Micro-CT analysis of alveolar bone healing using a rat experimental model of critical-size defects.

OBJECTIVE: This study was designed to establish a rat model of a critical size alveolar bone defect. MATERIALS AND METHODS: Standardized buccal or mesiobuccal alveolar bone defects were made around the right first mandibular molar of 12-week-old rats, and the left was used as a control. Alveolar bone healing was examined quantitatively by three-dimensional micro-computed tomographic imaging. Bone matrix production of osteoblasts and osteocytes during repair of alveolar bone defects was examined with in situ hybridization for type I collagen. RESULTS: Buccal defects were repaired significantly and the volume decreased by 88.3% in week 24, whereas mesiobuccal defects were repaired little. Osteoblasts and osteocytes expressed type I collagen in both defects in week 3 but showed little expression by week 6 and thereafter, leaving the mesiobuccal defects largely unrepaired. CONCLUSION: The mesiobuccal defect is a critical-size defect that is not ultimately repaired with bone. It may be an appropriate experimental model for investigating the effectiveness of bone regenerative agents in human alveolar bone loss.

Bone regeneration by synthetic octacalcium phosphate and its role in biological mineralization.

Octacalcium phosphate (Ca8H2(PO4)6 * 5H2O; OCP) has been advocated to be a precursor of biological apatite crystals in bone and tooth. Recent studies, using physical techniques, showed that OCP is present as a transient phase during biological apatite formation in human dentin, porcine enamel and murine bone. However, there is still a controversy regarding the chemical nature of the first mineral formed in the biominerals. A number of studies have demonstrated that synthetic OCP shows bone regenerative and biodegradable characteristics, rather than other calcium phosphate bone substitute materials, such as hydroxyapatite (Ca10(PO4)6(OH)2; HA) ceramic. It seems likely that synthetic OCP may be an alternative to autogenous bone graft. It is known that OCP contains alternative layers of water molecules and an apatite structure, and that the transition of OCP to HA is likely to be spontaneous and irreversible. The conversion process induces modification of local environment adjacent to OCP surface, including the changes in adsorption of serum proteins and concentration of calcium and inorganic phosphate ions. This article reviews the possible application to bone regeneration by synthetic OCP and the mechanism to enhance bone regeneration in relation to biological mineralization in bone and tooth.

Analysis of appositional bone formation using a novel rat experimental model.

AIM: To analyze the process of appositional bone formation using our original rat experimental model. MATERIALS AND METHODS: Rats were anesthetized and a ring made of polytetrafluorethylene was placed on the parietal bone surface in the surgical procedure. The time course of appositional bone formation was analyzed with histomorphometry and in situ hybridization for type I collagen and bone sialoprotein. RESULTS: The rat experimental model allowed new bone to be formed on the pre-existing bone surface and persist for 12 weeks. We demonstrated that bone is apposed actively for the first 4 weeks and less actively thereafter. CONCLUSIONS: The experimental model may contribute to biological analysis for appositional bone formation expected to occur in clinical procedures such as alveolar bone augmentation and sinus lifting.

Formation of bone-like apatite enhanced by hydrolysis of octacalcium phosphate crystals deposited in collagen matrix.

It has been shown that granules of synthetic octacalcium phosphate (OCP) or the composites with collagen are capable of enhancing bone regeneration, accompanied by a gradual conversion from OCP to apatite with time. The present study was designed to investigate whether formation of bone-like apatite can be accelerated by OCP deposited throughout collagen matrix (OCP collagen complex, OCC) immersed in simulated body fluid (SBF). The formation of bone-like apatite has been suggested to be essential to induce osteoconductivity of various substrates. The formation of OCP in collagen solution was investigated in calcium or phosphate ions in the range between 22.5 and 142.5 mM and pH 6.26 and 8.56. X-ray diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy (SEM) showed that condition to nucleate OCP was limited to that of a solution with Ca/P 0.43 around pH 7.16 in the presence of collagen. OCP was shown to be formed throughout the collagen matrix by SEM observation. The immersion of OCC in SBF up to 10 days enhanced apatite crystal deposition, probably through OCP-apatite conversion: the apatite formation in OCC took place within only 1 day. The present study indicated that the existence of OCP deposited throughout the collagen matrix promotes bone-like apatite formation under physiological condition.

