Whole-body MRI: a powerful alternative to bone scan for bone marrow staging without radiation and gadolinium enhancer.

PURPOSE: Whole-body magnetic resonance imaging (WB-MRI) is a radiation-free alternative to the 99mTc-HDP bone scan (BS) for the detection of bone metastasis. The major drawback is the long examination time and application of gadolinium enhancer. The aim of this study is to analyze (i) the performance of WB-MRI versus the BS and (ii) the diagnostic benefit of gadolinium (WB-MRI + Gd) compared to a non-enhanced protocol (NE WB-MRI). METHODS AND MATERIALS: 1256 eligible WB-MRI scans were analyzed retrospectively with a single inclusion criterion, a clinical 12-month follow-up or a biopsy as ground truth. N = 285 patients received both a WB-MRI and a BS within 12 months. All the patients were imaged with a coronal T1w and a STIR, and n = 528 (42%) received an additional T1w-mDixon with gadoteridol (0.1 mmol Gd-DTPA/kg). RESULTS: From 1256 eligible patients, n = 884 (70%) had breast cancer as a primary disease, n = 101(8%) prostate cancer, and n = 77(6%) lung cancer. The sensitivity (Se) and negative predictive value (NPV) of the WB-MRI was 98/99%, significantly higher compared to BS with 82/89%, P < 0.001 Mc Nemar's test. The specificity (Spe) and positive predictive value (PPV) of the WB-MRI and BS was 85/82% and 91/86%, respectively. The interobserver agreement between WB-MRI and BS was 71%, Cohen's kappa 0.42. Analysis of the added diagnostic value of gadolinium revealed Se/Spe/PPV/NPV of 98/93/92/98% for the NE WB-MRI and 99/93/85/100% for the WM-MRI + Gd, P > 0.05 binary logistic regression with Fischer's exact test. CONCLUSION: WB-MRI exceeds the sensitivity of BS without compromising the specificity, even after omitting the gadolinium enhancer.

The clinical significance of an incidentally detected open internal inguinal ring.

INTRODUCTION AND OBJECTIVE: An open internal inguinal ring (IIR) may be discovered incidentally either in the context of correcting pathology involving the contralateral side or at the time of surgical exploration for reasons unrelated to a patent processus vaginalis (PPV). The aim of this study is to determine the evolution of an incidentally encountered open IIR in patients undergoing laparoscopy for reasons not associated with unilateral inguinal hernia or cryptorchidism. MATERIALS AND METHODS: The authors conducted a prospective study of all patients who underwent laparoscopic surgery in the department of pediatric surgery at Agios Loukas hospital between 2004 and 2013 for various indications. Patients operated for inguinal hernia and cryptorchidism were excluded. During this period, 572 patients underwent laparoscopy for reasons not related to PPV. The median age at time of initial laparoscopy was 9,4 years (range 2 days-16 years). The IIRs were always inspected. No attempt was made to repair the open IIRs, as they were asymptomatic. Parents were informed after the operation, and instructions were given to inform us, in case that inguinal hernia symptoms manifested. The duration of the follow-up was 4 years. RESULTS: Among these 572 patients, 39 patients with 44 open IIRs were found (6,82%). From the 39 patients, 35 were male and four were female; 22 had a right open IIR, 12 had a left one, and five of them a bilateral open IIR. The median age was 7,82 years (3-14 years). Four patients were lost during follow-up. Of the remaining 35 patients with 40 open IIRs, four developed an inguinal hernia (11,43%) and were operated on with laparoscopically assisted (subcutaneous endoscopically assisted ligation [SEAL]) technique at the time of diagnosis. The study results are demonstrated on Fig. 1. DISCUSSION: The percentage of an incidentally discovered open IIR in this study is lower in comparison with studies including patients with PPV pathologies. There is a possibility, in those patients, of underlying pathology which can affect both sides. It is also lower in comparison with previous studies including younger patients. However, gender and side predominance is in accordance with most published studies. In this study group, the possibility of developing a symptomatic hernia from an asymptomatic open IIR is rather small. CONCLUSIONS: An incidentally discovered open IIR in patients without symptoms, excluding those with contralateral inguinal hernias or cryptorchidism, has relatively low chance of developing an inguinal hernia. Thus, the authors support the strategy of close follow-up in these patients.

