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.

Figure 1:

Quantitative coronary flow analysis model with six blood flows simultaneously measured. LAD: left anterior descending, Cx: circumflex artery, RCA: right coronary artery, RCCA: right common carotid artery, LIMA: left internal mammary artery.

Figure 2:

In our model of in situ lung ischemia-reperfusion the left pulmonary hilum is clamped with the use of a flexible clamp to induce left lung ischemia. Release of the clamp without further surgical manipulations results in the initiation of reperfusion. RV: right ventricle, LV: left ventricle.

Figure 3:

Blood flow and pressure measurements during in situ left lung ischemia and reperfusion. Plots show mean ± SD for each time point. I: Ischemia, R: reperfusion (I and R time in minutes), TCF: total coronary flow, LAD: left anterior descending, Cx: circumflex artery, RCA: right coronary artery, CO: cardiac output, RCCA: right common carotid artery, LIMA: left internal mammary artery, LVP-S: systolic left ventricular pressure, LVP-M: mean left ventricular pressure, RVP-S: systolic right ventricular pressure, RVP-M: mean right ventricular pressure.

Figure 4:

Cytokine measurements during in situ left lung ischemia and reperfusion. Plots show mean ± SD for each time point. I: Ischemia, R: reperfusion (I and R time in minutes), cTn: DcTn = Study cTn - Control cTn, IL-6: DIL-6 = Study IL-6 - Control IL-6, TCF: total coronary flow, LVP-S: systolic left ventricular pressure, AoP-S: systolic aortic pressure.