Preventive effect of renin-angiotensin system inhibitors on new-onset atrial fibrillation in hypertensive patients: a propensity score matching analysis.

It is still controversial whether treatment with renin-angiotensin system (RAS) inhibitors reduces the risk of incident atrial fibrillation (AF). This longitudinal observational study was performed to investigate the confounder-independent effects of RAS inhibitors on new-onset AF in hypertensive patients. Among 1263 consecutive hypertensive patients who underwent echocardiography, 964 eligible patients (mean age, 63 years) were enrolled as the study population. Forty-nine patients developed new-onset AF during the follow-up period (mean: 4.6 years). Kaplan-Meier analysis showed that the cumulative AF event rate was lower in patients receiving RAS inhibitors than in patients without these drugs, but the difference between these two groups was not significant (P=0.057). Since the use of RAS inhibitors was influenced by concomitant diabetes, chronic kidney disease and left ventricular hypertrophy, propensity score matching (1:1) was employed to minimize the influence of selection bias for RAS inhibitors. Clinical and echocardiographic parameters showed no significant differences between the propensity score-matched groups with and without RAS inhibitor therapy (both n=326), but the cumulative AF event rate was significantly lower in the group receiving RAS inhibitors (P=0.013). Univariate and multivariate Cox regression analyses also revealed that RAS inhibitor therapy was associated with a significantly lower risk of new-onset AF during the follow-up period. In conclusion, this propensity score matching study demonstrated that the incidence of new-onset AF was lower in hypertensive patients receiving RAS inhibitor therapy.

Long-term outcome of verapamil-sensitive sustained left ventricular tachycardia in patients without structural heart disease.

OBJECTIVES: This study attempted to determine the long-term outcome of verapamil-sensitive sustained left ventricular tachycardia in patients without apparent structural heart disease. BACKGROUND: Several types of idiopathic ventricular tachycardia have been reported, and their clinical, electrophysiologic and electropharmacologic characteristics are different. It is possible that the prognosis of each type of ventricular tachycardia might also be different. METHODS: We studied mortality and morbidity in 37 consecutive patients (27 male, 10 female; mean [+/- SD] age 33 +/- 14 years) with verapamil-sensitive sustained left ventricular tachycardia who had no apparent structural heart disease. Patients were followed up for 1 to 13 years (mean 5.8). Verapamil repeatedly terminated ventricular tachycardia in all patients. Ventricular tachycardia originated from the inferior and inferoseptal regions of the left ventricle in 33 patients and the superior and superioseptal regions in 4. Severity of ventricular tachycardia was classified according to the extent to which symptoms limited daily activities. Ventricular tachycardia was mild (minimal limitation) in 14 patients, moderate (some limitation) in 17 and severe (severe limitation) in 6. RESULTS: Fourteen patients with mild ventricular tachycardia were followed up without any drug therapy, and the ventricular tachycardia remained mild in all patients. Antiarrhythmic therapy was initiated empirically in the 23 patients with moderate and severe ventricular tachycardia (verapamil in 20, propranolol in 2, digoxin in 1). Moderate ventricular tachycardia became mild ventricular tachycardia after drug therapy in all patients, but the six patients with severe ventricular tachycardia showed no improvement. The six patients with severe ventricular tachycardia had nonpharmacologic therapy (cryosurgery in one, catheter ablation in four, antitachycardia pacing device in one). During the follow-up period, all patients remained alive except for one who died suddenly after implantation of an antitachycardia pacing device. CONCLUSIONS: 1) The long-term prognosis of verapamil-sensitive sustained left ventricular tachycardia in patients without apparent structural heart disease is good. 2) Verapamil is the drug of choice for alleviating symptoms, but nonpharmacologic therapy is necessary in some patients.

Frequency analysis of signal-averaged electrocardiogram in patients with right ventricular tachycardia.