Mucoceles of the lesser salivary glands in neonates demonstrate a particular clinicopathological pattern and mandate urgent management.

Mucoceles of the lesser salivary glands are common benign lesions affecting all ages, most commonly appearing on the lower lip. However, mucoceles in neonates demonstrate a different clinicopathological pattern than in older children or adults and mandate urgent management. We present a case of a large mucocele on the tongue of a neonate, which impaired feeding and could block the airway. The lesion was resected on the 3rd day of life. We describe a surgical technique that facilitates this procedure. Our literature review revealed 13 neonatal lesser salivary gland mucocele cases, 7 of which were located on the tongue. All tongue cysts were large, impaired feeding and sometimes blocked the airway. Early treatment is usually imperative. Inclusion cysts outnumbered extravasation cysts. Prenatal diagnosis is important in order to arrange delivery in an organized center. Resection is the preferable procedure.

Impaired stimulation of glucose transport in cardiac myocytes exposed to very low-density lipoproteins.

We recently observed that free fatty acids impair the stimulation of glucose transport into cardiomyocytes in response to either insulin or metabolic stress. In vivo, fatty acids for the myocardium are mostly obtained from triglyceride-rich lipoproteins (chylomicrons and Very Low-Density Lipoproteins). We therefore determined whether exposure of cardiac myocytes to VLDL resulted in impaired basal and stimulated glucose transport. Primary adult rat cardiac myocytes were chronically exposed to VLDL before glucose uptake was measured in response to insulin or metabolic stress, provoked by the mitochondrial ATP synthase inhibitor oligomycin. Exposure of cardiac myocytes to VLDL reduced both insulin-and oligomycin-stimulated glucose uptake. The reduction of glucose uptake was associated with a moderately reduced tyrosine phosphorylation of the insulin receptor. No reduction of the phosphorylation of the downstream effectors of insulin signaling Akt and AS160 was however observed. Similarly only a modest reduction of the activating phosphorylation of the AMP-activated kinase (AMPK) was observed in response to oligomycin. Similar to our previous observations with free fatty acids, inhibition of fatty acid oxidation restored oligomycin-stimulated glucose uptake. In conclusions, VLDL-derived fatty acids impair stimulated glucose transport in cardiac myocytes by a mechanism that seems to be mediated by a fatty acid oxidation intermediate. Thus, in the clinical context of the metabolic syndrome high VLDL may contribute to enhancement of ischemic injury by reduction of metabolic stress-stimulated glucose uptake.

Signalling of DNA damage and cytokines across cell barriers exposed to nanoparticles depends on barrier thickness.

The use of nanoparticles in medicine is ever increasing, and it is important to understand their targeted and non-targeted effects. We have previously shown that nanoparticles can cause DNA damage to cells cultured below a cellular barrier without crossing this barrier. Here, we show that this indirect DNA damage depends on the thickness of the cellular barrier, and it is mediated by signalling through gap junction proteins following the generation of mitochondrial free radicals. Indirect damage was seen across both trophoblast and corneal barriers. Signalling, including cytokine release, occurred only across bilayer and multilayer barriers, but not across monolayer barriers. Indirect toxicity was also observed in mice and using ex vivo explants of the human placenta. If the importance of barrier thickness in signalling is a general feature for all types of barriers, our results may offer a principle with which to limit the adverse effects of nanoparticle exposure and offer new therapeutic approaches.

Effect of an OT antagonist on the control of the midcycle LH surge in women.

