Influence of rotational speed on torque/force generation and shaping ability during root canal instrumentation of extracted teeth with continuous rotation and optimum torque reverse motion.

AIM: To evaluate how different rotational speeds affect the torque/force generation and shaping ability of rotary root canal instrumentation using JIZAI (MANI, Utsunomiya, Japan) nickel-titanium instruments in continuous rotation and optimum torque reverse (OTR) motion. METHODOLOGY: Mesial root canals of extracted mandibular molars were instrumented up to size 25, 0.04 taper using JIZAI instruments, and anatomically matched canals were selected based on geometric features of the canal [canal volume (mm3 ), surface area (mm2 ), length, 15°-20° curvature and radius of curvature (4-8 mm)] after micro-computed tomographic scanning. An automated root canal instrumentation and torque/force analysing device was programmed to permit a simulated pecking motion (2 s downward and 1 s upward at 50 mm min-1 ). The selected canals were prepared with size 25, 0.06 taper JIZAI instruments using continuous rotation or OTR motion and further subdivided according to the rotational speed (300 or 500 rpm, n = 10 each). Real-time clockwise/counterclockwise torque and downward/upward force were recorded using a custom-made torque/force analysing device. Then, the registered pre- and post-operative micro-computed tomographic datasets were examined to evaluate the canal volume changes and centring ratios at 1, 3, 5 and 7 mm from the apical foramen. Data were analysed using two-way analysis of variance or the Kruskal-Wallis test and Mann-Whitney U test with Bonferroni correction (α = 5%). RESULTS: Maximum upward force and clockwise torque were significantly smaller in 500 rpm groups than in 300 rpm groups (P < .05); however, no significant difference was found between continuous rotation and OTR motion (P > .05). OTR motion developed higher maximum counterclockwise torque than continuous rotation (P < .05). Maximum downward force, canal volume changes and centring ratios were not significantly different among all groups (P > .05). There was no file fracture in any of the groups. CONCLUSIONS: Under laboratory conditions using JIZAI instruments, a rotational speed of 500 rpm generated significantly lower maximum screw-in forces and torque values than rotational speed of 300 rpm. Continuous rotation and OTR motion performed similarly in shaping the canals.

Root surface strain during canal shaping and its influence on apical microcrack development: a preliminary investigation.

AIM: To determine the root surface strain (RSS) generated during root canal shaping and its effects on apical microcrack development. METHODOLOGY: Twenty-five extracted human mandibular premolars were selected and decoronated. The teeth were instrumented with either the ProTaper (PT) or WaveOne (WO) (Dentsply Maillefer) NiTi rotary systems (n = 10 per group) or used as controls (n = 5). Instrumented root canals were enlarged to ProTaper F4 (size 40, 0.06 taper) or using WaveOne LARGE (size 40, 0.08 taper) instruments according to the manufacturer's instructions. An electrical strain gage (KFG02-120-C1-16, Kyowa Dengyo, Tokyo, Japan) was fixed on the proximal root surface and connected to a strain amplifier via a bridge box in order to measure RSS. During canal shaping, the strain output of the amplifier was recorded. The instantaneous RSS induced by each instrument and the maximum RSSs were determined. All teeth were then stained with contrast media and imaged with micro-computed tomography (micro-CT) at an isotropic resolution of 10 µm to detect microcracks. The mean maximum RSS values (microstrain) and mean number of microcracks recorded for both groups were tested for statistical significance using Mann-Whitney U-test. Presence/absence of microcracks in both groups was compared by chi-square tests. RESULTS: Increased baseline RSS from strain accumulation during canal shaping was observed, with similar maximum RSS (mean ± SD) for PT (416.6 ± 185.1 µstrain) and WO (398.2 ± 163.8 µstrain) (P = 0.94). The interevaluator reliability for microcrack detection using micro-CT had a kappa value of 0.998. Compared to the PT group, there was a trend for fewer samples with microcracks in the WO group (P = 0.051). On the micro-CT images, apical microcracks were detected in 20 PT and 11 WO samples (P = 0.10). The microcracks were observed in the buccolingual direction in all WO and 81% of PT samples. No vertical root fractures were found. The maximum RSS obtained during canal shaping was poorly correlated with the number of microcracks found (R(2)  = 0.093). CONCLUSIONS: Based on these preliminary data, canal shaping appears to cause apical microcracks regardless of the type of rotary instrument motion. Contrast-enhanced micro-CT was able to identify microcracks in roots.

