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Biomedical subjects

M C Dalsing

Publications and source records attributed to M C Dalsing.

At least 19 recordsLinked to original sources

Shear level influences resistance artery remodeling: wall dimensions, cell density, and eNOS expression.

The magnitude of shear stimulus has been shown to determine the level of growth factor expression in cell culture. However, little is known regarding what effect shear level has on specific arterial wall remodeling events in vivo. We have hypothesized that the rate of luminal diameter change and specific remodeling events within the arterial wall layers are dependent on shear level. Selective ligations were made to alter the number of microvascular perfusion units of mesenteric arteries within the same animal to approximately 50%, 200%, and 400% of control. Arterial blood flow and wall shear rate were correlated with the degree of alteration in perfusion units. Luminal diameters were decreased in 50% arteries by day 2 and increased approximately 17% and 33% respectively, in 200% and 400% arteries at day 7. The rate of diameter change was greatest in 50% and 400% arteries. Wall areas (medial +37%; intimal +18% at day 2) and cell densities (intimal +26%; adventitial +44% at day 2) were altered only in the 400% arteries. A positive correlation existed by day 2 between endothelial staining for endothelial nitric oxide synthase and shear level. The results demonstrate that shear level influences the rate of luminal expansion, specific remodeling events within each wall layer, and the degree of endothelial gene expression. A greater understanding of how shear level influences specific remodeling events within each wall layer should aid in the development of targeted therapies to manipulate the remodeling process in health and disease.

Animals↗

Primary aortic mural thrombus: presentation and treatment.

The clinical presentation of patients with acute lower-limb ischemia and primary aortic thrombus prompted this review. Following recognition of the first case in early 1994, relevant patients (n = 6) were kept in a database and were reviewed for presentation, treatment, and follow-up. The median age was 41 and five patients were male. Angiography, computed tomography, and/or magnetic resonance angiography demonstrated one or more aortic sessile or pedunculated thrombus(i) without associated atherosclerotic disease. In two cases, a retropancreatic intraaortic mural thrombus was associated with severe pancreatitis. All other cases presented with acute lower-limb emboli requiring limb salvage embolectomy. Because of significant patient illness, systemic anticoagulation was chosen acutely to prevent recurrent emboli. Interestingly, serial studies demonstrated aortic thrombus resolution. Failure to continue warfarin therapy resulted in recurrent problems (n = 1) unless the instigating event had resolved (n = 3). There were no deaths or amputations. We concluded that surgical embolectomy, when required, with subsequent anticoagulation, results in limb salvage and allows for eventual resolution of the primary aortic thrombus. Long-term anticoagulation is required unless the etiologic process resolves. The literature describes patients with atherosclerosis and overlying thrombus but fails to describe the approach to patients with primary thrombus formation.

Acute Disease↗

A multicenter, phase I evaluation of cryopreserved venous valve allografts for the treatment of chronic deep venous insufficiency.

PURPOSE: A phase I feasibility study was conducted to determine whether cryopreserved venous valved segments would remain patent/competent in a short-term period (6 months). METHODS: The target group consisted of 10 patients (C(4-6), E, A(D), P(R)). The exclusion criteria included untreated superficial/perforator venous disease, significant venous or arterial obstruction, hypercoagulability or coagulopathy, and significant preexisting medical conditions. Required preoperative tests were venous duplex, ascending/descending venography, and a physiologic study (eg, APG, blood typing, an ankle/brachial index, and if post-thrombotic, a hypercoagulability work-up). A single-valve transplant was placed below all reflux, aided by anticoagulation with or without a distal arteriovenous fistula. Postoperative assessment included duplex scanning/clinical examination (at 1, 3, and 6 months), descending venogram (at 1 month), and physiologic study (at 1 and 6 months). The primary end point was valve patency/competence, with clinical outcome as a secondary end point. Adverse events were recorded. RESULTS: After eliminating protocol violations, nine patients with superficial femoral (5) or popliteal (4) vein valve transplants were studied. Six-month actuarial results show a patency rate of 67% +/- 16% and 78% +/- 13%, respectively, a primary and secondary competency rate of 56% +/- 17% and 67% +/- 16%, respectively, and a 100% patient survival rate. Clinical outcome averaged 1.1, with healing and/or freedom from ulcer recurrence, in six of nine patients. A postoperative risk of seroma formation (3) and cellulitis (1) exists. CONCLUSION: In patients with few remaining therapeutic options, one can achieve a 6-month assisted patency and competency rate of 78% and 67%, respectively, with an improved clinical outcome.

