[Volume reduction surgery for giant coronary sinus with valvular heart disease; report of a case].

A 64-year-old male with giant left atrium and giant coronary sinus, who had aortic valve regurgitation, prosthesis valve paravalvular leakage in mitral position and prosthesis valve malfunction in tricuspid valve position, was successfully treated with double valve replacement, paravalvular leakage repair and volume reduction of left atrium and coronary sinus. Giant coronary sinus was about 70 mm in diameter and was thought to be induced by persistent left superior vena cava, high right atrium pressure and prosthesis valve malfunction in tricuspid valve position. Lung volume was so much increased by volume reduction of left atrium and coronary sinus and patient's symptoms were much improved.

[Full-thickness resection of the focus site for adolescent idiopathic ventricular tachycardia].

We present a case of a 14-year-old male with incessant idiopathic ventricular tachycardia for which both pharmacological and catheter ablation treatments failed. Curative surgery was performed on this patient. By intraoperative epicardial isochronous mapping, arrhythmogenic focus was identified in the right ventricular infundibulum between the large conus branch and the proximal right ventricular coronary branch. After cryoablation both from the epi- and endo-cardial sides failed to terminate the arrhythmia, subsequent full-thickness resection of the identified focus was performed. There was no postoperative recurrence of tachyarrhythmia In idiopathic ventricular tachycardia, arrhythmogenic focus is not always situated on the endo- or epicardial side. Full-thickness resection of the focus site might be necessary in such patients as we experienced this time.

Microtubule stabilization in pressure overload cardiac hypertrophy.

Increased microtubule density, for which microtubule stabilization is one potential mechanism, causes contractile dysfunction in cardiac hypertrophy. After microtubule assembly, alpha-tubulin undergoes two, likely sequential, time-dependent posttranslational changes: reversible carboxy-terminal detyrosination (Tyr-tubulin left and right arrow Glu-tubulin) and then irreversible deglutamination (Glu-tubulin --> Delta2-tubulin), such that Glu- and Delta2-tubulin are markers for long-lived, stable microtubules. Therefore, we generated antibodies for Tyr-, Glu-, and Delta2-tubulin and used them for staining of right and left ventricular cardiocytes from control cats and cats with right ventricular hypertrophy. Tyr- tubulin microtubule staining was equal in right and left ventricular cardiocytes of control cats, but Glu-tubulin and Delta2-tubulin staining were insignificant, i.e., the microtubules were labile. However, Glu- and Delta2-tubulin were conspicuous in microtubules of right ventricular cardiocytes from pressure overloaded cats, i.e., the microtubules were stable. This finding was confirmed in terms of increased microtubule drug and cold stability in the hypertrophied cells. In further studies, we found an increase in a microtubule binding protein, microtubule-associated protein 4, on both mRNA and protein levels in pressure-hypertrophied myocardium. Thus, microtubule stabilization, likely facilitated by binding of a microtubule-associated protein, may be a mechanism for the increased microtubule density characteristic of pressure overload cardiac hypertrophy.

Mercury in a Greenland ice sheet: evidence of recent input by man.

The increased mercury content in a Greenland ice sheet over the last several decades suggests the dissemination of this element about the earth's atmosphere through the activities of man. The mercury content in the atmosphere appears to result primarily from the degassing of the earth's crust. Increased flux may come about as a result of the enhancement of this degassing process through the actions of man.

Selenium and sulfur in a greenland ice sheet: relation to fossil fuel combustion.

In the combustion of fossil fuels, selenium is mobilized in the atmosphere to a much lesser extent than is sulfur. This difference is ascribed to the chemical behavior of their respective tetravalent oxides. The ratio of selenium to sulfur in glacial ice is characteristic of terrestrial matter, and these elements may find their way to ice sheets by the formation of volatile compounds in biochemical processes.

Lead pollution: records in Southern California coastal sediments.

The present anthropogenic lead fluxes into sediments from the Santa Monica, San Pedro, and Santa Barbara basins of Southern California are, respectively, 0.9, 1.7, and 2.1 micrograms of lead per square centimeter of sea bottom per year; the natural (prepollution) rates for these three basins were, respectively, 0.24, 0.26, and 1.0 microgram of lead per square centimeter per year. Studies of isotopic composition indicate that lead pollutants in coastal sediments are derived mainly from the combustion of lead additives in gasoline.

[Reoperation for postoperative pseudoaneurysm after repair for acute aortic dissection associated with disseminated intravascular coagulation and chronic renal failure].

We report a very high risk case of reoperation for pseudoaneurysm after ascending aortic replacement for acute aortic dissection in a 78-year-old man with chronic renal failure and disseminated intravascular coagulation (DIC). Computed tomography 5 years after the 1st operation showed huge pseudoaneurysm originated from the distal anastomosis and the angiogram showed moderate aortic regurgitation. Hemodialysis and congestive heart failure associated with DIC complicated his general condition. Preoperative DIC score was 7 with D-dimer of 39.8 microg/ml. The patient underwent reoperation through night anterior thoracotomy. At 20 degrees C of urinary bladder temperature, we started re-median sternotomy and ablated the adhesion. When the pseudoaneurysm ruptured, we started hypothermic circulatory arrest with selective cerebral perfusion immediately. And Bentall operation and hemi-arch replacement were performed. Postoperative recovery required long period and he was transferred to another hospital at 3 months after the surgery. Postoperative data showed reduction of DIC score to 3.

Soluble interleukin-1 receptor type II levels in gingival crevicular fluid in aggressive and chronic periodontitis.

BACKGROUND: Interleukin (IL)-1 is closely related to the initiation and progression of periodontal disease. IL-1 levels in the gingival crevicular fluid (GCF) of subjects with periodontitis are higher than those in periodontally healthy controls, and the levels of IL-1 correlate with disease severity. However, soluble IL-1 receptor type II (sIL-1RII), which acts as a decoy receptor for IL-1s, has not been investigated in detail in periodontal disease. The purpose of this study was to measure sIL-1RII levels in the GCF of subjects with chronic or aggressive periodontitis; the correlation between the sIL-1RII levels in GCF and clinical parameters also was examined. METHODS: IL-1beta and sIL-1RII were measured in 64 GCF samples collected from 47 subjects with chronic periodontitis (CP) and 17 subjects with aggressive periodontitis (AgP). The clinical characteristics of each site were recorded at the time of GCF sampling. IL-1beta and sIL-1RII were measured by specific non-cross-reactive enzyme-linked immunosorbent assay. RESULTS: The disease severity was comparable in CP and AgP. IL-1beta was detected in 98% of CP GCF samples and 88% of AgP GCF samples. sIL-1RII was detected in 55% of CP GCF samples and 35% of AgP GCF samples. However, the concentrations of IL-beta and sIL-1RII detected in GCF from subjects with CP or AgP were similar. CONCLUSION: sIL-1RII was detected more often in CP GCF than in AgP GCF, and there was no correlation between GCF sIL-1RII concentration and clinical parameters.

[Mitral valve plasty for a 91-year-old woman with mitral valve prolapse].

We reported a successful mitral valve plasty for a 91-year-old woman with mitral valve prolapse. She has lived healthfully and independently without a big problem. She was admitted to another hospital for acute heart failure. Echo cardiography revealed prolapse of posterior mitral valve leaflet and severe mitral regurgitation. Drug therapy was not enough to control her complaint In spite of her age, the patient was able to support herself, and she and her family desired to have a surgical treatment. Therefore she referred to our hospital and underwent mitral valve plasty. Post operative course was almost uneventful. She discharged the hospital 3 months after the operation. If a selective criteria for individual patients is applied, the nonagenarian can safety undergo cardiac surgery.

[Valve-in-valve replacement of primary tissue valve failure of bovine pericardial valve minor].

A 73-year-old woman who underwent mitral valve replacement with a 31 mm Carpentier Edwards Pericardial Xenograft 19 years ago. She revealed sudden onset of a grade IV/VI a seagull like diastolic murmur at the apex, and severe hematuria. Echocardiography demonstrated severe mitral regurgitation. These findings were consistent with acute primary tissue valve failure. Therefore we performed emergency reoperation. At operation, valve leaflet was torn at the commissural stitch, and bioprosthesis strut was buried in the left posterior ventricular wall. The mitral prosthetic valve replaced with a 25 mm CarboMedics OptiForm using a technique of valve-in-valve replacement. This procedure would be one option for replacement of bioprosthetic mitral valve.

BK Channels in the Vascular System.

