Experimental study on a large animal model of a new thermoablation technique.

BACKGROUND: A novel technique of thermoablation, using a microtube to deliver pulses of hot water vapour, was tested on a large animal model in order to evaluate its efficacy and potential adverse effects. MATERIALS AND METHODS: The medical device consisted of a microtube extension connected to a hydropneumatic pump. Pulses of pure water were injected though the microtube where they were heated and delivered as vapour into the target zone. The method was tested on the liver of 12 healthy pigs, either during open surgery or percutaneously under ultrasounds. RESULTS: The technique was efficient and well-tolerated by the animals. Large volumes of necrotic tissue were created in a significantly short time compared to concurrent thermoablative techniques. CONCLUSION: Anticipating human application, this experimental study demonstrated a safe and efficient innovative thermoablation technique. The first human applications have been successfully performed and will be reported soon.

A new method of thermoablation with hot water vapour for localized tumours.

BACKGROUND: A new method of thermoablation with hot water vapour based on a new type of microtube was developed. This approach allows tumours, with volume and anatomical positions not accessible to other techniques (cryoablation, radiofrequency ablation, laser ablation) to be treated. MATERIALS AND METHODS: The method was tested on a human colon carcinoma grafted subcutaneously in Swiss nude mice and the experiment monitored under magnetic resonance imaging. RESULTS: It was found that 2.52 cal s(-1) per cm3 of tumour were necessary to reduce tumour size. The microtube is built to withstand a large range of temperatures and pressures and is biocompatible. CONCLUSION: A specific feature of this technique is that, besides hot vapour, several types of drugs can be delivered through the same microtube depending of the location, type or size of the tumour. These properties make it a unique device for multi-therapeutic treatments.

Endoscopic neck dissection in an animal model: comparison of nodal yield with open-neck dissection.

OBJECTIVE: To evaluate the possibility, complications, and efficacy of endoscopic neck dissection (END) in a porcine model. DESIGN: Experimental self-controlled study. SUBJECTS: Minipigs. INTERVENTION: Endoscopic neck dissection was performed using general anesthesia with techniques adapted from laparoscopic surgery. The tissue specimens removed were divided according to porcine equivalents of human neck groups. After the completion of END, open-neck dissection was performed using standard surgical techniques, and the remaining tissue within each neck group was retrieved. A pathologist evaluated each specimen without knowing its exact origin in terms of neck group or side and the type of surgical technique used. For each specimen, the number of retrieved lymph nodes and their anatomical integrity were analyzed. RESULTS: Ten neck dissections were performed in 8 minipigs without any major complications. The number of retrieved lymph nodes by END was 18.4 +/- 7.4 (mean +/- SD). Completed open-neck dissection retrieved an additional 3.3 +/- 1.8 lymph nodes. The efficacy rate of END was 88% +/- 10% (+/ -SD). The majority of retrieved lymph nodes were intact, with less than 5% of nodes exhibiting crushing artifacts. CONCLUSIONS: Endoscopic neck dissection in a porcine model seems to be free of major complications and able to retrieve the majority of neck lymph nodes. A larger number of animals and their survival need to be studied before human studies can begin.

Intraarterial beta irradiation induces smooth muscle cell apoptosis and reduces medial cellularity in a hypercholesterolemic rabbit restenosis model.

PURPOSE: Ionizing radiation has been shown to be a powerful inhibitor of neointimal hyperplasia following arterial injury in several animal models of post-percutaneous transluminal coronary angioplasty (post-PTCA) restenosis. This was previously shown to be associated with a reduction in smooth muscle cell (SMC) mitotic activity. This study evaluated the effect of intraarterial beta irradiation on the arterial wall SMC density and apoptosis. METHODS AND MATERIALS: Twenty-five carotid and 7 iliac arteries of hypercholesterolemic New Zealand white rabbits were injured using the Baumgartner technique. The impact of an 18 Gy beta radiation dose administered after balloon injury was studied and compared to a nonirradiated injured control group. The medial SMC density as well as the percentage of apoptotic cells were determined at 8 days, 21 days, and 6 weeks after injury using an automated computer-based software. Apoptotic cells were identified using in situ end-labeling of fragmented DNA. RESULTS: The values for medial apoptosis in control vs. irradiated arteries were: 0.014 +/- 0.023 vs. 0.23 +/- 0.28%, p = NS, at 8 days; 0.012 +/- 0.018 vs. 0.07 +/- 0.07%, p = 0.05, at 21 days; and 0 +/- 0 vs. 0.16 +/- 0.11%, p = 0.03, at 6 weeks. The overall incidence of medial apoptotic cells at all time points was 0.01 +/- 0.017 vs. 0.13 +/- 0.14% in controls and irradiated arteries respectively, p = 0.004. Medial SMC density was significantly decreased in irradiated arteries in comparison with controls (p < 0.01 at all time-points). CONCLUSIONS: Intraarterial beta irradiation stimulates medial SMC apoptosis in balloon-injured arteries. This, together with a decrease in SMC mitotic activity, contributes to a decrease in the arterial wall cellularity.

