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Biomedical subjects

H Otani

Publications and source records attributed to H Otani.

At least 217 records · Page 12Linked to original sources
PubMed1987

Age-related development profiles of the antioxidative defense system and the peroxidative status of the pig heart.

The developmental profiles of the antioxidative defense system and the peroxidative status of the heart during growth and development were studied in pigs of three different age groups. A unique age-specific myocardial lipid peroxidation expressed in terms of malonaldehyde formation occurred after incubation of neonatal and adult pig heart homogenates in the absence of any added factors. Very little malonaldehyde release was noticed in the 0- to 2-day age group, while considerably higher activity was found in the 8- to 10-day-old animals. The 2-month-old pig heart again formed very little malonaldehyde. Myocardial injury from lipid peroxidation was highest in the 0- to 2-day age group, as evidenced by the release of oxidized glutathione, lactate dehydrogenase (LDH) and creatine kinase (CK) activities. Release of glutathione, LDH and CK decreased with age and was minimal in the adult group. The antioxidative enzymes, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, increased during the first 10 days of neonatal growth and then levelled off. Glucose-6-phosphate dehydrogenase was present in appreciably lower amounts in adult hearts compared to neonatal hearts. Heart weight increased with aging, but myocardial water content decreased. Protein and DNA contents of hearts increased with age, such that the protein/DNA ratio almost doubled from the newborn to adult age. The results indicate that the newborn pig hearts are equipped with the antioxidative defense system, which undergoes significant development during the initial phase of neonatal growth and does not change appreciably thereafter. The results further suggest that the change in activity profile with aging is different for different enzymes, and the peroxidative status of the myocardium is not a function of these enzyme activities.

Aging↗
PubMed1987

Phorbol ester potentiates alpha 1-adrenoceptor-mediated positive inotropic effect in rat papillary muscle.

Tumor-promoting phorbol esters may alter alpha 1-adrenoceptor-mediated cardiac response by stimulating protein kinase C activity. We investigated the effect of phorbol-12,13-dibutyrate (PDBu) on the positive inotropic effect (PIE) in rat left ventricular papillary muscle. PDBu (1-100 nM) potentiated the phenylephrine (PE)-induced PIE in a dose- and time-dependent manner. The PIE induced by PE and PDBu was abolished by pretreatment with 3 x 10(-7) M prazosin. PDBu also enhanced PE-induced slow responses 2- to 3-fold. These results suggest that PDBu enhances alpha 1-adrenoceptor-mediated PIE by potentiating slow Ca2+ channels, presumably through the activation of protein kinase C.

Animals↗
PubMed1987

The mechanism of myocardial reperfusion injury in neonates.

Oxygen free radicals and phospholipid degradation have been implicated in the pathogenesis of ischemia and reperfusion injury. The present study examines the involvement of such mechanisms in myocardial reperfusion injury in neonatal hearts. The isolated neonatal pig hearts from two different age groups, 0 to 2 days old (newborn) and 7 to 9 days old (week-old), were subjected to 60 min of normothermic global ischemia followed by 60 min of reperfusion. Although myocardial ischemia reduced superoxide dismutase, catalase, and glutathione peroxidase activities in both age groups, superoxide dismutase and catalase activities remained significantly lower in the newborn pig heart during ischemia and reperfusion. Oxidized glutathione release from the neonatal pig hearts was at minimum levels before ischemia, but it increased 10-fold at the onset of reperfusion and was significantly higher in the newborn heart. This indicates that generation of oxygen free radicals was enhanced in the newborn compared with that in the week-old heart. The increase in phospholipase A2 activity and decrease in acyl CoA synthetase and lysophosphatidylcholine acyl transferase activities during ischemia and reperfusion were associated with comparable loss of membrane phospholipids and accumulation of lysophosphatidylcholine and free fatty acids in both age groups, except that oleic acid content was significantly higher in the newborn heart during reperfusion. Myocardial damage appears to be potentiated in the newborn heart during reperfusion, as evidenced by higher release of creatine kinase and a lower content of high-energy phosphates. These results indicate that oxygen free radicals may play a crucial role in the occurrence of reperfusion injury in immature hearts.

Animals↗
PubMed1986

Evidence that phosphoinositide response is mediated by alpha 1-adrenoceptor stimulation, but not linked with excitation-contraction coupling in cardiac muscle.

