Chang et al. introduced a novel method for contrast removal using a reflectance typed optical sensor. Five canines were anesthetized, and an 8-Fr Judkins catheter was used to access the coronary artery. An aspiration catheter with a fiberoptic sensor was inserted into the CS (Figure 4 ). They injected contrast to the coronary artery and analyzed reflected signals with the fiber optic sensor in the CS. Also, they assessed the contrast removal rate through a spectrophotometric absorbance assay. The mean contrast removal rate was reported to be 59.3 ±11% (range: 42-76%) (88).
Meyer and colleagues anesthetized two dogs and accessed CS from the right jugular vein through a 6-F balloon-tipped catheter (Pressure Products, Model BVCS 6180, San Pedro, CA). After contrast administration to the left main coronary artery, the balloon was inflated and the contrast agent was captured from CS (Figure 5 ). The procedure was performed two times for each recruited animal and the mean contrast extraction was reported to be 70 ± 6% (range: 60 – 88%) (89).
●      Studies of coronary sinus contrast removal in human
The effectiveness of contrast removal in the prevention of CI-AKI has been shown in different human studies. Danenberg et al. recruited seven male individuals (range of age: 56-83 years) who suffered from previous renal failure with a mean serum creatinine of 262 ± 46 mg% to assess the safety and feasibility of contrast removal from CS during CA procedure. They engaged CS in six patients through a femoral vein with the usage of a 5-Fr Simmons II catheter (Cordis, Miami, FL) and via jugular vein with the usage of a 6-Fr catheter (Cordis) in one patient.
A two-lumen balloon-tipped catheter equipped with multiple holes in its distal end (Reverse Berman Angiography Catheter, 7 Fr, Arrow Int, Reading, PA, USA) was exchanged over the wire in order to be positioned in proximal CS. Although they could not deploy the catheter in four patients, CS was successfully accessed in three subjects. The catheter tip located at CS was inflated prior to each contrast injection. Approximately 12-16 ml of blood was aspirated manually at 5-7 seconds post-injection. The contrast removal rate was reported to be 44 ± 8%. None of the patients experienced creatinine rise and the procedure was safely performed (90) (Figure 6 ).
Likewise, in another study, a designed 11-F aspiration catheter (CINCOR Contrast Removal System, Osprey Medical, St. Paul, Minnesota) was inserted successfully in 31 out of 41 patients and the contrast aspiration rate from the CS was 32 ± 3% (range: 6-64%) (Figure 7 ). 26 of them had eGFR of less than 60 ml/min and were assessed for further outcomes. No remarkable alteration in eGFR had been found from the baseline to 72 hours after completion of the procedure (41.8 ± 2.2 ml/min to 41.1 ± 2.3 ml/min, P= 0.55). They also analyzed data with 148 matched comparators under standard care (no CS aspiration) with the administration of the same contrast volume and figured out eGFR declined significantly from 42.7 ± 0.8 ml/min to 40.1 ± 0.9 ml/min (P< 0.001) at 48-h post-procedure and the comparator group showed a greater decrease in eGFR (-2.5 ± 0.5 ml/min vs. -0.7 ± 1.2 ml/min, P< 0.05). They also compared data of those with eGFR of less than 40 ml/min (n=11) and the comparator group (n=56) and reported eGFR was not significantly changed in the first group that underwent CS contrast aspiration (from 30.7 ± 1.6 ml/min to 31.4 ± 1.8 ml/min, P= 0.42). However, a significant decline was observed in the latter group that underwent standard care (from 33.1 ± 0.7 ml/min to 31.7 ± 0.8 ml/min, P= 0.003). Between-group eGFR difference was also significant (+ 0.5 ± 0.7 ml/min vs. -1.5 ± 0.5 ml/min, P< 0.05) (35,91,92)
Diab and colleagues recruited 43 CA candidates who suffered from diabetes mellitus with a serum creatinine of 1.5 – 3 mg/dl and divided them into CS aspirate groups (n= 18) and controls (n= 25) with matched laboratory and clinical parameters. A transseptal sheath (Mullins, Medtronic, and St Jude Medical; 8 or 8.5 F) was used to access CS through the left subclavian (n= 8) or right femoral vein (n= 10). The contrast was aspirated directly through the sheath or a balloon-tipped catheter (7 F, single lumen; Arrow Int, Reading, PA). The mean reported contrast aspiration percentage was 39.35 ± 10.47% (Figures 8 and 9 ). All subjects in the CS group tolerated the experiment well. Although one patient (5.55%) in the CS arm experienced CI-AKI, this percentage was higher among controls (n= 9 (36%)) (P= 0.028) (93). Also, the contrast extraction rate was reported to be 27% in a 60-year-old man who underwent CA using CINCOR contrast extraction catheter from CS (94) (Figure 10 ).
●      Devices and methods for coronary sinus contrast extraction: