Name: a murine model of hemodialysis access-related hand dysfunction
Uploaded: 2022-05-31T14:30:00
Description: Watch this Scientific Journal Video about A Murine Model of Hemodialysis Access-Related Hand Dysfunction at JoVE.com

We sincerely thank Dr. Guanyi Lu from the Division of Vascular Surgery and Endovascular Therapy at the University of Florida for the technical support on the development of the iliac AVF model, as well as surgical training, and Ravi Kumar from the Department of Applied Physiology and Kinesiology at the University of Florida for the technical support getting the live microsurgical images.
This work was supported by grants from the National Institutes of Health and National Heart, Lung, and Blood, Institute numbers R01-HL148697 (to S.T.S.), as well as the American Heart Association grant number POST903198 (to K.K.).

All procedures were approved by the Institutional Animal Care and Use Committee (IACUC) of the University of Florida and Malcom Randall Veterans Affairs Medical Center.
NOTE: Young adult (8-10 weeks old) male C57BL/6J mice were purchased from The Jackson Laboratory and housed in a light (12 h light: 12 h dark cycle), temperature (22 &#176;C &#177; 1 &#176;C), and humidity (50% &#177; 10%) controlled animal facility. Five mice were allowed to dwell per cage (W:18 cm x L:29 cm x H:12.5 cm) with ...

The prevalence of hemodialysis patients with ARHD following AVF creation has continued to increase30,31. Indeed, unresolved symptomatic complications4,32,33 such as pain, weakness, paresthesia, and/or reduced range of motion can negatively impact patient wellbeing4,32,33,</...

The establishment and preservation of functional vascular access remain an important primary goal for end-stage renal disease (ESRD) patients receiving renal replacement therapy via hemodialysis1. Repeated hemodialysis treatments are necessary to remove waste products, normalize electrolytes, and maintain fluid balance once kidney function becomes inadequate, and thus are necessary for long-term survival2. Therefore, vascular access represents a &#34;lifeline&#34; for patients with ESRD, and autogenous arteriovenous fistula (AVF) placement remains a preferred dialysis access option among this cohort3. However, approximately 30%-60% of hemodialysis patients experience a spectrum of hand disabilities, clinically defined as access-related hand dysfunction (ARHD). The symptoms of ARHD can range from weakness and discoordination to monoplegia and digital gangrene, which can occur early after AVF creation or develop gradually with fistula maturation. Further, ARHD complicates the ESRD treatment schedule, which is associated with poor quality of life, high risk of cardiovascular disease, and increased mortality2,3,4.
Several animal models have been developed to study vascular remodeling induced by hemodynamic alterations following AVF creation5,6,7,8,9,10,11,12,13,14,15. Large animal models with iliac or femoral AVF16,17,18,19,20 and rodent models using either carotid artery-jugular vein anastomosis or infrarenal aorta-inferior vena cava fistula formation are well established to examine the aforementioned aspects of AVF maturation and patency21. For example, venous hypertension, greater luminal diameter, and increased vein wall thickness are signatures of successful AVF maturation, whereas substantial fibrosis of the media and intimal hyperplasia or thrombus development with no changes in flow often characterize AVF failures6,15. However, large animal models lack the experimental flexibility or transgenic capabilities of murine models, while current rodent models do not readily facilitate the investigation of ARHD due to either the anatomic location and/or lack of associated limb pathology. Indeed, due to a lack of an established preclinical animal model that recapitulates the relevant clinical phenotype, research progress to elucidate the pathobiological mechanisms and develop novel therapeutic strategies has remained stagnant, despite a progressive increase in the number of symptomatic ARHD patients. Therefore, the primary aim of this study is to introduce a unique mouse model of ARHD, providing procedural steps of AVF microsurgery and characterization of AVF-related pathophysiology.

