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L Rochette

Publications and source records attributed to L Rochette.

At least 37 records · Page 2Linked to original sources
PubMed2002

Prevention of apoptosis by deferoxamine during 4 hours of cold cardioplegia and reperfusion: in vitro study of isolated working rat heart model.

INTRODUCTION: Heart transplantation is often accompanied by multiple functional alterations, especially in reperfusion period. These are probably related to the reactive oxygen species (ROS) formation catalyzed by transition metals such as iron and copper, and thus the preservation time of the donor hearts is limited. Metabolic protection of the heart grafts is a permanent objective of numerous experiments. Recently, an iron chelator deferoxamine (DFX) was proposed as antioxidant agent for storage solutions in heart grafts. Oxidative stress is also known to mediate the apoptotic cell death in different tissues during ischemia-reperfusion. METHODS: The aim of this study was to evaluate a possible role of DFX in prevention of apoptosis using in vitro model of isolated working rat heart and cold cardioplegia. Two groups of rats were evaluated: (a) group 'DFX 50 &mgr;M' (n=8) and (b) group 'controls' (n=8). Isolated rat hearts were perfused by Krebs-Henseleit buffer (KHB) for 30 min, arrested by cardioplegic solution and stored for 4 h in B21 solution at 4 degrees C. Then, the hearts were reperfused by KHB for 45 min. DFX was added to the cardioplegic and storage solutions and in KHB in reperfusion. Basic functional parameters were evaluated: coronary, aortic, cardiac outputs and heart rate. At the end of reperfusion period a tissue samples were taken from left ventricle and in situ detection of apoptotic cells was performed using an ApopTag kit. RESULTS: DFX significantly reduced the occurrence of apoptotic cells in myocardium (*P<0.05). Hearts treated by 50 &mgr;M of DFX showed also a better recovery of the cardiac output (***P<0.001). The presence of DFX in KHB, cardioplegic and storage solution reduced also the incidence of postischemic arrhythmias and fibrillation's but without statistical significance. CONCLUSIONS: Our results give evidence of the protective potential of DFX during cold ischemia and reperfusion, presumably due to its antioxidant properties. The significant decrease of apoptosis in hearts treated by DFX could be considered as an existence of close link between oxidative stress and apoptotic death promotion in ischemia-reperfusion injury.

Journal Article↗
PubMed2001

The neuropeptide calcitonin gene-related peptide differently modulates proliferation and differentiation of smooth muscle cells in culture depending on the cell type.

Calcitonin gene-related peptide (CGRP) is a neuropeptide present around vasculature very early during development, when smooth muscle cells (SMC) are still proliferating and not yet totally differentiated. We investigated the effects of CGRP on proliferation and differentiation of SMC in culture; 10(-7) M CGRP added in the medium of cultured smooth muscle cells every 2 days did not significantly changed cells growth rate in 1% FCS. At the opposite, this treatment modulated proliferation of cells grown in 10% FCS medium. Two distinct populations of SMC with different growth rates were obtained from our primary cultures. SMC which proliferated slowly in the presence of 10% fetal calf serum (FCS) had growth rates positively influenced by CGRP. The quantity of alpha-smooth actin expressed by these cells was not influenced by the peptide. On the contrary, SMC which proliferated more rapidly in 10% FCS medium had growth rate inhibited by CGRP. In these cells, CGRP significantly reduced the amount of expressed alpha-smooth actin, an index of SMC differentiation. In both cases, the peptide significantly increased the level of mRNA for all the actin genes. In the light of this dual role of CGRP, it can be presumed that this peptide controls smooth muscle cells proliferation and differentiation in vivo and could thus regulate the homeostasis of the vessel wall.

Actins↗
PubMed2001

Vitamin E-coated dialyzer reduces oxidative stress in hemodialysis patients.

The high incidence of cardiovascular disease in hemodialyzed (HD) patients is well established and oxidative stress has been involved in this phenomenon. The aim of our study was to evaluate if a vitamin E-coated dialyzer could offer protection to HD patients against oxidative stress. Sixteen HD patients were successively assessed for one month (i) on a high biocompatible synthetic dialyzer (AN) and (ii) on a vitamin E-coated dialyzer (VE). Blood samples were taken before and after the dialysis session at the end of each treatment period. HD session conducted with the AN dialyzer was responsible for acute oxidative stress, significantly assessed after HD by a decreased plasma vitamin C level and an increased ascorbyl free radical (AFR)/vitamin C ratio used as an index of oxidative stress. Plasma elastase activity, reflecting neutrophil activation, was also increased; soluble P-selectin, reflecting platelet activation, did not show any variation. The use of the VE dialyzer was associated with a less extended oxidative stress compared with the AN membrane: basal vitamin C level was higher, and after the HD session AFR/vitamin C ratio and elastase activity were not significantly increased. Plasma vitamin E levels were not affected. Our study demonstrates that HD is associated with oxidative stress, which can be partially prevented by the use of a vitamin E-coated dialyzer. Our data suggest that this dialyzer may exert a site-specific scavenging effect on free radical species in synergy with a reduced activation of neutrophils.

Aged↗
PubMed2001

Effects of phosphodiesterase inhibitors on hypoxic pulmonary vasoconstriction. Influence of K(+) channels and nitric oxide.

We studied the relaxant effects of the cyclic nucleotide phosphodiesterase inhibitors theophylline (non-selective), rolipram (type IV, 3',5'-cyclic monophosphate (cAMP)-specific) and zaprinast (type V, 3',5'-cyclic monophosphate (cGMP)-specific) on the hypoxic vasoconstriction in the isolated perfused rat lung and the involvement of K(+) channels and nitric oxide (NO) in these effects. K(+) channels were inhibited by glibenclamide, charybdotoxin, apamin and 4-aminopyridine and nitric oxide synthase by L-N(G)-nitroarginine methyl ester (L-NAME). Hypoxic ventilation produced a significant pressure response. L-NAME and 4-aminopyridine increased this response. Rolipram, zaprinast and theophylline shared the ability to oppose the hypoxic pulmonary vasoconstriction. The order of potency was zaprinast>rolipram>theophylline. Glibenclamide partially inhibited the relaxant effects of rolipram and theophylline. Charybdotoxin inhibited the dilator response to rolipram. Apamin inhibited partially the vasodilation induced by rolipram and zaprinast. 4-Aminopyridine inhibited partially the relaxant effects of theophylline. L-NAME failed to block the effects of the three compounds. These data illustrate different pharmacological profiles according to the phosphodiesterase inhibitors and support the potential interest of selective inhibitors as relaxant agents in pulmonary vessels.

4-Aminopyridine↗
PubMed2001

Effectiveness of a single dose of acellular pertussis vaccine to prevent pertussis in children primed with pertussis whole cell vaccine.

We estimated the protection given by one booster dose of acellular pertussis vaccine (aP) given at 18 months or before school entry to children already primed with whole cell vaccine (wP). Case-control studies were conducted in these two age groups. In children who received or were eligible to receive their 18 months booster, the risk of pertussis was 1.4 and 3.6 times higher for those with 4 and 3 wP, respectively, compared to those with 3 wP + 1 aP. In 5 and 6 yr old children, the risk of pertussis among the subjects with 5 and 4 wP, was 1.4 and 2.1 times higher respectively than in those who received 4 wP + 1 aP. A single dose of aP increased the protection against pertussis and this protection was greater than that obtained with a wP booster.

Age Factors↗
PubMed2001

Influence of deep hypothermia on the tolerance of the isolated cardiomyocyte to ischemia-reperfusion.

The influence of deep hypothermia (4 degrees C) during a substrate-free, hypoxia-reoxygenation treatment was investigated on cardiomyocytes (CM) prepared from newborn rat heart in culture in an in vitro, substrate-free model of ischemia-reperfusion. The transmembranous potentials were recorded with standard microelectrodes. The contractions were monitored photometrically. The RNA messenger (mRNA) and protein expression for protein (HSP70) were analysed by RT-PCR (reverse transcriptase-polymerase chain reaction) and Western blotting, respectively. Simulated ischemia (SI) caused a gradual decrease and then a cessation of the spontaneous electromechanical activity. During the reoxygenation, the CM recovered normal function, provided that SI did not exceed 2.5 h. When SI duration was increased up to 4 h, reoxygenation failed to restore the spontaneous electromechanical activity. Conversely, the exposure of the CM to SI together with deep hypothermia decreased the functional alterations observed, and provided a complete electromechanical recovery after 2.5 h as well as after 4 h of SI. Deep hypothermia alone failed to induce HSP70 mRNA and protein production. On the contrary, HSP70 mRNA production increased after 2.5 and 4 h of deep hypothermia followed by 1 h of rewarming, proportionally to the duration of the cooling period. This augmentation in mRNA was associated with a rise in HSP70 protein content. In summary, it appeared that deep hypothermia exerts a strong cytoprotective action during SI only, whereas cooling CM before SI has no beneficial effect on subsequent SI. Moreover, these results suggested the persistence of a signaling system and/or transduction in deeply cooled, functionally depressed cells. Finally, CM in culture appeared to be a model of interest for studying heart graft protection against ischemia-reperfusion and contributed to clarifying the molecular and cellular mechanisms of deep hypothermia on myocardium.

