Monocyte chemoattractant protein-1 is associated with silent cerebral infarction in patients on haemodialysis.

BACKGROUND: In patients with chronic renal failure undergoing haemodialysis (HD), silent cerebral infarctions (SCI) are associated with high mortality. Levels of monocyte chemoattractant protein-1 (MCP-1) increase with renal dysfunction and may be a novel predictor for cerebrovascular events. We tested the hypothesis that increased MCP-1 concentration correlate with the occurrence of SCI in HD patients. METHODS: Using cranial magnetic resonance imaging (MRI) findings, 52 Japanese patients undergoing HD were divided into two groups: with SCI (61 ± 7 years, mean ± SD, n= 28) and without SCI (60 ± 6 years, n= 24). The gender, metabolic profiles and MCP-1 concentration were compared between the two groups. RESULTS: The level of MCP-1 was higher in the with-SCI group than in the without-SCI group (P < 0.0001). The proportion of smokers was higher in the with-SCI group (P < 0.05) than in the without-SCI group. Plasma level of high-density lipoprotein cholesterol was lower, while uric acid level was higher, in the with-SCI group (P < 0.05 and P < 0.05 respectively) compared to the without-SCI group. Multiple logistic regression analysis identified MCP-1 level as being significantly associated with the presence of SCI (odds ratio 1.48, 95% confidence interval = 1.10-5.75, P < 0.0001). CONCLUSIONS: This study indicates that patients with chronic renal failure who are maintained on HD exhibit an increased prevalence of SCI, and that MCP-1 is significantly associated with the presence of SCI in HD patients.

Interleukin-6 and silent cerebral infarction in hemodialysis patients: a cross-sectional study.

BACKGROUND: In patients with chronic renal failure undergoing hemodialysis (HD), silent cerebral infarctions (SCI) are associated with high mortality. Levels of interleukin-6 (IL-6) increase with renal dysfunction and may be a novel predictor for cerebrovascular events. We tested the hypothesis that increased IL-6 levels correlate with the occurrence of SCI in HD patients. METHODS: Using cranial magnetic resonance imaging findings, we divided 50 Japanese patients undergoing HD into two groups: with SCI (60 ± 7 years, mean ± SD, n = 27) and without SCI (60 ± 6 years, n = 23). We compared the gender, body mass index, metabolic profiles, IL-6 levels, and smoking habits between the two groups. RESULTS: We made the following observations: (i) The prevalence of diabetes or hypertension did not differ between the two groups, (ii) the level of IL-6 was higher in the with-SCI group than in the without-SCI group (P < 0.0001), (iii) the proportion of smokers was higher in the with-SCI group (P < 0.05), (iv) plasma level of high-density lipoprotein cholesterol was lower, whilst uric acid level was higher, in the with-SCI group (P < 0.05 and P < 0.05, respectively), and (v) multiple logistic regression analysis identified IL-6 levels as being significantly associated with the presence of SCI (odds ratio 3.13, 95% CI = 1.42-7.89, P < 0.0001). CONCLUSIONS: This study indicates that patients with chronic renal failure who are maintained on HD exhibit an increased prevalence of SCI and that IL-6 is significantly associated with the presence of SCI in HD patients.

Visceral fat accumulation is a significant risk factor for white matter lesions in Japanese type 2 diabetic patients.

BACKGROUND: The presence of white matter lesions (WML) is an important prognostic factor for the development of stroke. The elevated visceral fat accumulation (VFA) has been reported to be closely related to the development of atherosclerosis. This preliminary study was therefore designed to test the hypothesis that the presence of WML correlates with VFA and insulin resistance in type 2 diabetic patients not receiving insulin treatment. MATERIAL AND METHODS: Based on brain magnetic resonance imaging (MRI), 95 type 2 diabetic patients were divided into two groups: WML-positive group (aged 59 +/- 7 years, mean +/- SD n = 37) and WML-negative group (aged 58 +/- 5, years, n = 58). The level of blood glucose was assessed by fasting plasma glucose (FPG), fasting immunoreactive insulin, homeostasis model assessment (HOMA) index, and haemoglobin A1c. The fat distribution was evaluated by measuring the visceral fat accumulation by abdominal computerized tomography at the umbilical level. RESULTS: The body mass index was higher in the WML-positive group than in the WML-negative group (P < 0.005). Plasma levels of triglycerides were higher while high-density lipoprotein cholesterol was lower in the WML-positive group than in the WML-negative group (P < 0.05 and P < 0.01, respectively). FPG (P < 0.01), insulin concentrations (P < 0.0001), HOMA index (P < 0.0001) and VFA (<0.0001) levels were higher in the WML-positive group than in the WML-negative group. Multivariate logistic analysis revealed that WML was independently predicted by the high VFA and insulin resistance (P < 0.001, P < 0.0001, respectively). CONCLUSIONS: The results of this preliminary study indicate that the presence of WML was associated with the high VFA and insulin resistance in Japanese patients with type 2 diabetes mellitus. Further larger cohort studies are warranted to confirm these findings.

