In spite improvements in methods of myocardial protection, peri-operative myocardial damage is still the commonest cause of early morbidity and mortality after technically successful CABG Surgery. What is the optimum method of myocardial protection is still debatable.

The investigators conducted this study to see effects of multiport antegrade cold blood cardioplegia on myocardial protection, along with continuous controlled warm blood perfusion through veins graft during proximal ends anastomosis in conventional CABG surgery in patients having multi-vessel disease.

A prospective randomized controlled study was conducted between April-2013 and June-2014, in the Department of Cardiac Surgery, Chaudary Pervaiz Elahi Institute of cardiology (CPEIC) Multan, Pakistan. The CPEIC is a tertiary cardiac care center and is presently performing over 600 coronary artery bypass surgery annually. The study was conducted in strict compliance of the rules established by the revised Helsinki convention and had approval from the ethical committee of the institute.

Patients undergoing isolated conventional CABG were included in the study except; The redo CABG, those who required 2 or less than 2 grafts, patients who had major postoperative neurological complications like stroke, 2nd arterial graft along with LIMA, patients who need CABG within a week of STEMI or NSTEMI and Patients with calcified or diseased aorta in which single cross clamp technique was used for proximal aorto-coronary anastomosis.

The patients were randomized into two groups by using draw randomization technique. The investigators made 112 sets, each set containing four patients. The staff nurse on duty was requested to pick up the two folded papers from four containing hidden identity of the patients. The patients chosen by draw were included in the study group, others in the control group.

Group I: Patients who received multiport antegrade cardioplegia and continuous controlled warm blood perfusion through vein grafts (Study Group) and Group II: Patients who underwent routine conventional CABG with antegrade aortic root cardioplegia without warm blood perfusion (Control Group).

All operations were carried out by two consultant surgeons at the investigators institution, who are certified cardiac surgeons with sufficient experience. Patients were premedicated with oral dose of 3mg bromazepam the night before surgery. Anaesthesia was induced with intra-venous morphine (0.1mg/kg), midazolam (0.05-0.1 mg /kg), and propofol (1.0-2.5 mg/kg titrated according to the response. They were given atracuronium (1mg/kg) before endotracheal intubation. The anaesthesia was maintained with sevoflorane/isoflurane.

In all patients the standard cardiopulmonary bypass (CPB) was established with an ascending aortic arterial cannula and a two stage single venous cannula in the right atrium. The CPB circuit was primed with crystalloid Ringer's solution. Heparin was administered in a dose of 400 U/Kg. The body temperature was lowered to 30-32°C. The local cooling was achieved with ice cold saline. Cold blood cardioplegia was used in each group. The first dose of cardioplegia was 10-15 ml/kg and further doses were given as 5-7ml/kg repeated after each graft or after 20 minutes. Cold blood cardioplegia was given by using cardioplegia delivery system including heat exchanger in both groups. A cardioplegia delivery cannula with a separate vent line (DLP Medtronic, Grand Rapids, MI, USA) was inserted into the ascending aorta. The pump flow rate was kept between 2.0 and 2.4 L/min/m2 to maintain a mean arterial pressure of 55 - 70 mmHg. In both groups, myocardial protection was achieved by an initial antegrade infusion of cold (4 °C) blood cardioplegic potassium solution followed by intermittent antegrade cold blood cardioplegia at the completion of each distal anastomosis via a cardioplegia delivery cannula from the aortic root. Whereas in Group I, a multiple perfusion set was used to deliver cardioplegia simultaneously in aortic root and vein grafts. After the distal anastomosis of each vein graft had been completed, the proximal ends were connected to the free branch of the multi- perfusion set. In this way, simultaneous intermittent antegrade graft cardioplegia was administered in addition to aortic root cardioplegia (named as multiport antegrade cardioplegia).

LIMA and great saphenous vein were used as conduits. LIMA was anastomosed to LAD and other coronary vessels received greater saphenous vein grafts as conduits.

Just before the removal of the aortic cross-clamp, warm blood shot (normo-kalemic) was started through multi-perfusion set attached to cardioplegia cannula in the aortic root and vein grafts in Group I. As contraction of heart started the multiport limb attached to cardioplegia cannula was off and cross clamp was removed .The warm perfusion through the vein grafts was continued at controlled pressures of about 50-70 mmHg, flow rate of 10-30ml/min/graft and temperature of 35-37 oC. Proximal anastmosis was performed in both groups using partial occluding clamp.

The necessity of inotropic support and the choice of inotropic drugs to be administered during weaning from cardiopulmonary bypass (CPB) were determined by a cardiac anaesthetist team, who were blinded and independent with respect to the study.

The CK-MB levels were determined at five points of time i.e. before operation, immediately after shifting to ICU, at 12, 24 hours and 36 hours after shifting of patient to ICU. The reagent used for determining the serum CK-MB levels was the product of Merck (Merck, France) and the designated reference value for detection of myocardial damage were >25 units/liter for CK-MB.

448 patient characteristics were prospectively entered in the investigators electronic database (CASCADE DATABASES, Lahore, Pakistan). The study specific data not included in the database were separately entered in a Microsoft Excel spreadsheet (MS Excel, version 2007, Microsoft Co USA). The statistical analysis was carried out using SPSS (SPSS version 20, SPSS Inc, Chicago, IL). The preoperative, operative and postoperative characteristics were summarized using means and standard deviation for the numeric variables. The groups were compared using Student's t-test for numeric variables and Chi-square test for categorical variables.

The significance of differences between the groups was expressed as p-value and a value of <0.05 was considered significant.

Inclusion Criteria:

• All patients undergoing isolated conventional CABG were included in the study

Exclusion Criteria:

The redo CABG surgery. Those who required 2 or less than 2 grafts. Patients who had major postoperative neurological complications like stroke. 2nd arterial graft along with LIMA. Patients who need CABG within a week of STEMI or NSTEMI. Patients with calcified or diseased aorta in which single cross clamp technique was used for proximal aorto-coronary anastomosis

All patients who was enrolled for trial age and gender was clearly defined and noted

1 month after surgery

Adverse event was considered as any complication that will be the direct result of technique used for myocardial protection in study and control group.