OBJECTIVES: The purpose of this study was to analyze the frequency content of signal-averaged electrocardiograms (ECGs) in patients with idiopathic ventricular tachycardia of right ventricular origin and in patients with arrhythmogenic right ventricular dysplasia. BACKGROUND: The late potentials in the time domains are usually found in patients with arrhythmogenic right ventricular dysplasia. They are not usually found in patients with idiopathic ventricular tachycardia of right ventricular origin. METHODS: Fast Fourier transform analysis of signal-averaged ECGs was performed with the use of a Blackman-Harris window in 43 subjects: 20 normal volunteers (group I), 12 patients with idiopathic ventricular tachycardia of right ventricular origin (group II) and 11 patients with arrhythmogenic right ventricular dysplasia (group III), and the frequency spectrum was displayed in a three-dimensional graph. Area ratio (ratio of the area under the spectral plot from 40 to 120 Hz to the area from 0 to 120 Hz) was calculated in all subjects. RESULTS: Area ratio was significantly higher in group II than in group I (243 +/- 45 vs. 196 +/- 15, p < 0.01) and significantly higher in group III (396 +/- 51) than in group I or II (p < 0.001). The high frequency components in group II were confined within the QRS complex in the three-dimensional graph, whereas those in group III extended outside the QRS complex. CONCLUSIONS: Frequency analysis of the signal-averaged ECG with fast Fourier transform analysis can detect the high frequency components in patients with right ventricular tachycardia, including idiopathic ventricular tachycardia and arrhythmogenic right ventricular dysplasia.

Frequency-dependent electrophysiologic properties of ventricular repolarization in patients with congenital long QT syndrome.

OBJECTIVES: This study was performed to evaluate the frequency dependency of ventricular repolarization and the effect of epinephrine in patients with congenital long QT syndrome (LQTS). BACKGROUND: The efficacy of pacemakers in addition to antiadrenergic therapy in the treatment of congenital LQTS has been reported. METHODS: Monophasic action potentials were recorded from right and left ventricular endocardium during atrial pacing at heart rates from 70 to 140 beats/min at baseline and from 100 to 140 beats/min during epinephrine infusion (0.1 microgram/kg body weight per min) in 11 patients with congenital LQTS and 10 control patients. The response of monophasic action potential duration at 90% repolarization (MAPD90) and the dispersion of MAPD90 were examined. RESULTS: At baseline, both the MAPD90 and the dispersion of MAPD90 were significantly (p < 0.001) longer in the congenital LQTS group than the control group. The differences in these variables between the two groups significantly decreased (MAPD90: from 105 to 31 ms; dispersion of MAPD90: from 55 to 13 ms, p < 0.001) at heart rate was increased. Epinephrine prolonged the MAPD90 and increased the dispersion of MAPD90 significantly (p < 0.001) at all paced heart rates in the congenital LQTS group without frequency dependency but did not change in the control group. Thus, epinephrine increased the differences in these variables between the two groups. CONCLUSIONS: The repolarization abnormalities in congenital LQTS were attenuated by increasing the heart rate, which supported the efficacy of pacemaker therapy. However, during sympathetic stimulation, the effects of increased heart rate on these repolarization abnormalities were limited.

Effects of verapamil and propranolol on early afterdepolarizations and ventricular arrhythmias induced by epinephrine in congenital long QT syndrome.

