Nikolaos Tsilimingas

The Role of Apolipoprotein E in Cognitive Decline and Delirium after Bypass Heart Operations

Cognitive decline and delirium are common complications after heart bypass surgery. Based on the reported role of the APOE-ε4 allele in neurodegenerative diseases, we studied its association with these complications. A neuropsychological test battery consisting of the Mini Mental State Examination, the Wechslers Memory Scale Revised, the Brief Psychiatric Rating Scale, and the Delirium Rating Scale was applied to 137 APOE-genotyped patients on admission and 1 month after bypass surgery. We correlated the APOE (apolipoprotein E) polymorphism with the postoperative test outcome by taking into account all factors known to influence cognitive capacity after heart surgery. There was a significant decline in all test results 1 month after surgery and a high frequency of postoperative delirium. Neither this decline nor the frequency of delirium was associated with the APOE-ε4 allele. This study confirms the high incidence of cognitive decline and delirium after coronary surgery, but it does not support the role of the APOE-ε4 allele in the occurrence of these complications.

Ranolazine enhances the antiarrhythmic activity of amiodarone by accelerating conversion of new-onset atrial fibrillation after cardiac surgery.

Ranolazine is a relatively novel antiischemic/antianginal compound with antiarrhythmic properties. We investigated its ability to shorten the time to conversion of postoperative atrial fibrillation (POAF) when added to amiodarone after coronary artery bypass graft (CABG) surgery. In this prospective, randomized, allocation-concealed, single-blind, single-site clinical trial, we enrolled consecutive eligible patients who developed POAF after elective on-pump CABG surgery. Participants were randomized to receive either ranolazine 375 mg twice daily orally plus intravenous amiodarone (active group) or intravenous amiodarone alone (control group). We enrolled 41 patients; 20 in the active and 21 in the control group. There were no significant differences between the groups in terms of age, procedural duration, extracorporeal circulation time, and aortic cross-clamp time. Mean time of conversion was significantly shorter in the active group (19.9 ± 3.2 vs 37.2 ± 3.9 hours, P < .001), suggesting that compared to amiodarone alone, the ranolazine–amiodarone combination had a superior antiarrhythmic effect against POAF.

Glycosaminoglycans as key molecules in atherosclerosis: the role of versican and hyaluronan.

Cardiovascular disease is the largest cause of death in Western societies and it primarily results from atherosclerosis of large and medium-sized vessels. Atherosclerosis leads to myocardial infarction, when it occurs in the coronary arteries, or stroke, when it occurs in the cerebral arteries. Pathological processes involved in macrovascular disease include the accumulation of lipids which are retained by extracellular matrix (ECM) molecules, especially by the chondroitin sulfate/dermatan sulfate (CS/DS) proteoglycans (CS/DSPGs), such as versican, biglycan and decorin. The sulfation pattern of CS is a key player in protein interactions causing atherosclerosis. Several studies have shown that lipoproteins bind CSPGs via their glycosaminoglycan chains. Galactosaminoglycans, such as CS and DS, bind low density lipoproteins (LDL), affecting the role of these molecules in the arterial wall. In this article, the role of CS and versican in atherosclerosis and hyaluronan in atherogenesis as well as the up to date known mechanisms that provoke this pathological condition are presented and discussed.

Ondasetron versus haloperidol for the treatment of postcardiotomy delirium: a prospective, randomized, double-blinded study

BackgroundTo investigate the controlling efficacy of ondasetron and haloperidol in regard to the postcardiotomy delirium.MethodsWe included in this prospective, randomized, double-blinded study 80 patients who developed delirium after heart surgery with the application of heart lung-machine. The patients were divided into two, equally-sized groups, which on detection of delirium received ondasetron 8 mg iv or haloperidol 5 mg iv respectively. The statistical analysis compared the baseline and demographic characteristics of the two groups (age, gender, comorbidities, years of education, type of surgery etc.).ResultsBoth ondasetron and haloperidol had very good delirium controlling effects, without statistically significant differences.Discussion-ConclusionsOndasetron and haloperidol are efficient agents as far as the treatment of postcardiotomy delirium is concerned. As, in addition, ondasetron bares milder side-effects, we believe this could be the agent of choice in patients developing postcardiotomy delirium in the future.

Effect of ranolazine in preventing postoperative atrial fibrillation in patients undergoing coronary revascularization surgery.

