Electrical stimulation induces propagated colonic contractions in an experimental model.

BACKGROUND: Direct colonic electrical stimulation may prove to be a treatment option for specific motility disorders such as chronic constipation. The aim of this study was to provoke colonic contractions using electrical stimulation delivered from a battery-operated device. METHODS: Electrodes were inserted into the caecal seromuscular layer of eight anaesthetized pigs. Contractions were induced by a neurostimulator (Medtronic 3625). Caecal motility was measured simultaneously by video image analysis, manometry and a technique assessing colonic transit. RESULTS: Caecal contractions were generated using 8-10 V amplitude, 1000 micros pulse width, 120 Hz frequency for 10-30 s, with an intensity of 7-15 mA. The maximal contraction strength was observed after 20-25 s. Electrical stimulation was followed by a relaxation phase of 1.5-2 min during which contractions propagated orally and aborally over at least 10 cm. Spontaneous and stimulated caecal motility values were significantly different for both intraluminal pressure (mean(s.d.) 332(124) and 463(187) mmHg respectively; P < 0.001, 42 experiments) and movement of contents (1.6(0.9) and 3.9(2.8) mm; P < 0.001, 40 experiments). CONCLUSION: Electrical stimulation modulated caecal motility, and provoked localized and propagated colonic contractions.

[Indications, limits and future of epidural spinal cord electrical stimulation for coronary and peripheral artery disease]. / Indications, perspectives et limites de la stimulation electrique epidurale en cas d'artériopathie périphérique ou coronarienne.

The electrical stimulation of the dorsal columns of the spinal cord exerts a dual analgesic and vasodilatory effect on ischemic tissues. It is increasingly considered a valuable method to treat severe and otherwise intractable coronary and peripheral artery disease. The quality of the results depends from both a strict selection of the patients by vascular specialists and the frequency and quality of the follow-up controls. However the indications, limits, mode of action and results of spinal cord stimulation are still poorly understood. This article, based on a personal experience of 164 implantations for peripheral and coronary artery disease, aims to draw attention to this technique and to provide information on recent and future developments.

Anticoagulation by ancrod for carbon dioxide removal by extracorporeal membrane lung in the dog.

Ten dogs were subjected to defibrinogenation with an intravenous perfusion of ancrod (1 unit/kg) (Arvin, Knoll AG, Ludwigshafen, Federal Republic of Germany) over a 2 1/2 hour period. Six of them were subjected to extracorporeal elimination of carbon dioxide with a polypropylene membrane lung by means of veno-venous bypass. The remaining four dogs did not undergo extracorporeal circulation and served as control subjects. In both groups, ancrod administration itself resulted in a marked drop in alpha 2-antiplasmin (33% and 67%, respectively, of the baseline values) and in slight but significant decreases in factor II and plasminogen activities of 25% and 20%, respectively (p less than 0.05), in the group subjected to carbon dioxide removal. There were no significant changes in platelet number or factor V and antithrombin III activities. During the 6-hour bypass period, platelet count and antithrombin III and factor II and V levels decreased significantly. No bleeding was observed. Histologic examination of lung biopsy tissue showed no pathologic features. Analysis of the membrane of the artificial lungs revealed no fibrin deposits. In the control group, except for a drop in alpha 2-antiplasmin levels (54%), no significant changes in hemostatic parameters occurred during the corresponding 6 hours. We conclude that, despite the drop in coagulation factors and in alpha 2-antiplasmin activity during bypass, ancrod can be considered as a valuable alternative anticoagulant for extracorporeal carbon dioxide removal.

Cardiorespiratory effects of an inspiratory hold and continuous positive pressure ventilation in goats.

The cardiorespiratory effects of three different patterns of mechanical ventilation were compared in sixteen anaesthetized goats. Intermittent positive pressure ventilation (IPPV), with an inspiratory: expiratory (I:E) time ratio of 1:3, was compared with an inspiratory hold pattern (IPPVH), with an I:E ratio of 3:1, and with continuous positive pressure ventilation (CPPV) adjusted to produce the same mean airway pressure. In eight animals with normal lungs, IPPVH reduced VD/VT and PaCO2, but produced no changes in oxygenation. CPPV did not significantly alter the efficiency of gas exchange. In a further eight animals, with oleic acid-induced lung damage, both IPPVH and CPPV produced a decrease in both VD/VT and PaCO2. Qs/Qt was significantly reduced by both CPPV and IPPVH, but the effect was more marked with CPPV, and the PaO2 was significantly increased only by CPPV. The increased effectiveness of CPPV in increasing PaO2 in this model may have been due to the greater increase in end-expiratory lung volume produced by this pattern of ventilation.

