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Biomedical subjects

D G Silverman

Publications and source records attributed to D G Silverman.

At least 91 records · Page 5Linked to original sources

Doppler ultrasound, laser Doppler, and perfusion fluorometry in bowel ischemia.

Improved accuracy and objectivity in the evaluation of intestinal viability has been reported by some investigators using Doppler ultrasound, and more recently laser Doppler velocimetry and perfusion fluorometry. To compare the sensitivity and clinical applicability of these techniques, intestinal viability was evaluated by each method in nine 15- to 50-cm loops of small bowel prepared by division of the mesenteric vasculature in five anesthetized dogs. The sensitivity of Doppler ultrasound was 86%, of laser Doppler flow velocity 85%, of laser Doppler index 94%, and of perfusion fluorometry 95%. Though the sensitivity of Doppler ultrasound is significantly less than that of laser Doppler and perfusion fluorometry, this is not unexpected since the latter two techniques are more quantitative than Doppler ultrasound. Clinically, Doppler ultrasound compares favorably with laser Doppler and perfusion fluorometry, and its low cost and simplicity suggest its adjunctive use in the operative setting.

Animals↗

Fluorescence assessment of skin perfusion after oral fluorescein.

This study evaluated oral ingestion as the route of fluorescein administration for fluorescence assessment of skin perfusion. In 10 anesthetized rats, dorsal pedicle flaps were raised to produce graded perfusion; then fluorescein (7.5 mg/kg) was administered via an oropharyngeal tube. Quantification of skin fluorescence, performed with the fiberoptic fluorometer 45 minutes after dye ingestion, delineated a significant difference between the perfusion of flap regions that remained viable and those that subsequently became dystrophic (p less than 0.05). The precision was equivalent to that previously reported after intravenous dye. In addition, the gradual delivery of dye after oral administration permitted monitoring of slope of uptake and time to peak. Each of these pharmacokinetic parameters delineated a significant difference between viable and nonviable sections. As measures of relative change in fluorescence, they are independent of skin color and thickness. This feature suggests that the oral route actually may improve the accuracy and reliability of the fluorescein test.

Administration, Oral↗

Fluorometric documentation of increased cutaneous blood flow after topical application of a PGE2 analog in man.

The present study employed fiberoptic fluorometry, a noninvasive means of documenting delivery and removal of fluorescein dye, to evaluate the local circulatory changes elicited by topical application of DHV-PGE2 ME, an investigational PGE2 analog. On Day 1, inactive vehicle was applied to a 5 X 4 cm study site on each thigh of healthy volunteer subjects (n = 12). Symmetrical perfusion was confirmed by similar determinations of dye delivery and removal at each site. On Day 2, DHV-PGE2 ME, 30 or 120 micrograms, was applied to one site while inactive vehicle again was applied to the other. After administration of 120 micrograms in a petrolatum vehicle, fluorometry detected a pronounced increase in nutritive perfusion. There was significant acceleration of dye delivery and removal (p less than 0.05 by ANOVA). Less pronounced changes were noted after the lower dose of DHV-PGE2 ME and when the drug was applied in a triethyl citrate vehicle. The local circulatory changes were not accompanied by systemic effects; there were no changes in vital signs or in fluorometric indices at remote sites.

Adolescent↗

Beneficial effects of ibuprofen on experimental microvascular free flaps: pharmacologic alteration of the no-reflow phenomenon.

Pharmacologic alteration of the no-reflow phenomenon was determined based on increased tolerance to ischemia in ibuprofen-treated free flaps. Sprague-Dawley rats (N = 60) were divided into control (lactated Ringer's) and treated (ibuprofen) groups and subdivided into six groups of ischemia: 1 hour, 6 hours, 8 hours, 10 hours, 12 hours, and 14 hours of ischemia. Fluorescein uptake was measured after 10, 30, and 60 minutes following microrevascularization. Dye elimination studies were done for each ischemia group that demonstrated good fluorescein uptake. All free flaps in the 1-, 6-, and 8-hour groups survived. The ibuprofen-treated 10- and 12-hour flaps all survived, whereas the 10-hour control and 14-hour ibuprofen-treated free flaps failed to survive. Despite high fluorescein uptake, the 14-hour ibuprofen-treated flaps did not eliminate the fluorescein, whereas all surviving free flaps adequately eliminated the fluorescein. Failure to eliminate dye despite adequate uptake suggested a deranged microcirculation with increasing ischemia time. By inhibiting cyclo-oxygenase, nonsteroidal anti-inflammatory agents such as ibuprofen may block the untoward effects mediated by thromboxane A2, such as vasoconstriction, microvasculature thrombus formation, and intravascular sludging. These effects are theorized in part to be responsible for the failure of a free flap to survive despite revascularization.

