Biomedical subjects

R K Strumpf

Publications and source records attributed to R K Strumpf.

16 recordsLinked to original sources

PubMed1996

Long-term gene transfer in porcine myocardium after coronary infusion of an adeno-associated virus vector.

BACKGROUND: Viral vector-mediated gene transfer into the heart represents a potentially powerful tool for studying both cardiac physiology as well as gene therapy of cardiac disease. We report here the use of a defective viral vector, which expresses no viral gene products, for gene transfer into the mammalian heart. Previous studies have used recombinant viral vectors, which retained viral genes and yielded mostly short-term expression, often with significant inflammation. METHODS: An adeno-associated virus vector was used that contains no viral genes and is completely free of contaminating helper viruses. The adeno-associated virus vector was applied to rat hearts by direct intramuscular injection; adeno-associated virus was also infused into pig hearts in vivo via percutaneous intraarterial infusion into the coronary vasculature using routine catheterization techniques. RESULTS: Gene transfer into rat heart yielded no apparent inflammation, and expression was observed for at least 2 months after injection. Infusion into pig circumflex coronary arteries resulted in successful transfer and expression of the reporter gene in cardiac myocytes without apparent toxicity or inflammation; gene expression was observed for at least 6 months after infusion. CONCLUSIONS: We report the use of adeno-associated virus vectors in the cardiovascular system as well as successful myocardial gene transfer after percutaneous coronary artery infusion of viral vectors in a large, clinically relevant mammalian model. These results suggest that safe and stable gene transfer can be achieved in the heart using standard outpatient cardiac catheterization techniques.

Animals↗

PubMed1995

Rotational atherectomy in restenotic lesions at the distal saphenous vein graft anastomosis.

Restenotic lesions at distal saphenous vein graft (SVG) anastomoses have been notoriously difficult to treat with standard angioplasty techniques. We explored the potential of rotational atherectomy in three patients with nonthrombotic, focal restenoses at the SVG touch down. The Rotablator safely and successfully recanalized the lesions, allowing further treatment with dilation or stenting or both. Rotational atherectomy may warrant investigation as a treatment for nonthrombotic restenotic SVG lesions.

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PubMed1993

New treatment approach for chronic total occlusions of saphenous vein grafts: thrombolysis and intravascular stents.

Balloon dilation of saphenous vein graft (SVG) occlusions has a lower success rate than angioplasty of native coronary arteries. To improve this outcome, a new therapy for chronic total SVG occlusions was developed. In three aortocoronary bypass graft patients with class III-IV angina and chronic occlusion of the SVGs to the left anterior descending artery (age of occlusions: 2-24 wk, age of graft 1-13 yr), standard recanalization was achieved with a guide wire and intracoronary urokinase infusion (0.5-1.0 million unit bolus followed by 100,000 IU/hr for 11-24 hr; mean infusion time: 19.7 hr). In each patient, a residual focal stenosis (average 82.5%) was successfully dilated and stented (single 4.0 mm Palmaz-Schatz in two patients and a 3.5 mm Strecker stent in the other). All patients had complete relief of symptoms and no sequelae. During a mean 7.7 mon follow-up, 6-mon arteriographic evaluation in two patients showed minimal intra-stent narrowing (26% and 34%). In the Strecker stent patient, the device proved too small for the vein graft, leading to an 89% stent stenosis found on follow-up arteriography at 5 mon. The stent was redilated successfully with a 5% residual narrowing. After urokinase recanalization of chronic total SVG occlusions, intravascular stents may improve the long-term results seen with conventional SVG angioplasty.

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PubMed1993

Angioscopy: a valuable tool in the deployment and evaluation of intracoronary stents.

