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Biomedical subjects

A Pierre

Publications and source records attributed to A Pierre.

At least 19 recordsLinked to original sources
PubMed2006

The effect of reflux and bile acid aspiration on the lung allograft and its surfactant and innate immunity molecules SP-A and SP-D.

Gastro-esophageal reflux and related pulmonary bile acid aspiration were prospectively investigated as possible contributors to postlung transplant bronchiolitis obliterans syndrome (BOS). We also studied the impact of aspiration on pulmonary surfactant collectin proteins SP-A and SP-D and on surfactant phospholipids--all important components of innate immunity in the lung. Proximal and distal esophageal 24-h pH testing and broncho-alveolar lavage fluid (BALF) bile acid assays were performed prospectively at 3-month posttransplant in 50 patients. BALF was also assayed for SP-A, SP-D and phospholipids expressed as ratio to total lipids: phosphatidylcholine; dipalmitoylphosphatidylcholine; phosphatidylglycerol (PG); phosphatidylinositol; sphingomyelin (SM) and lysophosphatidylcholine. Actuarial freedom from BOS was assessed. Freedom from BOS was reduced in patients with abnormal (proximal and/or distal) esophageal pH findings or BALF bile acids (Log-rank Mantel-Cox p < 0.05). Abnormal pH findings were observed in 72% (8 of 11) of patients with bile acids detected within the BALF. BALF with high levels of bile acids also had significantly lower SP-A, SP-D, dipalmitoylphosphatidylcholine; PG and higher SM levels (Mann-Whitney, p < 0.05). Duodeno-gastro-esophageal reflux and consequent aspiration is a risk factor for the development of BOS postlung transplant. Bile acid aspiration is associated with impaired lung allograft innate immunity manifest by reduced surfactant collectins and altered phospholipids.

Bile Acids and Salts↗
PubMed2004

[Arthroscopic knee arthrodesis: 4 cases].

PURPOSE OF THE STUDY: Arthroscopic arthrodesis of the knee joint is an alternative to classical surgery, which retains a few exceptional indications. We report the first four cases of our experience, describing the technical modalities and indications. MATERIAL AND METHODS: The four patients had undergone multiple operations for severe trauma. All four had persistent severe pain with a very limited walking distance. Before the procedure, the IKS score ranged from 11 to 44 and the mean function score was 20 to 45 points. Arthroscopic arthrodesis was proposed after several consultations and took into account the young age of the patient and a positive brace test. The successive arthroscopic times were: exploration and adherence release, complete extramural meniscectomy, joint surface avivement. Traction was not necessary. Careful avivement spared the anatomic curvatures of the condyles and slightly scraped out the plateaus. Finally, the arthrodesis was fixed in correct position under fluoroscopy using a single tube external fixator. The fixation was maintained until fusion (satisfactory x-ray and no pain). RESULTS: A drain was inserted only for the first patient. There were no cutaneous complications. Patients were discharged after 3 days on the average with immediate simulated weight bearing using two crutches. The external fixator was dynamized at two months (mean) and removed at five months. The functional gain was considerable in four patients, assessed at two years, with a mean IKS score of 75 and a mean function score of 80. The four patients walked without crutches and without pain. Single leg stance was stable. Final leg shortening was 1 to 2 cm. CONCLUSION: The arthroscopic approach provides several benefits: uneventful postoperative period, little bleeding, no cutaneous complications, shorter hospital stay. The time to fusion appears to be shorter than with classical techniques, but cannot be demonstrated clearly because of the diversity of the series reported in the literature. Arthroscopic arthrodesis does not require any special instruments, but does require surgical skill and a lengthy procedure. When arthrodesis is required the arthroscopic procedure is indicated for minimally deformed knees without major loss of bone stock.

Adult↗
PubMed2004

Molecular basis of bone morphogenetic protein-4 inhibitory action on progesterone secretion by ovine granulosa cells.