Animals↗
PubMed2001

Modification of the rat aortic wall during ageing; possible relation with decrease of peptidergic innervation.

Structural changes of the male rat aorta were followed from birth to old age in male and female rats. In males, the vessel media width and area progressively increase concomitantly with a decrease of nuclei density during ageing, suggesting an hypertrophy of the smooth muscle cells. These correlations were however not evidenced in females. TUNEL-positive cells were found in media of 4 and 6 months in both sexes, mainly on the luminal side and in the adventitia. When biochemical markers were investigated with immunohistochemistry, media was uniformly stained by the anti-vimentin and anti-alpha-smooth actin at all stages investigated. On the contrary, the surface of media stained with anti-desmin decreased during ageing, especially on the luminal side. As observed with electron microscopy, with ageing the endothelium is replaced by small cells with pseudopodia adhering to the vestigial elastic lamina and infiltrating into the extracellular matrix left after the disappearance of smooth muscle cells. In addition, in the older rats (25-29 months) the elastic laminae are completely disorganised. Hypertrophy of the smooth muscle cells was confirmed by this approach. In parallel to this study, perivascular peptidergic innervation was stained with antibodies against calcitonin gene-related peptide (CGRP), substance P (SP), neuropeptide Y (NPY), and vasoactive intestinal polypeptide (VIP) at different ages during the whole life of rats. These peptides are present in stages younger than 6 months, then gradually disappear. In one year animals and older, the peptidergic innervation has totally disappeared. We discuss the possible role of peptidergic innervation in the control of the vessel wall cellular stability during ageing.

Actins↗
PubMed2001

Postischemic myocardial recovery and oxidative stress status of vitamin C deficient rat hearts.

OBJECTIVE: To investigate the role of vitamin C tissue content as a protective agent during myocardial ischemia-reperfusion injury, we have evaluated the postischemic functional recovery and free radical release of osteogenic disorder Shionogi (ODS) inherently scorbutic rat hearts and compared them to healthy Wistar rat hearts. METHODS: Isolated perfused hearts of ODS or Wistar rats underwent 30 min of a global total normothermic ischemia followed by 30 min of reperfusion. The lipid-soluble spin trap alpha-phenyl N-tert-butylnitrone (3 mM) was perfused upstream of the coronary bed. Functional parameters were recorded and samples of coronary effluents were analysed using electron spin resonance spectroscopy to characterise and quantify the amount of radical species released. RESULTS: From the onset of reperfusion, a large and long-lasting release of alkyl/alkoxyl radicals was detected, with a peak value of 29.0+/-3.2 nM obtained after 13 min, which was associated with a persistent contractile dysfunction. However, ODS rat hearts showed a higher myocardial recovery with lower left ventricular end diastolic pressure (44.34+/-1.74 vs. 55.03+/-1.57 mmHg for Wistar), higher recovery of rate pressure product (12.3+/-1.4 vs. 1.9+/-1.7x10(3) mmHg beats/min for Wistar) and shorter duration of contractile abnormalities during reperfusion (3.7+/-1.0 vs. 20.8+/-5.3 min for Wistar). Moreover, free radical release was identical in ODS rat hearts as compared to control Wistar rats. Ascorbic acid tissue content was significantly altered in ODS rats (31.9+/-3.3 vs. 591.0+/-54.9 mmol/g of tissue for Wistar) but superoxide dismutases, glutathion peroxidases and inducible heat shock protein 70 genes were up-regulated. CONCLUSIONS: This study shows that ascorbic-acid-deficient ODS rat hearts are more resistant to an ischemic insult than control Wistar rats, probably through the development of alternative protective defences, like the induction of heat shock proteins. These paradoxical results raise the question of the relative importance of each endogenous antioxidant in the cardiac resistance to ischemia-reperfusion injury.

