Publications

2016

Rabya Saraf B, Feroze Mahmood M, Rabia Amir M, Robina Matyal M. Neuropeptide Y is an Angiogenic Factor in Cardiovascular Regeneration. European Journal of Pharmacology. Published online 2016.

In diabetic cardiomyopathy, there is altered angiogenic signaling and increased oxidative stress. As a result, anti-angiogenic and pro-inflammatory pathways are activated. These disrupt cellular metabolism and cause fibrosis and apoptosis, leading to pathological remodeling. The autonomic nervous system and neurotransmitters play an important role in angiogenesis. Therapies that promote angiogenesis may be able to relieve the pathology in these disease states. Neuropeptide Y (NPY) is the most abundantly produced and expressed neuropeptide in the central and peripheral nervous systems in mammals and plays an important role in promoting angiogenesis and cardiomyocyte remodeling. It produces effects through G-protein-coupled Y receptors that are widely distributed and also present on the myocardium. Some of these receptors are also involved in diseased states of the heart. NPY has been implicated as a potent growth factor, causing cell proliferation in multiple systems while the NPY3-36 fragment is selective in stimulating angiogenesis and cardiomyocyte remodeling. Current research is focusing on developing a drug delivery mechanism for NPY to prolong therapy without having significant systemic consequences. This could be a promising innovation in the treatment of diabetic cardiomyopathy and ischemic heart disease.

Khurram Owais M, Mario Montealegre-Gallegos M, Jelliffe Jeganathan M, Robina Matyal M, Kamal Khabbaz M, Feroze Mahmood M. Dynamic changes in the ischemic mitral annulus: Implications for ring sizing.. Annals of Cardiac Anesthesia. 2016;19(1):15-9.

OBJECTIVES:

Contrary to the rest of the mitral annulus, inter-trigonal distance is known to be relatively less dynamic during the cardiac cycle. Therefore, intertrigonal distance is considered a suitable benchmark for annuloplasty ring sizing during mitral valve (MV) surgery. The entire mitral annulus dilates and flattens in patients with ischemic mitral regurgitation (IMR). It is assumed that the fibrous trigone of the heart and the intertrigonal distance does not dilate. In this study, we sought to demonstrate the changes in mitral annular geometry in patients with IMR and specifically analyze the changes in intertrigonal distance during the cardiac cycle.

METHODS:

Intraoperative three-dimensional transesophageal echocardiographic data obtained from 26 patients with normal MVs undergoing nonvalvular cardiac surgery and 36 patients with IMR undergoing valve repair were dynamically analyzed using Philips Qlab ® software.

RESULTS:

Overall, regurgitant valves were larger in area and less dynamic than normal valves. Both normal and regurgitant groups displayed a significant change in annular area (AA) during the cardiac cycle (P < 0.01 and P < 0.05, respectively). Anteroposterior and anterolateral-posteromedial diameters and inter-trigonal distance increased through systole (P < 0.05 for all) in accordance with the AAs in both groups. However, inter-trigonal distance showed the least percentage change across the cardiac cycle and its reduced dynamism was validated in both cohorts (P > 0.05).

CONCLUSIONS:

Annular dimensions in regurgitant valves are dynamic and can be measured feasibly and accurately using echocardiography. The echocardiographically identified inter-trigonal distance does not change significantly during the cardiac cycle.

Background: Metabolic syndrome is associated with pathological remodeling of the heart and adjacent vessels. The early biochemical and cellular changes underlying the vascular damage are not fully understood. In this study, we sought to establish the nature, extent, and initial timeline of cytochemical derangements underlying reduced ventriculo-arterial compliance in a swine model of metabolic syndrome.

Methods: Yorkshire swine (n=16) were fed a normal diet (ND) or a high-cholesterol (HCD) for 12 weeks. Myocardial function and blood flow was assessed before harvesting the heart. Immuno-blotting and immuno-histochemical staining were used to assess the cellular changes in the myocardium, ascending aorta and left anterior descending artery (LAD).

