, for whom the 5-year survival rate was 11.9%. We consider that surgical resection is definitely indicated in patients with stage I disease. If the response to initial chemotherapy is very good, patients with stage II or T3N0M0 disease also probably should receive resection. Patients with N2 disease are not candidates for resection, unless distant metastases are controlled completely by intensive chemotherapy.

Actuarial Analysis↗
PubMed1986

Role of tumor-associated macrophages in lung cancer.

The percentage of tumor-associated macrophages recovered (TAMR) and antitumoral activity of tumor-associated macrophages (TAM) were examined in 77 patients with resectable primary lung cancer. TAM was obtained by plastic adherence following trypsinization. TAMR increased from Stage I to Stage II and decreased in Stage III. It also increased in N1 as compared with N0 and N2 but was unrelated to tumor size. However, the cytostatic activity of TAM declined with advance in stage of the disease and an increase of tumor size, but it was relatively unaffected by the presence of metastasis to regional lymph nodes. There was no correlation between TAMR and the recurrence rate; however, cytostatic activity of TAM was correlated significantly with the prognosis of totally resected cases. TAMR and cytostatic activity of TAM tended to be lower in palliatively resected cases. These results suggest that the assessment of the antitumor activity of TAM, but not merely TAMR, may give prognostic information for lung cancer patients.

Adenocarcinoma↗
PubMed1985

Microsomal calcium-accumulating ability of bovine coronary artery and aorta.

Calcium uptake and binding activities of microsomal fractions from bovine coronary artery and aorta were examined. The isolated microsomal fraction of the coronary artery and aorta showed 7- to 8-fold higher glucose-6-phosphatase activity and 4- to 6-fold higher NADPH-cytochrome c reductase activity as compared with the corresponding values for the homogenate fraction. Coronary artery and aorta microsomal calcium uptake activities were 118 and 159 nmoles Ca2+/mg protein/10 min in the presence of 100 microM CaCl2, respectively. These activities for bovine vascular smooth muscle microsomes are higher than those of other species investigated. The calcium uptake activities were dependent on calcium concentrations ranging from 5 to 50 microM in the assay medium. The onset of the reaction for aorta microsomal calcium uptake was faster than that for the coronary artery. The calcium uptake activity was also dependent on ATP, but it was practically independent of oxalate ions in the assay medium. Microsomal calcium binding activities of the coronary artery and aorta were maximal at 20 min of incubation under the present experimental conditions. A lower Km value of the aortic calcium binding for ATP was obtained as compared with that for the coronary artery. The present experiment explored several characteristics of the microsomal calcium-accumulating ability of vascular smooth muscle, which provides meaningful information for further study on cellular calcium movements in vascular smooth muscle.

Adenosine Triphosphatases↗
PubMed1985

A possible action of nicardipine on the cardiac sarcolemmal Na+-Ca2+ exchange.

The effects of nicardipine on sodium-calcium exchange activity of cardiac sarcolemma-enriched vesicles isolated from the rat heart were examined. Sodium-loaded, sarcolemma-enriched vesicles, when exposed to a medium containing 40 microM CaCl2, exhibited about 5 nmoles Ca2+/mg protein of the maximal calcium uptake; the initial rate was 21 nmoles Ca2+/mg protein/min. The calcium uptake was dependent on the extravesicular concentration of calcium ion. Nicardipine at concentrations of 0.1 to 10 microM depressed the rate of calcium uptake activity by 60-90%. The isolated membrane vesicles preloaded with Ca2+ showed a calcium efflux activity, when exposed to a medium containing sodium ion. The rate of calcium efflux was 2.5 nmoles Ca2+/mg protein/min, when measured in a medium containing 6.5 mM NaCl. The efflux rate was facilitated with increased concentrations of sodium ion in the medium. About 75% of the preloaded calcium in the vesicles was released within 3 min of incubation. The rate of calcium efflux was stimulated in the presence of 0.1 to 10 microM nicardipine (2.5- to 4-fold increase). The present results suggest a possible action of nicardipine on the sodium-calcium exchange mechanism at cardiac sarcolemmal sites.