Actuarial Analysis↗

The value of acetazolamide single photon emission computed tomography scans in the preoperative evaluation of asymptomatic critical carotid stenosis.

PURPOSE: Acetazolamide (ACZ)-enhanced single photon emission computed tomography (SPECT) scans can assess both cerebral perfusion and vascular reactivity. Patients with asymptomatic critical carotid artery stenosis were evaluated for cerebral vascular reactivity to determine the effect of extracranial occlusive disease and the effect of carotid endarterectomy (CEA) on intracerebral reactivity. METHODS: In 44 patients with asymptomatic critical carotid artery stenosis, cerebral perfusion and vascular reactivity were assessed before CEA with resting and ACZ-enhanced SPECT scans. All patients had a 70% or greater ipsilateral internal carotid artery stenosis. Preoperative ACZ-enhanced SPECT scans were obtained, usually 5 days before CEA. Postoperative ACZ-enhanced SPECT scans were obtained in 30 patients. RESULTS: Preoperative SPECT scans were asymmetric, revealing focal (n = 19) or global (n = 15) decreased reactivity in 34 patients (77%). Ten patients had symmetric or normal reactivity. After CEA, 23 patients demonstrated an improvement in reactivity ipsilateral to the side of surgery. The remaining seven patients failed to improve after surgery. CONCLUSION: Although all patients had a high-grade internal carotid stenosis, nearly a quarter of the patients had excellent intracerebral collateral flow. Only 71% of patients demonstrated improved intracerebral vasoreactivity after CEA. The lack of improvement in the other patients may have resulted from intracerebral pathology or lack of improvement in the extracranial carotid hemodynamics.

Acetazolamide↗

Drag reducing polymers may decrease atherosclerosis by increasing shear in areas normally exposed to low shear stress.

PURPOSE: Drag reducing polymers (DRPs) have been shown to decrease plaque formation. Their mechanism of action is unknown. Atherosclerosis tends to develop in areas of low shear stress. This study investigates whether DRPs increase shear stress in areas normally exposed to low shear stress. METHODS: Six dogs underwent surgical plication of the left half of the aorta. A specially modified 20-MHz Doppler ultrasound probe mounted at a 45-degree angle on a micromanipulator was used to measure blood flow velocity at six 4-mm intervals along both lateral sides of the aorta starting at the aortic wall and then at subsequent 0.1-mm depths moving into the lumen before and after administering DRP. Shear rates were calculated using linear regression and then compared using the paired t test. The blood viscosity remained constant at 0.04 poise during infusions of this amount of DRP. RESULTS: The maximum shear rate occurring during the cardiac cycle on the side of the aortic stenosis (plication) was 9.96 +/- 1.52/sec before the administration of the DRP and 14.27 +/- 2.01/sec after the administration of the DRP (P =.0240). The maximum shear rate on the side of the unstenosed aortic wall was 57.25 +/- 7.93/sec before the administration of the DRP and 44.80 +/- 6.23/sec after the administration of the DRP (P =. 0081). CONCLUSION: One of the ways that DRPs inhibit the development of atherosclerosis appears to be by increasing shear stress in areas normally exposed to low shear stress. Understanding this mechanism may lead to the development of pharmaceutical agents that inhibit the development of atherosclerosis.

Animals↗

Developments in diagnosis and classification of venous disorders: non-invasive diagnosis.

PURPOSE: This review examines the many techniques that have been used for the non-invasive diagnosis of acute and chronic venous disease and was conducted by members of the Committee on Research of the American Venous Forum. It proposes to identify those techniques with the greatest clinical potential, to suggest algorithms for the clinical application of non-invasive techniques in the identification of acute deep venous thrombosis and chronic venous insufficiency, and to identify areas of deficient knowledge and potential areas for future research initiatives. METHODS: Review of pertinent clinical and research material. RESULTS: Impedance plethysmography and ultrasonic imaging are the primary non-invasive tools used in the diagnosis of acute deep venous thrombosis. At present, ultrasonic imaging techniques are recommended on the basis of greater diagnostic accuracy in recent comparative clinical trials. Data would suggest that serial evaluation should probably be viewed as the preferred option for symptomatic patients with a negative initial examination and the presence of risk factors or physical findings suggesting a proximal deep venous obstruction/thrombosis. Chronic venous disease is the result of valvular incompetence, with or without associated venous obstruction. Duplex imaging can be used to determine the location and extent of reflux; however, there are reported procedural variations in the performance and interpretation of such studies. Recent innovations in air plethysmography may provide a means of quantifying volume changes, and permit an objective characterization of venous reflux and calf pump efficiency. CONCLUSIONS: There are still significant questions that need to be answered by well-designed research initiatives. Research applications that incorporate non-invasive diagnostic techniques may involve the diagnosis, treatment and natural history of acute deep venous obstruction/thrombosis and chronic venous insufficiency, assessment prior to and following venous reconstruction, and the basic science aspects of acute and chronic venous disease. At present, a lack of common standards is, by far, the greatest impediment to an organized research approach to venous disease.