We have recently reported that bone morphogenetic protein-4 (BMP-4) can inhibit progesterone production by ovine granulosa cells (GCs). Here, we have investigated the underlying mechanisms of this effect in basal as well as in FSH-induced conditions. We have confirmed that treatment with BMP-4 decreased basal GC progesterone secretion and totally abolished FSH-stimulating action. This inhibitory action was associated with a decrease in the expression of cAMP-regulated genes, steroidogenic acute regulatory protein (StAR) and P450 side-chain cleavage (P450 scc) at mRNA and protein levels. However, BMP-4 did not alter basal cAMP production by GCs. In contrast, BMP-4 decreased by half the FSH-induced cAMP production and strongly inhibited cAMP-induced progesterone production. Thus, the inhibitory effect of BMP-4 was exerted both upstream and downstream of cAMP signalling. We next examined the downstream effect, focusing on cAMP-dependent transcription factors, steroidogenic factor-1 (SF-1) and CREB, through the BMP factor signalling intermediary, Smad1. As expected, BMP-4 induced phosphorylation and transcriptional activity of Smad1 in ovine GCs. BMP-4-activated Smad1 did not affect CREB activity but inhibited the transcriptional activity of SF-1 on the canonical SF-1 responsive element. Interestingly, this transcriptional inhibitory mechanism occurred on transfected StAR and P450 scc promoter. Based on these results, we propose that SF-1 is a key target in the inhibitory mechanism exerted by BMP-4 on progesterone synthesis by ovine GCs in culture. Because SF-1 plays an essential role in the differentiation of GCs, our findings could have new implications in understanding the role of BMP family members in the control of ovarian folliculogenesis.

Animals↗
PubMed2003

[Treatment of piso-triquetral pain by excision of the pisiform: report of fifteen cases].

INTRODUCTION: Piso-triquetral joint could be painful and pisiformectomy can be the best procedure if conservative treatment have failed. The aim of this retrospective study was to evaluate clinical and functional results of pisiformectomy. MATERIAL AND METHOD: Thirteen patients with pisiformectomy were included in this retrospective study, 2 of them have bilateral procedure (n = 15). An ulnar neuropathy was associated in four cases. The average follow-up was 31.5 month. Professional traumatic injuries were the most common etiology. Surgical procedure was the same for all patients. Patients were reviewed clinically and subjective results were evaluated with an analogic scale (Eva). RESULTS: No postoperative complications were found. At the maximal follow-up, result was excellent for 12 cases, good for 2 cases and fair for one case. Analogic evaluation pain at maximal follow-up was 0.8 points compared to 6.4 points preoperatively (p < 0.001). Wrist range of motion was improved. DISCUSSION: Etiologies of piso-triquetral disorders were large and dominated by traumatic or microtraumatic injuries. Pisiformectomy is the best procedure if conservative treatment have failed. There is no place for piso-triquetral arthrodesis considering pisiformectomy's good results. Nevertheless, it's important to know that piso-triqueral disorder could be included in an authentic loco-regional disorder.

Adult↗
PubMed2003

The Booroola mutation in sheep is associated with an alteration of the bone morphogenetic protein receptor-IB functionality.