OBJECTIVE: Data in women regarding the role of OT in LH secretion during the LH surge are conflicting. As in previous studies blood samples for LH measurements were taken infrequently, we re-examined this matter in women with a fully characterized midcycle LH surge. DESIGN: Normal women were studied over two cycles. When the dominant follicle reached a diameter of either 16-17 mm (Group 1) or 18-19 mm (Group 2), the women were infused intravenously for 3 h with normal saline (cycle-1) or atosiban (cycle-2). PATIENTS: Fifteen women (10 in group 1 and 5 in group 2) aged 23-35 years. MEASUREMENTS: Blood samples were obtained every 6 h to characterize the midcycle LH surge. RESULTS: The time interval (mean +/- SEM) from the start of the infusion to the onset of the LH surge in the two cycles was 46.8 +/- 4.8 and 45.6 +/- 9.6 h in group 1 and 6.0 +/- 2.4 and 7.5 +/- 2.8 h, respectively, in group 2. LH values during the LH surge were similar in the two cycles except in group 1 at the point of 30 h at which LH value in cycle-2 (41.2 +/- 4.6 mIU/ml) was significantly lower than in cycle-1 (52.8 +/- 3.4 mIU/ml, P < 0.05). Nevertheless, in each group, the area under the curve for LH was similar in the two cycles. CONCLUSIONS: Antagonism of endogenous OT action by atosiban does not alter the LH profile during a fully characterized midcycle LH surge, suggesting that OT is not a major regulator of LH secretion in women.

Macrophages detoxify the genotoxic and cytotoxic effects of surgical cobalt chrome alloy particles but not quartz particles on human cells in vitro.

Particles of surgical cobalt chrome alloy are cytotoxic and genotoxic to human fibroblasts in vitro. In vivo orthopaedic patients are exposed to cobalt chrome particles as a result of wear of a joint replacement. Many of the wear debris particles that are produced are phagocytosed by macrophages that accumulate at the site of the worn implant and are disseminated to local and distant lymph nodes the liver and the spleen. In this study we have tested whether this process of phagocytosis could have altered the cytotoxic and genotoxic properties of the cobalt chrome particles. Quartz particles have been investigated as a control. Micron-sized particles of cobalt chrome alloy were internalised by either white cells of peripheral blood or by THP-1 monocytes for 1 week and 1 day, respectively. The particles were then extracted and presented at different doses to fibroblasts for 1 day. There was a reduction of the cytotoxicity and genotoxicity of the cobalt chrome particles after phagocytosis by white cells or THP-1 cells. Cobalt chrome particles that were internalised by fibroblasts also showed a reduction of their cytotoxicity but not their genotoxicity. In contrast the cytotoxicity and genotoxicity of quartz particles was increased after internalisation by THP-1 cells. The surface morphology of the cobalt chrome particles but not the quartz particles was changed after phagocytosis by THP-1 cells. This study suggests that the genotoxic and cytotoxic properties of particles that fall within the size range for phagocytosis may be highly complex in vivo and depend on the combination of material type and previous phagocytosis. These results may have relevance for particle exposure from orthopaedic implants and from environmental or industrial pollution.

Kinetic and mutational analysis of the Trypanosoma brucei NBT1 nucleobase transporter expressed in Saccharomyces cerevisiae reveals structural similarities between ENT and MFS transporters.

Parasitic protozoa are unable to synthesise purines de novo and thus depend on the uptake of nucleosides and nucleobases across their plasma membrane through specific transporters. A number of nucleoside and nucleobase transporters from Trypanosoma brucei brucei and Leishmania major have recently been characterised and shown to belong to the equilibrative nucleoside transporter (ENT) family. A number of studies have demonstrated the functional importance of particular transmembrane segments (TMS) in nucleoside-specific ENT proteins. TbNBT1, one of only three bona fide nucleobase-selective members of the ENT family, has previously been shown to be a high-affinity transporter for purine nucleobases and guanosine. In this study, we use the Saccharomyces cerevisiae expression system to build a biochemical model of how TbNBT1 recognises nucleobases. We next performed random in vitro and site-directed mutagenesis to identify residues critical for TbNBT1 function. The identification of residues likely to contribute to permeant binding, when combined with a structural model of TbNBT1 obtained by homology threading, yield a tentative three-dimensional model of the transporter binding site that is consistent with the binding model emerging from the biochemical data. The model strongly suggests the involvement of TMS5, TMS7 and TMS8 in TbNBT1 function. This situation is very similar to that concerning transporters of the major facilitator superfamily (MFS), one of which was used as a template for the threading. This point raises the possibility that ENT and MFS carriers, despite being considered evolutionarily distinct, might in fact share similar topologies and substrate translocations pathways.

