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Biomedical subjects

Campbell Rogers

Publications and source records attributed to Campbell Rogers.

29 records · Page 2Linked to original sources
PubMed2004

Deep myocardial ablation lesions can be created with a retractable needle-tipped catheter.

RF catheter ablation of ventricular tachycardia is sometimes limited by inadequate lesion depth. This study investigated the use of a retractable needle-tipped catheter to create deep RF lesions in vivo in porcine myocardium. An 8 Fr electrode catheter with an extendable 27-gauge needle at the tip was modified for RF ablation by embedding a thermocouple and attaching a pin connector. In three swine (32-58 kg) the left ventricle was entered via the femoral artery and endocardial contact was made. The needle was advanced 10 mm and 13 RF applications were made under a controlled temperature (90 degrees C x 120 s). Nine control lesions were made using a standard 4-mm tip catheter (60 degrees C x 120 s). The lesions were fixed, serially sectioned from the endocardium, digitally imaged, and quantified. Needle ablation lesions were deeper (10.15 +/- 0.77 vs 5.67 +/- 0.37 mm, P < 0.001) and more likely to be transmural (77 vs 11%, P = 0.008) than control lesions. The volume of control lesions, however, was larger (358.4 +/- 56.2 vs 174.7 +/- 18.6 mm(3), P = 0.002) due to a significantly larger cross-sectional area at the endocardium (0.548 +/- 0.04 vs 0.151 +/- 0.01 cm(2), P < 0.001). At depths > 6 mm, the needle electrode lesions had a greater cross-sectional area (0.136 +/- 0.01 vs 0.005 +/- 0.004 cm(2), P < 0.001). Catheter-based needle ablation is feasible and allows creation of deeper lesions that can be transmural. Although deep, the lesions had a small cross-sectional area such that precise targeting would be required for success.

Animals↗
PubMed2003

Phase I drug and light dose-escalation trial of motexafin lutetium and far red light activation (phototherapy) in subjects with coronary artery disease undergoing percutaneous coronary intervention and stent deployment: procedural and long-term results.

BACKGROUND: Motexafin lutetium (MLu; Antrin) is a photosensitizer that is taken up by atherosclerotic plaque and concentrated within macrophages and vascular smooth muscle cells. After photoactivation with far red light, MLu facilitates production of cytotoxic oxygen radicals that mediate apoptosis. We assessed the safety and tolerability of phototherapy (PT) with MLu in patients undergoing percutaneous coronary intervention with stent deployment. METHODS AND RESULTS: An open-label, phase I, drug and light dose-escalation clinical trial of MLu PT enrolled 80 patients undergoing de novo coronary stent deployment. MLu was administered to 79 patients by intravenous infusion 18 to 24 hours before procedure, and photoactivation was performed after balloon predilatation and before stent deployment. Clinical evaluation, serial quantitative angiography, and intravascular ultrasound were performed periprocedurally and at 6 months follow-up. MLu PT was well tolerated without serious dose-limiting toxicities, and side effects (paresthesia and rash) were minor. No adverse angiographic outcomes were attributed to phototherapy. CONCLUSIONS: This study demonstrates that coronary MLu PT seems safe, and the maximum well-tolerated MLu dose and range of tolerated light doses were identified. These data can be used in phase II efficacy trials of MLu PT for the treatment of coronary atherosclerosis or vulnerable plaque.

Adult↗
PubMed2003

Randomized comparison of distal protection with a filter-based catheter and a balloon occlusion and aspiration system during percutaneous intervention of diseased saphenous vein aorto-coronary bypass grafts.

BACKGROUND: The high rate of periprocedural complications resulting from atherothrombotic embolization after percutaneous intervention in diseased saphenous vein grafts is reduced by distal microcirculatory protection using a balloon occlusion and aspiration system. Whether filter-based catheters, which offer the inherent advantages of maintained perfusion and ease of use, are as effective for this purpose has not been established. METHODS AND RESULTS: A total of 651 patients undergoing percutaneous intervention of 682 saphenous vein graft lesions were prospectively randomized to distal protection with the filter-based FilterWire EX versus the GuardWire balloon occlusion and aspiration system. Device success was 95.5% and 97.2% with the FilterWire EX and GuardWire, respectively (P=0.25). Postprocedural measures of epicardial flow and angiographic complications were similar between the 2 groups, although bailout IIb/IIIa inhibitors were required slightly less frequently in the FilterWire EX group (0% versus 1.5%, P=0.03). The primary end point, the composite incidence of death, myocardial infarction, or target vessel revascularization at 30 days, occurred in 9.9% of FilterWire EX patients and 11.6% of GuardWire patients (difference [95% CI]=-1.7% [-6.4%, 3.1%]; P for superiority=0.53, P for noninferiority=0.0008). CONCLUSIONS: Distal protection with the FilterWire EX may be safely used as an adjunct to percutaneous intervention of diseased saphenous vein grafts and, compared with distal protection with the GuardWire balloon occlusion and aspiration system, results in similar rates of major adverse cardiac events at 30 days.