Analysis of Variance↗
PubMed2001

Changes in HSP70 and P53 expression are related to the pattern of electromechanical alterations in rat cardiomyocytes during simulated ischemia.

The objective was to relate the response of the HSP70 and P53 genes to the cessation and the recovery of cardiac muscle cell functions when submitted to ischemia-reperfusion. We have measured the electromechanical activity, the released enzymes and HSP70 RNA and protein levels in cultured neonatal rat cardiomyocytes (CM) in a substrate-free, hypoxia-reoxygenation model of ischemia-reperfusion. In parallel the expression of the two genes P53 (the key apoptosis regulator gene) and P21/Waf1 (the P53 target gene) has been evaluated. The functional recovery during post-'ischemic' reoxygenation was associated with an overexpression of HSP70 and P53 lasting until the functional parameters reverted back to the normal, prehypoxic values. In contrast, extending the substrate-free hypoxic treatment worsens the dysfunction of the cardiac muscle cell and, in these conditions, reoxygenation failed to restore cell functions and to activate HSP70. Finally, in the conditions of reversible 'ischemic' cell injury, an early and transitory activation of P53 was associated with the functional recovering process of the CM submitted to simulated ischemia. These observations are suggestive of a contributive role of both HSP70 and P53 to a cytoprotective program activated by reoxygenation in post-'ischemic' CM.

Animals↗
PubMed2001

Effects of dietary polyunsaturated fatty acids and hepatic steatosis on the functioning of isolated working rat heart under normoxic conditions and during post-ischemic reperfusion.

The purpose of this study was to modify the amount of 22:4 n-6, 22:5 n-6 and 20:5 n-3 in cardiac phospholipids and to evaluate the influence of these changes on the functioning of working rat hearts and mitochondrial energy metabolism under normoxic conditions and during postischemic reperfusion. The animals were fed one of these four diets: (i) 10% sunflower seed oil (SSO); (ii) 10% SSO + 1% cholesterol; (iii) 5% fish oil (FO, EPAX 3000TG, Pronova) + 5% SSO; (iv) 5% FO + 5% SSO + 1% cholesterol. Feeding n-3 PUFA decreased n-6 PUFA and increased n-3 PUFA in plasma lipids. In the phospholipids of cardiac mitochondria, this dietary modification also induced a decrease in the n-6/n-3 PUFA ratio. Cholesterol feeding induced marked hepatic steatosis (HS) characterized by the whitish appearance of the liver. It also brought about marked changes in the fatty acid composition of plasma and mitochondrial phospholipids. These changes, characterized by the impairment of deltaS- and delta6-desaturases, were more obvious in the SSO-fed rats, probably because of the presence of the precursor of the n-6 family (linoleate) in the diet whereas the FO diet contained large amounts of eicosapentaenoic and docosahexaenoic acids. In the mitochondrial phospholipids of SSO-fed rats, the (22:4 n-6 + 22:5 n-6) to 18:2 n-6 ratio was decreased by HS, without modification of the proportion of 20:4 n-6. In the mitochondrial phospholipids of FO-fed rats, the amount of 20:5 n-3 tended to be higher (+56%). Cardiac functioning was modulated by the diets. Myocardial coronary flow was enhanced by HS in the SSO-fed rats, whereas it was decreased in the FO-fed animals. The rate constant k012 representing the activity of the adenylate kinase varied in the opposite direction, suggesting that decreased ADP concentrations could cause oxygen wasting through the opening of the permeability transition pore. The recovery of the pump function tended to be increased by n-3 PUFA feeding (+22%) and HS (+45%). However, the release of ascorbyl free radical during reperfusion was not significantly modified by the diets. Conversely, energy production was increased by ischemia/reperfusion in the SSO group, whereas it was not modified in the FO group. This supports greater ischemia/reperfusion-induced calcium accumulation in the SSO groups than in the FO groups. HS did not modify the mitochondrial energy metabolism during ischemia/reperfusion. Taken together, these data suggest that HS- and n-3 PUFA-induced decrease in 22:4 and 22:5 n-6 and increase in 20:5 n-3 favor the recovery of mechanical activity during post-ischemic reperfusion.

Adenine↗
PubMed2001

Role of nitric oxide synthases in the infarct size-reducing effect conferred by heat stress in isolated rat hearts.