Acute Disease↗

Animal models for the study of lower extremity chronic venous disease: lessons learned and future needs.

The purpose of this review is to define animal models of chronic venous disease and to demonstrate how animal studies can impact our understanding and treatment of this disorder. To this end an extensive literature search was conducted highlighting potential animal models of chronic lower extremity venous disease. Scientific investigations using animals to study particular aspects of this disease are also reviewed. This review was conducted by members of the Committee on Research of the American Venous Forum to help provide direction for future venous research endeavors. Useful models of chronic venous occlusive disease involve controlled ligation of a major lower limb vein and multiple tributaries. Such a model can provide sustained venous hypertension and studies using this model have confirmed that an isodiametric graft can provide early hemodynamic relief. Models of primary, postphlebitic, and isolated chronic deep venous insufficiency are available for study. Valve repair or transplantation can positively impact the insufficiency observed in these models. Investigations into valve substitutes have generally been disappointing or are undergoing early evaluation. In conclusion, animal models for the study of some aspects of chronic venous disease do exist and have already affected our clinical approach to patients. The scientific study of basic pathophysiology, diagnostics, end-organ response, and long-term surgical treatments of this disorder in well-controlled animal experiments have not been conducted.

Animals↗

Lower-extremity arterial endovascular stenting.

Intraluminal arterial stenting for the management of arterial occlusive disease of the lower extremities has evolved over the years. Most stents are used to correct inadequacies of PTA or to correct a PTA complication. These include (1) restenosis within 90 days of PTA, (2) chronic iliac occlusion, (3) acute occlusions during PTA, (4) a significant residual gradient following PTA, (5) dissections longer than the angioplasty site, and (6) a 30% or greater residual stenosis after PTA. Both the Palmaz stent and the Wallstent have performed well in the iliac artery system. Their use in the femoropopliteal system has not been as successful and should be reserved for selected cases. Long-term anticoagulation is generally required for femoropopliteal stent patency. Placement in the lower superficial femoral or popliteal artery is best avoided. Re-angioplasty or additional stenting may be used to prolong patency, although with the risk of a second intervention. Progression of arteriosclerosis is a factor to consider when choosing an endoluminal treatment versus standard bypass.

Angioplasty, Balloon↗

Direct in vivo measurement of flow-dependent nitric oxide production in mesenteric resistance arteries.

PURPOSE: To determine whether the concentration of nitric oxide (NO) at the arterial wall is increased subsequent to the abrupt elevation of blood flow in resistance arteries. METHODS: Eight dogs underwent laparotomy with anesthesia, and their small bowels were exteriorized. NO concentration was measured with NO-specific electrodes (200-micro-tip diameter) at the outer wall of the mesenteric arteries. Flow was increased by occlusion of the adjacent mesenteric arteries. In four animals, flow and NO concentration were measured after the administration of Nomega-nitro-L-arginine-methyl ester (L-NAME) to inhibit NO production. RESULTS: As arterial flow was increased from a baseline of 5.4 +/- 1.3 ml/min to 10.9 +/- 1.8 ml/min (p = 0.001), NO electrode current was elevated in every animal. With repetition of the flow stimulus, the response tended to be attenuated. In the first experimental trial, NO electrode current measured at the arterial wall increased from 2.86 +/- 0.56 to 3.00 +/- 0.60 nA (p = 0.02). L-NAME (10 mg/kg intravenous) effectively inhibited NO synthase as indicated by the elevation of mean arterial pressure (11 +/- 1.7 mm Hg; p = 0.04). After administration of L-NAME, NO electrode current measured at the outer arterial wall fell 0.23 +/- 0.05 nA (p = 0.02). CONCLUSIONS: The data indicate that a doubling of blood flow in the canine mesenteric resistance arteries is associated with an increase in NO concentration of at least 100 nm at the outer arterial wall. This association is probably a substantial underestimation of the actual concentration because of the geometry of the electrode tip. To our knowledge, ours is the first report of direct in vivo measurement of flow-dependent NO release in resistance arteries.

Anesthesia, Intravenous↗

Aggressive management of vascular injuries of the thoracic outlet.

