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

Cardiac Surgery Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05691764
• Other study ID #: IndonesiaUAnes055
• Status: Completed
• Phase: N/A
• Start date: September 1, 2020
• Est. completion date: September 1, 2022

Study information

• Verified date: January 2023
• Source: Indonesia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: September 1, 2022
• Est. primary completion date: December 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 6 Years

Eligibility

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

Related Conditions & MeSH terms

• Cardiac Surgery
• Ischemia
• Myocardial Injury
• Tetralogy of Fallot
• Wounds and Injuries

Intervention

Drug:
• Cyclosporin
Cyclosporin was administered intravenously with the dose of 3 mg/ kg body weight

Procedure:
• remote ischemic preconditioning
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

Drug:
• Placebo
Intravenous placebo

Locations

Country	Name	City	State
Indonesia	Indonesia University	Jakarta	DKI Jakarta

Sponsors (1)

Lead Sponsor	Collaborator
Indonesia University

Country where clinical trial is conducted

Indonesia, 

References & Publications (4)

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. — View 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 Revie — View 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 — View 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 r — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Malondialdehyde (MDA)	ROS level is determined by measuring MDA concentration (nmol/mL)	1 year
Primary	Calcium cytosol concentration	Calcium concentration (nmol/mL) in cytosol is determined by ratiometric analysis on Fura Red- dyed heart cells.	1 year
Primary	Mitochondrial edema	Mitochondrial edema (%) is measured by decreasing of optical density that indicates change in mitochondrial matrix volume.	1 year
Secondary	Cardiac index	Examined with echocardiography, unit of measurement is litres per minute per square metre (L/min/m2).	1 year
Secondary	Troponin I	Measured from venous blood, unit of measurement is nanograms per milliliter (ng/mL).	1 year
Secondary	Creatine kinase- MB (CKMB)	Measured from venous blood, unit of measurement is units per liter (IU/L).	1 year
Secondary	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