Effect of Dexmedetomidine on Transcription Factors and Inflammatory Cytokines in Elective Aortic Aneurysm Repair Surgery

Background: Aortic clamping during abdominal aortic aneurysm repair surgery leads to complications such as systemic inflammatory response (SIRS) and dysfunction in various vital organs. This study aimed to investigate the effect of dexmedetomidine infusion on transcription factors and inflammatory cytokines during elective open abdominal aortic aneurysm repair surgery. Materials and Methods: A prospective, clinical trial performed on patients with abdominal aortic aneurysm surgery, which were divided into two groups (dexmedetomidine, 8 patients and control, 12 patients). Demographic characteristics, biochemical laboratory variables, fluid and blood transfusions during surgery, and levels of inflammatory cytokines and expression of inflammatory genes were evaluated and compared in both groups. Results: There were no significant differences between the two groups regarding demographic characteristics, biochemical laboratory variables, fluids, and blood transfusions during surgery (P> 0.05). The level of inflammatory cytokines and the expression of inflammatory genes in both groups decreased significantly after surgery (P <0.05). However, the level of inflammatory cytokines and the expression of inflammatory genes in the dexmedetomidine group were significantly lower at the end of the surgery (P <0.05). Conclusion: In abdominal aortic aneurysm surgery, dexmedetomidine could significantly reduce complications of clamping during surgery, which may result in hemodynamic stability and prevent significant inflammatory response to surgical stress and organ damage following ischemia-reperfusion damage

Polarizing versus depolarizing blood cardioplegia: An experimental study of myocardial function, metabolism and ultrastructure following cardiopulmonary bypass and cardioplegic arrest

In cardiothoracic surgery, the use of the heart-lung machine for cardiopulmonary bypass (CPB) and induced cardiac arrest, cardioplegia, is required for performing the majority of the surgical procedures. Myocardial protection is essential during the ischemic period of cardioplegia. The aim of this project is to evaluate and verify if a recently developed routine for myocardial protection is feasible, safe and suited for use in clinical practice. This pre-clinical translational animal research project is designed to bridge the gap between basic research and new routines that may benefit the patient. In three different protocols, two groups of animals (10 in each group) are randomized to polarized or depolarized cardioplegic arrest. The novel and unexplored cardioplegic solution with esmolol, adenosine and magnesium; St Thomas’ Hospital polarizing cardioplegia (STH-POL) is compared with today’s gold standard; potassium-based St Thomas’ depolarizing solution (STH-2), both administered as repeated, cold, oxygenated blood. Left ventricular regional and global function in the early hours after weaning from CPB are evaluated together with myocardial ultrastructure and metabolism. Our hypothesis is that STH-POL improves myocardial protection demonstrated as better preserved postoperative cardiac function in a large animal translational model. This knowledge is essential before initiating clinical studies and implementation. An optimal myocardial protection is important when performing cardiac surgery in an ageing population with increased occurrence of more complex heart diseases and comorbidity. Paper I demonstrated improved regional and global contractility following 60 min of cardioplegic arrest with STH-POL compared to STH-2 blood cardioplegia. After weaning from CPB and following reperfusion, left ventricular dP/dtmax, Preload Recruitable Stroke Work and radial peak systolic strain rate were maintained 180 min after declamping in the group with polarized arrest and decreased with depolarized arrest. Paper II focused on energy metabolism and ultrastructure with the STH-POL compared to the STH-2 cardioplegia during 60 min of cardiac arrest and at early reperfusion. The study demonstrated increased levels of creatine phosphate in left ventricular myocardial tissue samples at the end of the period of cardioplegic arrest and early after reperfusion in the STH-POL compared to the STH-2 group. Furthermore, the adenosine triphosphate content was increased and the mitochondrial surface-to-volume ratio decreased with polarizing compared to depolarizing cardioplegia 20 min after reperfusion. However, at 180 min after reperfusion these group differences were negligible. Paper III addressed myocardial function after prolonged cardioplegic arrest for 120 min. A temporary increase in the load-independent contractility variable Preload Recruitable Stroke Work was seen in the STH-POL compared to the STH-2 group 150 min after declamping. Neither regional nor global left ventricular function differed between groups up to 240 min after declamping. However, compared to the STH-2 group, the left ventricular myocardial tissue blood flow rate decreased in the STHPOL group at 150 and 240 min compared to 60 min after declamping. The relationship between the left ventricular total pressure-volume area and blood flow rate was maintained after declamping in the STH-POL group and decreased in the STH-2 group. Thus, cardioplegic arrest with STH-POL alleviated the mismatch between myocardial function and perfusion after weaning from CPB compared to STH-2. Conclusion: In a porcine model, cardioplegic arrest with St. Thomas´ Hospital polarizing solution offered comparable myocardial protection and improved myocardial function (Paper I), preserved energy status (Paper II) and enhanced contractile efficiency (Paper III) in the early hours after weaning from cardiopulmonary bypass compared to St. Thomas´ Hospital No 2 blood cardioplegia

