Tez (Tıpta Uzmanlık) - Süleyman Demirel Üniversitesi, Tıp Fakültesi, Kalp ve Damar Cerrahisi Anabilim Dalı, 2006. / Bibliyografya var.

Diss. (sammanfattning) Uppsala : Univ., 2002. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 5 uppsatser.

Diss. (sammanfattning) Uppsala : Univ., 2002. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 5 uppsatser.

Background: Glucagon-like Peptide 1 (GLP-1) is a human incretin hormone that has been demonstrated to protect against non-lethal ischaemia reperfusion injury in the left ventricle in humans. It has been suggested from some animal research that this protection may be mediated through the pathway of ischaemic conditioning, of which the opening of the mKATP channel is a key step. Furthermore, it is uncertain whether the protection applies to the right ventricle. Finally, there is limited human evidence of a protective effect against lethal ischaemia reperfusion injury. Methods: Two studies use non-lethal ischaemia to test whether GLP-1 protection is maintained despite blockade of the mKATP channel with the sulfonylurea, glibenclamide. A demand ischaemia study uses dobutamine stress echo to compare LV function. The other uses transient coronary balloon occlusion to generate supply ischaemia during GLP-1 infusion, assessed by conductance catheter. A further transient balloon occlusion is also used to assess the effect of supply ischaemia on RV function. Finally, the GOLD PCI study assesses whether GLP-1 protects against periprocedural myocardial infarction when administered during elective PCI in a randomised, placebo controlled double blind trial. Results: Glibenclamide did not affect GLP-1 cardioprotection in either supply of demand ischaemia suggesting that GLP-1 protection is not mediated through the mKATP channel. The RV experienced stunning with RCA balloon occlusion but there was little evidence of cumulative ischaemic dysfunction with further occlusions. GOLD PCI is continuing to recruit patients. The nature of the study means results cannot be assessed until recruitment is complete. Conclusions: GLP-1 is an agent with potential for clinical use as a cardioprotective therapy. It’s mechanism of action in the heart remains uncertain.

Ischaemia reperfusion injury (IR-injury) occurs when blood supply to a certain area of the body is blocked, and is subsequently followed by reperfusion. During the period of ischaemia, tissue is damaged as a result of lack of oxygen. Rapid reperfusion is mandatory, but unfortunately causes damage in addition to the damage induced by ischaemia alone. While a prolonged period of ischaemia is harmful to the bodily tissue, short periods of ischaemia interspersed with short bouts of reperfusion have protective effects. This mechanism is called ischaemic preconditioning (IPC). In this thesis, the impact of co-morbidity and age on IR-injury and IPC are explored. Moreover, the possible role of IPC to enhance exercise performance is investigated. Finally an attempt is made to understand the interchangeable effects of IPC and exercise performance in the prevention of IR-injury. Using the brachial artery endothelial function as a surrogate marker, first the consequences of IR-injury in both young and older individuals on endothelial function were studied. It was also assessed whether IPC could prevent endothelial IR-injury. It was found that endothelial function in both groups declined, when IR-injury was not preceded with IPC. However, when IPC was applied prior to IR-injury, a protective effect was detected in young subjects, but not in older participants. In chapter 5, this study was repeated in patients with heart failure, as they are at an increased risk for IR-injury. While in both groups a significant decline in endothelial function was observed, a much larger decline was established in the heart failure group. Moreover, IPC failed to protect against endothelial dysfunction in heart failure patients after IR-injury. The third study presented in this thesis, focused on the question whether exercise performance enhancement during a 5-km time trial was comparable when IPC on the upper legs was applied immediately before the time trial versus 24 hours (24-IPC) prior to exercise. Interestingly, a significant and strong correlation was found in finish time between acute IPC and 24-IPC, suggesting comparable effects of IPC and 24-IPC on exercise performance. In a follow-up study, it was determined whether local IPC applied on the upper arm, or remote IPC applied on the legs, would lead to an improved maximum incremental arm crank exercise test in individuals with a complete spinal cord lesion. The main finding was that upper arm IPC led to an increased performance enhancement, whilst remote IPC (stimulus below the lesion) did not lead to any significant differences. These studies help to inform the best or most practical application of IPC in daily life situations. Some previous work has suggested that exercise may resemble some of the effects of IPC. More specifically, acute exercise might possess the same protective effects against ischaemia-reperfusion injury as IPC. Therefore, in young healthy individuals it was studied, whether an acute bout of endurance or interval exercise is able to protect against brachial endothelial IR-injury. It was established that interval exercise prevented endothelial dysfunction after an IR stimulus, while no protective effect of endurance exercise was found. It was concluded that interval exercise, but not endurance exercise, prevented endothelial dysfunction after an ischaemic period. In conclusion, this thesis provides further evidence for the protective effects of (remote) IPC, both on the prevention of endothelial IR-injury as well as improvement in exercise performance. However, effects may depend on the protocol and population studied.

