Table 2.
Animal studies evaluating intestinal and pancreatic microhemodynamics
| Subjects | Ref. | Year | Title | Type of study | Scenario | No. subjects | Sensory blockade | Surrogate measure of splanchnic flow | Findings |
| Rabbits | Hogan et al[7] | 1993 | Effects of epidural and systemic lidocaine on sympathetic activity and mesenteric circulation in rabbits | Prospective randomized | Anesthetized animals receiving thoraco-lumbar epidural block with different anesthetic concentrations | 32 (7 lidocaine 6 mg/kg im vs 5 lidocaine 15 mg/kg im vs 5 TEA lido 0.5% vs 8 TEA lido 1.0% vs 7 TEA lido 1.5%) | T2-L5 | Mesenteric vein diameter, sympathetic efferent nerve activity (SENA) of post ganglionic splanchnic nerve | TEA ↑ splanchnic venous capacitance and ↓ SENA |
| Rabbits | Hogan et al[8] | 1995 | Region of epidural blockade determines sympathetic and mesenteric capacitance effects in rabbits | Prospective randomized | Anesthetized and non anesthetized animals receiving either a thoracic or lumbar block with special epidural catheters limiting anesthetic spread | 26 (6 lidocaine 1% TEA vs 6 lido 1% LEA, vs 8 thoracolumbar anesthesia in spontaneous ventilation with lido 1% vs 6 thoracolumbar anesthesia with lido 1% in fully awake animals) | T11-L7 (LEA group), T4-L1 (TEA group), T1-L4 (thoracolumbar anesthesia) | Mesenteric vein diameter, sympathetic efferent nerve activity (SENA) of post ganglionic splanchnic nerve | ↑ SENA and ↓ mesenteric vein diameter after lumbar epidural anesthesia while ↓ SENA and ↑ mesenteric vein diameter after thoracic epidural anesthesia |
| Rats | Sielenkämper et al[10] | 2000 | Thoracic epidural anesthesia increases mucosal perfusion in ileum of rats | Prospective randomized | Anesthetized and mechanically ventilated rats that underwent laparotomy to obtain access to the ileum | 19: 11 bupivacaine 0.4% (TEA); 8 normal saline (CTRL) | Catheter tip placed T7-T9 | Intravital microscopy on the ileum mucosa | TEA ↑ gut mucosal blood flow and ↓ the extent of intermittent flow in the villus microcirculation |
| Rats | Adolphs et al[12] | 2003 | Thoracic epidural anesthesia attenuates hemorrhage-induced impairment of intestinal perfusion in rats | Prospective randomized | Hemorragic shock model (PAM 30 mmHg for 60 min) induced by withdrawal of blood and subsequent retransfusion for resuscitation | 32 (4 groups of 8); epidural lidocaine 2% (TEA) or normal saline (CTRL), muscolaris or mucosa evaluated | catheter tip placed T11-T12 | Intravital microscopy with fluorescein (FCD = functional capillary density and erythrocyte velocity in the mucosa and muscularis of distal ileum) | TEA ↑ intestinal microvascular perfusion and ↓ hypotension-induced impairment of capillary perfusion in the muscularis, ↓ systemic acidemia during hypotension and ↓ leukocyte rolling after resuscitation |
| Rats | Adolphs et al[11] | 2004 | Effects of thoracic epidural anaesthesia on intestinal microvascular perfusion in a rodent model of normotensive endotoxaemia | Prospective randomized | Normotensive endotoxaemia model through LPS infusion in anesthetized animals | 32 (8 no TEA vs 24 TEA) +/- E.coli LPS infusion +/- epidural lidocaine 2% or saline infusion, muscolaris or mucosa evaluated | catheter tip placed T11-T12 | Intravital microscopy with fluorescein (densities of perfused and non-perfused capillaries and erythrocyte velocity in both the mucosa and the muscularis of the terminal ileum) | TEA ↓ MAP and HR, ↑ muscularis and ↓ mucosal microvascular perfusion |
| Dogs | Schwarte et al[15] | 2004 | Effects of thoracic epidural anaesthesia on microvascular gastric mucosal oxygenation in physiological and compromised circulatory conditions in dogs | Prospective randomized | Chronically instrumented and anaesthetized dogs. Animals were studied under physiological and compromised circulatory conditions (PEEP 10 cm H(2)O), both with and without fluid resuscitation | 12 (6 lidocaine vs 6 saline) | catheter tip placed T10, thoracolumbar - paresis of the ocular nictitating membrane, sensory block up to the neck region, and motor block of the limbs | Gastric mucosal oxygenation by measuring microvascular haemoglobin oxygen saturation (µHbO2) using reflectance spectrophotometry | Under physiological conditions, TEA preserved gastricmucosal oxygenation but aggravated its reduction during impaired circulatory conditions, thereby preserving the correlation between gastric mucosal and systemic oxygenation. Fluid resuscitation completely restored these variables |
