Lactated Ringers, albumin and mannitol as priming during cardiopulmonary bypass reduces pulmonary edema in rats compared with hydroxyethyl starch

Abstract

Background: Endothelial disorders with edema formation and microcirculatory perfusion disturbances are common in cardiac surgery with cardiopulmonary bypass (CPB) and contribute to disturbed tissue oxygenation resulting in organ dysfunction. Albumin is protective for the endothelium and could be a useful additive to CPB circuit priming. Therefore, this study aimed to compare organ edema and microcirculatory perfusion in rats on CPB primed with lactated Ringers, albumin and mannitol (LR/albumin/mannitol) compared to 6% hydroxyethyl starch (HES).

Results: Male rats were subjected to 75 min of CPB primed with either LR/albumin/mannitol or with 6% HES. Renal and lung edema were determined by wet/dry weight ratio. Pulmonary wet/dry weight ratio was lower in rats on CPB primed with LR/albumin/mannitol compared to HES (4.77 [4.44-5.25] vs. 5.33 [5.06-6.33], p = 0.032), whereas renal wet/dry weight ratio did not differ between groups (4.57 [4.41-4.75] vs. 4.51 [4.47-4.73], p = 0.813). Cremaster microcirculatory perfusion was assessed before, during and after CPB with intravital microscopy. CPB immediately impaired microcirculatory perfusion compared to baseline (LR/albumin/mannitol: 2 [1-7] vs. 14 [12-16] vessels per recording, p = 0.008; HES: 4 [2-6] vs. 12 [10-13] vessels per recording, p = 0.037), which persisted after weaning from CPB without differences between groups (LR/albumin/mannitol: 5 [1-9] vs. HES: 1 [0-4], p = 0.926). In addition, rats on CPB primed with LR/albumin/mannitol required less fluids to reach sufficient flow rates (0.5 [0.0-5.0] mL vs. 9 [4.5-10.0], p < 0.001) and phenylephrine (20 [0-40] µg vs. 90 [40-200], p = 0.004). Circulating markers for inflammation (interleukin 6 and 10), adhesion (ICAM-1), glycocalyx shedding (syndecan-1) and renal injury (NGAL) were determined by ELISA or Luminex. Circulating interleukin-6 (16 [13-25] vs. 33 [24-51] ng/mL, p = 0.006), interleukin-10 (434 [295-782] vs. 2120 [1309-3408] pg/ml, p < 0.0001), syndecan-1 (5 [3-7] vs. 15 [11-16] ng/mL, p < 0.001) and NGAL (555 [375-1078] vs. 2200 [835-3671] ng/mL, p = 0.008) were lower in rats on CPB primed with LR/albumin/mannitol compared to HES.

Conclusion: CPB priming with LR, albumin and mannitol resulted in less pulmonary edema, renal injury, inflammation and glycocalyx degradation compared to 6% HES. Furthermore, it enhanced hemodynamic stability compared with HES. Further research is needed to explore the specific role of albumin as a beneficial additive in CPB priming.

Keywords: Cardiopulmonary bypass; Edema; Glycocalyx; Microcirculation; Priming.

Fig. 1

Experimental set-up. Rats were subjected to 75 min of CPB primed with LR/albumin/mannitol or HES. One hour after weaning from CPB, rats were killed to determine pulmonary and renal edema. Microcirculatory perfusion measurements were performed at baseline, 10 and 60 min after initiation of CPB and 10 and 60 min after weaning from CPB

Fig. 2

Hemodynamic parameters during CPB. Mean arterial pressure (A), heart rate (B) and hematocrit (C) in rats during and after CPB primed with LR/albumin/mannitol (continuous line, n = 9) or with HES (dashed line, n = 9). The grey background indicates the period during CPB. Data are presented as median with interquartile range, ** p < 0.01, *** p < 0.001, **** p < 0.0001 HES vs. LR/albumin/mannitol priming

Fig. 3

Blood gas analyses during CPB. pH (A), base excess (B), bicarbonate (HCO₃⁻; C), partial pressure of carbon dioxide (pCO₂; D) and partial pressure of oxygen (pO₂; E) in rats during and after CPB primed with LR/albumin/mannitol (continuous line, n = 9) or HES (dashed line, n = 9). The grey background indicates the period during CPB. Data are presented as median with interquartile range, *** p < 0.001, **** p < 0.0001 HES vs. LR/albumin/mannitol priming

Fig. 4

Microcirculatory perfusion. Continuously perfused vessels (A), intermittently perfused vessels (B), non-perfused vessels (C) and proportion of perfused vessels (PPV; D) in cremaster muscle in rats during and after CPB primed with LR/albumin/mannitol (continuous line, n = 9) or HES (dashed line, n = 9). The grey background indicates the period during CPB. Data are presented as median with interquartile range

Fig. 5

Renal and pulmonary edema formation and fluid requirements. Renal (A) and pulmonary (B) wet/dry weight ratio, extra fluids (C) and phenylephrine given during CPB (D) in rats following CPB primed with LR/albumin/mannitol (LR/a/m; white box) or HES (grey box). Rats on CPB primed with LR/albumin/mannitol received albumin and primed with HES received HES as additional fluids. Data are presented as median, interquartile and full range, every dot represents an individual rat, * p < 0.05, **, p < 0.01, *** p < 0.001 HES vs. LR/albumin/mannitol priming

Fig. 6

Circulating markers of inflammation, adhesion, glycocalyx shedding and renal injury. Plasma levels of interleukin-6 (IL-6; A), interleukin-10 (IL-10; B), intercellular adhesion molecule 1 (ICAM-1; C), syndecan-1 (D) and neutrophil gelatinase-associated lipocalin (NGAL; D) in rats during and after CPB primed with LR/albumin/mannitol (LR/a/m; white box) or HES (grey box). Data are presented as median, interquartile and full range, every dot represents an individual rat, ** p < 0.01, *** p < 0.001, **** p < 0.0001 HES vs. LR/albumin/mannitol priming