Autoregulation of blood flow is essential for the preservation of organ function to ensure continuous supply of oxygen and essential nutrients and removal of metabolic waste. This is achieved by controlling the diameter of muscular arteries and arterioles that exhibit a myogenic response to changes in arterial blood pressure, nerve activity and tissue metabolism. Large-conductance voltage and Ca(2+)-dependent K(+) channels (BK channels), expressed exclusively in smooth muscle cells (SMCs) in the vascular wall of healthy arteries, play a critical role in regulating the myogenic response. Activation of BK channels by intracellular, local, and transient ryanodine receptor-mediated "Ca(2+) sparks," provides a hyperpolarizing influence on the SMC membrane potential thereby decreasing the activity of voltage-dependent Ca(2+) channels and limiting Ca(2+) influx to promote SMC relaxation and vasodilation. The BK channel α subunit, a large tetrameric protein with each monomer consisting of seven-transmembrane domains, a long intracellular C-terminal tail and an extracellular N-terminus, associates with the ß1 and γ subunits in vascular SMCs. The BK channel is regulated by factors originating within the SMC or from the endothelium, perivascular nerves and circulating blood, that significantly alter channel gating properties, Ca(2+) sensitivity and expression of the α and/or ß1 subunit. The BK channel thus serves as a central receiving dock that relays the effects of the changes in several such concomitant autocrine and paracrine factors and influences cardiovascular health. This chapter describes the primary mechanism of regulation of myogenic response by BK channels and the alterations to this mechanism wrought by different vasoactive mediators.

The molecular heterogeneity of the smg-21/Krev-1/rap1 proteins, a GTP-binding protein having the same effector domain as ras p21s, in bovine aortic smooth muscle membranes.

smg p21 is a member of the ras p21/ras p21-like small GTP-binding protein (G protein) superfamily, having the same putative effector domain as ras p21s. In the preceding report, we showed that smg p21 was a major G protein in bovine aortic smooth muscle membranes. Recently, two different smg p21 cDNA clones, designated smg-21A and -B, were isolated from a bovine brain cDNA library. In the present studies, we resolved the bovine aortic smg p21 fraction into two distinct G protein fractions on hydroxyapatite column chromatography and purified them separately to near homogeneity (22K G1 and -2). Both 22K G1 and -2 were specifically recognized by an anti-smg p21 polyclonal antibody. 22K G1 and -2 were identified as smg p21B and -A, respectively, by peptide map and amino acid sequence analyses. Purified smg p21A and -B showed GDP/GTP-binding and GTPase activities similar to each other. The GTPase activities of smg p21A and -B were equally stimulated by smg p21 GTPase activating protein 1 and -2. Moreover, both smg p21A and -B were phosphorylated by cyclic AMP-dependent protein kinase with a stoichiometry of one phosphate/molecule of protein. These results indicate that smg p21A and -B coexist in bovine aortic smooth muscle membranes and suggest that smg p21A and -B may serve as intermediates for cyclic AMP actions.

Bradycardia and the role of beta-blockade in the amelioration of left ventricular dysfunction.

BACKGROUND: It is clear that beta-blockers are effective for treatment of congestive heart failure, but their mechanism of action remains controversial. Hypothesized mechanisms include normalization of beta-receptor function and myocardial protection from the effects of catecholamines, possibly by the institution of bradycardia. We hypothesized that beta-blockade-induced bradycardia was an important mechanism by which these agents were effective for correction of LV dysfunction. METHODS AND RESULTS: In 2 groups of dogs with mitral regurgitation and LV dysfunction, beta-blockers were instituted. In 1 group that received beta-blockers and pacing (group beta+P), a pacemaker prevented the natural bradycardia that beta-blockers cause. In both groups, substantial LV dysfunction developed. Before beta-blockade, the end-systolic stiffness constant decreased from 3. 5+/-0.1 to 2.7+/-0.2 (P<0.01) at 3 months in group beta+P. A similar reduction occurred in the group that eventually received only beta-blockers (group betaB). In group betaB, end-systolic stiffness improved after 3 months of beta-blockade from 2.9+/-0.2 to 3.5+/-0.4 and was not different from baseline. However, in group beta+P, end-systolic stiffness failed to improve (2.7+/-0.2) after 3 months of mitral regurgitation, and was 2.9+/-0.2 at the end of the studies. The contractile function of cardiocytes isolated from the ventricles at the end of the studies confirmed these in vivo estimates of contractility. CONCLUSIONS: We conclude that institution of bradycardia is a major mechanism by which beta-blockers are effective for restoration of contractile function in a model of LV dysfunction.

Microtubule depolymerization normalizes in vivo myocardial contractile function in dogs with pressure-overload left ventricular hypertrophy.

