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1.
The effects of varying concentrations and types of volatile anesthetics on neurochemical sequelae of brain ischemia were evaluated in the rat. Rats were assigned to treatment defined by a 3×3 design (anesthetic type and dose) with 5 rats/cell. Each group received halothane, enflurane, or isoflurane 0.5, 1.0, or 2.0 MAC (minimal alevolar concentration). This was followed by preischemic plasma glucose sampling, 5 min hypotension (30 mmHg) and 5 min decapitation cerebral ischemia. Preischemia plasma glucose increased with increasing anesthetic concentration and was highest in the isoflurane groups, varying from a low (±SD) of 7.19±1.79 mol/ml in the 0.5 MAC halothane group to a high of 12.68±3.65 mol/ml in the 2.0 MAC isoflurane group. End-ischemic brain lactate correlated with preischemic plasma glucose (r=0.5, =0.5). We conclude that increasing concentration of volatile anesthesia with iv phenylephrine blood pressure support produces higher levels of plasma glucose and brain lactate with cerebral ischemia. 相似文献
2.
Kaumann Alberto J. Sanders Louise Lynham James A. Bartel Sabine Kuschel Meike Karczewski Peter Krause Ernst-Georg 《Molecular and cellular biochemistry》1996,163(1):113-123
Evidence from ventricular preparations of cat, sheep, rat and dog suggests that both 1-adrenoceptors (1AR) and 2-adrenoceptors (2AR) mediate positive inotropic effects but that only 1AR do it through activation of a cAMP pathway. On the other hand, our evidence has shown that both 1 AR and 2 AR hasten relaxation of isolated human myocardium consistent with a common cAMP pathway. We have now investigated in the isolated human right atrial appendage, a tissue whose -AR comprise around 2/3 of 1AR and 1/3 of 2AR, whether or not 2AR-mediated effects occur via activation of a cAMP pathway. We carried out experiments on atria obtained from patients without advanced heart failure undergoing open heart surgery. To activate 2AR, we used the 2AR-selective ligand zinterol. Experiments were carried out on paced atrial strips (1 Hz) and tissue homogenates and membrane particles. Zinterol caused positive inotropic and lusitropic (i.e. reduction of t1:2 of relaxation) effects with EC50 values of 3 and 2 nM, respectively. The zinterol-evoked effects were unaffected by the AR-selective antagonist CGP 20712A (300 nM) but blocked surmountably by the 2AR-selective antagonist ICI 118551 (50 nM) which reduced both EC50 values to 1 M. Zinterol stimulated adenylyl cyclase activity with an EC50 of 30 nM and intrinsic activity of 0.75 with respect to (–)-isoprenaline (600 M); the effects were resistant to blockade by CGP 20712A (300 nM) but antagonised surmountably by ICI 118551 (50 nM). Zinterol bound to membrane PAR labelled with (–)-[125I] cyanopindolol with higher affinity for 2AR than for - 1 AR; the binding to 2AR but not to - BAR was reduced by GTPyS (10 M). In the presence of CGP 20712A (300 nM) (–)-isoprenaline (400 M); (to activate both 1AR and 2AR maximally) and zinterol (10 M); increased contractile force 3.4-fold and 2.5-fold respectively and reduced relaxation tut by 32% and 18% respectively. These effects of (–)-isoprenaline and zinterol were associated (5 min incubation) with phosphorylation (pmol P/mg supernatant protein) of troponin I and C-protein to values of 8.4 ± 2.0 vs 12.4 ± 2.3 and 10.1 ± 2.5 vs 8.6 ± 1.6 respectively. (–)-Isoprenaline and zinterol also caused phosphorylation of phospholamban (1.8 ± 0.3 vs 0.4 ± 0.1 pmol P/mg respectively) specifically at serine residues. We conclude that in human atrial myocardium activation of both 1AR and 2AR leads to cAMP-dependent phosphorylation of proteins involved in augmenting both contractility and relaxation. 相似文献
3.
