Transcoronary pacing in an animal model : Second coated guidewire versus cutaneous patch as indifferent electrodes.

BACKGROUND: Transcoronary pacing is a seldom used treatment option for unheralded bradycardias in the setting of percutaneous coronary interventions (PCI). In the present study we compared a coated guidewire inserted proximally into a coronary artery with a cutaneous patch electrode as indifferent electrodes for transcoronary pacing in a porcine model. METHODS: Transcoronary pacing was investigated in 7 adult pigs in an animal catheterization laboratory. A standard guidewire insulated by a monorail-balloon was advanced into the periphery of a coronary artery serving as the cathode. As the indifferent anode, a special guidewire with electrical insulated by a polytetrafluoroethylene (PTFE) coating was positioned into the proximal part of the same coronary vessel. Transcoronary pacing parameters (threshold and impedance data and the magnitude of the epicardial electrogram) were compared with unipolar transcoronary pacing using a cutaneous patch electrode. RESULTS: Transcoronary pacing was successful against both indifferent electrodes. Pacing thresholds obtained with the coated guidewire technique (1.8 ± 1.3 V) were similar to those obtained by standard unipolar transcoronary pacing with a cutaneous patch electrode (1.8 ± 1.5 V). The impedance with the additional coated guidewire was 419 ± 144 Ω and thereby slightly higher compared to 320 ± 103 Ω obtained by pacing against the patch electrode (p < 0.05). Both settings yielded comparable R­wave amplitudes (8.0 ± 5.1 mV vs. 7.1 ± 3.6 mV). CONCLUSIONS: A second coated guidewire is as effective as a cutaneous patch electrode when added as an indifferent electrode in transcoronary pacing. This transcoronary pacing technique could replace temporary transvenous pacing in emergency situations during PCI, especially when using the radial approach.

Transcoronary mapping of ventricular asynchrony due to left bundle branch block in a porcine model.

BACKGROUND: Optimal positioning of the left ventricular (LV) lead at the latest activated part of the left ventricle is one of the major challenges in implantation of cardiac resynchronization therapy (CRT) devices with respect to ascertaining an optimal resynchronization effect resulting in a high responder rate. In the present study, we evaluated the feasibility of transcoronary measurement of LV electrical activation by a coated guidewire in a porcine model. METHODS AND RESULTS: Transcoronary measurement of ventricular activation was performed in 16 pigs under general anesthesia. Left bundle branch block (LBBB) was induced by transvenous pacing in the right ventricular apex (RVA). A specially coated guidewire (Vision Wire; Biotronik) serving as the different electrode was positioned subsequently in the proximal and distal part of each coronary main vessel. A cutaneous skin patch electrode was placed at the back of the thorax of the animal to act as the indifferent electrode. Both electrodes were connected to a portable electrophysiology lab system (EP Tracer 38; CardioTek). Mean QRS width during transvenous right ventricular pacing was 83 ± 5 ms with a typical LBBB pattern. The measured time interval between the beginning of the QRS complex in the surface electrocardiogram (ECG) and the local signal derived from the tip of the guidewire (QRS-EGM) was 32 ± 9 ms in the distal ramus circumflex (RCX) coronary artery and 51 ± 6 ms in the proximal RCX, yielding a mean delay of 18 ± 8 ms within this vessel. In the left anterior descending (LAD) coronary artery, the local signal was 23 ± 10 ms in the distal part and 41 ± 10 ms in the proximal part of the vessel, with an identical mean delay of 18 ± 8 ms. The QRS-EGM interval within the right coronary artery (RCA) was 14 ± 8 ms in the distal part and 40 ± 9 ms in the proximal part of the vessel, resulting in a mean delay of 25 ± 7 ms. The delay between the activation of the distal RCA and the activation of the distal LAD and RCX was statistically significant (P<.001). Within the proximal guidewire positions, the latest electrical activation of the left ventricle during pacing-induced LBBB could be observed in the RCX with 51.4 ± 6.3 ms (P<.01). CONCLUSION: Transcoronary measurement of LV excitation by a specially coated guidewire is feasible and could confirm the electrical asynchrony induced by LBBB. Since coronary angiography is a mandatory part of the evaluation of patients for CRT implantation, a "transcoronary mapping procedure" can be easily performed, thereby evaluating the latest activated part of the left ventricle in advance of the implantation procedure, aiming to improve the responder rate in CRT therapy.