Thesis (MTech (Biomedical Technology))--Cape Peninsula University of Technology, 2006 / Research has shown that the activation of the NO-cGMP pathway leads to myocardial protection from oxidative stress conditions, such as ischaemia and reperfusion. Few of these studies have however combined diet induced oxidative stress with ischaemia/reperfusion injury. Although little is known about the effects of supplements such as red palm oil (RPO) on the NO-cGMP pathway, research has shown that dietary RPO-supplementation improved reperfusion aortic output recovery through mechanisms that may include activation of the NO-cGMP- and inhibition of the cAMP pathway. RPO is an antioxidant-rich oil containing ~carotene and Vitamin E (tocopherols and tocotrienols). The aims of this study were to determine: 1) whether RPO-supplementation of an oxidative risk induced diet (ORD) and a high saturated fat diet (HFD) offers protection against ischaemia/reperfusion injury in the isolated perfused rat heart and 2) the possible mechanisms for this protection. Male Wistar rats were randomly divided into four groups for a period of 14 weeks according to the dietary supplementation they received. The control groups received either an oxidative risk induced diet (ORD) or a high saturated fat diet (HFD), while the experimental groups received an ORD supplemented with RPO (ORD+RPO) or a HFD supplemented with RPO (HFD+RPO).

A obstrução intestinal mecânica representa uma condição de urgência, necessitando diagnóstico precoce e terapêutica adequada, em virtude do seu elevado grau de morbidade e de mortalidade. Desta forma, o objetivo deste estudo foi avaliar o efeito da N-acetilcisteína associada ao Ringer lactato ou à solução salina hipertônica na resposta inflamatória, histologia e translocação bacteriana em modelo experimental de obstrução e isquemia intestinal. Para tanto, Foram constituídos quatro grupos experimentais, com 10 ratos Wistar em cada, além do grupo de referência: OI - Submetidos a obstrução e isquemia intestinal e enterectomia com anastomose intestinal, sem reanimação volêmica; RL - Submetidos a obstrução e isquemia intestinal, reanimação volêmica com Ringer lactato (32ml/kg, i.v., em 10 minutos) e enterectomia com anastomose intestinal; RLNAC - Submetidos a obstrução e isquemia intestinal, reanimação volêmica com Ringer lactato associado a NAC (32ml/kg + 150 mg/kg i.v. em 10 minutos) e enterectomia com anastomose intestinal; SHNAC - Submetidos a obstrução e isquemia intestinal, reanimação volêmica com solução salina hipertônica a 7,5% associado com NAC (4ml/kg + 150 mg/kg i.v., em 10 minutos) e enterectomia com anastomose intestinal. Grupo Referência (n=5): Animais anestesiados, submetidos a coleta de materiais para cultura e histologia e sacrificados por exsanguinação. Os animais receberam uma associação anestésica de cetamina e xilazina intramuscular em membro posterior direito, na dose de 60mg/kg e 10mg/kg, respectivamente. Decorridas 24 h do tratamento, a eutanásia foi realizada por exanguinação, sob anestesia, após a coleta dos tecidos / Mechanical intestinal obstruction represents a condition of urgency, necessary early diagnosis and appropriate therapy, due to their high degree of morbidity and mortality. In this way, the objective of this study was to evaluate the effect of N-acetylcysteine associated with lactated Ringer\'s or hypertonic saline solution in the inflammatory response, histology and translocation in an experimental model of intestinal obstruction and ischemia. For Four experimental groups were constituted with 10 Wistar rats each, in addition to the reference group: OI - submitted to obstruction and ischemia intestinal and enterectomy with intestinal anastomosis, without volume resuscitation; RL - Undergoing intestinal obstruction and ischemia, volume resuscitation with Ringer\'s lactate (32ml / kg, i.v., within 10 minutes) and anastomosis enterectomy intestinal; RLNAC - Undergoing obstruction and intestinal ischemia, resuscitation with lactated Ringer\'s lactating NAC (32 ml / kg + 150 mg / kg i.v. in 10 minutes) and enterectomy with intestinal anastomosis; SHNAC - Submitted to obstruction and intestinal ischemia, volume resuscitation with saline solution hypertension at 7.5% associated with CAP (4 ml / kg + 150 mg / kg i.v., in 10 minutes) and enterectomy with intestinal anastomosis. Reference Group (n = 5): Anesthetized animals, submitted to collection of materials for culture and histology and sacrificed by exsanguination. The animals received a anesthetic association of ketamine and intramuscular xylazine in limb posterior right, at the dose of 60mg / kg and 10mg / kg, respectively. After 24 h of treatment, euthanasia was performed by exsanguination, under anesthesia, after collection of tissues