BACKGROUND: Because initially compensatory myocardial hypertrophy in response to pressure overloading may eventually decompensate to myocardial failure, mechanisms responsible for this transition have long been sought. One such mechanism established in vitro is densification of the cellular microtubule network, which imposes a viscous load that inhibits cardiocyte contraction. METHODS AND RESULTS: In the present study, we extended this in vitro finding to the in vivo level and tested the hypothesis that this cytoskeletal abnormality is important in the in vivo contractile dysfunction that occurs in experimental aortic stenosis in the adult dog. In 8 dogs in which gradual stenosis of the ascending aorta had caused severe left ventricular (LV) pressure overloading (gradient, 152+/-16 mm Hg) with contractile dysfunction, LV function was measured at baseline and 1 hour after the intravenous administration of colchicine. Cardiocytes obtained by biopsy before and after in vivo colchicine administration were examined in tandem. Microtubule depolymerization restored LV contractile function both in vivo and in vitro. CONCLUSIONS: These and additional corroborative data show that increased cardiocyte microtubule network density is an important mechanism for the ventricular contractile dysfunction that develops in large mammals with adult-onset pressure-overload-induced cardiac hypertrophy.

Impaired force-frequency relations in patients with hypertensive left ventricular hypertrophy. A possible physiological marker of the transition from physiological to pathological hypertrophy.

BACKGROUND: The extent to which force-frequency and relaxation-frequency relations (FFR and RFR, respectively) and exercise-induced adrenergic stimulation affect myocardial inotropic and lusitropic reserves has not been established in patients with left ventricular (LV) hypertrophy (LVH). METHODS AND RESULTS: We calculated the maximum first derivative of LV pressure (LV dP/dtmax) and the LV pressure half-time (T1/2) during pacing, exercise, and isoproterenol infusion in 17 patients with hypertensive LVH and 9 control subjects to investigate the influence of increases in heart rate (HR) and adrenergic stimulation on inotropic and lusitropic reserves. Group A consisted of 10 LVH patients who showed a progressive increase in the HR-LV dP/dtmax relation. Group B consisted of 7 LVH patients in whom the HR-dP/dtmax relation at physiological pacing rates was biphasic. The LV mass index was larger and the LV ejection fraction was smaller in group B than in group A (244+/-72 g/m2 versus 172+/-22 g/m2 and 55+/-18% versus 72+/-6%, respectively; both P<0.05). The increase in LV dP/dtmax was greater during exercise than pacing alone for similar increases in HR in all groups (P<0.05) (group A, 111+/-22% versus 25+/-14%; group B, 105+/-35% versus 14+/-10%; control, 111+/-24% versus 25+/-12%). T1/2 was shorter (P<0.05) during exercise than with pacing alone in all groups (group A, 41+/-6% versus 11+/-3%; group B, 38+/-9% versus 14+/-4%; control, 44+/-6% versus 12+/-5%). Isoproterenol infusion caused similar increases in LV dP/dtmax and similar decreases in T1/2 in all groups. CONCLUSIONS: The FFR was biphasic in patients with severe LVH irrespective of LV function but was preserved in patients with less severe LVH and control subjects. Importantly, the RFR and adrenergic control of both inotropic and lusitropic reserves were well preserved in all LVH patients. A biphasic FFR at physiological pacing rates may be one of the earliest markers of the transition from physiological adaptation to the pathological process in LVH patients.

HLA antigens in Japanese patients with diabetes mellitus.

Lymphocytes of 84 Japanese patients with diabetes mellitus and 150 normal controls were tested for HLA antigens by the microcytotoxicity test. HLA-B12 was found in 37.5 per cent of 32 patients with juvenile-onset diabetes mellitus, 13.5 per cent of 52 patients with late-onset diabetes, and 9.3 per cent of 150 normal controls. In the insulin-dependent juvenile form, HLA-B12 was associated with the disease more frequently and at a significant level (p less than 0.0005). In Japanese patients with juvenile-onset insulin-dependent diabetes mellitus the association is with HLA-B12, not with HLA-B8 and BW15, as in Caucasian patients. There was no significant increase of HLA-B12 in patients with insulin-indpendent diabetes mellitus.

Effects of a new second generation calcium channel blocker, nilvadipine (FR34235), on exercise-induced hemodynamic changes in stable angina pectoris.

The mechanism of the antianginal actions of nilvadipine was investigated in 11 patients with effort angina pectoris. Hemodynamic data were obtained by angina-limited supine multistage bicycle ergometer exercise testing before and after a single 6 mg dose of nilvadipine. Compared with chest pain during control exercise testing, pain at peak exercise disappeared or abated and the ST segment at peak exercise also showed less significant depression after administration of nilvadipine. At rest and at peak exercise, mean blood pressure, pulmonary artery wedge pressure and systemic vascular resistance decreased significantly, whereas heart rate and cardiac index increased significantly after nilvadipine. Rate-pressure product and stroke volume index did not change significantly. Coronary sinus flow at peak exercise increased significantly and total coronary vascular resistance at rest and at peak exercise decreased significantly after nilvadipine. The plasma concentrations of nilvadipine 1.5 hours after administration ranged from 1.15 to 8.23 ng/ml. These data suggest that the principal factors in the antianginal actions of nilvadipine are an increase in myocardial oxygen supply due to increased coronary blood flow and a reduction in myocardial oxygen demand mainly by a decrease in afterload and additionally by a decrease in preload.