Induction of heat shock proteins prevents the arrhythmogenic substrate for atrial fibrillation.

Atrial fibrillation (AF) is the commonest arrhythmia. Studies have shown that atrial tachypacing (artificial persistent AF) causes electrical remodelling. This is characterised by the shortening of the atrial effective refractory period (ERP), in which reduction in L-type Ca(2+) channel current plays an essential part. Atrial fibrosis, a feature of structural remodelling, is induced by continuous infusion of angiotensin II, and has been associated with conduction delay in atria, which promotes AF. Acute atrial ischaemia, frequently observed during development of acute coronary syndrome, has been associated with atrial conduction heterogeneity, which also promotes AF. Induction of heat shock proteins (Hsp72 and Hsp27) by hyperthermia and/or geranylgeranylacetone has demonstrated to protect the heart against such atrial remodelling. The potent protective role of Hsp72 and Hsp27 against clinical AF in patients who underwent open heart surgery has been shown. Taken together, interventions that induce heat shock responses (including induction of Hsp72 and Hsp27) may prevent newly developed AF and delay the progression of paroxysmal AF to persistent AF.

Plasma HHV-6 viral load-guided preemptive therapy against HHV-6 encephalopathy after allogeneic stem cell transplantation: a prospective evaluation.

Human herpesvirus 6 (HHV-6) causes life-threatening encephalopathy in recipients of allogeneic SCT, but no consensus has been reached regarding appropriate preventive methods. This study evaluated a plasma HHV-6 viral load-guided preemptive approach against HHV-6-associated encephalopathy. Plasma real-time PCR assay was performed once a week. Among 29 patients, 19 developed positive plasma HHV-6 DNA. Median maximum plasma HHV-6 DNA was 4593.5 copies/ml plasma (range, 150.0-127 891.0 copies/ml plasma). In one of eight events with low-level HHV-6 DNA (defined as <1000 copies/ml plasma) and four of seven events with mid-level HHV-6 DNA (1000-9999.5 copies/ml plasma), HHV-6 loads in plasma subsequently continued increasing. Ganciclovir was administered against six of nine patients with high-level HHV-6 DNA (> or =10,000 copies/ml plasma). High-level HHV-6 DNA resolved similarly in both groups with or without ganciclovir therapy. Among the nine patients with high-level HHV-6 DNA two developed encephalopathy. As encephalopathy developed before the detection of high-level HHV-6 DNA in plasma, these two patients had not received preemptive ganciclovir therapy. In conclusion, our preemptive approach against HHV-6-associated encephalopathy cannot prevent all cases of HHV-6 encephalopathy in SCT recipients due to the dynamic kinetics of plasma HHV-6 viral load.

New squatting test indices are useful for assessing baroreflex sensitivity in diabetes mellitus.

