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Biomedical subjects

Itsuo Kodama

Publications and source records attributed to Itsuo Kodama.

At least 37 records · Page 2Linked to original sources
PubMed2005

Multicenter survey on the validity of the CD-ROM guideline for antiarrhythmic drug therapy produced by the Japanese Circulation Society and the Japanese Society on Electrocardiology: preliminary report of the survey of the Japanese guideline for Arrhythmia Management By Individual Therapy (J-GAMBIT).

BACKGROUND: A multicenter investigational survey (Japanese Guideline for Arrhythmia Management By Individual Therapy) was conducted to evaluate the validity of using CD-ROM guidelines vs physician choice for the selection of antiarrhythmic drugs. METHODS AND RESULTS: Patients with paroxysmal atrial fibrillation (PAF, n=274) or premature ventricular contractions (PVC, n=216) were enrolled. The rate of concordance for drug selection between the treating physician and the CD-ROM was 216 of 274 patients (78.8%) with PAF. Of these, 168 (61.3%) were concordant for first-line agents and the remaining 48 (17.5%) were concordant for second-line agents. The concordance for the treatment of PVC was 154/216 cases (71.3%). Of these, 106 (49.1%) were concordant for first-line agents and the remaining 48 (22.2%) were concordant for second-line agents. Nonconcordance for PAF therapy was more likely to occur for patients with underlying heart disease (p<0.05), depressed cardiac function (p<0.001), and with more frequent ECG abnormalities and renal dysfunction. These differences were not seen in patients with PVC. CONCLUSION: The CD-ROM guidelines appear to be valid in the selection of antiarrhythmic drugs for both PAF and PVC, but their usefulness is influenced by the patient's clinical characteristics.

Aged↗
PubMed2005

Subtype switching of L-Type Ca 2+ channel from Cav1.3 to Cav1.2 in embryonic murine ventricle.

BACKGROUND: Embryonic hearts exhibit spontaneous electrical activity, which depends on Ca2+ influx through L-type Ca2+ channels. In this study the expression of the L-type Ca2+ channel alpha1 subunit gene in the developing mouse heart was investigated. METHODS AND RESULTS: Mouse cardiac ventricles 9.5 days post coitum (dpc), 18 dpc and adult were used. At 9.5 dpc the level of Cav1.3 mRNA was higher than that of Cav1.2 mRNA. With development, Cav1.2 mRNA increased and Cav1.3 mRNA decreased. Analysis of Cav1.3 splicing variants showed that Cav1.3(1b) mRNA was expressed at a higher density than Cav1.3(1a) mRNA. Cav1.3 protein was detected only at 9.5 dpc, whereas Cav1.2 protein was expressed from 9.5 dpc and its expression increased with development. L-type Ca2+ currents were prominent at 9.5 dpc. The Ca2+ current amplitude at 9.5 dpc was comparable to that at 18 dpc, and was larger in adults than at the embryonic stage. L-type Ca2+ current at 9.5 dpc was activated and/or inactivated at more negative membrane potentials than at 18 dpc or adult. L-type Ca2+ channels at 9.5 dpc were less sensitive to inhibition by nisoldipine than at adult. CONCLUSIONS: The Cav1.3 channel is functionally expressed in early embryonic mouse ventricular myocytes and potentially underlies ventricular automaticity.

Animals↗
PubMed2005

Decreased vagal control over heart rate in rats with right-sided congestive heart failure: downregulation of neuronal nitric oxide synthase.

