Table 1.
Application of CO to donor, graft, and recipient in mitigating I/R injury
| Species/ organ |
Model | CO delivery method | Specific protective effects |
Proposed molecular mechanisms | Ref |
|---|---|---|---|---|---|
|
DONOR Rat, heart |
CS 24 hrs and Syn Tx |
CO inhalation donor (recipient) 400 ppm UW solution saturated with CO gas 1% |
Anti-apoptosis |
NA |
(79) |
| Rat, lung | CS 6 hr and Syn Tx | CO inhalation donor 1000 ppm | Anti-inflammatory Anti-thrombosis |
ERK inhibition, Egr-1 inhibition sGC activation |
(81) |
| Rat, lung | CS 6 hr ind Syn Tx | CO inhalation donor/recipient 250 ppm |
Anti-inflammatory | p38 MAPK activation ERK1/2 inhibition |
(80, 139) |
|
GRAFT Rat, Kidney |
CS 24 hrs and Syn Tx |
UW solution saturated with CO gas 5% (40 µM) |
Anti-inflammatory |
Inhibition of cytochrome P450 degradation and intracellular heme release |
(43) |
| Rabbit, Kidney |
CS 24 hrs and ex vivo perfusion |
CORM-A1, CORM-3 in Celsior solution 50 µM |
Vasodilatation | sGC activation | (69) |
| Pig, Kidney | CS 48 hrs and Auto Tx |
UW solution saturated with CO gas 5–10% (40–100 µM) |
Anti-inflammatory Anti-fibrotic |
NA | (64) |
| Rat, Liver | CS 18–24 hrs and Syn Tx |
UW solution saturated with CO gas 5% (40 µM) |
Anti-apoptosis Anti-inflammatory |
ERK1/2 inhibition | (62) |
| Rat, Liver | CS 48 hrs and ex vivo perfusion |
CORM-3 in UW solution 50 µM | Vasodilatation | NA | (71) |
| Rat, heart | CS 4–6 hrs ex vivo perfusion |
CORM-3 in St. Thomas H solution 50 µM |
Vasodilatation | NA | (70, 162) |
| Rat, lung | CS 6 hr and Syn Tx | UW solution saturated with CO gas 5% (~40 µM) |
Anti-inflammatory | NA | (63) |
| Rat, intestine |
CS 6 hr and Syn Tx | UW solution saturated with CO gas 5% (~40 µM) |
Anti-inflammatory Vasodilatation |
sGC activation | (65) |
|
RECIPIENT Rat, Kidney |
CS 24 hrs and Syn Tx |
CO inhalation recipient 250 ppm |
Anti-inflammatory Anti-apoptosis Vasodilatation |
HIF-1α activation and VEGF upregulation. |
(108, 157) |
| Pig, Kidney | WI 60 min + CS 24 hrs and Allo Tx |
CO inhalation recipient 2–3 mg/kg (COHb 4–9%) |
Anti-inflammatory Anti-apoptosis |
Enhance proliferative repair | (141) |
| Pig, Kidney | WI 10 min + CS 16– 18 hrs and ex vivo perfusion |
CORM-3 in perfusion solution 50– 400 µM |
Vasodilatation | NA | (74) (73) |
| Rat, Liver | CS 24 hrs and ex vivo perfusion |
Perfusate (Ht 15%) saturated with CO gas 300 ppm |
Vasodilatation | p38 MAPK activation | (59) |
| Rat, Liver | CS 18 hrs and Syn Tx |
CO inhalation recipient 20–250 ppm (COHb 5–25%) |
Anti-inflammatory Anti-thrombosis |
ERK1/2 MAPK inhibition | (115, 138, 163) |
| Rat, lung | CS 6 hr and Syn Tx | CO inhalation donor/recipient 250 ppm |
Anti-inflammatory | p38 MAPK activation ERK1/2 inhibition |
(80, 139) |
| Rat, intestine |
CS 6 hr and Syn Tx | CO inhalation recipient 250 ppm | Anti-inflammatory Anti-apoptosis |
sGC activation | (109, 140) |
|
WARM ISCHEMIA Mouse, kidney |
WI 40 min |
[Ru(CO)3Cl2]2 iv 10 mg/kg CORM-3 ip 40 mg/kg |
NA |
HO-1 upregulation |
(150) |
| Rat, Liver | WI 70% liver 60 min |
CORM-2 iv 8 mg/kg | Anti-inflammatory Anti-apoptosis |
NFκB inhibition | (164) |
| Mice, heart | LAD ligation 30 min | CORM-3 iv 3.54 mg/kg | NA | NA | (147) |
| Rat, heart | LAD ligation 30 min | CO inhalation 250–1000 ppm | Anti-inflammatory | p38 MAPK, Akt, eNOS, and sGC activation |
(146) |
| Rat, heart | LAD ligation 30 min | Hemospan saturated with CO gas | NA | NA | (165) |
| Rat, heart | WI 30min and ex vivo perfusion |
CORM-3 10–50 µM | NA | NA | (72, 166) |
| Pig, heart | LAD ligation 45 min | CO inhalation COHb 5% | NA | NA | (167) |
| Mouse, lung | WI left lung 60 min | CO inhalation 1000 ppm (COHb 24.8%) |
Anti-thrombosis | sGC activation PAI-1 inhibition |
(114) |
| Mouse, lung | WI left lung 30 min | CO inhalation 500 ppm | Anti-apoptosis | P38 MAPK activation | (119) |
| Pig, lung | WI left lung 90 min | CO inhalation 250 ppm (COHb 12.1%) |
Anti-inflammatory | Low HMGB-1 | (168) |
Allo Tx: allogenic transplantation
CS: cold storage
LAD: left anterior descending coronary artery
Syn Tx: syngenic transplantation
WI: warm ischemia