AIMS: The heart rate (HR) responses after performance of the squatting and standing manoeuvre are thought to be a useful tool to assess autonomic neuropathy in diabetics. Our aim was to develop new simple squatting test indices and to analyse their applicability to the assessment of baroreflex sensitivity (BRS) in patients with diabetes. METHODS: Twenty healthy volunteers (mean age 23.2 +/- 3.8 years) and 51 patients with diabetes (mean age 55.9 +/- 10.6 years) were enrolled in study 1 and study 2, respectively. Each subject stood for 3 min (basal period), then squatted down for 1 min (Sq) and stood up again for 1 min (St). In study 1, the squatting test was performed before and after pharmacological autonomic blockade. In study 2, we measured HR in each period and calculated the difference between basal HR and HRSq (DeltaHRSq) and between HRSt and HRSq (DeltaHRSt). BRS was also measured using the phenylephrine method in diabetic patients. RESULTS: In healthy individuals during autonomic blockade, HR changes were mainly controlled by the vagal tone during squatting and by the sympathetic tone during standing. In diabetic patients, DeltaHRSq and DeltaHRSt positively correlated (r = 0.86, P < 0.0001) and both DeltaHRSq and DeltaHRSt significantly correlated with BRS (r = 0.66, P < 0.0001 and r = 0.61, P < 0.0001, respectively). CONCLUSIONS: The new squatting test indices provide useful information for assessing autonomic neuropathy and for identifying diabetic patients at high risk of cardiovascular events.

Hyperhomocysteinaemia is a significant risk factor for white matter lesions in Japanese type 2 diabetic patients.

The presence of white matter lesions (WML) is an important prognostic factor for the development of stroke. Plasma total homocysteine (tHcy), which increases with diabetes, has been flagged as a novel predictor for cerebrovascular events. We tested the hypothesis that the presence of WML correlates with tHcy and insulin resistance in type 2 diabetic patients not receiving insulin treatment. Based on brain magnetic resonance imaging findings, 81 type 2 diabetic patients were divided into two groups, with-WML group (57 +/- 8 years, mean +/- standard deviation, n = 31) and without-WML group (57 +/- 6 years, n = 50). The blood glucose level was assessed by fasting plasma glucose (FPG), fasting immunoreactive insulin, Homeostasis Model Assessment (HOMA) Index and hemoglobin A1c. The body mass index was higher in the with-WML group than in the without-WML group (P < 0.05). Plasma levels of triglyceride were higher whilst high-density lipoprotein cholesterol was lower in the with-WML group than in the without-WML group (P < 0.05 and P < 0.0001 respectively). FPG (P < 0.005), insulin concentrations (P < 0.0001), HOMA Index (P < 0.0001) and tHcy (<0.0001) levels were higher in the with-WML group than in the without-WML group. Multivariate logistic analysis revealed that WML was independently predicted by the high tHcy and insulin resistance. Our findings indicate that the presence of WML was associated with the high tHcy and insulin resistance in these Japanese patients with type 2 diabetes mellitus.

Alteration of heart uncoupling protein-2 mRNA regulated by sympathetic nerve and triiodothyronine during postnatal period in rats.

To provide tissue-specific and developmental characteristics of gene expression of rat heart uncoupling protein-2 (UCP2), we investigated developmental alterations of UCPs mRNA expression in the heart and brown adipose tissue (BAT), and examined possible up-regulators of heart UCP2 expression using in vitro studies. Heart UCP2 mRNA expression was low during the early postnatal days followed by a rapid and significant increase in the 2nd postnatal week. Heart UCP3 mRNA remained undetectable until the 2nd postnatal week when the expression reached a small but significant peak. BAT UCP1 mRNA was abundantly expressed in the neonate, but the expression rapidly decreased to the adult level. The studies using cultured cardiomyocytes demonstrated that both 10(-8) M triiodothyronine and 10(-7) M isoproterenol, but not phenylephrine, increased UCP2 mRNA expression. These results indicate that the sympathetic nervous system and/or thyroid hormones may be involved in the up-regulation of heart UCP2 gene expression during postnatal development. The increase in postnatal heart UCP2 may provide a key link between the postnatal energy shift and adaptation of rat pups to their novel environment.

Rapid electrical stimulation of contraction reduces the density of beta-adrenergic receptors and responsiveness of cultured neonatal rat cardiomyocytes. Possible involvement of microtubule disassembly secondary to mechanical stress.

BACKGROUND: Although tachycardia is commonly present in patients with congestive heart failure, its role in the development of congestive heart failure remains unclear. We studied the effect of rapid electrical stimulation of contraction on beta-adrenergic receptor (beta-AR) signal pathway in cultured cardiomyocytes of neonatal rats. METHODS AND RESULTS: Contraction of cardiomyocytes was induced by electrical stimulation at 50 V with twice the threshold pulse width. beta-ARs were identified by [(3)H]CGP-12177 and [(3)H]dihydroalprenolol. Electrical stimulation reduced cell-surface but not total beta-AR density; the effect was dependent on pacing frequency (a reduction of 11%, 28%, and 18% in cells paced at 2.5, 3. 0, and 3.3 Hz, respectively). This reduction was apparent at 3 hours, in contrast to reduced beta-AR density after exposure to isoproterenol (ISP) for 1 hour. The fraction and inhibition constant of beta-AR binding agonist with high affinity were not affected by rapid electrical stimulation. In cardiomyocytes paced at 3.0 Hz for 24 hours, the response to ISP decreased compared with unpaced cells, 142% versus 204% of baseline with 1 micromol/L ISP, whereas the responses to forskolin or acetylcholine were not different. Treatment of cardiomyocytes with 2,3-butanedione monoxime (10 mmol/L) or taxol (10 micromol/L) inhibited the rapid pacing-induced reduction in beta-AR density. CONCLUSIONS: Our results suggest that contractile activity is involved in regulation of cardiac function by modulating the beta-AR system independently of hemodynamic and neurohormonal factors. This may help to elucidate the role of mechanical stress in the development of heart failure.

Single oral dose of geranylgeranylacetone induces heat-shock protein 72 and renders protection against ischemia/reperfusion injury in rat heart.

BACKGROUND: Induction of heat-shock proteins (HSPs) results in cardioprotection against ischemic insult. Geranylgeranylacetone (GGA), known as an antiulcer agent, reportedly induces HSP72 in the gastric mucosa and small intestine of rats. The present study tested the hypothesis that oral GGA would induce HSP72 in the heart and thus render cardioprotection against ischemia/reperfusion injury in rats. METHODS AND RESULTS: Cardiac expression of HSPs was quantitatively evaluated in rats by Western blot analysis. Ten minutes of whole-body hyperthermia induced HSP72 expression in the rat hearts. A single oral dose of GGA (200 mg/kg) also induced expression of HSP72, which peaked at 24 hours after administration. Therefore, isolated perfused heart experiments using a Langendorff apparatus were performed 24 hours after administration of 200 mg/kg GGA (GGA group) or vehicle (control group). After a 5-minute stabilization period, no-flow global ischemia was given for 20, 40, or 60 minutes, followed by 30 minutes of reperfusion. During reperfusion, the functional recovery was greater and the released creatine kinase was less in the GGA group than in the control group. Electron microscopy findings revealed that the ischemia/reperfusion-induced damage of myocardial cells was prevented in GGA-treated myocytes. CONCLUSIONS: The results suggest that oral GGA is cardioprotective against ischemic insult through its induction of HSP72.

Effect of essential hypertension on cardiac autonomic function in type 2 diabetic patients.

OBJECTIVES: The aim of this study was to examine the effects of essential hypertension on cardiac autonomic function in type 2 diabetic patients. BACKGROUND: Hypertension is common in type 2 diabetic patients and is associated with a high mortality. However, the combined effects of type 2 diabetes and essential hypertension on cardiac autonomic function have not been fully elucidated. METHODS: Thirty-three patients with type 2 diabetes were assigned to a hypertensive diabetic group (n = 15; age: 56 +/- 8 years, mean +/- SD) or an age-matched normotensive diabetic group (n = 18, 56 +/- 6 years). Cardiac autonomic function was assessed by baroreflex sensitivity (BRS), heart rate variability (HRV), plasma norepinephrine concentration and cardiac 123I-metaiodobenzylguanidine (MIBG) scintigraphic findings. RESULTS: Baroreflex sensitivity was lower in the hypertensive diabetic group than it was in the normotensive diabetic group (p < 0.05). The early and delayed myocardial uptake of 123I-MIBG was lower (p < 0.01 and p < 0.05, respectively), and the percent washout rate of 123I-MIBG was higher (p < 0.05) in the hypertensive diabetic group. However, the high frequency (HF) power and the ratio of low frequency (LF) power to HF power (LF/HF) of HRV and plasma norepinephrine concentration were not significantly different. The homeostasis model assessment index was higher in the hypertensive diabetic group than it was in the normotensive diabetic group (p < 0.01). CONCLUSIONS: Our results indicate that essential hypertension acts synergistically with type 2 diabetes to depress cardiac reflex vagal and sympathetic function, and the results also suggest that insulin resistance may play a pathogenic role in these processes.