OBJECTIVES: This study used monophasic action potentials to investigate the effects of verapamil and propranolol on epinephrine-induced repolarization abnormalities in congenital long QT syndrome. BACKGROUND: Early afterdepolarizations have been suggested to play a significant role in QT prolongation and ventricular arrhythmias in congenital long QT syndrome. Calcium channel blocking as well as beta-adrenergic blocking agents are reported to be effective in the management of this syndrome. METHODS: Monophasic action potentials from 2 to 4 sites were recorded simultaneously in eight patients with the long QT syndrome (22 sites) and in eight control patients (23 sites) and were obtained during constant atrial pacing 1) before epinephrine infusion; 2) during epinephrine infusion (0.1 microgram/kg body weight min); 3) after verapamil injection (0.1 mg/kg) during epinephrine infusion; and 4) after both propranolol (0.1 mg/kg) and verapamil injections. RESULTS: Early afterdepolarizations were recorded in two of the eight patients (2 of 22 sites) during the control state. During epinephrine infusion, early afterdepolarizations were recorded in six patients (six sites), and ventricular premature complexes were induced in three and torsade de pointes in one. Epinephrine prolonged 90% monophasic action potential duration from 348 +/- 48 (mean +/- SD) to 381 +/- 49 ms (22 sites, p < 0.0005) and increased the dispersion of action potential duration (difference between the longest and shortest action potential duration) from 36 +/- 20 to 64 +/- 34 ms (p < 0.005). Verapamil eliminated (two sites) or reduced (four sites) early afterdepolarizations and abolished ventricular premature complexes in two of the three patients as well as suppressing torsade de pointes. Verapamil shortened the action potential duration to 355 +/- 28 ms (p < 0.01 vs. epinephrine) and decreased the dispersion to 44 +/- 19 ms (p < 0.05 vs. epinephrine). Propranolol further eliminated (two sites) or reduced (two sites) early after depolarizations, abolished ventricular premature complexes in the remaining one patient and further shortened the action potential duration to 337 +/- 32 ms (p = 0.09 vs. verapamil). In the control patients, none of the early afterdepolarizations, ventricular arrhythmias or marked prolongations of action potential duration were induced by epinephrine, and neither verapamil nor propranolol changed repolarization variables. CONCLUSIONS: These results indicate that both verapamil and propranolol can improve repolarization abnormalities induced by epinephrine in congenital long QT syndrome.

Mode of onset of ventricular fibrillation in patients with Brugada syndrome detected by implantable cardioverter defibrillator therapy.

OBJECTIVES: We sought to demonstrate the mode of spontaneous onset of ventricular fibrillation (VF) in patients with Brugada syndrome. BACKGROUND: The electrophysiologic mechanisms of VF in Brugada syndrome have not been fully investigated. METHODS: Nineteen patients (all male, mean age 47 +/- 12 years) with Brugada syndrome were treated with an implantable cardioverter defibrillator (ICD). The implanted devices were capable of storing electrograms during an arrhythmic event. We investigated the mode of spontaneous onset of VF according to the electrocardiographic features during the episode of VF, which were obtained from stored electrograms of ICDs and/or electrocardiographic (ECG) monitoring. RESULTS: During a follow-up of 34.7 +/- 19.4 months (range 14 to 81 months), 46 episodes of spontaneous VF attacks were documented in 7/19 (37%) patients. The event-free period between ICD implantation and the first spontaneous occurrence of VF was 14.6 +/- 12.1 months (range 3.7 to 27.4 months). We investigated 33/46 episodes of VF, for which electrocardiographic features (10 to 20 s before and during VF) were obtained from ICDs and/or ECG monitoring in five patients. A total of 22/33 episodes of VF were preceded by premature ventricular contractions (PVCs), which were almost identical to the initiating PVCs of VF. Furthermore, in three patients who had multiple VF episodes, VF attacks were always initiated by the same respective PVC. The coupling interval of the initiating PVCs of VF was 388 +/- 28 ms. CONCLUSIONS: Spontaneous episodes of VF in patients with Brugada syndrome were triggered by specific PVCs. These findings may provide important insights into the pathophysiological mechanisms causing VF in Brugada syndrome.

Sympathetic stimulation produces a greater increase in both transmural and spatial dispersion of repolarization in LQT1 than LQT2 forms of congenital long QT syndrome.

OBJECTIVES: The study compared the influence of sympathetic stimulation on transmural and spatial dispersion of repolarization between LQT1 and LQT2 forms of congenital long QT sYndrome (LQTS). BACKGROUND: Cardiac events are more associated with sympathetic stimulation in LQT1 than in LQT2 or LQT3 syndrome. Experimental studies have suggested that the interval between Tpeak and Tend (Tp-e) in the electrocardiogram (ECG) reflects transmural dispersion of repolarization across the ventricular wall. METHODS: We recorded 87-lead body-surface ECGs before and after epinephrine infusion (0.1 microg/kg/min) in 13 LQT1, 6 LQT2, and 7 control patients. The Q-Tend (QT-e), Q-Tpeak (QT-p), and Tp-e were measured automatically from 87-lead ECGs, corrected by Bazett's method (QTc-e, QTc-p, Tcp-e), and averaged among all 87-leads and among 24-leads, which reflect the potential from the left ventricular free wall. As an index of spatial dispersion of repolarization, the dispersion of QTc-e (QTc-eD) and QTc-p (QTc-pD) were obtained among 87-leads and among 24-leads, and were defined as the interval between the maximum and the minimum of the QTc-e and the QTc-p, respectively. RESULTS: Epinephrine significantly increased the mean QTc-e but not the mean QTc-p, resulting in a significant increase in the mean Tcp-e in both LQT1 and LQT2, but not in control patients. The epinephrine-induced increases in the mean QTc-e and Tcp-e were larger in LQT1 than in LQT2, and were more pronounced when the averaged data were obtained from 24-leads than from 87-leads. Epinephrine increased the maximum QTc-e but not the minimum QTc-e, producing a significant increase in the QTc-eD in both LQT1 and LQT2 patients, but not in control patients. The increase in the QTc-eD was larger in LQT1 than in LQT2 patients. CONCLUSIONS: Our data suggest that sympathetic stimulation produces a greater increase in both transmural and spatial dispersion of repolarization in LQT1 than in LQT2 syndrome, and this may explain why LQT1 patients are more sensitive to sympathetic stimulation.

