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Biomedical subjects

J Megerman

Publications and source records attributed to J Megerman.

At least 37 records · Page 2Linked to original sources

Correlation of continuous-wave Doppler spectral flow analysis with gross pathology in carotid stenosis.

Preoperative continuous-wave Doppler spectral analysis was used to generate two parameters, peak frequency in the internal carotid artery (fmax) and the ratio of peak frequencies in the internal and common carotid arteries (carotid index). These were compared with direct measurement of residual lumen diameter in pathologic specimens obtained from carotid endarterectomy in 37 patients. Doppler shift frequency parameters were well correlated with residual lumen diameter when the latter was at least 1 mm. Residual lumens of less than or equal to 2 mm were found to have an fmax of greater than 7.5 kHz and a carotid index of greater than 3.8. If fmax was greater than 14 kHz or the carotid index was greater than 7, the residual lumen diameter was nearly always less than or equal to 1 mm. Thus, the severity of the stenosis correlated directly with Doppler shift frequencies. The length of stenoses did not affect the correlations.

Arteriosclerosis↗

Prediction of aneurysm formation in vascular grafts of biologic origin.

Other than review of clinical experience, no assay exists that can reliably predict the long-term potential for aneurysm formation in an arterial prosthesis of biologic origin. Since mural degeneration probably results from proteolytic digestion, an in vitro assay was devised that used graft perfusion with 1% collagenase to induce rapid changes in mechanical properties. The effect of enzyme on graft diameter, compliance, permeability, and burst pressure was measured in ficin-digested, adipoyl chloride and glutaraldehyde-tanned bovine carotid artery and glutaraldehyde-tanned human umbilical vein. Both grafts have recently been reported to have a significant incidence of aneurysm within several years of implantation. Compliance and diameter were also measured noninvasively in patients with bovine carotid artery and human umbilical vein for more than 40 weeks after implantation. In vitro, the response to enzyme could be categorized into three groups. In group III, a diameter increase of more than 14% was associated with a significantly decreased compliance, and this paralleled the results found in aneurysmal grafts in vivo. In both grafts there was a strong correlation between postenzyme compliance change and initial compliance, loss of compliance being significantly greater in grafts with group III responses (p less than 0.01). This response may be a good predictor of a graft's overall susceptibility to aneurysmal degeneration, and initial compliance measurement may effectively identify inadequate fixation. Thus measurement of compliance may prove useful in quality control of a fixation process used in mass production. In conclusion, measurement of mechanical properties of biologic vascular grafts before and after collagenase exposure forms the basis for an effective in vitro assay of aneurysm susceptibility.

Aneurysm↗

Glutaraldehyde release from vascular prostheses of biologic origin.

The inhibition of growth by adult human venous endothelial cells in culture forms the basis of a sensitive assay of glutaraldehyde (GA) concentration, valid between 0 and 5 parts per million. This cytotoxicity assay was used to measure residual (unbound) GA in commercial vascular prostheses of biologic origin following manufacturer-recommended rinsing procedures, from which as much as 13.8 ppm GA per gram of tissue per 24 hours continued to be released after 1 month. A brief (1 hour) exposure of cultured endothelial cells to 2 ppm GA delayed growth, while continuous exposure to 4 ppm totally prevented growth for at least 12 days. Endothelial cells exposed to GA demonstrated a reduced efficiency of attachment to standard test surfaces, although prior GA treatment of these surfaces was not detrimental to subsequent cell attachment. GA release from vascular prostheses may contribute to their lack of endothelial cell coverage in human implants and may be indicative of collagen cross-link instability. If so, in vitro cytotoxicity may be helpful in identifying the potential for aneurysm formation in preserved biologic grafts.

Aldehydes↗

Immunosuppressive treatment of aortic allografts.