Noninvasive assessment of the cardiac baroreflex: response to downward tilting and comparison with the phenylephrine method.

OBJECTIVES: We studied the relation between changes in systolic blood pressure and RR interval during downward tilting in comparison with assessment of baroreflex sensitivity (BRS) measured by the phenylephrine method (Phe-BRS) and with measures of heart rate variability (HRV). BACKGROUND: The method most extensively used for assessing BRS involves bolus injections of phenylephrine. Several noninvasive methods proposed to assess BRS have not been widely applied in the clinical setting. METHODS: Sixteen healthy male volunteers were studied (mean age +/- SD 27.5+/-4.6 years). Arterial blood pressure using tonometry and electrocardiogram was simultaneously recorded. After 20 min of 70 degrees upright tilting, the table was returned to supine position at a speed of 3.2 degrees/s. Subsequently, BRS was assessed using an intravenous bolus injection of phenylephrine (2 to 3 microg/kg). Heart rate variability under resting conditions also was analyzed. RESULTS: In all subjects, a beat to beat systolic blood pressure increase associated with corresponding RR interval lengthening was observed during downward tilting as well as during phenylephrine administration. During both testing procedures, these two variables showed linear correlation, and the slope of regression line during downward tilting (DT-BRS) correlated significantly with Phe-BRS (r = 0.79, p = 0.0003). The DT- and Phe-BRS also correlated significantly with the high frequency component of resting HRV (r = 0.70, p = 0.0023 for DT-BRS; r = 0.58, p = 0.0185 for Phe-BRS). CONCLUSIONS: We conclude that in a small homogeneous group DT-BRS provided an assessment of reflex cardiac vagal function comparable to that obtained by the phenylephrine method.

Nicorandil suppresses early afterdepolarisation and ventricular arrhythmias induced by caesium chloride in rabbits in vivo.

STUDY OBJECTIVE: Outward K current of cardiac membrane has been shown to be suppressed by caesium chloride (Cs) and enhanced by nicorandil, a coronary vasodilator. The aim of this study was to assess the effects of nicorandil on the Cs induced early afterdepolarisations and associated ventricular arrhythmias in the rabbit heart in vivo. DESIGN: Intravenous bolus injections of Cs (1 mmol.kg-1) were given three times at 20 min intervals. Monophasic action potentials of the left ventricular endocardium and the ECG (lead II) were recorded simultaneously over 60 min, under the intrinsic (sinus node) cardiac rhythm. EXPERIMENTAL MATERIAL: Eight rabbits were treated with Cs alone (control group); seven other rabbits were first treated with an intravenous infusion of nicorandil (0.2 mg.kg-1) (nicorandil treated group) and the effects of Cs were then examined. MEASUREMENTS AND MAIN RESULTS: In the control group, Cs produced early afterdepolarisations, premature ventricular beats and ventricular tachycardias. The ventricular tachycardias included two different types: (1) non-sustained polymorphic ventricular tachycardia mimicking the torsade de pointes in patients with long QT syndrome; (2) sustained monomorphic ventricular tachycardia. In the nicorandil treated group, the amplitude of the early afterdepolarisations and the incidence of ventricular tachycardias were significantly less than in the control group. CONCLUSIONS: Nicorandil suppresses the early afterdepolarisations and ventricular tachyarrhythmias induced by Cs, possibly by increasing the membrane K conductance.

Electrophysiological actions of mexiletine (Kö1173) on canine Purkinje fibres and ventricular muscle.

