Nutritional assessment using stable isotope ratios of carbon and nitrogen in the scalp hair of geriatric patients who received enteral and parenteral nutrition formulas.

BACKGROUND & AIMS: The δ13C and δ15N values in the scalp hair of geriatric patients in Japan who received the enteral or parenteral nutrition formula were measured to assess nutritional status. METHODS: The relations among δ13C, δ15N, calorie intake, BMI, albumin concentration, total cholesterol (T-CHO) and geriatric nutritional risk index (GNRI) in the patients were investigated. Furthermore, the enrichment of δ13C and δ15N from the nutrients to the hair was investigated. RESULTS: The δ13C values in the hair of patients who received enteral nutrition decreased with decreases in the calories received, while the δ15N values increased, suggesting malnutrition in some patients with a low calorie intake due to a negative nitrogen balance. The distribution of patients with a low calorie intake (below 20 kcal/kg/day) when δ13C was plotted against δ15N differed from that of control subjects, but the distribution of patients with a high calorie intake (above 20 kcal/kg/day) was similar to that of control subjects. No significant differences were observed in BMI, albumin concentration, T-CHO or GNRI between the low and high calorie groups. The enrichment of δ13C and δ15N from the enteral nutrients to the hair were inversely correlated with the δ13C and δ15N in the enteral nutrients. The enrichment levels of δ13C and δ15N tended to be higher and lower, respectively, in the high calorie group. On the other hand, the δ13C and δ15N values in the hair of patients who received parenteral nutrition were higher and lower than those in the control subjects and in the patients who received enteral nutrition, respectively, reflecting the higher δ13C and lower δ15N contents of the parenteral nutrients. CONCLUSIONS: The δ13C and δ15N values in the hair of patients who received enteral nutrition may be effective indicators for evaluating the long-term nutritional status of geriatric patients. A calorie intake of 20 kcal/kg/day may be a cut-off value for malnutrition in Japanese geriatric patients receiving enteral nutrition. However, caution is necessary when dealing with patients switching from parental nutrition as parenteral nutrition resulted in different changes in δ13C and δ15N. The enrichment levels of δ13C and δ15N from the enteral nutrients to the hair may be inversely correlated with the δ13C and δ15N values of enteral nutrients and vary according to the calorie intake.

Limited effect of testosterone treatment for erectile dysfunction caused by high-estrogen levels in rats.

Some studies suggest that high-estrogen levels lead to erectile dysfunction (ED); high-estrogen levels are known to decrease testosterone levels. However, no study has examined whether testosterone replacement can improve the ED induced by high-estrogen levels. We investigated the effects of testosterone on ED caused by high-estrogen levels in rats. Rats were distributed in the following groups: (1) control (vehicle for 2 weeks), (2) the estrogen-treated group (ES; estradiol (3 µg kg(-1) day(-1)) for 2 weeks), and (3) the estrogen- and testosterone-treated group (ES+TE; estradiol (3 µg kg(-1) day(-1)) and testosterone (3 mg kg(-1) day(-1)) for 2 weeks). We measured smooth muscle function via isometric tension and erectile function by measuring the intracavernosal pressure on cavernous nerve stimulation. In the ES group, the contraction of the corpus cavernosum smooth muscle increased in response to noradrenalin, and its relaxation decreased in response to the nitric oxide donor, sodium nitroprusside. Further, the erectile function was significantly decreased. In the ES+TE group, neither smooth muscle function nor erectile function was significantly improved. In conclusion, a high-estrogen milieu affected erectile function in rats, and testosterone treatment did not improve the ED caused by high-estrogen levels.

CAD/CAM systems available for the fabrication of crown and bridge restorations.

Dental biomaterials are widely used in all areas of routine dental practice. There are mainly two methods for their application. Firstly, dental biomaterials are placed into living tissues, such as teeth, to fill the space. Secondly, dental devices such as crown and bridge restorations and dentures are fabricated using various materials to restore the morphology and function of the dentition. Crown and bridge restorations are one of the main treatment methods used by general practitioners to achieve lifelike restoration of form and function. The recent introduction of osseointegrated implants has expanded the application of crown and bridge restorations for partially edentulous patients. Mechanical durability and precision fit are mandatory requirements for crowns and bridges. The development of various casting alloys and precise casting systems has contributed to the successful use of metal-based restorations. However, patient requests for more aesthetic and biologically 'safe' materials has led to an increased demand for metal-free restorations. There is also a growing demand to provide all-ceramic restorations more routinely. New materials such as highly sintered glass, polycrystalline alumina, zirconia based materials and adhesive monomers, will assist dentists to meet this demand. In addition, new fabrication systems combined with computer-assisted fabrication systems (dental CAD/CAM) and various networks are now available. Dental technology was centred on lost-wax casting technology but we now face a revolution in crown and bridge fabrication. This article reviews the history and recent status of dental CAD/CAM, the application of CAD/CAM fabricated tooth-coloured glass ceramic crowns, and the application of all-ceramic crowns and bridges using CAD/CAM fabricated zirconia based frameworks.

