Biomedical subjects

O Iimura

Publications and source records attributed to O Iimura.

284 records · Page 16Linked to original sources

PubMedDate not supplied

Effects of verapamil on myocardial stunning in xanthine-oxidase deficient hearts: pre-treatment vs. post-ischemic treatment.

The role of free radicals and the protective action of calcium antagonists have been established in myocardial stunning in canine hearts, which contain a considerable level of xanthine oxidase, a free radical producing enzyme. However, myocardial stunning in hearts which lack xanthine oxidase and its modification by calcium antagonists in vivo remain uncharacterized. The present study examined this issue using open-chest anesthetized rabbits. Myocardial stunning was induced by a 10-min coronary occlusion and reperfusion. Regional systolic thickening fraction (TF) was determined using an epicardial Doppler sensor, together with other hemodynamic parameters. In untreated control rabbits, recovery of TF from the 10 min transient ischemia was 43 +/- 3% of the baseline at 30 min after reperfusion. Administration of verapamil (200 micrograms/kg bolus plus 40 micrograms/kg/min), which was started before the onset of ischemia and continued until 20 min after reperfusion, significantly improved the recovery of TF to 74 +/- 6% (p < 0.05). A similar improvement in post-ischemic contractile function (TF = 77 +/- 10%) was observed when verapamil was injected at the same rate, but the infusion was discontinued 1 min after the coronary occlusion. Myocardial ATP depletion after the 10 min ischemia was significantly less in the verapamil-pretreated rabbits compared with untreated controls (10.1 +/- 1.0 vs. 6.2 +/- 0.7 mumol/g dry wt., p < 0.05). The difference in TF between the rabbit with and without verapamil treatment could not be explained by afterload reduction. When verapamil (100 micrograms/kg bolus plus 20 micrograms/kg/min) was given during the reperfusion period alone, TF recovery was poorer (TF = 22 +/- 8%) than the control value. Thus, it was concluded that verapamil attenuates myocardial stunning in the hearts with trace levels of xanthine oxidase, and that the beneficial effect is achieved only by pretreatment, not by post-ischemic treatment with verapamil.

Adenosine Triphosphate↗

PubMedDate not supplied

Suppression of the degradation of adenine nucleotides during ischemia may not be a sufficient mechanism for infarct size limitation by preconditioning.

Preconditioning is known to decelerate degradation of the tissue adenine nucleotides during ischemia and to delay ischemic myocardial necrosis. However, it is not known whether these two phenomena are related. To obtain an insight into this question, the present study examined whether adenosine and B2 receptor antagonists, which block the infarct size-limiting effect of preconditioning, modify the interstitial purine levels during preconditioning and subsequent sustained ischemia. In pentobarbital anesthetized open-chest rabbits, a microdialysis probe was placed in the territory of a branch of the left coronary artery, and perfused with Ringer solution. Preconditioning was performed with 5 min ischemia/5 min reperfusion. Dialysate adenosine and inosine were elevated from the baseline values of 0.064 +/- 0.011 and 0.329 +/- 0.044 microM to 0.189 +/- 0.069 and 4.106 +/- 1.451 microM, respectively during preconditioning, but their elevation during a subsequent 20 min of ischemia was significantly lower compared with that in the non-preconditioned myocardium. This suppression of the purine accumulation during ischemia by preconditioning was not abolished by 2 micrograms/kg of Hoe 140, a specific B2 receptor antagonist, or by 10 mg/kg of 8-phenyltheophylline, a non-selective adenosine receptor antagonist. Since the doses of Hoe 140 and 8-phenyltheophylline are sufficient to block the infarct size-limiting effect of preconditioning, the present results suggest that there is a dissociation between the suppression of adenine nucleotide degradation during ischemia by preconditioning and the enhancement of myocardial resistance against infarction. Thus, it is unlikely that a reduction of adenine nucleotide utilization by preconditioning is sufficient to protect the myocardium against ischemic necrosis.

