Evaluation of hydrophilic polymer embolization from endovascular sheath devices in an in vitro perfusion system.

Objective: Case reports, tissue pathology, and autopsies have suggested that the hydrophilic polymer coating designed to improve endovascular deliverability and minimize vessel trauma can embolize and be associated with adverse outcomes such as ischemia, infarction, and death. This study sought to determine whether hydrophilic polymers shed off commercially available sheaths in a controlled in vitro environment, with the hypothesis that significant differences between coated and uncoated (control) sheaths would be found. Methods: Six sheaths from each manufacturer, including Zenith Alpha abdominal endovascular stent grafts (Cook Medical), DrySeal sheaths (W.L. Gore & Associates), and Sentrant Introducer sheaths (Medtronic), were tested in an in vitro environment. Noncoated Check-Flo performer introducer sheaths (Cook Medical) were used as controls. Each test circuit ran for 150 minutes at an output of 3 L/min, the circuit was then drained and the fluid collected. Quantitative analysis included weighing the dried filter paper and using particle size light scattering to quantify the particle size and count. Attenuated total reflectance spectroscopy was also used. Results: Each of the three coated sheaths had significantly greater shedding compared with the control sheaths. The Cook Zenith alpha sheath had significantly more residue weight (2.87 ± 0.52 mg/L) than the Gore DrySeal (1.07 ± 0.06 mg/L) and Medtronic Sentrant introducer (0.98 ± 0.14 mg/L) sheaths. The average particle size was not significantly different between the coated and uncoated (control) sheaths. Attenuated total reflectance spectroscopy identified sheath particulate in the Cook Zenith Alpha and Medtronic Sentrant samples. Conclusions: Polymer embolization was present and significantly greater in all three commercially available hydrophilic sheaths compared with the control group. Further investigation is needed into the clinical significance of these findings.

Cryopreserved venous allograft in the treatment of a mycotic abdominal aortic aneurysm caused by group B Streptococcus.

We report a case of a mycotic abdominal aortic aneurysm caused by invasive group B streptococcus. Given the anatomical suitability with healthy segments of aortoiliac vessels, in situ repair was performed. A cryopreserved femoral vein graft was chosen because of risks of graft reinfection and negated the need for bilateral femoral vein harvest. The patient remained clinically well and the graft patent with no concerns at 6 months of follow-up. A review of literature on group B Streptococcus aortitis was performed.

Exploring the Utility of Brain Natriuretic Peptide Measurement in Vascular Surgery.

BACKGROUND: The Canadian Cardiovascular Society 2016 guidelines recommend pre-operative measurement of brain natriuretic peptide (BNP) to risk-stratify patients for a 30-day composite outcome of death, myocardial infarction, or asymptomatic myocardial injury after noncardiac surgery (MINS). Whether this practice affects outcomes is unclear. The aim of this study was to examine the clinical utility of brain natriuretic peptide and myocardial injury after noncardiac surgery. METHODS: Analysis of a prospectively maintained database identified all elective open vascular surgery cases at an academic teaching hospital from January 2015 to December 2018. Pre-operative BNP values were available from June 2018 onward after becoming institutionally mandated. Co-morbidities were also collected to stratify patients using the Revised Cardiac Risk Index. The composite outcome of 30-day mortality, myocardial infarction, or MINS was determined. RESULTS: Prior to BNP becoming an institutionally required test, data was available from 1176 open cases. The 30-day mortality was 1.3% (15/1176) and post-operative myocardial infarction rate was 2.3% (27/1176). BNP measurements were collected in 91 consecutive patients. Ten patients (11%) experienced the composite outcome of mortality, myocardial infarction, or MINS. Elevated BNP was associated with increased odds of the composite outcome (P = 0.04), but not with mortality or myocardial infarction. Revised Cardiac Risk Index score was not predictive of outcomes. The majority of patients who qualified for the composite outcome experienced only an asymptomatic troponin rise (80%). Two patients met the universal definition of myocardial infarction, one of whom died. No other deaths occurred within 30 days. Detection of MINS did not result in any significant changes to patient management. CONCLUSIONS: Elevated BNP correlates with increased MINS. An asymptomatic troponin rise is the most commonly observed event, with unclear clinical implications. BNP may over-estimate surgical risk. Further studies on the long-term outcomes of patients with elevated BNP and MINS are required before widely adopting this strategy in vascular surgery patients.