Identification of 11 novel mutations in USH2A among Japanese patients with Usher syndrome type 2.

Usher syndrome (USH) is an autosomal recessive disorder characterized by retinitis pigmentosa and hearing loss. USH type 2 (USH2) is the most common type of USH and is frequently caused by mutations in USH2A, which accounts for 74-90% of USH2 cases. This is the first study reporting the results of scanning for USH2A mutations in Japanese patients with USH2. In 8 of 10 unrelated patients, we identified 14 different mutations. Of these mutations, 11 were novel. Although the mutation spectrum that we identified differed from that for Caucasians, the incidence of mutations in USH2A was 80% for all patients tested, which is consistent with previous findings. Further, c.8559-2A>G was identified in four patients and accounted for 26.7% of mutated alleles; it is thus a frequent mutation in Japanese patients. Hence, mutation screening for c.8559-2A>G in USH2A may prove very effective for the early diagnosis of USH2.

Spectroscopic evidence for competing reconstructions in polar multilayers LaAlO3/LaVO3/LaAlO3.

We have studied the valence redistribution of V in LaAlO(3)/LaVO(3)/LaAlO(3) trilayers, which are composed of only polar layers grown on SrTiO3 (001) substrates, by core-level photoemission spectroscopy. We have found that the V valence is intermediate between V3+ and V4+ for thin LaAlO3 cap layers, decreases with increasing cap-layer thickness, and finally recovers the bulk value of V3+ at approximately 10 unit-cell thickness. In order to interpret these results, we propose that the atomic reconstruction of the polar LaAlO3 surface competes with the purely electronic V valence change so that the polar catastrophe is avoided at the cost of minimum energy.

Polar discontinuity doping of the LaVO_{3}/SrTiO_{3} interface.

We have investigated the transport properties of LaVO_{3}/SrTiO_{3} Mott-insulator-band-insulator heterointerfaces for various configurations. The (001)-oriented n-type VO_{2}/LaO/TiO_{2} polar discontinuity is conducting, exhibiting a LaVO3 thickness-dependent metal-insulator transition and low temperature anomalous Hall effect. The (001) p-type VO_{2}/SrO/TiO_{2} interface, formed by inserting a single layer of bulk metallic SrVO3 or SrO, drives the interface insulating. The (110) heterointerface is also insulating, indicating interface conduction arising from electronic reconstructions.

Nanometer scale electronic reconstruction at the interface between LaVO3 and LaVO4.

Electrons at interfaces, driven to minimize their free energy, are distributed differently than in bulk. This can be dramatic at interfaces involving heterovalent compounds. Here we profile an abrupt interface between V 3d2 LaVO3 and V 3d0 LaVO4 using electron energy loss spectroscopy. Although no bulk phase of LaVOx with a V 3d1 configuration exists, we find a nanometer-wide region of V 3d1 at the LaVO3/LaVO4 interface, rather than a mixture of V 3d0 and V 3d2. The two-dimensional sheet of 3d1 electrons is a prototypical electronic reconstruction at an interface between competing ground states.

Distribution and toxicity of mercury in rats after oral administration of mercury-contaminated whale red meat marketed for human consumption.

