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Biomedical subjects

K Kandarpa

Publications and source records attributed to K Kandarpa.

At least 19 recordsLinked to original sources

Animal models for atherosclerosis, restenosis, and endovascular graft research.

Animal models have significantly advanced our understanding of the mechanisms of atherosclerosis and restenosis formation and the evaluation of therapeutic options. The current focus of research is on preventive strategies against restenosis and includes pharmacologic and biologic interventions directed primarily against smooth muscle cell proliferation, endovascular devices for recanalization and/or drug delivery, and an integrated approach using both devices and pharmacobiologic agents. Devices aimed at the percutaneous endoluminal exclusion of aortic aneurysms have also generated interest recently. The experience over many decades with animal models in vascular research has established that a single, ideal, naturally available model for atherosclerosis, restenosis, or for that matter aneurysm formation, does not exist. Presently, rabbits and pigs are favored for the former two areas of study, and dogs and sheep appear to provide suitable models for testing devices for endoluminal repair of aneurysms. The development of transgenic variants of currently available models may widen our options in the future. Nevertheless, an appreciation of the individual features of natural or stimulated disease in each species is of the utmost importance for the proper design and execution of relevant experiments.

Animals

Study of catheter designs and drug mixing processes using 2D steady numerical simulations.

The effectiveness of substance delivery through catheters is an important issue in interventional radiology, especially for infusion therapies where the pharmacokinetic advantage of local intra-arterial drug administration has been firmly established. In principle, the procedure is used to provide appropriate local concentrations while maintaining low systemic values so as to minimise the global effect and toxicity of the intervention. However, poor drug mixing may produce excessive local concentrations potentially damaging for the surrounding tissues and may lead to unsuccessful therapies. These phenomena have been observed in the infusion therapies of liver cancers through the hepatic artery and with brain tumour therapies through the carotid artery. Many aspects of the drug delivery methodology have been explored in order to determine the infusion conditions that would provide optimal mixing: the catheter tip design is considered one of the most important characteristics to be investigated for this purpose. Interestingly, it turns out that angiographic procedures could also benefit from this, because better mixing properties are associated with designs that provide potentially less harmful flow conditions such as jets, whipping and recoil of the catheter on the vascular wall. A 2D steady numerical model is proposed, to simulate the main physical processes occurring during catheter substance infusion: blood dynamics is taken into account with the Navier-Stokes equations and substance dispersion by the flowing blood with the advection-diffusion equation. The model is used to evaluate mixing properties of certain catheter designs in different flow conditions. In particular, two types of side hole catheter are compared in the context of water bath injection and in the context of vessel injection. The simulations suggest that the improved mixing reported with water bath experiments would not be maintained in the clinical context of arterial circulation.

Catheterization

Prourokinase versus urokinase for recanalization of peripheral occlusions, safety and efficacy: the PURPOSE trial.

BACKGROUND: The intraarterial administration of thrombolytic agents is associated with clinical benefits in patients with acute peripheral arterial occlusion, and urokinase has been the agent that has become the standard of care in the United States. Recombinant prourokinase (r-ProUK) offers potential as a novel agent with improved fibrin specificity and, as such, may offer advantages as an attractive alternative to urokinase. METHODS: A randomized, double-blind, parallel, phase II, prospective multicenter trial was undertaken to compare three doses of intra-arterial, catheter-directed r-ProUK (2 mg, 4 mg, or 8 mg/hr for 8 hrs, then 0.5 mg/hr) versus one dose of tissue-culture urokinase (4,000 IU/min for 4 hrs, then 2,000 IU/min) for the treatment of acute lower extremity arterial occlusion of 14 days' duration or less (n = 241). The primary endpoint was complete (>95%) lysis of the occluding thrombus after 8 hours of infusion. RESULTS: Increased clot lysis at 8 hours, decreased fibrinogen concentration, and an increased rate of hemorrhagic events were observed as the r-ProUK dose was increased from 2 mg/hr to 8 mg/hr. Similarly, a decreased duration of study drug infusion was seen, decreasing from 16.7 +/- 0.90 hours in the 2 mg/hr group to 12.7 +/- 0.97 hours in the 8 mg/hr group. The results for the urokinase group decreased to a level between those observed for the 2 mg and 8 mg r-ProUK group with respect to clot lysis at 8 hours, fibrinogen decrement, and bleeding complications, approximating those observed in the 4 mg/hr r-ProUK group. These results were achieved with a relatively low rate of major bleeding events and no episodes of intracranial hemorrhage. CONCLUSIONS: The 8 mg/hr dose of r-ProUK was associated with an increased rate of thrombolysis relative to the other treatment groups, associated with a slightly increased frequency of bleeding complications and decrements in fibrinogen concentration. Conversely, the 2 mg/hr r-ProUK dose was associated with a slightly slower rate of thrombolysis, but bleeding complications and fibrinogenolysis were diminished. r-ProUK is a novel thrombolytic agent with a dose-related safety and efficacy profile. As such, it offers potential as a useful tool in the treatment of peripheral vascular occlusion.

Aged

Pulmonary embolism: comparison of cut-film and digital pulmonary angiography.

PURPOSE: To compare "cut-film" (film hard-copy) angiography (CFA) with digital pulmonary angiography in the detection of pulmonary embolism (PE). MATERIALS AND METHODS: Thirty-six adult patients (39 lungs) underwent selective digital pulmonary angiography for suspected PE. Imaging was repeated in one selected projection by using cut film. The standard was consensus interpretation of both CFA and digital angiographic images and clinical course. Three vascular radiologists subsequently reviewed the digital and cut-film images in a blinded fashion and ranked the likelihood of the presence of PE on a five-point scale. The two modalities were compared by means of receiver operating characteristic (ROC) analysis. Image quality (i.e., sharpness, opacification of subsegmental vessels, and exposure) was judged on a three-point scale. The highest-order pulmonary artery branch seen on each study was recorded. RESULTS: ROC curve analyses for all three operators showed similar diagnostic performance for digital pulmonary angiography and CFA, with one operator showing better performance with digital subtraction angiography than with CFA (P = .04). Compared with the final diagnosis, single-plane digital pulmonary angiography had higher sensitivity for the detection of PE than had CFA. The specificity was 100% for both modalities. The mean score in patients with findings positive for PE was higher in the digital pulmonary angiography group than in the CFA group (P < .005). There was no difference in the mean score in patients who did not have a PE. There also was no difference in the smallest detectable subsegmental branch (P = .87) or in the average estimate of image quality. CONCLUSION: Selective digital pulmonary angiography and CFA offer similar diagnostic performance and image quality. Digital pulmonary angiography is a reasonable alternative to CFA in the diagnosis of PE.

Adult

Removal of the protruding retention wire via a femoral approach while leaving the active-fixation atrial "J" lead in situ: a technique for the management of class III atrial "J" leads.

The Telectronics Accufix Atrial "J" pacing lead poses a mechanical risk to patients of retention wire fracture and protrusion. Standard lead extraction techniques include percutaneous approaches, which are associated with significant risk of morbidity and mortality, and open procedures, which necessitate thoracotomy. In nine patients referred with Class III retention wire fractures, attempts were made to snare the protruding retention wire from a femoral approach using snare devices and bioptomes. In six cases, the retention wire was successfully removed, leaving the lead body in place. In four patients with lead function that was able to be evaluated, the atrial lead remained functional after the procedure. There were no complications. Snare removal of the protruding retention wire via a femoral approach should be considered as an option in the management of patients with Class III Accufix leads.

Aged

Intraarterial thrombolysis of lower extremity occlusions: prospective, randomized comparison of forced periodic infusion and conventional slow continuous infusion.

A prospective randomized controlled trial compared forced infusion (FI) of urokinase (UK) with conventional slow continuous infusion (CI) in 25 patients with 25 acutely ischemic lower limbs. Demographics, ischemia categories, and infusion rates and doses were similar for both groups. A preliminary single-pass bolus of UK was injected into the thrombus in all patients with a pulsed-spray technique, and heparin was administered. UK was then infused with a CI pump (n = 13) or a prototype pulsed-spray pump (n = 12). The primary end point was patency, defined as at least 95% thrombolysis by volume, with brisk antegrade flow occurring within 4 hours. Eleven of the 12 patients (92%) who underwent FI and nine of the 13 (70%) who underwent CI had patency within 4 hours. However, 10 patients who underwent FI and nine who underwent CI had residual thrombi prolonging infusion. No significant differences between the two groups were apparent in speed of lysis, initial success rates, complication rates, or 30-day clinical outcome. Lytic therapy, however, was completed within 24 hours in 18 of 23 (78%) successfully treated patients (P = .01).

Aged

Relation of vessel wall shear stress to atherosclerosis progression in human coronary arteries.

