L7 heart failure practice essay
Heart failure is the result of high resistance to cardiac output, heart valves not closing properly and
or the presence of heart muscle disease. These all contribute to the ability of the heart to eject a
sufficient volume of blood with each heartbeat. Heart failure has a number of consequences such as
oedema or pulmonary oedema, sodium retention which results in reduced diuresis and high venous
pressure and muscle fatigue due to insufficient oxygen reaching muscle tissue. The main forms of
treatment aim to have a positive inotropic effect, meaning that there is increased cardiac output to
reduce muscle fatigue. Reduce venous pressure and reduce resistance to cardiac output by
vasodilation to reduce skeletal and cardiac muscle fatigue. The main classes of drugs given to heart
failure patients include cardioglycosides, B1 sympathomimetics and PDE inhibitors or
phosphodiesterase inhibitors. All these drugs act to increase calcium concentration in the ventricular
myocytes, where calcium will bind to troponin C and stimulate cardiac muscle contraction.
Cardioglycosides such as digitalis act on sodium potassium ATPase pumps in the sarcolemma of the
cardiac cell membrane. Digitalis partially inhibits the pump which leads to an increase in intracellular
sodium. The increase in sodium inside the cell leads to inhibition of the sodium calcium exchanger,
which depends on there being concentration of sodium inside and outside the cell. In turn this
results in increased free intracellular calcium which is then able to act on troponin C to stimulate
muscle contraction. B1 sympathomimetics such as dobutamine are given by IV. It acts on B1
adrenoreceptors which in turn activates adenylyl cyclase which uses ATP to synthesise cAMP.
Increased levels of cAMP then act to inhibits inactivation of the slow inward current which means
that the slow inward current is activated and the calcium channels which mediate this current are
opened resulting in influx of calcium. B1 sympathomimetics however can only be used in acute cases.
Phosphodiesterase inhibitors such milrinone act on phosphodiesterase to block metabolism of cAMP.
This results in cAMP inhibiting inactivation of the slow inward current which means the slow inward
current is activated and calcium channels that facilitate the current are opened, resulting in calcium
influx.
Heart failure is also treated by reducing central venous pressure or preload. These include
venodilators and diuretics. Venodilators like GTN dilate central veins that reduce venous pressure
and therefore reduce oedema. However, vein dilation can also reduce left ventricular end diastolic
pressure so can potentially lower cardiac output. For this reason venodilators are given in
combination with positive inotropes. Diuretics such as spironolactone act in the kidney and reduce
blood volume. It has been shown to reduce mortality but the mechanism remains unclear. Heart
failure is also treated using arteriolar dilators to reduce afterload. An example of an arteriolar dilator
is hydralazine which increases cGMP in arteriolar resistance vessels leading to reduced intracellular
Calcium. This means there is less constriction of those vessels and therefore vasodilation.
There are also drugs that act to reduce both afterload and preload. The drug classes used for this are
ACE inhibitors, B1 antagonists, ARBs, and A1 adrenoreceptor antagonists. A1 adrenoceptor
antagonists block the action of adrenaline and noradrenaline which therefore inhibits
vasoconstriction and venoconstriction from occurring. ACE inhibitors block angiotensin converting
enzyme from acting, meaning thee is less angiotensin II circulating. Angiotensin II is a
vaso/venoconstrictor so if there are reduced amounts it results in reduced overall blood pressure.
ACE inhibitors are particularly effective as there are elevated levels of angiotensin II in heart failure.
Blocking angiotensin II also produces an antidiuretic effect so blood volume is reduced. Adverse
ventricular remodelling is also reduced by ACE inhibitors and they also reduce mortality in heart
failure patients. One side effect of ACE inhibitors is cough, ARBs or angiotensin II receptor blockers
produce majorly the same beneficial effects as ACE inhibitors but without causing cough. B1
antagonists use initially worsens symptoms in heart failure patients. However it results in the
sympathetic drive to the heart being reduced so the heart is not pumping rapidly which leads to
enlargement and inefficiency. B1 antagonist use reduces symptoms and improves cardiac output.
