Background: Ultrasound measurement of brachial artery flow mediated dilation during reactive hyperemia has been widely used in research as a noninvasive measure of endothelial function. However, the need for B-mode ultrasonography to measure brachial artery diameter can be technically challenging and inconvenient for providers and patients. Hyperspectral imaging (HSI) is a technology that with limited training can noninvasively measure oxyhemoglobin (oxyHb) and deoxyhemoglobin (deoxyHb) concentrations in the skin to create an oxygenation map. The aim of this pilot study was to determine if HSI could be used to demonstrate vascular dysfunction in the upper extremity of patients with peripheral artery disease (PAD) and coronary artery disease (CAD).Methods: This prospective study included consecutive, consented patients presenting to the vascular clinic with and without diagnosed arterial disease as well as healthy volunteers. Patients underwent HSI at the right biceps, forearm, and palm before and after cuff occlusion (50 mm Hg above systolic) for 5 minutes. Patients with blood pressure differences between arms >15 mm Hg, indicating possible vascular disease in the measured extremity, were excluded. The absolute and percent changes in oxyHb and deoxyHb levels were assessed. Medical records of enrolled patients were reviewed for demographic data, medications, surgical history, and other pertinent information. Patients were separated into healthy control and disease (consisting of patients with PAD or CAD) groups. Results are mean 6 standard error. Baseline differences in categoric variables of medical history were evaluated using the c 2 and Fisher exact test. Differences in HSI values between the groups were evaluated using the two-tailed t-test with statistical significance determined as P < .05.Results: The study enrolled 20 controls, including vascular clinic patients without arterial disease as well as healthy volunteers, and 15 patients with disease. The distinct groups had similar values at baseline. Significant differences were noted in every area of the arm tested for absolute changes in oxyHb values after cuff occlusion (P < .05), with the greatest difference noted in the forearm (percent change oxyHb: 57% vs 125%; P ¼ .005) for disease vs control, respectively; Table. No differences were noted for deox-yHb values. There were no differences between younger (age 40 years) and older control patients. Subgroup analysis of patients with PAD and/or CAD in the Fig demonstrated decreasing arterial reactivity (change in oxyHb after occlusion) with increasing number of vascular beds affected.Conclusions: This study presents a novel way to measure endothelial dysfunction similarly to the brachial artery reactivity test. Our results suggest the ability of HSI (using forearm oxyHb changes after suprasystolic brachial cuff occlusion) to assess the presence and severity of PAD and CAD based on systemic vascular dysfunction at sites remote from the clinically diseased vascular bed. This could enable early screening and ...

Background: Heart failure (HF) is the leading cause of mortality in United States. Animal models used to test novel HF therapeutics are inadequate as pathological features of human HF are not replicated. Available large-animal swine myocardial ischemia (MI) models mimic human HF; however, do not achieve ejection fractions (EF) less than 40%. Objective: We sought to develop a reproducible swine MI model with EF below 35%. Methods: Yucatan miniature pigs (n=18) were anesthetized, catheterized and collagen suspension (COL) of microfibrillar hemostat (INSTAT MCH, Ethicon) mixed in contrast and saline solution was injected into the left anterior descending coronary artery (LAD) under fluoroscopic guidance. COL injections started distally and filled side branches during catheter retraction. Complete transient LAD occlusion was confirmed at 2hrs by coronary angiography. Cardiac function was evaluated at 3mos using a 1.5T MRI System (Siemens Magnetom Avanto). LV volumes at end systole (LVESD) and diastole (LVEDD), EF, wall thickness (WT) in area at risk (AAR) and normal zones (NZ) were calculated. Uninjected Yucatan pigs (n=3) served as controls. Results: Twelve of 18 pigs survived COL infarction. At 3mos, EF was reduced in COL injected pigs compared to control (27.0±2.3 vs. 61.6±1.3%, respectively, P<0.001). LVESV and LVEDV were 4- and 2-fold higher and WT in AAR and NZ were reduced 6- and 2-fold, respectively in COL injected compared to controls. Conclusions: A reproducible large animal model of MI was produced by catheter based LAD collagen delivery resulting in EFs below 35% and progression to HF. By closely resembles human HF, it a highly useful for testing potential HF therapies.

