Ischemic Preconditioning in Cardiac Cells: from Bench to Bedside

Ali Dabbagh

Journal of Cellular & Molecular Anesthesia, Vol. 3 No. 2 (2018), 2 September 2018 , Page 45-46

Ischemic Preconditioning in Cardiac Cells: from Bench to Bedside
Since 1986 that Dr Charles E. Murry and his colleagues published their discovery about the protective effects of ischemic preconditioning (IPC), a large number of Pro- and Con- studies have been published (1). Besides the protective effects of ischemia itself, a number of pharmaceutical agents may have protective effects against ischemia known as pharmacologic preconditioning. Having a long list of agents, these have been under examinations both clinically and/or in lab setting. Some disease states have been proposed to have a relationship with effects of IPC; including diabetes or high altitude diseases (2, 3). Another variety of IPC is remote IPC which has been acting at remote organ tissues (4-6)
How does IPC with such a wide range of effects work? In fact, IPC works both in cardiac and neurologic cells; two cell types that are highly "ischemia-sensitive"; more interestingly, volatile anesthetics-induced preconditioning (part of a larger phenomenon known as Anesthetic Preconditioning: APC) has protective effects in both cell types; i.e. myocardial cells and brain neurons (7). The underlying mechanisms for IPC and APC are mainly similar; the following items being the most important common mechanisms:
 ATP-sensitive potassium channels in mitochondria (mKATP): being one of the most important mechanisms in both IPC and APC, leads to intracellular protective mechanisms; including but not limited to PKCε phosphorylation (a subgroup of Protein Kinase C: PKC); among the main mitochondrial related mechanisms, inhibition of mitochondrial permeability transition pore (mPTP) opening, also, " the content of nitric oxide (NO) and also, inhibition of nitric oxide synthase (NOS)" and the role of mitochondrial connexins could not be neglected (7, 8)
 Reactive Oxygen Species (ROS): when mitochondria release small amounts of ROS, both APC and IPC could be triggered, leading to their cardio- and
neuro-protective effects (7, 9, 10)
 Inflammatory cytokines: a cascade of inflammatory cytokines are inhibited due to the protective effects of IPC and APC; mainly through attenuated activity of NF-κB and the downstream of NF-κB-inflammatory cytokines (7, 11-13)
 Apoptosis: increased anti-apoptotic effects of protein Bcl-2, leading to decreased expression of caspase-3 are the main mechanisms considered as IPC effects through inhibition of apoptosis (7, 14-16)
Considering the discovered mechanisms of IPC and APC, it seems reasonable that both cardiomyocytes and brain neurons are benefited from volatile anesthetics-induced preconditioning.
However, the above lines are not the complete picture of IPC and further studies, especially regarding the clinical aspects of the issue are under way. In this issue of the Journal of Cellular and Molecular Anesthesia, Anvaripour A, et al. have published their study demonstrating that 4% Sevoflurane could not have a protective effect on myocardial cells as an anesthetic with APC effects (17); a finding in controversy with some of the other previous studies. These results again confirm the delicate path from bench to bedside, which is not always a straight forward one. This time, the path goes through precondition effects of volatile anesthetics.

Original Articles

The relationship between s100β and cerebral oximetry trend in patients undergoing CABG with cardiopulmonary bypass

Kamal Fani, Mona Hashem-Aghaei, Hossein Ali Jelveh-Moghaddam, Golnar Radmand, Mahnoosh Foroughi, Samira Rajaei, Ali Dabbagh

Journal of Cellular & Molecular Anesthesia, Vol. 3 No. 2 (2018), 2 September 2018 , Page 47-53

Background: CABG is among the most common cardiac procedures often done as on pump surgery. There are however, there is always the risk for potential neurologic and neurocognitive insults in CABG. S100β is a biomarker for CNS damage. Cerebral oximetry using NIRS has been developed for CNS monitoring especially cardiac surgery. This study was designed to find the relationship between serum levels of s100β and cerebral oximetry in CABG patients.

Methods: in an observational study, 44 adult 40-75 years patients entered the study for elective CABG. Serum levels of s100β were assessed at two times during CPB; i.e. just after aortic clamping and immediately after aortic declamping; while the results were compared with right and left cerebral oximetry readings (NIRS); however, NIRS was measured at baseline, during start of cardiopulmonary bypass (CPB), during aortic clamping, and finally at off-clamping the aorta. Repeated Measures ANCOVA (analysis of covariance), multiple linear regression models and Spearman correlation coefficient with scatter plot were used for data analysis. P value less than 0.05 considered significant.