Nitric oxide (NO) donors are known to induce both delayed cardioprotection and myocardial heat stress protein (HSP) expression. Moreover, heat stress (HS), which also protects myocardium against ischaemic damages, is associated with a NO release. Therefore, we have investigated the implication of NO in HS-induced resistance to myocardial infarction, in the isolated rat heart model. Rats were divided in six groups (n=10 in each group), subjected or not to heat stress (42 degrees C internal temperature, 15 min) and treated or not with nitro-L-arginine-methylester (L-NAME) a non-selective inhibitor of NO synthase isoforms, or L-N(6)-(1-imino-ethyl)lysine (L-NIL), a selective inhibitor of the inducible NO synthase. Twenty-four hours after heat stress, their hearts were isolated, retrogradely perfused, and subjected to a 30-min occlusion of the left coronary artery followed by 120 min of reperfusion. Infarct-to-risk ratio was significantly reduced in HS (18.7+/-1.6%) compared to Sham (33.0+/-1.7%) hearts. This effect was abolished in L-NAME-treated (41.7+/-3.1% in HS+L-NAME vs 35.2+/-3.0% in Sham+L-NAME ) and L-NIL-treated (36.1+/-3.4% in HS+L-NIL vs 42.1+/-4.6% in Sham+L-NIL) groups. Immunohistochemical analysis of myocardial HSP 27 and 72 showed an HS-induced increase of these proteins, which was not modified by L-NAME pretreatment. We conclude that NO synthases, and in particular the inducible isoform, appear to play a role in the heat stress-induced cardioprotection, independently of HSP 27 and 72 levels. Further investigations are required to elucidate the precise role of HSPs in this adaptive response.

Animals↗
PubMed2001

Efficacy of eye patching for traumatic corneal abrasions: a controlled clinical trial.

STUDY OBJECTIVE: We sought to evaluate the efficacy of eye patching in the treatment of traumatic corneal abrasions in terms of time to healing and reduction in pain and discomfort. METHODS: One hundred sixty-three patients presenting at the emergency department of a large university-affiliated hospital with traumatic corneal abrasions were included in this single-blind prospective controlled trial. Eligible patients were assigned to 1 of 2 treatment regimens: topical antibiotic ointment and occlusive patch over the affected eye (n=82) or topical antibiotic ointment 4 times a day without an occlusive patch (n=81). Patients were reexamined every 24 hours until corneal healing occurred. Healing evaluation was performed by the emergency physician, using a slit lamp with fluorescein staining, without knowledge of the patient's assignment to a treatment group. The degree of discomfort was assessed at each visit by using a visual analog scale. RESULTS: Both treatment groups were similar regarding size of the corneal lesions, delay from trauma to first ED visit, presence of foreign body or siderosis, initial degree of discomfort, and presence of specific symptoms (irritation, foreign body sensation, photophobia, redness, and pain). In the patched group, cumulative incidences of healing were 51%, 78%, and 92% after 1, 2, and 3 days, respectively, compared with 60%, 83%, and 88% in the nonpatched group. In the patched group, symptoms of initial discomfort decreased by 4.8, 4.1, and 5.5 cm after 1, 2, and 3 days, respectively, compared with 3.3, 5.1, and 6.5 cm in the nonpatched group. CONCLUSION: Eye patching does not appear to be beneficial in the treatment of traumatic corneal abrasions compared with topical antibiotic ointment.

Administration, Topical↗
PubMed2001

Isolated perfused rat hearts release secondary free radicals during ischemia reperfusion injury: cardiovascular effects of the spin trap alpha-phenyl N-tert-butylnitrone.