BACKGROUND: Parasympathetic drive is attenuated in heart failure, and resulting autonomic imbalance may increase the risk of sudden cardiac death. The anatomic site(s) and molecular mechanisms underlying this parasympathetic withdrawal are unknown. METHODS AND RESULTS: We examined the effects of pre- and post-ganglionic vagal nerve stimulation (VS) and acetylcholine (ACh) application on the heart rate of rats with right-sided congestive heart failure (CHF) induced by monocrotaline. Heart rate reduction in response to pre-ganglionic VS in CHF rats in vivo was significantly less than in controls. The suppression of spontaneous beating of isolated right atria including the whole sinoatrial (SA) node in response to post-ganglionic VS was significantly attenuated in CHF rats as well. In contrast, ACh application to the right atria resulted in a significantly larger suppression of spontaneous beating in CHF rats than controls. Proteins of neuronal nitric oxide synthase (nNOS) in the right atria were significantly decreased, whereas muscarinic (M2) receptor was significantly increased in CHF rats compared with controls. CONCLUSIONS: Both pre-and post-ganglionic vagal nerve functions are diminished in CHF rats, whereas M2 receptor-mediated regulation of the SA node is upregulated. Downregulation of nNOS may be involved in this parasympathetic withdrawal.

Acetylcholine↗
PubMed2005

Combined effects of nifekalant and lidocaine on the spiral-type re-entry in a perfused 2-dimensional layer of rabbit ventricular myocardium.

BACKGROUND: Spiral re-entry plays the principal role in the genesis of ventricular tachycardia and ventricular fibrillation (VT/VF). The specific I(Kr) blocker, nifekakant (NIF) has, often in combination with lidocaine (LID), recently been used in Japan to prevent recurrent VT/VF, but the combined effects of these drugs on spiral re-entry had never been investigated. METHODS AND RESULTS: A ventricular epicardial sheet was obtained from 13 Langendorff-perfused rabbit hearts by means of a cryoprocedure, and epicardial excitations were analyzed with a high-resolution optical mapping system. Nifekakant (0.5 micromol/L) caused significant prolongation of action potential duration (APD) and LID (3 micromol/L) attenuated the APD prolongation without affecting the conduction velocity. VT were induced in 6 hearts by cross-field stimulation, and single- or double-loop spirals circulating around variable functional block lines were visualized during the VT. Nifekakant reduced VT cycle length and caused early termination in association with destabilization of the spiral dynamics (prolongation of functional block line, frequent local conduction block, and extensive meandering). These modifications of spiral-type re-entrant VT by NIF were prevented by addition of LID. CONCLUSIONS: The effects of NIF on the spiral excitations are reversed by LID. This interaction should be taken into account when these drugs are used in combination to treat VT/VF.

Animals↗
PubMed2004

Rapid electrical stimulation of contraction modulates gap junction protein in neonatal rat cultured cardiomyocytes: involvement of mitogen-activated protein kinases and effects of angiotensin II-receptor antagonist.

OBJECTIVES: The aim of this study was to investigate the effects of rapid electrical stimulation (RES) of contraction on the expression of connexin (Cx)43 gap junction in neonatal rat cultured ventricular myocytes and the consequent changes of conduction properties. BACKGROUND: The expression and distribution of gap junctions in cardiac muscle can be changed readily under a variety of pathological conditions because of dynamic turnover of Cxs. The effects of RES of contraction on gap junction remodeling are not well understood. METHODS: Neonatal rat ventricular myocytes cultured for five days were subjected to RES (field stimulation) at 3.0 Hz for up to 120 min. RESULTS: Rapid electrical stimulation resulted in a significant upregulation of Cx43 (by approximately 1.5-fold in protein and by approximately 1.9-fold in messenger ribonucleic acid at 60 min). Immunoreactive signal of Cx43 was also increased. Angiotensin II (AngII) content was increased significantly by RES >15 min. Phosphorylated forms of extracellular signal-regulated protein kinase (ERK), c-Jun NH(2)-terminal kinases, and p38 mitogen-activated protein kinases (MAPKs) were all increased dramatically by RES with peaks at 5 - 60 min. Propagation of excitation was visualized by extracellular potential mapping by using a multiple electrode array system. Conduction velocity was increased significantly by RES for 60 to 90 min (25% - 27% increase). Treatment of myocytes with losartan (100 nmol/l) prevented most of these effects of RES; RES-induced upregulation of Cx43 was also prevented by specific inhibitors for ERK and p38 MAPKs. CONCLUSIONS: A short-term RES causes upregulation of Cx43 in cardiomyocytes and a concomitant increase of conduction velocity, mainly through an autocrine action of AngII to activate ERK and p38 MAPKs.