Intracoronary stents were designed to improve balloon dilation results; however, to accomplish this, various criteria of optimal stent deployment must be met. Standard imaging techniques are neither sensitive nor specific enough for intraprocedural use in the verification of these implantation parameters. To assess the usefulness of angioscopy in the procedural and follow-up evaluations of Palmaz-Schatz and Strecker coronary stent deployment, 17 patients underwent angioscopy, 15 during stent placement and 2 during follow-up for stent restenosis. In the latter cases, thrombus formation was suspected; however, angioscopy showed tissue subtotally occluding the lumen without thrombus, so thrombolytic therapy was avoided. Similarly, among the 15 intraprocedural assessments, angioscopy disclosed intravascular thrombus unappreciated on angiography in two cases; another patient at high risk for intravascular thrombus was found not to have clot. In four patients, angioscopy disclosed residual narrowing in need of redilation at the Palmaz-Schatz stent articulation site. Thus in 9 (53%) of 17 stent patients, angioscopic findings either guided therapeutic selection or significantly modified the anticipated procedure. Angioscopy offers important information critical to the accurate placement and evaluation of intracoronary stents.

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PubMed1993

Use of the Doppler guide wire for intraluminal diagnosis to facilitate coronary intervention.

The FloWire Doppler flow guide wire has recently been approved for intracoronary application, joining angioscopy and intravascular ultrasonography as new methods for transluminal evaluation of coronary lesions. The 0.018-inch FloWire provides a high-fidelity continuous Doppler signal. Velocity measurements are continuously displayed on the FloMap monitor in a gray-scale spectral pattern, providing quantitation of an entire spectral distribution of flow velocities. This torquable, steerable guide wire can be used in small and distal branches of the coronary tree. We describe the clinical use of the FloWire Doppler guide wire in three patients who had coronary anatomic abnormalities that could not be assessed by other techniques. In each case the Doppler guide wire facilitated analysis of the physiologic significance of the coronary stenosis. The information gained was crucial in selecting safe and effective treatment for these patients.

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PubMed1993

Biaxial mechanical properties of passive and tetanized canine diaphragm.

The architecture, vascular supply, and ease of tetanization make the diaphragm an ideal structure in which to assess multidimensional mechanical properties of active and passive striated muscle. We developed an isolated, perfused canine diaphragm preparation suitable for the assessment of biaxial stress-strain relations in both the resting state and during tetanization. Each of 33 specimens had a wide, flat region (approximately 3 x 3 cm) wherein there was a single predominant fiber direction. Simultaneous, equal stretchings were imposed in the fiber and perpendicular cross-fiber directions over the same strain ranges in both the passive state and during tetanic contraction. Highly nonlinear behavior was seen in the passive state with a limit of extensibility in both directions. The specimens were also markedly anisotropic, with the cross-fiber direction being stiffer than the fiber direction (slopes of the regression line for the stresses in each direction averaged 3.97). Moreover, 31 of the 33 specimens were stiffer in the cross-fiber direction, one was isotropic, and one was stiffer in the fiber direction. During tetanization, the extent and distribution of anisotropy were significantly altered (regression slope averaged 1.08, and 18 specimens were now either isotropic or stiffer in the fiber direction). Disrupting the membranes covering each surface increased extensibility and decreased the anisotropy, thereby suggesting that these membranes bear most of the passive load and contribute greatly to the cross-fiber stiffness and anisotropy of the intact diaphragm. Both before and after disruption of the surface membranes, there was still a consistent increase in cross-fiber stress during tetanization, implying active force generation perpendicular to the fiber direction.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1992

Intracoronary stent implantation via the brachial approach: a technique to reduce vascular bleeding complications.

To reduce the incidence of vascular complications of intracoronary stent implantation, we used the brachial approach. We attempted implantation of the Palmaz-Schatz stent via the brachial artery approach at 10 lesions in 9 patients. Stent delivery was successful at 8 lesions. Balloon angioplasty was successfully performed in the 2 failed cases, 1 of whom required surgical repair of the brachial artery. Intravenous anticoagulation was uninterrupted from the time of stent placement until therapeutic prothrombin times from oral warfarin therapy were obtained. Neither acute nor long-term major bleeding occurred in the 9 patients. There were no embolic events, myocardial infarctions, or deaths. One subacute thrombosis occurred, and the patient underwent bypass surgery. To evaluate the risks and benefits of the brachial approach, we compared these 9 patients with 41 who had stent placement by the femoral approach during the same period. Lesion characteristics were similar in these 2 groups. There were no significant differences in the success rate or angiographic outcome between the 2 groups. Seven (17%) patients in the femoral group had vascular access complications requiring surgery, compared with 1 (11%) in the brachial group. No patient in the brachial group required transfusion, compared with all 7 of the patients who had femoral vascular complications. The potential reduction in bleeding complications makes the brachial approach to stent implantation attractive in selected patients.