Results: There was significant increase in body mass index, blood glucose and mean arterial pressures (p=0.002, p=0.001 and p=0.024 respectively) in HCD group. At the cellular level there was significant increase in anti-apoptotic factors p-Akt (p=0.007 and p=0.002) and Bcl-xL (p=0.05 and p=0.01) in the HCD aorta and myocardium, respectively. Pro-fibrotic markers TGF-β (p=0.01), pSmad1/5 (p=0.03) and MMP-9 (p=0.005) were significantly increased in the HCD aorta. The levels of pro-apoptotic p38MAPK, Apaf-1 and cleaved Caspase3 were significantly increased in aorta of HCD (p= 0.03, p=0.04 and p=0.007 respectively). Similar changes in coronary arteries were not observed in either group. Functionally, the high cholesterol diet resulted in significant increase in ventricular end systolic pressure and -dp/dt (p=0.05 and p=0.007 respectively) in the HCD group.

Conclusion: Preclinical metabolic syndrome initiates pro-apoptosis and pro-fibrosis pathways in the heart and ascending aorta, while sparing coronary arteries at this early stage of dietary modification.

Rabya Saraf B, Feroze Mahmood M. Cardiac Imaging - 3-Dimensional Echocardiography. International Anesthesia Clinics. 2016;54(1):39-53.

Perioperative transesophageal echocardiography (TEE) has gradually become an essential intraoperative imaging modality, evolving from being used as a hemodynamic monitor to becoming an important procedural adjunct. Minimally invasive approaches for structural heart diseases have gained wider popularity due to advances in cardiac surgery, thereby making TEE imaging an integral component of intraoperative decision-making. Although traditional two-dimensional (2D) TEE provides a dynamic display of cardiac anatomy, it is spatially limited. Recent technological advances have allowed for the development of three-dimensional (3D) TEE. Currently, 3D imaging is mainly used for qualitative imaging of intra-cardiac structures and the data has been used for 3D printing of intra-cardiac structures. It has also demonstrated value in quantitative analyses of structural heart diseases and hemodynamic calculations. 3D imaging is gaining widespread popularity due to its useful applicability, allowing anesthesiologists to expand their role as perioperative physicians.

2015

Matyal, Montealegre-Gallegos, Mitchell J, et al. Manual Skill Acquisition During Transesophageal Echocardiography Simulator Training of Cardiology Fellows: A Kinematic Assessment.. Journal of Cardiothoracic & Vascular Anesthesia. 2015;29(6):1504-10.

OBJECTIVE:

To investigate whether a transesophageal echocardiography (TEE) simulator with motion analysis can be used to impart proficiency in TEE in an integrated curriculum-based model.

DESIGN:

A prospective cohort study.

SETTING:

A tertiary-care university hospital.

PARTICIPANTS:

TEE-naïve cardiology fellows.

INTERVENTIONS:

Participants underwent an 8-session multimodal TEE training program. Manual skills were assessed at the end of sessions 2 and 8 using motion analysis of the TEE simulator's probe. At the end of the course, participants performed an intraoperative TEE; their examinations were video captured, and a blinded investigator evaluated the total time and image transitions needed for each view. Results are reported as mean±standard deviation, or median (interquartile range) where appropriate.

MEASUREMENTS AND MAIN RESULTS:

Eleven fellows completed the knowledge and kinematic portions of the study. Five participants were excluded from the evaluation in the clinical setting because of interim exposure to TEE or having participated in a TEE rotation after the training course. An increase of 12.95% in post-test knowledge scores was observed. From the start to the end of the course, there was a significant reduction (p<0.001 for all) in the number of probe. During clinical performance evaluation, trainees were able to obtain all the required echocardiographic views unassisted but required a longer time and had more probe transitions when compared with an expert.

CONCLUSION:

A curriculum-based approach to TEE training for cardiology fellows can be complemented with kinematic analyses to objectify acquisition of manual skills during simulator-based training.