Breakfast consumption frequency is associated with grip strength in a population of healthy Japanese adults.

BACKGROUND AND AIMS: Several studies have reported that regular consumption of breakfast is associated with health benefits. However, only a few studies have examined the association between frequency of breakfast consumption and muscular function. Therefore, this study aims to investigate the association between frequency of breakfast consumption and muscle strength among apparently healthy Japanese adults. METHODS AND RESULTS: A cross-sectional study design was used. Between 2008 and 2011 in Sendai, Japan, 1415 Japanese adult employees (1069 men and 346 women) aged between 19 and 83 years participated in the study. Grip strength, as measured by a handheld digital dynamometer, was used as an indicator of muscle strength. Frequency of breakfast consumption during the previous month was assessed using a brief self-administered dietary history questionnaire, and the results were divided into three categories for analysis: low (≤2 days week⁻¹), middle (3-5 days week⁻¹) and high (≥6 days week⁻¹). Multivariate analysis was performed using analysis of covariance, with covariates mainly including socio-demographic, lifestyle-related and health-related factors. After adjusting for several potential confounders, grip strength was shown to be positively associated with breakfast consumption frequency (geometric means, 95% confidence interval (CI): low frequency, 36.2 (35.7-36.8) kg; middle frequency, 36.7 (36.0-37.5) kg; high frequency, 37.0 (36.6-37.5) kg; P for trend = 0.03). Grip strength per kilogramme body weight (kg kg⁻¹) was also positively associated with frequency of breakfast consumption (P for trend = 0.01). CONCLUSIONS: This cross-sectional study reveals a positive association between breakfast consumption frequency and muscle strength in apparently healthy adults.

Skin advanced glycation end-product accumulation is negatively associated with calcaneal osteo-sono assessment index among non-diabetic adult Japanese men.

UNLABELLED: This study aims to determine the relationship between advanced glycation end-product (AGE) accumulation in skin tissue and bone strength, assessed by quantitative ultrasound, among healthy adult Japanese men. The results of the study suggest that men with higher AGE accumulation in skin tissue have a lower osteo-sono assessment index. INTRODUCTION: AGE accumulate in bone collagen with age and diabetes and decrease the mechanical properties of bone. Although increased AGE levels are associated with fractures among diabetic patients and elderly women, it is unclear whether a relationship between increased AGE levels and bone strength is present in apparently healthy adult males. The aim of this study was to determine the relationship between AGE accumulation in tissue and the mechanical properties of bone among adult Japanese men, using quantitative ultrasound as a surrogate measure of the latter. METHODS: Skin autofluorescence (AF), which is a noninvasive method for measuring tissue AGEs, and osteo-sono assessment index (OSI), which is determined by quantitative ultrasound, were measured in 193 adult Japanese men (median age 43 years; interquartile range 37.0-55.0 years). RESULTS: Adjusted for age, BMI, calcium intake, physical activity, smoking status, and education level, log-transformed skin AF had a negative association with log-transformed OSI (ß = -0.218, P < 0.01). Adjusted geometric means (95% CI) for OSI across the tertiles of skin AF were 2.81 (2.75-2.87) for the lowest tertile, 2.81 (2.74-2.87) for the middle tertile, and 2.66 (2.61-2.73) for the highest tertile; thus, OSI for the highest skin AF appeared to be 5.0% lower than that for the lowest and middle skin AF tertiles (P < 0.01). CONCLUSION: Among apparently healthy adult Japanese men, those with higher skin AF had a lower OSI, indicating a relationship between AGE accumulation and bone strength. A long-term prospective study is required to clarify the causality.

Alpha 1-adrenoceptor activation mediates the infarct size-limiting effect of ischemic preconditioning through augmentation of 5'-nucleotidase activity.

