Association between constitution, medical history, axiography and postural control in women aged between 21 to 30 years.

The aim of this study was to determine association between constitutional, medical history and axiographic parameters with postural control parameters. Overall, 106 healthy female subjects aged between 21 and 30 years were measured. Data collection was carried out by completing a questionnaire on constitutional parameters, illnesses, accidents and medical/orthodontic therapies, as well as by axio- and posturographic measurements. Data were analyzed using correlations, pair comparisons and group comparisons. The significance level was set at p ≤ 0.05. The statistical evaluation showed significant correlations between sporting exercise and body sway in the sagittal direction (p ≤ 0.03), the BMI and the load on the forefoot/rear foot (p ≤ 0.01), the mouth opening and the load on the forefoot/rearfoot (p ≤ 0.01) and the presence of a deviation with the load on the left/right foot (p ≤ 0.01). The physical condition as well as the temporo-mandibular system are associated with the postural control in young women. Therefore, a holistic diagnosis and therapy will be supported by the present outcomes.

Attenuation of atherogenic apo B-48-dependent hyperlipidemia and high density lipoprotein remodeling induced by vitamin C and E combination and their beneficial effect on lethal ischemic heart disease in mice.

BACKGROUND AND AIMS: Atherosclerotic cardiovascular disease is highly prevalent and its underlying pathogenesis involves dyslipidemia including pro-atherogenic high density lipoprotein (HDL) remodeling. Vitamins C and E have been proposed as atheroprotective agents for cardiovascular disease management. However, their effects and benefits on high density lipoprotein function and remodeling are unknown. In this study, we evaluated the role of vitamin C and E on non HDL lipoproteins as well as HDL function and remodeling, along with their effects on inflammation/oxidation biomarkers and atherosclerosis in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice. METHODS AND RESULTS: Mice were pre-treated for 5 weeks before and during atherogenic diet feeding with vitamin C and E added to water and diet, respectively. Compared to a control group, combined vitamin C and E administration reduced serum total cholesterol and triglyceride levels by decreasing apo B-48-containing lipoproteins, remodeled HDL particles by reducing phospholipid as well as increasing PON1 and apo D content, and diminished PLTP activity and levels. Vitamin supplementation improved HDL antioxidant function and lowered serum TNF-α levels. Vitamin C and E combination attenuated atherogenesis and increased lifespan in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice. CONCLUSIONS: Vitamin C and E administration showed significant lipid metabolism regulating effects, including HDL remodeling and decreased levels of apoB-containing lipoproteins, in mice. In addition, this vitamin supplementation generated a cardioprotective effect in a murine model of severe and lethal atherosclerotic ischemic heart disease.

Attenuation of atherogenic apo B-48-dependent hyperlipidemia and high density lipoprotein remodeling induced by vitamin C and E combination and their beneficial effect on lethal ischemic heart disease in mice

BACKGROUND AND AIMS: Atherosclerotic cardiovascular disease is highly prevalent and its underlying pathogenesis involves dyslipidemia including pro-atherogenic high density lipoprotein (HDL) remodeling. Vitamins C and E have been proposed as atheroprotective agents for cardiovascular disease management. However, their effects and benefits on high density lipoprotein function and remodeling are unknown. In this study, we evaluated the role of vitamin C and E on non HDL lipoproteins as well as HDL function and remodeling, along with their effects on inflammation/ oxidation biomarkers and atherosclerosis in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice. METHODS AND RESULTS: Mice were pre-treated for 5 weeks before and during atherogenic diet feeding with vitamin C and E added to water and diet, respectively. Compared to a control group, combined vitamin C and E administration reduced serum total cholesterol and triglyceride levels by decreasing apo B-48-containing lipoproteins, remodeled HDL particles by reducing phospholipid as well as increasing PON1 and apo D content, and diminished PLTP activity and levels. Vitamin supplementation improved HDL antioxidant function and lowered serum TNF-α levels. Vitamin C and E combination attenuated atherogenesis and increased lifespan in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice. CONCLUSIONS: Vitamin C and E administration showed significant lipid metabolism regulating effects, including HDL remodeling and decreased levels of apoB-containing lipoproteins, in mice. In addition, this vitamin supplementation generated a cardioprotective effect in a murine model of severe and lethal atherosclerotic ischemic heart disease.

