N Konno

Showa University, Shinagawa, Tōkyō, Japan

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Publications (36)38.12 Total impact

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    ABSTRACT: Drug-eluting stents (DESs) have been shown to decrease restenosis as compared with bare-metal stents. Recently, thiazolidinediones effectively reduced restenosis and the risk of repeat target vessel revascularization. We conducted a study to compare the performance of a DES with that of a bare-metal stent with pioglitazone in patients with Type 2 diabetes mellitus (DM). The study was a prospective cohort trial involving 38 Type 2 diabetic patients referred for coronary stenting who were assigned to either the sirolimus-eluting stent (SES) group or the pioglitazone group. Quantitative coronary angiography was performed at study entry and at 6 months of follow-up to evaluate in-stent late luminal loss and the percentage of the luminal diameter and the rate of restenosis. We also analyzed major adverse cardiac events (MACE) at 12 months. There were no significant differences in glycemic control levels or in lipid levels in the two groups at follow up. The insulin and homeostasis model assessment insulin resistance at follow-up were significantly lower in the pioglitazone group than in the SES group. The percentage of restenosis was similar between the SES group and the pioglitazone group. The incidence of MACE at 1 year tended to be lower in the pioglitazone group than in the SES group. The bare-metal stent with pioglitazone is not inferior to the SES in the present study and is one of therapeutic strategies of percutaneous coronary intervention for patients with DM.
    Cardiovascular revascularization medicine: including molecular interventions 01/2009; 10(1):5-11.
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    ABSTRACT: The aim of this study was to evaluate the effect of pioglitazone on nitric oxide in patients with type 2 diabetes and coronary artery disease. Twenty-seven patients with coronary artery disease and diabetes mellitus who had received coronary stenting were eligible for the study. They were assigned to the no insulin resistance (NIR) group, the insulin resistance (IR) group, and the pioglitazone group (30 mg once a day). Endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-alpha), interleukin-6, leptin, and adiponectin were measured. In the pioglitazone group, eNOS, iNOS, and leptin were significantly lower and adiponectin was significantly higher than those in the IR group. Stepwise multiple regression analyses showed that eNOS correlated with TNF-alpha and iNOS correlated with leptin and TNF-alpha. Leptin was the strongest predictor of iNOS. Treatment with pioglitazone significantly reduced eNOS and iNOS by improving adipocytokine levels.
    Journal of the CardioMetabolic Syndrome 02/2008; 3(4):200-4.
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    ABSTRACT: Recent studies have demonstrated that the treatment with thiazolidinediones reduces in-stent restenosis. The aim of this study was to elucidate the mechanism of the efficacy of pioglitazone for preventing in-stent restenosis in type 2 diabetic patients. We conducted a prospective, randomized trial involving 54 type 2 diabetic patients referred for coronary stenting who were randomly assigned to either the control or the pioglitazone group. Quantitative coronary angiography was performed at study entry and at 6 months follow-up. Endothelial nitric oxide synthase (eNOS), tumor necrosis factor alpha, interleukin-6, leptin, and adiponectin were measured at study entry and at 6 months follow-up. A total of 28 patients were randomly assigned to the control group, and 26 patients were assigned to the pioglitazone group. There were no significant differences in glycemic control levels or in lipid levels in the two groups at baseline or at follow-up. Insulin, homeostasis model assessment of insulin resistance, eNOS, and leptin at follow-up were significantly reduced in the pioglitazone group compared with the control group. The late luminal loss and in-stent restenosis were significantly less in the pioglitazone group than in the control group. Leptin independently correlated with late luminal loss at multiple regression analysis. The treatment with pioglitazone in type 2 diabetic patients significantly reduced leptin. This decreased leptin improved insulin resistance and endothelial function with the reduction of insulin. The improved endothelial function affected the reduction of in-stent restenosis.