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PubMed1992

ACS RX flow support catheter as a temporary stent for dissection or occlusion during balloon angioplasty: initial experience.

The ACS RX flow support catheter, which functions as a temporary stent, was placed successfully during four procedures in three patients who had suboptimal results following angioplasty. This investigational device allowed prolonged perfusion and supported the vessel wall when coronary blood flow was compromised, avoiding emergent coronary artery bypass graft surgery during two procedures. In the remaining procedures the device was used as a bridge to surgery. These early applications of the flow support catheter following failed balloon angioplasty suggest a rapid, effective alternative to the autoperfusion balloon when it fails or is contraindicated because of the lesion location.

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PubMed1992

Palmaz-Schatz stent implantation in stenosed saphenous vein grafts: clinical and angiographic follow-up.

Balloon-expandable stents may reduce the restenosis rate following coronary angioplasty. To evaluate this potential in saphenous vein grafts, 26 patients with 30 discrete stenoses underwent conventional balloon dilation and successful Palmaz-Schatz stent implantation as part of a multicenter trial. All patients had resolution of their angina following the procedure. In a mean 5-month follow-up period, 14 patients (54%, 16 lesions) had repeat arteriography; two patients (14%) developed recurrent ischemia ascribed to their venous grafts from in-stent restenosis (2 of 16 lesions, 13%). Two asymptomatic patients (8%) died: one from cardiac arrest (stent patent) and one from stroke (no autopsy). The clinical recurrence rate (cardiac death, myocardial infarction, bypass surgery, repeat angioplasty, or symptom recurrence) was 15%. These preliminary results show trends toward an improved primary success rate with combined vein graft angioplasty/stenting and a lower restenosis rate in stented saphenous vein grafts, but continuing follow-up will be needed to verify these observations.

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PubMed1992

A constitutive theory for biomembranes: application to epicardial mechanics.

We present a new theoretically motivated experimental approach for identifying the functional form of a constitutive relation for any nonlinear, anisotropic pseudoelastic biological membrane. The utility of this approach is illustrated by identifying, from biaxial data, a new constitutive relation for excised ventricular epicardium. Values of the associated material parameters are calculated and compared for right and left ventricular specimens. Based on our findings, we suggest that there are no significant differences in the biomechanical behavior of epicardium excised from the right and left ventricular free walls of canine hearts.

Animals↗

PubMed1990

Determination of a constitutive relation for passive myocardium: I. A new functional form.

The specific aim of this study is to determine a constitutive relation for non-contracting myocardium in terms of a pseudostrain-energy function W whose form is guided by both theory and experiment. We assume that the material symmetry of myocardium is initially and locally transversely-isotropic, and seek a W which depends upon only two coordinate invariant measures of the finite deformation. The specific functional form of such a W is inferred directly from experimental protocols in which one invariant is held constant while the other is varied, and vice versa. On the basis of data from families of these "constant invariant" tests on thin slabs of myocardium taken from the mid-walls of six canine left ventricles, we propose a new polynomial form of W containing only five material parameters.

Animals↗

PubMed1990

Determination of a constitutive relation for passive myocardium: II. Parameter estimation.

In the first paper of this series, we proposed a new transversely isotropic pseudostrain-energy function W for describing the biomechanical behavior of excised noncontracting myocardium. The specific functional form of W was inferred directly from biaxial data to be a polynomial function of two coordinate invariant measures of the finite deformation and five material parameters. In this paper, best-fit values of the material parameters are determined from biaxial data using a nonlinear least-squares regression. These values of the parameters are shown to be well-determined, and the final constitutive relation is shown to have good predictive capabilities. Since the proposed constitutive relation describes much broader classes of in-vitro biaxial data than previously proposed relations, it may be better applicable to analyses of stress in the passive heart.