Role of microtubules in the contractile dysfunction of hypertrophied myocardium.

OBJECTIVES: We sought to determine whether the ameliorative effects of microtubule depolymerization on cellular contractile dysfunction in pressure overload cardiac hypertrophy apply at the tissue level. BACKGROUND: A selective and persistent increase in microtubule density causes decreased contractile function of cardiocytes from cats with hypertrophy produced by chronic right ventricular (RV) pressure overloading. Microtubule depolymerization by colchicine normalizes contractility in these isolated cardiocytes. However, whether these changes in cellular function might contribute to changes in function at the more highly integrated and complex cardiac tissue level was unknown. METHODS: Accordingly, RV papillary muscles were isolated from 25 cats with RV pressure overload hypertrophy induced by pulmonary artery banding (PAB) for 4 weeks and 25 control cats. Contractile state was measured using physiologically sequenced contractions before and 90 min after treatment with 10(-5) mol/liter colchicine. RESULTS: The PAB significantly increased RV systolic pressure and the RV weight/body weight ratio in PAB; it significantly decreased developed tension from 59+/-3 mN/mm2 in control to 25+/-4 mN/mm2 in PAB, shortening extent from 0.21+/-0.01 muscle lengths (ML) in control to 0.12+/-0.01 ML in PAB, and shortening rate from 1.12+/-0.07 ML/s in control to 0.55+/-0.03 ML/s in PAB. Indirect immunofluorescence confocal microscopy showed that PAB muscles had a selective increase in microtubule density and that colchicine caused complete microtubule depolymerization in both control and PAB papillary muscles. Microtubule depolymerization normalized myocardial contractility in papillary muscles of PAB cats but did not alter contractility in control muscles. CONCLUSIONS: Excess microtubule density, therefore, is equally important to both cellular and to myocardial contractile dysfunction caused by chronic, severe pressure-overload cardiac hypertrophy.

Aging effect on plasma metabolites and hormones concentrations in riding horses.

Age effects on plasma metabolites, hormone concentrations, and enzyme activities related to energy metabolism were investigated in 20 riding horses. Animals were divided into two groups: Young (3-8 years) and aged (11-18 years). They were clinically healthy, and not obese. Plasma adiponectin (ADN) concentrations in aged horses were significantly lower than those in young horses (mean±SE, 6.5±1.3 µg mL(-1) vs, 10.9±1.7 µg mL(-1), Mann-Whitney U test, respectively; P=0.0233). Plasma non-esterified fatty acid levels and Insulin and malondialdehyde concentrations in aged group tended to increase compared to those in young group although there were not significant differences statistically. In aged group, malate dehydrogenase/lactate dehydrogenase (M/L) ratio, which is considered an energy metabolic indicator, did not change significantly compared to that in young group. Present data suggest that aging may negatively affect nutrition metabolism, but not induce remarkable changes in M/L ratio in riding horses.

Specific inhibitors of vacuolar H(+)-ATPase trigger apoptotic cell death of osteoclasts.

Osteoclasts are multinucleated bone-resorbing cells that play a critical role in bone remodeling. Specific inhibitors of vacuolar H(+)-ATPase (V-ATPase), concanamycin A and bafilomycin A1, abolish bone resorption by osteoclasts. In this study, we examined whether these V-ATPase inhibitors trigger apoptotic cell death in osteoclasts, using murine osteoclast-like multinucleated cells (OCLs) formed in vitro. Acridine orange staining revealed that the treatment of OCLs with concanamycin A resulted in chromatin condensation and alterations in nuclear morphology within a few hours. The TdT-mediated dUTP-nick-end labeling (TUNEL) reaction confirmed the apoptotic features of OCLs treated with concanamycin A. The accelerated apoptotic cell death induced by concanamycin A occurred in OCLs treated with interleukin-1 alpha or macrophage colony-stimulating factor as well, which are known to elongate the survival time of osteoclasts. In contrast, these inhibitors did not induce cell death of osteoblastic cells isolated from mouse calvaria. These results suggest that functional impairment of V-ATPase triggers apoptotic cell death in osteoclasts.