    Diabetes Care 02/2006; 29(1):101-6. · 7.74 Impact Factor
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    ABSTRACT: Recent studies have shown that insulin resistance (IR) is an independent predictor of early restenosis after coronary stenting. The aim of this study was to examine the effects of IR and its linkage to late loss with bare metal stenting in nondiabetic patients with acute myocardial infarction (AMI). We enrolled 61 nondiabetic patients with AMI who have undergone coronary stenting. Quantitative analyses of coronary angiographic data before and after the procedure and at 4 months were performed. Fasting plasma glucose (FPG) and insulin were measured every week until the subjects' hospital discharge. Stress hormones, endothelial nitric oxide synthase, tumor necrosis factor alpha, interleukin-6, leptin, and adiponectin were measured on admission and at 4 months after coronary stenting. Simple linear regression analyses showed a relationship between FPG and insulin [IR group: r=0.297, P=.0428; no insulin resistance (NIR) group: r=0.539, P=.0466] and that late loss was associated with the homeostasis model assessment of IR (HOMA-IR) at 4 months (r=0.435, P=.03). At multiple regression analyses, HOMA-IR on admission in the IR group significantly correlated with thyroid-stimulating hormone, glucagon, and cortisol. The HOMA-IR at 4 months correlated with leptin. Nondiabetic patients with AMI can be classified into two groups: the IR group and the NIR group. The IR consisted of the transient IR, which correlated with stress hormones, and the continuous IR, which correlated with leptin and contributed to restenosis after coronary stenting.
    Cardiovascular Revascularization Medicine 01/2006; 7(2):54-60.
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    ABSTRACT: The rationale of this study was to determine whether insulin resistance is an independent risk factor for restenosis after coronary stenting. Previous studies suggested that hyperinsulinemia may be an important risk factor for ischemic heart disease. Restenosis after coronary stenting is neointimal tissue proliferation and de-novo stenosis is atherosclerosis from the point of view of histology. However, it has not been determined whether insulin resistance is independently related to restenosis after coronary stenting. Clinical variables of unselected population of 110 patients were analyzed in multivariate logistic regression analyses for both restenosis and de-novo stenosis. Clinical, lesion-related, and procedural variables were analyzed by chi-square analysis, and relative risk. Multivariate logistic regression analysis showed that homeostasis model assessment insulin resistance (HOMA-IR) and HbA1c were associated with restenosis after coronary stenting (HOMA-IR; P=0.0447, HbA1c; P=0.0462), and HbA1c and low-density lipoprotein cholesterol (LDL-C) were associated with de-novo stenosis (HbA1c; P=0.0201, LDL-C; P=0.0204). Restenosis was influenced by insulin resistance [Relative Risk (RR) 2.06; 95 percent confidence interval (95%CI) 1.20 to 3.56], diabetes mellitus (DM: RR 1.92; 95%CI 1.25 to 2.95), and final minimal lumen diameter (RR 2.83; 95%CI 1.32 to 6.06). HOMA-IR and DM are the predictors of restenosis after coronary stenting, and HbA1c and LDL-C are the predictors of de-novo stenosis. These results may be reflected in histological differences between neointimal tissue proliferation as restenosis and atherosclerosis as de-novo stenosis.
    International Journal of Cardiology 09/2005; 103(2):128-34. · 6.18 Impact Factor
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    ABSTRACT: To characterize relationships between mineral homeostasis, bone turnover, bone mass, and congestive heart failure (CHF), we evaluated 75 women with mild to moderate CHF. We examined the association in annual rate of change in spinal bone mineral density (BMD) with polymorphism of the vitamin D receptor (VDR) gene. Compared with the control group, the CHF group had reduced left ventricular ejection fraction (LVEF: 68.2 +/- 7.5% vs. 60.2 +/- 12.9%; P = 0.0249), human atrial natriuretic peptide (hANP) was elevated (hANP: 10.7 +/- 4.7 pmol L-1 vs. 25.8 +/- 24.2 pmol L-1; P = 0.001) and had lower peak VO2 (22.3 +/- 7.5 mL kg-1 min-1 vs. 15.8 +/- 7.4 mL kg-1 min-1; P = 0.0429). The CHF patients with the VDR FF genotype had a significantly high annual rate of decrease in BMD. In the CHF patients with the VDR FF genotype, urinary calcium excretion (FECa) was elevated (1.40 +/- 0.91% vs. 2.39 +/- 1.40%; P = 0.028), and serum bone-type alkaline phosphatase (B-ALP) was reduced (62.6 +/- 13.7 IU L-1 vs. 47.0 +/- 18.6 IU L-1; P = 0.0123). Also, FECa was correlated positively with furosemide dose (R = 0.881; P = 0.0087) and hANP concentrations (R = 0.635; P = 0.0147) and negatively with DeltaBMD (R = 0.72; P = 0.044) in the CHF patients with the VDR FF genotype. The CHF patients with the VDR FF genotype have higher rates of bone loss. These patients may need to increase their calcium intake and BMD may need to be followed more carefully over time.
