Holistic Approaches Lead to Better Outcomes for Patients with Cardiovascular Disease

Feb 4, 2021, 09:07 AM by Sara Kruper

Each year, February is recognized in the United States as American Heart Month. The American Heart Association, Centers for Disease Control and Prevention, and others use this time to raise awareness about cardiovascular diseases.

The World Health Organization estimates that 17.9 million people die from cardiovascular disease each year, accounting for approximately 31% of all annual worldwide deaths.  Although many of these deaths may be preventable with proper evaluation and treatment, there are still instances where adequate treatments are yet to be discovered.  The SARS-CoV-2 pandemic has been especially difficult for people living with cardiovascular disease as they are more vulnerable to the virus and have had to worry about access to safe hospital space and resources.

Harvard Bioscience (HBIO) is proud to serve researchers looking to prevent, treat, and cure cardiovascular diseases.  DSI has been providing solutions to measure cardiovascular endpoints for nearly 40 years. Did you know that many of our solutions have been combined with other HBIO products to provide a more holistic approach? The following paragraphs highlight a sampling of publication reviews where both DSI and other HBIO solutions have been used.

G790del mutation in DSC2 alone is insufficient to develop the pathogenesis of ARVC in a mouse model
Several desmosomal genes are believed to play a role in the development of Arrhythmogenic Right Ventricular Cardiomyopathy (AVRC).  Mutations of the DSC2 gene account for approximately 2% of ARVC abnormalities, and this research team evaluated the effect of G790del mutation of DSC2 on the arrhythmogenic mechanism and cardiac function in mice.  As part of their assessment of cardiac function, the team used DSI’s implantable telemetry system to monitor ECG.  For the 24-hour period following a byan exercise test, performed with the Panlab treadmill, ECG was monitored.  The team concluded that G790del mutation of DSC2 was not enough to develop ARVC in a mouse model on its own.         


Role of defective calcium regulation in cardiorespiratory dysfunction in Huntington’s disease
Patients with Huntington’s Disease often suffer from cardiac and respiratory dysfunction, the underlying mechanisms of which are currently not well understood.  This research team aimed to uncover new insights into the causes of cardiorespiratory dysfunction and identify a novel therapeutic target.  The team used the Planer Lipid Bilayer system from Warner Instruments to reconstitute cortical RyR2 into lipid bilayers and conducted single-channel recordings. The results demonstrated an increased open probability in the presence of low non activating [Ca2+]cis conditions.  In addition, DSI’s implantable telemetry was used to measure ECG. DSI Ponemah software was also used to identify arrhythmias and calculate heart rate variability.  The study’s results indicate the calcium release of RyRs plays an important role in Huntington’s Disease pathology and could be a potential therapeutic target.


Cold-Inducible RNA-Binding Protein Prevents an Excessive Heart Rate Response to Stress by Targeting Phosphodiesterase
Plasticity of the sinoatrial node (SAN) is essential to cardiac function during stress response.  Cold-inducible RNA-binding Protein (CIRP) is a proven stress regulator.  This study evaluated the role of CIRP in SAN plasticity and heart rate regulation during stress.  The team used DSI’s implantable telemetry to measure ECG and showed excessive heart rate acceleration under isoprenaline stimulation in conscious CIRP knock out rats.  In addition, they used the HEKA Elektronik patch clamp system to record action potentials and found that isoprenaline stimulation led to faster spontaneous firing in CIRP knockout SAN cells than in wild type SAN cells.  The team concluded that CIRP serves as an mRNA stabilizer to control cAMP concentrations in SAN and therefore maintains the appropriate heart rate stress response.


Compensatory ion transport buffers daily protein rhythms to regulate osmotic balance and cellular physiology
Osmotic pressure exerted by changes in the soluble proteome must be compensated to maintain volume within narrow limits and cell viability.  However, the underlying mechanisms and consequences of compensation are not well understood, and this team aimed to shed light on them.  The team performed cellular and in vivo evaluation of compensation in SLC12A family cotransporters.  Micro electrode array (MEA) recordings with an MEA2100 recording system from Multi Channel Systems revealed that circadian variation in cardiomyocyte activity is partially driven by changes in ion content.  Mice were also implanted with DSI’s implantable telemetry to measure ECG for 10 seconds every five minutes and heart rate variability was calculated.  The study’s results show circadian regulation of the proteome impacts ion homeostasis with substantial consequences for the physiology of electrically active cells.


Transgenic LQT2, LQT5, and LQT2-5 rabbit models with decreased repolarisation reserve for prediction of drug-induced ventricular arrhythmias
Although most arrhythmic side effects from novel drug candidates are largely seen in patients with pre-existing repolarization disturbances, safety effects are typically used for pro-arrhythmia testing.  This team aimed to improve safety screening by using a transgenic long QT (LQTS) rabbit model with impaired repolarization reserve.  The team evaluated the effects of K+ channel blockers on cardiac repolarization and arrhythmia susceptibility in wild type and LQTS rabbits using DSI’s implantable telemetry to measure in vivo ECG, and the Hugo Sachs Isolated Heart Perfusion system for ex vivo monophasic action potential and ECG.  The study’s results indicate the LQTS model represents patients with repolarization reserve and could serve as a more reliable and thorough predictor of pro-arrhythmic potential of drug candidates. 


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