The hyperprolificacy phenotype of Booroola ewes is due to the presence of the FecB(B) allele at the FecB locus, recently identified as a single amino acid substitution (Q249R) in the bone morphogenetic protein (BMP) type-IB receptor (BMPR1B), and is associated with a more precocious differentiation of ovarian granulosa cells (GCs). To evaluate the consequences of the Booroola mutation on BMPR1B functions, the action of ligands of the transforming growth factor-beta (TGFbeta)/BMP family that act through (growth and differentiation factor-5, BMP-4) or independently of (activin A, TGFbeta-1) BMPR1B were studied on primary cultures of GCs from homozygous FecB(+) and FecB(B) ewes. All the tested TGFbeta/BMP family ligands inhibited progesterone secretion by FecB(+) GCs. Those inhibitory effects were lower for GCs from preovulatory (5-7 mm diameter) than from small antral follicles (1-3 mm diameter). The presence of the Booroola mutation was associated with a 3- to 4-fold (P<0.001) decreased responsiveness of GCs from FecB(B) compared with FecB(+) small follicles to the action of BMPR1B ligands. In contrast, TGFbeta-1 and activin A had similar inhibitory effects on progesterone secretion by GCs from FecB(+) and FecB(B) small follicles. No difference between genotypes was observed with GCs from preovulatory follicles. In transfection experiments with HEK-293 cells, co-expression of FecB(+) BMPR1B and BMPR2 resulted in a 2.6-fold (P<0.01) induction of the activity of a BMP-specific luciferase reporter construct by BMP-4. Interestingly, no response to BMP-4 was observed when cells were transfected with the FecB(B) form of the BMPR1B receptor. Overall, these data strongly suggest that the Q249R mutation is associated with a specific alteration of BMPR1B signaling in hyperprolific Booroola ewes.

Activins↗
PubMed2003

[Arthroscopic tibio-talar arthrodesis: limitations and indications in 20 patients].

PURPOSE OF THE STUDY: The purpose of this study was to present the clinical and radiological outcome in 20 patients who underwent arthroscopic tibiotalar arthrodesis. MATERIAL AND METHODS: Between 1993 and 1999, twenty patients (twelve men and eight women) underwent arthroscopic tibiotalar arthrodesis and have been followed for a minimum of one year. Mean age at the time of the procedure was 55 years. The left side was treated in eleven patients and the right in nine. There were a variety of underlying conditions, but post-traumatic osetoarthritis predominated (ten patients); five patients had primary degenerative disease, three had "neurological" ankles, one had polyarthrtis and one necrosis of the talus. Three patients had previously undergone a double fusion and one other had had a subtalar arthrodesis. The preoperative Broquin score, which accounts for pain and walking distance, was 3.3 points on a scale of 8. The walking distance was less than 1000 meters for most of the patients. Radiographically, ten feet presented a frontal valgus deformity (mean 5.3 degrees); three had a varus deformity (mean 8 degrees) and seven were well-aligned. In the sagittal plane, there were ten cases of pes equin, including five greater than 10 degrees. The mean tibiopedal angle was 94+/-8 degrees. RESULTS: Mean hospital stay was four days. There were four complications: two superficial infections that resolved and two cases of reflex dystrophy. First-intention fusion was achieved in 17 patients (85%) after a mean 3.7 months (range 3-10 months). Three patients presented a non-union, two undergoing successful open surgery and one preferring to decline surgery on a well tolerated non-fused ankle. At last follow-up, fifteen patients were satisfied or very satisfied and five were dissatisfied. Pain was minimal or absent in 67% of the cases. The Duquennoy score was good or very good in eleven patients, fair in eight, and poor in one. Radiographical data were available for nineteen patients: four had a correct alignment in the frontal plane, eight exhibited valgus (mean 4 degrees), and seven varus (mean 8 degrees). In the sagittal plane, fifteen feet exhibited pes equin (mean 7 degrees), three a neutral position and one pes talus (4 degrees). The mean tibiopedal angle at last follow-up was 95.4 degrees. CONCLUSION: Although arthroscopic tibiotalar arthrodesis cannot improve the rate and delay to fusion in comparison with open surgery, it does reduce morbidity and the length of the hospital stay. We reserve the arthroscopic approach for ankles which are correctly or nearly correctly aligned without loss of bone stock, especially if there are local or general risk factors for open surgery.

Arthrodesis↗
PubMed2001

Comparison of endocardial electromechanical mapping with radionuclide perfusion imaging to assess myocardial viability and severity of myocardial ischemia in angina pectoris.