Adenine Nucleotides↗

PubMedDate not supplied

Reduction of regional contractile function by preconditioning ischemia does not play a permissive role in the infarct size-limitation by the preconditioning.

Although previous studies have shown that preconditioning cannot be explained by concurrent myocardial stunning alone, it remains unclear whether reduction of contractile function by preconditioning ischemia is required for its cardioprotective effect. The present study examined whether preconditioning occurs in the absence of regional contractile dysfunction. In the first series of experiments, rabbits received two cycles of 2-min coronary occlusion separated by 5-min reperfusion, with or without dobutamine infusion (10 micrograms/kg/min, i.v.) commencing before the onset of ischemia. Regional thickening fraction measured by epicardial Doppler sensor was 72.8 +/- 4.7% of baseline (mean +/- SEM) in the untreated group and 102.9 +/- 3.1% in the dobutamine group at the end of the second cycle of ischemia/reperfusion. In the second series of the study, four groups of rabbits underwent 30-min coronary occlusion and reperfusion. The control group was untreated, and the PC group was preconditioned with two cycles of 2-min ischemia/5-min reperfusion before the 30-min ischemia. The PC-DOB group received both preconditioning and dobutamine infusion (10 micrograms/kg/min, i.v.), which was started 5 min before the preconditioning and continued for 19 min. The DOB group was given dobutamine infusion like the PC-DOB group, but was not preconditioned. After 72-h reperfusion, infarct size and area at risk were determined by histology and fluorescent particles, respectively. Infarct sizes in the PC and PC-DOB groups (25.0 +/- 3.4% and 22.7 +/- 3.3% of area at risk, respectively) were significantly smaller than that in the control group (48.2 +/- 2.6%). In the DOB groups, infarct size (43.5 +/- 4.0%) was similar to the control value. Infusion of dobutamine at a dose sufficient to abolish the contractile dysfunction which would have been induced by ischemic preconditioning did not attenuate the infarct size-limiting effect of preconditioning. Thus, it is unlikely that reduction of contractile function plays a permissive role in the appearance of the cardioprotective effect of preconditioning.

Animals↗

PubMedDate not supplied

Suppression of reperfusion arrhythmia by ischemic preconditioning in the rat: is it mediated by the adenosine receptor, prostaglandin, or bradykinin receptor?

The mechanism for the suppression of reperfusion arrhythmia by preconditioning (PC) remains unknown. This study aimed to examine the roles of the adenosine receptor, prostaglandin (PG), and bradykinin (BK) receptor in PC. Under pentobarbital anesthesia, the coronary artery of the rat was occluded for 5 min and then reperfused. In untreated controls, this protocol induced ventricular tachycardia (VT) in 100% of the rats and ventricular fibrillation (VF) in 60%. PC with 2 min ischemia/5 min reperfusion prior to the 5 min coronary occlusion significantly reduced the incidence of reperfusion VT and VF to 30% and 0%, respectively. This antiarrhythmic effect of the PC was not blocked when rats were pretreated with 8-phenyltheophylline (8-PT, 10 mg/kg), aspirin-DL-lysin (18 mg/kg), or a specific BK receptor antagonist, Hoe140 (20 nmol/kg). None of these agents alone significantly modified the incidence of reperfusion VT or VF. These results suggest that neither the adenosine receptor, endogenous PG, nor BK receptor play a major role in the mechanism of suppression of perfusion arrhythmias by PC in the rat heart.

Adrenergic beta-Antagonists↗

PubMedDate not supplied

Effects of a calcium channel blocker, manidipine, on insulin sensitivity in essential hypertensives.