1 The effects of mexiletine (Kö1173) were investigated in canine isolated cardiac Purkinje fibres and ventricular muscle with microelectrodes. Some Purkinje fibres were depolarized by mechanical stretch to induce spontaneous activity with slow upstroke velocity. The preparations were stimulated at rates of 1, 2, 3 and 4 Hz. The drug concentrations tested were 0.4, 2 and 10 mug/ml in Tyrode solution (KCl = 5.4 mM).2 The ;therapeutic' drug concentration (2 mug/ml) shortened action potential duration and effective refractory period of Purkinje fibres, the effect being pronounced at lower stimulation rates. In ventricular fibres, action potential duration changes were not consistent while the effective refractory period was prolonged.3 In depolarized Purkinje fibres showing automatic activity, the drug (0.4 or 2 mug/ml) depressed phase 4 depolarization and reduced the firing rate without changing maximum diastolic potential. However, when depolarized Purkinje fibres were electrically driven at a constant rate, the maximum diastolic potential became more negative with a concomitant decrease of pacemaker slope and increase of maximum rate of rise (V(max)) of action potentials.4 Moderate (2 mug/ml) to high (10 mug/ml) concentrations of the drug depressed V(max) in Purkinje fibres stimulated at 2 Hz by 12 and 42% respectively and depressed ;membrane responsiveness'. The decrease in V(max) depended upon the stimulation rate, being minimum at the lowest (1 Hz) and maximum at the highest (4 Hz) stimulation rate.5 The drug (2 mug/ml) improved V(max) of the earliest propagated premature action potentials by shifting the takeoff potential to more negative levels in both Purkinje and ventricular fibres.6 Membrane conductance in fibres mounted in a single sucrose gap chamber was increased by the drug (2 mug/ml) in both fibre types in normal and in Na(+)-deficient solutions. This increase was attributed to an increase in membrane K(+) permeability produced by the drug.7 All these effects are similar to those of lignocaine, diphenylhydantoin or aprindine, and can explain the antiarrhythmic action of mexiletine.

Clinical suppression of bradycardia dependent premature ventricular contractions by the potassium channel opener nicorandil.

OBJECTIVE: To assess the clinical antiarrhythmic effect of nicorandil, a potassium channel opener; on premature ventricular contractions. DESIGN AND PATIENTS: The effect of oral nicorandil (15 to 60 mg daily for four weeks) on premature ventricular contractions was investigated in 20 patients (11 female, nine male, mean (SD) age 63 (17) years) who underwent 24 hour ambulatory ECG. Patients were classified into two groups based on the relation between the frequency of premature ventricular contractions and heart rate: (1) those with a positive correlation (n = 9); and (2) those with a bidirectional correlation (n = 11), characterised by an increased frequency of premature contractions at low heart rates and a decreased frequency at high heart rates. RESULTS: Nicorandil reduced the frequency of premature ventricular contractions by 75% in five patients in group 2, but was not effective in any patient in group 1. The heart rate at which the frequency of premature ventricular contractions peaked was significantly lower in the five responders in group 2 than in the six non-responders (63.2 (3.7) v 76.3 (12.4) beats/min, p < 0.05). CONCLUSIONS: Nicorandil may suppress premature ventricular contractions when they occur mainly at a low heart rate.

Circadian rhythm of the signal averaged electrocardiogram and its relation to heart rate variability in healthy subjects.

OBJECTIVE: To examine the circadian variation in the signal averaged electrocardiogram (saECG) and heart rate variability and investigate their relations in healthy subjects. METHODS: 24 hour ECGs were obtained with a three channel recorder using bipolar X, Y, and Z leads in 20 healthy subjects. The following variables were determined hourly: heart rate, filtered QRS (f-QRS) duration, low and high frequency components of heart rate variability (LF and HF), and the LF/HF ratio. RESULTS: Heart rate, f-QRS duration, HF, and the LF/HF ratio showed significant circadian rhythms, as determined by the single cosinor method. Heart rate and the LF/HF ratio increased during daytime, and f-QRS duration and HF increased at night. f-QRS duration was negatively correlated with heart rate (r = 0.95, p < 0.001) and the LF/HF ratio (r = 0.94, p < 0.001) and positively with HF (r = 0.93, p < 0.001). CONCLUSIONS: f-QRS duration has a significant circadian rhythm in healthy subjects and is closely related to the circadian rhythm of autonomic tone.

A polymorphism of angiotensinogen gene codon 174 and coronary artery disease in Japanese subjects.