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			<td>0.15% Adenine diet</td>
			<td>ENVIGO</td>
			<td>TD.130899</td>
			<td>20% casein, 0.15% adenine, 0.9% P</td>
		</tr>
		<tr>
			<td>0.2% Adenine diet</td>
			<td>ENVIGO</td>
			<td>TD.130900</td>
			<td>20% casein, 0.2% adenine, 0.9% P</td>
		</tr>
		<tr>
			<td>10-0 Nylon suture</td>
			<td>AD surgical</td>
			<td>XXS-N1005T4</td>
			<td></td>
		</tr>
		<tr>
			<td>29 G needle syringes</td>
			<td>Exel International</td>
			<td>14-841-32</td>
			<td></td>
		</tr>
		<tr>
			<td>31 G needle syringes</td>
			<td>Advocate</td>
			<td>U-100 insulin syringe</td>
			<td></td>
		</tr>
		<tr>
			<td>4-0 silk suture</td>
			<td>AD surgical</td>
			<td>S-S41813</td>
			<td></td>
		</tr>
		<tr>
			<td>45-degree angled dumont forceps</td>
			<td>Fine Science Tools</td>
			<td>11253-25</td>
			<td></td>
		</tr>
		<tr>
			<td>5-0 PGA suture</td>
			<td>AD surgical</td>
			<td>PSGU-518R13</td>
			<td></td>
		</tr>
		<tr>
			<td>6-0 silk suture</td>
			<td>AD surgical</td>
			<td>S-S618R13</td>
			<td></td>
		</tr>
		<tr>
			<td>Absorbable gelatin sponge</td>
			<td>ETHICON</td>
			<td>1975</td>
			<td></td>
		</tr>
		<tr>
			<td>Alcohol preps</td>
			<td>Covidien</td>
			<td>5110-cs4000</td>
			<td>70% isopropyl alcohol</td>
		</tr>
		<tr>
			<td>Buprenorphine</td>
			<td>NA</td>
			<td>NA</td>
			<td>0.01 g/mL</td>
		</tr>
		<tr>
			<td>C57BL6/J mice</td>
			<td>Jaxon Laboratory</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Casein diet</td>
			<td>ENVIGO</td>
			<td>TD.130898</td>
			<td>20% casein, 0.9% P</td>
		</tr>
		<tr>
			<td>Cotton swabs</td>
			<td>CONSTIX</td>
			<td>SC-9</td>
			<td>Medium single-ended round cotton swab</td>
		</tr>
		<tr>
			<td>Cotton swabs</td>
			<td>CONSTIX</td>
			<td>SC-4</td>
			<td>Small double-ended hard, sharp, pointed cotton swab</td>
		</tr>
		<tr>
			<td>Curity non-woven sponges (2x2)</td>
			<td>Covidien</td>
			<td>9022</td>
			<td></td>
		</tr>
		<tr>
			<td>Curved Vannas spring scissors</td>
			<td>Fine Science Tools</td>
			<td>15001-08</td>
			<td></td>
		</tr>
		<tr>
			<td>Doppler ultrasound</td>
			<td>VisualSonics</td>
			<td>Vevo 2100</td>
			<td></td>
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		<tr>
			<td>Extra fine graefe forceps</td>
			<td>Fine Science Tools</td>
			<td>11150-10</td>
			<td>2 pairs</td>
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			<td>Eye lubricant</td>
			<td>CLCMEDICA</td>
			<td>Optixcare eye lube</td>
			<td></td>
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			<td>Heparin (5000 U/mL)</td>
			<td>National Drug Codes List</td>
			<td>63739-953-25</td>
			<td>100 IU/mL</td>
		</tr>
		<tr>
			<td>Hot bead sterilizer</td>
			<td>Fine Science Tools</td>
			<td>18000-50</td>
			<td></td>
		</tr>
		<tr>
			<td>Low-temperature cautery</td>
			<td>Bovie</td>
			<td>AA04</td>
			<td></td>
		</tr>
		<tr>
			<td>Pen trimmer</td>
			<td>Wahl</td>
			<td>5640-600</td>
			<td></td>
		</tr>
		<tr>
			<td>Powder-free surgical gloves</td>
			<td>Ansell</td>
			<td>7824PF</td>
			<td></td>
		</tr>
		<tr>
			<td>Round handled needle holders</td>
			<td>Fine Science Tools</td>
			<td>12076-12</td>
			<td></td>
		</tr>
		<tr>
			<td>Sterile towel drape</td>
			<td>Dynarex</td>
			<td>DY440-MI</td>
			<td></td>
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		<tr>
			<td>Sterilized 0.9% saline</td>
			<td>National Drug Codes List</td>
			<td>46066-807-25</td>
			<td></td>
		</tr>
		<tr>
			<td>Straight dumont forceps</td>
			<td>Fine Science Tools</td>
			<td>11253-20</td>
			<td></td>
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		<tr>
			<td>Straight needle holder</td>
			<td>Fine Science Tools</td>
			<td>FST 12001-13</td>
			<td></td>
		</tr>
		<tr>
			<td>Straight vannas spring scissors</td>
			<td>Fine Science Tools</td>
			<td>25001-08</td>
			<td></td>
		</tr>
		<tr>
			<td>TrizChLOR4</td>
			<td>National Drug Codes List</td>
			<td>17033-279-50</td>
			<td></td>
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a murine model of hemodialysis access-related hand dysfunction

Chronic kidney disease is a major public health problem, and the prevalence of end-stage renal disease (ESRD) requiring chronic renal replacement therapies such as hemodialysis continues to increase. Autogenous arteriovenous fistula (AVF) placement remains a primary vascular access option for ESRD patients. Unfortunately, approximately half of the hemodialysis patients experience dialysis access-related hand dysfunction (ARHD), ranging from subtle paresthesia to digital gangrene. Notably, the underlying biologic drivers responsible for ARHD are poorly understood, and no adequate animal model exists to elucidate the mechanisms and/or develop novel therapeutics for the prevention/treatment of ARHD. Herein, we describe a new mouse model in which an AVF is created between the left common iliac artery and vein, thereby facilitating the assessment of limb pathophysiology. The microsurgery includes vessel isolation, longitudinal venotomy, creation of arteriovenous anastomosis, and venous reconstruction. Sham surgeries include all the critical steps except for AVF creation. Iliac AVF placement results in clinically relevant alterations in central hemodynamics, peripheral ischemia, and impairments in hindlimb neuromotor performance. This novel preclinical AVF model provides a useful platform that recapitulates common neuromotor perturbations reported by hemodialysis patients, allowing researchers to investigate the mechanisms of ARHD pathophysiology and test potential therapeutics.

Animals exposed to an adenine diet have reduced glomerular filtration rates (control: 441.3 &#177; 54.2 &#181;L/min vs. CKD: 165.1 &#177; 118.3 &#181;L/min, p &#60; 0.05) and increased serum blood urea nitrogen levels (control: 20.39 &#177; 4.2 &#181;L/min vs. CKD: 38.20 &#177; 10.65 &#181;L/min, p &#60; 0.05) compared to the animals that received casein-based chow, confirming the presence of kidney insufficiency prior to arteriovenous fistula surgery.
Validation of A...

Watch this Scientific Journal Video about A Murine Model of Hemodialysis Access-Related Hand Dysfunction at JoVE.com

A Murine Model of Hemodialysis Access-Related Hand Dysfunction

This protocol details the surgical steps of murine common iliac arteriovenous fistula creation. We developed this model to study hemodialysis access-related limb pathophysiology.

Chronic kidney disease is a major public health problem, and the prevalence of end-stage renal disease (ESRD) requiring chronic renal replacement ...

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