Morphological and functional changes in regenerated primary afferent fibres following mental and inferior alveolar nerve transection.

BACKGROUND: It is important to know the mechanisms underlying pain abnormalities associated with inferior alveolar nerve (IAN) regeneration in order to develop the appropriate treatment for orofacial neuropathic pain patients. However, peripheral mechanisms underlying orofacial pain abnormalities following IAN regeneration are not fully understood. METHODS: Head withdrawal threshold (HWT), jaw opening reflex (JOR) thresholds, single-fibre recordings of the regenerated mental nerve (MN) fibres, calcitonin gene-related peptide (CGRP), isolectin B4 (IB4), peripherin, neurofilament-200 (NF-200) and transient receptor potential vanilloid 1 (TRPV1) expression in trigeminal ganglion (TG) cells, and electron microscopic (EM) observations of the regenerated MN fibres were studied in MN- and IAN-transected (M-IANX) rats. RESULTS: HWT to mechanical or heat stimulation of the mental skin was significantly lower in M-IANX rats compared with sham rats. Mean conduction velocity of action potentials recorded from MN fibres (n = 124) was significantly slower in M-IANX rats compared with sham rats. The percentage of Fluoro-Gold (FG)-labelled CGRP-, peripherin- or TRPV1-immunoreactive (IR) cells was significantly larger in M-IANX rats compared with that of sham rats, whereas that of FG-labelled IB4- and NF-200-IR cells was significantly smaller in M-IANX rats compared with sham rats. Large-sized myelinated nerve fibres were rarely observed in M-IANX rats, whereas large-sized unmyelinated nerve fibres were frequently observed and were aggregated in the bundles at the distal portion of regenerated axons. CONCLUSIONS: These findings suggest that the demyelination of MN fibres following regeneration may be involved in peripheral sensitization, resulting in the orofacial neuropathic pain associated with trigeminal nerve injury.

Diagnostic value of recovery time measured by body surface mapping in patients with congenital long QT syndrome.

The QT interval of the resting 12-lead electrocardiogram is normal or borderline in some patients with congenital long QT syndrome (LQTS). Recently, several in vivo experimental studies have shown that the time of maximum dV/dt in the ST-T segment is correlated with the time of local ventricular recovery. The purpose of this study was to examine the value of the body surface recovery time measured by 87-lead body surface mapping for detecting LQTS. Body surface mapping and 12-lead electrocardiography were performed simultaneously in 18 patients with LQTS and 40 controls of similar age and sex. The recovery time (RT), that is, the interval between QRS onset and the time of maximum dV/dt in the ST-T segment, was measured automatically by computer from each of the 87 mapping leads, and the corrected RT (RTc) was calculated by Bazett's method. The QT interval was measured from each of the 12 standard electrocardiographic leads, and the corrected QT (QTc) interval was also calculated. The maximum RT and RTc, the minimum RT and RTc, and the RT and RTc dispersions (difference between maximum and minimum RT and RTc in each patient) were significantly longer in the LQTS group than in the control group. In addition, a maximum RT of 390 msec, a maximum RTc of 430 msec 1/2, an RT dispersion of 170 msec, and an RTc dispersion of 170 msec1/2 separated the 2 groups completely (i.e., no overlap). The maximum QT and QTc, the minimum QT and QTc, and the QT and QTc dispersions (difference between maximum and minimum QT and QTc in each patient) were also significantly longer in the LQTS group than in the control group. However, the maximum QTc was normal (< or = 440 msec1/2) or borderline (< or = 460 msec1/2) in 5 of the 18 LQTS patients, and none of these parameters clearly separated the 2 groups. These results suggest that measurement of RT by 87-lead body surface mapping is useful for diagnosing latent or borderline LQTS.

