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Biomedical subjects

A Sawamura

Publications and source records attributed to A Sawamura.

62 records · Page 4Linked to original sources
PubMed1981

Trapidil stimulation of slow Ca2+ current in cardiac muscle.

The effect of trapidil, a coronary vasodilator and positive inotropic agent (associated with elevated tissue cyclic AMP levels due to phosphodiesterase inhibition), was examined on the electrophysiological properties of cardiac muscle. Specifically, the trapidil was tested for its ability to induce slow action potentials (APs), and to affect the maximum upstroke velocity (+Vmax) of the slow APs in the ventricular myocardial cells of isolated perfused chick hearts. The effect of trapidil on the contractions accompanying the slow APs and on the tissue cyclic AMP levels was also examined. To study the slow channels exclusively, the fast Na+ channels were voltage-inactivated by elevated (25 mM) K+. In this condition of functional removal of the fast channels, the hearts could not be excited even by intense electrical stimulation. It was found that trapidil (10(-4)--10(-3) M) induced slow APs accompanied by contractions. Elevation of the trapidil concentration produced dose-dependent increases in +Vmax, dT/dt (first derivative of developed tension) and cyclic AMP. These effects of trapidil were not affected by propranolol, suggesting that they were not mediated by beta-adrenergic receptors. These results support the hypothesis that intracellular cyclic AMP levels regulate the number of available slow channels, thereby controlling contractile force in the heart muscle via the Ca2+ influx mediated by slow channels.

Action Potentials↗
PubMedDate not supplied

Beneficial effect of coenzyme Q on myocardial slow action potentials in hearts subjected to decreased perfusion pressure-hypoxia-substrate-free perfusion.

Coenzyme Q, an important component of the electron transfer system in mitochondria, plays a central role in energy production aerobically. The effect of pretreatment with coenzyme Q10 (Co Q) on myocardial slow action potentials (APs) and accompanying contractions and on myocardial high energy phosphate content was studied in perfused hearts subjected to decreased perfusion pressure-hypoxia-substrate-free. Post-hatched chicks were treated i.p. with 10 mg/kg of Co Q daily for 5 days. To study the slow APs exclusively, the fast Na+ channels were voltage-inactivated by elevated K+ (25 mM) Tyrode solution. The Ca++-dependent slow APs were induced by elevating [Ca]o to 5.4 mM; hearts were paced at a rate of 40 per min. Hearts which had been pretreated with Co Q were protected against the deleterious effect of decreased perfusion pressure - hypoxia - substrate-free perfusion on mechanical performance accompanying the slow Ca++-Na+ APs. The slow APs in hearts pretreated with Co Q were also less affected than were non-treated hearts. However, the myocardial ATP and total adenine nucleotides were not affected by exogenous Co Q. It was suggested that exogenous Co Q could protect against the decline of cardiac contractions via improved availability of slow APs during decreased perfusion pressure - hypoxia - substrate-free, independently of the cellular high energy phosphate level.

Animals↗
PubMedDate not supplied

Locoregional immunotherapy of malignant ascites by intraperitoneal administration of OK-432 plus IL-2 in gastric cancer patients.

The clinical efficacy of intraperitoneal administration of OK-432 plus interleukin-2 (IL-2) for treating malignant ascites was evaluated in gastric cancer patients. Ten KE of OK-432 and 200,000 Jurkat units of IL-2 were intraperitoneally administered in tandem in the order given on alternate days at paracentesis. Of the 22 evaluable patients, 18 (81%) developed complete or partial responses, showing a cytologic disappearance of cancer cells and decrease of ascites. More than 50% of the patients obtained positive responses within 2 weeks after the initial administration of the drugs. Improvements of performance status and clinical symptoms such as abdominal fullness, followed by restoration of oral food intake and prolongation of survival time were observed in responders treated with OK-432 plus IL-2. Flow cytometric analysis demonstrated a predominant increase of the CD3+CD4+ cells, especially of the CD4+CD45RA- subset in the peritoneal cavity of the responders. Cytotoxicity assay after negative selection of the CD4+ cells with the antibody and complement revealed that the CD4+ subset possessed cytotoxic activity against autologous tumor cells. The results suggest that intraperitoneal administration of OK-432 plus IL-2 may not be only a practical but also an effective protocol for treating malignant ascites in gastric cancer patients.

Adult↗