We have reported that ischemic preconditioning may limit infarct size by increasing 5'-nucleotidase activity. The present study tested whether alpha 1-adrenoceptor stimulation in ischemic preconditioning mediates the infarct size-limiting effect through augmentation of 5'-nucleotidase activity. The coronary artery was occluded four times for 5 min separated by 5 min of reperfusion (ischemic preconditioning) in 82 dogs. Then the coronary artery was occluded for 90 min followed by 6 h of reperfusion. Infarct size normalized by risk area was smaller after ischemic preconditioning than in the control group (40.6 +/- 2.3 vs 6.7 +/- 2.0%, P < 0.001), even though no difference existed in endomyocardial collateral flow during ischemia (8.7 +/- 1.0 vs 8.9 +/- 1.0 ml/100 g per min). Ectosolic and cytosolic 5'-nucleotidase activity was increased after ischemic preconditioning. However, prazosin blunted the infarct size-limiting effect of ischemic preconditioning (infarct size: 42.8 +/- 3.7%). Intermittent alpha 1-adrenoceptor stimulation by methoxamine mimicked the increase in 5'-nucleotidase activity and the infarct size-limiting effect, which were abolished by alpha, beta,-methyleneadenosine 5'-diphosphate. Identical results were obtained in the conscious model (n = 20). Therefore, we conclude that increases in ectosolic 5'-nucleotidase activity due to alpha 1-adrenoceptor activation may contribute to the infarct size-limiting effect of ischemic preconditioning.

[Bronchial lipoma treated by surgical resection; report of a case].

We report a case of bronchial lipoma, which relapsed after endoscopic treatment, and was treated by surgical resection. An abnormal shadow on chest X-ray was noted at the annual medical checkup of a 44-year-old man. Chest computed tomography (CT) demonstrated a tumor in the right basal bronchus and linear opacity on the peripheral side of that tumor. Bronchoscopic examination demonstrated a smooth polipoid tumor occluding the right basal lobe bronchus. Bronchoscopic biopsy specimens were not sufficient for histological diagnosis. We performed endobronchial resection of the tumor using electrosurgical snare, but 2 months after endoscopic treatment, the tumor relapsed. We therefore performed right S(9+10) segmentectomy. The tumor was 11 x 9mm in size and the histological diagnosis was an endobronchial lipoma. More than 4 years after resection, the patient is alive without recurrence.

[Spontaneous pneumomediastinum].

We encountered 3 patients with spontaneous pneumomediastinum. The patients were a 14-year-old female, a 16-year-old male and an 18-year-old male. All 3 were previously healthy. They complained of chest pain or dyspnea. On admission, physical examination revealed subcutaneous emphysema. Chest computed tomography (CT) revealed pneumomediastinum and subcutaneous emphysema. All patients were treated with rest and all recovered in 7 to 9 days without any complication. Spontaneous pneumomediastinum is an uncommon, usually benign, self-limited disorder that usually occurs in young adults without any apparent precipitating factor or disease. Most patients require only conservative treatment.

Coronary vasoconstrictive effects of neuropeptide Y and their modulation by the ATP-sensitive potassium channel in anesthetized dogs.

OBJECTIVES: This study examined the coronary vasoconstrictive action of endogenous neuropeptide Y (NPY) during sympathetic nerve stimulation and its modulation by the adenosine triphosphate (ATP)-sensitive potassium (KATP) channel in vivo. BACKGROUND: Exogenous NPY was characterized by its potent vasoconstrictive effect. However, endogenous NPY has failed to show any vasoconstrictive activity in vivo. METHODS: We studied 70 anesthetized dogs with vagotomy under beta-adrenergic blockade. Ansae subclaviae stimulation and intracoronary administration of the neurotransmitters (NPY and norepinephrine) were done with or without alpha-adrenergic blockade, NPY antagonist BIBP3226 or KATP channel acting agents. We measured coronary vascular resistance (CVR) and the neurotransmitter levels in systemic arteries and the great cardiac vein, and the amount of overflow (venoarterial difference times myocardial blood flow). RESULTS: During nerve stimulation, NPY levels correlated significantly with CVR at the highest r value (r = 0.850, p < 0.0001) obtained for the venous level under alpha-blockade, but norepinephrine showed no correlation. Treatment with BIBP3226 abolished the correlation between NPY level and CVR under alpha-blockade. Without alpha-blockade, norepinephrine levels correlated significantly with CVR; however, NPY showed no correlation. The amount of NPY overflow during the stimulation was nearly 1,000-fold lower than norepinephrine overflow. Exogenous NPY had a 100-fold more potent coronary vasoconstrictive action than that of norepinephrine. The KATP channel antagonist glibenclamide enhanced vasoconstriction of NPY, and the agonist pinacidil suppressed it with a predominant effect in the subepicardial region. CONCLUSIONS: During sympathetic nerve stimulation, the vasoconstrictive actions of NPY are masked by norepinephrine under intact alpha-adrenoceptor conditions, manifest during alpha-blockade and modulated by KATP channel activity.

