Effekt der isovolämischen Hämodilution auf die Lungenmikrozirkulation bei experimenteller Pankreatitis

Abstract

Background: Isovolemic hemodilution (IHD) has been shown to ameliorate hemoconcentration and improve pancreatic capillary blood flow in severe experimental pancreatitis. This was associated with decreased pancreatic necrosis and mortality. The clinical practicability of this experimental concept has been tested in a pilot study and is now evaluated in a controlled randomized multicenter trial in patients with severe acute pancreatitis (AP). Meanwhile, further experimental evidence has suggested that improvement of microcirculation (by endothelin receptor blockade) does not only involve the pancreas, but also other organs including the colon, liver and lungs. The present study evaluates whether IHD also exhibits positive effects on pulmonary microcirculation. Method: ANP was induced in 12 male Sprague-Dawley rats by standardized time-, pressure- and volume- controlled intraductal infusion of 1.25 ml/kg glycodeoxycholic acid (10 mM/1) and consecutive exocrine hyperstimulation by 5 µg/kg cerulein i.v. over 6 h. Rats were then randomized for either conventional fluid resuscitation with 8 ml/kg/h Ringer’s lactate (RL) or isovolemic hemodilution (IHD), i.e. 8 ml/kg blood were replaced by 8 ml/kg hydroxyethyl starch (6% HES 200.000/0.5). Healthy sham-operated rats served as additional controls. Before and at several time points after therapy hematocrit, vital signs and arterial blood gases were measured. After 24 h, animals were mechanically ventilated, and a left thoracotomy was performed for exposure of the lung for intravital microscopic determination of leukocyte sticking, red blood cell velocity and capillary permeability. Results: Hematocrit significantly decreased with IHD (39 ± 2 after 7 h vs. 54 ± 2 at 6 h) and was significantly lower than in the RL group at 24 h (36 ± 1 vs. 48 ± 2%; p < 0.05). Pulmonary capillary blood flow was significantly reduced in animals with AP treated with RL (compared to healthy sham-operated animals), capillary permeability and leukocyte sticking were increased. IHD significantly enhanced pulmonary capillary blood flow (0.57 ± 0.02 vs. 0.41 ± 0.01 mm/s with RL) and decreased vascular permeability (114 ± 13 vs. 260 ± 14 % ) . The values recorded after 24 h for capillary blood flow and permeability in IHD-treated animals with AP were not significantly different from those of healthy shamoperated rats; leukocyte sticking, however, was still increased. Discussion: This study confirms that IHD also exhibits positive effects on pulmonary microcirculation in this model of severe AP in the rat. Thus, positive results of IHD in the treatment of ANP may not only be explained by enhanced pancreatic microcirculation, but a systemic effect with improvement of disturbed microcirculation in other organs including the lungs. These experimental data support the concept of IHD as a promising novel treatment strategy in severe acute pancreatitis.