Differential diagnosis of vertical root fractures using reconstructed three-dimensional models of bone defects.

OBJECTIVES: The purpose of this study was to evaluate the accuracy of diagnosing vertical root fractures (VRFs) by comparing the volume of bone defects in VRFs with those in non-VRFs on reconstructed three-dimensional (3D) models (TDMs) using CBCT. METHODS: 32 maxillary pre-molars and anterior teeth with radiolucent areas were evaluated on pre-operative CBCT images. Of the 32 teeth, 16 had a fractured root (VRF group) and 16 had a non-fractured root (non-VRF group). The radiolucent area of each tooth was traced in each dimension [mesiodistal, buccolingual and horizontal (the apicoincisal aspect)] by two observers, and 3D images were reconstructed with the Amira(®) software (Visage Imaging Inc., Richmond, Australia). The volume, V, of the TDM was divided into the coronal side and the periapical side at the horizontal slice through the apical foramen, and v was defined as the volume of the coronal side. The values of v/V were calculated for all cases. The Mann-Whitney U test was used to compare values between the VRF group and the non-VRF group (p < 0.05). A receiver operating characteristic (ROC) curve was constructed to select the optimal cut-point. RESULTS: There was a statistically significant difference in the value of v/V between the two groups (p < 0.05). With a cut-point derived from the ROC curve, and the sensitivity, specificity and accuracy of predicting the VRFs were 1.00, 0.75 and 0.88, respectively. CONCLUSIONS: Lesions resulting from VRFs can be distinguished from those of non-VRFs on 3D CBCT images with a high degree of accuracy, based on their different 3D shapes.

Nano-indentation testing of new and fractured nickel-titanium endodontic instruments.

AIM: To investigate the effect of cyclic fatigue on nickel-titanium (NiTi) endodontic instruments using a nano-indentation test. METHODOLOGY: Eight ProFile NiTi rotary instruments (size 30, taper 0.06; Dentsply Maillefer, Ballaigues, Switzerland) were tested using a cyclic fatigue set-up until fracture. The fractured instruments and eight new NiTi instruments of the same size and taper were used for a nano-indentation test on the internal surfaces of a NiTi instruments in the region just adjacent to their fractured edge (group I) and in the same region of the new group (group II), and the cutting part beside the shaft for both instruments [group III (fractured) and group IV (new)]. Data were statistically analyzed using one-way analysis of variance and Games-Howell post hoc test. The alpha-type error was set at 0.05. RESULTS: Significant differences in terms of hardness and elastic modulus for each group (P < 0.05) were found, with group I having the lowest mean values followed by group III. Additionally, standard deviations increased remarkably after failure, as represented by groups I and III. CONCLUSION: The nano-indentation technique can be applied to determine the performance and the failure mechanism of NiTi instruments. The fatigue process revealed a significant decrease in the hardness and elastic modulus of the NiTi instrument. As indicated by the low hardness, the fatigue process did not result in work hardening but rather work softening.

Initial fibroblast attachment to Erbium:YAG laser-irradiated dentine.