Thalamic stroke in a patient with aberrant right vertebral artery arising from an atherosclerotic carotid bulb.

Aberrant vertebral artery (VA) origins are uncommon, and those arising from the carotid bulb are exceedingly rare. We report a 79-year-old man with a right thalamic stroke and subsequent amaurosis fugax that was found to have severe right carotid bulb and internal carotid artery stenoses, as well as an aberrant VA arising from the bulb. He underwent carotid endarterectomy including eversion endarterectomy of the VA and had no recurrence of amaurosis fugax or posterior circulation symptoms at the 1-year follow-up. We also present a comprehensive review of the literature, focusing on symptomatic cases and those arising from the carotid bulb.

Ultrasound-guided cyanoacrylate injection for the treatment of incompetent perforator veins.

OBJECTIVE: The use of cyanoacrylate products (CA) in incompetent perforator vein (IPV) treatment has not been thoroughly examined. The primary objective of this study is to describe the technique of ultra sound guided direct injection of IPV with CA, and secondarily to determine early closure rates and safety of this technique. METHODS: A retrospective analysis of patients undergoing IPV injection at two centres between 2015-2018 was conducted. Demographics, CEAP classification and IPV location were collected. Outcomes were assessed at two follow-up appointments. RESULTS: A total of 83 perforator vein injections were completed. CEAP classifications include C2 - C6 classes. Location of perforators were posteromedial (6%), femoral canal (9%), paratibial (14%), and posterior-tibial (71%). IPV closure rates were 96.3% at initial follow-up (16 ± 2 days). Closure rates decreased to 86.5% at second follow-up (72 ± 9 days). There were no deep vein thromboses during follow-up. One patient developed septic thrombophlebitis that was successfully managed with antibiotics. CONCLUSION: Ultrasound-guided CA glue injection is a simple and low risk procedure that effectively closes incompetent perforator veins.

Evaluation of Aortic Zone 2 Proximal Landing Accuracy During Thoracic Endovascular Aortic Repair Following Carotid-Subclavian Revascularization.

BACKGROUND: Adequate seal for thoracic endovascular aortic repair (TEVAR) commonly requires landing in zone 2, but can prove to be challenging due to the tortuous and angulated anatomy of the region. OBJECTIVES: Our objective was to determine the proximal landing accuracy of zone 2-targeted TEVARs following carotid-subclavian revascularization (CSR) and its impact on clinical outcomes. METHODS: Retrospective review of patients that underwent CSR for zone 2 endograft delivery at a tertiary institute between January 2008 and March 2018 was conducted. Technical outcomes were assessed by examining the incidence of intraoperative corrective maneuvers, 1a endoleaks and reinterventions. Distance to target and incidence of LSA stump filling were examined as radiographic markers of landing accuracy. RESULTS: Zone 2-targeted TEVAR with CSR was performed in 53 patients for treatment of dissections (49%), aneurysms (30%) or trauma (21%). Nine (17%) cases required intraoperative corrective procedures: 5 (9%) proximal cuffs due to type 1a endoleak and 4 (8%) left common carotid artery (LCCA) stenting due to inadvertent coverage. Cases performed using higher resolution hybrid fluoroscopy machine compared to mobile C-arm were associated with increased proximal cuff use (OR 8.8; 95% CI 1.2-62.4). Average distance between the proximal edge of the covered graft to LCCA was 8 ± 1 mm and larger distances were not associated with higher rates of 1a endoleak. Twenty-eight (53%) cases of antegrade LSA stump filling were noted on follow-up imaging, but were not associated with higher rates of reinterventions (OR 0.8, 95% CI [0.2-4.6]). Three (6%) patients had a stroke within 30 days and 4 (8%) patients expired within 1 month. Intraoperative corrective maneuvers, post-operative 1a endoleak and reinterventions were not associated with higher rates of stroke or mortality. CONCLUSION: Using current endografts and imaging modalities, zone 2-targeted TEVARs have suboptimal technical accuracy.