Free radicals produced during myocardial post-ischemic reperfusion are aggravating factors for functional disturbances and cellular injury. The aim of our work was to investigate the significance of the secondary free radical release during non ischemic perfusion and post-ischemic reperfusion and to evaluate the cardiovascular effects of the spin trap used. For that purpose, isolated perfused rat hearts underwent 0, 20, 30 or 60 min of a total ischemia, followed by 30 min of reperfusion. The spin trap: alpha-phenyl N-tert-butylnitrone (PBN) was used (3 mM). Functional parameters were recorded and samples of coronary effluents were collected and analyzed using Electron Paramagnetic Resonance (EPR) to identify and quantify the amount of spin adducts produced. During non ischemic perfusion, almost undetectable levels of free radical release were observed. Conversely, a large and long-lasting (30 min) release of spin adducts was detected from the onset of reperfusion. The free radical species were identified as alkyl and alkoxyl radicals with amounts reaching 40 times the pre-ischemic values. On the other hand, PBN showed a cardioprotective effect, allowing a significant reduction of rhythm disturbances and a better post-ischemic recovery for the hearts which were submitted to 20 min of ischemia. When the duration of ischemia increased, the protective effects of PBN disappeared and toxic effects became more important. Our results have therefore confirmed the antioxidant and protective properties of a spin trap agent such as PBN. Moreover, we demonstrated that the persistent post-ischemic dysfunction was associated with a sustained production and release of free radical species.

Animals↗
PubMed2001

Levels of nitric oxide in the heart after experimental myocardial ischemia.

The effect of myocardial ischemia on nitric oxide (NO) production is controversial in part because of indirect NO quantification. In the present study, direct quantification of NO was investigated in an in vivo rat model of myocardial ischemia (MI). A NO spin-trapping technique using electron spin resonance (ESR) spectroscopy was used to study NO production in the ischemic and in the nonischemic area of the rat heart 2, 8, or 24 h after left main coronary artery ligation. The method was based on the trapping of NO by a metal-chelator complex consisting of N-methyl-D-glucamine-dithiocarbamate (MGD) and Fe(II) to form a stable NO-FeMGD complex that gives rise to a characteristic triplet ESR spectrum. This metal-chelator complex was administered half an hour before sacrifice of the rats. A large and time-dependent increase of the ESR signal corresponding to the NO-FeMGD complex was observed 8 h (11.6 +/- 0.9 arbitrary units [AU]) and 24 h (29.7 +/- 2.9 AU) in the ischemic area after MI. On the contrary, no ESR triplet was observed in the nonischemic region of the heart and in sham-operated rats. NO blood derivative levels (nitrosylhemoglobin and plasma nitrites and nitrates) were unchanged compared with sham-operated rats. Previous administration of aminoguanidine, a NO synthase inhibitor, in animals subjected to a 24-h ischemia resulted in a complete abolition in the NO-FeMGD spectrum in the ischemic area. These findings directly demonstrated an increase of the NO-FeMGD levels during in vivo myocardial ischemia that appeared to be specifically localized in the ischemic area.

Animals↗
PubMed2001

Effect of repeated regional myocardial ischemia in the rat heart on reperfusion arrhythmias and release of norepinephrine.

We tested the hypothesis that repetitive regional myocardial ischemia in the rat could decrease reperfusion ventricular arrhythmias, possibly acting by diminished release of norepinephrine. Isolated perfused working rat hearts were pre-labeled with tritiated norepinephrine (NE3H). The efflux of 3H-labeled compounds was measured in the effluent coronary flow. Each heart was subjected to two consecutive periods of regional myocardial ischemia induced by ligature of the left coronary artery. The duration of the first ischemic period was 5 or 10 min and that of the second was 10 min. Serious rhythm disturbances did not occur during the first period of ischemia but did after reperfusion. The amount of NE3H liberated during the reperfusion period was more marked after an initial ischemic period of 10 min than after 5 min of ischemia. Reperfusion arrhythmias were of little importance after 5 min of ischemia but developed in a sustained pattern when reperfusion followed 10 min of ischemia. After 5 min of ischemia, the mean duration of reperfusion arrhythmias was 12.8 +/- 10.4 s during the first 3 min of reperfusion, but after 10 min of ischemia the mean duration of serious rhythm disturbances was 149.7 +/- 16.7 s. Reperfusion after the second 10-min occlusion increased the release of NE3H. In series 5-10, the percentage of NE3H compared with the total radioactivity was a mean of 71.4 +/- 3.3% during the 5 min of ligature, 79.0 +/- 5.3% during the first 3 min of reperfusion. During the 10-10 series in which the ligature was maintained for 10 min, the percentage of NE3H compared with the total radioactivity was 70.6 +/- 5.1%, 81.1 +/- 8.7% during the first 3 min of reperfusion. These results show no reduction of any catecholamine release or of reperfusion arrhythmias by repetitive regional ischemia and provide no evidence for any preconditioning effect after short periods of regional ischemia. The antiarrhythmic effects of repetitive myocardial ischemia such as preconditioning previously reported may depend on the exact protocols used.