AIMS: To evaluate the effects of Erbium (Er):YAG laser irradiation on the morphology of resected dentine surfaces, and to investigate fibroblast attachment to laser-irradiated dentine surfaces. METHODOLOGY: Dentine blocks obtained from single-rooted human teeth were divided into the following groups after sterilization in an autoclave: (i) Laser group treated with Er:YAG laser irradiation (30 mJ per pulse, 10 pps, 60 s); (ii) L-MTAD group treated with laser irradiation as in (i) plus a mixture of doxycycline, tetracycline isomer and citric acid; (iii) RC-Prep group treated with EDTA gel or cream (RC-Prep) and (iv) Control group left untreated. After each treatment, the dentine blocks were incubated with NIH/3T3 fibroblasts cultured to subconfluency in Dulbecco's modified Eagle's medium supplemented with 10% foetal bovine serum and antibiotics. The number of attached cells amongst the groups was analysed statistically at the 5% significance level. The dentine surface morphologies and cell attachments were evaluated by counting assays, histological observations and scanning electron microscopy (SEM). RESULTS: The number of attached cells was significantly higher (P < 0.05) in the Laser group than in the RC-Prep and Control groups at 16 h. Dendritic cell extension of the fibroblasts was only observed in the Laser group at 8 h by SEM. In the histological analyses, significantly more attached cells were found on the dentine surfaces treated with laser irradiation. CONCLUSIONS: Er:YAG laser irradiation induced morphological alterations in dentine surfaces, which may improve the attachment of fibroblasts to dentine.

Heat treatment of nickel-titanium rotary endodontic instruments: effects on bending properties and shaping abilities.

AIM: To evaluate the bending properties and shaping abilities of nickel-titanium endodontic instruments processed by heat treatment. METHODOLOGY: K3 files were heated for 30 min at 400 °C (group 400), 450 °C (group 450) and 500 °C (group 500). Files that were not heat treated served as controls. A cantilever-bending test was used to evaluate changes in specimen flexibility caused by heat treatment. Curved root canal models were prepared. The times required for preparation, deformation and fracture were recorded. Pre- and postoperative images were superimposed. The amounts of resin removed from both the inner and the outer sides of the curvature in the apical 6 mm were determined. RESULTS: In the cantilever-bending test, load values of the control group and group 500 were higher than those of groups 400 and 450 at the elastic range (P<0.05). At the superelastic range, the bending load of the control group was the highest amongst all groups (P<0.05). Regarding shaping ability, in the control group, root canals at the apex were transported more to the outer side of the curvature compared with those of all heat-treated groups (P<0.05). Root canals of group 400 at 3 mm from the apex were transported less compared with those of other groups (P<0.05). No significant difference was found in working time amongst the groups. In group 450, there was no plastic deformation or fracture of the file. CONCLUSIONS: Heat treatment of files might improve their flexibility, making them more effective for preparation of curved canals.

RASSF7 negatively regulates pro-apoptotic JNK signaling by inhibiting the activity of phosphorylated-MKK7.

Members of the Ras-association domain family (RASSF) of proteins influence apoptosis and cell cycling but little is known about the mechanisms. Here, we show that RASSF7 interacts with N-Ras and mitogen-activated protein kinase kinase 7 (MKK7) to negatively regulate c-Jun N-terminal kinase (JNK) signaling. Stress-induced JNK activation and apoptosis were markedly enhanced in cells depleted of RASSF7 or N-Ras by RNAi knockdown. An interaction with RASSF7 promoted the phosphorylated state of MKK7 but inhibited this kinase's ability to activate JNK. RASSF7 required its RA domain for both interaction with GTP-bound N-Ras and the anti-apoptotic response to stress stimuli. Following prolonged stress, however, RASSF7's anti-apoptotic effect was eliminated because of degradation of RASSF7 protein via the ubiquitin-proteasome pathway. Our results indicate that RASSF7 acts in concert with N-Ras to constitute a stress-sensitive temporary mechanism of apoptotic regulation. With initial stress, RASSF7/N-Ras promotes cell survival by inhibiting the MKK7/JNK pathway. However, with prolonged stress, RASSF7 protein undergoes degradation that allows cell death signaling to proceed. Our findings may account for the association of elevated RASSF7 with tumorigenesis.

Phase transformation behaviour and bending property of twisted nickel-titanium endodontic instruments.