Vascular Access Complications and Clinical Outcomes of Vascular Surgical Repairs Following Transcatheter Aortic Valve Implantation (TAVI).

BACKGROUND: Transcatheter aortic valve implantation (TAVI) procedures have revolutionized the treatment of aortic stenosis. However, due to large sheaths, improperly deployed closure devices, and the comorbidities and challenges innate to this population, vascular access complications can be devastating. The objective of this study is to evaluate vascular access complications in one of the largest TAVI sites in North America. METHODS: This was a retrospective single center review between January 2014 and December 2018 of vascular access complications necessitating operative intervention by vascular surgery. Patient demographics and preoperative comorbidities were collected. Type of vascular access complication, types of repair, closure device used, and postoperative outcomes were analyzed. RESULTS: A total of 37 cases out of a total of 985 TAVI procedures were identified. TAVI was carried out in the operating suite (70%) or the catheterization lab (30%). Consults to vascular surgery were requested intraoperatively (60%), immediately postoperative (14%), later in the day of the TAVI (20%), and on postoperative day 1 (6%). The location of injury included common femoral artery (49%), superficial femoral artery (11%) and external iliac artery (41%), with some cases injuring multiple vessels. Closure devices were found in the subcutaneous tissue (26%), anterior wall (37%), posterior wall (11%), intra-arterial (11%), closing the anterior to the posterior wall (16%), and in the inguinal ligament (5%). Injuries included tears (11%), dissections (38%), and vessel rupture (19%). The majority of repairs were done primarily (64%), with patch (28%) and bypass (8%) less frequently. Four patients died perioperatively (11%), 2 from hemorrhage, 1 from cardiac arrest, and 1 from progressive respiratory disease. CONCLUSIONS: Access complications during TAVI procedures predispose complex patients to increased risk of morbidity and mortality. Careful patient selection, proper access techniques, and performing high risk patients in the operating suite with vascular surgery are fundamental in minimizing complications.

Cost-minimization study of the percutaneous approach to endovascular aortic aneurysm repair.

OBJECTIVE: Percutaneous access for endovascular aortic aneurysm repair (P-EVAR) is less invasive compared with surgical access for endovascular aortic aneurysm repair (S-EVAR). P-EVAR has been associated with shorter recovery and fewer wound complications. However, vascular closure devices (VCDs) are costly, and the economic effects of P-EVAR have important implications for resource allocation. The objective of our study was to estimate the differences in the costs between P-EVAR and S-EVAR. METHODS: We used a decision tree to analyze the costs from a payer perspective throughout the course of the index hospitalization. The probabilities, relative risks, and mean difference summary measures were obtained from a systematic review and meta-analysis. We modelled differences in surgical site infection, lymphocele, and the length of hospitalization. Cost parameters were derived from the 2014 National Inpatient Sample using "International Classification of Diseases, 9th Revision, Clinical Modification" codes. Attributable costs were estimated using generalized linear models adjusted by age, sex, and comorbidities. A sensitivity analysis was performed to determine the robustness of the results. RESULTS: A total of 6876 abdominal and thoracic EVARs were identified. P-EVAR resulted in a mean cost savings of $751 per procedure. The mean costs for P-EVAR were $1287 (95% confidence interval [CI], $884-$1835) and for S-EVAR were $2038 (95% CI, $757-$4280). P-EVAR procedures were converted to open procedures in 4.3% of the cases. The P-EVAR patients had a difference of -1.4 days (95% CI, -0.12 to -2.68) in the length of hospitalization at a cost of $1190/d (standard error, $298). The cost savings of P-EVAR was primarily driven by the cost differences in the length of hospitalization. In the base case, four VCDs were used per P-EVAR at $200/device. In the two-way sensitivity analysis, P-EVAR resulted in cost savings, even when 1.5 times more VCDs had been used per procedure and the cost of each VCD was 1.5 times greater. In our probabilistic sensitivity analysis, P-EVAR was the cost savings strategy for 82.6% of 10,000 Monte Carlo simulations when simultaneously varying parameters across their uncertainty ranges. CONCLUSIONS: P-EVAR had lower costs compared with S-EVAR and could result in dramatic cost savings if extrapolated to the number of aortic aneurysms repaired. Our analysis was a conservative estimate that did not account for the improved quality of life after P-EVAR.