Phosphoinositide metabolism is known to be associated with neuronal or humoral stimulation of excitable cells. The present study examined whether the phosphoinositide response is involved in such events using isolated rat papillary muscles labeled with [3H]inositol. It was found that neither increase in the stimulation frequencies (0-2 Hz) nor prolongation of the pulse duration (10-70 msec) altered the labeling of phosphoinositides and the accumulation of [3H]inositol phosphates in this preparation. However, phenylephrine, a known alpha 1-agonist, was capable of provoking the breakdown of phosphoinositides associated with a positive inotropic effect in this preparation. We report the evidence that phosphoinositide response is mediated by alpha 1-adrenoceptor stimulation, but not linked with excitation-contraction coupling in cardiac muscle.

Animals↗
PubMed1986

Amniogenic band anomalies in a fifth-month fetus and in a newborn from maternal oophorectomy during early pregnancy.

A fifth-month fetus and a newborn with amniogenic band anomalies were examined at autopsy. Both specimens were obtained from women who had undergone oophorectomy during early pregnancy. The dead male fetus was aborted spontaneously, and had a micrognathia, a right club foot, and a constriction ring on the left lower leg. The left fingers 2, 3, and 4 were attached to the placenta by a fibrous string. No internal anomaly was noted. In the other case, a male newborn was delivered at the 39th week of gestation and had an agenesis of the calvarium, a cleft lip with palate, an amputation of the right toe, and constriction rings on right fingers 3 and 4 and left finger 3. The placenta was attached to the left temporooccipital region of the head by a fibrous string. Also present was an atrial septum defect and a horseshoe kidney. Possible etiology is discussed in relation to the "amniogenic bands" hypotheses.

Abnormalities, Multiple↗
PubMed1986

Protection against oxygen-induced reperfusion injury of the isolated canine heart by superoxide dismutase and catalase.

While oxygen-derived free radicals have been implicated in the pathogenesis of myocardial injury, the exact nature of this injury is still unclear. To test the hypothesis that oxygen-induced injury may influence the recovery of cardiac function from ischemic damage, we used an oxygen free radical scavenger, superoxide dismutase (SOD), together with catalase, during the reperfusion of isolated canine heart which had been subjected to 15 min of normothermic ischemic arrest followed by 2 hr of hypothermic cardioplegic preservation using a modified Collins solution. Determinations of thiobarbituric acid reactive substances and coenzyme Q10 within the myocardium showed that the treatment with SOD and catalase was capable of inhibiting lipid peroxidation induced by reperfusion. This inhibition was apparently associated with the improvement of myocardial energy metabolism and cardiac performance. Coronary flow was significantly higher in the heart treated with SOD and catalase during the working stage with a corresponding increase in oxygen consumption. Myocardial adenosine triphosphate (ATP) was partially, but significantly restored during reperfusion in these hearts whereas no restoration was observed in the heart without the enzymes. The treatment with SOD and catalase also improved left ventricular stroke work index and left ventricular maximum dp/dt at an early stage of the working mode. These results suggest that the use of SOD and catalase during reperfusion can protect the ischemic heart against reperfusion injury by scavenging oxygen-derived free radicals.

Animals↗
PubMed1986

Mobilization of intracellular calcium as a mechanism for the positive inotropic effect by prostaglandin F2 alpha in isolated guinea pig atria.

The mechanism of the positive inotropic effect of prostaglandin F2 alpha (PGF2 alpha) was investigated using spontaneously beating isolated guinea pig atria. PGF2 alpha increased the contractile force in a concentration dependent fashion in a range between 10(-7)M to 10(-5)M. The maximal response to PGF2 alpha was obtained within 5 min and continued for at least 20 min. This positive inotropic effect of PGF2 alpha was not affected by verapamil, but was inhibited by procaine or TMB-8, potent inhibitors of Ca2+ release from intracellular Ca2+ compartments. Increase in extracellular Ca2+ concentration failed to provoke a significant positive inotropic effect by PGF2 alpha, suggesting that this response is relatively independent of extracellular Ca2+. These results suggest that the PGF2 alpha-mediated positive inotropic effect is produced by a mobilization of intracellular Ca2+.

Animals↗
PubMed1986

Enhanced prostaglandin synthesis due to phospholipid breakdown in ischemic-reperfused myocardium. Control of its production by a phospholipase inhibitor or free radical scavengers.