Opioid receptor contributes to ischemic preconditioning through protein kinase C activation in rabbits 总被引:27,自引:0,他引:27
Miki Takayuki Cohen Michael V. Downey James M. 《Molecular and cellular biochemistry》1998,186(1-2):3-12
Recent studies have reported that protection from ischemic preconditioning (PC) is blocked by the opioid receptor antagonist naloxone (NAL). We tested whether an opioid agonist could mimic PC in the rabbit heart, whether that protection involved protein kinase C (PKC) activation, and whether opioid receptors act in concert with other PKC-coupled receptors. Rabbit hearts were subjected to 30min coronary occlusions and were reperfused for either 3 (in situ) or 2 (in vitro) h. Infarct size was determined by staining with triphenyltetrazolium chloride. In untreated in situ hearts 38.5 ± 1.6% of the risk zone infarcted. PC with 5 min ischemia/10 min reperfusion significantly limited infarction to 12.7 ± 2.9% (p < 0.01). NAL infusion did not modify infarction (39.6 ± 1.6%) in non-PC hearts, but blocked the effect of one cycle of PC (34.4 ± 3.6% infarction). NAL, however, could not block cardioprotection when PC was amplified with 3 cycles of ischemia/reperfusion (9.9 ± 1.4% infarction, p < 0.01 vs. control). Morphine could also mimic ischemic preconditioning, but only at a dose much higher than would be used clinically (3 mg/kg). In isolated hearts pretreatment with morphine (0.3 M) significantly limited infarction to 9.3 ± 1.2% (p < 0.01 vs. 32.0 ± 3.1% in controls). This cardioprotective effect of morphine could be blocked by either the PKC inhibitor chelerythrine (30.4 ± 2.6% infarction) or NAL (34.0 ± 2.6% infarction). Neither chelerythrine nor NAL by itself modified infarction in non-PC hearts. NAL could not block protection from one cycle of PC in isolated hearts indicating that an intact innervation may be required for endogenous opioid production. Thus, opioid receptors, like other PKC-coupled receptors, participate in the triggering PC in the rabbit heart. 相似文献
4.
Several genetic and transgenic mouse models are currently being used for studying the regulation of myocardial contractility under normal conditions and in disease states. Little information has been provided, however, about myocardial energy metabolism in mouse hearts. We measured glycolysis, glucose oxidation and palmitate oxidation (using 3H-glucose, 14C-glucose and 3H-palmitate) in isolated working mouse hearts during normoxic conditions (control group) and following a 15 min global no-flow ischemic period (reperfusion group). Fifty min following reperfusion (10 min Langendorff perfusion + 40 min working heart perfusion) aortic flow, coronary flow, cardiac output, peak systolic pressure and heart rate were 44 ± 4, 88 ± 4, 57 ± 4, 94 ± 2 and 81 ± 4% of pre-ischemic values. Rates of glycolysis and glucose oxidation in the reperfusion group (13.6 ± 0.8 and 2.8 ± 0.2 mol/min/g dry wt) were not different from the control group (12.3 ± 0.6 and 2.5 ± 0.2 mol/min/g dry wt). Palmitate oxidation, however, was markedly elevated in the reperfusion group as compared to the control group (576 ± 37 vs. 357 ± 21 nmol/min/g dry wt, p < 0.05). This change in myocardial substrate utilization was accompanied by a marked fall in cardiac efficiency measured as cardiac output/oxidative ATP production (136 ± 10 vs. 54 ± 5 ml/mol ATP, p < 0.05, control and reperfusion group, respectively). We conclude that ischemia-reperfusion in isolated working mouse hearts is associated with a shift in myocardial substrate utilization in favour of fatty acids, in line with previous observations in rat. 相似文献
5.
