Cardiac PV Loop Data Analysis: Tips & Tricks

In this American Physiological Society (APS) webinar produced in partnership with ADInstruments, DeWayne Townsend, DVM, PhD and Adam Goodwill, PhD discuss how to collect and analyze quality pressure-volume loop data.

Specifically, they discuss why PV loops are considered the gold standard for measuring cardiac function in vivo, what equipment is required to collect PV loop data, and how to minimize variability in your data. The focus of the webinar is on data analysis – DeWayne and Adam demonstrate how to analyze load-independent measures of function and discuss what the data mean.

Key Learning Objectives Include:
– Why PV loops? What are the alternatives (e.g. echo, MRI, etc.) and how do PV loops compare?
– Why is the Starling effect important?
– Load independent measures: what are they and how are they measured? How are data analyzed and what do they mean?
– Equipment basics: what do you need to record PV loop data?
– What causes variability and how do you mitigate it?

1. Cardiac PV Loop Data Analysis: Tips & Tricks DeWayne Townsend, DVM, PhD Associate Professor, Department of Integrative Biology and Physiology University of Minnesota Medical School Adam Goodwill, PhD Assistant Research Professor, Anatomy Cell Biology & Physiology Indiana University School of Medicine

2. Cardiac PV Loop Data Analysis: Tips & Tricks Dr. DeWayne Townsend and Dr. Adam Goodwill discuss the fundamentals of pressure-volume loop analysis as a means to study cardiac function.

3. InsideScientific is an online educational environment designed for life science researchers. Our goal is to aid in the sharing and distribution of scientific information regarding innovative technologies, protocols, research tools and laboratory services

4. To access webinar content, Q&A reports, FAQ documents, and information on lab workshops, subscribe to our mail list

5. Cardiac PV Loop Data Analysis: Tips & Tricks Copyright 2020 A. Goodwill and InsideScientific. All Rights Reserved. Adam Goodwill, PhD Assistant Research Professor, Anatomy, Cell Biology & Physiology Indiana University School of Medicine

6. WHY Pressure-Volume Loops? - Alternatives Modified from: Lindsey, ML et al. Am J Physiol Heart Circ Physiol. 2018 Apr 1;314(4):H733-H752

7. WHY Pressure-Volume Loops? – Data Boron, Walter & Boulpaep , Emile. Medical Physiology 2 nd Edition Abundance of data Pressure and volume for every cardiac cycle Measured Parameters ESV, EDV, P max , P min P ES , P ED , SV, EF, CO Easily obtained load dependent measures

8. WHY Pressure-Volume Loops? – Data (Continuous) Classic Measures of Cardiac Function Tau Exponential decay of the ventricular pressure during isovolumic relaxation dP /dt Min Maximum rate of rate of LV pressure decrease (isovolumic index) Relaxation Time (RT) Duration of isovolumic relaxation Stroke Work (SW) Area of PV loop, often estimated by: SV * Mean arterial Pressure dP /dt Max Maximal rate of LV pressure generation (isovolumic index) Contraction Time (CT) Duration of isovolumic contraction Measures are continuous through entire study

9. WHAT are Starling Effects and WHY are they Important? What is a Starling Effect: The greater the preload (stretch) on cardiac muscle fibers prior to contraction, the greater their force of contraction. ( NOT change in contractility) Boron, Walter & Boulpaep , Emile. Medical Physiology 2 nd Edition What is Contractility? The innate ability of the heart muscle (cardiac muscle or myocardium) to contract (independent of preload)

10. WHAT are load-independent measures? – Assessing Contractility

11. WHAT are load-independent measures? – Assessing Contractility and Compliance Ees ESPVR Obtaining ESPVR and EDPVR Relationships End Systolic Pressure Volume Relationship (ESPVR); Contractility Linear Relationship Slope = End Systolic Elastance ( Ees ) X intercept = Volume Axis Intercept (V ) End Diastolic Pressure Volume Relationship (EDPVR); Compliance Curvilinear Relationship Modified from: Knaapen et al. Circulation 2007 Feb 20;115(7):918-27

12. https://www.cvphysiology.com/Cardiac%20Function/CF025 WHAT are load-independent measures? – Assessing Contractility