Angiotensin Receptor Antagonists↗
PubMed2004

Sinoatrial node dysfunction and early unexpected death of mice with a defect of klotho gene expression.

BACKGROUND: Homozygous mutant mice with a defect of klotho gene expression (kl/kl) show multiple age-related disorders and premature death from unknown causes. METHODS AND RESULTS: The kl/kl mice subjected to 20-hour restraint stress showed a high rate (20/30) of sudden death, which was associated with sinoatrial node dysfunction (conduction block or arrest). Heart rate and plasma norepinephrine of kl/kl mice, unlike those of wild-type (WT) mice, failed to increase during the stress. Intrinsic heart rate after pharmacological blockade of autonomic nerves in kl/kl mice was significantly lower than that in WT mice (380+/-33 versus 470+/-44 bpm; n=7). The sinus node recovery time after an overdrive pacing (600 bpm, 30 seconds) in kl/kl mice was significantly longer than in WT mice (392+/-37 versus 233+/-24 ms; n=6). In isolated sinoatrial node preparations, the positive chronotropic effect of isoproterenol was significantly less, whereas the negative chronotropic effect of acetylcholine was significantly greater in kl/kl than in WT mice. There was no degenerative structural change in the sinoatrial node of kl/kl mice. The precise localization of klotho was analyzed in newly prepared klotho-null mice with a reporter gene system (kl(-geo)). Homozygous kl(-geo) mice showed characteristic age-associated phenotypes that were almost identical to those of kl/kl mice. In the kl(-geo) mice, klotho expression was recognized exclusively in the sinoatrial node region in the heart in addition to parathyroid, kidney, and choroid plexus. CONCLUSIONS: In the heart, klotho is expressed solely at the sinoatrial node. klotho gene expression is essential for the sinoatrial node to function as a dependable pacemaker under conditions of stress.

Aging, Premature↗
PubMed2004

Cav3.2 subunit underlies the functional T-type Ca2+ channel in murine hearts during the embryonic period.

T-type Ca2+ channels are implicated in cardiac automaticity, cell growth, and cardiovascular remodeling. Two voltage-gated Ca2+ subtypes (Ca(v)3.1 and Ca(v)3.2) have been cloned for the pore-forming alpha(1)-subunit of the T-type Ca2+ channel in cardiac muscle, but their differential roles remain to be clarified. The aim of this study was to elucidate the relative contribution of the two subtypes in the normal development of mouse hearts. A whole cell patch clamp was used to record ionic currents from ventricular myocytes isolated from mice of early (E9.5) and late embryonic days (E18) and from adult 10-wk-old mice. Large T-type Ca2+ current (I(Ca,T)) was observed at both E9.5 and E18, displaying similar voltage-dependence and kinetics of activation and inactivation. The current was inhibited by Ni2+ at relatively low concentrations (IC(50) 26-31 microM). I(Ca,T) was undetectable in adult myocytes. Quantitative PCR analysis revealed that Ca(v)3.2 mRNA is the predominant subtype encoding T-type Ca2+ channels at both E9.5 and E18. Ca(v)3.1 mRNA increased from E9.5 to E18, but remained low compared with Ca(v)3.2 mRNA during the whole embryonic period. In the adulthood, in contrast, Ca(v)3.1 mRNA is greater than Ca(v)3.2 mRNA. These results indicate that Ca(v)3.2 underlies the functional T-type Ca2+ channels in the embryonic murine heart, and there is a subtype switching of transcripts from Ca(v)3.2 to Ca(v)3.1 in the perinatal period.

Animals↗
PubMed2004

ML-9, a myosin light chain kinase inhibitor, reduces intracellular Ca2+ concentration in guinea pig trachealis.