Dysphagia aortica secondary to thoracoabdominal aortic aneurysm resolved after endograft placement.

Dysphagia aortica is a rare entity defined as difficulty in swallowing due to external compression by the aorta. Aneurysmal dysphagia aortica successfully treated with thoracic endovascular aortic repair (TEVAR) is exceedingly rare. We report the case of a 74-year-old woman with known thoracoabdominal aneurysm who presented with acute shortness of breath and 3-month history of dysphagia. Computed tomography angiography revealed aneurysmal growth and massive esophageal dilation. She underwent TEVAR and visceral debranching, which led to complete symptom resolution correlated with sac regression. We also present a comprehensive review of the literature with a focus on cases of aneurysmal dysphagia aortica treated with TEVAR.

Hydrophilic polymer embolization after thoracic endovascular aortic repair.

Hydrophilic polymer embolization is a rare complication after endovascular procedures that is currently underappreciated. Present understanding on this phenomenon relies on sparse case reports with histologic evidence of foreign polymers in end-organ tissue. Here, we report two deaths associated with hydrophilic polymer embolization after complex thoracic endovascular aortic repair.

Outcomes of a Spinal Drain and Intraoperative Neurophysiologic Monitoring Protocol in Thoracic Endovascular Aortic Repair.

BACKGROUND: Adjuncts for early detection and treatment of spinal cord ischemia (SCI) in thoracic aortic surgery are supported by robust clinical experience in open repair. The utility of cerebrospinal fluid (CSF) drainage and neurophysiologic monitoring (NPM) in thoracic endovascular aortic repair (TEVAR) is less clear. The purpose of this investigation is to determine the influence of a selective institutional spinal cord protection protocol using prophylactic NPM and CSF on outcomes for standard TEVAR. METHODS: Patients undergoing standard TEVAR entered into a prospectively maintained database from a single institution from 2007 to 2016 were retrospectively reviewed. Preoperative characteristics, aneurysm extent, and etiology were reviewed. Utilization of CSF drains including volume of fluid removed, duration of drainage, and catheter-related complications were collected. NPM data were reviewed to determine the influence on intraoperative management. Exact logistic regression was used to identify independent predictors of SCI. RESULTS: Of 223 patients undergoing TEVAR, 130 met inclusion criteria for the study. CSF drains were used in 71 patients (54.6%), and 56 of 130 (43%) had NPM. SCI occurred in 7 patients (5.4%), of whom 5 had partial or complete recovery. Median time to symptoms of SCI was delayed in all cases (median 52 hr, range 8-312), and none of the 4 of 7 patients with adjunct NPM demonstrated intraoperative changes. Intraoperative changes in NPM occurred in 26 (46%), and represented unilateral leg ischemia in all but 2 cases. In both patients, changes consistent with SCI were associated with intraoperative hypotension and resolved with blood pressure augmentation. Neither patient developed postoperative SCI. Median length of stay (22 vs. 9 days, P = 0.012), operative room time (262 vs. 209, P = 0.040), and perioperative mortality (28.6% vs. 4.1%, P = 0.046) were significantly higher for patients with SCI versus those without. Length of aortic coverage was found to be the sole independent predictor of SCI (odds ratio 8.2, P = 0.026). Complications related to CSF drainage occurred in 4 patients (5.6%) with major complications occurring in 2 patients (2.8%), including 1 with an intrathecal hematoma and permanent bilateral paraparesis. CONCLUSIONS: Selective use of prophylactic CSF drainage in TEVAR was associated with moderate risk and questionable benefit. The use of neurophysiological monitoring allowed for early detection and treatment of spinal ischemia, but its utility is limited by logistical factors and to the minority of patients with intraoperative spinal ischemic events.

