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Biomedical subjects

M Haklin

Publications and source records attributed to M Haklin.

15 recordsLinked to original sources

Occlusion of experimentally created fusiform aneurysms with porous metallic stents.

BACKGROUND AND PURPOSE: Carotid fusiform aneurysms are most commonly treated with occlusion of the parent vessel. The purpose of our study was to assess the effectiveness of self-expanding, cobalt-alloy stents in the ablation of experimental fusiform aneurysms with preservation of the parent vessel in a carotid artery model. METHODS: Porous metallic stents were placed endovascularly along the lengths of experimentally created fusiform aneurysms in the carotid arteries of dogs; aneurysms were also created in the animals' opposite carotid arteries to serve as controls. RESULTS: Before stent placement, angiography of the carotid arteries showed large fusiform aneurysms along the lengths of the common carotid arteries and complex patterns of flow. Immediately after stent placement there was disruption of the usual flow patterns within the lumens of the fusiform aneurysms. The lumen between the wall of the aneurysm and stented carotid showed stasis of contrast material and blood. Near-complete ablation of all aneurysms was observed 8 weeks after stent placement. The stented carotid arteries remained widely patent; control aneurysms and carotid arteries were patent and unchanged. Histopathologic analysis revealed fibrotic reactive scar tissue filling the space between the stent wires and outer wall of the fusiform aneurysm. CONCLUSION: Changing blood flow dynamics within an aneurysm can promote thrombus formation. The stent promotes stasis and thrombus within the residual lumen between the stent wall and the outer wall of the aneurysm because its woven wire mesh interferes with usual blood flow patterns, which then promotes formation of thrombus and fibrosis within the residual aneurysmal lumen.

Aneurysm↗

Rapid drug infusion for termination of atrial fibrillation in an experimental model.

Episodes of paroxysmal atrial fibrillation (PAF) in the ambulatory patient might be terminated promptly by intravenous infusion from an implanted drug delivery system. We have explored this concept in a series of experiments using rapid intra-atrial infusions in dogs. In the acute studies, rapid intra-atrial infusions of procainamide were delivered during continual measurements of epicardial monophasic action potentials (MAP), atrial effective refractory periods (ERP), and right to left atrial conduction times (CT) in 9 dogs. In the chronic studies, 20 episodes of sustained PAF were induced in 4 dogs after six weeks of rapid or burst atrial pacing from a specially programmed implanted pacemaker. Rapid infusions of procainamide were then delivered to the right atrium through a previously implanted catheter connected to a subcutaneous access port. Procainamide significantly increased the duration of the atrial MAP, ERP and CT in the acute experiments. It also terminated induced PAF within five minutes of the end of infusion in all twenty of the chronic experiments. We conclude that rapid intra-atrial infusion of procainamide is very effective in this animal model of PAF, and that such infusion prolongs atrial MAP, ERP and CT.

Action Potentials↗

Experimental arteriovenous fistulas: treatment with silicone-covered metallic stents.

PURPOSE: To determine the efficacy of silicone-covered metallic stents in the treatment of experimentally created carotid-jugular fistulas. METHODS: Carotid-jugular fistulas were surgically constructed in six mongrel dogs. Silicone-coated, self-expanding metallic stents were placed across the fistula holes within the carotid artery, and carotid angiography was performed before, immediately after, and 4 and 8 weeks after stent placement. Fistula specimens were resected 2 months after stent placement and analyzed by means of gross and light microscopy. RESULTS: Angiography revealed complete closure of all fistulas immediately after stent deployment. The fistulas remained closed and all carotid arteries remained patent. Marked stenosis within the carotid lumen was seen along the proximal and distal ends of the stents. Gross and micropathologic specimens of the carotid-jugular fistulas revealed fibrous connective tissue and collagen across the fistula holes. Proliferative fibrous connective tissue, collagen, and fibromyoblasts were located at either end of the stents. The wires of the stents indented the intraluminal surface of the carotid arteries. CONCLUSIONS: Silicone-covered stents were effective in closing all experimentally created carotid-jugular fistulas. With further refinements and variations in technique, covered stents may prove a viable alternative to current endovascular devices.

Animals↗

Feasibility of using a swine portal vein containing a metallic stent for creating a portacaval shunt.