Recombinant Mal d 1 facilitates sublingual challenge tests of birch pollen-allergic patients with apple allergy.

It is still unclear whether allergen-specific immunotherapy (AIT) with birch pollen improves birch pollen-related food allergy. One reason for this may be the lack of standardized tests to assess clinical reactions to birch pollen-related foods, for example apple. We tested the applicability of recombinant (r) Mal d 1, the Bet v 1-homolog in apple, for oral challenge tests. Increasing concentrations of rMal d 1 in 0.9% NaCl were sublingually administered to 72 birch pollen-allergic patients with apple allergy. The dose of 1.6 µg induced oral allergy syndromes in 26.4%, 3.2 µg in 15.3%, 6.3 µg in 27.8%, 12.5 µg in 8.3%, 25 µg in 11.1%, and 50 µg in 4.2% of the patients. No severe reactions occurred. None of the patients reacted to 0.9% NaCl alone. Sublingual administration of 50 µg of rMal d 1 induced no reactions in three nonallergic individuals. Our approach allows straight forward, dose-defined sublingual challenge tests in a high number of birch pollen-allergic patients that inter alia can be applied to evaluate the therapeutic efficacy of birch pollen AIT on birch pollen-related food allergy.

Prostaglandin E2 in temporomandibular joint synovial fluid and its relation to pain and inflammatory disorders.

PURPOSE: The aim of this study was to investigate temporomandibular joint (TMJ) synovial fluid (SF) levels of prostaglandin E2 and its relation to general inflammatory activity and its influence on specific TMJ pain in patients with inflammatory TMJ disorders. PATIENTS AND METHODS: The study comprised 24 patients (30 joints) with inflammatory TMJ disorders and 4 healthy persons (6 joints). TMJ pain at rest, tenderness to palpation of the TMJ, and TMJ pressure pain threshold, as well as pain during joint movements (PM), were assessed. PGE2 levels were analyzed in synovial fluid samples (SF-PGE2) and blood plasma (P-PGE2). The erythrocyte sedimentation rate (B-ESR) as well as the serum levels of C-reactive protein (S-CRP) and antinuclear antibodies were determined. RESULTS: PGE2 was undetectable in the plasma and in the TMJ SF of the healthy persons. In the patients, PGE2 was detectable in 20 of the 30 (67%) SF samples. SF-PGE2 was significantly and positively correlated to PM in the patients. There were significant correlations between P-PGE2 and B-ESR as well as the S-CRP. CONCLUSIONS: This study shows that the synovial fluid in patients with TMJ inflammatory disorders frequently has a detectable level of PGE2 that is related to TMJ allodynia. The plasma levels of PGE2 seem to be related to the general inflammatory activity in these patients.

Prognostic value of the pilocarpine test to identify patients who may obtain long-term relief from xerostomia by acupuncture treatment.