Comparison of cyanoacrylate embolization and radiofrequency ablation for the treatment of varicose veins.

OBJECTIVE: To review clinical outcomes of varicose vein patients treated with cyanoacrylate embolization and radiofrequency ablation at our institution. METHODS: A retrospective review of patients who underwent cyanoacrylate embolization and radiofrequency ablation during a three-year period. Patient records were reviewed to assess demographics, location and severity of disease, treatment details and outcome at short- and mid-term follow-ups. Outcome parameters included treatment success and complications. RESULTS: Between January 2014 and December 2016, 335 patients with 476 veins were treated with either cyanoacrylate embolization (n = 148) or radiofrequency ablation (n = 328) at the Vancouver General Hospital Vascular Surgery Vein Clinic. The average age of patients were 57 ± 1 years with the majority being female (78%) and an average BMI of 24.8 ± 0.5. CEAP classes were 2 (49%), 3 (26%), 4a (22%) and >4b (3%). Of the veins treated with cyanoacrylate embolization, the vein types were as follows: 76% were great saphenous vein, 16% were small saphenous vein, 5% were anterior accessory great saphenous vein and 1.4% were perforator veins. The vein types for radiofrequency ablation were 88%, 9%, 3% and 0%, respectively. The average amount of cyanoacrylate embolization delivered for great saphenous vein treatment was 1.8 ± 0.1 ml with a treatment length of 43 ± 1 cm. Subgroup comparison was done for great saphenous vein segments. Treatment success was 100% in cyanoacrylate embolization and 99% in radiofrequency ablation. Superficial phlebitis was the most common complication noted at mid-term follow-up in 5% of cyanoacrylate embolization and 16% of radiofrequency ablation treatments (P < 0.05). One patient in each group had asymptomatic proximal thrombus extension treated with anticoagulation for 2-3 weeks. Three superficial infections from glue clumps were noted in the cyanoacrylate embolization group requiring excision and drainage. Five patients in the radiofrequency ablation group had persistent numbness and one wound complications at the access site. CONCLUSION: Cyanoacrylate embolization offers equivalent success rates with lower mid-term complication rates as radiofrequency ablation.

Critical Evaluation of Delayed Healing of Venous Leg Ulcers: A Retrospective Analysis in Canadian Patients.

BACKGROUND: Venous leg ulcers (VLUs) are common but challenging health problems. Better understanding of the risk factors involved in delayed healing of VLUs may therefore guide individualized treatment plans to improve patient outcomes. OBJECTIVE: We sought to identify the risk factors associated with delayed healing of VLUs in patients seen at a tertiary academic wound care clinic. METHODS: A retrospective analysis of 554 patients who presented to the Toronto Regional Wound Healing Clinic for VLUs in a 3-year period was performed. Patient and ulcer characteristics were recorded. Multivariate analyses were performed to compare patients with ulcer resolution and those whose ulcers did not resolve after 12-month follow-up. RESULTS: The average age of the patients was 67.3 ± 0.7 years, with 56 % being female. The most common comorbidities were hypertension (54 %), dyslipidemia (33 %), a history of smoking (30 %), and diabetes (26 %). Ulcer resolution was associated with a smaller ulcer size (odds ratio [OR] 0.984 [95 % confidence interval (CI) 0.973, 0.996]), shorter ulcer duration (OR 0.704 [95 % CI 0.574, 0.865]), and dyslipidemia (OR 1.848 [95 % CI 1.052, 3.246]). CONCLUSION: Pro-healing factors associated with VLUs were a smaller ulcer size and a shorter ulcer duration. Dyslipidemia was also associated with improved healing, potentially owing to the use of statins. Patients presenting with poorer-prognosis VLUs should receive more aggressive treatment with earlier referral to vascular surgery.

