Impaired microcirculatory perfusion in a rat model of cardiopulmonary bypass: the role of hemodilution

Abstract

Although hemodilution is attributed as the main cause of microcirculatory impairment during cardiopulmonary bypass (CPB), this relationship has never been investigated. We investigated the distinct effects of hemodilution with or without CPB on microvascular perfusion and subsequent renal tissue injury in a rat model. Male Wistar rats (375-425 g) were anesthetized, prepared for cremaster muscle intravital microscopy, and subjected to CPB (n = 9), hemodilution alone (n = 9), or a sham procedure (n = 6). Microcirculatory recordings were performed at multiple time points and analyzed for perfusion characteristics. Kidney and lung tissue were investigated for mRNA expression for genes regulating inflammation and endothelial adhesion molecule expression. Renal injury was assessed with immunohistochemistry. Hematocrit levels dropped to 0.24 ± 0.03 l/l and 0.22 ± 0.02 l/l after onset of hemodilution with or without CPB. Microcirculatory perfusion remained unaltered in sham rats. Hemodilution alone induced a 13% decrease in perfused capillaries, after which recovery was observed. Onset of CPB reduced the perfused capillaries by 40% (9.2 ± 0.9 to 5.5 ± 1.5 perfused capillaries per microscope field; P < 0.001), and this reduction persisted throughout the experiment. Endothelial and inflammatory activation and renal histological injury were increased after CPB compared with hemodilution or sham procedure. Hemodilution leads to minor and transient disturbances in microcirculatory perfusion, which cannot fully explain impaired microcirculation following cardiopulmonary bypass. CPB led to increased renal injury and endothelial adhesion molecule expression in the kidney and lung compared with hemodilution. Our findings suggest that microcirculatory impairment during CPB may play a role in the development of kidney injury.

Reduction of vascular leakage by imatinib is associated with preserved microcirculatory perfusion and reduced renal injury markers in a rat model of cardiopulmonary bypass

“…We recently showed in a rat CPB model that inflammation and endothelial activation contribute more to these microcirculatory-perfusion disturbances than haemodilution. 3 Moreover, microcirculatory dysfunction was paralleled by increases in markers of renal injury, and renal and pulmonary endothelial activation. 3 Clinical studies and in vitro experiments using cultured endothelial cells show that endothelial activation and inflammation during CPB elicit endothelial barrier dysfunction with subsequent vascular leakage.…”

“…3 Moreover, microcirculatory dysfunction was paralleled by increases in markers of renal injury, and renal and pulmonary endothelial activation. 3 Clinical studies and in vitro experiments using cultured endothelial cells show that endothelial activation and inflammation during CPB elicit endothelial barrier dysfunction with subsequent vascular leakage. 4e6 Moreover, vascular leakage is associated with postoperative pulmonary and renal dysfunction, 4,5 which may be mediated by a reduction in capillary perfusion due to interstitial fluid accumulation.…”

“…Anaesthesia was induced as described previously. 3 Briefly, anaesthesia was induced with isoflurane 5% in oxygen, and when the pedal withdrawal response to a nociceptive stimulus was absent, tracheal intubation with a 16G catheter was performed (Venflon Pro; Becton Dickinson, Helsingborg, Sweden). Mechanical ventilation (UMV-03; UNO Roestvaststaal BV, Zevenaar, The Netherlands; tidal volume 10 ml kg À1 , frequency 60e65 min À1 , PEEP 2e4 cm H 2 O) was initiated and anaesthesia was maintained with isoflurane 2e3% with the FiO 2 at 0.35.…”

“…M. Humbs, Valley, Germany) with a three-layer hollow fibre membrane (Oxyphan; Membrana, Wuppertal, Germany) for gas exchange, as described previously. 3 Detailed information can be found in the Supplementary File.…”

“…Intravital microcirculatory observation was performed on the cremaster muscle. 3 A 10Â objective (W N-Achroplan; Zeiss, Oberkochen, Germany; numerical aperture 0.30) on an intravital microscope (Axiotech Vario 100 HD; Zeiss) was connected to a digital camera (scA640; Basler, Ahrensburg, Germany). The final magnification was 640Â.…”