The effects of the inhibition of phospholipid degradation and superoxide radical generation on prostaglandin synthesis associated with myocardial ischemia and reperfusion were studied in the isolated, in-situ pig heart model subjected to 60 mins of regional ischemia and a further 60 mins of hypothermic potassium cardioplegic arrest, followed by 60 mins of reperfusion. Myocardial biopsies were taken from the ischemic and non-ischemic regions of the myocardium for measurement of phospholipids, and samples of the perfusate were drawn for estimation of the end-products of arachidonic acid metabolism, 6-keto-prostaglandin-F1 alpha and thromboxane B2. A significant amount of 6-keto-prostaglandin F1 alpha and thromboxane B2 appeared during reperfusion, corresponding with the loss of membrane phospholipids in control animals. Mepacrine, a phospholipase inhibitor, protected the depletion of membrane phospholipids and inhibited the products of arachidonate metabolism. Superoxide dismutase (SOD) and catalase, on the other hand, enhanced the formation of 6-keto-prostaglandin F1 alpha and thromboxane B2. The effects of both mepacrine and the free radical scavengers were pronounced during the reperfusion phase when the most significant depletion in membrane phospholipids occurred. These results suggest that the arachidonate cascade is activated during reperfusion of ischemic myocardium as a consequence of phospholipid breakdown, and this activation can be attenuated by inhibiting phospholipases or enhanced by scavenging oxygen-free radicals generated during reperfusion.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Role of membrane phospholipids in myocardial injury induced by ischemia and reperfusion.

Depletion of membrane phospholipids is known to be associated with myocardial ischemia, but its relationship to the injury involved with the reperfusion of ischemic myocardium is not known. The present study was designed to relate phospholipid degradation with reperfusion injury. The isolated in situ pig heart was subjected to 60 min of regional ischemia induced by occluding the left anterior descending (LAD) coronary artery and 60 min of global ischemia by hypothermic cardioplegic arrest followed by 60 min of reperfusion. The pigs were divided into two groups. In the treatment group, the heart was preperfused with mepacrine (0.05 mM), a known phospholipase inhibitor, for 15 min prior to LAD occlusion. In the control group, the total phospholipid content was not significantly decreased during LAD occlusion and arrest, but was reduced appreciably after reperfusion. Phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol followed a similar pattern. The lowering of these phospholipids during reperfusion was accompanied by enhancement of lysophosphatidylcholine. Mepacrine restored the normal levels of these phospholipids. During reperfusion, fatty acyl CoA synthetase, lysophospholipase, and lysophosphatidylcholine acyltransferase were depressed, whereas phospholipase A2 was enhanced. Mepacrine inhibited phospholipase A2, but had no effects on the other enzymes. Mepacrine also provided significant protection against reperfusion injury, as documented by the preservation of high-energy phosphate compounds and inhibition of the appearance of creatine kinase activity in the perfusate. These results suggest that membrane phospholipids play an important role in myocardial injury associated with ischemia and reperfusion, primarily because the deacylation-reacylation cycle of phospholipid biosynthesis becomes defective.

1-Acylglycerophosphocholine O-Acyltransferase↗
PubMed1986

Effect of superoxide dismutase and catalase on myocardial energy metabolism during ischemia and reperfusion.

Survival of cardiac patients undergoing heart surgery depends critically upon the recovery of myocardial energy metabolism during reperfusion of ischemic myocardium. The present study compares various parameters of myocardial energy metabolism using an isolated in situ pig heart. The left anterior descending (LAD) coronary artery was occluded for 60 min, followed by 60 min of global hypothermic cardioplegic arrest and 60 min of reperfusion. Free radical scavengers [superoxide dismutase SOD and catalase] were used to protect the ischemic heart from reperfusion injury. In both control and SOD plus catalase-treated groups, ATP, creatine phosphate (CP), ATP/ADP ratio, energy charge and phosphorylation potential dropped significantly during ischemic insult. After reperfusion, CP, ATP/ADP ratio and phosphorylation potential improved significantly, but they were restored to control level only in treated animals. In either case, free energy of ATP hydrolysis (delta G) lowered only by 5% during ischemia, but recovered promptly upon reperfusion. SOD and catalase also improved coronary blood flow and reduced creatine kinase release compared to those of untreated animals, suggesting improved myocardial recovery upon reperfusion. Our results suggest that SOD and catalase significantly improve the myocardial recovery during reperfusion by enhancing rephosphorylation steps, and the value of delta G is more critical compared to those of ATP and CP for myocardial recovery.

Adenosine Triphosphate↗
PubMed1986

Mepacrine, a phospholipase inhibitor. A potential tool for modifying myocardial reperfusion injury.