We investigated the effects of ML-9 [1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine], a myosin light chain kinase (MLCK) inhibitor, on intracellular Ca2+ concentration ([Ca2+]i), contraction induced by high K+ and an agonist, and capacitative Ca2+ entry in fura-2-loaded guinea pig tracheal smooth muscle. ML-9 inhibited both the increase in [Ca2+]i and the contraction induced by 60 mM K+, 1 microM methacholine or 1 microM thapsigargin, an inhibitor of the sarcoplasmic reticulum Ca2+-ATPase. However, another MLCK inhibitor, wortmannin (3 microM), inhibited the contraction elicited by these stimuli without affecting [Ca2+]i. Under the condition that the thapsigargin-induced contraction was fully suppressed by 3 microM wortmannin, 30 microM ML-9 caused a further decrease in [Ca2+]i. The inhibitory effects of ML-9 on [Ca2+]i and the contraction elicited by methacholine were similar to those of SKF-96365 (1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole hydrochloride), a Ca2+ channel blocker. These results indicate that ML-9 acts as a potent inhibitor of Ca2+-permeable channels independently of MLCK inhibition in tracheal smooth muscle.

Androstadienes↗
PubMed2004

Risk stratification and survival in post myocardial infarction patients: a large prospective and multicenter study in Japan.

BACKGROUND: Recent clinical trials suggest that the mortality in high-risk patients with ischemic heart disease can be significantly reduced with the use of implantable cardioverter-defibrillator (ICD). Given the high cost and invasiveness of the procedure, it is important to apply it to the patients after myocardial infarction (MI) highly susceptible to sudden arrhythmic death. OBJECTIVE: The purpose of this study was to assess clinical predictors of mortality in post-MI patients in Japan. METHODS AND RESULTS: In 495 consecutive MI survivors, 350 (71%) received acute-reperfusion therapy, whereas 145 (29%) did not. Nonsustained ventricular tachycardia (NSVT) was present in 136 patients (28%) in 24-h ambulatory ECGs at 7+/-6 in-hospital days. Left ventricular dysfunction (LVEF< or =35%) was present in 20/347 patients (5.7%) at 13+/-8 days. Forty-eight patients (9.7%) died during the follow-up period (48+/-13 months); 23 from cardiac and 25 from noncardiac causes. Kaplan-Meier survival analyses showed that mortality rates were higher among patients who were > or =70 years old (log-rank test, P<0.0001); had heart failure at admission (Killip scale> or =2, P=0.001); did not receive acute-reperfusion (P=0.004); and had left ventricular dysfunction with LVEF< or =35% (P=0.02). The presence of NSVT was a significant predictor of death (P=0.036) only in the patients who did not receive acute-reperfusion. Multivariate Cox regression analysis revealed that an independent predictor of total mortality was an age> or =70 (odds ratio, 1.06; 95% confidence interval, 1.01-1.11; P<0.00001). CONCLUSIONS: High-risk patients after acute MI can be identified on the basis of age, ventricular dysfunction, heart failure and acute-reperfusion therapy. The presence of NSVT before discharge has a prognostic value only in the patients without acute-reperfusion.

Aged↗
PubMed2004

Sotalol reverses remodeled action potential in patients with chronic atrial fibrillation but does not prevent arrhythmia recurrence.

INTRODUCTION: Recurrence of atrial fibrillation (AF) may be related to AF-induced electrical remodeling characterized by shortening of the atrial action potential duration (APD) and loss of its rate adaptation. We investigated the effects of pretreatment with oral d,l-sotalol on rate-dependent changes in atrial monophasic action potential (MAP) duration after cardioversion of chronic AF with reference to the efficacy in preventing the arrhythmia recurrence. METHODS AND RESULTS: MAPs were recorded from the right atrium at six pacing cycle lengths (CLs) from 300 to 750 ms in 19 chronic AF patients after electrical cardioversion; 9 had been pretreated with oral d,l-sotalol (196 +/- 42 mg/day) for 7 days and 10 were untreated. MAP duration at 90% repolarization (MAPD90) in 11 control patients increased progressively with increases in CLs from 209 +/- 19 ms at CL = 300 ms to 264 +/- 28 ms at CL = 750 ms. In AF patients without sotalol, the CL-MAPD relation was shifted downward and flattened at longer CLs; MAPD90 values were 206 +/- 11 ms and 227 +/- 16 ms at CLs of 300 and 750 ms, respectively. MAPD90 values at CLs > or =500 ms in AF were significantly shorter than controls. In AF patients with sotalol, the normal CL-MAPD relation was preserved; MAPD90 increased from 226 +/- 19 ms to 282 +/- 46 ms in the CL range. AF recurred within 2 weeks after cardioversion in 14 of 24 patients pretreated with d,l-sotalol (216 +/- 51 mg/day) despite of continuation of sotalol treatment. CONCLUSION: Sotalol reverses AF-induced decrease in MAPD adaptation to rate in the atria of chronic AF patients, but this effect does not lead to prevention of AF recurrence.