A novel approach for transcoronary pacing in a porcine model.

BACKGROUND: Transcoronary pacing for the treatment of bradycardias during percutaneous coronary intervention (PCI) is a useful technique in interventional cardiology. The standard technique is unipolar pacing with the guidewire in the coronary artery against a cutaneous patch electrode. We developed a novel approach for transcoronary pacing by using intravascular electrodes in different positions in the aorta in a porcine model. METHODS AND RESULTS: Unipolar transcoronary pacing was applied in 8 pigs under general anesthesia using a standard floppy guidewire in a coronary artery as the cathode with additional insulation of the guidewire by a monorail angioplasty balloon. Intravascular electrodes positioned in the aorta thoracalis and the aorta abdominalis served as indifferent anodes. The efficacy of transcoronary pacing with intravascular anodal electrodes was assessed by measurement of threshold and impedance data and the magnitude of the epicardial electrogram in comparison to unipolar transvenous pacing using the same indifferent anodal electrodes. Transcoronary pacing with the guidewire-balloon combination using indifferent intravascular electrodes was effective in all cases. Transcoronary pacing thresholds obtained against the indifferent coil electrodes in the aorta thoracalis (0.8 ± 0.5 V) and in the aorta abdominalis (0.8 ± 0.5 V) were similar to those obtained with unipolar transvenous pacing (0.7 ± 0.3 V and 0.6 ± 0.2 V, respectively), whereas the tip-electrode in the aorta thoracalis serving as indifferent anode produced significantly higher pacing thresholds (guidewire, 2.8 ± 2.6 V; transvenous lead, 1.5 ± 0.8 V). The lower pacing threshold of the coil-electrodes was associated with significantly lower impedance values (aorta thoracalis, 285 ± 63 ohm; aorta abdominalis, 294 ± 61 ohm) as compared to the tip-electrode in the aorta thoracalis (718 ± 254 ohm). The amplitude of the epicardial electrogram acquired by the intracoronary guidewire was without significant differences between the indifferent electrodes. CONCLUSIONS: Transcoronary pacing in the animal model using a standard guidewire with balloon insulation and intravascular indifferent electrodes is depending on the optimal configuration of the anodal electrode. The use of intravascular coil electrodes with a sufficient surface area can produce 100% capture at thresholds comparable to transvenous pacing. Therefore, technical integration of these coil electrodes into the access sheath or the guiding catheter with respect to handling these tools in daily clinical practice in the catheterization laboratory could further facilitate the transcoronary pacing approach.

Do pharmacokinetics explain persistent restenosis inhibition by a single dose of paclitaxel?

BACKGROUND: The purpose of this study was to investigate the elimination of paclitaxel from the arterial wall after a single short administration with a coated balloon. METHODS AND RESULTS: Slightly oversized paclitaxel-coated balloons (dose 3 or 9 µg/mm(2)) without or with premounted stents were inflated in nonatherosclerotic coronary arteries of either young domestic pigs or adult Goettingen minipigs. The paclitaxel content of plasma, arterial segments, and residual hearts (without treated arteries) was measured for up to 180 days using high-performance liquid chromatography/ultraviolet detection or mass spectrometry. Angiograms were evaluated for lumen narrowing. The paclitaxel concentration in plasma remained <10 ng/mL. In arteries of domestic pigs and minipigs treated with paclitaxel-coated balloons with premounted stents, 10%±5% or 21%±8% of dose, respectively, was initially detected and decreased to 3.5%±3.1% of dose (domestic pig) by Day 7. Within 6 months it fell with a half-life of 1.9 months to 0.40%±0.35%. After 3 months the concentration in the arterial wall was 17±11 µmol/L. Without a stent, drug transfer to the vessel wall was somewhat reduced and elimination faster. Immediately after treatment up to 26%±4% of dose was detected in the residual whole hearts. It dropped with a half-life of 45 days to 1.5%±0.6% of dose (0.3 µmol/L) within 6 months. CONCLUSIONS: After a single local administration with coated balloons, paclitaxel stays in the vessel wall of pigs long enough to explain persistent inhibition of neointimal proliferation. The pharmacokinetics of paclitaxel does, however, not exclude other reasons for sustained efficacy such as early blocking of processes initiating excessive and prolonged neointimal proliferation.