The assessment of left ventricular electromechanical activity using a novel, nonfluoroscopic 3-dimensional mapping system demonstrates considerable differences in electrical and mechanical activities within regions of myocardial infarction or ischemia. We sought to determine whether these changes correlate with indexes of myocardial perfusion, viability, or ischemia. A 12-segment comparative analysis was performed in 61 patients (45 men, 61 +/- 12 years old) with class III to IV angina, having reversible and/or fixed myocardial perfusion defects on single-photon emission computed tomographic perfusion imaging. A dual-isotope protocol was used, consisting of rest and 4-hour redistribution thallium images followed by adenosine technetium-99m sestamibi imaging. Average rest endocardial unipolar voltage (UpV) and local shortening (LS) mapping values were compared with visually derived perfusion scores. There was gradual and proportional reduction in regional UpV and LS in relation to thallium-201 uptake score at rest (p = 0.0001 and p = 0.0002, respectively) and redistribution studies (p = 0.0001 and p = 0.003, respectively). UpV > or = 7.4 mV and LS > or = 5.0% had a sensitivity of 78% and 65%, respectively, with a specificity of 68% and 67% for detecting viable myocardium. UpV values of 12.3 and 5.4 mV had 90% specificity and sensitivity, respectively, to predict viable tissue. UpV, but not LS, values differentiated between normal segments and those with adenosine-induced severe perfusion defects (11.8 +/- 5.3 vs 8.8 +/- 4.1 mV, p = 0.005). Catheter-based left ventricular assessment of electromechanical activity correlates with the degree of single-photon emission computed tomographic perfusion abnormality and can identify myocardial viability with a greater accuracy than myocardial ischemia.

Adenosine↗
PubMed2001

Transendocardial delivery of autologous bone marrow enhances collateral perfusion and regional function in pigs with chronic experimental myocardial ischemia.

OBJECTIVES: We tested the hypothesis that intramyocardial injection of autologous bone marrow (ABM) promotes collateral development in ischemic porcine myocardium. We also defined, in vitro, whether bone marrow (BM) cells secrete vascular endothelial growth factor (VEGF) and macrophage chemoattractant protein-1 (MCP-1). BACKGROUND: The natural processes leading to collateral development are extremely complex, requiring multiple growth factors interacting in concert and in sequence. Because optimal angiogenesis may, therefore, require multiple angiogenic factors, we thought that injection of BM, which contains cells that secrete numerous angiogenic factors, might provide optimal therapeutic angiogenesis. METHODS: Bone marrow was cultured four weeks in vitro. Conditioned medium was assayed for VEGF and MCP-1 and was added to cultured pig aortic endothelial cells (PAEC) to assess proliferation. Four weeks after left circumflex ameroid implantation, freshly aspirated ABM (n = 7) or heparinized saline (n = 7) was injected transendocardially into the ischemic zone (0.2 ml/injection at 12 sites). Echocardiography to assess myocardial thickening and microspheres to assess perfusion were performed at rest and during stress. RESULTS: Vascular endothelial growth factor and MCP-1 concentrations increased in a time-related manner. The conditioned medium enhanced, in a dose-related manner, PAEC proliferation. Collateral flow (ischemic/normal zone X 100) improved in ABM-treated pigs (ABM: 98 +/- 14 vs. 83 +/- 12 at rest, p = 0.001; 89 +/- 18 vs. 78 +/- 12 during adenosine, p = 0.025; controls: 92 +/- 10 vs. 89 +/- 9 at rest, p = 0.49; 78 +/- 11 vs. 77 +/- 5 during adenosine, p = 0.75). Similarly, contractility increased in ABM-treated pigs (ABM: 83 +/- 21 vs. 60 +/- 32 at rest, p = 0.04; 91 +/- 44 vs. 36 +/- 43 during pacing, p = 0.056; controls: 69 +/- 48 vs. 64 +/- 46 at rest, p = 0.74; 65 +/- 56 vs. 37 +/- 56 during pacing, p = 0.23). CONCLUSIONS: Bone marrow cells secrete angiogenic factors that induce endothelial cell proliferation and, when injected transendocardially, augment collateral perfusion and myocardial function in ischemic myocardium.