A randomized comparison of total extracorporeal CO2 removal with conventional mechanical ventilation in experimental hyaline membrane disease.

Apnoeic oxygenation (AO) combined with extracorporeal CO2 removal (ECCO2R), using venovenous perfusion across a membrane area of 0.1 m2 has been shown to be feasible in six healthy anaesthetized rabbits. In a further twelve rabbits, ECCO2R has been randomly compared with conventional mechanical ventilation (CMV) following saline lavage to induce respiratory failure. Blood gases were maintained for up to 6 h within the same range (PaO2 = 8-20 kPa, PaCO2 = 4-6 kPa) in two groups of six by varying airway pressures and the oxygen fraction delivered either to the membrane lung (ECCO2R group) or to the ventilator (CMV group). The influence of single hourly sustained inflations (SI) on oxygenation was studied. ECCO2R subjects remained stable and survived. CMV subjects deteriorated and had 80% mortality. Hyaline membranes were absent from ECCO2R subjects and present in all CMV subjects. The response to SI suggests that a lung volume recruitment is maintained during AO for up to 1 h but is ineffective during CMV.

Mechanisms by which dopamine alters blood flow distribution during lobar collapse in dogs.

Dopamine increases blood flow to a hypoxic left lower lobe in dogs. To elucidate possible mechanisms, left lower lobe collapse was induced in anesthetized dogs, and lobar (QLLL) and total (QT) pulmonary blood flow was measured by electromagnetic flow probes. Dopamine infusion increased mean pulmonary arterial pressure (Ppa), QT, and QLLL. However, the increase in QLLL was double that produced by a similar increase in Ppa without increase in QT (inflation of a Swan-Ganz balloon in right pulmonary artery) or by a similar increase in QT with smaller increase in Ppa (opening of arteriovenous fistulas). QLLL/QT was not changed by opening arteriovenous fistulas, but was increased by Swan-Ganz balloon inflation, and by infusion of dopamine. It is concluded that the increase in QLLL/QT produced by dopamine was due to a decrease in hypoxic vasoconstriction in the lobe secondary to an increase in mixed venous PO2 and to vasoconstriction in the oxygenated lung.

Transplantation of encapsulated bovine chromaffin cells in the sheep subarachnoid space: a preclinical study for the treatment of cancer pain.

Chromaffin cells have been shown to release a combination of pain-reducing neuroactive compounds including catecholamines and opioid peptides. The allogeneic transplantation of chromaffin cells in the subarachnoid space has been shown to alleviate pain in various rodent models and possibly in terminal cancer patients. Because of the shortage of human cadaver donor tissue, we are investigating the possibility of transplanting xenogeneic cells in polymer capsules. In this technique, cells are surrounded by a permselective synthetic membrane whose pores are suitably sized to allow diffusion of nutrients, neurotransmitters and growth factors, but restrict the diffusion of the large molecules of the immune system and prevent contact with immunocompetent cells. The encapsulation technique therefore allows transplantation of xenogeneic tissue between species as well as retrieval of transplanted cells. Previously we have reported that encapsulated bovine chromaffin cells survive and alleviate pain in various rodent models. The purpose of the present study was to assess the feasibility of implanting a human sized device in a large animal model. Adrenals from 5 calves were surgically removed; chromaffin cells were isolated from these glands using a collagenase-based digestion-filtration technique. Cells were loaded into acrylic-based tubular (5 cm long, 920 microns wide) permselective capsules attached to silicone tethers. The capsules were maintained in vitro for at least 7 days following the encapsulation procedure. Nicotine evoked release was analyzed in a defined subgroup from each batch. One capsule was then implanted using a guiding cannula system in the lumbar subarachnoid space of each sheep for 4 (n = 5) and 8 (n = 1) wk. All capsules were retrieved intact by gentle pulling on the silicone tether. Except for one capsule, the evoked catecholamine release of the retrieved capsules was in the same range as that of other capsules from the same cohort that had been maintained in vitro. All retrieved capsules were devoid of host cell reaction. Clusters of viable cells dispersed in an alginate immobilizing matrix were observed throughout all the implanted capsules. This study demonstrates the feasibility of transplanting functional encapsulated xenogeneic chromaffin cells into the cerebrospinal fluid of a large animal model using a capsule of appropriate dimensions for human implants. We believe that these results suggest the appropriateness of human clinical trials in patients suffering from refractory terminal cancer pain.