Action Potentials↗
PubMed2004

Two components of delayed rectifier K+ current in heart: molecular basis, functional diversity, and contribution to repolarization.

Delayed rectifier K+ current (IK) is the major outward current responsible for ventricular repolarization. Two components of IK (IKr and IKs) have been identified in many mammalian species including humans. IKr plays a pivotal role in normal ventricular repolarization. A prolongation of action potential duration (APD) under a variety of conditions would favor the activation of IKs so that to prevent excessive repolarization delay causing early afterdepolarization. The pore-forming a subunits of IKr and IKs are composed of HERG (KCNH2) and KvLQT1 (KCNQ1), respectively. KvLQT1 is associated with a function-altering beta subunit, minK to form IKs. HERG may be associated with mink (KCNE1) and/or minK-related protein (MiRP1) to form IKr, but the issue remains to be established. IKs is enhanced, whereas IKr is usually attenuated by beta-adrenergic stimulation via cyclic adenosine 3',5'-monophosphate (cAMP)/protein kinase A-dependent pathways. There exist regional differences in the density of IKr and IKs transmurally (endo-epicardial) and along the apico-basal axis, contributing to the spatial heterogeneity of ventricular repolarization. A decrease of IKr or IKs by mutations in either HERG, KvLQT1, or KCNE family results in inherited long QT syndrome (LQTS) with high risk for Torsades de pointes (TdP)-type polymorphic ventricular tachycardia and ventricular fibrillation. As to the pharmacological treatment and prevention of ventricular tachyarrhythmias, selectively block of IKs is expected to be more beneficial than selectively block of IKr in terms of homogeneous prolongation of refractoriness at high heart rates especially in diseased hearts including myocardial ischemia.

Action Potentials↗
PubMed2003

Mechanosensitivity of GIRK channels is mediated by protein kinase C-dependent channel-phosphatidylinositol 4,5-bisphosphate interaction.

Gprotein-activated inwardly rectifying K+ channel (GIRK or Kir3) currents are inhibited by mechanical stretch of the cell membrane, but the underlying mechanisms are not understood. In Xenopus oocytes heterologously expressing GIRK channels, membrane stretch induced by 50% reduction of osmotic pressure caused a prompt reduction of GIRK1/4, GIRK1, and GIRK4 currents by 16.6-42.6%. Comparable GIRK current reduction was produced by protein kinase C (PKC) activation (phorbol 12-myristate 13-acetate). The mechanosensitivity of the GIRK4 current was abolished by pretreatment with PKC inhibitors (staurosporine or calphostin C). Neither hypo-osmotic challenge nor PKC activation affected IRK1 currents. GIRK4 chimera (GIRK4-IRK1-(Lys207-Leu245)) and single point mutant (GIRK4(I229L)), in which the phosphatidylinositol 4,5-bisphosphate (PIP2) binding domain or residue was replaced by the corresponding region of IRK1 to strengthen the channel-PIP2 interaction, showed no mechanosensitivity and minimal PKC sensitivity. IRK1 gained mechanosensitivity and PKC sensitivity by reverse double point mutation of the PIP2 binding domain (L222I/R213Q). Overexpression of Gbetagamma, which is known to strengthen the channel-PIP2 interaction, attenuated the mechanosensitivity of GIRK4 channels. In oocytes expressing a pleckstrin homology domain of PLC-delta tagged with green fluorescent protein, hypo-osmotic challenge or PKC activation caused a translocation of the fluorescence signal from the cell membrane to the cytosol, reflecting PIP2 hydrolysis. The translocation was prevented by pretreatment with PKC inhibitors. Involvement of PKC activation in the mechanosensitivity of muscarinic K+ channels was confirmed in native rabbit atrial myocytes. These results suggest that the mechanosensitivity of GIRK channels is mediated primarily by channel-PIP2 interaction, with PKC playing an important role in modulating the interaction probably through PIP2 hydrolysis.