Immunosuppression with cyclosporine (CsA) was explored as a means of preventing arterial allograft rejection and failure. Aortic allografts across the major histocompatibility barrier were studied in Brown-Norway and Lewis inbred rats. Grafts 1 cm long were interposed into the infra-abdominal aorta of Lewis recipients; five groups included two groups of untreated isograft and allograft control animals and three groups had allograft-CsA treatment regimens. The grafts were examined at 30, 60, and 100 days for patency, aneurysmal dilation, gross structural changes, inflammatory responses, and infiltration of W3/25- and OX8-positive lymphocytes. Only three allograft controls became occluded; the rest showed significant dilation (p less than 0.01), medial thinning and necrosis, intimal proliferation, and prominent cellular infiltration at 30 days. With all CsA regimens, aneurysmal dilation was significantly reduced or prevented (p less than 0.01), correlating with medial smooth muscle cell preservation. Cellular infiltration was delayed by an average daily dose of 5 to 10 mg/kg subcutaneous CsA for 30 days and was suppressed at 100 days by a continuous 5 mg/kg dose every 4 days. Intimal thickening in the graft was delayed but not prevented. We conclude that a low maintenance dose of CsA provides effective immunosuppression, thereby preventing aneurysm formation, and that the potential use of arterial allografts in vascular surgery may need to be readdressed.

Animals↗

The evolution of morphologic and biomechanical changes in reversed and in-situ vein grafts.

A comparative study of experimental reversed (RV) and in-situ (INS) vein grafts with respect to the evolution of morphologic and compliance characteristics was done in a canine model. In addition, the compliance characteristics in a series of human INS vein grafts were recorded as a function of time after operation. At 6 months after implantation, all experimental grafts displayed well-developed intimal hyperplasia. There was no significant difference in either absolute intimal thickness (INS 0.133 +/- 0.09 mm vs. RV 0.085 +/- 0.06 mm; NS) nor in the percentage of the total wall thickness occupied by the intima when experimental INS grafts were compared with RV grafts after 6 months. Similarly, compliance values of INS and RV vein grafts were similar at all time intervals examined up to 6 months after operation. Thirty-three human INS vein grafts had a mean compliance value of 1.74 +/- 0.72 (percent radial changes per mmHg X 10(-2) at a median postoperative interval of 14 weeks. This value did not differ significantly from those measured in the INS vein grafts. Although all vein grafts examined retained their native viscoelastic properties, this study suggests that functioning human INS vein grafts are less compliant than previously suspected on the basis of prior ex-vivo and clinical studies of RV saphenous vein grafts. The purported clinical superiority of the INS vein graft cannot be explained on the basis of superior biomechanical performance or failure to develop intimal hyperplasia.

Animals↗

Continuous monitoring of oxygen tension with a transcutaneous sensor during hypotensive anesthesia.

Transcutaneous oxygen tension (TCPO2) is a useful noninvasive technique for monitoring arterial oxygen tension under stable circulatory conditions. This study was undertaken to determine if TCPO2 is also reliable during sodium nitroprusside-induced hypotension under general anesthesia. Arterial blood gases and TCPO2 were measured prior to inducing hypotension (baseline), at 20-min intervals during hypotension, and when systemic arterial pressure had returned to within 10% of the control (pre-hypotension) value. With induced hypotension, PaO2 and TCPO2 decreased significantly (P less than 0.05), and were well correlated by linear regression (r greater than 0.85); however, regressions were strongly dependent on the individual patient. The mean regression line for all patients as a group was given by TCPO2 = 0.69 PaO2 + 20.7 mmHg (r = 0.93, P less than 0.01); significantly different regressions were obtained for each patient (P less than 0.0001). Comparing changes in TCPO2 versus those in PaO2 (relative change from baseline values) did not substantially reduce the variability among patients. It is concluded that TCPO2 reliably reflects changes in arterial oxygen tension during controlled hypotension under general anesthesia, but that a separate calibration of TCPO2 vs. PaO2, obtained prior to inducing hypotension, may be required for each individual patient.

Adult↗

Effect of compliance mismatch on vascular graft patency.