The purpose of this study was to determine the relation between vessel wall shear stress and the rate of atherosclerosis progression. Quantitative angiography was used to calculate the change in coronary arterial diameter over 3.0 years in patients enrolled in the Harvard Atherosclerosis Reversibility Project pilot study (n = 20 arterial segments). Vessel wall shear stress was calculated by means of a validated finite-difference model of the Navier-Stokes' equation that assumes a coronary flow rate of 8 ml/sec. The correlation between vessel wall shear stress and the change in arterial diameter at multiple points (mean, 70) along the length of the artery was then calculated for each of the 20 segments with a focal stenosis. In 15 of the 20 arterial segments there was a significant correlation (p < 0.05) between low shear stress and an increased rate of atherosclerosis progression. A Fisher's z transformation was then used to combine the correlation coefficients from all 20 segments. Low shear stress was significantly correlated (z = 0.37 +/- 0.00074, p < 0.0001) with an increased rate of atherosclerosis progression. This serial quantitative evaluation of human coronary arteries is consistent with previous data that have suggested that low shear stress promotes atherosclerosis progression. Variations in local vessel wall shear stress may explain the previously reported near-independent rate of atherosclerosis progression in multiple lesions within the same patient despite exposure to the same circulating lipoprotein values and systemic hemodynamics.

Computer Simulation

Risks and benefits of femoropopliteal percutaneous balloon angioplasty.

PURPOSE: The purpose of this study was to evaluate the efficacy of angioplasty in the treatment of femoropopliteal arterial disease. METHODS: From 1980 to 1991, 126 angioplasty procedures were performed in 131 limbs of 106 patients with 175 femoropopliteal lesions (26 common femoral, 118 superficial femoral, and 31 popliteal). Critical ischemia was present in 55 limbs (42%), and claudication was present in 76 (58%). Angioplasty was performed for a single lesion in 87 limbs (66%) and for multiple lesions in 44 (34%). In 13 limbs (10%) the most severe lesion was an occlusion; in 118 (90%) all lesions were stenoses. Distal runoff was good (2 or 3 vessels patent) in 72 limbs (55%) and poor (0 or 1 vessel patent) in 59 (45%). RESULTS: Death within 30 days occurred in 0.8%, nonfatal systemic morbidity in 7.1%, and local morbidity in 1.6% of procedures. Multivariate analysis revealed that indication and age were predictive of increased morbidity and mortality rates. Immediate success was achieved in 95% of limbs treated. Mean follow-up time was 2.0 years. The overall 5-year cumulative primary patency rate was 45% (+/- 5%). In a proportional hazards model indication and lesion type were predictive (p < 0.01) of long-term failure, with relative risks of 2.0 (1.2 to 3.3) and 2.7 (1.3 to 5.6), respectively. The 5-year primary patency rate after angioplasty for stenoses and claudication was 55% (+/- 7%), for stenoses and critical ischemia it was 29% (+/- 11%), and for occlusions it was 36% (+/- 14%). CONCLUSION: These results suggest that femoropopliteal angioplasty is a low-risk procedure with acceptable long-term results in patients with claudication and stenoses.

Angioplasty, Balloon

Endoluminal thermal occlusion of the ureter with the electromagnetic field-focusing device.

The authors attempted ureteral occlusion by means of heat application in nine ureters (24 sites) of New Zealand White rabbits with the electromagnetic field-focusing (EFF) device. The EFF device generates heat at the tip of a grounded probe by focusing eddy currents that have been induced within the tissues by an external radio-frequency field. The power settings were varied from 30 to 150 W. Heat was applied at multiple sites in each ureter. Immediate functional occlusion was seen in all nine ureters. Long-term complete occlusion was seen in six ureters at power settings ranging from 40 to 150 W, while long-term partial occlusion was seen in two ureters at 30-50 W. All sites at 30 W resulted in partial occlusions. Perforation of the ureter resulted in urinoma formation in one ureter at a site that was treated with 150 W. The EFF device can be used to endoluminally occlude the ureter by causing a fibrotic reaction to thermal injury. The effective power range for this application appears to be 40-100 W.

Animals

Prospective double-blinded comparison of MR imaging and aortography in the preoperative evaluation of abdominal aortic aneurysms.

The authors conducted a prospective double-blind study comparing spin-echo axial and coronal magnetic resonance (MR) imaging with aortography in the preoperative evaluation of 20 patients with abdominal aortic aneurysms. Receiver-operating-characteristic (ROC) analysis was used to evaluate the performance of MR imaging versus aortography in assessing arterial stenotic disease. Both modalities were equivalent in demonstrating the upper extent of the abdominal aortic aneurysms with respect to the renal and visceral arteries. MR imaging was superior in demonstrating aneurysmal iliac arteries and intraluminal thrombus. Although aberrant venous anatomy, associated pathologic changes, and other concomitant lesions were demonstrated with MR imaging, it performed poorly in assessing arterial stenoses and occlusions. Thus, the authors caution against the routine substitution of spin-echo MR imaging for aortography in the evaluation of abdominal aortic aneurysms. Conventional angiography should continue to be performed in patients with suspected mesenteric ischemia, significant hypertension, and symptomatic iliofemoral atherosclerosis, at least until robust MR angiographic techniques have proved themselves under similar rigorous clinical evaluation.