AIM: To investigate the relationship between phase transformation behaviour and bending property of nickel-titanium endodontic instruments manufactured by a twisting process. METHODOLOGY: The phase transformation behaviour and bending property of Twisted Files (TF; SybronEndo, Orange, CA, USA) and K3 (SybronEndo) with.06 taper and size 30 tip were investigated. K3 was used as control group. Phase transformation behaviour was estimated by differential scanning calorimetry (DSC). Transformation temperatures were calculated from the DSC curve. Bending load of the instruments was measured by cantilever-bending test at 37°C. Data were analysed by Student's t-test and Mann-Whitney U-test. RESULTS: The phase transformation temperatures of TF were significantly higher (P<0.05) than those of K3. The bending load values were significantly lower for TF than that of K3 (P<0.05), both in the elastic and super-elastic ranges. CONCLUSIONS: The new method of manufacturing NiTi instruments by twisting coupled with heat treatment might contribute to the increased phase transformation temperatures and superior flexibility.

Effect of heat treatment on transformation temperatures and bending properties of nickel-titanium endodontic instruments.

AIM: To investigate the effect of heat treatment on the bending properties of nickel-titanium endodontic instruments in relation to their transformation behaviour. METHODOLOGY: Nickel-titanium super-elastic alloy wire (1.00 mm Ø) was processed into a conical shape with a 0.30 mm diameter tip and 0.06 taper. The heat treatment temperature was set at 440 or 500 degrees C for a period of 10 or 30 min. Nonheat-treated specimens were used as controls. The phase transformation behaviour was examined using differential scanning calorimetry. A cantilever-bending test was used to evaluate the bending properties of the specimens. Data were analyzed by ANOVA and the Tukey-Kramer test (P = 0.05). RESULTS: The transformation temperature was higher for each heat treatment condition compared with the control. Two clear thermal peaks were observed for the heat treatment at 440 degrees C. The specimen heated at 440 degrees C for 30 min exhibited the highest temperatures for M(s) and A(f), with subsequently lower temperatures observed for specimens heated at 440 degrees C for 10 min, 500 degrees C for 30 min, 500 degrees C for 10 min, and control specimens. The sample heated at 440 degrees C for 30 min had the lowest bending load values (P < 0.05), both in the elastic range (0.5 mm deflection) and in the super-elastic range (2.0 mm deflection). The influence of heat treatment time was less than that of heat treatment temperature. CONCLUSIONS: Change in the transformation behaviour by heat treatment may be effective in increasing the flexibility of nickel-titanium endodontic instruments.

Changes of optical properties of retroreflector installed in LHD.

This article describes changes of optical properties of retroreflectors installed on the inner wall of the vacuum vessel of the Large Helical Device. They were made of stainless steel and were used for a CO(2) laser polarimeter. The reflectivity for a CO(2) laser beam dropped up to 40% after the start of glow discharge cleanings and main plasma experiments. Then it decreased gradually. The reflectivity in a wavelength range shorter than 10 mum decreased significantly through one experimental campaign (about 4 months). On the other hand the reflectivity in a wavelength range longer than 50 mum was larger than 70%. Decrease in the reflectivity in the central region of mirrors was more significant (the reflectivity for visible beams became almost zero) than that in the edge. The distribution of the reflectivity along the radial direction is expected to be related to the shape of the retroreflector. The parallelism of the reflected beam to an incident one also deteriorated. The changes in the polarization angle and in the ellipticity of reflected light polarization were not observed from the visible to the far infrared range.

Phase transformation behaviour and bending properties of hybrid nickel-titanium rotary endodontic instruments.