Mosca Susana M. Carriquiriborde Martín Cingolani Horacio E. 《Molecular and cellular biochemistry》1996,160(1):123-128
The present study provides evidences of left ventricular diastolic alterations following reperfusion in a model of global ischemia. Isolated perfused rabbit and rat hearts, were subjected to ischemia for 15 and 20 min respectively, followed by 30 min of reperfusion. In rabbit heart at the end of the reperfusion period, isovolumic left ventricular developed pressure (LVDP) and +dP/dtmax stabilized at 55 ± 3% and 60 ± 2% of preischemic values respectively and, in rat heart LVDP = 61 ± 8% and +dP/dtmax = 57 ± 9% of preischemic values. Stunned heart was then obtained from both species. Left ventricular end diastolic pressure (LVEDP) values stabilized at the end of reperfusion period at values higher than preischemic conditions in both species (38.9 ± 4.4 mmHg and 30.3 ± 3.1 mmHg in rabbit and rat respectively). The time constant of relaxation (T) increased early in reperfusion in both species, but then decreased and stabilized at the end of reperfusion period at values lower than preischemic values. The ratio between both maximal velocities (+P/-P), also showed a transitory impairment in relaxation, followed by normalization and stabilization at values lower than preischemic values. This biphasic pattern in relaxation was detected in both species. The changes in relaxation were dissociated from the diastolic compliance and could be the result of a transitory calcium overload and/or sarcoplasmic reticulum dysfunction. The faster myocardial relaxation at the end of reperfusion period is consistent with the decreased myofilament sensitivity, which characterizes the stunned myocardium. 相似文献
6.
Awan MM Makaula S Forresti S Sack MN Opie LH 《Molecular and cellular biochemistry》2000,211(1-2):111-121
Transient glucose deprivation of the heart [GLU (-)] confers a preconditioning-like protection against subsequent ischemic/reperfusion (I/R). The mechanisms involved remain unclear. We hypothesized that GLU (-) would induce the classic ischemic preconditioning activated signaling cascade. Potential metabolic consequences and putative cell signaling events induced by transient glucose deprivation were evaluated as candidate mediators of this cardioprotection.Isolated glucose-perfused rat hearts were subjected to 30 min global ischemia followed by 30 min reperfusion (index I/R). Cardiac contractile recovery following I/R was used as the functional end-point in these studies. Metabolic preconditioning was stimulated by 15 min GLU (-) followed by 10 min glucose repletion prior to the index I/R. The potential metabolic consequences of GLU (-) were evaluated by using excess octanoate (11 mM OCT Hi) or 11 mM 2-deoxy-D-glucose (2-DG) in place of GLU (-) and by combining GLU (-) with fuels known to inhibit glycolysis supply (20 mM pyruvate or 1 mM octanoate, OCT Lo). The roles of -adrenoceptors, -adrenoceptors, adenosine receptors, protein kinase C (PKC) and mitochondrial KATP channels were investigated using inhibitors prazosin (10 M), propranolol (10 M), 8-(p-sulfophenyl) theophylline, (SPT 100 M), chelerythrine (CHEL 10 M) and 5-hydroxydecanoate (5 HD 100 M) respectively.GLU (-) increased mechanical recovery (59.8 ± 4.0 vs. 32.3 ± 4.7%; p < 0.01). Protection was abolished by pyruvate 26.6 ± 3.1; SPT 36.6 ± 3.0; CHEL 35 ± 4.8 or 5 HD 23.8 ± 3.3%. In a separate set of experiments, the specificity of SPT in this model was tested by preconditioning with adenosine (100 M) (34.7 ± 4 vs. control 16.8 ± 1.3%, p = 0.01) and blocking this protection with the same dose of SPT (16.3 ± 1.5%) used in the GLU (-) studies. Protection was unaltered by prazosin (50.2 ± 3.3%), propranolol (55.5 ± 4.0%), or OCT Lo (50.2 ± 2.5%). Protection was not mimicked by OCT Hi (35.6 ± 3.8%) or 2-DG (34 ± 4.3%).Transient glucose deprivation does not seem to achieve preconditioning-like cardioprotection by decreased glycolysis. Rather, the signal system may involve enhanced adenosine release, PKC, and activation of the mitochondrial KATP channel. 相似文献
7.