Aged↗
PubMed2003

The porcine coronary model of in-stent restenosis: current status in the era of drug-eluting stents.

Drug-eluting stents are revolutionizing interventional cardiology. Sirolimus-eluting stents are in widespread clinical use, associated with well-documented remarkably low restenosis rates, and a number of other agents appear promising in clinical trials. These human studies have been preceded by numerous animal studies, foremost among them the pig coronary model of in-stent restenosis (ISR). The histologic response to porcine coronary stenting was described over a decade ago. Porcine stenting studies now provide examinations not only of histology, but also mechanisms of action, toxicity, and biocompatibility. This review therefore examines the current status of this porcine coronary model of ISR. Contemporary methods of pig coronary stenting are discussed. The morphometric, cellular, and molecular analyses of the responses to stent injury are then described. Finally, recent pig coronary drug-eluting stent studies are examined, with a discussion of their advantages, limitations, and possible future modifications.

Animals↗
PubMed2003

Leukocyte recruitment and expression of chemokines following different forms of vascular injury.

UNLABELLED: Inflammation plays a central role in restenosis following coronary intervention. Recent human and animal data suggest important differences between the inflammatory responses to simple balloon angioplasty compared with stent implantation. To investigate the mechanisms of these differences, New Zealand white rabbits underwent bilateral iliac artery balloon denudation. Half received intravascular stents. Arteries were harvested at three, seven and 14 days for immunohistochemistry, and 4 hours, 8 hours and 14 days for chemokine mRNA analysis. Leukocyte content was quantified utilizing immunohistochemistry (RPN357, monoclonal antibody (mAb) against rabbit neutrophil; RAM-11, mAb against rabbit macrophage). We analyzed the mRNA levels of the chemokines monocyte chemoattractant protein 1 (MCP-1) and interleukin 8 (IL-8) through semi-quantitative polymerase chain reaction. We demonstrated the spatial pattern of MCP-1 mRNA levels through in situ mRNA hybridization. In balloon-injured arteries, leukocyte recruitment was confined to early neutrophil infiltration. IL-8 and MCP-1 mRNA levels peaked within hours and were undetectable at 14 days. In contrast, in stented arteries, early neutrophil recruitment was followed by prolonged macrophage accumulation. IL-8 and MCP-1 mRNA levels peaked within hours but were still detectable 14 days post injury. CONCLUSIONS: In contrast to balloon injury, stent-induced injury results in sustained chemokine expression and leukocyte recruitment. These data may have important implications for antirestenotic strategies.

Angioplasty, Balloon↗
PubMed2002

Distal filter protection during saphenous vein graft stenting: technical and clinical correlates of efficacy.

OBJECTIVES: The aim of this study was to evaluate the clinical, angiographic, and technical factors related to successful stenting of diseased saphenous vein grafts (SVGs) using a novel filter-based distal protection device. BACKGROUND: Protection of the distal microvasculature with a balloon occlusion and aspiration system has been shown to reduce atherothrombotic embolization and peri-procedural myocardial infarction (MI) after percutaneous coronary intervention (PCI) in SVGs. The safety, efficacy, and technical factors relating to procedural success with filter-based distal protection devices are unknown. METHODS: Percutaneous coronary intervention was performed in 60 lesions in 48 patients undergoing SVG intervention with the FilterWire EX distal protection system in a phase I experience at six sites. A larger phase II study was then performed in 248 lesions in 230 SVGs at 65 U.S. centers. RESULTS: Cumulative adverse events to 30 days occurred in 21.3% of patients in phase I, including a 19.1% rate of MI. Numerous anatomic, device-specific, and operator-related contributors to these adverse events were identified, resulting in significant changes to the protocol and instructions for use. Subsequently, despite similar clinical and angiographic characteristics to the phase I patients, the 30-day adverse event rate in phase II was reduced to 11.3% (p = 0.09), due primarily to a lower incidence of peri-procedural Q-wave and non-Q-wave MI. CONCLUSIONS: Distal protection during SVG PCI with the FilterWire EX is associated with a low rate of peri-procedural adverse events compared to historical controls. A unique set of anatomic, technical, and operator-related issues exist with distal filters which, if ignored, may reduce their effectiveness.

