Biomedical subjects

M Katsuoka

Publications and source records attributed to M Katsuoka.

11 recordsLinked to original sources

PubMed1991

Why does halothane relax cardiac muscle but contract malignant hyperthermic skeletal muscle?

We have studied the question of the possible role of sarcoplasmic reticulum (SR) in the interaction of volatile anesthetics (such as halothane, enflurane and isoflurane) with muscle. We used two cardiac muscle models, i.e., isolated rat myocytes and Langendorff perfused rat hearts. We compared the results with those for skeletal muscle SR from rabbits, rats and pigs susceptible to malignant hyperthermia (MH). In both skeletal and cardiac muscle SR, volatile anesthetics enhanced the calcium release from the SR. In cardiac muscle, these agents are known to decrease contractility (negative inotropism). We found that caffeine, a well-known agent which releases calcium from the SR, also had a negative inotropic effect in cardiac muscle, raising the possibility of an unexpected link between the potentiation of calcium release and mechanism underlying the observed negative inotropism. Current understanding of anesthetic mechanisms does not include this possibility. We further found that both volatile anesthetics and caffeine decrease the content of calcium in the SR, suggesting that the increase of calcium permeability results in the decrease of calcium ions in the SR which are available for excitation-contraction (E-C) coupling. In MH-susceptible skeletal muscle, a similar increase in calcium permeability does not cause a decrease of contractility, but rather may contribute to a fatal syndrome of temperature increase provoked by abnormal contracture. This difference may be because in skeletal myoplasm calcium ions recycle internally, while in the cardiac muscle cell they are in dynamic equilibrium with extracellular calcium ions.

Animals↗

PubMed1989

A prostaglandin oligomeric derivative inhibits activities of phospholipase and protease: a possible mechanism of membrane protection during ischemia.

A prostaglandin oligomeric derivative was synthesized by alkaline treatment of prostaglandin E1. This compound protected the perfused rat heart from global ischemia. This compound was found to inhibit several lipolytic and proteolytic enzymes in vitro. When phospholipase A2 from Naja naja venom was used as an enzyme and phosphatidylcholine was used as a substrate, 50 per cent inhibition was achieved at 50 microM of the prostaglandin derivative. When trypsin and casein were used as enzyme and substrate, 50 per cent inhibition was obtained at 80 microM. A possible mechanism of beneficial effect of this compound in protecting membranes during ischemia is discussed.

Animals↗

PubMed1989

Prostaglandin derivatives inhibit the growth of malarial parasites in mice.

New prostaglandin oligomeric derivatives, termed MR-256 and MR-356, were found to inhibit the growth of murine malarial parasites, P. chabaudi and P. vinckei, within red blood cells in vivo. When mice were infected with P. chabaudi, both MR-256 and MR-356 suppressed the growth of parasites, but MR-356 had a greater inhibitory effect than MR-256. With P. vinckei, MR-356 also inhibited the growth of parasites, and improved the survival rate. The effect of MR-256 was much less. A possible inhibitory mechanism of action of these drugs is discussed.

Alprostadil↗

PubMed1989

Protection of the heart from ischemia by a new oligomeric derivative of prostaglandin E1.

A lipophilic oligomeric ester was synthesized from prostaglandin E1. The compound was found to protect a Langendorff perfused rat heart from ischemic insult. After 15 minutes cessation of perfusion, the flow was restarted, and the recovery of contraction was measured. In control experiments, the recovery was 16.1 +/- 7.3%. In the case of pre-ischemic addition of the compound (10 micrograms/ml at 10 minutes before ischemic insult), the recovery was 31 +/- 13.2% (n = 7; the difference was not significant). In post-ischemic addition (10 micrograms/ml), the recovery was 75.9 +/- 9.0% (n = 7; p less than 0.01). The compound was also effective in protecting rat heart myocytes against a 60 minutes anoxia/15 minutes reoxygenation injury as judged by the loss of "rod-shaped" intact myocytes. At a 10 micrograms/ml concentration, the compound protected against the loss of rod-shaped myocytes by 30% in pre-anoxia addition and 35% in post-anoxia addition. The levels of significance in these experiments were p less than 0.001. Possible mechanisms of action of this compound are discussed.

Alprostadil↗

PubMed1989

Pharmacologic protection of perfused rat heart against global ischemia.

Using a Langendorff rat heart model, studies were performed on the effects of three drugs in protecting the heart against global ischemia. The drugs used were: (a) MR-256, a prostaglandin oligomeric derivative, which is a calcium chelating agent and at the same time, is an inhibitor of phospholipase A2 activity, (b) chlorpromazine which is not a calcium chelator, but is a calmodulin antagonist and is an inhibitor of phospholipase A2 activity, and (c) BAPTA/AM, a calcium chelating agent, but which is not an inhibitor of phospholipase A2 activity. The perfused heart was exposed to 15 minutes of global ischemia. In control experiments (no drug), the ventricular pressure recovered to 26.4 +/- 6.7% (n = 22) of the original level. With pretreatment of (a) MR-256 (b) chlorpromazine, and (c) BAPTA/AM, maximum recoveries were 0.5 +/- 6.7% (n = 5), 88.7 +/- 8.5% (n = 5), 45.3 +/- 26.6% (n = 5), respectively. MR-256 and chlorpromazine were found to react with free radicals. The modes of action of these three different types of drugs are discussed.

Animals↗

PubMed1989

Prostaglandin oligomeric derivatives inhibit in vitro formation of dehydrated cells from sickle red cells.