Glycosuria-mediated urinary uric acid excretion in patients with uncomplicated type 1 diabetes mellitus.

Plasma uric acid (PUA) is associated with metabolic, cardiovascular, and renal abnormalities in patients with type 2 diabetes but is less well understood in type 1 diabetes (T1D). Our aim was to compare PUA levels and fractional uric acid excretion (FEUA) in patients with T1D vs. healthy controls (HC) during euglycemia and hyperglycemia. PUA, FEUA, blood pressure (BP), glomerular filtration rate (GFR-inulin), and effective renal plasma flow (ERPF-paraaminohippurate) were evaluated in patients with T1D (n = 66) during clamped euglycemia (glucose 4-6 mmol/l) and hyperglycemia (9-11 mmol/l), and in HC (n = 41) during euglycemia. To separate the effects of hyperglycemia vs. increased glycosuria, parameters were evaluated during clamped euglycemia in a subset of T1D patients before and after sodium glucose cotransporter 2 (SGLT2) inhibition for 8 wk. PUA was lower in T1D vs. HC (228 ± 62 vs. 305 ± 75 µmol/l, P < 0.0001). In T1D, hyperglycemia further decreased PUA (228 ± 62 to 199 ± 65 µmol/l, P < 0.0001), which was accompanied by an increase in FEUA (7.3 ± 3.8 to 11.6 ± 6.7, P < 0.0001). In T1D, PUA levels correlated positively with SBP (P = 0.029) and negatively with ERPF (P = 0.031) and GFR (P = 0.028). After induction of glycosuria with SGLT2 inhibition while maintaining clamped euglycemia, PUA decreased (P < 0.0001) and FEUA increased (P < 0.0001). PUA is lower in T1D vs. HC and positively correlates with SBP and negatively with GFR and ERPF in T1D. Glycosuria rather than hyperglycemia increases uricosuria in T1D. Future studies examining the effect of uric acid-lowering therapies should account for the impact of ambient glycemia, which causes an important uricosuric effect.

Renal hyperfiltration is associated with glucose-dependent changes in fractional excretion of sodium in patients with uncomplicated type 1 diabetes.

OBJECTIVE: Renal hyperfiltration is a common abnormality associated with diabetic nephropathy in patients with type 1 diabetes (T1D). In animal models, increased proximal tubular sodium reabsorption results in decreased distal sodium delivery, tubuloglomerular feedback activation, afferent vasodilatation, and hyperfiltration. The role of tubular factors is less well understood in humans. The aim of the current study was therefore to compare the fractional sodium excretion (FENa) in hyperfiltering (T1D-H) versus normofiltering (T1D-N) patients and healthy control (HC) subjects, as well as the role of ambient hyperglycemia on FENa. RESEARCH DESIGN AND METHODS: Blood pressure, renal function (inulin for glomerular filtration rate [GFR], and paraaminohippurate for effective renal plasma flow), FENa, and circulating neurohormones were measured in T1D-H (n = 28, GFR ≥135 mL/min/1.73 m(2)), T1D-N (n = 30), and HC (n = 35) subjects during clamped euglycemia. Studies were repeated in a subset of patients during clamped hyperglycemia. RESULTS: During clamped euglycemia, T1D-H exhibited lower FENa than T1D-N and HC subjects (0.64 ± 0.06% vs. 0.91 ± 0.12% and 0.90 ± 0.10%, P < 0.05). During clamped hyperglycemia, FENa increased (Δ + 0.88 ± 0.22% vs. Δ + 0.02 ± 0.21%; between-group effect, P = 0.01) significantly in T1D-H, whereas FENa did not change in T1D-N. When treated as continuous variables, elevated GFR values were associated with hyperglycemia-induced increases in FENa (R(2) = 0.20, P = 0.007). CONCLUSIONS: Patients with uncomplicated T1D-H exhibit lower FENa under euglycemic conditions, which may help to identify patients with hyperfiltration outside of a controlled laboratory setting. Increased FENa in T1D-H but not T1D-N under clamped hyperglycemic conditions suggests that the mechanisms responsible for increased sodium reabsorption leading to hyperfiltration can be saturated.