BACKGROUND: Xerostomia (dry mouth) is a clinical symptom due to a number of factors, including Sjögren syndrome and radiation treatment to the head and neck region. It has been reported that acupuncture increases the salivary flow rate (SFR) in healthy subjects and in patients with xerostomia. A prognostic tool that would allow the care provider to identify patients who may respond to acupuncture treatment will aid in early intervention and thus lead to normalized SFR or relief of symptoms. OBJECTIVES: To determine the prognostic value of a test using pilocarpine chloride to identify those patients with xerostomia who may achieve a long-term increase in SFR in response to acupuncture. DESIGN: Cohort clinical study of 10 months' duration. SETTING: School of dentistry in a large, urban, research institute. PATIENTS: Thirty-two consecutive patients with xerostomia due to radiation treatment (n = 21) or Sjögren syndrome (n=11). INTERVENTION: Salivary flow rates for unstimulated whole saliva and paraffin-chewing stimulated whole saliva were measured before and after the administration of individualized doses of pilocarpine. All patients were then given 24 acupuncture treatments and followed up at 1 and 6 months. The effects of acupuncture treatment on SFR were recorded and response compared with the results of the pilocarpine test. MAIN OUTCOME MEASURES: Sensitivity, specificity, and positive and negative predictive value of the pilocarpine test based on changes in SFR, defined as a 20% increase or greater, following acupuncture treatment, compared with response to the pilocarpine test. RESULTS: At the 1-month follow-up, 18 (72%) of 25 patients with a positive pilocarpine test result had defined significant changes in SFR; 4 (67%) of 6 patients with a negative pilocarpine test result had an unchanged SFR. At this point, the sensitivity of the pilocarpine test was 0.90 (95% confidence interval [CI], 0.68-0.99) and the specificity was 0.36 (95% CI, 0.11-0.69). The positive predictive value was 0.72 (95% CI, 0.51-0.88), and the negative predictive value was 0.67 (95% CI, 0.22-0.96). At the 6-month follow-up, 17 (74%) of 23 patients with a positive pilocarpine test result had defined significant changes in SFR; 3 (60%) of 5 patients with a negative pilocarpine test result had an unchanged SFR. At this point, the sensitivity of the pilocarpine test was 0.89 (95% CI, 0.67-0.99), and the specificity was 0.33 (95% CI, 0.07-0.70). The positive predictive value was 0.74 (95% CI, 0.52-0.90), and the negative predictive value was 0.60 (95% CI, 0.15-0.95). CONCLUSION: The pilocarpine test was found to have a high sensitivity and good positive predictive value in identifying patients who may respond to acupuncture for the treatment of xerostomia.

Synovial fluid sampling from the temporomandibular joint: sample quality criteria and levels of interleukin-1 beta and serotonin.

The aims of this study were to compare two sets of quality criteria (SQC A and B) with respect to synovial fluid (SF) sampling and to present temporomandibular joint (TMJ) SF levels of IL-1 beta and 5-HT. The study comprised 310 TMJ SF samples from 12 healthy individuals (HI) and 59 patients with TMJ inflammatory disorders. Ten HI and 37 patients were selected for investigation of TMJ SF levels and samples were obtained by a push-and-pull method with quantification by vitamin B12. The SQC comprised aspirate weight (AW), dilution factor (DF), blood contamination and hemolysis. IL-1 beta and 5-HT levels did not differ between the samples that satisfied SQC A or B. The proportion of samples that satisfied SQC A was higher than for SQC B. Patients with polyarthritides had significantly higher TMJ SF concentrations of 5-HT and IL-1 beta than HL. In conclusion, there is a recovery of TMJ SF of 0.1-0.2 g with the method used and the criteria set with the highest success rate do not differ from the other one with respect to SF levels of IL-1 beta and 5-HT. This set of sample quality criteria comprised no hemolysis, no or only minor blood contamination, AW > 0.5 g and DF < 0.98. The higher SF levels in the diseased TMJ (polyarthritides) compared to the healthy joint with respect to 5-HT and IL-1 beta is of clinical diagnostic relevance and the presence of 5-HT or IL-1 beta in TMJ SF seems to indicate a pathological joint condition probably of an inflammatory nature.

Interleukin-1beta in synovial fluid from the arthritic temporomandibular joint and its relation to pain, mobility, and anterior open bite.

PURPOSE: The purpose of this study was to investigate whether interleukin-1beta in synovial fluid or blood plasma is involved in the development of pain or hyperalgesia of the temporomandibular joint (TMJ), as well as reduced mandibular mobility and anterior open bite. PATIENTS AND METHODS: Twenty-nine patients with TMJ arthritis and seven healthy subjects were studied. VAS measurement of TMJ tenderness on palpation of the TMJ (TDP), TMJ pressure pain threshold and tolerance level (PPTL), mandibular mobility, pain during joint movements, and degree of anterior open bite (AOB) were assessed. IL-1beta levels were analyzed in TMJ synovial fluid (SF-IL-1beta) and blood samples and correlated with the preceding factors. RESULTS: SF-IL-1beta showed significant positive correlations with VAS measurement of pain, TDP, and AOB and a negative correlation with PPTL. CONCLUSIONS: This study indicates that IL-1beta in the synovial fluid is associated with pain and hyperalgesia in the TMJ region as well as an anterior open bite. Concerning the latter condition, IL-1beta seems to be a warning signal of tissue destruction.

