Noninvasive assessment of human microvascular function in health and disease using incident dark-field microscopy.

Reduced peripheral microvascular reactivity is associated with an increased risk for major adverse cardiac events (MACEs). Tools for noninvasive assessment of peripheral microvascular function are limited, and existing technology is poorly validated in both healthy populations and patients with cardiovascular disease (CVD). Here, we used a handheld incident dark-field imaging tool (CytoCam) to test the hypothesis that, compared with healthy individuals (no risk factors for CVD), subjects formally diagnosed with coronary artery disease (CAD) or those with ≥2 risk factors for CAD (at risk) would exhibit impaired peripheral microvascular reactivity. A total of 17 participants (11 healthy, 6 at risk) were included in this pilot study. CytoCam was used to measure sublingual microvascular total vessel density (TVD), perfused vessel density (PVD), and microvascular flow index (MFI) in response to the topical application of acetylcholine (ACh) and sublingual administration of nitroglycerin (NTG). Baseline MFI and PVD were significantly reduced in the at-risk cohort compared with healthy individuals. Surprisingly, following the application of acetylcholine and nitroglycerin, both groups showed a significant improvement in all three microvascular perfusion parameters. These results suggest that, despite baseline reductions in both microvascular density and perfusion, human in vivo peripheral microvascular reactivity to both endothelial-dependent and -independent vasoactive agents remains intact in individuals with CAD or multiple risk factors for disease.NEW & NOTEWORTHY To our knowledge, this is the first study to comprehensively characterize in vivo sublingual microvascular structure and function (endothelium-dependent and -independent) in healthy patients and those with CVD. Importantly, we used an easy-to-use handheld device that can be easily translated to clinical settings. Our results indicate that baseline microvascular impairments in structure and function can be detected using the CytoCam technology, although reactivity to acetylcholine may be maintained even during disease in the peripheral microcirculation.

Characterization of early-onset motor deficits in the Pink1-/- mouse model of Parkinson disease.

In Parkinson disease (PD), a complex neurodegenerative disorder that affects nearly 10 million people worldwide, motor skills are significantly impaired. However, onset and progression of motor deficits and the neural correlates of these deficits are poorly understood. We used a genetic mouse model of PD (Pink1-/-), with phenotypic similarities to human PD, to investigate the manifestation of early-onset sensorimotor deficits. We hypothesized this mouse model would show early vocalization and gross motor dysfunction that would be progressive in nature. Pink1-/- mice, compared to wild type (WT) controls, were evaluated at 2, 3, 4, 5, and 6 months of age. To quantify deficit progression, ultrasonic vocalizations and spontaneous locomotor activity (cylinder test and pole test) were analyzed. Although somewhat variable, in general, Pink1-/- mice produced significantly more simple calls with reduced intensity as well as a larger percentage of cycle calls compared to WT counterparts. However, there were no significant differences in duration, bandwidth, or peak frequency for any of the ultrasonic call types between genotypes. Pink1-/- mice showed a significant impairment in limb motor skills with fewer hindlimb steps, forelimb steps, and rears and lands in the cylinder test compared to WT. Additionally, Pink1-/- mice took significantly longer to turn and traverse during the pole test. Immunohistochemical staining showed no significant difference in the number of tyrosine hydroxylase (TH) positive cells in the substantia nigra or density of TH staining in the striatum between genotypes. These data suggest the Pink1-/- mouse model may be instrumental in defining early motor biomarkers of PD in the absence of nigrostriatal dopamine loss.