Animals↗
PubMed2001

Hypoxic vasoconstriction of rat main pulmonary artery: role of endogenous nitric oxide, potassium channels, and phosphodiesterase inhibition.

This study investigated the influence of NO, potassium (K+) channel blockade, and the phosphodiesterase inhibitors (PDEIs) theophylline (non-selective PDEI), siguazodan (PDE3I), rolipram (PDE4I), and zaprinast (PDE5I) on rat isolated main pulmonary artery hypoxic (95% N2 and 5% CO2) vasoconstriction. Hypoxic vasoconstriction increased by 27% (p < 0.01) in the presence of the NO synthase inhibitor L-NAME (10(-4) M), and by 15% (p < 0.05) in the presence of the K(ATP) channel blocker glibenclamide (10(-6) M), without potentiation by the combination of these two drugs. Hypoxic vasoconstriction decreased by 28% (p < 0.01) in presence of the Kv,-voltage-dependent channel blocker 4-aminopyridine (10(-3) M), whereas the other K+ channel blockers, charybdotoxin (BKCa, large-conductance Ca2+-sensitive K+ channels) and apamin (SKCa, small-conductance Ca2+-sensitive K+ channels) had no effect. The nonselective PDEI theophylline induced a concentration-dependent relaxation (pD2 = 4.05, Emax = 90% [expressed as a percentage of maximal relaxation induced by papaverine 10(-4) M]). Among the selective PDEIs, siguazodan was significantly (p < 0.01) more efficient than rolipram and zaprinast (Emax values were 84%, 67%, and 58%, respectively) and significantly (p < 0.05) more potent than zaprinast (pD2 values were 6.48, 6.34, and 6.16 for siguazodan, rolipram, and zaprinast). Glibenclamide and L-NAME significantly (p < 0.05) shifted the concentration-response curve (CRC) for zaprinast to the right, and L-NAME shifted the CRC significantly to the right for siguazodan. In the presence of L-NAME, glibenclamide had no effect on the CRC of zaprinast. We conclude that (a) NO exerts a permanent inhibitory effect against hypoxic vasoconstriction that might be mediated in part by an activation of K(ATP) channels; (b) a 4-aminopyridine-sensitive K+ channel is involved in vasoconstriction under hypoxic conditions; (c) PDEs 3 and 5 are the predominant PDE isoforms in rat pulmonary artery relaxation; and (d) NO and K(ATP), but neither BK(Ca), SK(Ca), nor Kv channels, are involved in the relaxant effect of PDEIs.

Animals↗
PubMed2001

In vitro free radical scavenging capacity of thyroid hormones and structural analogues.

It was reported that thyroid hormones decreased Cu(2+)-induced low-density lipoprotein (LDL) oxidation in vitro. Here, we investigated free radical scavenging capacities of thyroid hormones (3,5,3'-tri-iodo-L-thyronine (T(3)), thyroxine (T(4)) and 3,3',5'-tri-iodo-L-thyronine (rT(3))) and structural analogues (L-thyronine (T(0)), 3,5,3'tri-iodothyroacetic acid (TA(3)) and 3,5,3',5'-tetra-iodothyroacetic acid (TA(4))), using three different models of free radical generation. T(0), T(3) and TA(3) slowed down production of conjugated diene and thiobarbituric acid-reactive substances during LDL oxidation by 2,2'-azobis-[2-amidinopropane] (water-soluble), whereas rT(3), T(4) and TA(4) had practically no effect. In this system, T(0) was the more active compound. Using a 1,1-diphenyl-2-picrylhydrazyl (lipid-soluble) test, all compounds also revealed free radical scavenging capacities, but rT(3), T(4) and TA(4) were more active than T(0), T(3) and TA(3). T(3) was able to scavenge superoxide anion and hydroxyl radicals generated in an aqueous phase by a xanthine-xanthine oxidase system, as measured by electron paramagnetic resonance spectroscopy. It may be concluded that: (1) thyroid hormones and analogues with a 4'-hydroxy diphenylether structure have free radical scavenging capacities, (2) this property is influenced by the number of iodines on the phenolic ring, and (3) thyroid hormone scavenging capacity should not be the only mechanism explaining their protective effect on Cu(2+)-induced LDL oxidation. The physiological significance of the findings is discussed.

Analysis of Variance↗