Animals↗

Fluorometric quantification of low-dose fluorescein delivery to predict amputation site healing.

This retrospective study evaluated quantification of skin fluorescein delivery by fiberoptic fluorometry as a means of predicting the healing potential of an amputation site. Fluorometry uses a dual-channel fiberoptic light guide--one channel transmits blue light to excite the fluorescein in the skin under study, and the other transmits emitted fluorescence from the skin to a photomultiplier tube where it is measured. Ten minutes after intravenous administration of sodium fluorescein (4 to 8 mg/kg), fluorometric readings were obtained at more than 100 reading sites. In the 86 cases without preoperative cellulitis at the site of amputation, preoperative fluorometry clearly distinguished between healing and nonhealing sites. Healing sites averaged 79% of the fluorescence of a healthy reference area (dye fluorescence index [DFI] = 79), while failing sites averaged only 27% (p less than 0.01 by ANOVA). In all but one case where the DFI was greater than 42, the amputation healed. In all cases where the DFI was less than 38, the amputation failed. In general, uncertainty was limited to sites with values between these limits. The technique maintained its high accuracy in patients with diabetes and for distal amputations. However, it was not accurate at sites of active cellulitis (12 cases). There were no significant adverse effects from the slow injection of the low dose of fluorescein used for this technique. We conclude that fluorometry is an effective means of predicting healing in patients undergoing amputation.

Amputation, Surgical↗

Intravenous nitroglycerin as a means of improving ischemic tissue hemodynamics and survival.

The effects of intravenous nitroglycerin infusion on experimental skin flap survival and fluorescein dye kinetics were studied in animals. Perfusion fluorometry was utilized to examine changes in flap hemodynamics and viability. An improvement in skin flap survival was found in the nitroglycerin-infused animals, whether the nitroglycerin was initiated 30 minutes before or 30 minutes after flap elevation. Dye elimination in the flap appeared to be significantly improved with the drug therapy, indicating an improvement in flap blood flow with nitroglycerin.

Animals↗

Fluorescein elimination as a measure of island flap perfusion.

The fluorescein test has been used as a means of assessing flap viability for almost 40 years. This study was performed in an attempt to determine if recording of the elimination of dye--combined with dye uptake measurement--could provide reliable and consistent monitoring of island flap perfusion.

Animals↗

Comparative assessment of blood flow to canine island flaps.

Fluorometric quantification of dye delivery, laser Doppler flowmetry, and transcutaneous measurement of tissue oxygen level were evaluated in canine island flaps subjected to vascular occlusion. Each technique readily identified the clamping insult. Relative fluorescein delivery to the flap (compared with a reference area) decreased from 66% before clamping to almost zero during clamping. Laser Doppler readings rapidly declined from an average of 230 to an average of 31 mV. Oxygen readings rapidly declined from 57 to 1 mm Hg. Laser Doppler flowmetry and transcutaneous oxygen monitoring seem best suited for continuous monitoring of trends at a single site. Fluorometry is more precise and can be used to monitor multiple sites. One should weigh the benefits of this technique against the need for dye injection.

Animals↗

Ischemic induction of neovascularization: a study by fluorometric analysis.

The dynamic process of skin flap neovascularization can be quantitated in a relatively non-invasive fashion in an "in-vivo" model using the technique of perfusion fluorometry. The extent of skin flap ischemia can be monitored, and its effect on angiogenesis rapidly determined. Evidence is presented that indicates that angiogenesis develops from a distal to proximal direction corresponding to the degree of ischemia as measured by fluorescein uptake and elimination. Furthermore, although certain proximal segments of skin flaps demonstrated no uptake or elimination, survival could still occur, indicating that neovascularization need not be complete at the time of pedicle interruption.