Critical limb ischemia (CLI) patients have an increased risk of major amputation of 25‐40% and an annual mortality of 20%. We observed a marked attenuation of nitric oxide (NO) bioavailability and NO signaling in tissue from CLI patients. Skeletal muscle nitrite levels were significantly attenuated in CLI patients compared to controls (89.9 ± 9.3 µM vs. 428.4 ± 65.6 µM; p<0.001). We hypothesized that NO‐based therapy would enhance blood flow to the ischemic limb and ameliorate skeletal muscle necrosis in CLI. We investigated the effects of oral, sustained release (SR)‐nitrite (Theravasc Inc., Cleveland, OH) in a clinically relevant model of CLI with central obesity and metabolic syndrome. Obese Ossabaw swine (n=9 per group) were subjected to percutaneous occlusion of their common and external iliac arteries, which induced CLI. After 14 days of CLI, pigs were randomized to oral placebo or SR‐nitrite therapy (80mg/tablet 2x per day) for 35 days. Weekly, limb cuff mean blood pressure and Doppler ultrasound superficial femoral artery vessel area were measured in the ischemic limb. Despite trends for improved blood flow with SR‐nitrite there were no significant differences in ischemic limb blood pressure (A) and superficial femoral artery area (B) between study groups. Additional animals have been enrolled in the study to more fully assess the effects of SR‐nitrite therapy for the treatment of CLI. $graphic_FBCB7A13‐37D9‐43D4‐9359‐9360D8AFA024$ Grant Funding Source: NIH 1R01 HL092141, NIH 1R01 HL093579, NIH 1U24 HL094373, NIH 1P20 HL113452, The CFHC

Background: Aging is associated with increased mortality following acute myocardial infarction (AMI). Early cell therapy clinical trials for AMI have shown a modest improvement in cardiac function. Previous evidence suggest that B cells may be protective in tissue injury. Our initial studies showed that intramyocardial delivery of bone marrow derived B cells improves cardiac function in young rats. Aim: In this study, we determined the effect of B cell therapy in aged animals subjected to AMI using a clinically relevant protocol. Methods: Human PB B cells were isolated from buffy coats using CD19+ selection. Young (8-10wks) and aged (10-12mos) athymic rats had baseline echocardiography then coronary artery ligation (d1). At d7, rats had repeat echocardiography and received 1×10 7 B cells or vehicle intravenously. At d9 and d21, rats underwent follow-up echocardiography. Explanted hearts were measured for infarct size and B cell localization was determined in infarcted aged rat hearts after d8 in a subset of animals by IHC. Results: Fractional ventricular diameter shortening (FS) decreased at d7 compared to baseline in young (27.9 ±0.9 vs. 55.6±0.6%, P <0.001) and aged (31.6±0.9 vs. 53.4±0.5%, P <0.001) rats. At d9, FS was higher in B cell compared to control treated aged rats (44.9±2.6 vs. 29.3±3.0%, P <0.001). FS was minimally changed in B cell compared to control treated young rats (37.3±3.3 vs. 31.2±3.5%, P =NS). At d21, FS was higher in aged rats receiving B cells compared to controls (38.6±2.2 vs. 30.0±2.6%, P <0.001) and trended higher in B cell treated young rats compared to control (34.1±1.8 vs. 28.0±2.6%, P =0.058). FS was higher in aged rats receiving B cells stored for 1.5hrs at room temperature compared to freshly prepared B cells (35.1±3.2% vs. 27.1±2.4%, P =0.035). Infarct size was smaller in B cell treated aged rats compared to controls (12.9±2.3 vs. 22.4±2.4% LV, P =0.010); no difference in infarct size was detected in young rats. B cells were detected in the infarct of aged rats at d8. Conclusion: These data support that intravenous delivery of peripheral blood B cells is efficacious in improving cardiac function and limiting infarct size in aged rats, an experimental model more relevant to clinical population.