13. WHY Pressure-Volume Loops?- Assessing Contractility Boron, Walter & Boulpaep , Emile. Medical Physiology 2 nd Edition

14. WHAT are load-independent measures? – Assessing Ventricular Compliance Diastolic volume is influenced by the loading conditions and elastic properties of the heart Decreases in diastolic function shift the end-diastolic pressure-volume relationship upward LV Compliance is a reciprocal of the slope of EDPVR https://www.cvphysiology.com/Cardiac%20Function/CF014

15. WHY Pressure-Volume Loops? – Cardiac Energetics External work (EW) – energy that propels blood from the ventricles into the aorta or pulmonary artery - stroke work = pressure x stroke volume Potential work (PW/PE) – energy generated with contraction that is NOT converted to external work i.e. energy to stretch and lengthen viscous elements in the ventricles. Pressure Volume Area (PVA) – Sum of total work and potential work. Directly proportionate to myocardial oxygen consumption Cardiac Power – external (stroke) work x HR - work per unit time Cardiac Efficiency – external work per unit energy consumed Knaapen et al. Circulation 2007 Feb 20;115(7):918-27

16. Cardiac PV Loop Data Analysis: Tips & Tricks DeWayne Townsend, DVM, PhD Associate Professor, Department of Integrative Biology and Physiology University of Minnesota Medical School Copyright 2020 D. Townsend and InsideScientific. All Rights Reserved.

17. Surgical and Anesthesia Blood loss is a big deal in mice Total blood volume is 77-88 ml/kg 1.54 – 1.76 mL in a 20 g mouse 2.31 – 2.64 mL in a 25 g mouse Thus losses of 0.1-0.2 mL are hemodynamically significant Insensible fluid loss Water lost through evaporation Respiratory loss (≈4ml/kg/ hr ) Exposed Tissue (≈2-3 ml/kg/ hr ) Recommend ≈5ml/kg IV 10% Albumin in 0.9% NaCl More if blood loss- 1 Q-tip ≈ 0.1 ml Must replace lost blood Sources of Variability in PV Loops in Rodents

18. Catheter Placement – Carotid Approach Advantages Closed-Chest Approach Ventilation not required Although often used to allow respiratory control Disadvantages Catheter placement defined by aortic anatomy Laparotomy required to occlude the vena cava Potential for outflow track obstruction in smaller hearts

19. Catheter Placement – Apical Approach Advantages Catheter Placement can be optimized No outflow track obstruction No additional surgery for inferior vena cava occlusion Disadvantages Requires ventilation Extensive surgical manipulation Potential to damage the myocardium

20. Catheter Placement – Papillary Entrapment A ventricular pressure artifact resulting from the direct interaction of cardiac structures with the pressure transducer.

21. Positive pressure ventilation creates changes in left ventricular pre-load This creates respiratory dependent oscillation in left ventricular pressure Collecting data during brief periods of apnea results in more stable measures of cardiac function Respiratory Artifacts

22. IVCO Abdominal Compression Modulating Cardiac Loading

23. Evaluating Passive Properties of the Heart Increasing afterload of the heart increases end diastolic pressure Increased EDP allows the evaluation of the passive properties of the left ventricle

24. Analysis Issues Pause for 10–15 seconds after inferior vena caval occlusion The drop in blood pressure resulting from this maneuver activates the baroreceptor reflex. This increases the sympathetic nervous system output to the heart Any measures taken immediately after an occlusion will have increased contractility because of this nervous input. Similar, but reversed, for abdominal compression Loop rejection Occasionally there will be an arrhythmic beat during a period of measurement. The data from these loops will be outliers and should be removed Removed loops should be recorded and original data maintained to preserve the integrity of the data workflow

25. DeWayne Townsend, DVM, PhD Associate Professor, Department of Integrative Biology and Physiology University of Minnesota Medical School Adam Goodwill, PhD Assistant Research Professor, Anatomy Cell Biology & Physiology Indiana University School of Medicine Thank You! To learn more about PV loop analysis solutions from ADInstruments , please visit: www.adinstruments.com/products/pv-loop