Amino Acid Sequence↗
PubMed2003

Pacing-induced spontaneous activity in myocardial sleeves of pulmonary veins after treatment with ryanodine.

BACKGROUND: Recent clinical electrophysiology studies and successful results of radiofrequency catheter ablation therapy suggest that high-frequency focal activity in the pulmonary veins (PVs) plays important roles in the initiation and perpetuation of atrial fibrillation, but the mechanisms underlying the focal arrhythmogenic activity are not understood. METHODS AND RESULTS: Extracellular potential mapping of rabbit right atrial preparations showed that ryanodine (2 micromol/L) caused a shift of the leading pacemaker from the sinoatrial node to an ectopic focus near the right PV-atrium junction. The transmembrane potential recorded from the isolated myocardial sleeve of the right PV showed typical atrial-type action potentials with a stable resting potential under control conditions. Treatment with ryanodine (0.5 to 2 micromol/L) resulted in a depolarization of the resting potential and a development of pacemaker depolarization. These changes were enhanced transiently after an increase in the pacing rate: a self-terminating burst of spontaneous action potentials (duration, 33.6+/-5.0 s; n=32) was induced by a train of rapid stimuli (3.3 Hz) applied after a brief rest period. The pacing-induced activity was attenuated by either depletion of the sarcoplasmic reticulum of Ca2+ or blockade of the sarcolemmal Na+-Ca2+ exchanger or Cl- channels and potentiated by beta-adrenergic stimulation. CONCLUSIONS: PV myocardial sleeves have the potential to generate spontaneous activity, and such arrhythmogenic activity is uncovered by modulation of intracellular Ca2+ dynamics.

Action Potentials↗
PubMed2003

Chamber-specific differentiation of Nkx2.5-positive cardiac precursor cells from murine embryonic stem cells.

Embryonic stem (ES) cells are a useful system to study cardiac differentiation in vitro. It has been difficult, however, to track the fates of chamber-specific cardiac lineages, since differentiation is induced within the embryoid body. We have established an in vitro culture system to track Nkx2.5(+) cell lineages during mouse ES cell differentiation by using green fluorescent protein (GFP) as a reporter. Nkx2.5/GFP(+) cardiomyocytes purified from embryoid bodies express sarcomeric tropomyosin and myosin heavy chain and heterogeneously express cardiac troponin I (cTnI), myosin light chain 2v (MLC2v) and atrial natriuretic peptide (ANP). After 4-week culture, GFP(+) cells exhibited electrophysiological characteristics specific to sinoatrial (SA) node, atrial, or ventricular type. Furthermore, we found that administration of 10(-7) M retinoic acid (RA) to embryoid bodies increased the percentage of MLC2v(-)ANP(+) cells; this also increased the expression of atrial-specific genes in the Nkx2.5/GFP(+) fraction, in a time- and dose-dependent fashion. These results suggest that Nkx2.5(+) lineage cells possess the potential to differentiate into various cardiomyocyte cell types and that RA can modify the differentiation potential of Nkx2.5(+) cardiomyocytes at an early stage.

Animals↗
PubMed2003

Overexpression of calpastatin by gene transfer prevents troponin I degradation and ameliorates contractile dysfunction in rat hearts subjected to ischemia/reperfusion.