Animals↗

A new technique for evaluating cutaneous vascularity in complicated conjoined twins.

Ischiopagus tripus conjoined twins were recently encountered. All organ systems were thoroughly evaluated using radiographic, angiographic, radionuclide, and CT imaging techniques. None of these studies were capable of accurately assessing the vascular territories of the skin at the level of the pelvis, the most critical area in terms of separation. Qualitative visual assessment of tissue fluorescein delivery under ultraviolet illumination is subject to subjective errors. Perfusion fluorometry is a recently developed technique whereby tissue fluorescence can be quantitated over time in very small amounts, even with repeated injections. In these conjoined twins, using sequential fluorescein injections in each twin, it was possible to accurately determine which portions of the pelvis and the shared leg belonged to which twin and exactly where the skin incisions should be made. Additionally, during operation it was possible to accurately predict the viability of skin flaps used for closure. Both twins survived. This is the first time it has been possible to accurately assess vascular territories of the skin in a complicated form of conjoined twinning. The technique is also useful in the evaluation of flow patterns in various other parts of the body.

Aortography↗

Fluorometric prediction of successful amputation level in the ischemic limb.

The present study was undertaken to compare fluorometric documentation of fluorescein dye delivery with the standard means of determining the level at which an amputation should be performed in the dysvascular extremity. Thirty-nine patients underwent lower-extremity amputation at the level determined by the surgeon based upon physical examination, angiography, segmental pressure indices, and/or pulse volume recordings. In addition, fiberoptic fluorometry was performed preoperatively. After intravenous administration of sodium fluorescein (4-8 mg/kg), fluorometric readings were obtained by placing the fluorometer's light guide on 126 reading sites. Fluorometric findings were evaluated retrospectively, and therefore did not influence the surgeon's decision. Of the 39 amputations performed overall, only 26 healed. The accuracy of the standard criteria was lowest for the 20 below-ankle amputations, where only 12 cases healed. Alternatively, fluorometric indices separated healing from nonhealing sites in 36 of the 39 cases and in 18 of the 20 below-ankle amputations. Overall, healing sites averaged 94 percent of the fluorescence of the healthy reference area, while nonhealing sites averaged only 29 percent. We conclude that fluorometry should prove to be a valuable adjunct in the assessment of the dysvascular extremity. It uses a low dose of dye, is easy to perform, and is readily repeatable.

Amputation, Surgical↗

Serial fluorometric documentation of fluorescein dye delivery.

Since its introduction in 1980, fiberoptic fluorometry has improved the precision and objectivity of the fluorescein test as a means to delineate nutritive blood flow and predict tissue viability. This study was undertaken primarily to determine if fiberoptic fluorometry could be repeated reliably at close time intervals. Four injections of fluorescein dye were administered at varying dose and time schedules to determine what factors influenced the repeatability of this technique. The results confirm the high accuracy of fluorometric indices as a means to predict the ultimate fate of a skin flap. A method of scanning the flap within 2 minutes after injection of 1.5 mg/kg of fluorescein dye correctly predicted the fate of almost 100% of flap sections. Repeated injections of 1.5, 3.0, and 6.0 mg/kg of dye at 15-minute intervals provided virtually identical predictions of flap viability. Thus fluorometry is readily repeatable and should be of value in assessing the state of tissue perfusion as well as changes in perfusion caused by pharmacologic manipulation or surgical intervention.

Animals↗

Assessment of delay in bilateral thoracoabdominal island flaps in the rat.

This study demonstrates improved perfusion and viability following surgical delay in a bilateral paired flap model that minimizes the effects of systemic variables in the rat. Surgical delay was achieved in one of two paired thoracoabdominal island flaps by ligating and cutting the inferior epigastric (distal) pedicle three days before flap construction. This created a hypoperfused zone. Within three days of delay, perfusion of the delayed region, as documented by quantification of tissue fluorescein delivery, increased markedly and often exceeded nondelayed values. Construction of 2 X 11-cm island flaps based on the superior epigastric pedicle at this time was associated with an average of 1.1-cm necrosis, compared with 2.6 cm in nondelayed flaps.

