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Clinical pharmacy 2024/2025 Level 3 Pharm D Pharmacology 1 (PO 502)

Role of physiologic compensatory mechanisms in the progression of HF

➢ Chronic activation of sympathetic nervous system, the rennin angiotensin-
aldosterone axis ➔ remodeling of cardiac tissue ➔ loss of myocytes, hypertrophy,
and fibrosis.

➢ Geometry of the heart ➔ less elliptical, more spherical➔interfering with its ability
to efficiently function as a pump.

➢ Additional neurohumoral activation, creating a vicious cycle that, if left untreated,

leads to death.

Cardiac ✔ force of contraction of the cardiac muscle is directly related to the
contraction concentration of free (unbound) cytosolic calcium.

 First is from outside the cell
Sources of free Opening of voltage sensitive calcium channels causes an immediate.

intracellular  Inside the heart
calcium ➔ 1. Exchange with sodium. (Na /Ca exchanger).
+
+2
Calcium comes 2. from the sarcoplasmic reticulum and mitochondria.
from several ➢ Rise in free cytosolic calcium.
sources ➢ ↑ calcium levels or increase the sensitivity ➔ Of contractile

machinery to calcium ➔ ↑ force of contraction (inotropic effect)

Removal of free cytosolic calcium

✓ If free cytosolic calcium levels were to remain high, the cardiac muscle would be
in a constant state of contraction rather than showing a periodic contraction

Mechanisms of removal include the following two alternatives:

1. Sodium/calcium exchange: reversibly exchanges calcium ions for sodium ions across
the cell membrane.

2. Uptake of calcium by the sarcoplasmic reticulum and mitochondria.

1- ↑ sympathetic activity. (contractility ↑)
2- Activation of the renin-angiotensin system (blood supply to

kidney ➔ activation renin-angiotensin system ➔renin released by
Compensatory β1
physiological 3- Myocardial hypertrophy.

responses in ✓ pumping capacity only properties do not appear in ECG (can be
heart failure evaluated by left ejection fraction & right ejection fraction) but
measured by echocardiogram
✓ These 3 mechanisms on long term have deleterious effects on

heart

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