Abstract Ischaemic cerebral injury follows a well attested sequence of events including three phases, i.e. depolarization, biochemical cascade and reperfusion injury. Glutamate excitotoxicity plays an important role in the development of ischaemic brain injury following prolonged hypothermic circulatory arrest (HCA), and leukocyte infiltration and a cytokine-mediated inflammatory reaction are known to play a pivotal role in the reperfusion phase. The aim of this series of experimental studies was to develop biochemical and reperfusion-related strategies to improve brain protection. We tested the hypotheses that the Na+ channel blocker lamotrigine (I) or the N-Methyl-D-Aspartate-receptor antagonist memantine (III) could improve the cerebral outcome after HCA and studied whether a leukocyte-depletion filter (L-DF; LeukoGuard LG6®, Pall Biomedical, Portsmouth, U.K) could mitigate brain injury (II). The aim of the fourth study was to find out whether lamotrigine combined with the leukocyte-depleting filter can potentiate cerebral protection (IV). A chronic porcine model was used, in which haemodynamic, electrophysiological, metabolic and temperature monitoring were performed for four hours after the instigation of rewarming and S-100β measured up to 20 hours. Cytokines were measured, microdialysis was performed, and daily behavioural assessments were made until death or elective sacrifice on the seventh postoperative day, upon which a histopathological analysis of the brain was carried out. The rate of EEG burst recovery was higher in the lamotrigine-treated animals, the median being 40% of the baseline compared with 17% in the placebo group at 4 hours after the start of rewarming (p = 0.02) and 80% compared with 20% at 4 hours (p = 0.01). Complete behavioural recovery was seen in 5/8 of cases (63%) after lamotrigine administration, compared with 1/8 (13%) in the placebo group (p = 0.02). The median behavioural score among the animals that survived for 7 days was higher in the lamotrigine group (8) than in the controls (7) (p = 0.02). Mortality was 2/10 in the L-DF group and 5/10 in the controls, the median behavioural score on day 7 being higher in the L-DF group (8.5 vs. 3.5 p = 0.04). The median of the total histopathological score was 6.5 in the L-DF group and 15.5 in the control group (p = 0.005). In the memantine group 5/10 animals survived seven days, as compared with 9/10 in the placebo group, and the median behavioural score on day 7 was 3.5 compared with 7.5 in the placebo group (p = 0.39). The median of the total histopathological score was 16 in the memantine group and 14 in the placebo group (p = 0.25). In the LD-F + lamotrigine group 7/8 animals survived for seven days, as compared with 4/8 in the lamotrigine only group and 3/8 among the controls. EEG burst recovery 7 hours after the start of rewarming was highest in the LDF + lamotrigine group, the median being 94% (p = 0.024 vs. controls), compared with 81% in the lamotrigine group and 64% in the control group. The median behavioural score on day 7 was 9 in the LD-F + lamotrigine group (p = 0.004 vs. controls), 4 in the lamotrigine group and 0 in the control group, while the median of total histopathological score was 14 (p = 0.046 vs controls), 14.5 (p = 0.062 vs. controls) and 21, respectively. The control group had the highest intracerebral lactate, glutamate and glycerol levels after HCA. In conclusion, the results indicate that the NA+ channel blocker lamotrigine improves the neurological outcome after a prolonged period of HCA but that the NMDA receptor antagonist memantine does not have this property in the present setting. The leukocyte-depleting filter mitigates brain injury after a prolonged period of HCA, and lamotrigine can potentiate this effect.