Inhibition of neointimal hyperplasia with a novel zotarolimus coated balloon catheter.

BACKGROUND: Non stent based delivery of antiproliferative agents using drug coated balloon catheters may offer additional flexibility and efficacy in a broad range of applications. The lipophilic antiproliferative drug zotarolimus makes it a potential candidate for balloon delivery. The aim of the present study was to evaluate the safety and efficacy of a prototype zotarolimus coated balloon (ZCB) catheter in comparison to a zotarolimus eluting stent (ZES) in the porcine coronary overstretch model. METHODS: Eighty-four stents (diameters 3.0 and 3.5 mm; length 15 mm) were implanted in LAD and Cx of 42 domestic pigs: control (TriMaxx, Abbott, polymer coated stent without drug, implanted with uncoated PCI catheter, n = 56); ZES (ZoMaxx, Abbott, stent coated with zotarolimus in polymer, implanted with uncoated PCI catheter, n = 14); ZCB (TriMaxx, Abbott, polymer coated stent without drug, implanted with zotarolimus coated PCI catheter, n = 14). Drug content of the vessel wall (n = 9) was measured about 10-30 min post intervention with ZCB in additional pigs. RESULTS: Immediately after ZCB treatment 101 ± 31 µg of zotarolimus was detected in the coronary arteries. After 28 days ZES led to a reduction of neointimal area from 4.32 ± 1.45 to 3.32 ± 1.11 mm2 (P = 0.019 vs. control). The effect of neointimal inhibition was more pronounced with the novel ZCB (2.79 ± 1.43 mm², P = 0.001 vs. control). Inflammation score was significantly reduced in vessels treated with the ZCB (0.75 ± 0.86 compared to control (1.45 ± 0.94, P = 0.013) and ZES (1.65 ± 0.90, P = 0.012). CONCLUSION: Zotarolimus coated balloons and stents were found to effectively reduce neointimal proliferation in the porcine coronary model. Inflammation scores were significantly reduced after treatment with the coated balloon. Zotarolimus balloon coating might be a novel option in preventing and treating restenosis.

Inhibition of neointimal proliferation after bare metal stent implantation with low-pressure drug delivery using a paclitaxel-coated balloon in porcine coronary arteries.

A variety of mechanical and laser-based methods remove or shift atherosclerotic plaques and reopen the artery to its original lumen. Subsequent treatment with drug-coated balloons (DCB) may smooth the vessel wall but does not require high-pressure inflation. We investigated the efficacy of paclitaxel-coated balloons inflated with only 2 atm after bare metal stent implantation in coronary arteries of 24 pigs. Angiography and histomorphometry was performed on day 28. DCB inflated with 2 atm caused similar reduction of late lumen loss (LLL) as high-pressure inflation with 12 atm (0.89 ± 0.58 vs. 0.72 ± 0.39 mm, p = 0.34). Both DCB treatments significantly (p < 0.01) reduced LLL versus uncoated balloons (1.50 ± 0.51 mm). Treatment with low-pressure DCB resulted in less maximal intimal thickness (0.45 ± 0.15 vs. 0.67 ± 0.25 mm) and neointimal area (2.93 ± 0.73 vs. 3.82 ± 1.27 mm(2)) than treatment with uncoated balloons (p < 0.05). In conclusion, low-pressure treatment with DCB was similarly effective as high-pressure treatment justifying clinical trials in vessels which will benefit from inhibition of neointimal proliferation but may not tolerate high inflation pressure.