Animals↗
PubMed2001

Encapsulation of deoxyribonucleic acid molecules in silica and hybrid organic-silica gels.

The encapsulation of small DNA molecules was attempted in pure silica and in hybrid polyvinyl alcohol-silica gels. The materials which were obtained were examined by nitrogen adsorption, and by 29Si and 31P NMR spectroscopy. The extraction of the DNA molecules from the gels was examined in a buffer aqueous solution as well as in an acidic medium. The results suggested that the DNA molecules remained trapped inside the gels due to a permanent bonding to the gel network.

Journal Article↗
PubMed2001

[Outcome of 95 stable meniscal tears left in place after reconstruction of the anterior cruciate ligament].

PURPOSE OF THE STUDY: The purpose of this retrospective analysis was to study clinical and radiological outcome of 95 stable meniscal tears left in place after arthroscopic reconstruction of the anterior cruciate ligament with a free patellar autograft (with or without a lateral component). MATERIAL AND METHODS: We reviewed 86 patients who had undergone arthroscopic treatment for chronic anterior laxity (56% solely anterior laxity) with at least one meniscal lesion left in place after ligamentoplasty. IKDC criteria and ARPEGE scores were recorded. A total of 95 stable meniscal lesions had been left in place: 35 lateral lesions (80% longitudinal tears and 77% posterior lesions) and 60 medial lesions (55% peripheral disinsertions and 90% posterior lesions). The lesions measured a mean 10 mm (range 5-20 mm) for the lateral and medial menisci. Mean follow-up was 4 years (range 3-9 years). These patients were young (mean age 26 years), and predominantly men (75%). The right knee was involved in 53% of the cases. RESULTS: At last follow-up, 26% of the patients were grade A, 65% B, 7% C and 2% D according to the IKDC criteria. No revision procedure was required for lateral menisci despite the large size of the lesions left in place in certain cases. Among the 60 medial lesions left in place, 10 (17%) had become symptomatic (8 bucket-handle, 1 longitudinal tear, 1 posterior fragment) and required surgery a mean 3 years (range 1-6 years) after ligamentoplasty. There was no statistical difference between functional score, residual laxity, or type of stabilization in patients who had revision surgery for symptomatic meniscal lesions and the others. Inversely, these lesions were statistically larger (p=0.038) than the others (mean 13 mm versus 9.8 mm). CONCLUSION: Outcome of stable meniscal lesions left in place after treatment for anterior laxity depends on the meniscus involved. For the lateral meniscus, irrespective of the size of the lesion, therapeutic abstention has no clinical impact at 4 years. Inversely, for the medial meniscus, 37.5% of the lesions measuring more than 10 mm that were left in place required revision while only 9% of those measuring less than 10 mm necessitated subsequent surgery. Beyond 10 mm, therapeutic abstention led to a revision procedure in 17% of the cases, suggesting the usefulness of a discussion on other indications. Stable lesions of the medial meniscus should not be left in place if they measure more than 10 mm.

Adult↗
PubMed2000

S-nitrosoglutathione reduces nonocclusive thrombosis rate following balloon overstretch injury and intracoronary irradiation of porcine coronary arteries.