Bradycardia-induced abnormal QT prolongation in patients with complete atrioventricular block with torsades de pointes.

Fourteen patients with complete atrioventricular block with or without torsades de pointes (TdP) were included in this study. They were divided into 2 groups, 6 patients with TdP (TdP[+] group) and 8 patients without TdP (TdP[-] group). The patients were evaluated at 2 different periods, before (acute period) and after (chronic period) pacemaker implantation. In the acute period, the QRS and heart rate during the escape rhythm were not significantly different between the 2 groups; however, the QT and QTc intervals were significantly longer in the TdP(+) group than in the TdP(-) group: 753 +/- 57.5 vs 635 +/- 78.4 ms (p less than 0.01) and 585 +/- 44.8 vs 476 +/- 58.3 ms (p less than 0.01). In the chronic period (greater than 2 months after pacemaker implantation), we changed the pacemaker rate from 90 or 100 beats/min to 50 beats/min and examined the QT interval changes in relation to the heart rate. The QT interval in the TdP(+) group was significantly prolonged compared with the TdP(-) group when the pacing rate was decreased less than or equal to 60 beats/min: 551 +/- 40 vs 503 +/- 36 ms at 60 beats/min (p less than 0.05), and 700 +/- 46 vs 529 +/- 43 ms at 50 beats/min (p less than 0.001). Patients with complete atrioventricular block with TdP had a bradycardia-sensitive repolarization abnormality and this characteristic remained after pacemaker implantation. The critical heart rate that induced abnormal QT prolongation in the TdP(+) group was less than or equal to 60 beats/min.

Relation between the widening of the fragmented atrial activity zone and atrial fibrillation.

Fragmented electrical activity is often recorded by a local atrial electrogram in response to atrial extrastimuli. To assess the relation between fragmented activity and the spontaneous occurrence of atrial fibrillation or flutter (AFF), the fragmented activity zone was measured in 57 patients. The electrograms of the high right atrium, low right atrium and left atrium (through the coronary sinus) were recorded simultaneously during high right atrial stimulation. The fragmented activity zone was defined as the S1-S2 interval (S1 = stimulus of a basic beat, S2 = stimulus of a premature beat) during which a significant fragmented activity was recorded by a high right atrial electrogram after S2. Fifteen patients had neither sinoatrial disease nor atrial arrhythmias (Group I, controls), 16 had sick sinus syndrome (SSS) with a history of paroxysmal AFF (Group II), 14 had SSS without a history of paroxysmal AFF (Group III), and 12 had idiopathic paroxysmal AFF (Group IV). The fragmented activity zone was significantly wider in Group II (112 +/- 26 ms [mean +/- standard deviation], p less than 0.001), Group III (77 +/- 38 ms, p less than 0.001) and Group IV (86 +/- 19 ms, p less than 0.001) than in Group I (31 +/- 25 ms). Patients in Group II had a wider fragmented activity zone than those in Group III (p less than 0.01). Thus, the widening of the fragmented atrial activity zone is characteristic of AFF and may be a good index of a tendency to develop spontaneous AFF.

Arrhythmogenic right ventricular cardiomyopathy underlies syndrome of right bundle branch block, ST-segment elevation, and sudden death.

Right ventricular morphologic and/or histologic abnormalities were present in 5 of 6 Japanese men with the Brugada syndrome. Results indicate that arrhythmogenic right ventricular cardiomyopathy may underlie the cardiac manifestations in the Brugada syndrome.

Reverse use dependence of human ventricular repolarization by chronic oral sotalol in monophasic action potential recordings.