Intra-arterial beta irradiation prevents neointimal hyperplasia in a hypercholesterolemic rabbit restenosis model.

BACKGROUND: Intra-arterial gamma irradiation has been shown to reduce restenosis after balloon angioplasty. The use of beta emitters should allow similar effects while inducing less undue tissue irradiation radioprotection problems. METHODS AND RESULTS: Flexible 90-yttrium (90Y) coils inside a centering balloon were used to allow homogeneous intraarterial dose delivery. One carotid and one iliac artery of 21 hypercholesterolemic rabbits were deendothelialized and then irradiated. Four dose schedules were studied: (1) control (dilated, nonirradiated); (2) 6 Gy; (3) 12 Gy; and (4) 18 Gy. Arterial specimens were histologically evaluated at 8 days and at 6 weeks. For all radiation doses at 8 days compared with controls, there was a significant decrease in bromodeoxyuridine-labeled cells (245 +/- 93 cells/cm in control, 42 +/- 27 in 6 Gy, 72 +/- 107 in 12 Gy, and 2 +/- 2 in 18 Gy groups; P < .001) and in total neointimal cells (891 +/- 415 cells/cm in control, 79 +/- 43 in 6 Gy, 192 +/- 264 in 12 Gy and 22 +/- 13 in 18 Gy groups; P < .0002). At 6 weeks, computer-derived histological percent area stenosis was reduced from 26 +/- 10% in the control group to 1 +/- 1.3% in the 18 Gy group (P < .0001), but lower doses had no significant effect. CONCLUSIONS: Administration of intra-arterial beta irradiation with a 90Y source is technically feasible and compatible with an ordinary catheterization laboratory environment. A dose of 18 Gy effectively induces long-term inhibition of neointimal hyperplasia.

Magnetic resonance imaging with superparamagnetic iron oxide particles to evaluate hepatic macrophage-monocytic phagocytosis after arterial devascularization in minipigs.

RATIONALE AND OBJECTIVES: We examined the effects of arterial ischemia on the phagocytic activity of the hepatic macrophage-monocytic phagocytic system (MMPS). METHODS: Six minipigs were studied before and 24 hr after complete arterial devascularization of the liver. Magnetic resonance (MR) imaging was performed at 1.5 T using superparamagnetic iron oxide (SPIO) particles (18 mumol Fe/kg body weight) as an MMPS-specific contrast agent. Hepatobiliary scintigraphy, measurements of serum liver enzymes, and histology also were obtained. RESULTS: On MR imaging, the postcontrast-to-precontrast ratios of the arterially devascularized livers were significantly higher than the corresponding baseline values (p < .01). The greatest difference (52%) between the baseline and the postoperative values was observed on gradient-echo (GE) images. Scintigraphy, laboratory analyses, and histology results indicate that the MR imaging findings were probably predominantly attributable to a reduction in phagocytic activity of the hepatic MMPS. CONCLUSION: SPIO particles have already proved useful for improving detection of liver neoplasms on MR imaging, but they also may provide a novel way of evaluating the function of the hepatic MMPS in liver diseases.

Vecuronium neuromuscular blockade reflects liver function during hepatic autotransplantation in pigs.