This study was designed to investigate the effects of the calcium channel blocker manidipine on insulin-dependent glucose uptake (insulin sensitivity) and insulin action to renal sodium handling and pressor systems in essential hypertensive (EHT). Seven EHT were hospitalized and a 2-h euglycemic hyperinsulinemic glucose clamp was performed in a fasting condition before and after 2 weeks administration of manidipine (20 mg/day). Insulin sensitivity was evaluated as M-value calculated from the infusion rate of glucose. Manidipine administration decreased mean blood pressure and increased M-value significantly in EHT. Before the manidipine treatment, hyperinsulinemia during the clamp induced a decrease of urinary sodium excretion and increases of plasma norepinephrine and plasma renin activity in EHT. After manidipine treatment, however, hyperinsulinemia induced natriuresis and did not augment the pressor systems activity. Thus, the calcium channel blocker improved insulin resistance as assessed by glucose clamp technique in EHT. Suppression of augmented renal sodium reabsorption and pressor system activities of insulin may be connected with the hypotensive mechanisms and the natriuresis caused by calcium channel blockers.

Blood Glucose↗

PubMedDate not supplied

Role of renal dopaminergic activity on renal sodium-water metabolism in congestive heart failure.

1. The role of the renal dopaminergic system in water-sodium metabolism in heart failure remains unclear. 2. In this study, the urinary free dopamine excretion (uDA), delivery of L-dopa to renal proximal tubules (plasma L-dopa x creatinine clearance (Ccr)), and the production of dopamine in the kidney [uDA/(plasma L-dopa x Ccr)] were investigated in patients with congestive heart failure (n = 30) and in normal controls (n = 12). In both groups, endogenous Ccr, urinary excretion of sodium (UNaV), fractional excretion of sodium (FENa), plasma noradrenaline concentration (pNA) and plasma L-dopa concentration were also estimated. 3. uDA, plasma L-dopa, delivery of L-dopa and dopamine production in the kidney showed successively lower values in congestive heart failure with progression in NYHA functional class. 4. UNaV (r = 0.458, P < 0.05) and Ccr (r = 0.539, P < 0.01) positively correlated with uDA. Linear correlations were found between left ventricular ejection fraction and uDA (r = 0.574, P < 0.01), pNA (r = -0.495, P < 0.01) or plasma L-dopa (r = 0.423, P < 0.05). 5. From these findings, it was suggested that (i) uDA was clearly suppressed in patients with CHF, and (ii) the possible mechanisms of its suppression might be due to decrease of delivery of L-dopa into the proximal tubules and suppressed production of dopamine from L-dopa in the kidney.

Adult↗

PubMedDate not supplied

A case of a right coronary artery to left ventricle fistula observed over twenty years.

Since the natural history of a coronary artery to left ventricle fistula is not well known, a case of such a fistula in 36-year-old female patient, followed for 20 years is presented. Two-dimensional echocardiography performed as a follow-up examination revealed enlargement of the right coronary artery and the right Valsalva sinus. Two-dimensional color flow mapping showed the jet flow to the apex from the base of the left ventricle only during the diastolic phase. An aortogram confirmed that enlargement of both the right coronary artery and the right Valsalva sinus had occurred during the 20 years. The shunt flow ratio was about 50%. The Symbas procedure, closing of the coronary artery fistula by arteriotomy directly over the site of the fistula, was performed with the aid of extracorporeal circulation. Our findings indicate that enlargement of the shunted coronary artery and its Valsalva sinus can occur gradually where there is a relatively large shunt flow. Therefore, early surgical treatment is recommended in cases like this one.

Adult↗

PubMedDate not supplied

A case of swallow syncope induced by vagovagal reflex.

A 65-year-old man experienced syncope associated with advanced atrioventricular (AV) block upon swallowing. Continuous electrocardiogram (ECG) monitoring revealed first and second degree AV block. ECG revealed advanced AV block (Max R-R 6.38 s) upon swallowing, a cold drink. Demand ventricular pacing alleviated his symptoms. In this patient, the advanced AV block might have been precipitated by a vagovagal reflex triggered by expansion of the esophagus, resulting in selective suppression of the atrioventricular node.

Aged↗

PubMedDate not supplied

Comparative hypertensionology-renal dopaminergic activity in experimental hypertensive rats.