AIM: To investigate the bending properties of hybrid rotary nickel-titanium endodontic instruments in relation to their transformation behaviour. METHODOLOGY: Four types of nickel-titanium rotary endodontic instruments with different cross-sectional shapes (triangular-based and rectangular-based) and different heat treatment conditions (super-elastic type and hybrid type with shape memory effect) were selected to investigate bending properties and phase transformation behaviour. Bending load of the instruments was measured in a cantilever-bending test at 37 degrees C with the maximum deflection of 3.0 mm. A commercial rotary instrument, ProFile (PF; Dentsply Maillefer, Ballaigues, Switzerland) was used as a reference for the bending test. Phase transformation temperatures were calculated from the diagrams obtained from differential scanning calorimetry. Data were analysed by anova and Scheffe's test. RESULTS: The bending load values of the hybrid type that had undergone additional heat treatment at the tip were significantly lower (P < 0.05) than those of the super-elastic type with no additional heat treatment. The bending load values of rectangular-based cross-sectional shaped instruments were significantly lower (P < 0.05) than those of triangular-based cross-sectional shaped instruments. Phase transformation temperatures (M(s) and A(f) points) of the hybrid type were significantly higher (P < 0.05) than the super-elastic type. The M(f) and A(s) points of the tip part were significantly higher (P < 0.05) than those of the whole part of the hybrid instrument. CONCLUSIONS: Additional heat treatment of hybrid nickel-titanium instruments may be effective in increasing the flexibility of nickel-titanium rotary instruments.

Influence of phase transformation on the torsional and bending properties of nickel-titanium rotary endodontic instruments.

AIM: To investigate the relationship between the functional properties and the phase transformation of nickel-titanium endodontic instruments. METHODOLOGY: Five types of rotary nickel-titanium endodontic instruments with a 0.30 mm diameter tip (EndoWave, HERO 642, K3, ProFile.06, and ProTaper) were selected to investigate torsional and bending properties, and phase transformation behaviour. A torsional test was performed according to ISO publication 3630-1, and maximum torque and angular deflection at fracture were measured. Bending load of the instruments was measured in a cantilever-bending test at 37 degrees C with the maximum deflection of 4.0 mm. A stainless steel K-file was used for reference. Phase transformation behaviour was measured by differential scanning calorimetry (DSC). From the DSC curve, transformation temperatures were calculated. Data were analysed by anova and the Tukey-Kramer's test. RESULTS: The maximum torsional torque values of HERO, K3 and ProTaper were significantly higher (P < 0.05) than those of EndoWave, ProFile and K-file. The K-files had the lowest torque value. Angular deflection at fracture was significantly higher (P < 0.05) for K-files than that for any nickel-titanium instrument. The bending load values of HERO and K3 were significantly higher (P < 0.05) than those of EndoWave, ProFile, ProTaper and K-file. The K-files had the lowest load value, although residual deflection remained. The transformation temperatures of HERO and K3 were significantly lower (P < 0.05) than those of EndoWave, ProFile and ProTaper. CONCLUSIONS: The functional properties of nickel-titanium endodontic instruments, especially their flexible bending load level, were closely related to the transformation behaviour of the alloys.

Garrè's osteomyelitis managed by root canal treatment of a mandibular second molar: incorporation of computed tomography with 3D reconstruction in the diagnosis and monitoring of the disease.

AIM: To report the healing of Garrè's osteomyelitis involving a mandibular second molar following root canal treatment. SUMMARY: To describe the endodontic management of Garrè's osteomyelitis involving a mandibular second molar. In this case, computed tomography (CT) was used to evaluate the status of the periapical lesion. Five years after root canal treatment, the tooth and supporting tissues appeared healthy both clinically and radiographically and were functioning well. KEY LEARNING POINTS: Garrè's osteomyelitis of an adult can be managed by root canal treatment. Computed tomography could be used for diagnosis and treatment planning in endodontics.

Er:YAG laser modification of root canal dentine: influence of pulse duration, repetitive irradiation and water spray.

The aim of this study was to determine the effects of varying parameters of Er:YAG laser irradiation with and without water spray cooling on root canal dentine in vitro. After horizontally removing tooth crowns from extracted human teeth, roots were axially sectioned into thin slices, exposing the root canal surface. An Er:YAG laser delivered 10-30 J/cm(2) into a 0.4-mm diameter laser spot on the root canal surface. Single pulses of different lengths (80-280 micro s) were applied with and without water spray cooling/irrigation, and sequences of three pulses at a repetition rate of 30 Hz were applied at selected pulse parameters. The irradiated samples were investigated using both confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). At most irradiation conditions, the root canal dentine surface was ablated. Three-dimensional images from CLSM revealed that the cavity walls were not smooth. Depths of the cavities revealed significant differences between the cavities. No debris was observed at the surface of cavities at any irradiation condition. Strong melting and recrystallisation, or unusually flat surfaces with open dentinal tubules were obtained with sequences of three pulses without water cooling. CLSM is an effective tool for investigation of laser effects on root canal dentine. By varying the irradiation conditions, the Er:YAG laser can induce different modifications of root canal surface, which may be very interesting for root canal preparation.

