Cellular and Molecular Anesthesia: from Bench to Bedside

Ali Dabbagh, Hedayatollah Elyassi

Journal of Cellular & Molecular Anesthesia, Vol. 1 No. 1 (2016), 21 December 2015 , Page 1-2

Cellular and Molecular Anesthesia: from Bench to Bedside
In the current practice of anesthesia, each day, anesthesiologists deal with a great work: they use the cellular mechanisms of drug molecules to induce their desired effects for induction and maintenance of anesthesia to achieve appropriate tolerance of surgery and its pain, modulation of stress response, sedation needed for performing a variety of procedures, emergency anesthesia care, acute and chronic pain management or other everyday jobs of anesthesiologists during perioperative period.
As a matter of fact, molecular anesthesia has been cited for more than 6 decades though in a
very limited scale. In 1956, the molecular mechanisms of morphine and pethidine are described (1). Pauling in 1961 published an article in Science describing a molecular theorey for general anesthesia (2).
In its report “the World in 2025”, Thomson Reuters has predicted clinical medicine would be the most active research front; while molecular biology has the 9th rank (3). But are we still practicing in clinic the same as today?
In fact, the future trend of anesthesia is highly dependent on finding the novel cellular and molecular mechanisms and the possible interactions of the newly discovered molecules and inreraction mechanisms with organ systems. Today, we emphasize on the role of pharmacologists, physiologists, immunologists, anatomists, embryologists, geneticians, cellular medicine specialists, physicists and other basic science specialists; some very interesting examples are published in this volume of the Journal (4-7).
However, changes that have well started now would “revolutionize” our daily practice during the next decade in such a way that it will change the basis of medicine: presumably we will have a new model medicine known as “personalized medicine” or “precision medicine”. In this approach, the content of each patient’s genes accompanied with his/her cellular and molecular analysis is used as the basis for further diagnosis and treatment, tailoring the most appropriate treatment for each individual; some aspects of this novel approach like genetic makeup or genetic profile of an individual’s tumor is nowadays approved by FDA (8-10).
In the approach of personalized medicine, not only clinical and psychological modalities are used for clinical management of patients, genetic, proteomic and pharmacogenomic methods are used as well. Techniques known as “bench techniques” are much more used in clinic, at times even more than the conventional assessment tools and diagnostic methods (11, 12). Personalized medicine has satrted a few years ago and we will be incorporated in every day practice; clinical anesthesia practice is not only excluded, but seems to be among the front line fields due to the nature of anesthesia; especially when looking at the nearly 7 decades history of interactions between cellular and molecular medicine and anesthesia.
Cellular and molecular anesthesia is going to pave its way from bench to bedside. Possibly, in the next years, the remnants of the arbitrary line between clinical and basic medicine is completely removed ; this would not take to many years.
The Thomson Reuters report “the World in 2025” has very well quoted François Voltaire just the line after its title: “It is said that the present is pregnant with the future”.

Original Articles

Midazolam-induced learning and memory impairment is modulated by cannabinoid CB1 receptor agonist and antagonist

Abdolaziz Ronaghi, Saeedeh Karamzadeh, Sahar Jowkar, Zahra Mousavi, Nima Naderi

Journal of Cellular & Molecular Anesthesia, Vol. 1 No. 1 (2016), 21 December 2015 , Page 3-11

Background: Memory impairment is a well-known effect of many benzodiazepine compounds which is mediated through their action on gamma-aminobutyric acid type A (GABAA) receptors. On the other hand, cannabinoids can affect learning and memory process through presynaptic modulation of the release of both excitatory glutamate and inhibitory GABA transmitters in brain regions involved in learning and memory. The aim of the present study was to investigate the effect of cannabinoids on memory impairment and long-term potentiation (LTP) reduction properties of the short acting benzodiazepine midazolam.
Materials and Methods: One week after insertion of guide cannula by stereotaxic surgery, cannabinoid compounds or midazolam were administered by intracerebroventricular (i.c.v.) injection into lateral ventricle of male rats. Spatial memory task was evaluated using Morris water maze (MWM) test. Electrophysiological evaluation was done by field potential recording of hippocampal neurons in unconscious rats.
Results: In MWM test, while i.c.v. administration of AM251 (200 and 500 ng) per se could not change learning and memory function in rats, pretreatment of rats with AM251 (500 ng; i.c.v.) attenuated midazolam-induced memory impairment. In field potential recording, while i.c.v. administration of AM251 (500 ng) and WIN55212-2 (10 μg) did not have any effect on population spike amplitude, pretreatment of rats with both AM251 and WIN55212-2 significantly diminished midazolam-induced PS amplitude reduction in hippocampal neurons.
Conclusion: Our
Our results suggest the involvement of cannabinoid CB1 receptors in both memory impairment and LTP reduction in hippocampal neurons which was produced by midazolam. This interaction is likely through their effect on both GABAergic and glutamatergic receptors in hippocampus.

Anti-hyperalgesic and anti-inflammatory effects of long termcalcium administrationduring adjuvant-induced arthritisin rats

Setareh Khashaee, Homa Manaheji, Nazanin Nikzad, Jalal Zarringhalam

Journal of Cellular & Molecular Anesthesia, Vol. 1 No. 1 (2016), 21 December 2015 , Page 12-18


Inflammation and edema Symptoms are physiological response to triggers that can be induced by different mediators such as cytokines. Rheumatoid arthritis is the most common form of arthritis which is characterized by chronic inflammation of the synovial membrane, severe and debilitating pain and progressive cartilage injury. It is clear that cytokines are involved in different stages of inflammation by inducing pro-inflammatory effects; TNF-α as a cytokine involved in the pathogenesis of rheumatoid arthritis. In this study we attempted to investigate the role of prescription of calcium to reduce inflammatory edema and serum TNF-α level during different stages of arthritic inflammation induced by Complete Freund Adjuvant (CFA) injection in male Wistar rats.


In this Applicable-Fundamental study, we used male Wistar rats and adjuvant arthritis was created by once subcutaneous injection of CFA in the right hindpaw of animals on day zero in experimental groups. Various doses of calcium were prepared and injected within 21 days of study. Hyperalgesia and paw volume changes wereassessed byradiant heat andplethysmometer over several days, respectively. The serum levels of TNF-α were studied by ELISA standard kit of rat during various phases and were measured according to the kit.


The results indicated dose related effects of long term calcium administration on edema, hyperalgesia and serum TNF-α level reduction. Daily treatment with effective dose of calcium (5 mg/kg) in AA+ Ca group significantly decreased paw edema, hyperalgesia and serum TNF-α level incomparison to AA and AA+ Vehicle groups on days 7, 14 and 21 of study.


Findings of this study showed;long term administration of calcium in the proper dosage can act as an anti-inflammatory agent and pain modulator during adjuvant-induced arthritis and a part of those effects may conducted by decreasing of serum TNF-α level.

Coagulation Factor XIII-A A614T gene Variation is Suggestive of Founder Effect in Iranian Patients with Sever Congenital Factor XIII Deficiency

Majid Naderi, Shadi Tabibian, Shaban Alizadeh, Zahra Sadat Abtahi, Akbar Dorgalaleh

Journal of Cellular & Molecular Anesthesia, Vol. 1 No. 1 (2016), 21 December 2015 , Page 19-22

Background: Factor XIII (FXIII) is a heterotetramer composing two subunits including FXIII-A and FXIII-B. Several common gene variations were observed in FXIII-A gene with obvious ethnic difference. This study assessed pattern of Tyr204Phe as a common FXIII-A gene variation among Iranian population.

Materials and methods: This study was conducted on eighty Iranian unrelated individuals. Genotype analysis for factor XIII-A Tyr204Phe gene variation was performed for all individuals.

Results: Molecular analysis of these Iranian populations revealed that all studied patients were homozygous for TGG CGG mutation at codon 187, in exon 4 of FXIII-A1 gene.

Conclusion: Tyr204Phe gene variation is one of the most common mutations of FXIII-A subunit that shows a different pattern in Iranian population.

Effect of Local Fibrinogen Administration on Postoperative Bleeding in Coronary Artery Bypass Graft Patients

Narges Payani, Mahnoush Foroughi, abdolhamid Bagheri, Samira Rajaei, Ali Dabbagh

Journal of Cellular & Molecular Anesthesia, Vol. 1 No. 1 (2016), 21 December 2015 , Page 23-27

Introduction: there is always concerns regarding postoperative bleeding in Coronary Artery Bypass Graft (CABG) patients; a number of different strategies have been used to compensate for it and to reduce the amount of blood transfusion. We designed this study to see if local fibrinogen could decrease postoperative bleeding in adult CABG, which is not studied yet.

Materials and methods: in a double blind clinical trial, after matching the inclusion and exclusion criteria, 50 patients entered the study. Pre- and postoperative data, including clinical and laboratory variables were assessed. Among them, pre- and postoperative fibrinogen levels were measured. One group received 1 g fibrinogen as 50 mL solution flushed over the epicardium before sternal closure; the other received 50 mL normal saline as placebo in the same method.

Results: no difference between the two groups regarding preoperative and postoperative fibrinogen levels. Also, two groups were the same regarding PT, PTT, INR and platelet. However, bleeding was less and hematocrit level was higher in local fibrinogen group.

Conclusion: local fibrinogen could decrease postoperative bleeding in CABG patients leading to decreased need for blood transfusion.