The hypothesis that a mismatch in compliance between a vascular graft and its host artery is detrimental to graft patency was tested by implanting paired arterial autografts, prepared with differential glutaraldehyde fixation of carotid arteries in the femoral arteries of dogs. These grafts differed only in circumferential compliance: they were 100% (compliant) vs. 40% (stiff) as compliant as the host artery. Their flow surfaces were equivalent, as determined by physicochemical measurements and scanning electron microscopy; both lacked viable cells, as determined by in vitro cell culture. In 14 dogs, eight stiff and two compliant grafts became occluded within 3 months, the latter doing so within 24 hours after their contralateral counterparts. Cumulative patencies were 85% and 37% for compliant and stiff grafts, respectively (p less than 0.05) and 100% and 43%, excluding the two dogs with bilateral graft failures (p less than 0.01). We conclude that even with near optimal flow surfaces, compliance mismatch is deleterious to graft patency.

Animals↗

Compliance changes in glutaraldehyde-treated arteries.

Glutaraldehyde tanning of carotid arteries was used to develop a model for studying the effects of compliance on arterial graft performance, independent of other graft parameters. Canine carotid segments were filled with dilute phosphate-buffered glutaraldehyde (0-0.5%, pH 7.4), maintained at physiological pressure, and then immersed in either saline or 10.0% glutaraldehyde for up to 1 hr. After rinsing with saline, compliance was measured in vitro. All vessels which were immersed in 10% glutaraldehyde exhibited a significant reduction in compliance compared to native artery control [C = 11.8 +/- 1.3 (mean +/- SEM), % radial change/mm Hg X 10(-2), measured at 100 mm Hg], but maximum stiffness (C = 1.1 +/- 0.3) required that the lumen be specifically exposed to at least 0.025% glutaraldehyde in addition to simple immersion of the vessel segment in 10% fixative. Exposing the artery to 0.5% glutaraldehyde internally, without immersion of the entire structure, caused a decrease in compliance similar to that obtained after immersion in 10% glutaraldehyde, with only saline present in the lumen. Matched pairs of stiff and compliant grafts were generated by exposing the lumen to 0.025% glutaraldehyde and immersing the vessels in 10% fixative or saline, respectively. Light and scanning electron microscopy, internal reflection spectroscopy, and measurements of critical surface tension revealed nearly identical wall morphology and lumenal surface chemistry for these matched pairs. Differential tanning of the internal and external surfaces of carotid arteries thus provides a good model of arterial prostheses, wherein a substantial compliance mismatch can be studied without the complicating influences of varying diameter or differing flow surface properties.

Aldehydes↗

Suture technique and para-anastomotic compliance.

We previously described a para-anastomotic hypercompliant zone (PHZ), located 3 to 4 mm from end-to-end continuous anastomoses in canine femoral arteries, in which arterial compliance first increases approximately 50% above adjacent reference values before falling to a minimum at the anastomosis. To determine if PHZ is affected by suture technique, 16 interrupted and 21 continuous end-to-end anastomoses were studied. Pulsed ultrasound was used to obtain detailed longitudinal profiles of compliance and diameter vs. distance, at 1 mm intervals within a 2 cm region centered at the anastomoses. Both compliance and diameter at the anastomosis were lower in continuous compared with interrupted anastomoses (p less than 0.003). The PHZ was present in 86% of continuous but in only 50% of interrupted anastomoses (p less than 0.03). The site of peak compliance averaged 3.8 +/- 1.2 mm from the anastomosis and was independent of suture technique. The increase in peak compliance at the PHZ, when normalized to adjacent references values, was the same in continuous and interrupted anastomoses. PHZ augments any preexisting compliance mismatch between artery and graft, which may contribute to the development of para-anastomotic subintimal hyperplasia. Interrupted anastomoses, which create a smaller compliance mismatch than do continuous and have a lower incidence of PHZ, may be preferred in certain settings.

Animals↗

Noninvasive measurements of nonlinear arterial elasticity.

To describe fully the compliance characteristics of an artery with nonlinear elastic properties, measurements must be obtained over a wide range of pressures. Furthermore, repeated measurements, as required in temporal studies of arterial implants, require that the measuring technique be noninvasive. The application of a pulsed ultrasound echo-tracking device is described, which fulfills both criteria. Nonlinear compliance-pressure (CP) curves were obtained from the femoral arteries of dogs, with the use of halothane anesthesia to vary systemic pressure, and were used to compare the gross elastic properties of different vessels. Studies using controlled hemorrhage or the vasoactive drugs, nitroprusside and levarterenol (norepinephrine), were used to verify that the CP curves obtained during halothane anesthesia did not reflect varying degrees of smooth muscle activation. However, surgical exposure did temporarily reduce arterial compliance at pressures between 60 and 140 mmHg. The effect of vasoactive intervention and of postsurgical changes in arterial or graft compliance can thus be quantitated by use of CP curves or by comparing incremental elastic moduli, which can also be estimated from the noninvasively derived measurements.