Comparison between a low molecular weight and standard heparin for anticoagulation during extracorporeal CO2 removal in the dog.

Anticoagulant properties towards an artificial surface of a chemically depolymerized low molecular weight heparin (LMWH) have been compared to those of a standard heparin (SH). The experimental model consisted in a seven hours extracorporeal veno-venous bypass for CO2 removal (EC-CO2R) using a membrane lung. Four animals received 150 anti-FXa U/kg followed by 40 anti-FXa U/kg/h of LMWH or 300 IU/kg followed by 100 IU/kg/h of SH. Mean Factor Xa inhibition was 49% in LMWH group and 28.5% in SH group. Mean Factor IIa inhibition was 31% and 49% respectively. After three hours of bypass fibrin deposition occurred in the reservoir in three out of four dogs receiving LMWH while none was observed under SH. No statistically significant difference between the two groups was found for any of the coagulation parameters tested (fibrinogen, factor V, antithrombin III, plasminogen, alpha 2-antiplasmin, platelet counts). At the end of bypass 5000 U protamine abolished both anti-FXa and anti-FIIa activities in the SH group but failed to neutralize more than half of the anti-FXa activity in the LMWH group. These results suggest that high anti-FIIa activities are required to prevent fibrin formation induced by artificial surfaces and that equivalent amounts of anti-FXa activities are ineffective for this purpose. In addition the use of LMWH may raise problems when emergency neutralization procedures are required.

Effect of clonidine on ICP and on the hemodynamic responses to nociceptive stimuli in patients with brain tumors.

The effect of clonidine on intracranial pressure (ICP), mean arterial pressure (MAP), cerebral perfusion pressure (CPP), heart rate (HR), and drug requirements was studied in 24 patients scheduled for elective cerebral tumor resection (ICP < or = 20 mm Hg). The patients were randomly assigned to one of two groups: Group P (placebo), 12 patients; Group C (clonidine 3 micrograms/kg 10 min before induction), 12 patients. In all patients, anesthesia was induced with a propofol infusion (500 micrograms/kg/min) combined with fentanyl 2 micrograms/kg, lidocaine 1.5 mg/kg, and vecuronium 0.1 mg/kg. Propofol was also used for maintenance. During the preinduction period, clonidine had no effect on ICP or HR, but in clonidine-treated patients, MAP and CPP decreased significantly in comparison to those of the placebo group. During induction, ICP and HR were stable and similar in both groups. MAP and CPP remained significantly lower in Group C. At intubation and Mayfield clamp application, ICP increased in both groups, with similar values at all times. MAP increased in both groups at intubation, Mayfield clamp application, and incision, staying lower, however, in Group C. CPP followed a pattern similar to that of MAP. Propofol requirements up to the 20th min were lower in Group C than in Group P (2.08 +/- 0.83 vs. 3.3 +/- 0.7 mg/kg, p < 0.05). Finally, throughout the study, eight patients in Group C versus two in Group P had a CPP value < 60 mm Hg for > or = 1 min (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Hemoglobin substitute and cardiopulmonary bypass.

The effects of diaspirin crosslinked hemoglobin (DCLHb, Baxter Health Care Corp., Round Lake, IL) on oxygen exchange in the setting of cardiopulmonary bypass (CPB) are unknown. Six calves (71.2 +/- 1.3 kg) were connected to CPB by jugular venous and carotid arterial cannulation for 5 hours. Each 1 hour period included 45 min of partial CPB (mean flow rate of 50 ml/kg per min) followed by 15 min without CPB, at the end of which 500 ml of blood were substituted for with either 500 ml of hydroxyethyl starch (Haes; n = 3) or 500 ml of DCLHb (n = 3). A total of 2 liters of blood was, thus, exchanged (28 ml/kg of blood substitute). Values are expressed as mean +/- 1 SD. Analysis of variance for repeated measurements was used. The cardiac output (CO) values at 1 h, 3 h, and 5 h were in the Haes group: 5.7 +/- 2, 6.7 +/- 2.5, and 7.7 +/- 2.5L/min, and in the DCLHb group: 5.7 +/- 0.6, 4 +/- 1, and 4.7 +/- 1.2 L/min, respectively. The arteriovenous oxygen content difference (Ca-Cvo2) values at 1 h, 3 h, and 5 h were in the Haes group: 4.6 +/- 1, 3.3 +/- 1.5, and 3.5 +/- 1.5 ml/dl, and in the DCLHb group: 4.9 +/- 0.6, 7.4 +/- 0.7, and 6.6 +/- 0.6 ml/dl, respectively. The oxygen consumption (Vo2) values at 1 h, 3 h, and 5 h were in the Haes group: 244 +/- 29, 198 +/- 58, and 249 +/- 42 ml/min, and in the DCLHb group: 273 +/- 28, 296 +/- 75, and 306 +/- 65 ml/min, respectively. CO and Ca-Cvo2 showed a significant difference (p < 0.01), whereas Vo2 did not (p = 0.52). In the DCLHb group of this CPB animal model, the cardiac output is lower and the arteriovenous oxygen content difference higher than in the Haes group, allowing for preserved oxygen consumption.