The relationship between coronary artery disease (CAD) and polymorphisms of genes encoding angiotensinogen (AGT) and angiotensin converting enzyme (ACE) was analyzed in Japanese subjects. One hundred and four patients with CAD and 170 healthy subjects were enrolled in the study. CAD was defined as having a luminal diameter stenosis > or =50% in at least one of three major coronary arteries by coronary angiography. The genotypes (determined by polymerase chain reaction) of AGT gene codon 174 were not significantly associated with CAD in the total study population. However, the frequency of T/T homozygotes of AGT codon 174 was significantly higher in CAD patients compared to controls in each of three subgroups: 1) body mass index (BMI) below the median value of 24.1 kg/m2; 2) not more than two CAD risk factors out of five (hypercholesterolemia, hypertension, diabetes mellitus, smoking, and family history of CAD); and 3) the ACE I/I genotype. The M/M genotype of AGT codon 235 was negatively associated, and the ACE D/D genotype was positively associated, with CAD in the total study population. Our results indicate that the T/T genotype of AGT codon 174 may be a risk factor for CAD in Japanese individuals with low BMI, lesser CAD risk factors, or ACE I/I genotype.

Silent cortical strokes associated with atrial fibrillation.

To clarify whether silent cortical strokes (SCS) could be a predictor of symptomatic stroke in patients with atrial fibrillation (AF), 72 patients with AF (50 with chronic AF, 22 with paroxysmal AF) were studied. Patients with mitral stenosis, history of myocardial infarction, or dilated cardiomyopathy were excluded from this study. Using cranial magnetic resonance imaging (MRI), the patients were divided into those with SCS (23 patients, Group 1) and those without SCS (49 patients, Group 2). The incidence of symptomatic stroke was then compared between the two groups. Three patients (13%) in Group 1 developed symptomatic brain infarction; this is statistically significant (p < 0.05), compared with the patients in Group 2, none of whom experienced symptomatic stroke. We suggest that SCS is a predictor of symptomatic cerebral infarct in patients with AF. Therefore, it is thought to be important to diagnose SCS using cranial MRI or computed tomography and to keep patients with SCS under close surveillance.

QT intervals as an index of high serum calcium in hypercalcemia.

The relationship between QT interval and serum calcium concentration (s-Ca) was examined in 9 hypercalcemic (s-Ca greater than 11 mg/dl) patients. Three QT intervals corrected by Bazett's formula were used for the analysis: the intervals from the beginning of the QRS to the onset (QoTc), the apex (QaTc), and the end of T wave (QeTc). The measurements of s-Ca and other electrolytes were made on the blood sample taken on the same day of the electrocardiogram (ECG) recordings. The normal range of s-Ca and three QTc intervals was determined in 50 outpatients with no cardiac disease. Three QT intervals in the hypercalcemic patients were significantly shortened with a diminution in the s-Ca. The QTc intervals showed significant negative correlation with s-Ca. Sensitivity of QoTc, QaTc, and QeTc in predicting high s-Ca was 83%, 57%, and 39%, respectively, and specificity was 100%, 100%, and 89%. The PQ interval tended to be prolonged in the case of hypercalcemia, but the change was statistically insignificant. These observations suggest that QT intervals can serve as an indicator of high s-Ca and that the QoTc seems to be a good indicator of the three QTc's.

QT interval shortening and ST elevation in intracoronary ECG during PTCA.

Percutaneous transluminal coronary angioplasty (PTCA) can provide a unique model of transient and reversible myocardial ischemia. The aim of this study was to assess the serial changes in QT interval during elective PTCA-induced transient ischemia. The serial changes in QT interval before, during, and after PTCA of the left anterior descending artery (LAD) were measured in patients who showed ST elevation in intracoronary electrocardiogram. Twelve consecutive patients who showed ST-segment elevation during PTCA-induced ischemia anterior precordial leads of the electrocardiogram (ECG) were enrolled in the present study. Target lesions for PTCA were all in the LAD. There were six patients with angina pectoris, two with non-Q-wave infarction, and four with Q-wave myocardial infarction. During balloon inflation, QTc interval shortened in both intracoronary ECG (ic-ECG) (0.472 +/- 0.013 vs 0.436 +/- 0.014) and surface ECG (0.462 +/- 0.012 vs 0.438 +/- 0.011). However, a significant shortening of the QT interval was more rapidly observed in the ic-ECG (20 s) than in the surface ECG (40 s). We conclude that the QT interval in both ic-ECG and surface ECG becomes shortened in PTCA-induced myocardial ischemia, and that the ic-ECG might be a good probe for detecting survived viable myocardium in the infarcted zone.