Renal hyperfiltration and systemic blood pressure in patients with uncomplicated type 1 diabetes mellitus.

BACKGROUND: Patients with type 1 diabetes mellitus (DM) and renal hyperfiltration also exhibit systemic microvascular abnormalities, including endothelial dysfunction. The effect of renal hyperfiltration on systemic blood pressure (BP) is less clear. We therefore measured BP, renal hemodynamic function and circulating renin angiotensin aldosterone system (RAAS) mediators in type 1 DM patients with hyperfiltration (n = 36, DM-H, GFR≥135 ml/min/1.73 m(2)) or normofiltration (n = 40, DM-N), and 56 healthy controls (HC). Since renal hyperfiltration represents a state of intrarenal RAAS activation, we hypothesized that hyperfiltration would be associated with higher BP and elevated levels of circulating RAAS mediators. METHODS: BP, glomerular filtration rate (GFR - inulin), effective renal plasma flow (paraaminohippurate) and circulating RAAS components were measured in DM-H, DM-N and HC during clamped euglycemia (4-6 mmol/L). Studies were repeated in DM-H and DM-N during clamped hyperglycemia (9-11 mmol/L). RESULTS: Baseline GFR was elevated in DM-H vs. DM-N and HC (167±6 vs. 115±2 and 115±2 ml/min/1.73 m(2), p<0.0001). Baseline systolic BP (SBP, 117±2 vs. 111±2 vs. 109±1, p = 0.004) and heart rate (76±1 vs. 67±1 vs. 61±1, p<0.0001) were higher in DM-H vs. DM-N and HC. Despite higher SBP in DM-H, plasma aldosterone was lower in DM-H vs. DM-N and HC (42±5 vs. 86±14 vs. 276±41 ng/dl, p = 0.01). GFR (p<0.0001) and SBP (p<0.0001) increased during hyperglycemia in DM-N but not in DM-H. CONCLUSIONS: DM-H was associated with higher heart rate and SBP values and an exaggerated suppression of systemic aldosterone. Future work should focus on the mechanisms that explain this paradox in diabetes of renal hyperfiltration coupled with systemic RAAS suppression.

Improved blood glucose disposal and altered insulin secretion patterns in adenosine A(1) receptor knockout mice.

Type 2 diabetes mellitus (T2DM) is characterized by the inability of the pancreatic ß-cells to secrete enough insulin to meet the demands of the body. Therefore, research of potential therapeutic approaches to treat T2DM has focused on increasing insulin output from ß-cells or improving systemic sensitivity to circulating insulin. In this study, we examined the role of the A(1) receptor in glucose homeostasis with the use of A(1) receptor knockout mice (A(1)R(-/-)). A(1)R(-/-) mice exhibited superior glucose tolerance compared with wild-type controls. However, glucose-stimulated insulin release, insulin sensitivity, weight gain, and food intake were comparable between the two genotypes. Following a glucose challenge, plasma glucagon levels in wild-type controls decreased, but this was not observed in A(1)R(-/-) mice. In addition, pancreas perfusion with oscillatory glucose levels of 10-min intervals produced a regular pattern of pulsatile insulin release with a 10-min cycling period in wild-type controls and 5 min in A(1)R(-/-) mice. When the mice were fed a high-fat diet (HFD), both genotypes exhibited impaired glucose tolerance and insulin resistance. Increased insulin release was observed in HFD-fed mice in both genotypes, but increased glucagon release was observed only in HFD-fed A(1)R(-/-) mice. In addition, the regular patterns of insulin release following oscillatory glucose perfusion were abolished in HFD-fed mice in both genotypes. In conclusion, A(1) receptors in the pancreas are involved in regulating the temporal patterns of insulin release, which could have implications in the development of glucose intolerance seen in T2DM.