PURPOSE: Intracoronary radiation (IR) suppresses neointima formation following balloon injury in animal models. High doses of radiation exacerbate thrombosis and delay re-endothelialization. The free radical nitric oxide (NO) has been reported to inhibit platelet aggregation, reduce neointimal hyperplasia, and stimulate re-endothelialization. This study examined the effects of a chemical NO donor on neointima formation, thrombosis, and healing of irradiated porcine coronary arteries. METHODS AND MATERIALS: Vascular lesions were created in the coronary arteries of 59 domestic swine by overstretch balloon injury. Arteries were then left untreated or were treated with intracoronary gamma-radiation using Iridium-192 in each artery to deliver 5 or 15 Gy at 2 mm from the center of the source. The chemical NO donor S-nitrosoglutathione (GSNO) was infused i.v. at a rate of 250 microg/min for 10 min before injury, followed by a continuous infusion for 60 min. Animals were euthanized at 14 days and their arteries were analyzed for histomorphometric indices of proliferation and thrombosis. RESULTS: A dose of 15 Gy reduced the ratio of intimal area to medial fracture length (IA/FL) versus control (0.06 +/- 0.05 0.54 +/- 0.10 [p < 0. 001]) but increased the nonocclusive thrombosis rate compared to controls (85% vs. 30%; p < 0.05). A low dose of 5 Gy did not affect neointima formation. Treatment with GSNO reduced thrombosis in all treated groups: control, 15%; 5 Gy, 18%; and 15 Gy, 35% (p < 0.05) without affecting neointima formation. CONCLUSION: Systemic administration of GSNO during balloon injury and IR was tolerated well by the swine and resulted in reduction of the thrombosis rate, especially at high doses, without apparent effect on neointima formation.

Animals↗
PubMed2000

Electromagnetic guidance for catheter-based transendocardial injection: a platform for intramyocardial angiogenesis therapy. Results in normal and ischemic porcine models.

OBJECTIVES: To test the feasibility of myocardial angiogenic gene expression using a novel catheter-based transendocardial injection system. BACKGROUND: Angiogenesis has been induced by direct injection of growth factors into ischemic myocardium during open-heart surgery. Catheter-based transendocardial injection of angiogenic factors may provide equivalent benefit without need of surgery. METHODS: A new guidance system for intramyocardial therapy utilizes magnetic fields and catheter-tip sensors to locate a position in space and reconstruct three-dimensional left ventricular (LV) electromechanical maps without using fluoroscopy. A retractable 27G needle was coupled with the guidance system for LV transendocardial injection. In 12 pigs, the catheter was used to inject 0.1 ml of methylene-blue (MB) dye and 8 pigs had myocardial injections of adenoviral vector (1 x 10(10) particles per site) containing the LacZ transgene. Ten pigs underwent catheter-based transendocardial injection and six pigs were injected using transepicardial approach with the gene encoding adenovirus vascular endothelial growth factor-121 (Ad.VEGF121; 1 x 10(10) viral particles x 6 sites) and sacrificed at 24 h. Injection sites were identified with ultraviolet light by coinjection of fluorescent beads. RESULTS: Overall, 138 of 152 attempted injection MB tracks (91%) were found after sacrifice. Tissue staining was 7.1+/-2.1 mm in depth and 2.3+/-1.8 mm in width. No animal had pericardial effusion or tamponade. In Ad.LacZ injected animals, gross pathology showed positive staining in injected zones, and histology confirmed positive myocyte staining. Adenovirus vascular endothelial growth factor-121 injected sites showed high levels of VEGF121 production that was of similar magnitude whether injected using the transendocardial (880.4+/-412.2 pg VEGF121/mg protein) or transepicardial (838.3+/-270 pg VEGF121/mg protein) delivery approach (p = 0.62). CONCLUSIONS: Using this magnetic guidance catheter-based navigational system, transgenes can effectively be transfected into designated myocardial sites. Thus, if it is determined that direct intramyocardial injection of angiogenic factors enhances collateral function in patients, this less invasive catheter-based system offers a similar gene delivery efficiency and, thus, may have clear advantages compared with the surgically-based transepicardial injection approach.

Animals↗
PubMed2000

Transplant immunosuppression increases and prolongs transgene expression following adenoviral-mediated transfection of rat lungs.