[Pulmonary thromboembolism after thoracoscopic pulmonary wedge resection; report of a case].

We encountered a case of acute pulmonary embolism after lung cancer surgery. The case was a 64-year-old female. She was admitted to our hospital with an abnormal shadow on chest X-ray. There was a past history of hypopituitarism medicated with steroids. Chest computed tomography (CT) demonstrated ground glass attenuation shadow measuring 10 mm in the left upper lobe. She underwent left thoracoscopic pulmonary wedge resection due to bronchioloalveolar cell carcinoma. Postoperatively, the patient suddenly complained of chest pain and dyspnea the day after surgery. Chest CT showed left and right pulmonary arterial thromboembolism. Thrombolytic and anticoagulation therapy with urokinase and heparin sodium were immediately started. Venography demonstrated thrombus located in the vein of the bilateral lower leg region. We inserted an inferior vena cava filter to prevent aggravation of pulmonary embolism. After 11 days, CT showed completed thrombolysis in the bilateral pulmonary artery. The patient was discharged on the 25th postoperative day, and has been followed with anticoagulation therapy.

Inhibitory effects of nicorandil on sympathetic coronary vasoconstriction.

OBJECTIVE: The aim was to investigate whether nicorandil suppresses the rise in coronary vascular resistance that occurs during stimulation of the sympathetic nerve supply to the heart and, if so, what are the mechanisms of action. METHODS: The effects of nicorandil on coronary vascular resistance during ventrolateral cardiac nerve stimulation and on the reactivity of the coronary vasculature to intracoronary infusion of noradrenaline or neuropeptide Y (NPY) were examined under beta receptor blockade. The effects of nicorandil on the overflow of noradrenaline and NPY during ansae subclaviae stimulation were compared with those in a control group and in a group treated with glyceryl trinitrate and N omega-nitro-L-arginine (L-NNA) under both alpha and beta receptor blockade with vagotomy. RESULTS: Intracoronary infusion of nicorandil decreased coronary vascular resistance prior to cardiac nerve stimulation, and during stimulation it suppressed the percentage increase in resistance from the prestimulation value. Nicorandil suppressed the reactivity of the coronary vasculature to exogenous noradrenaline and NPY. Intra-atrial infusion of nicorandil significantly reduced the overflow of NPY but not of noradrenaline during stimulation of the ansae subclaviae at 20 Hz. This suppressive effect was not observed in the glyceryl trinitrate + L-NNA group. CONCLUSIONS: Nicorandil reduces sympathetic coronary vasoconstriction by decreasing the reactivity of the vasculature to sympathetic neurotransmitters and by suppressing NPY overflow during cardiac sympathetic nerve stimulation. The suppressive action on NPY overflow is thought to be due to the opening of ATP sensitive potassium channels in the sympathetic nerve endings rather than to a glyceryl trinitrate-like action of nicorandil.

Radical radiotherapy for medically inoperable non-small cell lung cancer in clinical stage I: a retrospective analysis of 149 patients.