Cardioprotective effects of phospholipase inhibitor, mepacrine, on ischemic reperfused myocardium were investigated in the isolated in situ pig heart preparation, which was subjected to 120 minutes of regional ischemia, with the final 60 minutes having superimposed global cardioplegic arrest followed by 60 minutes of reperfusion. Mepacrine (0.05 mmol/L) was administered before ischemia into the perfusion circuit in 15 of 29 experiments. Significant depletion of myocardial phospholipids occurred in nontreated animals during 60 minutes of reperfusion. Mepacrine prevented the reperfusion-induced phospholipid degradation. Further, the level of high-energy phosphate compounds was higher during ischemia and reperfusion in the mepacrine-treated hearts. Left ventricular developed pressure, maximum rate of rise of left ventricular pressure, and left ventricular end-diastolic pressure were measured under isovolumic conditions to assess cardiac contractility and compliance. During incubation with mepacrine, before ischemia, left ventricular developed pressure and maximum rate of rise of left ventricular pressure decreased to 45% and 51% of baseline values, respectively. This initial decline was improved to 65% and 70% in mepacrine-treated animals during the early period of regional ischemia. In the nontreated control heart, a progressive decline in contractility was observed with ischemia such that no significant difference was apparent in the two groups. Reperfusion resulted in a further deterioration of global cardiac performance in both mepacrine-treated and control animals. Although pretreatment with mepacrine did not improve contractility, myocardial oxygen consumption, coronary flow, and cardiac compliance significantly improved. These results suggest that myocardial injury may develop during reperfusion after temporary ischemia. Mepacrine inhibits such injury by acting as a phospholipase inhibitor, but it also behaves as a negative inotropic agent in ischemic reperfused myocardium.

Animals↗
PubMed1986

Cardiac performance during reperfusion improved by pretreatment with oxygen free-radical scavengers.

We studied the effects of oxygen free radicals on cardiac performance during reperfusion of ischemic myocardium. The pig heart, isolated in situ, was subjected to 60 minutes of regional ischemia at normothermia by occlusion of the left anterior descending coronary artery followed by 60 minutes of hypothermic cardioplegic arrest and 60 minutes of normothermic reperfusion. The oxygen free-radical scavengers, superoxide dismutase and catalase, were administered before occlusion of the left anterior descending coronary artery in the experimental group. The generation of free radicals in the untreated group, estimated by the measurement of malondialdehyde in the perfusate, was significant during reperfusion and was associated with a corresponding increase in creatine kinase. Superoxide dismutase and catalase significantly slowed the appearance of malondialdehyde and the release of creatine kinase during reperfusion. Superoxide dismutase and catalase did not alter coronary flow and myocardial oxygen extraction or consumption during occlusion of the left anterior descending coronary artery; however, coronary flow and oxygen consumption were significantly higher (p less than 0.05) during reperfusion in hearts treated with antioxidants. Left ventricular developed pressure and its maximum first derivative were measured under isovolumic conditions. In the untreated group, left ventricular developed pressure and its maximum first derivative declined to 61.1% and 57.1% of baseline values, respectively, after 60 minutes' occlusion of the left anterior descending, and to 45% of baseline values after 15 minutes of reperfusion. The decline in left ventricular developed pressure and its maximum first derivative during reperfusion was significantly (p less than 0.05) inhibited by superoxide dismutase and catalase, but left ventricular end-diastolic pressure was not significantly altered. These results implicate oxygen-derived free radicals in the injury resulting from reperfusion of ischemic myocardium and suggest that oxygen free-radical scavengers effectively protect against such injury.

Animals↗
PubMed1985

Reperfusion injury induced by augumented oxygen uptake in the initial reperfusion period. Possible efficacy of extreme hemodilution.

This study was designed to investigate the relationship between myocardial oxygen consumption and oxygen-induced myocardial injury. Dog hearts were exposed to 40 min normothermic ischemia and then reperfused for 10 min with three oxygenated perfusates containing different hemoglobin concentrations and with moderate hemodilution. The experimental groups consist of a moderate hemodilution group (Group M) receiving 8 g/dl of hemoglobin, an extreme hemodilution group (Group E) given 4 g/dl of hemoglobin, and a hemoglobin-free autologous plasma group (Group F). Hearts in the non-ischemic control group (Group C) were also perfused with moderate hemodilution throughout. In Group C, Group M and Group E, the O2 tension of perfusates was maintained at about 100 mmHg and in Group F, at over 300 mmHg. Oxygen extraction at 5 min after reperfusion in Group C was 14%, in Group M and Group E less than 10%, but in Group F 70%. Oxygen consumption in Group F was more than twice that in Group E and surpassed that in Group C. Group M also showed a significant increase in oxygen consumption compared with Group E at 5 min after reperfusion. Among the ischemic groups, Group E showed improvement of left ventricular function almost comparable to Group C accompanied by a rapid decrease in myocardial lactate, improved preservation of myocardial adenine nucleotides and prevention of myocardial lipid peroxidation. In contrast, Group F showed persistently higher values of lipid peroxides and lactate, the poorest recovery of adenine nucleotides, and impairment of left ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