Urinary tract effects after multifocal nonthermal irreversible electroporation of the kidney: acute and chronic monitoring by magnetic resonance imaging, intravenous urography and urinary cytology.

PURPOSE: The nonthermal irreversible electroporation (NTIRE) is a novel potential ablation modality for renal masses. The aim of this study was the first evaluation of NTIRE's effects on the renal urine-collecting system using intravenous urography (IVU) and urinary cytology in addition to histology and magnetic resonance imaging (MRI). METHODS: Eight percutaneous NTIRE ablations of the renal parenchyma, including the calyxes or pelvis, were performed in three male swine. MRI, IVU, histology, and urinary cytology follow-ups were performed within the first 28 days after treatment. RESULTS: MRI and histological analysis demonstrated a localized necrosis 7 days and a localized scarification of the renal parenchyma with complete destruction 28 days after NTIRE. The urine-collecting system was preserved and showed urothelial regeneration. IVU and MRI showed an unaltered normal morphology of the renal calyxes, pelvis, and ureter. A new urinary cytology phenomenon featured a temporary degeneration by individual vacuolization of detached transitional epithelium cells within the first 3 days after NTIRE. CONCLUSIONS: This first urographical, urine-cytological, and MRI evaluation after porcine kidney NTIRE shows multifocal parenchyma destruction while protecting the involved urine-collecting system with regenerated urothelial tissue. NTIRE could be used as a targeted ablation method of centrally located renal masses.

Transcoronary pacing in a porcine model--impact of guidewire insulation.

BACKGROUND: Bradycardia complicating percutaneous coronary intervention (PCI) can require temporary pacing. A transcoronary approach using the guidewire in the coronary artery may be a useful alternative to transvenous pacing. The purpose of the present study was to compare the efficacy of two different coronary guidewires in transcoronary pacing: a novel guidewire (VisionWire®, Biotronik, Germany) which has a coating to electrically insulate the shaft, thereby maximizing current delivery through the intracoronary section compared to a standard guidewire (without insulation) and a standard guidewire/balloon combination. METHODS AND RESULTS: Unipolar transcoronary pacing was performed in 15 pigs under general anesthesia. In each animal, the new VisionWire was compared to a standard floppy guidewire and to a standard floppy guidewire loaded with a standard angioplasty balloon (which provides additional shaft insulation). The coronary guidewire was the cathode and a skin patch electrode (on the anterior or posterior chest wall) was the anode. We examined the effect of different electrode combinations on transcoronary pacing as assessed by threshold and impedance data and the magnitude of the epicardial electrocardiogram. Transcoronary pacing with the bare standard guidewire was effective in 77% of cases using an anterior skin patch electrode and in 87% with a posterior patch at pacing thresholds of 6.7 ± 2.9 V and 4.1 ± 3.0 V, respectively. Loading the same guidewire with an angioplasty balloon increased the pacing efficacy to 100% with significantly lower pacing thresholds of 2.4 ± 1.6 V with an anterior patch and 1.6 ± 1.3 V with a posterior patch (p < 0.001). The bare VisionWire yielded 100% pacing efficacy, with the lowest pacing thresholds of 1.6 ± 0.7 V and 1.0 ± 0.6 V anterior and posterior patch positions, respectively (p < 0.001). In all studies the pacing efficacy was higher and thresholds lower with the skin patch electrode on the posterior chest wall than on the anterior chest wall. CONCLUSIONS: Transcoronary pacing in the animal model is an effective technique. The VisionWire, (even without the additional insulation of a balloon in place) performed better than a standard guidewire (with or without balloon use), and enabled 100% pacing efficacy at acceptable thresholds. Thus, transcoronary pacing, particularly with specific coronary guidewires may be a useful alternative to transvenous pacing during PCI, particularly in the emergency situation when unexpected bradycardias arise during transradial angioplasty when no central venous access is immediately available for transvenous pacing.

Dose response to Paclitaxel-coated balloon catheters in the porcine coronary overstretch and stent implantation model.