Substance P-associated increase of intra-articular temperature and pain threshold in the arthritic TMJ.

Neuropeptides are considered mediators and modulators of inflammatory joint disease. Substance P (SP) has been proposed as a mediator of pain, and its vasoactive properties are well documented. In this study, the presence of SP-like immunoreactivity in the synovial fluid was correlated to intra-articular temperature (IAT) and pain from the arthritic temporomandibular joint (TMJ) 3 to 5 weeks after one intra-articular injection of glucocorticosteroids. Eighteen TMJs were investigated for IAT and the presence of SP-like immunoreactivity in the synovial fluid in 12 patients with systemic inflammatory joint disease. After arthrocentesis, the aspirates were analyzed for SP-like immunoreactivity by means of competitive radio immunoassay. A visual analogue scale and an algometer determining the pressure pain threshold and tolerance level assessed arthritic pain and hyperalgesia in the TMJ. Our results indicate that SP-like immunoreactivity is associated with IAT and that increased concentrations of joint fluid SP-like immunoreactivity correspond to increased pain threshold and tolerance and a concomitantly decreased visual analogue scale. These findings suggest that SP is implicated in the vascular and nociceptive response of the arthritic joint and that SP, possibly assisted by the antinociceptive effect of local corticosteroids, has a modulatory role in arthritic pain and hyperalgesia.

Interleukin-1beta in plasma and synovial fluid in relation to radiographic changes in arthritic temporomandibular joints.

The aim of this study was to investigate the level of the cytokine IL-1beta in plasma and temporomandibular joint (TMJ) synovial fluid of patients with arthropathies, and to study the relation between IL-1beta levels of synovial fluid and plasma as well as radiographic changes of the TMJ. 31 patients with general disease, 14 with rheumatoid arthritis (RA) and 17 with various arthritides were included in the study. Synovial fluid and blood samples were collected, and an individualized tomography of the TMJ was performed. Detectable levels of IL-1beta were found in 5 out of 39 synovial fluids and in 10 out of 27 plasma samples. The presence of IL-1beta in both plasma and synovial fluid was more frequent in RA patients than in the non-RA group. The extension of radiographic erosion was significantly greater in joints with IL-1beta than in those without. Both the extension of erosion and grade of radiographic changes of the TMJ were greater in patients with detectable IL-1beta level of plasma than in patients without. Our study indicates that presence of IL-1beta in plasma and synovial fluid is related to radiographic changes of the TMJ.

Pain and synovial fluid concentration of serotonin in arthritic temporomandibular joints.

The aim of this study was to investigate the relation between serotonin in the synovial fluid (SF-5-HT) and pain of arthritic temporomandibular joints (TMJ). The study comprised 1 male and 10 female patients (22 TM joints) with bilateral TMJ pain or tenderness and a mean age of 42 years. The patients were studied regarding pain from the TMJ at rest and during mandibular movements as well as regarding pressure pain thresholds and tolerance levels over the TMJ. TMJ samples, obtained by saline washing of the joint, and blood serum samples were taken for measurement of the 5-HT content. There was a positive correlation between SF-5-HT and pain in the TMJ upon movement. Maximum voluntary mouth opening ability was negatively correlated to SF-5-HT. In conclusion, the results of this study indicate that 5-HT in the TMJ synovial fluid is related to pain perceived upon movement of the joint and to decreased mandibular mobility.

Effects of capsaicin in temporomandibular joint arthritis in rats.