Aged↗
PubMed2002

Inflammation and restenosis in the stent era.

The pathophysiology of restenosis involves early elements of direct injury to smooth muscle cells, deendothelialization, and thrombus deposition. Over time, this leads to smooth muscle cell proliferation/migration and extracellular matrix deposition. There is an increasing body of evidence to suggest that inflammation plays a pivotal role linking early vascular injury to the eventual consequence of neointimal growth and lumen compromise. The widespread use of coronary stents has fundamentally altered the vascular response to injury by causing a more intense and prolonged inflammatory state. Many of the cellular and molecular elements responsible for leukocyte recruitment have been elucidated, providing potential therapeutic targets for restenosis. This review seeks to provide an integrated view of the pathophysiology of restenosis that explains the central role of inflammation.

Animals↗
PubMed2002

Simvastatin reduces neointimal thickening in low-density lipoprotein receptor-deficient mice after experimental angioplasty without changing plasma lipids.

BACKGROUND: Statins exert antiinflammatory and antiproliferative actions independent of cholesterol lowering. To determine whether these actions might affect neointimal formation, we investigated the effect of simvastatin on the response to experimental angioplasty in LDL receptor-deficient (LDLR-/-) mice, a model of hypercholesterolemia in which changes in plasma lipids are not observed in response to simvastatin. METHODS AND RESULTS: Carotid artery dilation (2.5 atm) and complete endothelial denudation were performed in male C57BL/6J LDLR-/- mice treated with low-dose (2 mg/kg) or high-dose (20 mg/kg) simvastatin or vehicle subcutaneously 72 hours before and then daily after injury. After 7 and 28 days, intimal and medial sizes were measured and the intima to media area ratio (I:M) was calculated. Total plasma cholesterol and triglyceride levels were similar in simvastatin- and vehicle-treated mice. Intimal thickening and I:M were reduced significantly by low- and high-dose simvastatin compared with vehicle alone. Simvastatin treatment was associated with reduced cellular proliferation (BrdU), leukocyte accumulation (CD45), and platelet-derived growth factor-induced phosphorylation of the survival factor Akt and increased apoptosis after injury. CONCLUSIONS: Simvastatin modulates vascular repair after injury in the absence of lipid-lowering effects. Although the mechanisms are not yet established, additional research may lead to new understanding of the actions of statins and novel therapeutic interventions for preventing restenosis.

Angioplasty↗
PubMed2002

Targeting CCR2 or CD18 inhibits experimental in-stent restenosis in primates: inhibitory potential depends on type of injury and leukocytes targeted.

A central role for leukocytes in neointimal hyperplasia after arterial injury is suspected. However, the relative importance of neutrophils and monocytes in balloon or stent-induced injury are not well understood, and mechanistic targeting of leukocyte recruitment or function is crude. We determined the temporal and spatial distribution of different leukocytes after balloon and stent-induced injury in primate iliac arteries. Based on these data, we targeted neutrophil and monocyte recruitment selectively after angioplasty or stent implantation and demonstrated that monocyte-specific blockade achieved via blockade of the MCP-1 receptor CCR2, was effective at reducing neointimal hyperplasia after stenting. In contrast, combined neutrophil and monocyte blockade achieved by targeting the leukocyte beta(2)-integrin beta-subunit CD18 was required to reduce neointimal hyperplasia after balloon injury. Distinct patterns of leukocyte infiltration in balloon versus stent-injured arteries predict distinct mechanisms for antiinflammatory strategies targeting neutrophils or monocytes in primates and may assist design of effective clinical strategies for optimizing vascular interventions.

Animals↗
PubMed2001

Chronic Coronary Occlusions.

The goal of management of chronic coronary occlusions is primarily the relief of cardiac ischemic symptoms. This may be achieved through the use of medical therapy, recanalization by percutaneous endovascular intervention or coronary artery bypass grafting (CABG). Recanalization of the occluded vessel also may have the additional benefits of improved cardiac function and long-term survival.

Journal Article↗