Physiological Basis: Contractility and Pumping Function
The basic and most important function of working cardiomyocytes is contractility, which is referred to in medical literature as inotropy. It is precisely through the coordinated contraction of these cells that the heart is able to perform its primary physiological task: acting as a continuous pump.
The pumping function of the heart is critical for maintaining overall homeostasis. It ensures the uninterrupted delivery of the required volume of blood to all peripheral tissues and organs.
The target of cardiotonic drugs is exclusively working cardiomyocytes. It is important to understand that their primary target is not vascular smooth muscle cells, endothelial cells, or elements of the cardiac conduction system, but specifically the contractile apparatus of the working myocardium.
Pathology: When Cardiotonics Are Indicated
When the pumping function of the heart decreases for any reason, a pathological condition known as heart failure (HF) develops. In this pathology, the heart loses its ability to pump a volume of blood sufficient to meet the metabolic demands of peripheral tissues.
Clinically, heart failure is classified into two main forms:
- Acute heart failure.
- Chronic heart failure.
Cardiotonic agents are used specifically for the pharmacological correction of this condition and to stimulate the weakened myocardium. Their main therapeutic goal is to make the heart contract more forcefully, overcoming the manifestations of failure.
Pharmacological Effects and Terminology
In pharmacology, the action of drugs that increase the force of myocardial contractions is strictly defined as a positive inotropic effect.
To precisely understand the subject, it is necessary to distinguish this effect from other types of cardiac actions. Cardiotonics primarily increase contractility, which differentiates them from drugs that mainly affect myocardial excitability, heart rate (positive chronotropic effect), or impulse conduction velocity (positive dromotropic effect). Their action is also the exact opposite of a negative inotropic effect, in which contractile force decreases.
Classification by Mechanism of Action
All cardiotonic agents are divided into two large groups depending on the exact way they cause cardiomyocytes to contract more forcefully.
- Agents that increase cytoplasmic calcium ($Ca^{2+}$) concentration.
For a muscle fiber to contract, calcium must accumulate inside the cell. Drugs in this subgroup increase the number of free $Ca^{2+}$ ions in the cytoplasm through various pathways. These include:
- Cardiac glycosides.
- $\beta_1$-adrenergic agonists (note: $\beta_1$-receptors are responsible for cardiac stimulation, unlike $\alpha_1$- or $\beta_2$-adrenergic agonists, whereas $\beta$-blockers inhibit this function).
- Phosphodiesterase type III inhibitors.
- Agents that increase calcium sensitivity (calcium sensitizers).
Their uniqueness lies in the fact that they do not increase the absolute concentration of $Ca^{2+}$ ions inside the cell. Instead, they increase the affinity of the contractile protein troponin for the calcium already present. A prime example of this mechanism is the drug levosimendan.
Classification by Chemical Structure
In addition to their mechanism of action, traditional pharmacology divides cardiotonics based on their chemical structure. This classification is straightforward and includes two classes:
- Cardiac glycosides. These are drugs whose molecules feature a characteristic glycoside structure.
- Non-glycoside cardiotonics. This is a broad, collective group that includes all other drugs with a positive inotropic effect that lack a glycoside structure (including the aforementioned adrenergic agonists, phosphodiesterase inhibitors, and calcium sensitizers).