BACKGROUND: Gene therapy provides the potential to modify donor organs to better withstand transplantation, but this has yet to be realized. In vivo gene transfer using adenoviral vectors has had limited success because of host immune response that induces inflammation and limits the amount and duration of transgene expression. We hypothesize that transplantation immunosuppression can attenuate the post-transfection host-immune response to allow for improved gene transfer following adenoviral-mediated transfection. METHODS: We intratracheally transfected with adenovirus containing the beta-galactosidase gene and randomized the rats to either the immunosuppression group, receiving daily cyclosporine, azathioprine, and methylprednisolone, or the control group, receiving no immunosuppression. We evaluated transgene expression and post-transfection inflammation at time points ranging from 1 day to 5 weeks. RESULTS: Following transfection, control rats showed relatively low levels of transgene expression, which rapidly decreased to non-detectable levels. In contrast, immunosuppressed rats demonstrated significantly higher levels of transgene expression overall (p < 0.00005), peaking at almost 3 times that of the control group (p < 0.02), and showing prolonged and elevated transgene expression at 5 weeks (p < 0.02). On histologic sections of the lungs, immunosuppressed rats exhibited overall lesser grades of post-transfection inflammation. CONCLUSIONS: Transplant immunosuppression provides the means to attenuate the severe immune response to adenoviral-mediated gene transfection and thereby increase and prolong transgene expression.

Adenoviridae↗
PubMed2000

Design, synthesis and biological activity of 7-O-(4-O-acetyl-3-iodo-2,3,6-trideoxy-alpha-L-arabino-hexopyranosyl) daunomycinone and 7-O-(3-chloro-2,3,6-trideoxy-4-O-propanoyl-alpha-L-lyxo- hexopyranosyl)daunomycinone.

The synthesis and pharmacological evaluation of 7-O-(4-O-acetyl-3-iodo-2,3,6-trideoxy-alpha-L-arabino-hexopyranosyl) daunomycinone and 7-O-(3-chloro-2,3,6-trideoxy-4-O-propanoyl-alpha-L-lyxo-hexopyrano syl) daunomycinone are described. Their cytotoxic activity was evaluated against normal and resistant cell lines. Both compounds exhibited activity against the adriamycin resistant cell line KB-A1. These results support the hypothesis that the increased lipophilicity of the sugar part of anthracyclines is associated with their ability to overcome multidrug resistance (MDR).

Antibiotics, Antineoplastic↗
PubMed1999

Evaluation of the acute and chronic safety of the biosense injection catheter system in porcine hearts.

Direct myocardial injection of therapeutic agents has been explored as a new method for myocardial revascularization. The integration of a 3D electromechanical mapping catheter with a retractable injection needle should allow for intramyocardial injection to identified sites, obviating the need for open heart surgery. This study assessed the procedural safety and performance characteristics of a novel guided catheter-based transendocardial injection system. The electromagnetic guidance system was coupled with a retrievable 27G needle for left ventricular endocardial injection. Using this system, we injected, transendocardially, methylene-blue (MB) dye tracer at a volume of 0.1 or 0.2 ml per injection in eight normal pigs. Animals were sacrificed acutely, at 1, 3, and 7 days (two animal in each time). Three animals served as controls. The injections were followed by coronary angiography and echocardiogram to assess possible ventricular or coronary perforation and wall motion abnormalities. CK-MB levels were measured up to 24 hr following the procedure. The animals were sacrificed at the assigned time for gross and histopathology evaluation. A total of 101 injections were made in all regions of the heart except the apex and the mitral valve. No animal died as a result of the mapping or injection procedures. Vital signs did not change relative to baseline after the mapping and injection procedures. CK-MB values did not increase over time and there was no evidence of sustained arrhythmia or hemodynamic compromise. There was no evidence of left ventricular or coronary perforation, global or regional wall motion abnormalities, or hemopericardium. On histologic evaluation, the estimated volume of tissue staining was greater than the volume of the injected MB dye due to dispersion of the injectate in the interstitial and intracellular fluid compartments. It is concluded that using this magnetic guidance catheter-based navigational system, it is feasible and safe to perform the transendocardial injection procedure. Thus, if it is determined that direct intramyocardial injection of drugs is a valid therapeutic strategy, this approach offers a clear advantage over surgically based transepicardial injection procedures. Cathet. Cardiovasc. Intervent. 48:447-453, 1999.

Animals↗