PURPOSE: In order to obtain the standard treatment results of medically inoperable non-small cell lung cancer (NSCLC) in Stage I in the post-CT scan era, a retrospective analysis of patients who were treated by radical radiotherapy was performed. METHODS AND MATERIALS: 149 cases treated between 1980 and 1989 were accumulated from ten large hospitals in Japan. All patients received a total dose of 55-75 Gy (mean 64.7 Gy) with conventional fractionation. For evaluation of treatment results, complete response (CR) rate, median survival period and long-termed survival rates were used. RESULTS: The median survival of the all cases was 27.2 months and the actuarial 3- and 5-year survival rates were 34.2% and 22.2%, respectively. CR was obtained in 57 cases (38%). The CR rate was strongly correlated with the long-term survival (5-year survival rate in CR group: 35.1% compared with PR + NC group: 14.1% (P < 0.0001)). The size of tumor was also of prognostic importance. In 116 patients who died within 5 years after treatment, 66 patients (57%) died of local tumor regrowth. CONCLUSION: Although the medically inoperable NSCLC patients in Stage I should be offered curative radiation therapy, development of some new steps to increase the CR rate and local control rate is urgently needed.

Lymphatic drainage of carbon particles injected into the pleural cavity of the monkey, as studied by video-assisted thoracoscopy and electron microscopy.

OBJECTIVES: The aim of this study was to clarify the dynamics of lymphatic drainage of the pleural cavity to understand the mechanism of malignant pleural effusion. METHODS: We injected carbon particles into the pleural cavity of monkeys subjected to general anesthesia. We then observed the parietal pleura with a video-assisted thoracoscope and scanning and transmission electron microscopes to examine the regions of the parietal pleura where the carbon particles had been absorbed. RESULTS: The video-assisted thoracoscope showed that the carbon particles had gone directly to the costal, mediastinal, and diaphragmatic pleura by 10 to 15 minutes after injection. From the scanning and transmission electron microscopes, we found that the parietal pleura in the costal and mediastinal regions consisted of 3 elements: a layer of small mesothelial cells, the macula cribriformis, and lymphatic lacunae. Stomata (3-5 microm in diameter) were found between the small mesothelial cells. The macula cribriformis was composed of densely packed collagen fibrils and had many foramina (3-10 microm in diameter). Intrapleurally injected carbon particles were carried into the lymphatic lacunae via the stomata and vesicles of the mesothelial cells and the foramina of the macula cribriformis. The lymphatic lacunae filled with carbon particles were richly distributed in both the anterior costal pleura and the mediastinal pleura. CONCLUSION: We suggest that the mesothelial stomata and the macula cribriformis are structures essential to the absorption of macromolecules and cellular elements from the pleural cavity into the lymphatic system.

Disseminated intravascular coagulation in chickens inoculated with Erysipelothrix rhusiopathiae.

In a first experiment, 28 specific pathogen-free chickens aged 3 weeks showed clinical signs 1 to 5 days after intramuscular inoculation with Erysipelothrix rhusiopathiae. Twelve of 28 birds died 2 to 4 days after inoculation. Macroscopically, the liver, spleen and kidneys were seen to be enlarged and congested. Histologically, fibrinous thrombus formation, seen in the hepatic sinusoids, renal glomerular capillaries and small pulmonary blood vessels, was a characteristic feature. In addition, the liver showed marked congestion, increase of mononuclear cells and heterophils in the sinusoids, hyperplasia of sinusoidal lining cells, and vacuolar changes in hepatic cells. The spleen showed fibrinous exudation of the lymphoid follicles and ellipsoids with lymphocytic depletion, and hyperplasia of ellipsoidal reticular cells. There was oedema, congestion and cellular infiltration in the interstitium of the kidney. The bursa of Fabricius and thymus showed marked lymphocytic depletion. In a second experiment, the blood chemical values (uric acid, glutamic-oxalacetic transaminase, lactate dehydrogenase and gamma-glutamyl transpeptidase) of birds inoculated intramuscularly with E. rhusiopathiae were significantly higher than those of uninfected controls. The blood prothrombin times and activated partial thromboplastin times of the inoculated group were significantly greater than those of the control group. The pathological and haematological findings demonstrated that E. rhusiopathiae induced disseminated intravascular coagulation in the chickens.

[A case of congenital partial pericardial defect and anomaly of phrenic nerve with cystic bronchiectasis].

