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Cardiac Catheterization in Mice to Measure the Pressure Volume Relationship: Investigating the Bowditch Effect
Published on: June 14, 2015
Cardiac Catheterization in Mice to Measure the Pressure Volume Relationship: Investigating the Bowditch Effect
Bo Zhang1, Jonathan P Davis2, Mark T Ziolo3
1Department of Physiology & Cell Biology, Davis Heart and Lung Research Institute, The Ohio State University; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.
Insights
The neuronal nitric oxide synthase (NOS1) knockout mouse exhibits reduced heart contractility. This study details a method to measure left ventricular (LV) pressure/volume changes at increasing heart rates in this model.
Area of Science:
- Cardiovascular physiology
- Animal models of cardiac disease
- Pharmacology
Background:
- Evaluating therapeutic strategies for cardiac disorders requires precise assessment of heart function.
- Left ventricular (LV) pressure/volume analysis offers superior precision and insight into LV function compared to echocardiography.
- This method allows real-time recording of functional changes during interventions like beta-adrenergic stimulation or ischemia/reperfusion injury.
Purpose of the Study:
- To describe a procedure for measuring LV pressure/volume dynamics with increasing heart rates.
- To investigate cardiac function in the neuronal nitric oxide synthase (NOS1) knockout mouse model.
- To assess the impact of heart rate on contractility and contractile reserve in this specific mouse model.
Main Methods:
- Utilized catheterization for real-time left ventricular (LV) pressure/volume analysis.
- Measured load-independent indexes of LV function, including end-systolic pressure-volume relationship and preload recruitable stroke work.
- Implemented a protocol to incrementally increase heart rate while monitoring LV pressure/volume parameters.
Main Results:
- The NOS1 knockout mouse model demonstrates decreased cardiac contractility.
- The described method allows for detailed assessment of cardiac mechanics and contractility reserve.
- Changes in LV pressure/volume were observed with increasing heart rates in the NOS1 knockout mice.
Conclusions:
- Accurate assessment of cardiac function, particularly contractility reserve, is crucial for evaluating cardiac disease models.
- The NOS1 knockout mouse exhibits impaired contractility, highlighting the role of NOS1 in cardiac function.
- This LV pressure/volume measurement technique provides valuable insights into cardiac hemodynamics and response to heart rate changes.
Abstract:
Animal models that mimic human cardiac disorders have been created to test potential therapeutic strategies. A key component to evaluating these strategies is to examine their effects on heart function. There are several techniques to measure in vivo cardiac mechanics (e.g., echocardiography, pressure/volume relations, etc.). Compared to echocardiography, real-time left ventricular (LV) pressure/volume analysis via catheterization is more precise and insightful in assessing LV function. Additionally, LV pressure/volume analysis provides the ability to instantaneously record changes during manipulations of contractility (e.g., β-adrenergic stimulation) and pathological insults (e.g., ischemia/reperfusion injury). In addition to the maximum (+dP/dt) and minimum (-dP/dt) rate of pressure change in the LV, an accurate assessment of LV function via several load-independent indexes (e.g., end systolic pressure volume relationship and preload recruitable stroke work) can be attained. Heart rate has a significant effect on LV contractility such that an increase in the heart rate is the primary mechanism to increase cardiac output (i.e., Bowditch effect). Thus, when comparing hemodynamics between experimental groups, it is necessary to have similar heart rates. Furthermore, a hallmark of many cardiomyopathy models is a decrease in contractile reserve (i.e., decreased Bowditch effect). Consequently, vital information can be obtained by determining the effects of increasing heart rate on contractility. Our and others data has demonstrated that the neuronal nitric oxide synthase (NOS1) knockout mouse has decreased contractility. Here we describe the procedure of measuring LV pressure/volume with increasing heart rates using the NOS1 knockout mouse model.

