title: Does lung ischemia and reperfusion have an impact on coronary flow? A quantitative coronary blood-flow analysis with inflammatory cytokine profile.
abstract: OBJECTIVE
  Ischemia-reperfusion (IR) injury remains a major cause of early morbidity and mortality after lung transplantation with poorly documented extrapulmonary repercussions. To determine the hemodynamic effect due to lung IR injury, we performed a quantitative coronary blood-flow analysis in a swine model of in situ lung ischemia and reperfusion.
  
  
  METHODS
  In 14 healthy pigs, blood flow was measured in the ascending aorta, left anterior descending (LAD), circumflex (Cx), right coronary artery (RCA), right common carotid artery (RCCA), and left internal mammary artery (LIMA), along with left-and right-ventricular pressures (LVP and RVP), aortic pressure (AoP), and pulmonary artery pressure (PAP). Cardiac Troponin (cTn), interleukin 6 and 10 (IL-6 and IL-10), and tumor necrosis factor A (TNF-A) were measured in coronary sinus blood samples. The experimental (IR) group (n=10) underwent 60 min of lung ischemia followed by 60 min of reperfusion by clamping and releasing the left pulmonary hilum. Simultaneous measurements of all parameters were made at baseline and during IR. The control group (n=4) had similar measurements without lung IR.
  
  
  RESULTS
  In the IR group, total coronary flow (TCF=LAD+Cx+RCA blood-flow) decreased precipitously and significantly from baseline (113±41 ml min"1) during IR (p<0.05), with the lowest value observed at 60 min of reperfusion (-37.1%, p<0.003). Baseline cTn (0.08±0.02 ng ml(-1)) increased during IR and peaked at 45 min of reperfusion (+138%, p<0.001). Baseline IL-6 (9.2±2.17 pg ml(-1)) increased during IR and peaked at 60 min of reperfusion (+228%, p<0.0001). Significant LVP drop at 5 min of ischemia (p<0.05) was followed by a slow return to baseline at 45 min of ischemia. A second LVP drop occurred at reperfusion (p<0.05) and persisted. Conversely, RVP increased throughout ischemia (p<0.05) and returned toward baseline during reperfusion. Coronary blood flow and hemodynamic profile remained unchanged in the control group. IL-10 and TNF-A remained below the measurable range for both the groups.
  
  
  CONCLUSIONS
  In situ lung IR has a marked negative impact on coronary blood flow, hemodynamics, and inflammatory profile. In addition, to the best of our knowledge, this is the first study where coronary blood flow is directly measured during lung IR, revealing the associated increased cardiac risk.
authors: Mayo Clinic Lung Transplant Program, William J. von Liebig Transplant Center, Rochester, MN, USA.
authors: Nikolaos Tsirikos
authors: NT
authors: Karapanos
authors: Peter J
authors: PJ
authors: Wettstein
authors: Zhuo
authors: Z
authors: Li
authors: Marianne
authors: M
authors: Huebner
authors: Soon J
authors: SJ
authors: Park
authors: Claude
authors: C
authors: Deschamps
authors: Stephen D
authors: SD
authors: Cassivi
mesh_terms: D000818:Animals; D003326:Coronary Circulation / Q000502:physiology*; D016207:Cytokines / Q000097:blood*; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000502:physiology; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000098:blood supply*; D008297:Male; D015427:Reperfusion Injury / Q000097:blood / Q000503:physiopathology*; D034421:Sus scrofa
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators