Effect of Cyclosporine and Remote Ischemic Preconditioning in Reperfusion Ischemia Injury on Tetralogy Fallot Patients With Correction Surgery

Study Overview
=================
Brief Summary
-----------------
The study aimed to evaluate the combined effects of cyclosporine and remote ischemic preconditioning on MDA, calcium cytosol concentration, and mitochondrial edema in tetralogy Fallot patients undergoing corrective surgery.

Detailed Description
-----------------
Forty patients undergoing tetralogy Fallot corrective surgery were randomized to RIPC and cyclosporine (n=20) and control (n=20). Cyclosporin was administered 2 hour pre induction of anesthesia with the dose of 3 mg/kg body weight intravenously. RIPC was performed preoperatively after induction of anesthesia by inflating pressure cuff on the extremity 30 mmHg higher than systolic blood pressure of the patient for 5x5 minutes with 5 minutes reperfusion interval. Blood samples from coronary sinus and biopsies from the myocardial infundibulum were obtained three times at the condition of pre ischemic, ischemic, and reperfusion. MDA was measured from the blood samples, meanwhile calcium cytosol concentration and mitochondrial edema was measured from the biopsy samples.

Official Title
-----------------
Effect of Cyclosporine and Remote Ischemic Preconditioning on MDA, Calcium Cytosol Concentration, and Mitochondrial Edema in Reperfusion Ischemia Injury: Research on Tetralogy Fallot Patients With Correction Surgery

Conditions
-----------------
Myocardial Injury, Cardiac Surgery

Intervention / Treatment
-----------------
* Drug: Cyclosporin
* Procedure: remote ischemic preconditioning
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Tetralogy Fallot patient that is undergoing correction surgery Has an ideal anatomy for corrective surgery, namely: Pulmonary artery size within normal limits (according to the kirklin table), Mc Goon ratio> 1.5, Nakata index> 200, normal coronary artery ostium and good biventricular function. Exclusion Criteria: Patient refuses the procedure Patient with acute kidney injury Patient without lower extremity Patient with cyclosporin allergy

Ages Eligible for Study
-----------------
Minimum Age: 1 Year
Maximum Age: 6 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cyclosporin + RIPC<br>This group received cyclosporin intravenously 2 hours pre-induction of anesthesia, with the dose of 3 mg/ kg body weight. RIPC was performed preoperatively after induction of anesthesia by inflating pressure cuff on the extremity 30 mmHg higher than systolic blood pressure of the patient for 5x5 minutes with 5 minutes reperfusion interval. | Drug: Cyclosporin<br>* Cyclosporin was administered intravenously with the dose of 3 mg/ kg body weight<br>* Other names: Sandimmun;Procedure: remote ischemic preconditioning<br>* Performed by inflating pressure cuff on the extremity 30 mmHg higher than systolic blood pressure of the patient for 5x5 minutes with 5 minutes reperfusion interval<br>* Other names: RIPC;|
| Placebo Comparator: Control<br>This group received placebo intravenously 2 hours pre-induction of anesthesia. | Drug: Placebo<br>* Intravenous placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Malondialdehyde (MDA) | ROS level is determined by measuring MDA concentration (nmol/mL) | 1 year | 
| Calcium cytosol concentration | Calcium concentration (nmol/mL) in cytosol is determined by ratiometric analysis on Fura Red- dyed heart cells. | 1 year | 
| Mitochondrial edema | Mitochondrial edema (%) is measured by decreasing of optical density that indicates change in mitochondrial matrix volume. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac index | Examined with echocardiography, unit of measurement is litres per minute per square metre (L/min/m2). | 1 year | 
| Troponin I | Measured from venous blood, unit of measurement is nanograms per milliliter (ng/mL). | 1 year | 
| Creatine kinase- MB (CKMB) | Measured from venous blood, unit of measurement is units per liter (IU/L). | 1 year | 
| Vasoactive inotropic score (VIS) | VIS was calculated as: dopamine dose (μg/kg/min) + dobutamine dose (μg/kg/min) + 100 × epinephrine dose (μg/kg/min) + 10 × milrinone dose (μg/kg/min) + 10 000 × vasopressin dose (unit/kg/min) + 100 × norepinephrine dose (μg/kg/min). | 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
RIPC, cyclosporine, ischemia reperfusion injury, MDA, calcium cytosol, tetralogy Fallot, mitochondrial edema, infundibulum