Effectiveness of Assistance Circulations for Distal Circulatory Support during Cross-clamping of the Descending Thoracic Aorta

In order to find the ideal distal circulatory support during cross-clamping of the descending thoracic aorta, the author compared the effects of simple shunting (SS) and centrifugal pump (CP) on hemodynamics and metabolisms in mongrel dogs. In group I (control), the aorta was cross-clamped for two hours without SS or CP; in group II (SS), a temporary shunt was placed between the left common carotid and left femoral arteries during cross-clamping; in group III (CP), with left heart bypass, the flow was maintained about the same as that in group II; in group IV (CP), proximal pressure was maintained unchanged. Hemodynamic and metabolic parameters were recorded prior to cross-clamping and every 30 min for four hours during and after cross-clamping. All animals in group I suffered from hemodynamic instability, metabolic abnormalities and neurologic injury and died within 12 hours. Hemodynamic changes were more unstable in group III than in groups II and IV. Three dogs in group III and also in group IV but none in group II, suffered from neurologic injury. Metabolic changes in groups II, III and IV were not significant. The author conclude that hemodynamic and metabolic abnormalities can be minimized through the efficient use of a shunt in cross-clamping of the descending thoracic aorta and postoperative complications such as paraplegia, renal failure and hepatic dysfunction can be prevented. The centrifugal pump as a distal circulatory support device is able to maintain stable hemodynamics and normal distal organic metabolisms if aortic pressure proximal to the clamp is maintained essentially unchanged through regulation of pump flow. However, it is unable to prevent paraplegia during cross-clamping of the descending thoracic aorta for two hours. Shortening the time of cross-clamping of the descending thoracic aorta is necessary to prevent paraplegia

Left ventricular dysfunction after two hours of polarizing or depolarizing cardioplegic arrest in a porcine model

Introduction: This experimental study compares myocardial function after prolonged arrest by St. Thomas’ Hospital polarizing cardioplegic solution (esmolol, adenosine, Mg2+) with depolarizing (hyperkalaemic) St. Thomas’ Hospital No 2, both administered as cold oxygenated blood cardioplegia. Methods: Twenty anaesthetized pigs on tepid (34°C) cardiopulmonary bypass (CPB) were randomised to cardioplegic arrest for 120 min with antegrade, repeated, cold, oxygenated, polarizing (STH-POL) or depolarizing (STH-2) blood cardioplegia every 20 min. Cardiac function was evaluated at Baseline and 60, 150 and 240 min after weaning from CPB, using a pressure-conductance catheter and epicardial echocardiography. Regional tissue blood flow, cleaved caspase-3 activity and levels of malondialdehyde were evaluated in myocardial tissue samples. Results: Preload recruitable stroke work (PRSW) was increased after polarizing compared to depolarizing cardioplegia 150 min after declamping (73.0±3.2 vs. 64.3±2.4 mmHg, p=0.047). Myocardial tissue blood flow rate was high in both groups compared to the Baseline levels and decreased significantly in the STH-POL group only, from 60 min to 150 min after declamping (p<0.005). Blood flow was significantly reduced in the STH-POL compared to the STH-2 group 240 min after declamping (p<0.05). Left ventricular mechanical efficiency, the ratio between total pressure-volume area and blood flow rate, gradually decreased after STH-2 cardioplegia and was significantly reduced compared to STH-POL cardioplegia after 150 and 240 min (p<0.05 for both). Conclusion: Myocardial protection for two hours of polarizing cardioplegic arrest with STH-POL in oxygenated blood is non-inferior compared to STH-2 blood cardioplegia. STH-POL cardioplegia alleviates the mismatch between myocardial function and perfusion after weaning from CPB.publishedVersio

Clinical and experimental investigation: relationship of ischaemia/reperfusion injury with oxidative stress in abdominal aortic aneurysm repair and in extracranial brain artery endarterectomy and possibilities of protection against ischaemia using a glutathione analogue in a rat model of global brain ischaemia

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