Blood profile during and after hemoglobin substitute administration.

The in vivo effects of Diaspirin Crosslinked Hemoglobin (DCLHb, Baxter Healthcare Corp.) on hematology and biochemistry are unknown. This study includes 6 calves (71.2+/-1.3 kg). In each animal a total of 2 litres of blood was exchanged for the same amount of hydroxylethyl starch (Haes, Fresenius) (n=3) or DCLHb (n=3), which is equivalent to 28cc/kg of blood substitute, over a period of 5 hours. The animals were allowed to survive 7 days. Blood samples were taken hourly during the perfusion protocol, at postoperative day (POD) 1, 2 and 7. ANOVA test was used for repeated measurements. Blood cell profiles were similar in both groups. Peak methemoglobinemia was 4.2% in the DCLHb group. Osmolarity was significantly higher in the DCLHb group with the greatest difference at POD 1 and 2. Postmortem analysis of the major organs did not show any sign of hemoglobin deposit in the DCLHb group. In the given setup DCLHb can be administered in a large quantity with good hematological tolerance and without any deposits in major organs. A prolonged plasma expander effect was observed.

[Intubation conditions: importance of the rate of repetition of the train-of-four]. / Conditions d'intubation: importance de la fréquence de répétition du train de quatre.

OBJECTIVES: To assess that neuromuscular relaxation onset of the adductor pollicis (AP) is related to neuromuscular stimulation rate. To assess that train-of-four (TOF) at 0.05 Hz is a more accurate indicator of optimal tracheal intubation time and conditions, than TOF at 0.08 Hz. STUDY DESIGN: Prospective, comparative, randomized double-blind study. PATIENTS: Forty adults, physical class ASA 1 or 2, undergoing general anaesthesia with tracheal intubation were allocated to two groups (n = 20) according to the sequence of stimulation of the AP: either TOF at 0.05 Hz (test group) or TOF at 0.08 Hz (control group). METHODS: Induction of anaesthesia was achieved with thiopentone, fentanyl and vecuronium (0.1 mg.kg-1). Neuromuscular monitoring was obtained with force displacement transducers attached to each AP. Tracheal intubation was performed once AP muscular response obtained with TOF at 0.05 Hz for test group and TOF at 0.08 Hz for control group was abolished. Results are expressed as mean +/- SEM. Fisher exact test was used for intubation conditions comparison. Curarization time between groups was compared with unpaired Student's t test (P < 0.05 accepted). RESULTS: TOF with 0.05 Hz stimulation significantly increased curarization time: 217 +/- 7 versus 162 +/- 6 s (P < 0.001). Intubation conditions were excellent in 95% and good in 5% of patients in the study group, compared to 15 and 40% in the control group, respectively (P < 0.01) in 45% of the control group patients coughing at intubation occurred. CONCLUSION: Low stimulation rate (TOF at 0.05 Hz) of AP is a reliable technique to determine the appropriate intubation time for patients paralyzed with vecuronium.

[Efficacy of ketanserin on postanesthetic shivering]. / Efficacité de la kétansérine sur le frisson postanesthésique.

OBJECTIVE: To evaluate the clinical and electromyographic (EMG) effects of ketanserin (K), a serotoninergic receptor antagonist (5-HT2), on postoperative shivering (POS). STUDY DESIGN: Prospective, randomised, double-blind study. PATIENTS: Fifty ASA class 1 and 2 patients with major clinical postoperative tremor were studied. METHODS: POS was assessed clinically (0 = nil, 1 = moderate, 2 = severe). Inclusion criterion was a POS of 2 at admission in the recovery room. The mean arterial blood pressure, rectal temperature, SpO2 were recorded at admission (T0) and subsequently at T5, T10, T15, T30 and T60 minutes. Either 10 mg of K (n = 25) or a corresponding volume of a placebo (P) (n = 25) were intravenously injected. The EMG activity of the deltoid and quadriceps muscles was recorded continuously. Blood lactic acid concentration was measured at the end of POS. Results are expressed as mean +/- SEM. Parametric values were analysed with unpaired Student's t-test, and nonparametric values with chi 2 analysis. P < 0.05 was accepted. RESULTS: Demographic data, duration of anaesthesia, postoperative temperature, oxygen saturation, blood pressure and blood lactate concentration were similar between groups. The POS duration in the K group was significantly shorter than in the P group: 8.8 +/- 1.5 min and 15.5 +/- 1.5 min respectively (P < 0.01). The number of patients in the K group experiencing POS at T5 and T10 was significantly lower, when compared with those who had received the P (P < 0.05). CONCLUSION: At a dose of 10 mg, K administered in patients with POS during recovery, reduced significantly the duration and intensity of the shivering without noticeable side effects. This study suggests that this 5-HT2 antagonist is an efficient therapeutic tool for POS in adults.