Margarete Arras Adelheid Höche Rainer Bohle Peter Eckert Walter Riedel Jutta Schaper 《Cell and tissue research》1996,285(1):39-49
The relationship between myonuclear number, cellular size, succinate dehydrogenase activity, and myosin type was examined in single fiber segments (n=54; 9±3 mm long) mechanically dissected from soleus and plantaris muscles of adult rats. One end of each fiber segment was stained for DNA before quantitative photometric analysis of succinate dehydrogenase activity; the other end was double immunolabelled with fast and slow myosin heavy chain monoclonal antibodies. Mean±S.D. cytoplasmic volume/myonucleus ratio was higher in fast and slow plantaris fibers (112±69 vs. 34±21x103 m3) than fast and slow soleus fibers (40±20 vs. 30±14x103 m3), respectively. Slow fibers always had small volumes/myonucleus, regardless of fiber diameter, succinate dehydrogenase activity, or muscle of origin. In contrast, smaller diameter (<70 m) fast soleus and plantaris fibers with high succinate dehydrogenase activity appeared to have low volumes/myonucleus while larger diameter (>70 m) fast fibers with low succinate dehydrogenase activity always had large volume/myonucleus. Slow soleus fibers had significantly greater numbers of myonuclei/mm than did either fast soleus or fast plantaris fibers (116±51 vs. 55±22 and 44±23), respectively. These data suggest that the myonuclear domain is more limited in slow than fast fibers and in the fibers with a high, compared to a low, oxidative metabolic capability. 相似文献
8.
9.
Raymond R. Padua Rajat Sethi Naranjan S. Dhalla Elissavet Kardami 《Molecular and cellular biochemistry》1995,143(2):129-135
To examine whether basic fibroblast growth factor (bFGF) administered to the heart by perfusion can improve cardiac resistance to injury we employed an isolated rat heart model of ischemia-reperfusion injury and determined the extent of functional recovery in bFGF-treated and control hearts. Global ischemia was simulated by interruption of flow for 60 min. Recovery of developed force of contraction (DF), recorded after reestablishment of flow for 30 min, reached 63.8±1.5% and 96.5±3.5% of preischemic levels in control and bFGF-treated hearts (10 g/heart), respectively, indicating that bFGF induced significantly improved recovery of mechanical function. Recoveries of the rates of contraction or relaxation were also significantly improved in bFGF-treated hearts. Extent of myocardial injury, assessed by determination of phosphocreatine kinase in the effluent, was reduced as a result of bFGF treatment. As a first step towards understanding the mechanism and direct cellular target(s) of bFGF-induced cardioprotection, we investigated its fate after perfusion. Perfusion of 10 g bFGF/heart resulted in a 4-fold increase in bFGF associated with the heart compared to control levels, as estimated by biochemical fractionation and immunoblotting. Immunofluorescent staining of the bFGF-perfused hearts revealed intense anti-bFGF staining in association with blood vessels as well as the periphery of cardiomyocytes, suggesting that the latter may be a target for direct bFGF action. In conclusion, our findings of bFGF-induced increases in cardiac resistance to, and improved functional recovery from, ischemia-reperfusion injury indicate that bFGF may have clinical applications in the treatment of ischemic heart disease. 相似文献
10.
Gupta Ramesh C. Neumann Joachim Watanabe August M. Sabbah Hani N. 《Molecular and cellular biochemistry》1998,187(1-2):155-161
In intact guinea pig ventricles, acetylcholine (ACH) has been shown to attenuate the positive inotropic effects of isobutylmethylxanthine (IBMX), a phosphodiesterase inhibitor, by reducing protein phosphorylation without altering cAMP levels. In the present study, we tested the hypothesis that the cAMP-independent inhibitory action of ACH is also evident in isolated cardiomyocytes. cAMP-dependent protein kinase (PKA) activity ratio (-cAMP/+cAMP) and phosphorylation of phospholamban (PLB) were determined in unlabeled and 32P-labeled guinea pig ventricular cardiomyocytes, respectively. IBMX increased PKA activity ratio and phosphorylation of PLB in a dose-dependent manner. When cardiomyocytes were incubated simultaneously with IBMX (0-1 mM) and ACH (2 M), ACH attenuated PLB phosphorylation stimulated by low concentration (10-100 M) but not by high concentrations (> 200 M) of IBMX. EC50 value for IBMX-induced phosphorylation of PLB was 32 ± 6 M and increased nearly 3-fold after addition of ACH while PKA activity ratio remained unchanged. The rank order of cyclic nucleotide derivatives to phosphorylate PLB was 8 bromo-cAMP > dibutyryl cAMP > 8 bromo-cGMP > dibutyryl cGMP. ACH reduced phosphorylation of PLB stimulated by 8 bromo-cAMP. We conclude that in isolated cardiomyocytes (1) ACH inhibits phosphorylation of PLB stimulated by either IBMX or 8 bromo-cAMP and (2) ACH does not lower IBMX-stimulated PKA activity ratio. These effects of ACH on PLB phosphorylation cannot be explained by a reduction in IBMX-stimulated cAMP levels but may involve the activation of protein phosphatases. 相似文献
11.