OBJECTIVE: There is little published information regarding the efficacy of paclitaxel-coated balloon catheters except for the iopromide-containing formulation, and less is known about the kind of toxicity at overdose. The aim of our study was to assess 2 different paclitaxel matrix formulations on angioplasty balloon catheters in vitro, with respect to pharmacokinetics, and efficacy and tolerance to determine the minimum effective dose and local toxicity at extremely high dose which is only achieved in experimental studies. METHODS AND MATERIALS: Adherence of coatings was tested in vitro in dry state and during passage through hemostatic valves, guiding catheters, and blood. Drug release, transfer to the vessel wall during coronary angioplasty, inhibition of neointimal proliferation, and tolerance were investigated in swine. Efficacy and tolerance of balloons were examined for doses ranging from 1 to 9 µg/mm2 and 3 overlapping applications of balloons coated with 3 times the regular dose of 3 µg/mm2. Paclitaxel concentrations were determined by high performance liquid chromatography, efficacy and tolerance by vital signs, clinical observation, quantitative coronary angiography, and histomorphometry 4 weeks after implanting premounted bare stents in coronary arteries applying 1:1.2 overstretch. RESULTS: Under worst-case conditions, drug loss on the way through the guiding catheter and blood was in the range of 30%. After inflation of balloons coated with the clinically tested dose of 3 µg/mm2 in a coronary artery about 10% of drug remained on balloons, 20% to 30% was taken up into the vessel wall (∼200 µg). Neointimal area on cross sections was 6.8 ± 2.2 mm2 (uncoated control); 3.1 ± 1.1 mm2 (iopromide-matrix) and 3.0 ± 0.5 mm2 (urea-matrix) at 1 µg/mm2; 2.0 ± 0.4 mm2 versus 1.7 ± 1.1 mm2 at 3 µg/mm2 with no further decrease at higher doses. Thrombotic occlusions were observed in 3 of 15 vessel segments treated with overlapping inflations of 3 high-dose balloons but without any signs of aneurysms. CONCLUSION: In the animal model, 2 paclitaxel matrix formulations were similar in respect of uptake in the vessel wall, and effective already at a dose of 1 µg/mm2. Except thrombotic events for the intentionally excessive dose, paclitaxel-coated balloons were well tolerated in the animal model.

Optimizing of transcoronary pacing in a porcine model.

BACKGROUND: Transcoronary pacing for the treatment of bradycardia during percutaneous coronary intervention (PCI) is not well established, but may be a useful technique in interventional cardiology. We developed a porcine model to examine the feasibility and efficacy of transcoronary pacing during PCI. METHODS AND RESULTS: Eight pigs under general anesthesia underwent unipolar transcoronary pacing with a standard floppy guidewire in a coronary artery (as the cathode) and a skin patch electrode (as the anode). We examined the effect of skin-patch position (groin vs. anterior or posterior chest wall), the presence of an angioplasty balloon on the guidewire and also which coronary artery was "wired" on the efficacy of pacing as assessed by capture and threshold data. Pacing with the bare guidewire and a maximum output of 10 V was successful in 54% of the animals with a groin patch and the anterior chestwall patch, but in 100% with a posterior chest-wall patch. The pacing thresholds were 8.3 +/- 2.2 V, 7.6 +/- 2.8 V and 3.4 +/- 2.4 V with the patch in these sites, respectively. With an angioplasty balloon over the guidewire, pacing efficacy increased to 100% (irrespective of the target vessel or patch location) and pacing thresholds were significantly reduced (p < 0.05) to 2.7 +/- 1.5 (with a groin patch) and 1.0 +/- 0.7 V (with a posterior chestwall patch). With optimal pacing set-up (posterior chest-wall patch and angioplasty-balloon insulation), pacing thresholds were similar to those obtained with standard bipolar transvenous pacing at 1.2 +/- 0.8 V. We did not observe any adverse effects of coronary pacing. Skeletal muscle contraction was only generated at high-output levels. CONCLUSIONS: This pig model examines the practicalities of transcoronary pacing and shows that this technique can produce 100% capture at thresholds comparable to the transvenous approach. This technique may have a role during PCI, particularly in an emergency situation.