BACKGROUND: Rapid assessment of hepatic function early after reperfusion of the liver graft is of great importance, because it may allow for prompt detection of incipient hepatic graft failure. The current study was undertaken to determine whether the continuous recording of neuromuscular transmission could be used as an on-line assessment of hepatic function during liver transplantation when a muscle relaxant with high hepatic uptake is used. METHODS: We quantified and compared the effect of liver exclusion and graft reperfusion on the level of vecuronium-induced neuromuscular blockade in nine pigs studied twice within 3 days. During the 1st day (control session), an intravenous infusion of vecuronium was administered to maintain a constant 90-95% twitch depression during 180 min. The twitch response was then allowed to recover spontaneously to 75% of its prerelaxant value. Neuromuscular transmission was continuously measured on the right anterior leg using an acceleration transducer. During the same time period, the metabolic rate of 14C-labeled aminopyrine (a well-established quantitative test of the liver microsomal function) was determined by measuring the excretion of 14CO2 in expired air after administration of an intravenous bolus of 14C-labeled aminopyrine. Two days later, the pigs underwent a hepatic autotransplantation, during which vecuronium was administered to maintain a constant 90-95% twitch depression. After reperfusion of the liver graft, the vecuronium infusion rate was maintained at its anhepatic level, and the recovery index of the neuromuscular blockade (the time from 25% to 75% recovery of twitch height) was calculated. The aminopyrine breath test was performed during the last 30 min of the anhepatic phase, and during 3 h after reperfusion of the liver graft. RESULTS: During control studies, the mean infusion rate of vecuronium was 1.30 +/- 0.33 mg.kg-1.h-1 and the recovery index was 3.4 +/- 0.5 min. During liver dissection, the infusion rate of vecuronium was similar to the control value (1.18 +/- 0.16 mg.kg-1.h-1), then considerably decreased to 0.05 +/- 0.03 mg.kg-1.h-1 during the anhepatic phase. After reperfusion of the liver graft, the recovery index was markedly prolonged to 35.5 +/- 15.8 min, indicating a prolongation of the recovery of neuromuscular blockade by a factor of 10.4. Excretion of 14CO2 was equal to zero during the anhepatic phase and then increased to 0.19 +/- 0.11% during the 1st h after reperfusion of the liver graft, an excretion rate corresponding to 11.2% of control conditions. The relationship between individual changes in the recovery index of the neuromuscular blockade and 14CO2 excretion in expired air after reperfusion of the liver graft showed a strong significant correlation (r2 = 0.71). CONCLUSIONS: These results indicate that, compared with the control studies, there is a similar decrease in the recovery rate of vecuronium-induced neuromuscular blockade and in the metabolic rate of 14C-labeled aminopyrine during the progressive recovery of hepatic function immediately after unclamping of the liver vessels. Metabolism of 14C-labeled aminopyrine increased progressively during the reperfusion phase. Therefore, recording of neuromuscular transmission during liver transplantation could serve as a continuous and easy to perform assessment of liver graft function provided that a muscle relaxant with a high hepatic uptake is used for neuromuscular blockade.

Hepatic function during general hypothermia in the pig: assessment by aminopyrine breath test.

We investigated the influence of pre-harvesting general hypothermia on liver metabolic activity by means of Aminopyrine Breath Test (ABT). This study was conducted in pigs which were anesthetized, curarised and cooled on an ice bed. Each animal received labelled aminopyrine and 14CO2 in expired air was measured between 37.5 and 25.5 degrees C. The liver metabolic activity at 31.5 degrees C represents 53.3% of the normothermic value. At 25.5 degrees C, this activity is reduced by 75.1%. The mean decreasing rate is 6.2%/degrees C for a fall in temperature of 12 degrees C. A change of slope occurred at 31.5 degrees C. The first decreasing rate is 7.47 +/- 1.62%/degrees C and the second one is 4.48 +/- 2.27%/degrees C. Thus, use of general hypothermia during liver harvesting should improve the quality of organ preservation: the important reduction of metabolism should decrease the oxygen debt resulting from anaerobic cold perfusion.

[Aminopyrine breath test in hepatic auto-transplantation in pigs]. / L'aminopyrine breath test (ABT) au cours de l'autotransplantation hépatique chez le porc.

The aminopyrine breath test (ABT) was performed during hepatic autotransplantation in the pig. The test is reproducible in this animal and only hepatic cytochromes perform the demethylation of aminopyrine. Ischemia, varying from 90 to 200 minutes, generated a major decrease in the elimination of the 14CO2 and a marked change in the elimination curve. In this specific model it was not possible to assess survival of the animal by the ABT.

Influence of hepatic dysfunction on cyclosporine metabolism in the pig.

Cyclosporine (CyA) is eliminated from the body via biliary excretion at a rate directly proportional to bile production and the functional status of the liver. Previous reports demonstrated that disturbances in the hepatic excretory function with a rise in the plasma bilirubin level are positively correlated with high blood concentrations of CyA and CyA plus metabolites (CyA + M). Less information is available about the blood concentrations of the CyA parental substance or CyA metabolites in the case of liver dysfunction when there was no elevation of serum bilirubin content. To answer this question, we compared the pharmacokinetic profile of CyA in a cholestatic and in a ischemic model in pigs. Our results show that in pigs receiving a single dose of CyA after liver ischemia, the blood concentrations of CyA and CyA + M are significantly increased independently of the serum bilirubin concentration, probably through a slow down of CyA metabolism by impairment of cytochrome P450 III A.

Early assessment of tissue viability with radioiodinated heptadecanoic acid in reperfused canine myocardium: comparison with thallium-201.