Congenital partial pericardial defect is a rare anomaly that causes no symptoms and is often noticed by chance at autopsy or thoracotomy. During an operation on a patient with bronchiectasis, a partial pericardial defect and anomaly of left phrenic nerve were found incidently. A 58-year-old man complaining hemoptysis was referred to our hospital for surgical treatment of the left cystic bronchiectasis. During a thoracotomy, a partial pericardial defect was noticed. Moreover the left phrenic nerve could not be found within the operative field. We performed left pneumonectomy without repair of pericardial defect, and the patient had a satisfactory postoperative course. A relationship was suggested between congenital pericardial defect and the anomaly of the phrenic nerve.

[Clinical significance of regional cerebral blood volume and flow-to-volume ratio in ischemic cerebrovascular disease measured by SPECT].

Regional cerebral blood volume (rCBV) and flow-to-volume ratio (rCBF/rCBV) were evaluated for clinical significance in comparison to rCBF and findings in X-ray CT (XCT) and radionuclide (RNA) and contrast angiography (CAG). A total of 109 cases were studied within 90 days after cerebrovascular ischemic attack. CBV SPECT was performed following CBF SPECT with I-123-IMP and RNA with Tc-99m-RBC, and processed for subtraction of I-123 contamination fraction. CBF/CBV image was obtained as the count ratio of CBF to CBV image at the same slice-level. Parametric rCBV and rCBF/rCBV were estimated as the count ratio of the focus to the contralateral normal region of interest. Image findings were scored by visual judgement. Student's t-test was applied for statistical analysis with a significance level of p = 0.01. The rCBV-ratio was inversely proportional to rCBF/rCBV-ratio, and was different between the two groups with high and low score on flip-flop perfusion in RNA and among three groups with different postictal neurological course. The ratio was the highest for the group of improved course. The rCBF/rCBV-ratio was possibly correlated to rCBF-ratio, and was different between the two groups with high and low score on low density area in XCT, early perfusion in RNA and arterial stenosis in CAG. In the group of improved course, the ratio was different between the second and the third postictal week's duration. These results, therefore, suggest that rCBV-ratio reflects collateral perfusion, and is valuable for assessing postictal prognosis in cerebrovascular disease, and that rCBF/rCBV-ratio may reflect regional oxygen extraction fraction, and is valuable for speculating cerebral perfusion reserve.

Pinacidil but not nicorandil opens ATP-sensitive K+ channels and protects against simulated ischemia in rabbit myocytes.

It has been proposed that ischemic preconditioning involves the regulation of ATP-sensitive potassium (K(ATP)) channels. The evidence is based largely on the ability of certain K(ATP) channel modulators to modify the protection in the various models of preconditioning. This study has investigated how two K(ATP) channel openers, pinacidil and nicorandil, affect both membrane currents and viability in isolated and ischemic rabbit cardiomyocytes. We used the whole-cell recording technique and in separate experiments viability was assessed by exposure to these drugs during ischemia. Pinacidil (50 micromol/l) increased K(ATP) current approximately four-fold in isolated cardiomyocytes. This increase reversed rapidly after treatment with the K(ATP) channel blocker glibenclamide (200 nmol/l). After simulated ischemia, pinacidil protected cardiomyocytes (the area under cell-death curve was 29.5 +/- 1.1% x h) which was significantly less than that in control (46.9 +/- 2.0% x h). The protection from pinacidil could be completely eliminated by pretreatment with 10 microM glibenclamide (46.9 +/- 2.0% x h). In contrast, nicorandil (1 mmol/l), which opens K(ATP) channels in some tissues, caused no detectable effect on the K(ATP) current. Similarly, nicorandil did not produce cardioprotection. These results indicate that pinacidil and nicorandil have very different effects on rabbit cardiomyocyte K(ATP) channels. Furthermore, because protection correlated with the ability of the agent to open the channel, they support a role for K(ATP) channels in preconditioning.

Visualization of penetrating transmural arteries in situ by monochromatic synchrotron radiation.