Aged

Improving the patient evaluation process in a cardiovascular and interventional radiology department.

Brigham & Women's Hospital (BWH) has adopted total quality management (TQM) to increase productivity and efficiency and to improve the quality of patient care services. This article reports on a quality improvement project in the department of radiology designed to improve the process of pre-procedure workup of patients referred for cardiovascular and interventional radiology (CVIR) procedures. The project was initiated, led, and conducted by a physician.

Boston

Quality assurance in cardiovascular and interventional radiology.

In summary, quality assurance in medicine and in CVIR must be an important part of daily practice. The JCAHO is gradually moving toward quality improvement as a goal, rather than simply monitoring performance. Physicians must lead the way in dealing with the issues of monitoring performance, with the ultimate goal being the welfare of their patients. The model SCVIR QA program described above will help cardiovascular and interventional radiology sections of all sizes to meet these goals. Resources applied toward QA activities are investments for maximizing efficiency and productivity, while minimizing morbidity and mortality. These well-spent efforts will hopefully decrease the spiraling costs of medical care.

Cardiovascular System

Efficacy of thrombolysis in infrainguinal bypass grafts.

The initial outcome of a consecutive series of 43 intra-arterial urokinase infusions for thrombosed infrainguinal grafts in 37 patients was analyzed. There was an 88% (38/43) technical success rate (complete clot lysis) and a 74% (32/43) clinical success rate. Complications occurred in 10 patients (23%) and were related to bleeding in four patients (9%). Patient age, graft age, location, material, and the duration of occlusion did not significantly influence the initial outcome, although there was a trend toward a higher bleeding complication rate among grafts less than or equal to 1 month of age at the time of thrombolysis. A second group of 43 infrainguinal grafts successfully recanalized using regional infusions of thrombolytic agents were followed for long-term patency. This group included 32 grafts successfully treated with urokinase and 11 grafts recanalized with streptokinase. By life-table analysis there was a 55.6% 1-year patency, which fell to 42.4% at 4 years. Vein grafts had significantly (p = 0.01) better long-term patency than prosthetic grafts (69.3% versus 28.6% at 30 months). Grafts with flow-limiting lesions identified and corrected by angioplasty or surgery also had significantly (p = 0.01) better long-term patency than those without such lesions (79.0% versus 9.8% at 2 years). Based on the results of our study compared with a survey of long-term results following secondary surgical procedures for thrombosed infrainguinal grafts, thrombolysis can be recommended in several circumstances. Thrombolysis is indicated for thrombosed vein grafts or when thrombus is present in distal runoff vessels. Thrombosed prosthetic grafts should be replaced by autogenous vein grafts whenever possible.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Recombinant tissue-type plasminogen activator versus urokinase in peripheral arterial and graft occlusions: a randomized trial.

A randomized prospective trial was undertaken to compare intraarterial administration of recombinant human tissue-type plasminogen activator (rt-PA) with urokinase (UK) in 32 patients with peripheral arterial or bypass graft occlusions. Sixteen patients were randomized to receive rt-PA and 16 to receive UK. The rt-PA dose was administered as a 10-mg bolus into the thrombus, followed by 5 mg/h for up to 24 hours. The UK dose was administered as a 60,000 IU bolus into the thrombus, followed by 240,000 IU/h for 2 hours, 120,000 IU/h for 2 hours, and 60,000 IU/h for up to 20 hours. Serial arteriograms were obtained at baseline and at 4, 8 or 16, and 24 hours. The endpoint was defined as 95% of greater clot lysis. The cumulative numbers of patients with successful thrombolysis (rt-PA vs UK) were four vs none at 4 hours, seven vs one at 8 hours, seven vs three at 16 hours, and eight vs six at 24 hours. Lysis occurred more rapidly in the rt-PA group (P = .04). Major bleeding complications occurred in five rt-PA patients and two UK patients (P = .39). At 24 hours, fibrinogen levels were significantly lower in the rt-PA group than in the UK group (P = .01). There was no apparent difference in 30-day clinical success.

Adult