Callus was initiated from immature leaf and stem segments of rose (Rosa hybrida cv. Landora) and subcultured every four weeks on a basal medium of half-strength Murashige & Skoog (1962) salts plus 30 g l-1 sucrose (1/2 MS) and supplemented with 2.2 M BA, 5.4 M NAA and 2.2–9.0 M 2,4-D. Embryogenic callus and subsequently somatic embryos were obtained from 8-week-old callus culture on 1/2 MS+2.2 M BA+0.05 M NAA+0.3 M GA3+200–800 mg l-1 L-proline. Long-term cultures were established and maintained for up to 16 months by repeated subculture of embryogenic callus on L-proline deficient medium. About 12% of cotyledonary stage embryos taken from cultures cold-stored at 8±1°C for 4 days germinated on 1/2 MS+2.2 M BA+0.3 M GA3+24.7 M adenine sulphate.Abbreviations BA
benzyladenine
- NAA
-naphthaleneacetic acid
- 2,4-D
2,4-dichlorophenoxyacetic acid
- GA3
gibberellic acid 相似文献
12.
Summary Although ADPKD is one of the first kidney diseases to be understood from the gene to the pathogenesis of clinical abnormalities, there were no data concerning the renal handling of amino acids and possible disorders of amino acid (AA) pattern in these patients. Therefore, in 9 patients suffering from ADPKD and in 8 healthy normal persons (NP) renal amino acid excretion was measured before and after extracellular volume expansion (ECVE) (21 of physiological electrolyte solution). Renal function was stable in both groups (serum creatinine: ADPKD: 85.1 ± 18.4 vs. NP 84.4 ± 13.5 mol/l; GFR: 93.8 ± 16.4 vs. 104.4 ± 9.4 ml/min/1.73 m2). Mean blood pressure was higher in ADPKD patients than in NP (99.4 ± 2.6 vs. 85.5 ± 2.4 mmHg), but did not change after ECVE. After ECVE in both groups, urine volume increased distinctly, whereas GFR was only slightly enhanced. The plasma concentrations of leucine, glycine, valine, threonine, glutamine, and alanine were significantly higher in controls than in ADPKD patients. The amino acid reabsorption capacity was reduced in ADPKD patients in 12 of 21 amino acids before ECVE. After ECVE, the fractional excretion of amino acids (FEAA) increased only in NP. In parallel with changes in amino acid handling, the FENa (%) after ECVE increased both in ADPKD patients and in NP (before ECVE - ADPKD: 1.22 ± 0.23 vs. NP: 1.53 ± 0.23; after ECVE: 3.17 ± 0.25 (ADPKD) vs. 2.74 ± 0.22/NP; (ADPKD p 0.01, NP p 0.02) whereas FELi (%) increased significantly only in ADPKD (p 0.045) range (before ECVE - ADPKD: 25.8 ± 8.9 vs. NP: 20.5 ± 4.0; after ECVE: 41.4 ±15.4 vs. 25.2 ± 3.9). Furthermore, concentrations of cGMP (pmol/ml) in plasma increased after ECVE (before ECVE - ADPKD: 5.31 ± 0.56 vs. NP: 6.65 ±0.79; after ECVE: 11.31 ± 1.66 vs. 11.30 ± 1.91; p 0.05). Na+-dependent and, perhaps, NO-mediated processes in the reabsorption of AA in the proximal tubule seem to be different in ADPKD and may be related to different distributions of receptors and ATP-dependent transport systems with pathogenetic impact on abnormal transtubular fluid transport in ADPKD. 相似文献
13.