Abdomen↗

Qualitative and quantitative fluorescein fluorescence in determining intestinal viability.

Clinical evaluation and qualitative (visual) and quantitative (fluorometric) fluorescence for predicting intestinal viability were compared in an animal model of temporary arterial occlusion with early revascularization. Quantitative fluorescence was determined with a perfusion fluorometer after an intravenous bolus of fluorescein. Qualitative fluorescence was determined by examination under a Wood's lamp in a darkened room. The effectiveness of each diagnostic technique in determining nonviability was expressed in terms of sensitivity, specificity, and accuracy. All three methods had 100 percent specificity; only bowel deemed nonviable proved to be so. Quantitative fluorescence also had a 100 percent sensitivity, but clinical evaluation and qualitative fluorescence had only a 33 and 11 percent sensitivity, respectively (some segments of bowel that were ultimately nonviable were not correctly predicted to be so). The inaccuracy of qualitative fluorescence was due to the fact that ischemic intestine with a hyperfluorescent pattern often progressed to necrosis. Fluorometric quantitation identified those hyperfluorescent segments that were viable. This study suggests that visual fluorescence is not reliable in assessing intestinal viability after early revascularization after arterial occlusion, but quantitative fluorometric fluorescence is reliable in almost all instances.

Animals↗

Assessment of neovascularization and timing of flap division.

These studies were undertaken to determine if perfusion fluorometry can provide an accurate, reliable means of monitoring neovascularization and predicting optimal time of flap division. An animal model was developed that permitted daily assessment of neovascularization of the flap using fluorescein injections and the fluorometer. An increase in fluorescence of the pedicle-occluded flap of approximately 12 percent the normal skin fluorescence was associated with 100 percent flap survival. This occurred after only 4 days in the rat. Fluorometry proved valuable in the evaluation of clinical flaps. The fluorescence of flaps during pedicle occlusion was observed to increase with each successive fluorometric evaluation performed at 3- to 7-day intervals. It appears that flaps after pedicle occlusion exhibiting at least 25 percent of the fluorescence of normal skin will tolerate pedicle division. Based on the neovascularization studies of the clinical flaps, all pedicles were severed earlier than originally anticipated. Two cross-leg flaps were successfully divided after 11 days. Quantitative assessment of serial fluorescein injections allows reliable evaluation of neovascularization in clinical interpolation flaps and is useful in the timing of flap division.

Animals↗

Vascular island skin-flap tolerance to warm ischemia: an analysis by perfusion fluorometry.

Fiberoptic perfusion fluorometry and assessment of ultimate viability were used to analyze the tolerance to warm ischemia of rat vascular island skin flaps. Both acute flaps and flaps raised 24 hours previously and then reraised were subjected to 0 (control), 6, 8, 10, and 12 hours of vascular pedicle clamping. Following clamp release, serial fluorometry documented the progressive delay in effective reflow resulting from extended periods of ischemia. Fluorometry, furthermore , suggested that flaps constructed 24 hours previously had an improved hemodynamic status with a significantly reduced period of poor reflow following clamp release. The improved hemodynamics were associated with increased viability, confirming the increased tolerance of 24-hour-old flaps to warm ischemia.

Animals↗

Serial fluorometric assessment of experimental neurovascular island flaps.

Quantification of tissue sodium fluorescein delivery was used to monitor neurovascular island flaps subjected to various manipulations of the vascular pedicle. In 20 anesthetized rats, inferior epigastric neurovascular island flaps were studied during transient arterial or venous occlusion and presumed vascular spasm. During clamping, there was no substantial fluorescein uptake by the flaps. Reinjection of fluorescein after removal of the clamps resulted in adequate fluorescein uptake and elimination in those flaps that remained viable. Three of the flaps with presumed vascular spasm eventually evidenced an increase in fluorescence with subsequent injections and remained viable; one flap did not show adequate fluorescence after any of the four injections and subsequently necrosed. It is concluded that documentation of tissue fluorescein delivery following serial injections of dye permits accurate monitoring of the functional status of the vascular pedicle at close-time intervals during the critical hours immediately after flap construction.

Animals↗