Advent of genetic engineering made small rodents a powerful platform for investigation of the genetic foundation of normal and pathological cardiovascular physiology. Through these studies, primarily in mice, many cardiovascular diseases have been linked to a particular protein or group of molecules in the heart or nervous system. Large animals are used to study heart rhythm disorders associated with abnormally high rate achieved by rapid pacing of the atria or ventricles, and which results in heart failure and atrial fibrilation. Unfortunately, genetic engineering of large animals is not available or prohibitively expensive, which limits our ability to study the molecular basis of cardiovascular disease in these animals. In contrast, unlike large animal models, chronic studies in mouse and other small mammals are limited due to our inability to stimulate the heart and nerves. The size of existing pacemakers is a limiting factor, and prevents us from extending electronic implantable devices to studies of heart rhythm disorders in genetically engineered mice. Thus, there is an unmet need to combine genetic engineering in small rodents with implantable device technology for heart rhythm control. In this project, we propose to develop an implantable programmable miniature pacemaker, which can be used in mouse and other species for long-term chronic pacing at desired rate and pulse durations. We will use state- of-the-art electrical engineering technology to create a miniature implantable device. Successful completion of this project will allow bridging the gap between two state of the art technologies: (1) genetic engineering of the mouse and (2) implantable device technology for heart rhythm control. Combination of these two technologies will allow investigation of molecular mechanisms responsible for heart rhythm disorders and heart failure secondary to rapid rate. These studies will advance pre-clinical research of arrhythmia and heart failure. In the future we also plan to extend this technology to both pacing and sensing the cardiac electrical activity.
Genetic engineering of large animals is not available or prohibitively expensive, which limits our ability to study the molecular basis of cardiovascular disease in these animals. In contrast, unlike large animal models, chronic studies in mouse and other small mammals are limited due to our inability to stimulate the heart and nerves. The size of existing pacemakers is a limiting factor, and prevents us from extending electronic implantable devices to studies of heart rhythm disorders in genetically engineered mice. In this project, we propose to develop an implantable programmable miniature pacemaker, which can be used in mouse and other species for long-term chronic pacing at desired rate and pulse durations. We will use state-of-the-art electrical engineering technology to create a miniature implantable device.
| Boukens, Bastiaan J; Gutbrod, Sarah R; Efimov, Igor R (2015) Imaging of Ventricular Fibrillation and Defibrillation: The Virtual Electrode Hypothesis. Adv Exp Med Biol 859:343-65 |
| Sulkin, Matthew S; Widder, Emily; Shao, Connie et al. (2013) Three-dimensional printing physiology laboratory technology. Am J Physiol Heart Circ Physiol 305:H1569-73 |
| Laughner, Jacob I; Zhang, Song; Li, Hao et al. (2012) Mapping cardiac surface mechanics with structured light imaging. Am J Physiol Heart Circ Physiol 303:H712-20 |
| Laughner, Jacob I; Ng, Fu Siong; Sulkin, Matthew S et al. (2012) Processing and analysis of cardiac optical mapping data obtained with potentiometric dyes. Am J Physiol Heart Circ Physiol 303:H753-65 |
| Cheng, Ya-Jian; Lang, Di; Caruthers, Shelton D et al. (2012) Focal but reversible diastolic sheet dysfunction reflects regional calcium mishandling in dystrophic mdx mouse hearts. Am J Physiol Heart Circ Physiol 303:H559-68 |
| Laughner, Jacob I; Sulkin, Matthew S; Wu, Ziqi et al. (2012) Three potential mechanisms for failure of high intensity focused ultrasound ablation in cardiac tissue. Circ Arrhythm Electrophysiol 5:409-16 |
| Pietka, Terri A; Sulkin, Matthew S; Kuda, Ondrej et al. (2012) CD36 protein influences myocardial Ca2+ homeostasis and phospholipid metabolism: conduction anomalies in CD36-deficient mice during fasting. J Biol Chem 287:38901-12 |