RATIONALE AND OBJECTIVES: We evaluated the feasibility of using a metallic stented portal vein as a conduit for portacaval shunt in pigs. METHODS: A metallic self-expanding stent was placed in the portal vein of five pigs under combined ultrasound and fluoroscopic guidance via a percutaneous transhepatic approach. After 6 weeks, a portacaval shunt was performed using the stented portal vein as a conduit. A single angiogram followed immediately by sacrifice and histologic examination was performed on each pig at a varying time interval postshunt. RESULTS: One pig died 3 days after the shunt procedure because of a presumed surgical technical failure and a consequent thrombosed portal vein. Angiographic patency of the portacaval shunt was confirmed in the four remaining pigs. Postmortem histologic evaluation showed more complete endothelialization and subintimal organization in the more chronic stents. Thrombus occurred only in the stent of the pig that died. There was no significant luminal obstruction in the other four stents. CONCLUSION: Our results suggest that a stented portal vein can be used successfully as a conduit for portacaval shunt in pigs.

Angiography↗

An evaluation of leflunomide in the canine renal transplantation model.

Leflunomide is an isoxazole with newly discovered immunosuppressive properties. Its mechanism of action operates later in the cell cycle than cyclosporine and appears to interfere with lymphocyte IL-2 responsiveness. With the encouraging results from in vitro and small-animal studies, we subjected leflunomide to the rigorous canine renal transplantation model in a dose response protocol. Thirty-eight female mongrel dogs underwent renal transplantation and bilateral nephrectomy. Immunosuppression was stratified from controls with no immunosuppression to monotherapy with leflunomide at 2, 4, 8, and 16 mg/kg/day given orally and in a combination therapy with cyclosporine. To evaluate its toxicity while maintaining a low constant blood level, eight dogs were treated by continuous intravenous infusion at doses of 2, 4, 6, and 8 mg/kg/day. The mean survival time for nonimmunosuppressed controls (n = 2) was 9 days, leflunomide 2 mg/kg/day (n = 2) was 9 days, leflunomide 4 mg/kg/day (n = 4) was 16 days, leflunomide 8 mg/kg/day (n = 5) was 28 days, leflunomide 16 mg/kg/day (n = 7) was 21 days. Cyclosporine alone at 10 mg/kg/day (n = 4) resulted in a mean survival time of 13 days. The mean survival time with the combination of cyclosporine 10 mg/kg/day with leflunomide 4 mg/kg/day (n = 6) was 68 days. The mean survival time for continuous intravenous leflunomide 2 mg/kg/day (n = 2) was 10 days; for leflunomide 4 mg/kg/day, 20 days; for leflunomide 6 mg/kg/day, 14 days; and leflunomide 8 mg/kg/day, 21 days. The mean serum trough levels of leflunomide ranged from 10 micrograms/ml at the 2 mg dose to 55 micrograms/ml for the 16 mg dose, levels that have been well tolerated in man. Leflunomide at 16 mg/kg/day reliably prevented acute allograft rejection, but the dogs died of inanition with normal renal function. Leflunomide at a nontoxic dose of 4 mg/kg/day extended survival to 16 days, but all dogs died of rejection. A combination of inadequate doses of leflunomide (4 mg/kg/day) and cyclosporine (10 mg/kg/day) resulted in all animals having normal renal function and weight for > or = 30 days. Even at a high dose of 16 mg/kg/day, no viral or bacterial infections were noted. These observations in a canine system add to the growing enthusiasm for the evaluation of leflunomide in human transplantation.

Administration, Oral↗

Embolization of experimentally created aneurysms with intravascular stent devices.

PURPOSE: To assess the effectiveness of self-expanding, cobalt-alloy stents in the treatment of aneurysms in a canine model and to observe the pattern of blood flow and formation of fibrotic scar tissue. METHODS: Porous metallic stents were endovascularly placed across the necks of experimentally created side aneurysms in the carotid arteries of three dogs; aneurysms were also created in the opposite carotid arteries in these animals to serve as controls. RESULTS: Before stent placement, angiography of the carotid arteries demonstrated whirl-like, vortex flow of blood within the lumens of the aneurysms. Inflow was seen along the distal aneurysm wall; outflow was demonstrated along the proximal wall; slower vortex flow was present in the central lumen. Immediately after stent placement there was disruption of the usual vortex flow with stasis of contrast media and blood within the lumen. Inflow and outflow patterns were no longer seen. Complete ablation of these aneurysms was evident at follow-up angiographic studies--1 week, 1 month, and 2 months after stent placement. The stented carotid arteries remained widely patent; control aneurysms and carotid arteries were patent and unchanged. Histopathologic analysis revealed fibrotic reactive scar tissue completely filling the stented aneurysm pouches. CONCLUSION: Treatment of selected intracranial aneurysms via an endovascular approach has merit and could supplant more invasive, risky, and costly surgical procedures in some cases.