In our laboratory, it had been found that the renal natriuretic and depressor systems are suppressed in essential hypertension, and that suppression of the dopaminergic system may be primary and dominant in this condition. Moreover, close relationships among the renal dopamine, kallikrein-kinin, and prostaglandin systems have also been found. Therefore, we attempted to evaluate the pathogenetic and pathophysiological role of renal dopamine in connection with renal kallikrein-kinin and prostaglandin systems in various experimental hypertensive models. Two kidney 1 clip hypertensive rats (2K1C), 5/6 reduced renal mass hypertensive rats (5/6 RRM), deoxycorticosterone acetate-salt hypertensive rats (DOCA-salt), spontaneously hypertensive rats/Izumo (SHR/Iz), Dahl salt sensitive hypertensive rats/John Rapp (Dahl/Jr), Dahl/Iwai (Dahl/Iw), and respective controls were employed in this study. Urinary excretions of free dopamine (uDA), kallikrein (uKAL), and prostaglandin E2 (uPGE2) were measured before, during and after treatment in each of these hypertensive models. In these experimental hypertensive models, renal dopamine in DOCA-salt and SHR/Iz, and renal kallikrein in 2K1C, 5/6 RRM and two types of Dahl strains were primarily and dominantly suppressed in the renal natriuretic and depressor systems. Renal dopamine was transiently suppressed in Dahl/Jr, and PGE2 was suppressed in the two types of Dahl strains. Compensatory augmentation of renal kallikrein was found in DOCA-salt and SHR/Iz, and that of PGE2 was found in 5/6 RRM and DOCA-salt. Although these three renal natriuretic depressor systems are suppressed in Dahl/Jr, the dominantly suppressed system is not renal dopamine but renal kallikrein. Thus, it was summarized that, 1) decreased renal dopamine production is important in the pathogenesis of human essential hypertension, 2) pressor mechanisms of experimental hypertensive rats are different from human essential hypertension, 3) decreased renal dopamine is important in DOCA-salt and SHR/Iz, 4) decreased renal kallikrein is the dominant mechanism in the pathogenesis of 2K1C, 5/6 RRM, Dahl/Jr and Dahl/Iw hypertensive rats, and 5) we have to be careful when considering human essential hypertension through results taken from experimental rat hypertensive models.

Animals↗

PubMedDate not supplied

Studies on experimental coronary insufficiency. I. Effects of a physiological dose of adrenaline and noradrenaline on myocardial metabolism in dogs with graded coronary constriction.

To investigate the mechanism by which catecholamines produce myocardial ischemia, the effect of intracoronary-administered adrenaline and noradrenaline was studied in dogs with graded coronary constriction. A physiological dose of catecholamines was favorable for augmentation or improvement of myocardial metabolism and cardiac function in dogs without or with slight coronary constriction. However, in dogs with moderate or severe coronary constriction, similar doses of catecholamines produced myocardial ischemia and cardiac dysfunction.

Animals↗

PubMedDate not supplied

Studies on experimental coronary insufficiency. II. Effects of beta-adrenergic blocking agent (propranolol) on metabolic response to adrenaline and noradrenaline in dogs with coronary constriction.

To obtain further information on the mechanism by which catecholamines produce myocardial ischemia, the effects of propranolol on metabolic and mechanical responses to adrenaline or noradrenaline were investigated in coronary-constricted dogs. Propranolol suppressed the myocardial ischemia produced by noradrenaline and adrenaline in dogs with moderate coronary constriction.

Animals↗

PubMedDate not supplied

Effect of superoxide dismutase plus catalase on myocardial infarct size in rabbits.