Background
Interstitial cystitis (IC) is a debilitating disease characterized by chronic inflammation of the urinary bladder, yet specific cellular mechanisms of inflammation in IC are largely unknown. Multiple lines of evidence suggest that β-adrenergic receptor (AR) signaling is increased in the inflamed urothelium, however the precise effects of these urothelial cell signals have not been studied. In order to better elucidate the AR signaling mechanisms of inflammation associated with IC, we have examined the effects of β-AR stimulation in an immortalized human urothelial cell line (UROtsa). For these studies, UROtsa cells were treated with effective concentrations of the selective β-AR agonist isoproterenol, in the absence or presence of selective inhibitors of protein kinase A (PKA). Cell lysates were analyzed by radioimmunoassay for generation of cAMP or by Western blotting for induction of protein products associated with inflammatory responses.Results
Radioligand binding demonstrated the presence of β-ARs on human urothelial UROtsa cell membranes. Stimulating UROtsa cells with isoproterenol led to concentration-dependent increases of cAMP production that could be inhibited by pretreatment with a blocking concentration of the selective β-AR antagonist propranolol. In addition, isoproterenol activation of these same cells led to significant increases in the amount of phosphorylated extracellular signal-regulated kinase (pERK), inducible nitric oxide synthase (iNOS) and the induced form of cyclooxygenase (COX-2) when compared to control. Moreover, preincubation of UROtsa cells with the selective PKA inhibitors H-89 or Rp-cAMPs did not diminish this isoproterenol mediated phosphorylation of ERK or production of iNOS and COX-2.Conclusion
Functional β-ARs expressed on human urothelial UROtsa cell membranes increase the generation of cAMP and production of protein products associated with inflammation when activated by the selective β-AR agonist isoproterenol. However, the increased production of iNOS and COX-2 by isoproterenol is not blocked when UROtsa cells are preincubated with inhibitors of PKA. Therefore, UROtsa cell β-AR activation significantly increases the amount of iNOS and COX-2 produced by a PKA-independent mechanism. Consequently, this immortalized human urothelial cell line can be useful in characterizing potential AR signaling mechanisms associated with chronic inflammatory diseases of the bladder. 相似文献14.
Quevedo J Vianna MR Roesler R Martins MR de-Paris F Medina JH Izquierdo I 《Neurochemical research》2005,30(1):61-67
Adult male Wistar rats were trained and tested in a step-down inhibitory avoidance task (0.4 mA footshock, 24 h training-test interval). Fifteen minutes before or 0, 1.5 or 3 hours after training, animals received a 0.8 l intrahippocampal infusion of the protein synthesis inhibitor anisomycin (80 g), the PKA inhibitor Rp-cAMP (0.05 g), the MAPK kinase inhibitor PD 098059 (50 M solution) or vehicle (phosphate buffer in saline, pH 7.4). Anisomycin, Rp-cAMP and PD 098059 impaired retention test performance in animals injected at different times, prior and after training. Pretraining with a low footshock intensity (0.2 mA) 24 h before training prevented the amnestic effect of all drugs studied. However, simple preexposure to the inhibitory avoidance apparatus did not alter the amnestic effects of all drugs. The results suggest that memory processing requires hippocampal mechanisms dependent on protein synthesis, PKA and MAPK kinase at different times after training. These findings suggest that weak training must be sufficient to produce some lasting cellular expression of the experience so that the enhancement of consolidation of a previously acquired memory is not dependent on protein synthesis, PKA or MAPK. 相似文献
15.