BACKGROUND: Penetrating transmural arteries with a diameter of < 500 microns are considered to be a critical vascular component that causes a transmural variation of myocardial blood flow under various pathophysiological conditions. However, the conventional coronary angiographic system is not oriented to the visualization of such small arteries as these. METHODS AND RESULTS: We magnified and monochromatized the inherently narrow beam (3 mm along the vertical direction) of synchrotron radiation by using an asymmetrically cut silicon crystal with 311 reflecting planes to obtain a monochromatic x-ray with relatively large beam size (60 x 25 mm) and with an energy of just above (+130 eV) the K-absorption edge of the contrast materials (33.17 and 37.41 ke V for iodine and barium, respectively). We irradiated dogs or excised hearts with the monochromatic x-ray and obtained coronary angiograms using an image intensifier and video system with a spatial resolution of 170 microns. In the anesthetized dog experiments, we visualized the transmural penetrating arteries (5 to 15 mm in length) arising every 4 to 7 mm from the epicardial branch. Visualization of these arteries filled with heavy element-loaded microspheres (15 microns in diameter) in the excised-heart experiments, in which the monochromatic x-ray was irradiated to the hearts through a 10- to 20-cm acrylic plate, indicated that this system could be used for human patients, in whom body absorption of x-ray is substantial. CONCLUSIONS: Coronary angiogram by means of monochromatic x-ray is useful for a precise evaluation of coronary circulation, both in clinical setting and in physiological animal experiments.

Modulation of adrenergic coronary vasoconstriction via ATP-sensitive potassium channel.

We examined humoral and/or locally produced vasoactive factors involved in modulating sympathetic coronary vasoconstriction via the ATP-sensitive K (KATP) channel in 42 anesthetized dogs. Glibenclamide (30 micrograms.kg-1.min-1 ic or 0.6 mg.kg-1.min-1 left atrial injection) augmented coronary vascular resistance (CVR) at baseline and during cardiac sympathetic nerve stimulation (2-20 Hz), with a greater increase seen in the subepicardial region than in the subendocardial region both during beta-adrenergic receptor blockade and alpha- and beta-receptor blockade [P < 0.05 and P < 0.05 (n = 6 and 18 dogs), analysis of variance]. In contrast, pinacidil (10 micrograms.kg-1.min-1; n = 8 dogs) suppressed CVR. Glibenclamide enhanced CVR response to locally administered norepinephrine of 0.001-0.1 microgram.kg-1.min-1 (P < 0.05, analysis of covariance; n = 5 dogs) but did not enhance norepinephrine or neuropeptide Y overflow (n = 18 dogs). CVR was not modified by calcitonin gene-related peptide (CGRP) antagonist [CGRP-(8-37)], 8-phenyltheophylline, or N omega-nitro-L-arginine (n = 11 dogs). Thus sympathetic coronary vasoconstriction is modified by coronary vascular KATP channels with a transmural difference. However, CGRP, adenosine, and endothelial nitric oxide production are not involved in the modulation.

Local continuity of myocardial blood flow studied by monochromatic synchrotron radiation-excited x-ray fluorescence spectrometry.

We have developed a monochromatic synchrotron radiation-excited system for two-dimensional mapping of x-ray fluorescence evoked from heavy element-loaded microspheres, which can evaluate myocardial blood flow in small contiguous regions with a small methodological error: 10.8 +/- 2.4% of the average of difference of the dual flow for 7- to 10-mg myocardial tissue (4 dogs). The fractal D value obtained from the slope of the log relative dispersion-log mass plot was 1.21 +/- 0.08 for a voxel size of 7 to 1260 mg (5 dogs) and that for a voxel size of 2.5 to 40 mg (1.12 +/- 0.06) was smaller than that for a voxel size of 40 to 1280 mg (1.25 +/- 0.14, P < .05, ANOVA, 4 dogs). The distance-correlation coefficient relation for paired myocardial regions was attenuated (correlation analysis), and the correlation coefficients between the original grouping and the two aggregates of the adjacent regions were dissociated (extended correlation analysis) under reduction of coronary perfusion pressure (6 dogs). Suppression of myocardial contraction with lidocaine (3 dogs) and vasodilation with adenosine partly improved the distance-correlation coefficient relation under reduced coronary perfusion pressure. Thus, an x-ray fluorescence system designed for precise flow measurement shows that the fractal nature of local flow distribution can be extended into regions smaller than previously reported, that in these regions the flow becomes more homogeneous, and that the self similarity and continuity of local flow are attenuated by the reduction of coronary perfusion pressure and improved by contractile suppression and coronary vasodilation.