Comparison of two different paclitaxel-coated balloon catheters in the porcine coronary restenosis model.

BACKGROUND: Drug-eluting balloon (DEB) catheters coated with paclitaxel in a water-soluble matrix have shown beneficial effects in the treatment and prevention of restenosis in the porcine coronary overstretch model and in clinical trials. Adherence of paclitaxel, same dose, on another recently introduced coated percutaneous coronary intervention (PCI) catheter (DIOR) is mediated by a roughened balloon surface. Only scarce experimental and clinical data has been published on the new coating method. The aim of the present study was to compare the safety and efficacy of the two coatings in the porcine model. METHODS AND RESULTS: Twenty-eight stainless steel stents were implanted in the left anterior descending and circumflex coronary arteries of 14 domestic pigs using either matrix-coated (n = 8), roughened DEB (n = 9), or uncoated PCI catheters, which served as control (n = 11). After 28 days, quantitative angiography and histomorphometry of the stented arteries were performed. Matrix-coated DEB led to a highly significant (P < 0.01) reduction of all parameters indicating neointimal proliferation compared to both, uncoated control and the roughened DEB; late lumen loss in-segment was 0.4 +/- 0.2, 1.9 +/- 0.5, and 1.4 +/- 0.5 mm, respectively. In contrast, the roughened DEB failed to produce statistically significant effects on angiographic measures of stenosis or morphometric parameters such as maximal neointimal thickness and luminal area, except for neointimal area (5.7 +/- 1.5 mm(2) in the control group, 4.1 +/- 1.7 mm(2) roughened DEB, P < 0.05 vs. control, and 2.5 +/- 0.8 mm(2) matrix-coated DEB, P < 0.01 vs. control). CONCLUSION: Inhibition of neointimal proliferation in the porcine coronary overstretch model by paclitaxel depends critically on the coating method.

Drug-eluting balloon: very short-term exposure and overlapping.

Paclitaxel balloon coating has shown promising effects in inhibiting restenosis in initial clinical trials. The aim of the present study was to evaluate the influence of two critical features of drug-eluting balloon (DEB) application - inflation time and increased dose due to overlapping balloons. Fifty-six stainless steel stents were implanted in the left anterior descending and circumflex coronary arteries of 28 domestic pigs using a 1.2:1.0 overstretch ratio. Stents were mounted on conventional uncoated and paclitaxel-coated angioplasty balloon catheters. The animals were randomized to five different treatments with a range of short (10 seconds [s] inflation using 1 DEB) to extended (2x60 s inflation using 2 DEB) intima contact time. After 28 days, quantitative angiography and histomorphometry of the stented arteries was performed on a total of 23 pigs. Paclitaxel balloon coating led to a marked reduction of parameters characterizing in-stent stenosis: Late lumen loss was 1.37 +/- 0.49 mm for uncoated balloons, 0.23 +/- 0.42 mm for one coated balloon 60 s inflation time, 0.37 +/- 0.28 mm for 10 s inflation time and 0.30 +/- 0.19 mm for the vessel segment treated by two coated balloons with 60 s inflation each. Neointimal areas were 4.26 +/- 1.18, 1.68 +/- 0.23, 1.83 +/- 0.40 and 1.67 +/- 0.46 mm(2), respectively (p = 0.001 versus control, p > 0.05 between paclitaxel-treated groups). Despite the marked reduction of neointimal proliferation, endothelialization of stent struts was present in all samples. DEB were found to effectively reduce neointimal proliferation regardless of inflation time and dose within the tested range. No adverse reactions were seen as dose was increased to more than three times the clinically tested dose.

Short- and long-term effects of a novel paclitaxel coated stent in the porcine coronary model.