Insulin improves contractile function after ischemia, but does not increase glucose uptake in the isolated working rat heart. We tested the hypothesis that the positive inotropic effect of insulin is independent of the signaling pathway responsible for insulin-stimulated glucose uptake. We inhibited this pathway at the level of phosphatidyl inositol 3-kinase (PI3K) with wortmannin. Hearts were perfused for 70 min at physiological workload with Krebs-Henseleit buffer containing [2-3H] glucose (5 mM, 0.05 Ci/ml) and oleate (0.4 mM, 1% BSA) in the presence (WM, n = 5) or absence (control, n = 7) of wortmannin (WM, 3 mol/L). After 20 min, hearts were subjected to 15 min of total global ischemia followed by 35 min of reperfusion. Insulin (1 mU/ml) was added at the beginning of reperfusion (WM + insulin n = 8, insulin n = 8). Cardiac power before ischemia was 8.1 ± 0.7 mW. Recovery of contractile function after ischemia was significantly increased in the presence of insulin (73.5 ± 8.9% vs. 38.5 ± 6.7%, p < 0.01). The addition of wortmannin completely abolished the effect of insulin on recovery (32.6 ± 6.4%). Glucose uptake was 1.84 ± 0.32 mol/min/g dry before ischemia and was slightly elevated during reperfusion (2.68 ± 0.35 mol/min/g dry, n.s.). Insulin did not affect postischemic glucose uptake. In the presence of wortmannin, glucose uptake was lowest during reperfusion (n.s.). The results suggest that PI3K is involved in the insulin-induced improvement in postischemic recovery of contractile function. This effect of insulin is independent of its effect on glucose uptake. 相似文献
16.
The main purpose of this study was to determine the transmural adaptive changes that occur in cell size, myofibrils, and myosin isoforms from the endocardium (ENDO) to the epicardium (EPI) of the left ventricle (LV) of the rat heart during compensatory hypertrophy. Hypertrophy was induced by supra-renal aortic constriction for periods of 2, 7, 15 and 30 days. Percent left ventricular hypertrophy averaged 63±9.7% at 30 days following constriction. A significant (p <0.05) transmural gradient in the V3 myosin isoform (9±0.7% ENDO vs. 5±1.8% EPI) was initially observed at 7 days and was still evident by 30 days (25±3.6% ENDO vs 15±2.0% EPI). Cell cross-sectional area was also greater (p <0.05) in the ENDO than in the EPI at 7,15 and 30 days. MF diameter was determined only at 30 days and was found to be similar to control values in both the hypertrophied ENDO (sham 1.24±0.05 vs hyp 1.18±0.09 m) and EPI (sham 1.17±0.08 vs hyp 1.06±0.08 m). The combined effects of cardiac myocyte hypertrophy with no change in MF diameter resulted in a calculated increase of approximately 70% in the number of myofibrils per myocyte both in the ENDO and EPI. It was concluded that the adaptive strategy of the left ventricular free wall to pressure overload was to initially increase myocyte cross-sectional area and then switch myosin expression from V1 to V3, both of which proceeds transmurally from the sub-endocardium towards the sub-epicardium. Along with these transmural adaptations, myofibrils increased in number while maintaining myofibrillar diameter with the apparent intent of conserving diffusion distance for calcium from the sarcoplasmic reticulum to the innermost contractile filaments of the myofibrils. 相似文献
17.
Stephen J. Ellis William A. Kachadorian Vincent A. DiScala 《The Journal of membrane biology》1980,52(2):181-184
Summary Paired toad urinary bladders were prepared without or with an osmotic gradient (175 mosm) across them, stimulated for 2.5 (n=6), 5 (n=6), 30 (n=6) or 60 (n=6) min with ADH (20 mU/ml), and studied by freeze-fracture electron microscopy. Water permeability at these times was assessed in additional bladders (n=6 for each case) after tissue fixation according to the technique of Eggena. After both 60 and 30 min of ADH stimulation, the presence of a gradient compared with the absence of one was associated with fewer aggregates (242±35vs. 382±14 ×235 m–2 at 60 min,P<0.01; 279±36vs. 470±51 ×235 m–2 at 30 min,P<0.01) and lower water permeability (8.4±1.1vs. 18.8±1.8g×min–1×cm–1 ×mosm
–1 at60min,P<0.005; 9.2±1.0vs. 22.0±2.1 g ×min–1×cm–2×mosm
–1 at 30 min,P<0.001). In addition, with a gradient both maximum water permeability and maximum aggregate frequency were reached nearly together; a similar correspondence occurred without a gradient. We conclude that in the presence of an osmotic gradient both the ADH-associated aggregates and the water permeability response to ADH are prevented from reaching the higher levels observed in bladders not exposed to a gradient. 相似文献
18.