Role of activation of protein kinase C in the infarct size-limiting effect of ischemic preconditioning through activation of ecto-5'-nucleotidase.

BACKGROUND: We have reported previously that ischemic preconditioning limits infarct size by increasing ecto-5'-nucleotidase activity. Since we have also reported that protein kinase C activation increases ecto-5'-nucleotidase activity in rat cardiomyocytes, we tested whether activation of protein kinase C during ischemic preconditioning contributes to the infarct size-limiting effect through augmentation of ecto-5'-nucleotidase activity in the canine heart. METHODS AND RESULTS: The coronary artery was occluded four times for 5 minutes with alternating 5-minute periods of reperfusion (ischemic preconditioning). Then the coronary artery was occluded for 90 minutes followed by 6 hours of reperfusion. Infarct size, normalized by the risk area, in the ischemic preconditioning group was smaller than in the control group (42.6 +/- 3.6% in the control group versus 7.9 +/- 1.8% in the ischemic preconditioning group, P < .001). Myocardial ecto-5'-nucleotidase activity was increased after the ischemic preconditioning procedure but the increase in ecto-5'-nucleotidase was attenuated by inhibitors of protein kinase C (polymyxin B and GF109203X). Both polymyxin B and GF109203X blunted the infarct size-limiting effect of ischemic preconditioning (infarct size 33.1 +/- 6.9% and 35.1 +/- 6.4%, respectively). The infarct size-limiting effect was also blunted by an inhibitor of ecto-5'-nucleotidase. Transient administration of methoxamine mimicked the increase in ecto-5'-nucleotidase activity and the infarct size-limiting effect, both of which were abolished by inhibitors of protein kinase C. CONCLUSIONS: We conclude that activation of ecto-5'-nucleotidase and protein kinase C contributes to the infarct size-limiting effect of ischemic preconditioning.

Bidirectional effects of aminophylline on myocardial ischemia.

BACKGROUND: Aminophylline blocks adenosine receptors and increases levels of plasma catecholamines. We investigated the effect of aminophylline on myocardial ischemia by varying its severity and attempted to identify the mechanism by which aminophylline modulates myocardial ischemia in the canine model. METHODS AND RESULTS: In 41 open-chest dogs, the left anterior descending coronary artery was cannulated and perfused with blood through a bypass tube from the left carotid artery. When coronary blood flow (CBF) was reduced to 80% of the control, aminophylline increased fractional shortening (FS) from 11.0 +/- 0.4% to 18.5 +/- 1.7% (P < .05) and lactate extraction ratio (LER) from 7.5 +/- 0.1% to 13.6 +/- 1.0% (P < .01). The endocardial to epicardial flow ratio (Endo/Epi ratio) of regional myocardium was also increased. Release of adenosine was increased compared with the nonischemic condition (7 +/- 3 versus 28 +/- 5 pmol/mL). Prazosin, an alpha 1-adrenoceptor antagonist, blunted the aminophylline-induced improvement in contractile and metabolic function. Administration of 8-phenyltheophylline, a selective antagonist of adenosine receptors, did not increase FS, LER, or the Endo/Epi ratio when CBF was reduced to 80% of control. When CBF was reduced to 60% of control, aminophylline did not change the metabolic and contractile function. In contrast, when CBF was reduced to 33% of control, release of adenosine was increased markedly (243 +/- 19 pmol/mL) and aminophylline induced decreases in FS, LER, and Endo/Epi ratio similar to those observed with 8-phenyltheophylline. CONCLUSIONS: Aminophylline had opposite effects on the ischemic myocardium depending on the severity of ischemia. It improved mild ischemia but worsened severe ischemia. The beneficial effect of aminophylline was attributable to alpha 1-adrenoceptor stimulation, which improves endomyocardial flow in the ischemic myocardium. The deleterious effect was attributable to the aminophylline-induced blockade of adenosine receptors.