PURPOSE: We present a review of 35 patients who underwent an operation for subclavian (n = 18) or axillary (n = 17) vessel injury. In some patients, both an artery and a vein were damaged, resulting in a total of 30 arterial and 16 venous injuries. METHODS: The wounding source included a gunshot (n = 19), a stab wound (n = 9,) and blunt trauma (n = 7). Seven patients had hypotension and were taken immediately to the operating room. Seventeen patients had diminished or absent pulses, whereas 13 patients had normal pulses despite an arterial injury. Associated injuries included nerve injury (n = 15), pneumohemothorax (n = 5), and fractures (n = 7). Angiography in 21 patients demonstrated an intimal flap (n = 8), extravasation (n = 5), a pseudoaneurysm (n = 3), an arteriovenous fistula (n = 2), and occlusion (n = 1). Two angiograms were normal. Arterial repair was accomplished by interposition graft (n = 17), primary repair (n = 9), patch angioplasty (n = 3,) and ligation (n = 1). RESULTS: No functional deficits occurred in patients with an isolated vascular injury. Seven patients with associated brachial plexus injuries experienced severe disability. One arm of a patient was amputated. Two patients died. CONCLUSIONS: The use of angiography helps to confirm and localize injuries. Prompt correction of the vascular injury avoids disability resulting from ischemia. Although the amputation rate is low with vascular repair, the functional disability resulting from associated nerve injuries can be devastating.

Adolescent↗

Cerebral vascular reactivity assessed with acetazolamide single photon emission computer tomography scans before and after carotid endarterectomy.

BACKGROUND AND METHODS: In 64 patients, cerebral perfusion and vascular reactivity were assessed before and after carotid endarterectomy (CEA) using acetazolamide (ACZ)-enhanced single photon emission computer tomography (SPECT). Twenty-five patients were asymptomatic, whereas the remainder were symptomatic. Sixty-one patients had a > or = 70% ipsilateral internal carotid artery stenosis. RESULTS: Fifty SPECT scans revealed decreased vascular reactivity. Twenty-three showed infarcts. Fourteen patients had normal studies. Twenty of the SPECT scans of asymptomatic patients demonstrated poor vascular reactivity. After CEA, 39 patients had improved ipsilateral vasoreactivity. In 12 patients, contralateral improvement was also found. CONCLUSION: ACZ-enhanced SPECT scans, by assessing cerebral perfusion and vascular reactivity, may help to identify patients at risk of stroke should perfusion further diminish. Postoperative studies confirm improvement in vascular reactivity. ACZ-enhanced SPECT scans may provide objective evidence for the selection of patients with a high-grade asymptomatic carotid stenosis for CEA.

Acetazolamide↗

Experimental repair of venous valvular insufficiency using a cryopreserved venous valve allograft aided by a distal arteriovenous fistula.

PURPOSE: To evaluate the patency and hemodynamic impact of a cryopreserved allograft venous valve transplanted to the superficial femoral vein (SFV) of a canine insufficiency model aided by a distal arteriovenous fistula (dAVF). METHODS: Eight greyhounds had intravenous hemodynamic parameters measured (venous filling time [VFT], 90% of venous refilling time [VRT90], and simulated ambulatory venous pressure [AVP]) before (T0) and after complete hindlimb venous valvulotomy (T1) to produce venous insufficiency. Simultaneously, a valve-containing vein segment was harvested from the opposite SFV or external jugular vein (n = 1) and cryopreserved. Three weeks later a blood type-matched cryopreserved valve was transplanted to the insufficient SFV aided by a low-flow (n = 4) or high-flow (n = 4) dAVF. The fistula was ligated in 3 to 6 weeks, and venous indexes (T2) were obtained 3 weeks later. Analysis of variances compared the venous indexes at T0, T1, and T2 for statistical significance. Gross and histologic inspection assessed valve integrity. RESULTS: Two valves aided by a low-flow dAVF exhibited thrombosis and scarring. The hemodynamics of the six remaining valves demonstrated normalization of the VRT90, an AVP consistent with insufficiency, and a VFT between normal and total venous insufficiency. The patent valves were normal on gross examination and by histologic examination with signs of normal external healing. CONCLUSIONS: A cryopreserved venous valve allograft transplanted to the SFV of an incompetent hindlimb partially corrects venous hemodynamics. A high-flow arteriovenous fistula most consistently preserves transplant patency.

Animals↗

Research and clinical issues in chronic venous disease.