    Journal of Internal Medicine 05/2003; 253(4):439-46. · 6.46 Impact Factor
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    ABSTRACT: Free radicals have been implicated in myocardial reperfusion injury. Hydrogen peroxide (H(2)O(2)) is one possible source of reactive oxygen intermediates. We studied the formation and toxicity of H(2)O(2) in isolated myocytes during hypoxia-reoxygenation with the use of cerium. This method involves formation of an electron-dense precipitate when H(2)O(2) reacts with cerium chloride (CeCl(3)). Single myocytes were obtained from rat hearts by collagenase digestion. Isolated myocytes were reoxygenated for 15 min after 30 min of hypoxia. The cells were treated with digitonin to increase the permeability of the plasma membrane, and CeCl(3) was added to detect intracellular H(2)O(2) on electron microscopy. In the nonhypoxia control group, the ultrastructure of cells was well preserved, and no dense deposits were found in myocytes. In the hypoxia-reoxygenation group, precipitates, i.e., Ce-H(2)O(2) reaction products, were found inside and along swollen mitochondria, and cell viability was reduced to 72.3% of control. These results indicate that endogenous H(2)O(2) is generated by mitochondria and that its release into the cytosol may lead to myocyte death under pathological situations such as hypoxia-reoxygenation.
    Medical Electron Microscopy 04/2003; 36(1):41-6.
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    ABSTRACT: Free radical generation was studied by the electron spin resonance (ESR) technique using alpha-phenyl N tert butyl nitrone (PBN) in a brief ischemia-reperfusion model of the canine heart, and correlated with biochemical changes of the sarcoplasmic reticulum (SR). ESR spectra (aH=0.3-0.4mT, aN=1.43-1.58mT) were observed as PBN spin adducts, which peaked at levels 5-fold above the control levels at 5 min after reperfusion. The simulated coupling constants of PBN spin adducts suggested that the sample should contain at least 2 carbon-centered radicals at 5 min after reperfusion (radical A: aH=0.350mT, aN=1.485mT; radical B: aH=0.370mT, aN=1.615 mT). At this time point, a significant reduction in Ca-ATPase activity of the SR was found without degradation of the major ATPase protein. Superoxide dismutase (SOD) significantly reduced the intensity of the PBN spin adduct signals and preserved the Ca-ATPase activity of the SR to 80% of the control level. Reperfusion injury after brief ischemia may be the result of inactivation of intracellular Ca-ATPase by free radicals generated during reperfusion, and SOD contributes to the protective effect by scavenging the radicals.
    Japanese Circulation Journal 06/1999; 63(5):373-8.
  • Journal of Cardiac Failure - J CARD FAIL. 01/1999; 5(3):60-60.
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    ABSTRACT: Free radicals have been implicated in myocardial reperfusion injury. Hydrogen peroxide (H2O2) is a precursor of highly reactive oxygen intermediates. In this study, we investigated myocardial injury caused by endogenous H2O2 during the early reperfusion period following brief ischemia with electron microscopy and the cerium method. This method involves formation of an electrondense precipitate when H2O2 reacts with cerium chloride (CeCl3). We used isolated, functioning hearts prepared according to the working heart model, which were reperfused with a solution containing 0.5mM CeCl3 for 5 min after 10 min of ischemia. Some hearts were treated with 3-amino-1,2,4-triazole (ATZ) to inhibit catalase; others were treated with ATZ and superoxide dismutase (SOD), which dismutates the superoxide anion to hydrogen peroxide. In the control group (no drugs given) and the ATZ-treated group, the CeCl3–H2O2-dependent reaction products during the reperfusion period appeared in 12% and 28%, respectively, of the microvascular spaces. Treatment with SOD did not produce a decrease in electron-dense precipitates or a decrease in myocardial injury during ischemia-reperfusion. Moreover, in the ATZ group, moderately injured myocytes were seen (swelling of mitocondria, intermyofibrillar edema). Our results indicate that in myocytes, catalase plays an important role in the defense against H2O2 and that the increase in H2O2 is a cause of reperfusion injury. However, SOD does not protect against H2O2 in the absence of catalase.
    Medical Electron Microscopy 01/1998; 31(2):77-84.