Temporomandibular joint (TMJ) arthritis was induced in female Lewis rats by unilateral injection of a suspension of heat-killed Mycobacterium butyricum in paraffin oil into the TMJ. Control rats received paraffin oil by the same route. Arthritic and control rats were pretreated either with capsaicin or denervation of the mandibular branch of the trigeminal nerve. Tissues were collected for neuropeptide extraction and analysed by radioimmunoassay and reverse-phase high-performance liquid chromatography. In all groups, the levels of substance P-(SP), calcitonin gene-related peptide- (CGRP) and neuropeptide Y- (NPY) like immunoreactivity (LI) were higher in the trigeminal ganglia than in the TMJs. In control rats, capsaicin significantly lowered the levels of SP-LI in the trigeminal ganglia and TMJ, but not CGRP-LI and NPY-LI. In the arthritic rats, capsaicin pretreatment significantly lowered the SP-LI and CGRP-LI in the trigeminal ganglia and TMJ, but not the NPY-LI. In the trigeminal ganglia the unilateral denervation significantly lowered SP-LI in control rats, and in arthritic rats SP-LI and CGRP-LI. On the denervated side of the arthritic TMJ, NPY-LI, SP-LI and CGRP- LI were significantly lowered as compared to the arthritic control rats and to the contralateral side. In this rat model, pretreatment with capsaicin and surgical denervation decreased the neuropeptide content in the trigeminal ganglia and the TMJ. The results clearly demonstrate a close interaction between increased neuropeptide release from sensory and sympathetic neurones after induction of arthritis in the rat.

A model for the study of experimentally induced temporomandibular arthritis in rats: the effect of human recombinant interleukin-1 alpha on neuropeptide-like immunoreactivity.

To study the interaction between human recombinant interleukin-1 alpha and the nervous system, substance P-, neurokinin A-, calcitonin gene-related peptide-, and neuropeptide Y-like immunoreactivity in the cerebrospinal fluid, plasma, and temporomandibular joint (TMJ) perfusates of rats during acute experimental monarthritis were examined. The right TMJs of the experimental rats were injected with 0.01 mL of human recombinant interleukin-1 alpha. The right TMJs of control rats were injected with 0.01 mL of saline. Cerebrospinal fluid, plasma, and perfusates from the right TMJs were obtained at 2, 6, and 24 hours following injection, and neuropeptide-like immunoreactivity was analyzed by specific radioimmunoassays. Values of neuropeptide-like immunoreactivity for the experimental rats were compared with those of the control rats. In the experimental group, substance P-, neurokinin A-, and calcitonin gene-related peptide-like immunoreactivities were increased in cerebrospinal fluid compared to those of the control group. In plasma, no changes in neuropeptide-like immunoreactivities rose significantly in the TMJ perfusates. Most pronounced changes in neuropeptide Y-like immunoreactivity occurred intra-articularly in the TMJ perfusates. The results indicate that the contribution of the nervous system to human recombinant interleukin-1 alpha-induced monarthritis is most pronounced in the affected joint.

Determination of temporomandibular joint fluid concentrations using vitamin B12 as an internal standard.

The aim of the investigation was to test the reproducibility and accuracy of a new method to measure temporomandibular joint (TMJ) fluid concentrations of various substances by saline washing, using exogenous B12 as a marker. An in vitro test was first performed with glucose as a test substance. The difference between a B12-calculated and known standard concentration of glucose was very small. Saline washing of the TMJ was performed on 13 patients having signs of TMJ arthritis, and the aspirates obtained were analyzed for neuropeptide Y-like immunoreactivity (NPY-LI) and interleukin-1 beta (IL-1 beta). Vitamin B12 was mixed with the saline immediately before injection, and a sample of the aspirate was later compared photometrically with the injection solution. There were positive correlations between saline aspirate and joint fluid concentrations for NPY-LI and IL-1 beta, and the correlations were stronger for saline aspirates with high joint fluid content. This study shows that the method is reliable for measurement of joint fluid concentrations of various substances, such as NPY-LI and IL-1 beta.

Co-variation of neuropeptide Y, calcitonin gene-related peptide, substance P and neurokinin A in joint fluid from patients with temporomandibular joint arthritis.