BACKGROUND/OBJECTIVE Ranolazine is a new anti-ischemic agent approved for chronic angina with additional electrophysiologic properties. The purpose of the present trial was to investigate its effect in preventing postoperative atrial fibrillation (POAF) after on-pump coronary artery bypass graft (CABG) surgery. METHODS In the current prospective, randomized, (1 active: 2 control), single-blind (outcome assessors), single-centre clinical trial we recruited consecutive eligible patients scheduled for elective on-pump CABG. Participants were assigned to receive either oral ranolazine 375 mg twice daily for 3 days prior to surgery and until discharge, or to receive usual care. Patients were monitored for the development of POAF. RESULTS We enrolled 102 patients. Significantly lower incidence of POAF was noted in the ranolazine group compared with the control group (3 out of 34 patients, 8.8%, vs 21 out of 68 patients, 30.8%; p< 0.001). Mean values of left atrial diameter and left ventricular ejection fraction between the control and the ranolazine group were not significantly different. CONCLUSION Our findings suggest a protective role of oral ranolazine when administered in a moderate dose preoperatively in patients undergoing on-pump CABG surgery. Future studies based on a wider sample of patients will eventually support our conclusions.

Monitoring of brain oxygen saturation (INVOS) in a protocol to direct blood transfusions during cardiac surgery: a prospective randomized clinical trial

BackgroundBlood transfusions are common in cardiac surgery, but have been associated with increased morbidity and long-term mortality. Efforts to reduce blood product use during cardiac surgery include fluid restriction to minimize hemodilution, and protocols to guide transfusion decisions. INVOS is a modality that monitors brain tissue oxygen saturation, and could be useful in guiding decisions to transfuse. However, the role of INVOS (brain tissue oxygen saturation) as part of an algorithm to direct blood transfusions during cardiac surgery has not been evaluated. This study was conducted to investigate the value of INVOS as part of a protocol for blood transfusions during cardiac surgery.MethodsProspective, randomized, blinded clinical trial, on 150 (75 per group) elective cardiac surgery patients. The study was approved by the Institution Ethics committee and all patients gave written informed consent. Data were initially analyzed based on “intention to treat”, but subsequently were also analyzed “per protocol”.ResultsWhen protocol was strictly followed (“per protocol analysis”), compared to the control group, significantly fewer patients monitored with INVOS received any blood transfusions (46 of 70 patients in INVOS group vs. 55 of 67 patients in the control group, p = 0.029). Similarly, patients monitored with INVOS received significantly fewer units of red blood cell transfusions intraoperatively (0.20 ± 0.50 vs. 0.52 ± 0.88, p = 0.008) and overall during hospital stay (1.31 ± 1.20 vs. 1.82 ± 1.46, p = 0.024). When data from all patients (including patient with protocol violation) were analyzed together (“intention to treat analysis”), the observed reduction of blood transfusions in the INVOS group was still significant (51 of 75 patients transfused in the INVOS group vs. 63 of 75 patients transfused in the control group, p = 0.021), but the overall number of units transfused per patient did not differ significantly between the groups (1.55 ± 1.97 vs. 1.84 ± 1.41, p = 0.288).ConclusionsOur data suggest that INVOS could be a useful tool as part of an algorithm to guide decisions for blood transfusion in cardiac surgery. Additional data from rigorous, well designed studies are needed to further evaluate the role of INVOS in guiding blood transfusions in cardiac surgery, and circumvent the limitations of this study.Trial registrationClinicalTrials.gov: NCT00879463

Ranolazine-induced postrepolarization refractoriness suppresses induction of atrial flutter and fibrillation in anesthetized rabbits.

Ranolazine (Ran) is a novel anti-ischemic agent with electrophysiologic properties mainly attributed to the inhibition of late Na+ current and atrial-selective early Na+ current. However, there are only limited data regarding its efficacy and mechanism of action against atrial flutter (Afl) and atrial fibrillation (AF) in intact animals. Therefore, we aimed to investigate the electrophysiologic mechanism of Ran in a rabbit model of inducible atrial tachyarrhythmias elicited by acetylcholine (ACh). Arrhythmias were produced in 19 rabbits by rapid atrial burst pacing during control, after intravenous ACh and after Ran + ACh administration. Recording of right atrial monophasic action potentials (MAPs) and programmed stimulation were utilized to determine the duration of atrial repolarization at various cycle lengths and voltage levels of action potential, including 75% of total MAP duration (MAPD75), effective refractory period (ERP), and postrepolarization refractoriness (PRR = ERP − MAPD75) prior to and after Ran. Control stimulation yielded no arrhythmias or maximal nonsustained runs of Afl/AF. Upon ACh, 17 of 19 rabbits exhibited sustained Afl and AF as well as mixed forms of Afl/AF, while 2 animals revealed none or short runs of nonsustained arrhythmias and were excluded from the study. High-frequency burst pacing during the first 30 minutes after Ran + ACh failed to induce any arrhythmia in 13 of 17 rabbits (76%), while 2 animals displayed sustained Afl/AF and 2 other animals nonsustained Afl/AF. At basic stimulation cycle length of 250 milliseconds, Ran prolonged baseline atrial ERP (80 ± 8 vs 120 ± 9 milliseconds, P < .001) much more than MAPD75 (65 ± 7 vs 85 ± 7 milliseconds, P < .001), leading to atrial PRR which was more pronounced after Ran compared with control measurements (35 ± 11 vs 15 ± 10 milliseconds, P < .001). This in vivo study demonstrates that Ran exerts antiarrhythmic activity by suppressing inducibility of ACh-mediated Afl/AF in intact rabbits. Its action may predominantly be related to a significant increase in atrial PRR, resulting in depressed electrical excitability and impediment of arrhythmia initiation.