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    ABSTRACT: Oxygen consumption may be disproportionately high relative to contractile function in postischemic reperfused myocardium. The study reported in this chapter investigated the mechanism of the dissociation between oxygen consumption and contractile function in postischemic reperfused myocardium using isolated rat hearts. Mitochondrial dysfunction secondary to increased calcium uptake has been implicated as an important mediator of reperfusion injury in the heart. In postischemic, isovolumic, antegrate-perfused rat hearts, the myocardial oxygen consumption rate (MVO2) and contractile function were studied in relation to mitochondrial function. Left ventricular pressure, coronary blood flow, and oxygen consumption were determined. Mitochondrial respiration and the mitochondrial membrane potential were measured by polarography and flow cytometry, respectively. To examine the role of mitochondrial calcium uptake in ischemia reperfusion injury, isolated rat hearts perfused with ruthenium red, which inhibits calcium uptake by mitochondria, were compared to control perfused hearts. After stabilization, hearts were subjected to 60 minutes of no-flow ischemia, followed by 60 minutes of reperfusion. At 15 minutes after the onset of reperfusion, there was poor recovery of left ventricular developed pressure to 64% of the control level, but myocardial oxygen consumption was increased to 134% of control. The addition of 2.5 μM ruthenium red to the perfusate resulted in a decrease of myocardial oxygen consumption. The oxygen consumption rate in state 3 of mitochondria decreased similarly following reperfusion in control and ruthenium red hearts. The mitochondrial membrane potential was reduced to 89% (logarithmic scale) after 15 minutes of reperfusion and then returned to preischemic level. These data suggest that the dissociation between oxygen consumption and contractile function following early reperfusion is partly caused by the repair of intracellular damage resulting from calcium accumulation to mitochondria.
    12/1997: pages 125-135;
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    ABSTRACT: Active oxygen species, including hydrogen peroxide (H2O2), have been implicated in myocardial reperfusion injury. Recently, spin-trap agents and biochemical techniques applied to intact hearts have shown that H2O2 is generated by leukocytes, by endothelial cells, and by mitochondria in myocytes. In this study, we used electron microscopy and the cerium (Ce) method to histologically investigate H2O2 formation during hypoxia—reoxygenation and its toxic effects on myocardium. This Ce method involves the formation of an electron-dense precipitate when H2O2 reacts with cerium chloride (CeCl3). Single myocytes were obtained from rat hearts by the collagenase method. Isolated myocytes were reoxygenated for 15 minutes after 30 minutes of hypoxia. Digitonin and CeCl3, were added to make cell membranes permeable and to detect intracellular H2O2 by electron microscopy. In the control group, the ultrastructure was well preserved and no dense deposits were found in myocytes. However, in the hypoxia—reoxygenation group, precipitates, which were cerium—H2O2 reaction products, were found along swollen mitochondria. Moreover, in the hypoxia-reoxygenation group, cell viability was reduced to 72% of control. These results indicate that H2O2 is generated by mitochondria and that its relese into cytosol may lead to myocyte death during hypoxia—reperfusion.
    12/1997: pages 67-76;
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    ABSTRACT: The myocardium under severe ischemia and reperfusion exhibits four types of different pathophysiologic behaviors: coagulation necrosis, stunning, ischemic preconditioning, and reperfusion injury. This chapter describes these changes in the postischemic myocardium in relation to the length of ischemia. Canine hearts were made ischemic by occludmg the left anterior descending coronary artery (LAD), and the sarcoplasmic reticulum (SR) from the ischemia-reperfused myocardium was analyzed. In permanent occlusion of the LAD, Ca2+-ATPase activity of the SR was reduced simultaneously with the degradation of the major ATPase protein in ischemia for 20 to 30 minutes. In the stunned myocardium, with occlusion of the LAD for 15 minutes and reperfusion, long-term reduction in the activity of the SR was noted simultaneously with a reduction in the percent of segment shortening, but without degradation of the ATPase protein of the SR. In the preconditioned myocardium, in which the LAD was occluded four times for five minutes each prior to LAD occlusion for 60 minutes and reperfusion, both ATPase activity and the SR ATPase protein were preserved In reperfusion of the LAD after occlusion for 10 to 30 minutes, reduction in Ca2+-ATPase activity and degradation of the ATPase protein occurred earlier, simultaneously with generation of free radicals, suggesting reperfusion injury. We conclude that pathophysiologic behaviors of the postischemic myocardium proceed in quite different ways depending upon the length of ischemia and will only be fully understood in the light of studies on ischemia and reperfusion of the heart muscle.