Animals↗

Endothelial preservation in reversed and in situ autogenous vein grafts. A quantitative experimental study.

The hypothesis that superior endothelial preservation occurs when in situ (as opposed to harvested and reversed) autogenous veins are used as arterial grafts was investigated in a canine model by quantitating endothelial loss as seen on scanning electron micrographs. In situ grafts were compared to atraumatically dissected, nondistended, reversed grafts and to grafts distended to 500 mmHg pressure. Two hours after arterial transplantation, endothelial denudation averaged 3.9 +/- 6.7% on in situ grafts, 18.6 +/- 5.9% on reversed grafts (p less than 0.01), and 35.3 +/- 5.4% on reversed and distended grafts (p less than 0.001). At 24 hours after grafting, a significant increase (p less than 0.01) in endothelial destruction on in situ grafts resulted in a smaller, yet still significant difference in endothelial preservation between in situ and reversed grafts (15.2 +/- 9.5% vs. 25.1 +/- 23.4%, p less than 0.05). Endothelial healing was largely accomplished at 2 weeks regardless of technique. No difference in endothelial fibrinolytic activity could be detected between in situ and gently handled, reversed grafts at 24 hours or 6 weeks after surgery. An obligatory, although modest, degree of endothelial destruction occurred on the undissected portion of in situ grafts as a consequence of exposure to arterial hemodynamics. However, in the immediate postoperative period, endothelial preservation on in situ grafts surpassed that seen in even the most gently handled reversed vein grafts.

Animals↗

Increased compliance near vascular anastomoses.

Mismatch in mechanical properties (compliance mismatch) between host artery and prosthetic graft has been suggested as a cause of graft failure, but no mechanism linking the two has been identified. With the use of a simplified model based on isocompliant arterial grafts, pulsed ultrasound was used to generate detailed longitudinal profiles of diameter and compliance near the anastomoses. These longitudinal profiles revealed that although arterial diameter decreases monotonically to a minimal level at an anastomosis, arterial compliance first increases by approximately 50% before decreasing to 60% of the control value. This para-anastomotic hypercompliant zone (PHZ) is centered 3.6 mm from the anastomosis. PHZ also occurs in the artery adjacent to compliant or stiff grafts and is probably caused by transmitted effects of the suture line on the arterial wall. PHZ adds to any mismatch in compliance that already exists between artery and graft and can produce a compliance mismatch even between an artery and a nominally isocompliant prosthetic graft. It is hypothesized that PHZ, a region of increased cyclic stretch, promotes subintimal hyperplasia near anastomoses and may thus be a link between the mechanical properties of arteries and the failure of bypass grafts.

Animals↗

Postsurgical changes in arterial compliance.

Mismatch in elasticity between artery and graft, a possible contributing factor to graft failure, has traditionally been believed to be caused by the graft. Compliance of the artery and/or graft may change after surgery, resulting in a different compliance mismatch. To study the arterial contribution to compliance mismatch, we measured compliance-pressure (CP) curves noninvasively in the femoral arteries of five dogs. One femoral artery was then simply exposed, and the incision was closed. Repeated CP curves were obtained after 24 hours, and after 1, 2, 3, and 4 weeks. Compliance remained normal after 24 hours, but by one week compliance of the dissected arteries had dropped significantly at all pressures between 70 and 120 mm Hg. Compliance reached a minimum after two weeks and remained low until after four weeks. Postsurgical arterial stiffening causes a significant decrease of arterial-graft compliance mismatch and may suggest an upper limit for synthetic graft compliance.

Animals↗

Transcutaneous oxygen tension in selection of amputation level.