A previous study by the authors showed that myocardial infarct size in the rabbit, measured after 45 mins of ischemia and 3 h of reperfusion, could be limited by administration of superoxide dismutase (SOD) plus catalase. The present study examined whether this infarct size limitation is sustained for the following three days. Under anesthesia, a coronary branch of the Japanese white rabbit was occluded for 45 mins and then reperfused. Three days after surgery, the heart was excised and the volume of myocardium supplied by the occluded coronary branch (ischemic zone size) was assessed with fluorescent particles and the infarct size was estimated by hematoxylin and eosin and with Mallory's staining. The SOD plus catalase group (n = 14) received 15,000 units/kg of SOD plus 50,000 units/kg of catalase in saline over 90 mins, starting 15 mins before the coronary occlusion. Saline was infused in the control group (n = 15). Three rabbits in the control group and three in the SOD plus catalase group died of ventricular fibrillation during the ischemic period. Three control and two SOD plus catalase rabbits were excluded because the ischemic zone was ambiguous. The percentage of the ischemic zone which was infarcted was 59.4 +/- 6.9% (mean +/- SE) in the control group (n = 9) and 49.4 +/- 5.1% in the SOD plus catalase group (n = 9). These were not statistically different. Ischemic zone size and hemodynamic parameters were similar in the two groups. These findings suggest that SOD plus catalase may serve only to delay rather than prevent myocardial infarction.

Animals↗

PubMedDate not supplied

Diltiazem reduced infarct size but not ventricular arrhythmias in 48 hour coronary embolized dogs.

The calcium antagonist, diltiazem, was examined for its ability to limit infarct size and to diminish the severity and frequency of the ventricular arrhythmias in closed chest dogs following coronary occlusion. Diltiazem was administered 100 micrograms/kg as a bolus, followed by 15 micrograms/kg/min infusion for 48 h, starting 10 min after coronary occlusion (11 dogs). The control groups (9 dogs) received an equal volume of saline. Risk area and regional myocardial blood flow was measured with radioactive microspheres 5 min after coronary embolization. Forty-eight hours after embolization, the dogs were sacrificed, the hearts sectioned into 4 mm slices and the slices were stained with triphenyl tetrazolium chloride to measure the infarct size. Risk size was determined by autoradiography of the microspheres. Infarct size, expressed as a percentage of the area at risk, was significantly lower in the diltiazem treated group than in the control group (47.4 +/- 8.9 vs. 76.1 +/- 6.4%). However, the severity and frequency of the ventricular arrhythmias for the first 24 h was not any different between two groups.

Animals↗

PubMedDate not supplied

[Fatty acid metabolic and perfusion abnormalities in hypertrophied myocardium assessed by dual tracer tomography using thallium-201 and iodine-123-beta-methylpentadecanoic acid].

Fatty acid metabolic and perfusion abnormalities associated with cardiac hypertrophy were investigated using dual tracer tomography with thallium and a cardiac metabolic tracer, 15-(p-iodophenyl)-3-R, S-methylpentadecanoic acid (BMIPP), in eight patients with hypertrophic cardiomyopathy (HCM) and in three with hypertension (HT). Thallium and BMIPP uptakes were scored and analyzed in 143 segments (13/heart) by comparison with the left ventricular wall thickness measured by two-dimensional echocardiography. Complete agreement of both scores in HT patients was significantly higher than that in HCM patients (64% vs 24%, p < 0.001), while a lower BMIPP uptake compared to that of thallium (mismatching) was observed more frequently in HCM than in HT patients (65% vs 31%, p < 0.001). The wall thickness significantly (p < 0.005) correlated with BMIPP uptake score. HCM patients showed a low BMIPP uptake in 22 hypertrophic segments (59%) and 15 non-hypertrophic segments (41%), and reduced BMIPP uptake in 29% hypertrophic segments, while HT patients showed just five segments with decreased BMIPP uptake of which 4 were non-hypertrophic and only one hypertrophic. The left ventricular ejection fraction assessed by radionuclide ventriculography was normal and no regional wall motion abnormality was detected in any patient by echocardiographic and scintigraphic studies. Metabolic abnormalities detected by the iodine-123-beta-methyl fatty acid analog in hypertrophic cardiomyopathy may be independent of thallium myocardial perfusion, regional wall motion, or the magnitude of cardiac hypertrophy, suggesting that fatty acid imaging may be useful in investigating the pathogenesis and subclinical abnormality of hypertrophic cardiomyopathy, and differentiation from secondary, induced cardiac hypertrophy.

Adult↗