Renal damage and salt-dependent hypertension in aged transgenic mice overexpressing endothelin-1.

The recent development of endothelin-1 (ET-1) antagonists and their potential use in the treatment of human disease raises questions as to the role of ET-1 in the pathophysiology of such cardiovascular ailments as hypertension, heart failure, renal failure and atherosclerosis. It is still unclear, for example, whether activation of an endogenous ET-1 system is itself the primary cause of any of these ailments. In that context, the phenotypic manifestations of chronic ET-1 overproduction may provide clues about the tissues and systems affected by ET-1. We therefore established two lines of transgenic mice overexpressing the ET-1 gene under the direction of its own promoter. These mice exhibited low body weight, diminished fur density and two- to fourfold increases in the ET-1 levels measured in plasma, heart, kidney and aorta. There were no apparent histological abnormalities in the visceral organs of young (8 weeks old) transgenic mice, nor was their blood pressure elevated. In aged (12 months old) transgenic mice, however, renal manifestations, including prominent interstitial fibrosis, renal cysts, glomerulosclerosis and narrowing of arterioles, were detected. These pathological changes were accompanied by decreased creatinine clearance, elevated urinary protein excretion and salt-dependent hypertension. It thus appears that mild, chronic overproduction of ET-1 does not primarily cause hypertension but triggers damaging changes in the kidney which lead to the susceptibility to salt-induced hypertension.

Vascular abnormalities and elevated blood pressure in mice lacking adrenomedullin gene.

BACKGROUND: Adrenomedullin (AM) is a vasodilating peptide involved in the regulation of circulatory homeostasis and in the pathophysiology of certain cardiovascular diseases. Levels of AM are markedly increased in the fetoplacental circulation during pregnancy, although its function there remains unknown. To clarify the physiological functions of AM, we chose a gene-targeting strategy in mice. METHODS AND RESULTS: Targeted null mutation of the AM gene is lethal in utero: the mortality rate among AM(-/-) embryos was >80% at E13.5. The most apparent abnormality in surviving AM(-/-) embryos at E13.5 to E14.0 was severe hemorrhage, readily observable under the skin and in visceral organs. Hemorrhage was not detectable at E12.5 to E13.0, although the yolk sac lacked well-developed vessels. Electron microscopic examination showed endothelial cells to be partially detached from the basement structure at E12.5 in vitelline vessels and hepatic capillaries, which allowed efflux of protoerythrocytes through the disrupted barrier. The basement membrane was not clearly recognizable in the aorta and cervical artery, and the endothelial cells stood out from the wall of the lumen, only partially adhering to the basement structure. AM(+/-) mice survived to adulthood but exhibited elevated blood pressures with diminished nitric oxide production. CONCLUSIONS: AM is indispensable for the vascular morphogenesis during embryonic development and for postnatal regulation of blood pressure by stimulating nitric oxide production.

Profiles of patients who control the doses of their antihypertensive drugs by self-monitoring of home blood pressure.