Adenosine Triphosphatases↗
PubMed1985

Characterization of membrane-bound adenosinetriphosphatase activity of sarcolemma-enriched fraction from vascular smooth muscle.

Membrane-bound adenosinetriphosphatase (ATPase) activities of the sarcolemma-enriched fraction from bovine aorta were characterized. The membranes, isolated by a sucrose density gradient method, were enriched about 31-fold in sodium- and potassium-stimulated, magnesium-dependent ATPase (Na,K-ATPase) activity, and about 8-fold in 5'-nucleotidase activity compared to the homogenate, suggesting that the isolated membranes were substantially enriched with the sarcolemma. The membranes exhibited about 31, 33 and 42 mumol Pi/mg protein/h of Na,K-ATPase, magnesium-dependent ATPase and calcium-dependent ATPase activities, respectively, in the presence of 4 mmol/l ATP. The sarcolemma-enriched membranes required considerably high concentrations of well-known inhibitors for Na,K-ATPase such as vanadate (more than 1 mumol/l), lanthanum (more than 1 mmol/l) and calcium (10 mmol/l), to induce a significant inhibition in the Na,K-ATPase activity. Treatments of the membrane with physical disruptions and sodium dodecyl sulfate or deoxycholate reduced the total Na,K-ATPase activity, and did not expose fully the ouabain sensitivity of the Na,K-ATPase. These results indicate that there are marked differences in the properties of the ATPase between vascular smooth muscle sarcolemma and cardiac sarcolemma.

Adenosine Triphosphatases↗
PubMed1985

Calcium accumulating ability of mitochondria from bovine coronary artery. Comparison with aortic mitochondria.

The calcium accumulating ability of mitochondria isolated both from bovine coronary artery and aorta was investigated. Coronary artery and aorta were pretreated with 0.1% collagenase. Cytochrome c oxidase activities of mitochondria isolated from coronary artery and aorta showed 25-fold and 19-fold increases, respectively, as compared with those of each homogenate, whereas NADPH-cytochrome c reductase, potassium-phosphatase and Na+-K+ ATPase activities increased less than 2-fold. This suggests that the isolation procedure is capable of obtaining a subcellular fraction highly enriched with mitochondria. Mitochondrial calcium uptake activity of the coronary artery was approximately 250 nmoles Ca2+/mg protein/10 min, and was markedly depressed with metabolic inhibitors such as NaN3, ruthenium red and 2,4-dinitrophenol. Calcium uptake activity of bovine aortic mitochondria showed similar activity and a similar trend in sensitivity to metabolic inhibitors. By contrast, the onset of the calcium binding reaction of the aortic mitochondria was slower and the azide-sensitivity of the mitochondria to magnesium ATPase activity was lower than those for coronary artery mitochondria. The present study has provided a method for isolation of mitochondria with a high capacity of calcium uptake activity, which may prove meaningful for future physiological and pharmacological evaluation of mitochondrial calcium accumulation in vascular smooth muscle.

Alkaline Phosphatase↗
PubMed1985

Effects of nipradilol (K-351) on cardiac function in anesthetized open-chest dogs.

Effects of nipradilol (K-351) on cardiac performance and myocardial oxygen consumption were investigated in anesthetized open-chest dogs. Nipradilol 0.1 mg/kg i.v. induced falls in systolic and diastolic aortic blood pressure and left ventricular pressure, and decreases in cardiac output, coronary sinus outflow, left ventricular dP/dt and heart rate. Stroke volume was transiently increased and left ventricular stroke work index was significantly decreased, while left ventricular mechanical efficiency was not significantly changed. Myocardial oxygen consumption was significantly decreased. Total peripheral vascular resistance and coronary vascular resistance were persistently increased. Left ventricular enddiastolic pressure was not significantly changed. These results suggest that nipradilol has a possible antianginal property through a decrease in myocardial oxygen consumption due to a fall in aortic blood pressure and a decrease in heart rate.

Adrenergic alpha-Antagonists↗