Animals↗

PubMed1990

Biaxial mechanical behavior of excised ventricular epicardium.

We present results from in vitro biaxial stress-strain experiments on epicardium excised from the right and left ventricular free walls of canine hearts. These data reveal that the biomechanical behavior of ventricular epicardium is qualitatively similar to atrial epicardium and parietal pericardium but different from noncontracting myocardium. In particular, ventricular epicardium exhibits a highly nonlinear stress-stretch behavior, being initially compliant but then very stiff near the limits of its extensibility. In addition, the epicardium appears to be initially isotropic but becomes markedly anisotropic upon rapid stiffening. Finally, specimens taken from the right and left ventricular free walls behaved similarly. We submit that excised ventricular epicardium is capable of carrying significant in-plane loads and that there is a need to investigate further its role in local and global cardiac mechanics and physiology.

Animals↗

PubMed1989

A theoretically-based experimental approach for identifying vascular constitutive relations.

We employ a structurally-motivated phenomenological formulation to identify biomechanical experiments which can be used to determine a vascular constitutive relation directly from data. Large deformations, nonlinear material behavior, load-dependent anisotropy, material heterogeneity and incompressibility are accounted for in the analysis. For purposes of illustration, we outline a procedure for studying elastic arteries wherein the behavior of the media and adventitia is considered separately. This general approach for identifying vascular constitutive relations can be applied to any vessel or airway, however, and should provide certain advantages over previous microstructural or purely phenomenological formulations.

Arteries↗

PubMed1988

Structural three-dimensional constitutive law for the passive myocardium.

A three-dimensional constitutive law is proposed for the myocardium. Its formulation is based on a structural approach in which the total strain energy of the tissue is the sum of the strain energies of its constituents: the muscle fibers, the collagen fibers and the fluid matrix which embeds them. The ensuing material law expresses the specific structural and mechanical properties of the tissue, namely, the spatial orientation of the comprising fibers, their waviness in the unstressed state and their stress-strain behavior when stretched. Having assumed specific functional forms for the distribution of the fibers spatial orientation and waviness, the results of biaxial mechanical tests serve for the estimation of the material constants appearing in the constitutive equations. A very good fit is obtained between the measured and the calculated stresses, indicating the suitability of the proposed model for describing the mechanical behavior of the passive myocardium. Moreover, the results provide general conclusions concerning the structural basis for the tissue overall mechanical properties, the main of which is that the collagen matrix, though comprising a relatively small fraction of the whole tissue volume, is the dominant component accounting for its stiffness.

Animals↗

PubMed1987

Quantification of the mechanical properties of noncontracting canine myocardium under simultaneous biaxial loading.

Detailed understanding of cardiac mechanics depends upon accurate and complete characterization of the three-dimensional properties of both normal and diseased myocardial tissue. This, however, can only be obtained by performing multiaxial tests on cardiac tissue. In this study we subjected thin sheets of passive canine left ventricular myocardium to various combinations of simultaneous biaxial stretching. During each stretch the ratio of the orthogonal strains was kept constant and the corresponding stresses remained proportional. We fitted the biaxial stress-strain data both with exponential strain-energy functions with quadratic powers of strains as well as with an alternative function with nonintegral powers of strains. We used our recently developed nonparametric method to assess the reliability of the coefficients for each of these functions. The quadratic strain-energy functions resulted in wide intra- and interspecimen variability in the coefficients. Moreover, both their absolute and relative values demonstrated marked load history dependence such that interpretation of the direction of anisotropy was difficult. Fitting the data with the alternative nonintegral strain-energy function seemed to alleviate these problems. This alternative strain-energy function may provide more self-consistent results than the more commonly used quadratic strain-energy functions.

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