Clinical trial NCT05691764: Effect of Cyclosporine and Remote Ischemic Preconditioning in Reperfusion Ischemia Injury on Tetralogy Fallot Patients With Correction Surgery
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Myocardial Injury
Cardiac Surgery
Keywords: RIPC
cyclosporine
ischemia reperfusion injury
MDA
calcium cytosol
tetralogy Fallot
mitochondrial edema
infundibulum
Lead sponsor: Indonesia University
Sponsor class: OTHER
First posted: 2023-01-20
Enrollment: 40
Sex: ALL
Minimum age (years): 1
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Malondialdehyde (MDA)
timeFrame: 1 year
measure: Calcium cytosol concentration
timeFrame: 1 year
measure: Mitochondrial edema
timeFrame: 1 year
Secondary outcomes:
measure: Cardiac index
timeFrame: 1 year
measure: Troponin I
timeFrame: 1 year
measure: Creatine kinase- MB (CKMB)
timeFrame: 1 year
measure: Vasoactive inotropic score (VIS)
timeFrame: 1 year
Other outcomes:
Locations:
city: Jakarta
country: Indonesia
facility: Indonesia University
state: DKI Jakarta
Study officials:
affiliation: Indonesia University
name: Jefferson K Hidayat, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wu Q, Wang T, Chen S, Zhou Q, Li H, Hu N, Feng Y, Dong N, Yao S, Xia Z. Cardiac protective effects of remote ischaemic preconditioning in children undergoing tetralogy of fallot repair surgery: a randomized controlled trial. Eur Heart J. 2018 Mar 21;39(12):1028-1037. doi: 10.1093/eurheartj/ehx030.
citation: Davidson SM, Ferdinandy P, Andreadou I, Botker HE, Heusch G, Ibanez B, Ovize M, Schulz R, Yellon DM, Hausenloy DJ, Garcia-Dorado D; CARDIOPROTECTION COST Action (CA16225). Multitarget Strategies to Reduce Myocardial Ischemia/Reperfusion Injury: JACC Review Topic of the Week. J Am Coll Cardiol. 2019 Jan 8;73(1):89-99. doi: 10.1016/j.jacc.2018.09.086.
citation: Zalewski J, Claus P, Bogaert J, Driessche NV, Driesen RB, Galan DT, Sipido KR, Buszman P, Milewski K, Van de Werf F. Cyclosporine A reduces microvascular obstruction and preserves left ventricular function deterioration following myocardial ischemia and reperfusion. Basic Res Cardiol. 2015 Mar;110(2):18. doi: 10.1007/s00395-015-0475-8. Epub 2015 Feb 27.
citation: Chen HW, Chien CT, Yu SL, Lee YT, Chen WJ. Cyclosporine A regulate oxidative stress-induced apoptosis in cardiomyocytes: mechanisms via ROS generation, iNOS and Hsp70. Br J Pharmacol. 2002 Nov;137(6):771-81. doi: 10.1038/sj.bjp.0704908.