The utility of transcutaneous oxygen tension measurements in selection of a reliable amputation level was evaluated. Measurements were made at the proposed level of amputation in 37 patients, 22 of whom underwent major limb amputation and in 15 amputation was confined to the forefoot or toes. In patients with successful amputation healing, mean transcutaneous oxygen tension on the anterior skin surface was 50 +/- 8 mm Hg (index 0.79 +/- 0.1 mm Hg). In contrast, patients with failure of healing had a mean transcutaneous oxygen tension of 22 +/- 16 mm Hg (index 0.32 +/- 0.19 mm Hg) (p less than 0.001). Measurements on the posterior or plantar skin surface and posteroanterior differences provided even greater separation between success and failure groups, with no overlap of transcutaneous oxygen tension values or index. Transcutaneous oxygen tension measurement is easily obtained and noninvasive, and can be applied to all patients irrespective of Doppler signals, noncompressible vessels, or painful lesions. Transcutaneous oxygen tension appears to predict successful healing with accuracy, and should be a useful addition to clinical judgment in selection of optimal amputation level.

Adult↗

Utility of transcutaneous oxygen tension measurements in peripheral arterial occlusive disease.

The use of transcutaneous oxygen tension (TCpO2) measurements to objectively and noninvasively diagnose peripheral arterial occlusive disease (PAOD) and to aid in the planning of vascular surgery was investigated. Thirty-two normal subjects and 100 patients with PAOD were studied. TCpO2 values decreased with age; when normalized by measurements on the chest, they did not. Absolute and normalized values of TCpO2 were equally effective in identifying the presence of PAOD and accurately characterized different degrees of severity (claudication vs. rest pain vs. impending gangrene; p less than 0.001). This was true even in diabetic patients, in whom tests based on hemodynamic function were less reliable. Healing of amputations was observed when TCpO2 greater than or equal to 38 mm Hg either preoperatively or after reconstruction; failure to heal in the absence of infection was associated with TCpO2 less than or equal to 38 mm Hg. The need for revascularization was associated with TCpO2 less than 30 mm Hg. A similar distribution of TCpO2 values was associated with success vs. failure of ulcer healing. TCpO2 is a useful complement to standard hemodynamic tests in the diagnosis and management of PAOD and, in addition, provides some distinct advantages.

Adult↗

Noninvasive intraoperative assessment of arterial reconstruction. Experimental validation of the role of central and regional hemodynamics.

We developed an experimental model of graded arterial stenosis to emulate conditions that might be encountered immediately following arterial grafting. Noninvasive measurements of systolic BP and limb blood flow were recorded with a Doppler probe and segmental air plethysmography, respectively, under conditions of different cardiac output and local arterial resistance. These measurements were correlated with direct intra-arterial pressure recordings and flow measurements taken with an electromagnetic flowmeter. There was an excellent correlation between noninvasive and intra-arterial measurements of systolic pressure over a range of cardiac outputs and degree of arterial stenosis. Pulse volume recordings correlated with direct measurements of blood flow at high and baseline cardiac outputs, but the calibration of pulse volume amplitude varied between cuff applications in this canine model. Noninvasive intraoperative monitoring techniques can faithfully represent known physiologic responses to graded arterial stenoses, irrespective of a high cardiac output or peripheral vasodilation.

Animals↗

Imaging vascular grafts in vivo with Indium-111-labeled platelets. Influence of timing on image interpretation.

Platelets labeled with Indium-111 were used to visualize polytetrafluoroethylene (PTFE) bypass grafts in vivo and to quantitate platelet deposition vs. time. The grafts were inserted into the femoral and carotid arteries of dogs and were first exposed to unlabeled blood for 0 to 3 hours. They were then imaged for up to 5 days. An index of activity, designed to correct for isotope decay and changing levels of background, was used to quantitate platelet deposition. Grafts exposed to unlabeled blood for, at most, 1 hour were visible immediately. When labeled platelets were administered to the circulation after at least 2 hours, grafts became visible only after 3 days. Continuous imaging of fresh implants, showing that platelet deposition does not increase monotonically with time, was used to explain this phenomenon. The interpretation of nuclear images of synthetic grafts depends on the delay between establishing flow in the grafts and the administration of labeled platelets.

Animals↗