Animals↗

The role of C-reactive protein and polyarginine in tumor immunotherapy.

C-reactive protein (CRP) is an acute-phase reactant whose serum level rises rapidly in response to tissue injury. C-reactive protein binding to cells can activate the classical complement pathway, and enhance opsonophagocytosis. The polycation poly-L-arginine (PLA) can artificially fix CRP to target cells. The effects of CRP and PLA on tumor growth were evaluated, both independently and synergistically, using the V X 2 tumor line in the rabbit host. Ten normal animals and seven acute-phase animals were bilaterally inoculated with V X 2 cells (control side) and PLA-treated V X 2 cells (experimental side). Tumor growth was significantly retarded on the treatment side (P less than 0.005), in both animal groups. It is concluded that topical PLA is a potent inhibitor of V X 2 tumor growth. Comparison of normal and acute-phase animals revealed no persistent difference in tumor growth for either cell inoculum. Similarly, cell treatment with topical CRP did not inhibit tumor growth, whether PLA was present or not. Thus, circulating and topical CRP did not alter the rate of V X 2 tumor growth. PLA cytotoxicity remains to be evaluated when the agent is administered orthotopically, selectively, or systemically.

Animals↗

A model for the treatment of accidental severe hypothermia.

Central to the controversy that surrounds the treatment of accidental severe hypothermia is the question of how the method of rewarming affects myocardial performance, and therefore survival. We induced severe hypothermia and cardiac arrest in 15 mongrel dogs. Each dog was rewarmed by one of three methods: partial cardiac bypass (Group I); peritoneal dialysis (Group II); or external rewarming with a fluid-circulated blanket (Group III). The cardiac arrest state was supported by partial cardiac bypass in Group I and by standard mechanical cardiopulmonary resuscitation (CPR) in Groups II and III. In all dogs, the hypothermically depressed myocardial performance returned to normal upon rewarming. Groups I and II had similar rewarming times and required similar volumes of crystalloid and bicarbonate solutions to maintain adequate cardiac filling pressures and arterial pH. However, Group III had a significantly slower rewarming time and required significantly greater volumes of crystalloid and bicarbonate solutions. The sole procedural death occurred in Group III. Our results show that partial cardiac bypass, peritoneal dialysis, and the fluid-circulated blanket are equally effective in rewarming severely hypothemic dogs with cardiac arrest, provided that the cardiac arrest is relieved by partial cardiac bypass or standard mechanical CPR and that physiologic levels of intravascular volume, oxygenation, and pH are maintained.

Accidents↗

Subendocardial myocardial necrosis: a preventable lesion.

Left ventricular subendocardial hemorrhagic necrosis, a lesion entirely different from conventional myocardial infarction, has been an important cause of serious morbidity and mortality in open heart surgery, particularly aortic valve replacement. An established experimental model in which this lesion could be consistently produced in calves, was utilized to examine the protective role of hypothermia and/or Solumedrol infusion. Solumedrol infusion and systemic hypothermia were not sufficiently effective in protecting the myocardium against 40 minutes of left coronary artery occlusion during total cardiopulmonary bypass. Profound continuous irrigation of the pericardial cavity with 4 degrees centigrade Ringers lactate solution, with or without Solumedrol infusion, under similar circumstances yielded excellent results, both in terms of myocardial performance and preservation. This experiment has encouraged the clinical use of this technique in our institution.

Animals↗

Experimental arteriovenous fistulas: treatment with porous metallic stents.

PURPOSE: To determine the efficacy of porous metallic stents in the treatment of experimentally created carotid-jugular fistulas. METHODS: Carotid-jugular fistulas were constructed surgically in five mongrel dogs. Porous metallic stents were placed endovascularly across the fistula holes within the carotid artery; carotid angiography was performed before, immediately after, and 1 and 2 months after stent placement. The fistula specimens were resected 2 months after stent placement; gross and light microscopic analyses were performed. RESULTS: Angiography revealed complete closure of three of the five fistulas 1 month after stent placement; two of the five fistulas remained patent but demonstrated diminished flow rate. All carotid arteries were widely patent throughout the study. Gross pathology of the carotid-jugular specimens revealed fibrous connective tissue and collagen within the fistula hole. A thin layer of endothelium covered the stent wires and the fibrous connective tissue overlying the fistula hole. CONCLUSIONS: The stents were effective in closing three of the five fistulas and reducing flow through the fistulas in the remaining animals. With further refinements and variations in technique, porous metallic stents may prove a viable alternative to current endovascular devices for treatment of certain arteriovenous fistulas.

Angiography↗