Oxytocin is not important for the control of gonadotrophin secretion in the late follicular phase of the cycle.

OBJECTIVE: To study the role of oxytocin in basal and GnRH-induced gonadotrophin secretion in normal women. DESIGN: Normal women were studied in three cycles. When the diameter of the leading follicle was 15-16 mm, the women were infused intravenously (i.v.) for 3 h with normal saline (cycle 1), atosiban (cycle 2) or oxytocin (cycle 3). PATIENTS: The study included 12 normally cycling women aged 23-38 years. MEASUREMENTS: After cessation of treatment, two injections of GnRH, 10 microg each, were administered i.v. 2 h apart and blood samples were collected every 30 min for a total of 240 min. The 30-min pituitary response (sensitivity) to a single GnRH injection (10 microg i.v.) was investigated thereafter every 12 h from the end of the 3-h infusion until the day of LH surge onset. RESULTS: No significant differences in LH and FSH response to GnRH (sensitivity and reserve) during the 240-min experiment were found between the three cycles. The time of LH surge onset from the initiation of the infusion was similar in the three cycles. Also similar in the three cycles were oestradiol (E2) and gonadotrophin levels as well as the 30-min response to GnRH for 48 h following the 3-h infusion. CONCLUSIONS: The present study demonstrates that neither exogenous oxytocin administration nor blockage of endogenous oxytocin action influences pituitary sensitivity to GnRH in cycling women.

The effect of nano- and micron-sized particles of cobalt-chromium alloy on human fibroblasts in vitro.

Wear debris from metal on polyethylene joint replacements causes asceptic loosening as a result of an inflammatory reaction of macrophages to micron-sized particles. Metal on metal implants, which generate nanoparticles, have been reintroduced into surgical practise in order to avoid this problem. There is a current concern about possible long-term effects of exposure to metal particles. In this study, the cytotoxic and genotoxic effects of nanoparticles and micron-sized particles of cobalt chrome alloy have been compared using human fibroblasts in tissue culture. Nanoparticles, which caused more free radicals in an acellular environment, induced more DNA damage than micron-sized particles using the alkaline comet assay. They induced more aneuploidy and more cytotoxicity at equivalent volumetric dose. Nanoparticles appeared to disintegrate within the cells faster than microparticles with the creation of electron dense deposits in the cell, which were enriched in cobalt. The mechanism of cell damage appears to be different after exposure to nanoparticles and microparticles. The concept of nanotoxicology is, therefore, an important consideration in the design of future surgical devices.

Systemic lupus erythematosus - associated acute severe thrombocytopenia and leukopenia first presented in pregnancy.

We report a rare case of acute severe thrombocytopenia and leukopenia, which first presented at 37 weeks' gestation. Based on clinical as well as on laboratory findings the diagnosis of systemic lupus erythematosus was made. The patient was successfully managed with an emergency transfusion of 6 units of platelets and intravenous immunoglobulin infusion followed by methylprednisolone administration. A caesarean section was performed at 39 weeks. The neonate was not thrombocytopenic at birth, nor at the age of 1 month.

Effect of synovial fluid, phosphate-buffered saline solution, and water on the dissolution and corrosion properties of CoCrMo alloys as used in orthopedic implants.

The corrosion and dissolution of high- and low-carbon CoCrMo alloys, as used in orthopedic joint replacements, were studied by immersing samples in phosphate-buffered saline (PBS), water, and synovial fluid at 37 degrees C for up to 35 days. Bulk properties were analyzed with a fine ion beam microscope. Surface analyses by X-ray photoelectron spectroscopy and Auger electron spectroscopy showed surprisingly that synovial fluid produced a thin oxide/hydroxide layer. Release of ions into solution from the alloy also followed an unexpected pattern where synovial fluid, of all the samples, had the highest Cr concentration but the lowest Co concentration. The presence of carbide inclusions in the alloy did not affect the corrosion or the dissolution mechanisms, although the carbides were a significant feature on the metal surface. Only one mechanism was recognized as controlling the thickness of the oxide/hydroxide interface. The analysis of the dissolved metal showed two mechanisms at work: (1) a protein film caused ligand-induced dissolution, increasing the Cr concentration in synovial fluid, and was explained by the equilibrium constants; (2) corrosion at the interface increased the Co in PBS. The effect of prepassivating the samples (ASTM F-86-01) did not always have the desired effect of reducing dissolution. The release of Cr into PBS increased after prepassivation. The metal-synovial fluid interface did not contain calcium phosphate as a deposit, typically found where samples are exposed to calcium rich bodily fluids.