Key words: fibrinogen; coronary artery bypass graft; postoperative bleeding

Effect of Vitamin C on serum cortisol reduction after Etomidate Induction of Anesthesia

Navid Nooraee, Mohammad Fathi, Leila Edalat, Faranak Behnaz, Seyed Amir Mohajerani, Ali Dabbagh

Journal of Cellular & Molecular Anesthesia, Vol. 1 No. 1 (2016), 21 December 2015 , Page 28-33

Objectives: Etomidate is suitable for induction of anesthesia, especially in elderly patients and patients who have cardiovascular compromise. Vitamin C has been introduced as a treatment option to decrease Etomidate induced adrenal insufficiency but its actual effect is still controversial. Objective is to determine the effect of Vitamin C on reduction of serum cortisol after etomidate induction of anesthesia.

Methods: In a randomized clinical trial, 40 patients of ASA class I & II, aged between 25 to 70 years old, candidate for elective laparatomy were selected. One hour before induction of surgery, 1 gram of intravenous Vitamin C were administered to the patients in Vitamin C group. Two blood samples were obtained 5 minutes before induction and then another sample 4 hours after induction with etomidate after surgery. All samples were measured for serum free cortisol, ACTH, and C-reactive protein (CRP).

Results: There were no significant differences between duration of surgery, preoperative and post-operative blood pressure and heart rate in two groups (p>0.05). Serum cortisol was significantly declined in control group from 16.2±6.3 μg/dl in preoperative to 8.5±4.2 in postop (p=0.0005), but not in Vitamin C group from 17.5±5.6 in preop to 16.8±6.4 in postop (p=0.75). ACTH levels increased non-significantly from preop to postop period in both Vitamin C (pre: 52.1±15 vs. post: 56.4±18 pg/ml) (p=0.48) and in control group (pre:50.5±16 vs. post:56.2±20).

Conclusion: Etomidate could significantly decrease postoperative serum free cortisol and induce adrenocortical suppression and CRP increase. This effect could be reversed by using Vitamin C premedication to maintain serum cortisol at preoperative level.


Toll-Like Receptor 4 in Ventilator-Induced Lung Injuries

Bahador Bagheri, Seyed Sajad Razavi, Ali Gohari, Sara Salarian, Ali Dabbagh

Journal of Cellular & Molecular Anesthesia, Vol. 1 No. 1 (2016), 21 December 2015 , Page 34-39

Toll like receptors (TLRs) recognize pathogens and generate an immediate defense response by inducing the production of pro-inflammatory cytokines, which rapidly destroy or limit the pathogens. In their bridging role, TLR downstream signals link innate and adaptive immunity, particularly by mediating DC maturation and activation of pathogen specific T lymphocytes. These pathways lead to the activation of professional APCs, which is followed by enhanced expression of surface molecules, MHC and co-stimulatory molecules [CD40, CD80, CD86 and CD70].TLRs are expressed in a variety of cell types, mostly within the immune system where they have been linked to different cellular activation states, immune defense, maintenance of homeostasis, and various diseases. TLRs and related immunological pathways are being extensively studied for research, diagnostic and therapeutic purposes. Most mammalian species have between ten and fifteen types of TLRs. Ten functional TLRs (TLR1-10) have been identified in human. 

Brief Communications

Management of Alveolar Proteinosis by Bronchopulmonary lavage under Extra Corporeal Membrane Oxygenation (ECMO)

Tahereh Parsa, Ardeshir Tajbakhsh, Zargham Hossein Ahmadi, Behrooz Farzanegan, Alireza Jahangirifard

Journal of Cellular & Molecular Anesthesia, Vol. 1 No. 1 (2016), 21 December 2015 , Page 40-42

The gold standard of treating Pulmonary Alveolar Proteinosis (PAP) is bronchopulmonary lavage (BPL). We describe a rare case of BPD for PAP, who underwent ECMO due to hypoventilation in the setting of one lung ventilation. First, the clinical course of the patient is presented; furthermore, the biomolcular basis of PAP and new treatment approaches is discussed.


Letter to the Editor

Tissues, Cells and Biomarkers in ARDS

Seyed Mohammad Reza Hashemian, Makan Sadr, Ali Dabbagh

Journal of Cellular & Molecular Anesthesia, Vol. 1 No. 1 (2016), 21 December 2015 , Page 43-44

 The utility of biomarkers for the action of endothelium and epithelium of the pulmonary microvasculars is unknown and their action of being barrier for edema and dysfunction of them cause ARDS and its mortality rate with no specific drugs efficiency is high (1).

Recently, there are many important information about biomarkers in ARDS (2). These biomarkers in ARDS can effect either cellular activation or cell injury. Currently, biomarkers are the most important research tool. The biomarkers have an important role in ARDS treatment in the function.

There is an executive phase with some damage like edema and necroses. Then, fibro-proliferative phase will be happen. To understand the mechanism of repair, we focus on the function of alveolar type I (3).