Effect of Topically-applied Milrinone or Nitroglycerin on Internal Mammary Artery Free Flow

Forty-six consecutive patients undergoing elective primary coronary artery bypass grafting were enrolled. After the left IMA was harvested, free flow was measured under controlled hemodynamic conditions before any intervention (flow 1) and at a mean of 12.5 minutes after the topical application of one of three agents (milrinone, nitroglycerin or normal saline) on the IMA (flow 2).

Study Overview

• Status: Completed
• Conditions: Vasodilation; Internal Mammary Artery Syndrome
• Intervention / Treatment: Drug: The topical application of a vasodilator on the LIMA graft

Detailed Description

Fifty consecutive patients undergoing elective primary coronary artery bypass grafting were enrolled in this study. Patients were randomly assigned to receive the topical application of one of three agents: milrinone (Baxter Pharmaceuticals, Ahmedabad, India) 10 mg in 20 ml of dextrose 5%, nitroglycerin (Caspian Tamin Pharmaceutical, Guilan, Iran) 10 mg in 20 ml of normal saline, or normal saline (0.9% sodium chloride solution) as control.

All surgical procedures and measurements were carried out by a single surgeon who was blinded to the topical agent which was applied. Each patient enrolled in the study gave a written informed consent, and the study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the local human research committee.

Operative Technique After sternal incision, the skeletonized left IMA was harvested from the subclavian artery to its bifurcation with low-powered electrocautery, and major collaterals were ligated with hemoclips. Following systemic heparinization (300 units/kg to achieve an activated clotting time target of 480 seconds), the IMA was divided proximal to its bifurcation. The first IMA flow (flow 1) was measured by reading the volume of blood ejected from the tip of the freely bleeding IMA through a one-minute period. Heart rate, mean arterial pressure and central venous pressure were documented at the same time. The tip of the artery was occluded with a bulldog clamp, and a swab which was soaked with the selected vasodilator at room temperature (18.0 to 20.0 degrees C) was wrapped around the IMA, and was left undisturbed until the second set of measurements.

Cannulation for cardiopulmonary bypass was carried out, and the pump was used to transfuse or drain blood from the patient in order to restore the mean arterial and central venous pressures as nearly as possible to the previous values. Systemic vasopressors or vasodilators were not used. The IMA was then unwrapped and the second IMA flow (flow 2) was measured in the same way. Time, heart rate, and mean arterial and central venous pressures were also recorded.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 3

Contacts and Locations

Study Locations

• Syrian Arab Republic
  • Damascus, Syrian Arab Republic
    • Damascus University Cardiac Surgery Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• patients undergoing elective primary coronary artery bypass grafting

Exclusion Criteria:

• patients who developed ischemic events during surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Group 1: Normal saline; Patients in this group were randomly assigned to receive the topical application of normal saline (0.9% sodium chloride solution) on the LIMA graft as control	Drug: The topical application of a vasodilator on the LIMA graft; Patients were randomly assigned to receive the topical application of one of three agents: milrinone (Baxter Pharmaceuticals, Ahmedabad, India) 10 mg in 20 ml of dextrose 5%, nitroglycerin (Caspian Tamin Pharmaceutical, Guilan, Iran) 10 mg in 20 ml of normal saline, or normal saline (0.9% sodium chloride solution) as control.; Other Names: milrinone (Baxter Pharmaceuticals, Ahmedabad, India), nitroglycerin (Caspian Tamin Pharmaceutical, Guilan, Iran)
Active Comparator: Group 2: Nitroglycerin; Patients were randomly assigned to receive the topical application of nitroglycerin (Caspian Tamin Pharmaceutical, Guilan, Iran) 10 mg in 20 ml of normal saline on the LIMA graft.	Drug: The topical application of a vasodilator on the LIMA graft; Patients were randomly assigned to receive the topical application of one of three agents: milrinone (Baxter Pharmaceuticals, Ahmedabad, India) 10 mg in 20 ml of dextrose 5%, nitroglycerin (Caspian Tamin Pharmaceutical, Guilan, Iran) 10 mg in 20 ml of normal saline, or normal saline (0.9% sodium chloride solution) as control.; Other Names: milrinone (Baxter Pharmaceuticals, Ahmedabad, India), nitroglycerin (Caspian Tamin Pharmaceutical, Guilan, Iran)
Active Comparator: Group 3: milrinone; Patients were randomly assigned to receive the topical application of milrinone (Baxter Pharmaceuticals, Ahmedabad, India) on the LIMA graft	Drug: The topical application of a vasodilator on the LIMA graft; Patients were randomly assigned to receive the topical application of one of three agents: milrinone (Baxter Pharmaceuticals, Ahmedabad, India) 10 mg in 20 ml of dextrose 5%, nitroglycerin (Caspian Tamin Pharmaceutical, Guilan, Iran) 10 mg in 20 ml of normal saline, or normal saline (0.9% sodium chloride solution) as control.; Other Names: milrinone (Baxter Pharmaceuticals, Ahmedabad, India), nitroglycerin (Caspian Tamin Pharmaceutical, Guilan, Iran)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LIMA free flow	Reading the volume of blood ejected from the tip of the freely bleeding IMA through a one-minute period	Immediately following harvesting the LIMA and 10 mintues following the topical application of the drug

Collaborators and Investigators

• Sponsor: Damascus University
• Investigators: Principal Investigator: Mohammad Bashar Izzat, FRCS(CTh), Damascus university

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Actual): January 31, 2023
• Study Completion (Actual): January 31, 2023

Study Registration Dates

• First Submitted: March 4, 2024
• First Submitted That Met QC Criteria: March 4, 2024
• First Posted (Actual): March 8, 2024

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: graft; coronary artery bypass grafting; milrinone; spasm
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Cardiotonic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Nitroglycerin; Milrinone; Vasodilator Agents
• Other Study ID Numbers: 3200

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data has been deposited in data repository 10.6084/m9.figshare.24905154 License CC BY 4.0
• IPD Sharing Time Frame: Data is currently and permanently available
• IPD Sharing Access Criteria: open access
• IPD Sharing Supporting Information Type: CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No