Identification of the first pyrimidine nucleobase transporter in Leishmania: similarities with the Trypanosoma brucei U1 transporter and antileishmanial activity of uracil analogues.

While purine transport has been widely studied in protozoa, almost nothing is known about their capacity to salvage pyrimidines. Here, we report a Leishmania major transporter with high affinity for uracil (Km=0.32+/-0.07 microM) which we designated LmU1. This transporter displayed a high degree of specificity, as it had virtually no affinity for cytosine, thymine or purine nucleobases, nor did it transport pyrimidine nucleosides. Highest affinity was for 5-fluorouracil. The results show that the permeant binding site of LmU1 interacts strongly with the keto groups of uracil, as shown by a low affinity for 2-thio- and 4-thiouracil. LmU1 appears to further bind uracil through a weak hydrogen bond with N(1)H of the pyrimidine ring in addition to a stronger H-bond with N(3)H. Substrate binding and selectivity were strikingly similar to that of the U1 transporter in the related kinetoplastid Trypanosoma brucei. Uracil analogues likely to be transported by LmU1 were also screened for antileishmanial activity, with 5-fluorouracil displaying strong activity against promastigotes and intracellular amastigotes. Overall, the results show that, like purine nucleobase transport, pyrimidine nucleobase transport function is very similar in L. major and T. brucei insect forms.

Relation between leptin and cortisol values in umbilical vessels at normal vaginal delivery.

To study the role of various hormones in the control of fetal leptin secretion during labour, 33 pregnant women with normal singleton term pregnancy were recruited. At the time of spontaneous vaginal delivery, a venous blood sample was taken from the women together with a venous and an arterial cord blood sample. In all blood samples, leptin, cortisol, prolactin and progesterone were measured. Serum leptin and cortisol values were significantly higher, while those of prolactin and progesterone were significantly lower in the mother than in the two umbilical vessels (p < 0.01). Cortisol levels were significantly higher in the umbilical artery than in the umbilical vein (p < 0.01). Serum leptin values in the umbilical artery and vein correlated significantly with the corresponding values of cortisol (r = 0.523 and r = 0.580 respectively, p < 0.01), but not with those of prolactin and progesterone. A weak but significant correlation was found between leptin values in the two umbilical vessels and birth weight (r = 0.385 and r = 0.401 respectively, p < 0.05). In multiple regression analysis, cortisol values but not birth weight was the most important determinant of leptin values. Birth weight, however, correlated significantly with placental weight (r = 0.776, p < 0.001). These results demonstrate for the first time that leptin concentrations in the umbilical vessels at normal vaginal delivery correlate significantly with cortisol values, thus providing evidence that cortisol mediates a labour stimulating effect on fetal leptin secretion. It is suggested that cord blood leptin values at delivery are not a good predictor of neonatal weight.

Postinfarction heart failure in rats is associated with upregulation of GLUT-1 and downregulation of genes of fatty acid metabolism.

