Ganong's Review of Medical Physiology, 23rd Edition

CHAPTER 31

The Heart as a Pump 517

3',5'-monophosphate (cAMP). Xanthines such as caffeine and
theophylline that inhibit the breakdown of cAMP are predictably
positively inotropic. The positively inotropic effect of digitalis
and related drugs (Figure 31–8), on the other hand, is due to
their inhibitory effect on the Na

• –K


• 
  

  ATPase in the myocardium
  (see Chapter 5). Hypercapnia, hypoxia, acidosis, and drugs such
  as quinidine, procainamide, and barbiturates depress myocardial
  contractility. The contractility of the myocardium is also reduced

  
  

in heart failure (intrinsic depression). The causes of this depres-

sion are not fully understood, but may reflect down-regulation of

β

-adrenergic receptors and associated signaling pathways and

impaired calcium liberation from the sarcoplasmic reticulum. In

acute heart failure, such as that associated with sepsis, this

response could be considered an appropriate adaptation to a situ-

ation where energy supply to the heart is limited, thereby reduc-

ing energy expenditure and avoiding cell death.

FIGURE 31–7
Effect of systolic and diastolic dysfunction on the pressure–volume loop of the left ventricle. Left:
Systolic dysfunction
shifts the isovolumic pressure–volume curve (see Figure 31–2) to the right, decreasing the stroke volume from b–c to b'–c'.
Right:
Diastolic dys-
function increases end-diastolic volume and shifts the diastolic pressure–volume relationship upward and to the left. This reduces the stroke vol-
ume from b–c to b'–c'.
(Reproduced with permission from McPhee SJ, Lingappa VR, Ganong WF [editors]:
Pathophysiology of Disease,
4th ed. McGraw-Hill, 2003.)

200

100

50 130

c

b'

d'

d a

a'

c'

b

200

100

c

c' b'

a'

a

d'

d

b

50 130

Pressure (mm Hg)

Volume (mL)

Pressure (mm Hg)

Volume (mL)

0 0

FIGURE 31–8
Effect of changes in myocardial contractility on the Frank–Starling curve.
The curve shifts downward and to the right as
contractility is decreased. The major factors influencing contractility are summarized on the right. The dashed lines indicate portions of the ven-
tricular function curves where maximum contractility has been exceeded; that is, they identify points on the “descending limb” of the Frank–
Starling curve. EDV, end-diastolic volume.
(Reproduced with permission from Braunwald E, Ross J, Sonnenblick EH: Mechanisms of contraction of the normal and
failing heart. N Engl J Med 1967;277:794. Courtesy of Little, Brown.)

Ventricular EDV

Force-frequency

relation

Contractile state

of myocardium

Loss of myocardium

Digitalis, other

inotropic agents

Circulating

catecholamines

Pharmacologic

depressants

Intrinsic

depression

Hypoxia

Hypercapnia

Acidosis

Sympathetic and

parasympathetic

nerve impulses

Stroke volume