Toothed-whales and dolphins have been hunted for human consumption in Japan, and their muscles (red meats) are highly contaminated with mercury (Hg). We investigated the distribution and toxicity of Hg in rats after oral administration of Hg-contaminated whale red meat marketed for human consumption in Japan. Rats were orally administered the red meat homogenate for seven consecutive days (0.5 g red meat/kg-bw/day). The red meat administered to rats contained 81microg/g of total mercury (T-Hg) and 13.4 microg/g of methyl mercury (M-Hg). This dose corresponds to the human consumption of 210 g red meat/60 kg-bw/week, exceeding by about 29 times the provisional tolerable weekly intake of M-Hg at 1.6 microg/kg-bw/week set by JECFA [JECFA, 2003. Joint FAO/WHO expert committee on food additives. 61st meeting, Rome]. Twenty-four hours after the last administration, the distribution of T-Hg in rat organs and biochemical parameters in serum were analyzed. The administration of red meat significantly elevated T-Hg concentrations in the liver, kidney, erythrocytes, cerebral cortex and medulla oblongata from the control levels but did not elevate the T-Hg concentration in serum, showing the typical distribution pattern of M-Hg, not of inorganic Hg. The administration slightly but significantly increased GTP activity and P concentration and decreased BUN concentration in serum, although no abnormalities were observed in rat body weight gain and movement during the 7 days. The occasional consumption of red meat from small cetaceans, therefore, could pose a health problem for not only pregnant women but also for the general population.

Contamination by mercury and cadmium in the cetacean products from Japanese market.

Cetaceans hunted coastally in Japan include several species of odontocete (dolphins, porpoises and beaked whales), and fresh and frozen red meat and blubber, as well as boiled internal organs, such as liver, lung, kidney and small intestine, are still sold for human consumption. Furthermore, red meat and blubber products originating from mysticete minke whales caught in the Antarctic and Northern Pacific are also sold for human consumption. We surveyed mercury and cadmium contamination levels in boiled liver, lung, kidney and red meat products being marketed in Japanese retail outlets. We also analyzed the DNA of these products to obtain information concerning gender and species. Total mercury (T-Hg) and methyl mercury (M-Hg) contamination levels in all the cetacean products were markedly higher in odontocete species than in mysticete species, and slightly higher in females than in males. T-Hg contamination in the organs was seen in the following order: boiled liver>boiled kidney=boiled lung>red meat. In particular, T-Hg concentrations in the boiled liver were high enough to cause acute intoxication even from a single ingestion: the mean +/-SD (range) of T-Hg was 388+/-543 (0.12-1980) microg/wetg. In contrast, although M-Hg contamination in the liver was not markedly higher than that in other organs, M-Hg contamination was in the following order: boiled liver>odontocete red meat>boiled kidney>boiled lung. The contamination levels of T-Hg and M-Hg in odontocete red meat, the most popular whale product, were 8.94+/-13.3 and 5.44+/-5.72 microg/wetg, respectively. These averages exceeded the provisional permitted levels of T-Hg (0.4 microg/wetg) and M-Hg (0.3 microg/wetg) in marine foods set by the Japanese Ministry of Health, Labor and Welfare by 22 and 18 times, respectively, suggesting the possibility of chronic intoxication by T-Hg and M-Hg with frequent consumption of odontocete red meat. Cadmium contamination levels in boiled liver, kidney and lung were 8.59+/-12.0, 10.4+/-8.6 and 1.66+/-1.27 (microg/wetg), respectively.

Coxsackievirus and adenovirus receptor (CAR)-positive immature osteoblasts as targets of adenovirus-mediated gene transfer for fracture healing.

Adenovirus vectors are expected to be a powerful tool for gene therapy to treat severe fractures. Adenovirus invades cells through binding to the coxsackievirus and adenovirus receptor (CAR) on the cell membrane. CAR expression is low in normal adult animals, but it is induced on regenerating cells in some experimental models. We made a rib fracture model in mice and evaluated the histological changes and CAR mRNA expression by RT-PCR 1, 5, 10, 14, and 21 days after the fracture. CAR mRNA was expressed exclusively in the fractured ribs at each time point, but not in the normal ribs. We detected the CAR protein immunohistochemically in fibroblast-like cells in the fracture callus on days 10 and 14 after fracture. In situ hybridization showed that these fibroblast-like cells expressed mRNA of type I collagen and osteopontin, but not osteocalcin, defining the cells as immature osteoblasts. We then transferred small doses (10(4)-10(8) PFU) of lacZ-expressing adenovirus vector into immature osteoblasts on day 14. beta-galactosidase was detected only on the immature osteoblasts at every dose. Immature osteoblasts play an important role in the matrix replacement step in fracture healing. CAR-mediated gene transfer into immature osteoblasts can be reasonable for adenovirus-mediated treatment of fracture healing.

Mercury contamination in the red meat of whales and dolphins marketed for human consumption in Japan.