OBJECTIVES: Increasing evidence suggests that left ventricular remodeling is associated with a shift from fatty acid to glucose metabolism for energy production. The aim of this study was to determine whether left ventricular remodeling with and without late-onset heart failure after myocardial infarction is associated with regional changes in the expression of regulatory proteins of glucose or fatty acid metabolism. METHODS: Myocardial infarction was induced in rats by ligation of the left anterior descending coronary artery (LAD). In infarcted and sham-operated hearts the peri-infarction region (5-mm zone surrounding the region at risk), the interventricular septum and the right ventricular free wall were separated for analysis. RESULTS: At 8 and 20 weeks after LAD ligation, the peri-infarction region and the septum exhibited marked re-expression of atrial natriuretic factor [+252+/-37 and +1093+/-279%, respectively, in the septum (P<0.05)] and of alpha-smooth muscle actin [+34+/-10 and +43+/-14%, respectively, in the septum (P<0.05)]. At 8 weeks, when left ventricular hypertrophy was present without signs of heart failure, myocardial mRNA expression of glucose transporters (GLUT-1 and GLUT-4) was not altered, whereas mRNA expression of medium-chain acyl-CoA dehydrogenase (MCAD) was significantly reduced in the peri-infarction region (-25+/-7%; P<0.05). In hearts exhibiting heart failure 20 weeks after infarct-induction there was a change in all three ventricular regions of both mRNA and protein content of GLUT-1 [+72+/-28 and +121+/-15%, respectively, in the peri-infarction region (P<0.05)] and MCAD [-29+/-9 and -56+/-4%, respectively, in the peri-infarction region (P<0.05)]. CONCLUSION: In rats with large myocardial infarction, progression from compensated remodeling to overt heart failure is associated with upregulation of GLUT-1 and downregulation of MCAD in both the peri-infarction region and the septum.

Oestradiol plus progesterone treatment increases serum leptin concentrations in normal women.

BACKGROUND: Previous studies have alluded to a role for both oestradiol and progesterone in the secretion of leptin from fat cells in the human, although direct evidence has yet to be obtained. The study aim was to assess serum leptin concentrations in normally cycling women receiving exogenous oestradiol and progesterone. METHODS: Normally cycling women were investigated in an untreated spontaneous cycle (control, n = 10), a cycle treated with oestradiol (oestradiol cycle, n = 10) and a cycle treated with oestradiol plus progesterone (oestradiol+progesterone cycle, n = 6). Oestradiol was given to the women through skin patches on cycle days 2, 3 and 4, and progesterone intravaginally on cycle days 3, 4 and 5. Serum concentrations of leptin, oestradiol, progesterone, FSH and LH were measured in daily blood samples. RESULTS: During the treatment, serum oestradiol and progesterone concentrations increased significantly. In the oestradiol cycles, leptin concentrations were not affected by treatment and did not differ from those in controls. In the oestradiol+progesterone cycles, leptin concentrations (mean +/- SEM) increased in all women from cycle day 3 (8.6 +/- 1.1 ng/ml) to days 5 (12.2 +/- 1.8 ng/ml, P < 0.01) and 6 (11.9 +/- 2.0, P < 0.05), and were at these points significantly higher than in the control cycles (P < 0.05). The mean percentage increase from day 3 to the peak concentration on days 5 or 6 was 62.6 +/- 6.8%. Leptin concentrations returned to the pretreatment value on day 7, together with the concentrations of oestradiol and progesterone. In the oestradiol+progesterone cycles, leptin concentrations correlated significantly with oestradiol and progesterone concentrations, but not with FSH and LH concentrations. CONCLUSIONS: These results show, for the first time, that leptin secretion can be stimulated in women by the administration of oestradiol plus progesterone. This may explain the increased concentrations of leptin during the luteal phase of the normal menstrual cycle.

Syringomyelia and pregnancy-case report.

The course of a pregnancy in a woman with syringomyelia is presented. She was first admitted at 28 weeks' gestation suffering neurologic symptoms associated with a spinal cord injury, which had happened in the past. The disease was diagnosed with a magnetic resonance imaging (MRI). Delivery was accomplished by elective caesarean section under general anaesthesia at 37 weeks, in order to avoid straining during the second stage of an imminent labour.

Calcium-mediated activation of pyruvate dehydrogenase in severely injured postischemic myocardium.