Myocardial scintigraphy with heptadecanoic acid labeled with iodine-123 (123I-HDA) may allow early noninvasive delineation of viable myocardium after reperfusion. In this study myocardial uptake of 123I-HDA was compared with that of thallium-201 in six closed-chest dogs after 5 hours of occlusion followed by 1 hour of reperfusion of the left anterior descending coronary artery. Myocardial blood flow was measured with microspheres, and myocardial viability was assessed by means of triphenyltetrazolium chloride staining. In viable areas of the reperfused region, 123I-HDA uptake, thallium-201 uptake, and myocardial blood flow were similar to those measured in the control circumflex region. However, in infarcted areas they were reduced to 48 +/- 2% (mean +/- SEM; p less than 0.001), 59 +/- 3% (p less than 0.001), and 74 +/- 5% (p less than 0.001) of control values, respectively. Results of multiple regression analysis showed that thallium-201 uptake primarily reflected the level of flow during reperfusion, whereas 123I-HDA uptake was dependent on both myocardial blood flow and viability. At each level of flow, 123I-HDA uptake was significantly lower in infarcted than in viable myocardium. By means of discriminant analysis, 123I-HDA uptake was found to be the single most important predictor of viability, whereas thallium-201 was only of limited importance. Myocardial 123I-HDA uptake greater than or equal to 71% or myocardial thallium-201 uptake greater than or equal to 73% best differentiated viable from infarcted myocardium. According to these criteria, 123I-HDA predicted myocardial viability with a sensitivity of 77%, a specificity of 84% and a predictive accuracy of 81%.(ABSTRACT TRUNCATED AT 250 WORDS)

[Trefoil balloon, a new instrument for percutaneous valvuloplasty]. / "Trefoil balloon", un nouvel instrument pour la valvuloplastie percutanée.

Complete obstruction of blood flow during balloon inflation is a major problem of percutaneous balloon valvuloplasty. To ensure continued transvalvular blood flow the authors have developed the "Trefoil balloon" consisting of three identical angioplasty balloons mounted on a single catheter. The Trefoil balloon was tested in the aorta and aortic valve in 4 dogs and produced a pressure gradient from 5 to 40 mm Hg where conventional balloons were completely occlusive. The Trefoil balloon was then used in 3 children with congenital valvular stenoses (2 pulmonary and 1 aortic stenosis). The immediate results of these valvuloplasties were satisfactory. Continued flow during balloon inflation was documented by right ventricular injection of contrast medium in the cases of pulmonary stenosis and by a systolic aortic pressure of 75 mm Hg during balloon inflation in the case of aortic stenosis. The Trefoil balloon is a promising new device for percutaneous valvuloplasty.

Trefoil balloon for percutaneous valvuloplasty.

A new balloon (Trefoil balloon) was developed to avoid complete interruption of blood flow during percutaneous balloon valvuloplasty. It consists of three identical 2- to 4-cm-long angioplasty balloons mounted in a parallel fashion on a single catheter. Filled simultaneously, they assume the cross section of a rosette, allowing for continued blood flow. Trefoil balloons of various sizes were tested in five dogs (aorta and aortic valve). They created a gradient ranging from 5 to 40 mmHg where conventional, single balloons of comparable size were completely obstructive. In three consecutive patients with congenital pulmonary stenosis, Trefoil balloons were used successfully and without significant complications. Continued transvalvular blood flow during the actual dilatation process was documented in all cases. The Trefoil balloon is a promising new device for percutaneous valvuloplasty and, perhaps, coronary angioplasty.

[Emergency cardiac pacing via a coronary vessel during percutaneous coronary angioplasty]. / Stimulation cardiaque d'urgence par voie coronaire lors de l'angioplastie coronaire percutanée.

Percutaneous coronary angioplasty (PCA) is sometimes complicated by bradyarrhythmias necessitating emergency temporary cardiac pacing. This is usually performed by the classical transvenous endocardial approach. This experimental study investigated the possibility of using the metallic guide wire used during PCA as a monopolar electrode. Systematic electrical stimulation at different levels of the coronary arteries in 6 anaesthetised pigs showed threshold levels in the distal segments of 3 to 15 mA, close to the values observed in the right ventricule. Short periods of pacing were well tolerated. On the other hand, prolonged pacing (2 to 5 days) invariably led to the formation of a thrombus in the coronary segment occupied by the metallic guide wire and so should be avoided. This study shows that the metallic guide wire can be used as an emergency pacing electrode during PCA but this should be limited to a short period. This technique could replace the systematic introduction of classical transvenous pacing catheters.

[New approaches in ECG automatic monitoring in intensive care]. / Nouvelle approche de l'ECG destinée au monitoring automatique des soins intensifs.

Much of the information to be obtained from the electrocardiogram is hidden in its conventional form of presentation. A study of the first and second differentials of the signal illustrates this point and shows future potential for using this approach in investigative and automated monitoring procedures.