Forty-one patients (37 female and four male) with signs and symptoms of temporomandibular joint arthritis, were separated into two diagnostic groups (group I: inflammatory; group II: degenerative/non-specific joint disease). They were examined clinically, fluid was aspirated from the joint with saline and venous blood samples were collected at the same time. The joint fluid and plasma samples were analysed for neuropeptide-like immunoreactivity, i.e. neuropeptide Y (NPY-LI), calcitonin gene-related peptide (CGRP-LI), substance P (SP-LI) and neurokinin A (NKA-LI), using competitive radioimmunoassays. The aim was to investigate any co-variation of the peptides in the joint fluid and plasma. In group I, the median values of peptide concentrations in joint fluid were SP-LI = 129, CGRP-LI = 75, NKA-LI = 36 and NPY-LI = 676 pmol/l and in group II, SP-LI = 52, CGRP-LI = 64, NKA-LI = 45 and NPY-LI = 318 pmol/l. There were no significant differences between the groups for peptide concentrations. In group I, all the neuropeptides were strongly correlated. In group II, SP-LI and NKA-LI were strongly correlated while CGRP-LI was weakly correlated with NPY-LI and NKA-LI. Multiple step-wise regression analysis showed that most of the variation in NPY-LI, CGRP-LI and SP-LI in group I was explained by NKA-LI, but the regression did not reach statistical significance in group II.

Effects of dietary fish oil on cardiovascular responsiveness to adrenergic agonists in spontaneously hypertensive rat.

To test the hypothesis that dietary fish oil supplementation decrease systolic blood pressure in hypertensive rats by modifying cardiovascular responsiveness to adrenergic agonists, spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) received either a corn or fish oil diet, 5% (g/kg) for 10 weeks. Mean aortic pressure was lower in fish oil treated (161 +/- 7 mm Hg (1 mmHg = 133.3 Pa)) than corn oil treated (191 +/- 6 mmHg) SHR. Although dietary fish oil supplementation decreased responsiveness to norepinephrine in isolated thoracic aorta from SHR, there was no change in cardiovascular responsiveness to the beta 1 agonist dobutamine or the alpha 1 agonist phenylephrine when these adrenergic agonists were administered in vivo. However, dietary fish oil did decrease the spontaneous basal tone in aorta from both SHR and WKY. This study provides further evidence that dietary fish oil lowers blood pressure in an animal model genetically predisposed to hypertension. However, the mechanism for this decrease in mean aortic pressure in vivo does not appear to be related to modification of cardiovascular responsiveness to alpha 1- or beta 1-adrenergic agonists and may be related to a decrease in basal vasomotor tone.

Relation between the intra-articular temperature of the temporomandibular joint and the presence of neuropeptide Y-like immunoreactivity in the joint fluid. A clinical study.

Arthritic temporomandibular joints were examined for the joint fluid content of neuropeptide Y-like immunoreactivity (NPY-LI) and the intra-articular temperature at two separate sessions. Sixteen patients (23 joints) with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and unspecific polyarthritis or monarthritis were investigated in this study. The intra-articular temperature ranged between 35.6 and 37.5 degrees C. The concentration of NPY-LI ranged between 72.1 and 4466.0 pmol/l and was above the normal plasma level in all patients. The intra-articular temperature was negatively correlated with the joint fluid concentration of NPY-LI. Moreover, patients with low intra-articular temperature and high concentration of NPY-LI had a shorter duration of TMJ symptoms than those with high intra-articular temperature and low concentration of NPY-LI.

Sustained postischemic cardiodepression following magnesium-diltiazem cardioplegia.

Magnesium-diltiazem cardioplegia was evaluated in the intact, perfused rat heart to determine whether the joint administration of these agents would adversely affect myocardial contractile and high-energy phosphate recovery following intermittent, normothermic global ischemic arrest. Sequential metabolic and functional analyses were performed on isolated perfused rat hearts during each phase of the experimental protocol: control (10 min), normoxic cardioplegia (10 min), intermittent global ischemic arrest (two 15-min periods separated by 2 min infusion of the normoxic cardioplegic perfusate), and normoxic postischemic control reperfusion (60 min). Four different cardioplegic solutions were evaluated: 30 mM KCl, 30 mM KCl with 2 mg diltiazem/liter, 20 mM MgCl2, and 20 mM MgCl2 with 2 mg diltiazem/liter. Myocardial phosphatic metabolite levels and intracellular pH were analyzed nondestructively in the intact hearts by phosphorus-31 NMR spectroscopy. Corresponding measurements of peak left intraventricular pressure, rate of peak pressure development (dP/dt), and contraction frequency were performed at the midpoint during each 5-min interval of 31P NMR signal averaging. Magnesium plus diltiazem-treated hearts were distinguished from all other groups by a marked delay in postischemic functional recovery consisting of a prolonged depression in contractility (34% of control, P less than 0.01) that persisted throughout the first 50 min of postischemic reperfusion. Diltiazem in combination with magnesium cardioplegia was detrimental to postischemic functional recovery, despite a rapid restoration of high-energy phosphate stores. The apparent adverse interactive effects of excess magnesium and diltiazem suggest that elective ischemic arrest with magnesium cardioplegia in combination with diltiazem may be contraindicated clinically. The mechanistic basis and drug specificity of this response require further clarification. The present findings appear to exclude ATP and PCr production, and structural causes as the basis for the observed aberrant functional recovery from global ischemia of magnesium plus diltiazem-arrested hearts.