Two types of oligomeric derivatives of prostaglandin E1 were synthesized, a free-acid type and a lipophilic ester type. Neither compound inhibited sickling of red blood cells from sickle cell anaemia patients. However, both were found to inhibit the in vitro formation of dehydrated, dense cells (DC) caused by repeated cycles of sickling and unsickling of sickle cells. Both inhibited the formation of DC in a dose-related manner, but the ester type compound was more effective than the acid-type compound. Concentrations at which these compounds inhibit the DC formation by 50% were 5.2 microM and 40 microM for ester and free-acid compounds, respectively. A possible inhibition mechanism is discussed.

Alprostadil↗

PubMed1989

Inhibition of ischemic brain edema formation by post-ischemic administration of a prostaglandin oligomer.

We studied the efficacy of an oligomeric derivative of prostaglandin E1 in protecting the rat brain against focal ischemia. The degree of ischemic damage was evaluated from three parameters, namely, the degree of edema formation, reduction of motor performance, and memory disturbance as measured by a passive avoidance test. The pre-ischemic administration of the drug (6 mg/kg i.p.) had some effects, but the differences were not significant. The post-ischemic administration (6 mg/kg i.p.) produced significant improvement in all three parameters. The increase of water content of the ischemic hemisphere was reduced (p less than 0.05); the total motor score was improved (p less than 0.01); and the memory disturbance as estimated by the passive avoidance test was reduced (p less than 0.01). A possible mechanism of protection is discussed.

Alprostadil↗

PubMed1989

Inhalation anaesthetics decrease calcium content of cardiac sarcoplasmic reticulum.

In a Langendorff perfused rat heart model, caffeine was shown to have a negative inotropic effect similar to that of inhalation anaesthetics. Both inhalation anaesthetics and caffeine decreased calcium content of left ventricular muscle as measured by atomic absorption spectroscopy. Halothane 2.8% decreased left ventricular pressure by 75.4 (SEM 4.4)% and decreased the calcium content by 30%. Enflurane 5.1% decreased the pressure by 72.4 (6.0)% and decreased calcium content by 31%. Both halothane and enflurane decreased the calcium content of sarcoplasmic reticulum (SR) as measured by caffeine-induced calcium release. There was a high degree of correlation between the negative inotropic effect of inhalation anaesthetics and the decrease in calcium content of the SR (r = 0.95 for halothane, r = 0.91 for enflurane). These data suggest that inhalation anaesthetics increase the calcium permeability of cardiac SR, thereby decreasing the calcium content of SR, resulting in the negative inotropic effect.

Anesthetics↗

PubMed1989

Volatile anesthetics decrease calcium content of isolated myocytes.

The calcium transient of myocytes was measured using a fluorescent dye, Fura-2. Caffeine, halothane, enflurane, and isoflurane increased the resting calcium level and decreased the calcium transient. The amount of caffeine-induced calcium release was suppressed if myocytes were pretreated with halothane. The amount of halothane-induced calcium release was suppressed if myocytes were pretreated with caffeine. Both halothane and caffeine were found to have similar effects on the sarcoplasmic reticulum (SR). The effect of 4 mM halothane (equivalent to 13.6% v/v) was approximately equivalent to that of 10 mM caffeine. Caffeine, halothane, enflurane, and isoflurane all decreased the total calcium content of myocytes by 10-70%. These data suggest that volatile anesthetics decrease the calcium content of the cardiac SR by increasing the calcium permeability of the SR, and that the mechanism of action of volatile anesthetics may be similar to certain actions of caffeine.

Animals↗

PubMed1989

Protection of rat spinal cord against contusion injury by new prostaglandin derivatives.

Two prostaglandin oligomeric compounds, an acid-form compound and an ester-form compound, were synthesized from alprostadil (prostaglandin E1). They were found to provide significant protection to the rat spinal cord against contusion injury. After laminectomy at the T-11 segment of the spinal cord, a weight drop (10 g x 5 cm) caused a "dynamic" injury. The degree of recovery was estimated by several neurologic deficit indices; the Tarlov score, inclined plane test and hot plate test. In the control group (no drug), animals were still paralyzed 4 weeks after injury (Tarlov score 1 to 2). By administering these prostaglandin oligomers, either pre-injury (30 min before injury; one dose of 6 mg/kg i.p.) or post-injury (3 doses, each of 6 mg/kg i.p. at 30 min, 6 h, and 12 h after injury), the Tarlov scores recovered to 3.5 to 4.5 by 4 weeks, and animals were able to either support body weight or to walk with a slight deficit. Although both acid- and ester-forms of the compound demonstrated efficacy, the ester-form provided greater protection to the spinal cord. Other neurologic deficit indices also supported these observations.

Animals↗

PubMedDate not supplied

Effects of membrane acting-drugs on plasmodium species and sickle cell erythrocytes.

The effects of several membrane-acting drugs on malaria and sickle cell anemia was studied. In the initial experiments, propranolol and W-7 were shown to increase red cell density. In vitro, these drugs inhibited the growth of P. falciparum. However, in vivo experiments using the murine malarial parasite, P. vinckei, demonstrated little, if any, anti-parasite activity with the doses of drugs employed. Subsequently, prostaglandin oligomeric derivatives were found to inhibit the growth of P. falciparum in vitro and P. vinckei in vivo. Since prostaglandin oligomers inhibited the formation of dense, dehydrated cells (irreversible sickle cells), they may also have therapeutic efficacy in sickle cell anemia.

Alprostadil↗