Results: no linear correlation between s100β and NIRS was found according to correlation coefficients. Only among the patients whose s100β was more than 10, the scatter plots demonstrated a positive linear relationship between s100β and right NIRS (spearman correlation coefficient= 0.792; P value=0.006).

Conclusions: the study failed to demonstrate a relationship between on-CPB NIRS numbers and serum s100β in adult patients undergoing CABG during the bypass interval; further studies are suggested to evaluate potential predictive value of NIRS in brain ischemia.

The effects of selenium supplementation on clinical outcomes in mechanically ventilated, non-surgical/traumatic critically ill patients

Kamran Heydari, Reza Goharani, Masoome Lakestani, Mohammadreza Hajiesmaeili

Journal of Cellular & Molecular Anesthesia, Vol. 3 No. 2 (2018), 2 September 2018 , Page 54-59

Background: Selenium presents anti-inflammatory and antioxidant properties which plays a critical role in nutrition of patients following devastating conditions. Furthermore, several lines of evidence reported that most of patients who admitted to intensive care unit (ICU) have lower plasma levels of selenium. Therefore, this study was designed to define the impact of selenium supplementation on clinical outcomes of mechanically ventilated non-surgical/traumatic critically ill patients.Materials and Methods: This study was conducted on 105 subjects hospitalized in ICU of Shohadaye Haft-e Tir Hospital, Tehran, Iran. Here the acute physiologic assessment and chronic health evaluation (APACHE) II score of patients was documented on the day of their ICU admission. The patients were divided to two groups based on block randomization technique and were assigned to receive selenium or placebo. Then the effect of selenium supplementation was evaluated based on the APACHE II score, the occurrence of ventilator associated pneumonia (VAP), length of ICU stay and the rate of mortality.Results: The acquired data revealed no significant difference between two experimental groups based on the demographical information. Also it was demonstrated that selenium supplementation of critically ill patients was associated with better APACHE II score, fewer length of ICU stay and fewer mortality rate. Incidence of VAP indicated no significant difference between groups.Conclusion: The obtained data of this single center clinical trial showed that selenium supplementation could improve clinical outcomes of critically ill patients.

Keywords: Selenium supplementation; APACHE II score; ventilator associated pneumonia; mortality rate; length of ICU stay

Distribution of Bupivacaine in Epidural Space

Hamid Haji Gholam Saryazdi, Gholamreza khalili, Reihanak Talakoub, Masoud Shahbazi, Saeed Abbasi

Journal of Cellular & Molecular Anesthesia, Vol. 3 No. 2 (2018), 2 September 2018 , Page 60-65

Background: There is no consensus regarding the spread of local anesthesia in thoracic epidural space to obtain regional analgesia or anesthesia. We aimed to determine the distribution of Bupivacaine injected into the thoracic epidural space to evaluate its cranial or caudal spread in patients undergoing epidural anesthesia.Materials and Methods: In a prospective clinical trial, thirty adults patients (12 males and 18 females) with ASA class I and II, scheduled for elective cholecystectomy under thoracic epidural anesthesia with 0.5% Isobaric Bupivacaine were studied. Clinical and radiological outcomes were evaluated to assess the correlation between the volume of the local anesthetic injected to the thoracic epidural space and the extension of its spread within the epidural space. Immediately after insertion and fixation of epidural catheter, patients were transferred to MRI unit to receive 8 mL of 5% Bupivacaine plus 1 mL Magnevist through the epidural catheter. Then, the patterns of spread were evaluated. Data were obtained prospectively during the procedure.Results: Mean distribution of bupivacaine in thoracic epidural space was 0.64 level/ml of local anesthetics and the average of spread was 5.21 levels. The mean spread of bupivacaine was more in females (5.5 ± 1.1) than males (4.8 ± 1.1); but the difference was not significant. Unlike Patients’ age and weight, the height and body mass index had a significant negative correlation with the distribution of Bupivacaine.Conclusion: Distribution of Bupivacaine in epidural space in female patients is more than male ones and the tendency of spread is more toward the cephalad direction than caudal.

