Person:

Hess, Philip

Objective We investigated the role of neuropeptide Y (NPY), abundant in the myocardial sympathetic nervous system and endothelial cells, in angiogenesis during chronic myocardial ischemia.

Methods Adult male Yorkshire swine underwent ameroid constrictor placement on the proximal left circumflex coronary artery. After three weeks, an osmotic pump was placed to deliver either placebo (control, n=8) or NPY3-36 (NPY, n=8) to the collateral dependent region. Five weeks after pump placement, after cardiac catheterization and hemodynamic assessment, the heart was harvested for analysis.

Results NPY treated animals demonstrated increased mean arterial pressures and improved left ventricular function (+dP/dt). Cardiac catheterization demonstrated a significant increase in the blush score in the NPY group (p<0.001). Blood flow to the ischemic myocardium was not different between groups at rest or during ventricular pacing. Immunohistochemical double staining for CD-31 and smooth muscle actin demonstrated an increase in capillary and arteriole formation in NPY treated animals (p=0.02 and p<0.001). Immunoblotting showed a significant upregulation of DPPIV (p=0.009) and NPY receptors 1 (p=0.008), 2 (p=0.02) and 5 (p=0.03) in the NPY treated group. Additionally, there was significant upregulation of VEGF (p=0.04), eNOS (p=0.014), phospho-eNOS(ser1177)(p=0.02), and PDGF (p<0.001) in NPY treated group. The anti-angiogenic factors endostatin and angiostatin were significantly decreased in NPY treated animals (endostatin, p=0.03, angiostatin p=0.04).

Conclusion Exogenous NPY3-36 resulted in improved myocardial function and increased angiogenesis and arteriogenesis by stimulating growth factor, pro-angiogenic receptor upregulation, and decreasing anti-angiogenic expression, but did not increase blood flow to the ischemic myocardium. NPY may act as a good adjunct to primary agents of therapeutic angiogenesis.

Background: Mitral valve (MV) annular dynamics have been well described in animal models of functional mitral regurgitation (FMR). Despite this little, if any, data exists regarding the dynamic MV annular geometry in humans with FMR. In the current study we hypothesized that three-dimensional (3D) echocardiography, in conjunction with commercially available software, could be used to quantify the dynamic changes in MV annular geometry associated with FMR. Methods: Intraoperative 3D transesophageal echocardiographic data obtained from 34 patients with FMR and 15 controls undergoing cardiac surgery were dynamically analyzed for differences in mitral annular geometry with TomTec© 4D MV Assessment 2.0 software. Results: In patients with FMR, the mean mitral annular area (14.6cm2 vs. 9.6cm2), circumference (14.1cm vs. 11.4 cm), anteroposterior (4.0cm vs. 3.0cm) and anterolateral-posteromedial (4.3cm vs. 3.6cm) diameters, tenting volume (6.2mm3 vs. 3.5mm3) and nonplanarity angle (154° ± 15 vs. 136° ± 11) were greater at all points during systole compared to controls (p<0.01). Vertical mitral annular displacement (5.8mm vs. 8.3mm) was reduced in FMR compared to controls (p<0.01). Conclusions: There are significant differences in dynamic mitral annular geometry between patients with and without FMR. We were able to analyze these changes in a clinically feasible fashion. Ready availability of this information has the potential to aid comprehensive quantification of mitral annular function and possibly assist in both clinical decision-making and annuloplasty ring selection.

Background: Proficiency in transthoracic echocardiography (TTE) requires an integration of cognitive knowledge and psychomotor skills. Whereas cognitive knowledge can be quantified, psychomotor skills are implied after repetitive task performance. We applied motion analyses to evaluate psychomotor skill acquisition during simulator-based TTE training.

Methods and Results: During the first month of their fellowship training, 16 cardiology fellows underwent a multimodal TTE training program for 4 weeks (8 sessions). The program consisted of online and live didactics as well as simulator training. Kinematic metrics (path length, time, probe accelerations) were obtained at the start and end of the course for 8 standard TTE views using a simulator. At the end of the course TTE image acquisition skills were tested on human models. After completion of the training program the trainees reported improved self-perceived comfort with TTE imaging. There was also an increase of 8.7% in post-test knowledge scores. There was a reduction in the number of probe accelerations [median decrease 49.5, 95% CI = 29-73, adjusted P < 0.01], total time [median decrease 10.6 s, 95% CI = 6.6-15.5, adjusted P < 0.01] and path length [median decrease 8.8 cm, 95% CI = 2.2-17.7, adjusted P < 0.01] from the start to the end of the course. During evaluation on human models, the trainees were able to obtain all the required TTE views without instructor assistance.

Conclusion: Simulator-derived motion analyses can be used to objectively quantify acquisition of psychomotor skills during TTE training. Such an approach could be used to assess readiness for clinical practice of TTE.