Ming-Yao Chang Chih-Han Chang Chien-Hsi Chen Bill Cheng Yi-Dong Lin Chwan-Yau Luo Hua-Lin Wu Yu-Jen Yang Jyh-Hong Chen Patrick C. H. Hsieh 《PloS one》2015,10(3)
Background
We previously showed that injection of peptide nanofibers (NF) combined with autologous bone marrow mononuclear cells (MNC) immediately after coronary artery ligation improves cardiac performance in pigs. To evaluate the clinical feasibility, this study was performed to determine the therapeutic time window for NF/MNC therapy in acute myocardial infarction (MI).Methods and Results
A total of 45 adult minipigs were randomly grouped into 7 groups: sham or MI plus treatment with NS (normal saline), or NF or MNC alone at 1 day (1D) post-MI, or NF/MNC at 1, 4, or 7 days post-MI (N≥6). Cardiac function was assessed by echocardiography and ventricular catheterization. Compared with the NS control, pigs treated with NF/MNC at 1 day post-MI (NF/MC-1D) had the greatest improvement in left ventricle ejection fraction (LVEF; 55.1±1.6%; P<0.01 vs. NS) 2 months after MI. In contrast, pigs treated with either NF/MNC-4D or NF/MNC-7D showed 48.9±0.8% (P<0.05 vs. NS) and 43.5±2.3% (n.s. vs. NS) improvements, respectively. The +dP/dt and -dP/dt, infarct size and interstitial collagen content were also improved in the NF/MNC-1D and -4D groups but not in the -7D group. Mechanistically, MNC quality and the states of systemic inflammation and damaged heart tissue influence the therapeutic efficiency of NF/MNC therapy, as revealed by another independent study using 16 pigs.Conclusions
Injection of NF/MNC at 1 or 4 days, but not at 7 days post-MI, improves cardiac performance and prevents ventricular remodeling, confirming the importance of early intervention when using this therapy for acute MI. 相似文献19.
Blasig I. E. Dickens B. F. Weglicki W. B. Kramer J. H. 《Molecular and cellular biochemistry》1996,160(1):167-177
The contribution of mitochondrial free radical production towards the initiation of lipid peroxidation (LPO) and functional injury in the post-ischemic heart is unclear. Using the isolated rat heart model, the effects of the uncoupler of mitochondrial oxidative phosphorylation dinitrophenol (DNP, 50 M final) on post-ischemic lipid peroxidation-derived free radical production and functional recovery were assessed. Hearts were subjected to 30 min total global ischemia followed by 15 min of reperfusion in the presence of DNP. As expected, DNP enhanced oxygen consumption before (11.3 ± 0.9 mol/min, p < 0.001) and during reperfusion (at 10 min: 7.9 ± 0.7 umol/min), compared to the heart with control treatment (8.2 ± 0.5 and 6.7 ± 0.3, respectively). This effect was only associated with a higher incidence of ventricular tachycardia during reperfusion (80 vs. 50% for control treatment, p < 0.05). Electron spin resonance spectroscopy (ESR) and spin trapping with u.-phenyl-tert-butylnitrone (PBN, 3 mM final) were used to monitor free radical generation during reperfusion. The vascular concentration of PBN-radical adducts (untreated: 6.4 ±1.0 nM, at 10 min) decreased in the presence of DNP (1.7 ± 0.4 nM, p < 0.01). The radical concentration inversely correlated with myocardial oxygen consumption. Total liberation of free radical adducts during the initial 10 min of reperfusion was reduced by DNP (0.59 ± 0.09 nmol, p < 0.01) compared to the respective control treatment (1.26 ± 0.16 nmol). Similar effects, prevention of PBN adduct formation and unchanged viability in the presence of DNP, were obtained with endothelial cells during post-hypoxic reoxygenation. Since inhibition of mitochondrial phosphorylation can inhibit the formation of LPO-derived free radicals after an ischemic/hypoxic interval, mitochondria may represent an important source of free radicals capable of initiating lipid peroxidative injury during reperfusion/reoxygenation. (Mol Cell Biochem 160/161: 167–177, 1996) 相似文献
20.
Marianne Dorsch Friederike Behmenburg Miriam Raible Dominic Blase Hilbert Grievink Markus W. Hollmann André Heinen Ragnar Huhn 《PloS one》2016,11(3)