Indirect evidence suggests that activity of pyruvate dehydrogenase (PDH) influences recovery of the myocardium after transient ischemia. The present study examined the relationship between postischemic injury and activity of PDH and the role of mitochondrial calcium uptake for observed changes in PDH activity. Isovolumically beating isolated rat hearts perfused with erythrocyte-enriched buffer containing glucose, palmitate, and insulin were submitted to either 20 or 35 min of no-flow ischemia. After 20 min of no-flow ischemia, hearts exhibited complete recovery of developed left ventricular pressure (DLVP). The proportion of myocardial PDH in the active state was modestly increased to 38% (compared with 13% in control hearts) without a change in glucose oxidation. In contrast, in hearts subjected to 35 min of no-flow ischemia (which exhibited poor recovery of DLVP), there was marked stimulation of glucose oxidation (+460%; P < 0.01) and pronounced increase in the active fraction of PDH to 72% (P < 0.01). Glycolytic flux was not significantly altered. Ruthenium red (6 microM) completely abolished the activation of PDH and the increase in glucose oxidation. The results indicate that variable stimulation of glucose oxidation during reperfusion is related to different degrees of activation of PDH, which depends on the severity of the ischemic injury. Activation of PDH seems to be mediated by myocardial calcium uptake.

Altered expression of proteins of metabolic regulation during remodeling of the left ventricle after myocardial infarction.

Non-infarcted myocardium after coronary occlusion undergoes progressive morphological and functional changes. The purpose of this study was to determine whether non-infarcted myocardium exhibits (1) alteration of the substrate pattern of myocardial metabolism and (2) concomitant changes in the expression of regulatory proteins of glucose and fatty acid metabolism. Myocardial infarction was induced in rats by ligation of the left coronary artery. One day and eight weeks after coronary occlusion, glucose and palmitate oxidation were measured. Expression of selected proteins of metabolism were determined one day to 12 weeks after infarction. One day after coronary occlusion no difference of glucose and palmitate oxidation was detectable, whereas after eight weeks, glucose oxidation was increased (+84%, P<0.05) and palmitate oxidation did not change significantly (-19%, P=0.07) in infarct-containing hearts, compared with hearts from sham-operated rats. One day after coronary occlusion, myocardial mRNA expression of the glucose transporter GLUT-1 was increased (+86%, P<0.05) and the expression of GLUT-4 was decreased (-28%, P<0.05) in surviving myocardium of infarct-containing hearts. Protein level of GLUT-1 was increased (+81%, P<0.05) and that of GLUT-4 slightly, but not significantly, decreased (-16%, P=NS). mRNA expressions of heart fatty acid binding protein (H-FABP), and of medium chain acyl-CoA dehydrogenase (MCAD), were decreased by 36% (P<0.05) and 35% (P=0. 07), respectively. Eight weeks after acute infarction, the left ventricle was hypertrophied and, at this time-point, there was no difference in the expression of GLUT-1 and GLUT-4 between infarcted and sham-operated hearts. However, myocardial mRNA and protein content of MCAD were decreased by 30% (P<0.01) and 27% (P<0.05), respectively. In summary, in surviving myocardium, glucose oxidation was increased eight weeks after coronary occlusion. Concomitantly, mRNA and protein expression of MCAD were decreased, compatible with a role of altered expression of regulatory proteins of metabolism in post-infarction modification of myocardial metabolism.

Postischemic recovery of heart metabolism and function: role of mitochondrial fatty acid transfer.

Postischemic recovery of contractile function is better in hearts from fasted rats than in hearts from fed rats. In this study, we examined whether feeding-induced inhibition of palmitate oxidation at the level of carnitine palmitoyl transferase I is involved in the mechanism underlying impaired recovery of contractile function. Hearts isolated from fasted or fed rats were submitted to no-flow ischemia followed by reperfusion with buffer containing 8 mM glucose and either 0.4 mM palmitate or 0.8 mM octanoate. During reperfusion, oxidation of palmitate was higher after fasting than after feeding, whereas oxidation of octanoate was not influenced by the nutritional state. In the presence of palmitate, recovery of left ventricular developed pressure was better in hearts from fasted rats. Substitution of octanoate for palmitate during reperfusion enhanced recovery of left ventricular developed pressure in hearts from fed rats. However, the chain length of the fatty acid did not influence diastolic contracture. The results suggest that nutritional variation of mitochondrial fatty acid transfer may influence postischemic recovery of contractile function.