    12/1997: pages 137-149;
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    ABSTRACT: Diabetes mellitus is associated with alterations in lipid metabolism and cardiac dysfunction despite an absence of coronary arteriosclerotic changes. To investigate mechanisms of cardiac dysfunction in diabetic cardiomyopathy, we studied the relation between activities of membrane-bound enzymes and surrounding phospholipids in rats with diabetes induced with a single intravenous injection of streptozotocin (65 mg/kg). We found that total phospholipid content of sarcoplasmic reticulum membrane increased significantly 8 weeks after treatment with streptozotocin owing to increases in phosphatidylcholine and phosphatidylethanolamine, a decrease in arachidonic acid, and an increase in docosahexaenoic acid in the early stage of diabetes. Sarcolemmal Na+/K(+)-ATPase activity and the number of receptors decreased in isolated cardiomyocytes of diabetic rats 8 weeks after streptozotocin administration. The Ca2+ uptake of both sarcoplasmic reticulum and mitochondria decreased simultaneously in permeabilized, isolated cardiomyocytes from diabetic rats. The depression of membrane-bound enzyme activities was correlated with alterations in phospholipids, which are closely related to the microenvironment of membrane-bound enzymes and influence intracellular Ca2+ metabolism. Because these changes in phospholipids and fatty acids were reversible with insulin therapy, they are diabetes-specific and might be a cause of cardiac dysfunction in diabetes.
    Archiv für Kreislaufforschung 09/1997; 92(4):214-22. · 5.90 Impact Factor
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    ABSTRACT: We evaluated the effects of angiotensin-converting enzyme (ACE) inhibition on metabolic changes in myocardial organelles, myocardial hypertrophy, and interstitial fibrosis in the early stage of hypertension. An ACE inhibitor, imidapril (2.5 mg/kg per day), a calcium-channel blocker, diltiazem (30 mg/kg per day), or vehicle was given to spontaneously hypertensive rats (SHRs) from 10 to 18 weeks of age. Single myocytes were isolated enzymatically from the left ventricles of these SHRs and normotensive Wistar-Kyoto (WKY) controls at 18 weeks of age. In single ventricular myocytes, enzyme activities in the sarcoplasmic reticulum (SR) and the sarcolemma (SL) and the mitochondrial respiratory control ratio (RCR) were determined. In 18-week-old SHRs receiving vehicle, myocardial hypertrophy and interstitial fibrosis developed, and SR Ca2+ AT-Pase activity and the mitochondrial RCR were significantly lower and SL Na+, K(+)-ATPase activity was significantly higher than in age-matched WKYs. However, compared with diltiazem, imidapril was better able to prevent the development of myocardial hypertrophy and interstitial fibrosis, to improve SR Ca(2+)-ATPase activity and the mitochondrial RCR, and to increase SL Na+, K(+)-ATPase activity. These results suggest that ACE inhibition can prevent the development of morphologic changes associated with hypertension-induced left ventricular remodeling, such as myocardial hypertrophy and interstitial fibrosis, and can counteract ongoing dysfunction of organelle metabolism early in the development of hypertension.
    Japanese Heart Journal 08/1997; 38(4):503-14. · 0.40 Impact Factor
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    ABSTRACT: The impairment of mitochondrial in non-infarcted myocardium under cardiogenic shock complicated by acute myocardial infarction was studied. We induced acute myocardial infarction in dogs by ligating the circumflex branch of the left coronary artery (LCX). On basis of left ventricular systolic pressure (LVPs) after 60 minutes, we divided the dogs into two groups: a group in which LVPs fell to below 70% of the pre-LCX ligation level, and a Control group in which LVPs remained more than 90%. The former group was further divided into four subgroups, depending on infusion of dopamine, dobutamine, amrinone or saline after 90 minutes. Mitochondria were prepared and mitochondrial respiratory activity determined. In the Saline group, hemodynamics became reduced to less than 70% of the preligation level after 120 minutes, however, in the Dopamine and Dobutamine groups, hemodynamics became restored to the preligation level. In the Amrinone group, LVPs decreased slightly, while cardiac output, LV Max. dp/dt and myocardial blood flow increased. In the Saline group, mitochondria in the non-infarcted myocardium functioned at a lower level of activity than that of the Control group. However, in the Dopamine, Dobutamine, and Amrinone groups, the mitochondria functioned at a higher level. Electron microscopy revealed mitochondrial damage in the Saline group only. The results indicate that an energy production disorder in the non-infarcted myocardium may have pathogenetic implications in cardiogenic shock associated with acute myocardial infarction, while dopamine, dobutamine, and amrinone improve mitochondrial function, and ultimately improve cardiac function.
