Role of ischaemic preconditioning in liver regeneration following major liver resection and transplantation

Table 1 Previous published human studies on the results of ischaemic preconditioning following liver resection and transplantation

Study group	Sample1	Surgery	IPC2	Ischaemia and reperfusion time (min)3	Parameters assessed	Outcome of IPC
Clavien et al[17] (2000)	24 (12)	Liver resection	10I + 10R	IPC and control (TI: 30)	PT, Bilirubin, ALT, AST, Histology, Caspase-3 and 8 activity, SEC apoptosis, Blood loss, Transfusion, ITU stay, LOS	Protective against IRI Beneficial in patients with steatosis
Clavien et al[204] (2003)	100 (50)	Liver resection	10I + 10R	IPC (TI: 36 ± 5.9, Op: 225 ± 73), Control (TI: 35 ± 6.8, Op: 240 ± 92)	PT, Bilirubin, ALT, AST, Histology, Hepatic ATP, Blood loss, Transfusion, ITU stay, LOS	Protective against IRI Beneficial in younger patients, those with steatosis and longer periods of occlusion
Li et al[205] (2004)	29 (14)	Liver resection	5I + 5R	IPC (TI: 18 ± 3.6, Op: 191.3 ± 74.9), Control (TI: 17.4 ± 2.3, Op: 208.2 ± 45.3)	Bilirubin, ALT, AST, Histology, Caspase-3 activity, SEC apoptosis, LOS	Protective against IRI, mainly HCC patients with cirrhosis Shorter hospital stay
Nuzzo et al[209] (2004)	42 (21)	Liver resection	10I + 10R	IPC (TI: 54 ± 19, Op: 321 ± 92), Control (TI: 36 ± 14, Op: 339 ± 112)	PT, Bilirubin, ALT, AST, Transfusion, Morbidity, Mortality	Reduces operative bleeding Protective against IRI
Chouker et al[206] (2004)	68 (22)	Liver resection	10I + 10R	IPC (TI: 32 ± 6.3, Op: 251 ± 46), Control without PR (TI: NA, Op: 52 ± 30), Control with PR (TI: 35 ± 11, Op: 257 ± 83)	ALT, AST, Fluid loss, Transfusion, 4Cardiovascular status	Protective against IRI Improves haemodynamic stability
Chouker et al[207] (2005)	75 (25)	Liver resection	10I + 10R	IPC (TI: 35.5 ± 2.7, LR: 32.2 ± 2.0), Control without PR (TI: NA, LR: 39 ± 4.5), Control with PR (TI: 35.6 ± 2.6, LR: 33.2 ± 2.3)	IL-6, IL-8, Cytochrome c, Adhesion molecules [B2-integrins (CD18)], Histology (neutrophil infiltration)	Protective against IRI by attenuating neutrophil activation and IL-8 release
Chouker et al[208] (2005)	73 (25)	Liver resection	10I + 10R	IPC (TI: 35.12 ± 13.6, LR: 31.50 ± 9.1), Control without PR (TI: NA, LR: 34.77 ± 16.5), Control with PR (TI: 34.2 ± 10.9, LR: 32.13 ± 10)	PT, ALT, AST, α-GST	Protective against IRI Prevented early rise of α-GST
Koneru et al[210] (2005)	62 (34)	Transplant	5I + 5R	IPC (CI: 384 ± 92, WI: 41 ± 5.8), Control (CI: 415 ± 87, WI: 37 ± 5.6)	INR, Bilirubin, ALT, AST, Histology (apoptosis, hepatocyte swelling), LOS, Survival (6 mo)	No beneficial effect
Azoulay et al[212] (2005)	91 (46)	Transplant	10I + 10R	IPC (CI: 436 ± 116, Op: 441 ± 119), Control (CI: 461 ± 96, Op: 462 ± 98)	PT, Bilirubin, ALT, AST, Histology, Graft function, Morbidity, Mortality	Better ischaemic tolerance Decreased early graft function
Jassem et al[211] (2005)	23 (9)	Transplant	10I + 10R	IPC (CI: 620 ± 190, WI: 43.9 ± 13), Control (CI: 665 ± 280, WI: 40.4 ± 9)	AST, INR, Lactate, ITU stay, Histology (neutrophil infiltration, platelet deposition), Graft function	Protective against IRI Reduces inflammatory response Shorter ITU stay
Cescon et al[213] (2006)	47 (23)	Transplant	10I + 15R	5IPC [TI: 388 (259-830), Op: 440 (225-725)], Control [TI: 383 (279-695), Op: 465 (280-1015)]	PT, Bilirubin, ALT, AST, Histology (neutrophil, lymphocyte infiltration, iNOS, apoptosis), Graft function, Survival (1 yr)	Protective against IRI No clinical benefit

¹Patients stated in brackets are the number of patients who had ischaemic preconditioning treatment;

²IPC was performed by portal triad clamping in all these studies;

³Ischaemia and operative times are presented as mean ± SD unless otherwise stated;

⁴Cardiovascular status refers to mean arterial pressure, central venous pressure, heart rate, stroke volume index, systemic vascular resistance index, fluid infusion and catecholamines requirements;

⁵Ischaemia and reperfusion times in this study were presented as median (range). I: Ischaemia; R: Reperfusion; IPC: Ischaemic preconditioning group; PR: Pringle maneuver; TI: Total ischaemia time; CI: Cold ischaemia time; WI: Warm ischaemia time; Op: Total operative time; LR: Liver resection time; ITU: Intensive therapy unit; LOS: Length of hospital stay; PT: Pro-thrombin time; INR: International normalized ratio of pro-thrombin time; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; α-GST: Alpha-Gluthathione S-Transferase; iNOS: Inducible form of nitric oxide synthase; ATP: Adenosine triphosphate; HCC: Hepatocellular carcinoma; IL: Interleukin; SEC: Sinusoidal endothelial cell; IRI: Ischaemia-reperfusion injury.