| Rabbits | Kosugi et al[9] | 2005 | Epidural analgesia prevents endotoxin-induced gut mucosal injury in rabbits | Prospective randomized | Normotensive endotoxaemia model through LPS infusion in anesthetized animals | PROTOCOL 1: 28 = 14 saline (C = CONTROL) vs 14 lidocaine (E = EPIDURAL); PROTOCOL 2: 20, into groups C or E (10 each group) | catheter placed via T11-T12 interspace | PROTOCOL 1: Measurements of systemic and splanchnic variables using catheter inserted through the mesenteric vein and perivascular probe attached around the portal vein. Intramucosal pH using tonometer catheter surgically inserted into the terminal ileum. Mucosal edema and microstructure of the terminal ileum using tissue sampling to determine wet-to-dry weight ratio and histological analysis (histopathological injury scores of gut mucosa). PROTOCOL 2: gut permeability using fluorescence spectrometry | The application of epidural analgesia in endotoxemic hosts attenuates the progression of intramucosal acidosis, the increase of intestinal permeability, and the structural alterations of intestinal villi, possibly throught the restoration of microcirculation, despite a significant decrease of perfusion pressure and arterial oxygen content |
| Rats | Freise et al[13] | 2006 | Thoracic epidural analgesia augments ileal mucosal capillary perfusion and improves survival in severe acute pancreatitis in rats | Prospective randomized | Animal model of acute pancreatitis (AP) induced by taurocholate injection or sham lesion | 28 (4 groups of 7): sham + saline TEA (Sham) vs AP + saline TEA (PANC) vs AP + TEA (EPI) vs AP + delayed TEA (delayed EPI). Outcome protocol: (n = 30): 15 AP vs 15 TEA | catheter tip placed T6 | Intravital microscopy of the ileal mucosa | TEA ↓ intercapillary area (↑ local perfusion) ↓ IL-6 and serum lactate and ↓ 66% mortality |
| Rats | Daudel et al[14] | 2007 | Continuous thoracic epidural anesthesia improves gut mucosal microcirculation in rats with sepsis | Prospective randomized, blinded image analysis | Sepsis model induced with cecal ligation and perforation (CLP) | 27 (10 CLP/TEA vs 9 CLP/Control vs 8 sham laparotomy) | catheter tip placed T6 | Intravital videomicroscopy performed on villi of ileum mucosa | Smaller intercapillary area hence ↑ villus perfusion in CLP/TEA vs CLP/Control. Diameter of terminal arterioles and red blood cell velocity didn't differ |
| Pigs | Bachmann et al[16] | 2013 | Effects of thoracic epidural anesthesia on survival and microcirculation in severe acute pancreatitis: a randomized experimental trial | Prospective randomized | Animal model of SAP induced by intraductal injection of glycodesoxycholic acid in the main pancreatic duct followed by closure | 34: 17 bupivacaine via TEA after induction of SAP (TEA) vs 17 no TEA (control) | catheter introduced T7-T8 and advanced 2 cm (documented by epidurogram) | Continuous measurement of the tissue oxygen tension (tpO2) using a flexible polarographic measuring probe placed in the pancreatic head and pancreatic microcirculation using Laser-Doppler imager during a period of 6 h after induction SAP. Histopathologic tissue damage (histopathologic severity score of acute pancreatis) by postmortem examination of the animals sacrificed after 7 d of observation | TEA improved survival as well as pancreatic microcirculation and tissue oxygenation resulting in reduced histopathologic tissue-damage |
↑: Increase; ↓: Decrease. TEA: Thoracic epidural anesthesia; LEA: Lumbar epidural anesthesia; SAP: Severe acute pancreatitis.