31P NMR studies of the intact perfused rat heart: a novel analytical approach for determining functional-metabolic correlates, temporal relationships, and intracellular actions of cardiotoxic chemicals nondestructively in an intact organ model.

Intact hearts isolated from adult male, Sprague-Dawley rats were perfused under standardized conditions in an apparatus designed for use in a high-resolution nuclear magnetic resonance (NMR) spectrometer system. Myocardial phosphate metabolite concentrations (ATP, PCr, Pi, and phosphomonoesters) and intracellular pH were determined sequentially at timed intervals coincident with the functional assessments of the intact heart by phosphorus-31 (31P) NMR spectroscopic methods. Myocardial functional and metabolic parameters were unaffected by sustained control perfusion (2 hr). The negative inotropic actions of cadmium were associated with significant changes in the chemical environment of inorganic phosphate (Pi) within the cells. This initial cellular response to cadmium, which correlated with the onset and magnitude of the contractile disturbances, appeared to represent the formation of an acidic, intracellular Pi pool (pH, 6.0). This pH compartment reached a steady state during the period in which maximal changes in contractile function were manifested, and before cellular ATP and PCr concentrations were altered. These findings are consistent with the interpretation that the functional deficits caused by cadmium originated primarily from changes in the chemical environment experienced by intracellular metabolites, rather than changes in the amounts of cellular high energy substrates. In contrast, the time-dependent negative inotropic effects of arsenate were proportional to the loss of cellular ATP stores. Intracellular pH was not affected in these hearts. A distinctive metabolic finding associated with the cardiotoxicity of arsenate was the time-dependent accumulation of previously undetected phosphate metabolites in the arsenate-treated hearts. Efforts to chemically identify these metabolites proved inconclusive; however, existing evidence suggests the possibility that these phosphorus-containing compounds may be arsenophosphate derivatives of naturally occurring cellular metabolites. The present findings provide experimental evidence demonstrating that toxicologic assessments in an intact organ model are feasible using whole organ 31P NMR spectroscopic methods and that meaningful, new insights regarding the biochemical mechanisms responsible for the cardiotoxic actions of xenobiotic agents can be obtained by this analytical approach.

Phosphorus nuclear magnetic resonance and ocular metabolism.

Phosphorus (31P) nuclear magnetic resonance (NMR) represents a noninvasive technique for the assessment of ocular metabolism. The measurement of a spectrum of phosphorus-containing metabolites (e.g., phosphorylated sugars and ATP), including a number of heretofore uncharacterized metabolites, can be made with a single analysis. In addition to quantitating phosphatic metabolites, 31P NMR can be employed to monitor (1) the rate of metabolic change in a specific biochemical reaction via T1 and T2 relaxation times, and (2) the rate of change in the concentration of a particular metabolite. Several calculations indicating tissue energy status (health) can be made using quantitative spectroscopic information including: the phosphorylation potential, the energy charge of the adenylate system, and the 31P spectral modulus. Tissue pH can be determined as a function of shift in 31P NMR signals. 31P NMR techniques have both research and diagnostic applications in ophthalmology since potentially it provides a noninvasive method to analyze ocular tissues metabolically and detect subtle biochemical changes that precede overt manifestation of disease states. Such detection may allow for early and more effective therapeutic intervention of disease. Furthermore, the noninvasive quality of NMR spectroscopy will permit continual evaluation of therapy.