The purpose of this study was to summarize the current issues in chronic venous disease by reviewing of the literature relating to the condition. The review was conducted by members of the Committee on Research of the American Venous Forum and includes the Committee's venous disease and current/future directions. Progress in the understanding and management of chronic venous problems has lagged behind that in arterial disease, despite the large number of patients affected. The complex pathophysiology of venous problems, lack of accepted evaluation standards and lack of prosthetic conduits are some of the factors which contribute to this. New information in these areas has laid the foundation for advances in both operations and non-operative therapy. In conclusion, many opportunities for clinical and basic research in the area of chronic venous disease are available. Application of basic science techniques, including those of molecular biology, will lead to new insights into pathophysiology of chronic venous syndrome. Developments in technology, classification and basic science suggest multiple new potentials therapeutic approaches in the next decade.

Blood Vessel Prosthesis Implantation↗

Inhibition of NO synthase prevents acute collateral artery dilation in the rat hindlimb.

The role of endothelium-derived nitric oxide (EDNO) in the initial opening and sustained dilation of collateral vessels in the peripheral circulation was investigated. Abrupt arterial occlusion was produced by clamping the rat superficial femoral artery (SFA). Arterial pressures were measured proximal (MAP) and distal (PD) to the occlusion site. In one group (INITIAL DILATION), the clamp was removed after PD reached a plateau, and then the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME), was administered and the occlusion repeated in the same limb to evaluate the role of nitric oxide in the initial opening of collateral vessels. In another group (SUSTAINED DILATION), L-NAME was administered after acute compensation to SFA occlusion had occurred to determine if inhibition of nitric oxide synthase would reverse any acute compensation. Collateral dilation was evaluated by recovery in PD relative to MAP (PD-%MAP) and by the percent of total resistance in the collateral-dependent circuit due primarily to collaterals (%Rc). The acute compensation indicated by an increase in PD-%MAP (14 +/- 1.9% to 27 +/- 2.6%) and decrease in %Rc (86 +/- 1.9 to 73 +/- 2.6%) in the INITIAL DILATION group was prevented by L-NAME (P < 0.0005). L-NAME also reversed the compensation in the SUSTAINED DILATION group; PD-%MAP decreased from 28 +/- 2.3% to 11 +/- 1.9% and %Rc increased from 72 +/- 2.3% to 93 +/- 1.1% after administration of L-NAME. Although collateral flow was not measured, the results are consistent with the hypothesis that acute collateral dilation is mediated by increases in flow or shear stress which stimulate the release of EDNO.

Animals↗

Comparison of spiral CT scan and arteriography for evaluation of renal and visceral arteries.

Renal and visceral artery images obtained concurrently with spiral CT and conventional arteriography were compared for 32 patients. Indications for imaging were occlusive disease (n = 12), aneurysmal disease (n = 9), and renal or visceral artery disease (n = 11). Conventional arteriography enabled visualization of 64 renal arteries and 15 accessory renal arteries. Lateral aortograms obtained in 15 patients enabled visualization of 14 superior mesenteric (SMA) and 14 celiac arteries. Spiral CT enabled visualization of 60 renal arteries, 12 accessory renal arteries, 27 SMAs, and 22 celiac arteries. Calcification or a disparity in timing of contrast material injection and scanning prevented visualization of the celiac artery in 10 patients and the SMA in four patients. With conventional arteriography as the standard for comparison, spiral CT had a sensitivity of 67% and a specificity of 95% for depiction of at least 75% stenosis in the main renal artery. By means of the Pearson correlation coefficient, significant correlation (p < 0.001) was confirmed between spiral CT and arteriography for evaluation of stenosis of the main renal artery, SMA, and celiac artery. This early experience suggests that spiral CT may be useful in evaluation of renal and visceral arteries and their relationship to aortic disease.

Adult↗

Early collateral and microvascular adaptations to intestinal artery occlusion in rat.

The technique to repeatedly observe exactly the same vessels in the rat intestine was used to investigate vascular compensation during the 1st wk after abrupt arterial ligation. A collateral-dependent tissue region was created by ligation of three to four sequential intestinal arteries. At the center of the collateral-dependent region, arterial pressure decreased from 96 +/- 3.7 to 29 +/- 2.5 mmHg, and intestinal blood flow fell approximately 80% during maximal dilation initially postligation. One week later, pressure and blood flow at the center had increased 31 and 250%, respectively. Relative to preligation values, the only compensatory adaptation was an enlargement (31 +/- 11%) of the collateral arteries located between normal tissue and the center; no increase was observed in the diameter or numbers of arterioles or collateral arteries at the center. Wall shear rate was increased 173 +/- 35% initially postligation at the site where luminal enlargement occurred. The selective enlargement of collateral arteries away from the center region is consistent with the hypothesis that collateral enlargement is induced by chronic increases in wall shear rate and can occur independently of tissue ischemia.

Adaptation, Physiological↗