Stroke volume

• Typical end-diastolic volume = 120-130mL
• Typical end-systolic volume = 50mL
• Typical stroke volume = 70-80mL

 

Preload

... the load on the myocardial muscles just prior to the onset of contraction

• Optimal sarcomere length: 2.2 micrometer

Preload influence contractility due to:

• Changing number of myofilament crossbridges
• Changing calcium sensitivity of the myofilaments

 

Best index of preload

• LV end-diastolic volume (LVEDV) (on the x-axis of the P-V loop)

Other indices of preload

• LV end-diastolic pressure (LVEDP)
• Left atrial pressure (LAP)
• Right atrial pressure or central venous pressure (CVP) can be used because they usually correlates well with left sided filling pressure

Pulmonary capillary wedge pressure

Pulmonary capillary wedge pressure (PCWP) (or pulmonary artery occlusion pressure (PAOP)) correlates well with LAP most of the time

• Because the path from the pulmonary veins to LA is low resistance and at same horizontal level
• PAOP measured with Swan-Ganz catheter

 

Afterload

... the impedance to the ejection of blood from the heart into the arterial circulation

Best index of afterload

• Slope of the afterload line (which connects LVEDV on x-axis to the LVESPV in P-V loop)

Other index of afterload

• End-systolic pressure

Contractility

[KB2:p47] ... the factor that is responsible for changes in myocardial performance which are not due to changes in heart rate, preload, or afterload.

[BL8] Performance of the heart at a given preload and afterload.

Best index of contractility

• Slope of LVESPV curve (in P-V loop)

Other index of contractility

• Tension time index [KB2:p52]
• (dp/dt)max [KB2:48]
• Ejection fraction

 

Factors influencing contractility

All mechanisms that increase contractility do so by increasing intracellular [Ca2+]

e.g. decrease in sodium gradient, increase in extracellular [Ca2+]

NB:

• Decrease Na+ gradient
  --> Decreased expulsion of Ca2+ via Na/Ca exchanger
  --> Increased intracellular [Ca2+]

Neural influences

Sympathetic influence

e.g.

Sympathetic stimulation

--> beta1 receptor stimulation

--> Increased cAMP

--> Increased contractility and faster relaxation

Also, catecholamines also increase sensitivity of myofilaments to Ca2+

(See ANS innervation of the heart)

Parasympathetic influence

e.g.

Parasympathetic stimulation

--> Muscarinic acetylcholine

--> Decreased cAMP

--> Decreased Ca2+ influx

--> Decreased contractility

(See ANS innervation of the heart)

Hormonal influences

Adrenomedullary hormones

Mainly epinephrine, and some norepinephrine

Adrenocrotical hormones

i.e. corticosteroids

Possibly potentiating in human [BL8:p109]

But is permissive for the permissive effect of catecholamine [WG21: p372]

Thyroid hormones

Enhance contractility via

1. Increased Ca2+ uptake by SR
2. Increased protein synthesis in heart
   --> Hypertrophy
3. Affect composition of myosin isoenzymes in cardiac muscle (esp the ones with greatest ATPase activity)

Insulin

Prominent, direct, positive inotropic effect [BL8:p111]

Glucagon

Potent positive inotropic and chronotropic effect on the heart

Mechanism very similar to catecholamines.
* i.e. also increases cAMP via adenylyl cyclase

NB:

• Epinephrine increases both BSL and lactate
• Glucagon increases only BSL

Other factors

• Moderate hypoxia generally increase cardiac output, HR, and contractility
  * Indirectly via sympathetic stimulation
• Moderate-to-severe hypoxia and hypercapnia depresses contractility
• Intracellular acidemia diminishes Ca2+ release from SR and sensitivity of myofilaments to Ca2+

Digitalis glycoside

Inhibits Na-K ATPase pump

--> Decrease Na+ chemical gradient

--> Decreased Na+ influx

--> Decrease Ca2+ efflux via Na/Ca exchanger

--> Increase in intracellular Ca2+ level

--> Increase contractility

Also increases inward Ca2+ current

--> Also increase intracellular Ca2+ level

--> Increase contractility

Xanthines (e.g. caffeine, theophylline)

(e.g. caffeine, theophylline)

Inhibit breakdown of cAMP

--> Inotropic effect