Reverse use dependence of action potential duration and effective refractory period by chronic oral sotalol was demonstrated by monophasic action potential recordings in the human ventricle. There were no changes of the QRS duration over the cycle length, indicating that sotalol had no sodium channel blocking effects.

Differentiation between late potentials of right ventricular and of left ventricular origin.

The aim of this study was to determine whether late potentials of right and left ventricular origin could be differentiated with the use of a signal-averaging technique. Nineteen patients with both late potentials and recurrent sustained ventricular tachycardia were divided into 2 groups according to the origin of their late potentials. Group I consisted of 10 patients with late potentials that originated from the right ventricle. Group II consisted of 9 patients with late potentials originating from the left ventricle. Signal-averaged electrocardiograms (Marquette Electronics MAC I unit) were recorded using 3 bipolar and 3 augmented unipolar leads (the electrode positions were V1, V5 and V6R) with a band-pass filter of 100 to 300 Hz. The augmented unipolar V5 lead (aV5) was used for left-side recording and the augmented unipolar V1 lead (aV1) was used for right-side recording. In group I, the mean maximal late potential amplitude was larger in lead aV1 than in lead aV5 (5.1 +/- 2.5 vs 3.7 +/- 1.8 microV, p less than 0.005) and the maximal late potential amplitude was larger in lead aV1 in all except 1 patient. In group II, however, the mean maximal late potential amplitude was smaller in lead aV1 than in lead aV5 (4.0 +/- 3.0 vs 5.7 +/- 3.2 microV, p less than 0.005) and the maximal late potential amplitude was smaller in lead aV1 in all patients. Thus, the origin of late potentials (right ventricular vs left ventricular origin) can be determined by comparing the maximal amplitudes of late potentials in the right- and left-sided leads. This method might be useful in determining ventricular tachycardia origins.

The stereoselective effects of bucolome on the pharmacokinetics and pharmacodynamics of racemic warfarin.

The objective of this study was to investigate the stereoselective influence of bucolome on the pharmacokinetics and pharmacodynamics of warfarin in Japanese inpatients with heart disease. Thirty patients were administered a fixed-maintenance dose of warfarin alone once a day for at least 7 days. The other 25 patients were concomitantly administered warfarin and a 300 mg dose of bucolome once a day, and blood samples were collected on days 1, 4, 7, 14, or 21 after administration of bucolome. Serum concentration of warfarin enantiomers was measured by a chiral reversed-phase HPLC-ultraviolet detection method. The PT-INR was used as a measure of the pharmacodynamic effect of warfarin. Coadministration of bucolome and warfarin had no effect on serum (R)-warfarin concentration and significantly increased serum (S)-warfarin concentration compared with warfarin alone. The PT-INR of warfarin alone was significantly lower with bucolome cotreatment. These results indicate that the augmented anticoagulant effect of warfarin by bucolome is due to inhibition of (S)-warfarin metabolism in vivo. When bucolome is added to a stabilized regimen of warfarin therapy, the dose of warfarin should be reduced by about 30% to 60%, and caution should be exercised during the first 7 days after coadministration of bucolome.

Implantation of octacalcium phosphate (OCP) in rat skull defects enhances bone repair.

Synthetic octacalcium phosphate (OCP) enhances bone formation if implanted into the subperiosteal region of murine bone. Such implanted OCP may be resorbed and replaced by bone with time. We hypothesized that OCP could be used as an effective bone substitute. To test this hypothesis, we designed the present study to investigate if bone repair in a rat skull defect is enhanced by the implantation of OCP. Rats were divided into two groups: OCP-treated animals and untreated controls. Six rats from each group were fixed at 4, 12, and 24 weeks after implantation. A full-thickness standardized trephine defect was made in the parietal bone, and synthetic OCP was implanted into the defect. After being examined radiographically, the specimens were decalcified and processed for histology. OCP implantation significantly promoted bone repair compared with the controls. A statistical analysis showed an increase in the area of radiopacity within the skull defect between week 4 and week 12. Histologically, bone was formed on the implanted OCP and along the defect margin at week 4. At week 12, the implanted OCP was surrounded by newly formed bone. At week 24, the defect was almost completely filled with bone. In the control, bone formation was observed only along the defect margin. The present results demonstrate that OCP could be used as an effective bone substitute.