Cetacean products sold for human consumption in Japan originate from a wide range of whale, dolphin, and porpoise species caught off several areas of the Japan coast, Antarctic and North Pacific Oceans. We surveyed the total mercury (T-Hg) levels in red meat, the most popular cetacean products in Japan. We also analyzed the DNA of these to obtain information regarding species. According to the genetic analysis, the red meats originating from nine species of odontocete and six species of mystecete were sold in Japanese markets. T-Hg concentrations in all odontocete red meats (0.52-81.0 microg/wet g, n = 137) exceeded the provisional permitted level of T-Hg in marine foods set by the Japanese government (0.4 microg/wet g). The highest and second highest levels of T-Hg in the red meats were found in the false killer whale (81.0 microg/wet g) and striped dolphin (63.4 microg/wet g), respectively. These concentrations of T-Hg exceeded the permitted level of T-Hg by about 200 and 160 times, respectively, suggesting the possibility of chronic intoxication by methyl mercury due to frequent consumption of odontocete red meats. The T-Hg concentration levels were higher in odontocete species such as Baird's beaked whales and pilot whales caught off southern areas than those caught off northern areas, probably reflecting a higher Hg concentration in the seawater and/or their diet (squid and fish) in the southern area. On the other hand, T-Hg concentrations in all mystecete red meat samples except for one (0.01-0.54 microg/ wet g, n = 62) were below the permitted level of T-Hg, probably reflecting their lower trophic levels.

Protective effects of FK409, a novel nitric oxide donor, against postischemic myocardial dysfunction in guinea-pig hearts.

Effects of FK409 were investigated in perfused guinea-pig Langendorff hearts subjected to ischemia and reperfusion. Nitric oxide electrode, fluorometry, and 31P nuclear magnetic resonance imaging were used to monitor changes in cellular high-phosphorous energy and nitric oxide and Ca2+ content in the heart together with simultaneous recordings of left ventricular developed pressure. After cardioplegic arrest with St. Thomas' Hospital solution, normothermic (37 degrees C) global ischemia was induced for 40 min, and hearts were reperfused for 40 min. FK409 at 10(-8) M, which has a minimum inotropic effect on nonischemic hearts, was added to the cardioplegic solution. Treatment with FK409 reduced left ventricular developed pressure during and after ischemia and improved postischemic recovery of left ventricular developed pressure from 55.4% at 40 min of reperfusion in FK409-free hearts up to 80.4% in hearts treated with FK409 (p < 0.01). Flow rate at 1.5 min after treatment with the cardioplegic solution was 27.7 ml/min in hearts treated with FK409 compared with 21.2 ml/min in drug-free hearts (p < 0.01). Treatment with FK409 significantly effected preservation of tissue level of beta-adenosine triphosphate at the end of ischemia or reperfusion. During ischemia, arrested with the cardioplegic solution, intracellular Ca2+ accumulation and nitric oxide release were reduced. At the end of ischemia in FK409-treated hearts, nitric oxide release was 86% greater than in drug-free hearts without reference to the Ca2+ concentration. In cardiac surgery, normothermic arrested hearts are subject to damage by oxygen free radicals in reperfusion injury. Therefore, nitric oxide exogenously supplied by FK409 was responsible for the cardioprotective action, presumably by acting directly as an oxygen radical scavenger during reperfusion. A specific nitric oxide donor, like FK409, may have therapeutic use as a nitric oxide-mediated vasorelaxant and additional protective action for reperfusion-injury hearts.

Screening for synaptic defects revealed a locus involved in presynaptic and postsynaptic functions in Drosophila embryos.

To identify genes involved in synaptic functions, we screened lethal enhancer trap lines by monitoring synaptic activities at the neuromuscular junction in Drosophila embryos. It was found that MY7919, thus isolated, has moderate defects in both pre- and postsynaptic functions. The mean amplitudes of spontaneous as well as evoked synaptic currents were smaller than those in wild-type. The failure rate was higher than normal at any given concentration of external Ca(2+), indicating that presynaptic functions were impaired. In addition, the mean amplitude of miniature synaptic currents was smaller, and the unitary current amplitudes of junctional glutamate receptor channels were slightly but significantly smaller. Thus, postsynaptic functions were also altered. The gene was cloned and found to be identical to the previously reported apontic (=tracheae defective) locus, which is believed to be a transcription factor expressed in the central nervous system (CNS) as well as in the head, tracheae, and heart. Immunohistochemical analysis using an antiapontic antibody revealed that the protein is localized to nuclei. Null alleles of the apontic locus were obtained by imprecise excision of the enhancer trap vector. Synaptic activities in null mutants were not different from those of the original allele, even though null homozygotes had uncontracted ventral nerve cords and more severe behavioral phenotypes. The morphology of the neuromuscular junction of the null mutant was qualitatively similar to that of wild-type, with the presence of typical pre- and postsynaptic specializations, but with some suggestions of quantitative differences. This strategy for screening mutants with synaptic defects will reveal more genes directly or indirectly affecting synaptic transmission.