Electrical colonic stimulation reduces mean transit time in a porcine model.

Electrical stimulation is a new way to treat digestive disorders such as constipation. Colonic propulsive activity can be triggered by battery operated devices. This study aimed to demonstrate the effect of direct electrical colonic stimulation on mean transit time in a chronic porcine model. The impact of stimulation and implanted material on the colonic wall was also assessed. Three pairs of electrodes were implanted into the caecal wall of 12 anaesthetized pigs. Reference colonic transit time was determined by radiopaque markers for each pig before implantation. It was repeated 4 weeks after implantation with sham stimulation and 5 weeks after implantation with electrical stimulation. Aboral sequential trains of 1-ms pulse width (10 V; 120 Hz) were applied twice daily for 6 days, using an external battery operated stimulator. For each course of markers, a mean value was computed from transit times obtained from individual pig. Microscopic examination of the caecum was routinely performed after animal sacrifice. A reduction of mean transit time was observed after electrical stimulation (19 +/- 13 h; mean +/- SD) when compared to reference (34 +/- 7 h; P = 0.045) and mean transit time after sham stimulation (36 +/- 9 h; P = 0.035). Histological examination revealed minimal chronic inflammation around the electrodes. Colonic transit time measured in a chronic porcine model is reduced by direct sequential electrical stimulation. Minimal tissue lesion is elicited by stimulation or implanted material. Electrical colonic stimulation could be a promising approach to treat specific disorders of the large bowel.

Late outcome of spinal cord stimulation for unreconstructable and limb-threatening lower limb ischemia.

OBJECTIVES: To determine whether the initial benefits of spinal cord stimulation (SCS) treatment for critical limb ischemia (CLI) persist over years. DESIGN: Analysis of data prospectively collected for every CLI patient receiving permanent SCS. Follow-up range 12 to 98 months (mean 46+/-23, median 50 months). POPULATION: 87 patients (28% stage III, 72%stage IV) with unreconstructable CLI due (83%) or not (17%) to atherosclerosis and with an initial sitting/supine transcutaneous pO2 gradient >15 mmHg. METHODS: Assessment of actuarial patient survival (PS), limb salvage (LS) and amputation-free patient survival (AFPS). Analysis of the impact of 15 risk factors on long-term outcomes using the Fischer's exact test for categorical variables and the t test for continuous variables. RESULTS: Follow-up was complete for patient and limb survival. A single non-atherosclerotic patient died during follow-up. Among atherosclerotic patients PS decreased from 88% at 1y, to 76% at 3y, 64% at 5y and 57% at 7y. LS reached 84% at 1y, 78% at 2y, 75% at 3y and remained stable thereafter. Diabetes was found to affect LS (p<0.05) and heart disease to reduce PS (p<0.01). AFPS was reduced in heart patients (p<0.01), diabetics (p<0.05) and in patients with previous stroke (p<0.05). CONCLUSIONS: In CLI patients the beneficial effects of SCS persist far beyond the first year of treatment and major amputation becomes infrequent after the second year.

CO2 and mechanical factors reduce blood flow in a collapsed lung lobe.

Left lower lobe-to-total blood flow ratio (Ql/QT) was measured with electromagnetic flow probes in anesthetized open-chest dogs. There was a 66% reduction in Ql/QT during lobar collapse, a 53% reduction during lobar ventilation hypoxia with pulmonary venous PO2 and PCO2 equal to mixed venous tensions, and a 45% reduction during a similar degree of ventilation hypoxia but with normal end-tidal PCO2. We concluded that the reduction in blood flow during lobar collapse is due predominantly to hypoxic vasoconstriction, but that this mechanism is augmented by the raised PCO2 and mechanical factors present during collapse.