Thoracic epidural analgesia with levobupivacaine for 6 postoperative days attenuates sympathetic activation after thoracic surgery.

OBJECTIVE To investigate the impact of 2 postoperative analgesic regimens on heart rate variability in patients who underwent thoracotomy. DESIGN A prospective, randomized trial. SETTING A single-institutional study in a university hospital. PARTICIPANTS Fifty patients who underwent thoracotomy under combined general anesthesia and thoracic epidural analgesia divided by a number generator into 2 equal groups (A and B). INTERVENTIONS In group A, postoperative analgesia consisted of thoracic epidural analgesia with levobupivacaine for 6 postoperative days. In group B, on the 3rd postoperative day this regimen was changed to patient-controlled intravenous morphine. Heart rate variability recordings were performed on the day before surgery, after the epidural, after operation, and on every postoperative day. Statistical analysis used chi-square and Student t tests (Bonferroni correction). MEASUREMENTS AND MAIN RESULTS In both groups, the low-frequency component of the analyzed recordings declined after epidural and after surgery. In group A, the low-frequency component was significantly lower compared with baseline from the 2nd postoperative day onward, whereas in group B it was significantly higher compared with A on the 4th and 6th postoperative days. In both groups, the changes in high frequency were statistically insignificant. Intergroup comparisons of the low-/high-frequency ratio showed statistical difference on the last day of observation. There was no difference between the groups in hemodynamic variables and visual analog scale/10 scores. CONCLUSIONS Postoperatively decreased cardiac sympathetic outflow continues with epidural analgesia, whereas it is abolished by the change to intravenous patient-controlled morphine.

Vision impairment during cardiac surgery and extracorporeal circulation: current understanding and the need for further investigation

The aim of this article was to provide a comprehensive review of current knowledge regarding ocular hemodynamic alterations affecting the retinal neuroglial cells and optic nerve head (ONH) function during cardiac surgery. Literature indicates that visual loss after heart surgery is a rare but devastating complication provoked by two main causes of optic ischaemia and infarction during on‐pump cardiac procedures: microembolism and/or hypoperfusion. Retinal ischaemia and ischaemic optic neuropathy are two possible major consequences of extracorporeal circulation in cardiac surgery. The hemodynamic modifications within the vascular beds of retina and ONH during cardiovascular operations have been incompletely studied. Consequently, it is of great interest to investigate the hemodynamic changes during cardiopulmonary bypass within the choroidal, retinal and optic nerve microcirculations as well as other potential causes of vaso‐occlusion. Maintaining stable hemodynamic parameters during cardiovascular surgery seems to be the key to prevent visual impairment.

Remote preconditioning in normal and hypertrophic rat hearts

BackgroundThe aim of our study was to investigate whether remote preconditioning (RPC) improves myocardial function after ischemia/reperfusion injury in both normal and hypertrophic isolated rat hearts. This is the first time in world literature that cardioprotection by RPC in hypertrophic myocardium is investigated.MethodsFour groups of 7 male Wistar rats each, were used: Normal control, normal preconditioned, hypertrophic control and hypertrophic preconditioned groups. Moderate cardiac hypertrophy was induced by fludrocortisone acetate and salt administration for 30 days. Remote preconditioning of the rat heart was achieved by 20 minutes transient right hind limb ischemia and 10 minutes reperfusion of the anaesthetized animal. Isolated Langendorff-perfused animal hearts were then subjected to 30 minutes of global ischemia and reperfusion for 60 minutes. Contractile function and heart rhythm were monitored. Preconditioned groups were compared to control groups.ResultsLeft ventricular developed pressure (LVDP) and the product LVDP × heart rate (HR) were significantly higher in the hypertrophic preconditioned group than the hypertrophic control group while left ventricular end diastolic pressure (LVEDP) and severe arrhythmia episodes did not differ. Variances between the normal heart groups were not significantly different except for the values of the LVEDP in the beginning of reperfusion.ConclusionsRemote preconditioning seems to protect myocardial contractile function in hypertrophic myocardium, while it has no beneficial effect in normal myocardium.