Late-onset form of lattice corneal dystrophy caused by leu527Arg mutation of the TGFBI gene.

PURPOSE: To report two Japanese patients who were clinically diagnosed with late-onset and sporadic lattice corneal dystrophy (LCD) in whom a Leu527Arg mutation in the TGFBI gene was found. METHODS: Molecular genetic analysis was performed on DNA extracted from peripheral leukocytes from the patients. Exons 4, 11, and 12 of the TGFBI gene were amplified by polymerase chain reaction and directly sequenced. Histopathologic study was performed on the corneal tissue obtained during deep lamellar keratoplasty (DLK) from one of the patients. RESULTS: Patient 1 was a 74-year-old man who noticed a visual disturbance at the age of 72 years. Deep stromal opacities with nodular deposits and thick lattice lines were observed only in the right cornea, and DLK was performed. Patient 2 was an 82-year-old man who had LCD (similar in appearance to that in patient 1) in both eyes without visual disturbance. Neither of the patients had a family history of corneal problems and had no episode of corneal erosion. A heterozygous single base-pair transition (CTG to CGG, leucine to arginin) was detected in codon 527 of the TGFBI gene in both patients. No mutation was found in codons 124, 501, 518, 546, or 555. Histopathologically, relatively large amyloid deposits in the deep corneal stroma and ribbons of amyloid deposits just beneath the Bowman's layer were observed in the corneal tissue of patient 1. CONCLUSIONS: Clinical features and pathologic findings of the late-onset form of LCD with an L527R mutation in the TGFBI gene were made clear.

Triple anterior chamber after full-thickness lamellar keratoplasty for lattice corneal dystrophy.

PURPOSE: To report a patient with lattice corneal dystrophy type I (LCDI) who developed a triple anterior chamber after full-thickness lamellar keratoplasty (LKP). METHODS: A 46-year-old woman underwent a full-thickness LKP in her right eye for visual disturbances caused by LCDI. Her visual acuity was 20/200 OD before surgery. A complete ophthalmic examination, including slit lamp biomicroscopy and optical coherence tomography (OCT), was performed before and after surgery. Molecular genetic analysis was performed on DNA extracted from the peripheral leukocytes. RESULTS: The surgery was performed uneventfully; however, extra spaces posterior to the graft, along with the severe graft edema, were observed to form a triple anterior chamber a few days after surgery. The extra spaces resolved in 3 weeks with no surgical treatment, and her visual acuity improved to 20/20 OD without correction 3 months after surgery. The triple anterior chamber was clearly demonstrated by OCT, but not by slit lamp biomicroscopy. A heterozygous single base-pair transition (CGC to TGC, arginin to cysteine) was detected in codon 124 of the TGFBIgene in the patient. CONCLUSION: The separation of the graft and the host's deep corneal tissue and a Descemet's membrane detachment in the host's cornea caused the triple anterior chamber. The Descemet's membrane detachment demonstrated the weak adhesion of the stroma and the Descemet's membrane, probably resulting from a dysfunction of the TGFBI protein caused by the mutation of the TGFBIgene. OCT is useful for the objective documentation of the posterior corneal region even with severe corneal edema.

Effects of SM-20550, a selective Na+-H+ exchange inhibitor, on the ion transport of myocardial mitochondria.