The present study profiled patients who control doses of antihypertensive drugs by themselves based on self-monitoring of their blood pressure (self-controllers). A total of 1,028 consecutive outpatients who were taking antihypertensive drugs and who were attending the cardiovascular outpatient clinic of our institute responded to a questionnaire in 1998. They were asked how often they measured their blood pressure, how often they missed taking their medication, and whether or not they had a chance to adjust the doses of antihypertensive drugs by themselves based on self-monitored blood pressure. The frequency of self-controlling of antihypertensive drugs was also examined in 918 patients on antihypertensive drugs in 1997. In 1997, 23 of 918 patients (2.5%) were self-controllers, and 26 of 1,028 patients (2.5%) were self-controllers in 1998. The frequency of home blood-pressure measurement was significantly greater in self-controllers than in the remaining patients (non self-controllers) (p<0.01). The prevalence of proteinuria was significantly less in the former than in the latter. Prior to the start of antihypertensive drugs, blood pressure was significantly lower for the self-controllers (154.4+/-3.8/96.4+/-1.4 mmHg) than for the non self-controllers (169.3+/-0.7/101.7+/-0.4 mmHg) (p<0.001). Clinically measured blood pressures did not differ significantly between the self-controllers and non self-controllers. Thus, about 2.5% of patients on antihypertensive drugs controlled their drug doses by themselves based on self-monitoring of their blood pressure. These patients were characterized by having a milder form of hypertension and by more frequent home blood-pressure measurement than non self-controllers.

Effect of fluvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on nitric oxide-induced hydroxyl radical generation in the rat heart.

We examined the effect of fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on the production of hydroxyl radical (*OH) generation via nitric oxide synthase (NOS) activation by an in vivo microdialysis technique. The microdialysis probe was implanted in the left ventricular myocardium of anesthetized rats and tissue was perfused with Ringer's solution through the microdialysis probe at a rate of 1 microl/min. Sodium salicylate in Ringer's solution (0.5 nmol/microl/min) was infused directly through a microdialysis probe to detect the generation of *OH. Induction of [K(+)](o) (70 mM) or tyramine (1 mM), significantly increased the formation of *OH trapped as 2,3-dihydroxybenzoic acid (DHBA). The application of N(G)-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor, significantly decreased the K(+) depolarization-induced *OH formation, but the effect of tyramine significantly increased the level of 2,3-DHBA. When fluvastatin (100 microM), an inhibitor of low-density lipoprotein (LDL) oxidation, was administered to L-NAME-pretreated animals, both KCl and tyramine failed to increase the level of 2,3-DHBA formation. The effect of fluvastatin may be unrelated to K(+) depolarization-induced *OH generation. To examine the effect of fluvastatin on ischemic/reperfused rat myocardium, the heart was subjected to myocardial ischemia for 15 min by occlusion of the left anterior descending coronary artery (LAD). When the heart was reperfused, a marked elevation of the level of 2,3-DHBA was observed. However, in the presence of fluvastatin (100 microM), the elevation of 2,3-DHBA was not observed in ischemia/reperfused rat heart. Fluvastatin, orally at a dose of 3 mg/kg/day for 4 weeks, significantly blunted the rise of serum creatine phosphokinase and improved the electrocardiogram 2 h after coronary occlusion. These results suggest that fluvastatin is associated with a cardioprotective effect due to the suppression of noradrenaline-induced *OH generation by inhibiting LDL oxidation in the heart.

[An autopsied case of marked cardiac hypertrophy due to multifactorial heart disease in an 85 year-old man who had been socially active].

An autopsied 85-year-old man had suffered from a mild form of diabetes mellitus since the age of 67 and had experienced the first episode of heart failure with arapid ventricular rate of atrial fibrillation at the age of 72. He had remained socially active until he died suddenly of ventricular fibrillation, although he had complications of aortic regurgitation at the age of 76 and later mitral regurgitation at the age of 80. Chest roentgenograms showed gradual increase in the cardiothoratic ratio which reached 68.1% at the final stage. Autopsy revealedmarked left ventricular hypertrophy with a heart weight of 580 g, degeneration ofaortic valves, thickening of mitralvalve cusps and moderate coronary atherosclerosis without ischemic myocardial lesions. There were no specific lesions suggestive of primary cardiomyopathies on microscopic observations and the lesions of both aortic and mitral valves were not significant enough to explain the clinical findings of aortic and mitral regurgitation. Because the pathological examination failed to identify a single disease which was responsible for the marked cardiachypertrophy, we eventually reached the conclusion that the cardiac hypertrophy developed based on a multifactorial heart disease.