Calpain is a Ca(2+)-activated neutral protease that supposedly plays a key role in myocardial dysfunction following ischemia/reperfusion, by degrading certain proteins involved in the contraction mechanism. It is possible that overexpression of calpastatin, an endogenous calpain inhibitor, lessens contractile dysfunction in the heart after reperfusion by preventing cardiac troponin I (TnI) degradation. This claim is tested by overexpression of human calpastatin (hCS) in rat hearts ex vivo using an adenovirus vector; the hearts were transplanted heterotopically into the abdomens of recipient rats to allow expression of hCS. On the fourth day after surgery, the hearts were excised and perfused in vitro to study their recovery from 30 min of global ischemia, which was followed by 60 min of reperfusion. The peak recovery of the left ventricular developed pressure (LVDP), and the values of its first derivative (max dP/dt, min dP/dt) in the hCS-overexpressed hearts were 88.9 +/- 4.8%, 90.8 +/- 9.2% and 106.4 +/- 9.8%, respectively; these values were all significantly greater than in the control hearts transfected with LacZ alone (51.4 +/- 6.9%, 52.6 +/- 8.1% and 54.7 +/- 6.6%, P < 0.05). In western blot analysis of ventricular myocardial samples (at 60-min reperfusion) using a monoclonal anti-TnI antibody, two bands corresponding to intact TnI (30 kDa) and TnI fragments (27 kDa) were distinguished. The fraction of 27-kDa TnI (percent of total TnI immunoreactivity) in hCS-overexpressed hearts was significantly less than the controls (5.7 +/- 2.7% vs. 18.1 +/- 3.2%, P < 0.05), implying a protective action of hCS against TnI degradation. These results suggest that adenovirus-mediated overexpression of hCS in the heart could be a novel biological means to minimize myocardial stunning by ischemia/reperfusion.

Adenoviridae↗
PubMed2003

Electrocardiographic prediction of the development and site of acute myocardial infarction in patients with unstable angina.

BACKGROUND: ST-T changes on 12-lead electrocardiograms (ECGs) in patients with unstable angina (UA) have limited values for prediction of subsequent acute myocardial infarction (AMI). The aim of the present study is to obtain more useful ECG signs during UA in predicting the risk and the site of AMI. METHODS: ECGs were recorded from 238 consecutive patients with UA; 149 developed AMI, whereas 89 did not in the following 60 days after the UA episodes. P, ST-T and U wave changes in these AMI and non-AMI patients were analyzed retrospectively. Three groups of ECG leads were referred to reflect ischemic changes of anterior (V1-V5), lateral (I, aVL and V6) and inferior (II, III, and aVF) left ventricular walls. To explore the site-dependent predictors, the 149 AMI patients were divided into two groups; group A/L with anterior, antero-septal, apical or lateral AMI, versus group I/P with inferior or posterior AMI. RESULTS: ST depression > or =1 mm and abnormal T wave or U wave changes and P wave abnormalities were observed more frequently in AMI patients than non-AMI patients. On multivariate analysis, an independent ECG finding of the development of AMI was a biphasic U wave (odds ratio (OR) 5.4, 95% confidence interval (CI), 1.9-15.6, P=0.002) in the anterior leads. An inverted T wave (OR 5.1, 95%CI, 1.7-15.5, P=0.0036) and a biphasic U wave (OR 6.0, 95%CI, 2.2-16.1, P=0.0004) in the anterior leads were independent predictors of AMI in group A/L. There was no independent ECG predictor of group I/P. CONCLUSIONS: Biphasic U wave in anterior leads during UA is a useful ECG observation in the risk stratification of subsequent AMI. The independent ECG predictors of antero-lateral MI are inverted T wave and biphasic U wave.

Aged↗
PubMed2003

Sophisticated architecture is required for the sinoatrial node to perform its normal pacemaker function.

The heart's pacemaker, the sinoatrial node, does not consist of a group of uniform sinoatrial node cells embedded in atrial muscle. Instead, it is a heterogeneous tissue with multiple cell types and a complex structure. Evidence suggests that from the periphery to the center of the sinoatrial node, there is a gradient in action potential shape, pacemaking, ionic current densities, connexin expression, Ca2+ handling, myofilament density, and cell size. This complexity may be necessary for the sinoatrial node to pacemake under diverse conditions, drive the more hyperpolarized atrial muscle, and resist proarrhythmic perturbations.

Action Potentials↗