The effect of a novel Na+-H+ exchange inhibitor, SM-20550 [N-(aminoiminomethyl)-1,4-dimethyl-1H-indole-2-carboxamide methanesulfonate] (SM) on the ion transport of myocardial mitochondria was studied using ion fluorometry and superfusion techniques. Isolated mitochondria from the guinea-pig heart were pre-loaded with fluoroprobes of either BCECF AM for H+, SBFI AM for Na+ or fura-2 AM for Ca2+. Initially, the treated mitochondria were superfused with a normal medium (MOPS-buffer, pH 7.4, 24 degrees C), subsequently fluorometric experiments on the Na+, H+, Ca2+ mobilization across the mitochondrial membrane were performed. The intramitochondrial pH (pHm) was increased by the superfusion of Na+ at physiological cytosolic concentrations of 10 mM, indicating the existence of a Na+-H+ exchange in mitochondrial membranes. The Na+ induced elevation of pH was dose-dependently inhibited by SM 1 microM (delta pHm; 45% as drug-free 100%), and 10 microM (delta pHm; 70%), as observed in our experiments with the myocardial sarcolemmal membrane. The selective Na+-H+ exchange inhibitor SM reduced such pHm elevations more markedly than that of EIPA [5-(N-ethyl-N-isopropyl) amiloride]. The Na+-H+ exchange inhibitors, SM and EIPA suppressed the intramitochondrial Ca2+ elevation ([Ca2+]m) brought on by external Ca2+ concentration changes: The pretreatment with SM 1 microM, 10 microM and EIPA 10 microM reduced the [Ca2+]m influx by 28.3, 56.5 and 63%, respectively. Additionally, the [Ca2+]m elevation induced by acidification of the perfusate was reduced by the prior infusion of SM and EIPA. Pretreatment of mitochondria with SM or EIPA which had beneficial effects on the left ventricular developed pressure (LVDP) in the ischemia-reperfusion injury of Langendorff hearts, reduced the intramitochondrial Na+ and pHm levels, indicating interplay of the inhibitory mechanism of Ca2+-uptake into mitochondria coupled with Na+-H+ exchange. These findings suggested that protective effects of Na+-H+ exchange inhibitors on reperfused myocardium are due in part to the Ca2+-paradox at the mitochondria level.

Pathfinding analysis in a glia-less gcm mutant in Drosophila.

Many lines of evidence suggest that glial cells function as guide post cells for axonal pathfinding. However, due to the difficulty in completely eliminating glial cells during development, their functions in axonal pathfinding have not been critically evaluated. In Drosophila gcm mutant embryos, glial cells were genetically eliminated providing us with a unique opportunity to investigate glial functions in nervous system formation. We showed that even in the absence of glial cells the initial axonal extension of pioneer neurons was essentially normal. However, at later stages, axon bundle formation and pathfinding were disturbed in the absence of glial cells, and abnormal migration of glial cells led to misrouting of axons. This indicates that glial cells are required for correct pathfinding at later stages. We propose that glial cells function in a stage-specific manner; they are not required for the initial extension of pioneers but essential for the subsequent extension of pioneers and followers as well as axon bundle formation.

Protective effect of SM-20550, a selective Na+ - H+ exchange inhibitor, on ischemia-reperfusion-injured hearts.

The protective effects of Na+ - H+ exchange inhibitors SM-20550 (SM) and 5-(N-ethyl-N-isopropyl)-amiloride (EIPA) against ischemia-reperfusion injury were investigated in guinea pig Langendorff hearts. The changes in intracellular pH (pHi), high-energy phosphates, and biologic intracellular active ions ([Na+]i and [Ca2+]i) were regarded using the 31P-NMR and specific fluorescent signals from the heart tissues together with simultaneous recordings of the left ventricular developed pressure (LVDP). The recovery rate of LVDP from ischemia (40 min) by reperfusion was 36.8% in the control experiments, whereas in the presence of SM 10(-7) M, a gradual increase to 75.9% (55.5% with 10(-8) M), in contrast to EIPA (10(-7) M), 47.5% was observed. SM 10(-7) M restored the ATP level by 70% in 40-min reperfusion, which was already higher than the control in the latter half (20-40 min) of the ischemic period. The recovery rate of phosphocreatine by pretreatment of the heart with SM 10(-7) M was 75% in 40 min reperfusion. The pHi estimated from Pi/phosphocreatine chemical shift became highly acidic in ischemic heart so that SM 10(-7) M caused slight but significant pHi reduction from control pHi of 5.89 to 5.75. The level returned to pHi at around 7.38 during 30-40 min reperfusion, and the recovery was significantly greater than the control pHi of 7.24. The fura-2 Ca2+ or SBFI-Na+ signals during Langendorff ischemia heart increased, and rapidly returned to the control level after the reperfusion. SM suppressed the [Na+]i or [Ca2+]i elevation induced in the late stage during ischemia, resulting in LVDP restoration after reperfusion; Diastolic Ca2+ in the end period of ischemia, SM 10(-7) M 194% versus drug-free 220.7%. Na+: SM 10(-7) M 121.6% versus drug-free 128.0%. The present results suggest that the selective Na+ - H+ exchange inhibitor SM is promising as a potent and specific protective agent against ischemia-reperfusion injuries with Ca2+ overload induced via Na+ - H+, Na+ - Ca2+ exchange.