Cardiac Contractility II. In vivo assessment Tams Radovits MD, PhD - - PowerPoint PPT Presentation

Cardiac Contractility II. In vivo assessment

Tamás Radovits MD, PhD associate professor

Heart and Vascular Center Semmelweis University Budapest 2018.

Anatomy of the heart

Anatomy of the heart II.

Atrioventricular valve Semilunar valve

Anatomy of the heart III.

Excitatory and conductive system

• Basic rules:

– Liquid (blood) is incompressible – Direction of flow is determined by the pressure gradient – Valves open/close passively, depending

• n the pressure on both sides

– Valves prevent backflow of blood

• Cardiac cycle:

– alternation of systole (contraction) and diastole (relaxation) – Cardiac events occuring from the beginning of one heartbeat till the beginning of the next one

Cardiac biomechanics

• 1. (Double) diastole (passive diastolic filling)
• after repolarisation, the atrium (A) and the ventricle (V) are relaxed for 0.4s
• P central veins >P atrium > P ventricle  atrioventricular valve is open 

blood flows continually from veins to A then to V (passive diastolic filling of V, 80% of total V filling).

• Semilunar valve is closed
• Volume of ventricle increases, pressure of ventricle remains low
• phases: 1: rapid filling, 2: diastasis (slow filling)
• 2. Atrial systole
• action potential of sinus node  depolarization spreads to the atrial

myocardium  atrial contraction (ECG: p-wave)

• V is still in diastole inflow of blood into V (20% of total V filling)
• P atrium increases (+5mmHg, „a” wave), P ventricle increases (+4mmHg)
• Volume of atrium decreases, volume of ventricle increases (at the end of

diastole: end-diastolic volume, EDV: 120ml)

Cardiac cycle I.

• 3. Systole (of the ventricle) 0.27s
• Atrial systole is followed by the depolarisation of the ventricular myocardium

(ECG: QRS-complex)  contraction of the ventricle

• At the beginning of ventricular systole, the ventricular pressure rises 

closing of the atrioventricular valve  1st heart sound

• Aortic diastolic pressure keeps the semilunar valve closed
•  1st phase of systole: isovolumic contraction (or pre-ejection phase, 0.05s) P

ventricle rises rapidly, (+70mmHg), ventricular volume is unchanged

• P ventricle rises and reaches the aortic diastolic pressure (80mmHg)
•  semilunar valve opens  2nd phase of systole: ejection (0.22s)
• Parallel rise of ventricular and aortic pressure
• Decrease of ventricular volume (ejection of 70ml blood into the aorta: stroke

volume, SV)

• 2 phases of ejection: period of rapid ejection (first third, 70% of SV),

period of slow ejection (30% of SV)

• At the end of ejection, 50ml blood remains in the ventricle (end-systolic

volume, ESV)

Cardiac cycle II.

• 3. Systole (of the ventricle) cont.
• Ejection fraction (EF): the fraction of the end-diastolic volume that is

ejected during systole

• EF= SV/EDV (EF= 0.5-0.7, or 50-70%)
• Pressure rise in the aorta depends on

– Stroke volume – Elasticity/distensibility of the aorta – Rate of blood flow to the periphery

• Aortic systolic pressure: 120-130 mmHg,

Pulmonary artery systolic pressure: 24 mmHg

• The whole SV ejected into the aorta does not flow towards the periphery

during systole. The aorta distends during systole and acts as an elastic reservoir, and recoils during diastole (Windkessel effect)  continuous blood flow towards the periphery during the whole cardiac cycle

• Repolarization begins suddenly (ECG: T wave) relaxation of ventricular

myocardium starts  P ventricle falls rapidly P aorta > P ventricle  closing of semilunar valve  2nd heart sound

Cardiac cycle III.

• 4. Ventricular diastole
• Both the semilunar and atrioventricular valves are closed  ventricle is a

closed chamber, no volume change, pressure falls rapidly  Isovolumic relaxation

• P atrium increases due to the continuous inflow of blood from the central

veins, P ventricle falls  P atrium > P ventricle  atrioventricular valve

• pens ventricular filling

Cardiac cycle IV.

Cardiac cycle V. – Summary of the phases

• 1. Systole (0.27s)

Isovolumic contraction (0.05s) Ejection (0.22s) Period of rapid ejection Period of slow ejection

• 2. Diastole (0.53s)

Isovolumic relaxation (0.08s) Ventricular filling (0.45s) Passive diastolic filling Rapid inflow Diastasis Atrial systole

Left ventricular pressure-volume loop

Basic hemodynamic parameters I.

Heart rate (HR) 70/min Left ventricular (LV) pressures LV maximal systolic pressure (LVSP) 120mmHg LV end-systolic pressure (LVESP) 100mmHg LV end-diastolic pressure (LVEDP) 8mmHg LV volumes LV end-diastolic volume (LVEDV) 120ml LV end-systolic volume (LVESV) 50ml Stroke volume (SV=LVEDV-LVESV) 70ml Cardiac Output (CO=SV* HR) 5 l/min Cardiac index (CI=CO/body surface area) 2.6-4.2 l/min/m2 Ejection fraction (EF=SV/LVEDV) 0.5-0.7, or 50-70% Left atrial pressure (estimated by pulmonary capillary wedge pressure, PCWP) 5-12mmHg

Basic hemodynamic parameters II.

Systolic aortic (arterial) pressure 120mmHg Diastolic aortic (arterial) pressure 80mmHg Mean arterial pressure (MAP ≈ 1/3 systolic + 2/3 diastolic arterial pressure) 90-100mmHg Total peripheral resistance (TPR= perfusion pressure/CO; TPR ≈ MAP/CO) 18mmHg/(l/min) Stroke work (or external work, area of the P-V loop) (SW ≈ LVESP*SV) Right ventricle and pulmonary circulation: analogue to the left heart, but lower pressures Right ventricular (RV) pressures RV maximal systolic pressure (RVSP) 24mmHg RV end-diastolic pressure (RVEDP) 4mmHg Right atrial pressure (≈ central venous pressure, CVP) 1-6mmHg Systolic pulmonary arterial pressure 24mmHg Diastolic pulmonary arterial pressure 9mmHg SV values of the LV and RV are equal on average

Regulation of cardiac pump function

• 1.: PRELOAD (~filling) - Frank-Starling mechanism

the degree of tension on the myocardium when it begins to contract

• the greater is the myocardium is stretched during filling, the greater is the force
• f contraction and the greater is the SV
• possible subcellular explanations:
• optimal sarcomere-length (Ca2+-sensitivity depends on sarcomere length)
• mechanosensitive Ca2+-channels

Regulation of cardiac pump function

• increase of afterload leads to a transient decrease of SV (dotted loop)
• due to the unchanged inflow of blood EDV increases, resulting in stronger

contraction and normalisation of SV (red loop)

Regulation of cardiac pump function

• 2.: AFTERLOAD (~ aortic pressure)

the load against which the myocardium exerts its contractile force

– Heart rate↑  force of contractions↑  cardiac output↑ – At extreme high HR force of contractions ↓ – Mechanism: inability of the Na+/K+-ATPase to keep up with influx of Na+ at higher heart rates  higher ic. Ca2+  stronger contractions

Regulation of cardiac pump function

• 3.: HEART RATE - Bowditch effect (Treppe phenomenon)

• 4.: CONTRACTILITY
• intrinsic ability of the myocardium to contract
• increased contractility
• increased force and velocity of contractions
• increased pressure generation by the ventricle
• increased SV and CO

Inotropic effect: change of force of contractions Cellular mechanisms:

• increased Ca2+ transient
• increased Ca2+ sensitivity of the contractile apparatus

Regulation of cardiac pump function

Regulation of cardiac pump function

Contractility is influenced by:

• Structure of the myocardium
• Metabolic state of the myocardium
• Ion concentrations
• Neurohumoral effects
• Sympathetic and
• Parasympathetic activation
• Temperature
• Drugs
• …

Regulation of cardiac pump function

• Sympathetic and parasympathetic activation alters

contractility

Regulation of cardiac pump function

• Beta-adrenergic agonists increase contractility
• mechanisms:

Assessment of contractility in vivo

• … is difficult!
• No exact parameters
• No proper non-invasive approaches
• Ideal contractility parameter is:

– independent of preload – independent of afterload – independent of heart rate – sensitive to inotropic effects

• Ejection fraction (EF)
• SV/EDV
• dependent on preload and afterload
• widely used in the clinical routine for determining

contractility

• advantage: easy to measure

(echocardiography)

• Maximal rate of systolic pressure

increment in the LV (dP/dtmax)

• requires ventricular catheterisation
• refers to the isovolumic contraction

phase

• dependent on loading conditions

Conventional contractility parameters

Precise assessment of contractility

LV pressure-volume analysis during preload reduction (caval vein occlusion)

ESPVR (End-Systolic-Pressure-Volume-Relationship)

Slope of the line connecting end-systolic points of P-V loops during caval vein occlusion maneuver Independent of pre- and afterload

Load-independent contractility parameters I.

Control Increased contractility

Load-independent contractility parameters II.

PRSW (Preload-Recruitable-Stroke-Work)

• Slope of the linear relationship between stroke work and end-

diastolic volume during caval vein occlusion maneuver

• Independent of pre- and afterload
• Very sensitive to inotropic changes
• This relationship is always linear
• Gold standard index of

LV contractility in vivo

dP/dtmax - EDV Maximal rate of LV systolic pressure increment – end- diastolic volume relationship

• Slope of this linear

relationship

• Independent of loading

conditions

• Sensitive index of LV

contractility

Load-independent contractility parameters III.

Diastolic parameters derived from LV P-V analysis

• Active relaxation

– ATP-consuming process – In the phase of isovolumic relaxation – dP/dtmin – Tau (time constant of LV pressure decay): p(t)= P∞+(P0–P∞)exp(–t/τ) Weiss-method (assumption of a zero pressure asymptote) Glantz-method (monoexponential model of LV pressure tracing assuming a nonzero asymptote)

• Passive diastolic function –

LV stiffness/compliance

– Ventricular distensibility – Determined by structural properties – of the LV wall – EDPVR

• Stroke work (SW)

– Area within a PV loop

• Pressure-Volume Area (PVA)

– PE (Potential Energy) + SW

• Efficiency of LV work

(Eff=SW/PVA)

• Arterial elastance (Ea=Pes/SV)

– integrative index of afterload

• End-systolic elastance

(Ees: slope of ESPVR)

• Ventriculo-arterial coupling

– (VAC=Ea/Ees) – Characterizes the relation between LV contractility and arterial afterload

LV mechanoenergetics

• Simultaneous measurement of LV pressure and

volume (combined pressure-conductance catheter

• Measuring conductance of the blood in the LV =>

LV volume assessment

• Baan’s equation:

α = correction factor ρ = specific conductivity of blood (Ohm•cm) L = electrode distance (mm) G = segmental conductance (µsiemens (µS)) Gp= paralell conductance (µS)

LV P-V analysis in practice –

the pressure-conductance catheter

The pressure-conductance catheter

PS = Pressure sensor E1 and E4 = Excitation electrodes E2 and E3 = Sensor electrodes PS = Pressure sensor E1 and E12 = Primary excitation electrodes E2 and E11 = Secondary excitation electrodes E3-E10 = Sensor electrodes Single segment, single field Multi segment, dual field

The pressure-conductance catheter

Pressure-volume analysis - examples

Steady state Vena cava occlusion (reduction in preload)

Calibration, validation of the volume

signal

α = correction factor ρ = specific conductivity of blood (Ohm•cm) L = electrode distance (mm) G = segmental conductance (µsiemens (µS)) Gp= paralell conductance (µS) (conductance of the sorrounding tissues) calculation: 20% saline bolus injection (virtual increase of LV volume /right shift of the P-V loops)

LV contractility in health and disease

Healthy heart diabetic heart

Diabetic cardiomyopathy in rat models

ESPVR

PRSW

LV contractility in health and disease

Diabetic cardiomyopathy in rat models

dP/dtmax - EDV

LV contractility in health and disease

Diabetic cardiomyopathy in rat models

LV contractility in health and disease

Pressure (mmHg) Pressure (mmHg) Volume (ul) Volume (ul)

ESPVR ESPVR EDPVR EDPVR

Healthy heart Failing heart

Severe heart failure in a LV volume overload rat model (A-V shunt)

LV contractility in health and disease

Pressure (mmHg) Pressure (mmHg) Volume (ul) Volume (ul)

ESPVR ESPVR EDPVR EDPVR

Healthy heart Failing heart

Severe heart failure in a LV pressure overload rat model (TAC)

LV contractility in health and disease

Pressure (mmHg) Pressure (mmHg) Volume (ul) Volume (ul)

ESPVR ESPVR EDPVR EDPVR

Healthy heart Failing heart

Severe heart failure in postinfaction HF rat model (LAD ligation)

LV contractility in health and disease

Rat model of athlete’s heart

LV contractility in health and disease

Rat model of athlete’s heart

PRSW

LV contractility in health and disease

Rat model of athlete’s heart

dP/dtmax - EDV

References

• Guyton and Hall: Textbook of Medical

Physiology 13th edition

• Koeppen and Stanton: Berne and Levy

Physiology 6th edition

• Boron and Boulpaep: Medical Physiology

2nd edition

• Pacher et al. Nat Protoc 2008;3:1422-34.