    Japanese Heart Journal 08/1997; 38(4):515-29. · 0.40 Impact Factor
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    ABSTRACT: The protective effect and mechanism of action of the angiotensin-converting enzyme inhibitor (ACE-I) captopril was investigated in organelles from ischemic myocardial cells in a canine coronary ligation model. Sarcoplasmic reticulum (SR) and mitochondrial fractions were extracted from ischemic and nonischemic myocardial cells from captopril- and saline-treated (control) hearts. Heart rate, cardiac output, and right ventricular systolic blood pressure were similar in the captopril-treated and control groups. Left ventricular systolic blood pressure (LVPs) decreased gradually to 89% of the baseline value after captopril administration, and to 78% of the baseline value after ligation. Ca-ATPase activity in the SR, the respiratory control ratio (RCR) in the mitochondria, and dinitrophenol (DNP)-stimulated ATPase activity were significantly higher in ischemic myocardium from the captopril-treated group than from the saline-treated (control) group. The SH group content of both organelles was higher in the captopril-treated group. Our results suggest that, in addition to their hemodynamic effects, ACE-I agents containing SH groups protect the myocardium from ischemic damage by preventing enzyme oxidation.
    Japanese Circulation Journal 03/1997; 61(2):161-9.
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    ABSTRACT: Myocellular injury induced by acute ischemia and subsequent reperfusion was studied in 38 dogs, with special reference to sarcolemmal permeability as determined by the vital ionic lanthanum (La3+) probe technique and electron microscopy. The left anterior descending coronary artery (LAD) was occluded in 14 dogs for 10 to 60 min, and the ischemic zone was perfused slowly for 7 min with a La(3+)-containing solution. In 21 dogs, the LAD was released for 10 min after occlusion and was then reperfused for 7 min with arterial blood plus the La(3+)-containing solution. Subsequently, in both groups of animals, the ischemic myocardium was subjected to perfusion fixation in preparation for electron microscopy. In normal cardiac myocytes, La3+ was localized exclusively in the extracellular space. After 10 to 20 min of ischemia, more than 80% of myocytes appeared normal or were damaged only slightly, and the majority continued to exclude La3+. After 10 min of ischemia, deposits of lanthanum were detected in 1 and 6% of myocytes in the absence or presence of reperfusion, respectively. The number of cells with such deposits was markedly increased after 30 min of ischemia (19%), as well as after 20 min of ischemia followed by reperfusion (17%), prior to the development of irreversible myocardial damage. After 60 min of ischemia with or without reperfusion, about 30% of myocytes showed severe injury with particulate deposits of lanthanum throughout the entire cell. These results indicate that sarcolemmal permeability increases during the early stage of myocardial injury due to ischemia or ischemia-reperfusion and contributes to the development of myocardial damage.
    Archiv für Kreislaufforschung 01/1995; 90(3):203-10. · 5.90 Impact Factor
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    ABSTRACT: Sarcolemmal permeability during reperfusion in early myocardial ischemia was investigated in dogs by the vital ionic lanthanum probe (La3+) technique and electron microscopy. The left anterior descending coronary artery was occluded for 10–120 min and released for 10 min, and then a 4 mM solution of La3+ ions was injected, and perfusion fixation was performed. In the normal myocardium, La3+ ions were localized in extracellular spaces. After 20 min of ischemia and subsequent reperfusion, deposits of lanthanum were found in 17% of the myocytes prior to the development of irreversible myocardial damage. The number of cells with such deposits increased in proportion to the increased duration of ischemia. These findings indicate that the disruption of sarcolemmal permeability, during the early stages of myocardial injury due to ischemia and reperfusion, contributes to the development of irreversible myocardial damage.
    Medical Electron Microscopy 01/1994; 27(1):15-25.
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    ABSTRACT: Impairment of sarcolemmal permeability after the initiation of acute ischemic myocardial injury was studied using an ionic lanthanum (La3+) probe in electron microscopy. Acute ischemic myocardium was induced by ligation of the left anterior descending coronary artery in dogs. In normal cardiac myocytes La is localized exclusively in the extracellular space. i.e. on the glycocalyx, in the T-system and in intercalated discs, with normal fine structures. In ischemic myocardial cells, La deposits were found in the cytosolic space in 22% of subendocardial cells with mild to moderate, but non-necrotic, fine structural changes as early as 30 min. The number of myocytes with La deposition increased with advancing ischemic injury, and necrotic fine structural changes were recognized following ischemia for 60 min. These results indicate that deposition of La occurs before the appearance of irreversible morphologic alterations in ischemic myocardial cells, and suggest an increased permeability of the sarcolemma for Ca2+ and the development of degradation of plasma membrane integrity.
    Japanese Circulation Journal 10/1992; 56(9):911-20.