BACKGROUND: Drug eluting stents (DES) are unique in allowing sustained release for weeks after a single short intervention. The challenge with DES still remaining is the combination of a biocompatible drug-eluting matrix including an antiproliferative drug showing efficacy and safety in restenosis prevention. The aim of the present animal studies was to evaluate the novel paclitaxel coated Coroflex. Please stent in the porcine coronary model. METHODS AND RESULTS: Stents were implanted into LAD and CX arteries of 49 domestic pigs. After 5 days, 4 weeks, 3 months, or 6 months, the animals underwent control angiography including dissection of the stented coronary arteries for histology. After 5 days, 3 and 6 months the Coroflex. Please stent was compared with its uncoated counterpart and a paclitaxel free but polymer coated version. After 28 days, an additional group received the Taxus Express(2) stent. After 5 days, healing with the paclitaxel coated stent was comparable to the uncoated bare metal stent as reflected in a similar neointimal proliferation. Compared to the Taxus stent, the new Coroflex. Please stent showed a similar neointimal proliferation after 4 weeks. Inflammatory reaction was comparable among the bare stent and polymer coated stent groups. Paclitaxel coating was associated with a slightly increased inflammatory reaction with both DES. After 3 and 6 months, all groups showed a similar neointimal proliferation and inflammatory reaction. CONCLUSION: The present porcine studies demonstrate excellent safety of the new paclitaxel coated Coroflex stent in the porcine coronary stent model.

Inhibition of restenosis in stented porcine coronary arteries: uptake of Paclitaxel from angiographic contrast media.

RATIONALE AND OBJECTIVES: Paclitaxel added to angiographic contrast medium (CM) has been shown to inhibit restenosis in the porcine coronary overstretch model. This study determined early local tissue concentrations after the administration of different paclitaxel doses and preparations. MATERIALS AND METHODS: Fifteen pigs received 2 stents each in the left coronary artery. During and/or after the intervention, paclitaxel-containing CM or diluted Taxol was injected. Fifteen minutes after the last intracoronary injection, paclitaxel concentrations in the arterial wall and myocardium were measured by high-performance liquid chromatography. RESULTS: Mean paclitaxel concentrations in the left coronary arteries reached 3-10 microM. Higher volumes and higher paclitaxel concentrations resulted in higher tissue concentrations. Paclitaxel in CM was better tolerated and led to higher local concentrations than diluted Taxol. Low paclitaxel concentrations in the uninjected right coronary artery and in plasma indicate selectivity. CONCLUSION: When admixed to CM, paclitaxel results in local tissue concentrations proportional to the amount of the drug injected.

Catheter ablation of ventricular tachycardia by intramyocardial injection of ethanol in an animal model of chronic myocardial infarction.

INTRODUCTION: Direct injection of ethanol into myocardium has been shown to create large, well-demarcated lesions with transmural necrosis in normal ventricular myocardium and in regions of healed myocardial infarction. The aim of this study was to investigate the effects of direct ethanol injection on the inducibility of ventricular tachycardia (VT) in an animal model of chronic myocardial infarction. METHODS AND RESULTS: Eight sheep with reproducibly inducible VT underwent an electrophysiologic study 139 +/- 65 days after myocardial infarction. Noncontact mapping was used to analyze induced VT. Fifteen different VTs were targeted for catheter ablation. Ablation was achieved by catheter-based intramyocardial injection of a mixture of 96% ethanol, glycerine, and iopromide (ratio 3:1:1). Direct intramyocardial ethanol injection resulted in noninducibility of any VT 20 minutes after ablation in 7 of 8 animals. Four of 5 animals with initially successful ablation remained noninducible for any VT at follow-up study at least 2 days after the ablation procedure. Microscopic examination revealed homogeneous lesions with interstitial edema, intramural hemorrhage, and myofibrillar degeneration at the lesion border. The lesions were well demarcated from the surrounding tissue by a border zone of neutrophilic infiltration. CONCLUSION: Catheter ablation of VT by direct intramyocardial injection of ethanol during the chronic phase of myocardial infarction is feasible. It may be a useful tool for catheter ablation when the area of interest is located deep intramyocardially or subepicardially or when a more regional approach requires ablation of larger amounts of tissue.