Keywords: Bupivacaine distribution, Epidural anesthesia, Local Anesthesia, Bupivacaine, Magnevist

The Preconditioning Effect of Sevoflurane on Coronary Artery Bypass Surgery Patients

Abdorasoul Anvaripour, Houshang Shahryari, Sayed Mehran Marashian, Alireza Jahangirifard

Journal of Cellular & Molecular Anesthesia, Vol. 3 No. 2 (2018), 2 September 2018 , Page 66-73

Background: One of the most important issues in the field of surgery is ischemic preconditioning (IPC) of the myocardium during the coronary artery bypass grafting (CABG). The current study attempted to reevaluate the issue to find a potential approach to diminish morbidity, inotrope administration, ischemia and possibly intensive care unit stay after CABG in adult patients.Materials and Methods: Through randomized single-blind clinical trial, all elective coronary bypass surgeries in 40 to 80 years-old patients enrolled the study. Atrioventricular (AV) block (mobitz2); complete heart block; left bundle branch block (LBBB); acute heart failure (ejection fraction (EF) <30%); re-exploration due to surgical complications and MI cases in the last 7 days were excluded. In all patients, induction (sufentanil, cis-atracurium and etomidate) and maintenance phase (sufentanil, midazolam, cis-atracurium) of anesthesia were done following the same protocol. After cross-clamp of aorta in intervention group, the patients received oxygen (2Lit/min) and sevoflurane (4%) during coronary bypass surgery. After rewarming of the patients, sevoflurane was discontinued. Main outcome measures were troponin 4, 8, 24, 48 hours after surgery with charting the electrocardiogram (ECG) changes, need for inotrope agents and hemodynamic indices during and after CABG in ICU.Results: 58 CABG candidates enrolled the current study: 29 in intervention group and 29 in control group. There were no statistical differences between the groups concerning hemodynamic issues, Central Venous Pressure (CVP), hematocrit (HCT), ECG changes, demands for inotrope, or ICU stay between the groups.Conclusion: No significant relationship between application of 4% sevoflurane and IPC was found in adult CABG patients. However, the effect of Sevoflurane on IPC might be dose-related.

Keywords: Ischemic preconditioning (IPC); Sevoflurane; Coronary Artery Bypass Surgery (CABG)

Effects of Preemptive and Preventive intravenous Paracetamol on postoperative pain and opioid consumption in patients undergoing laparoscopic nephrectomy

Alireza Jafari, Mohammadreza Kamranmanesh, Homayoun Aghamohammadi, Babak Gharaei, Mehranoosh Noori Khorramabadian, Behzad Narouie, Payam Sarmadi, Reza Valipour, Abbas Vali

Journal of Cellular & Molecular Anesthesia, Vol. 3 No. 2 (2018), 2 September 2018 , Page 74-80

Background: Adequate pain control is a goal in post operative recovery. However opioids provide good analgesic effects, their side effects such as postoperative nausea and vomiting (PONV) limit their administration. Intravenous Paracetamol as a safe and well tolerated drug with lower side effects can be used instead of opioids for pain management.

Objectives: The aim of this study is to compare preemptive or preventive administration of paracetamol with placebo group to investigate its effects on pain control and opioid consumption in patients undergoing laparoscopic nephrectomy.

Patients and Methods: Ninety patients were randomly divided to three groups. Preemptive group received 1 gr paracetamol in 100 ml normal saline 30 minutes before induction of anesthesia, Preventive group received 1 gr paracetamol in 100 ml normal saline before closure of the skin and placebo group just received 100 ml normal saline. Post surgical pain was assessed using Verbal Rating Scale (VRS). Pethidine 0.25 mg/kg was administered and repeated each 10 minutes to control pain. Pain scores, total dose of opioid and symptoms like nausea and vomiting were recorded. 

Results: Preemptive and Preventive groups had lower pain scores than placebo group. Opioid consumption and PONV were significantly higher in placebo group. 

No significant differences were observed between Preemptive and Preventive groups.

Conclusion: IV Paracetamol can provide an adequate pain control with low side effects and may be an effective choice in management of post operative pain in patients undergoing laparoscopic nephrectomy

Brief Communications

Rh-Incompatibility-Induced Delayed Hemolytic Transfusion Reaction: Role of Immunologic Reactions in Rh-Incompatibility

Mohammadreza Moshari, Ronak Karbalaeifar, Maryam Vosoghian, Bahman Malek, Mastaneh Dahi-Taleghani

Journal of Cellular & Molecular Anesthesia, Vol. 3 No. 2 (2018), 2 September 2018 , Page 81-85

Blood transfusions are given to increase oxygen-carrying capacity and intravascular volume. Despite all the benefits of transfusion, it may have some complications. When mistransfusions occur, or when no other option is available, incompatible packed-cells may be infused, which puts the patient at risk of experiencing a Hemolytic Transfusion Reaction (HTR). HTRs are classified as acute or delayed reactions having wide spectrum of clinical presentations. In this report, we present a case of delayed hemolytic reaction due to Rh incompatibility in the operation room. Critical incident reporting and evaluation of adverse transfusion reactions may provide effective patient management and prevent the occurrence or repetition of these events.