The Cardiac Physiome: at the heart of coupling models to measurement

Physiological models in pharmacokinetics are instrumental in understanding the distribution and elimination of drugs within the body. These models describe the drug concentration within target organs, influenced by factors such as drug uptake, tissue volume, and blood flow. Drug uptake is governed by the partition coefficient, which signifies the drug concentration ratio in tissue to that in the blood. The blood flow rate to a specific tissue is expressed as Qt, and the rate of change in tissue...

The cardiac cycle describes the events from one heartbeat to the next. It includes three main phases: diastole, atrial systole, and ventricular systole, all driven by changes in chamber pressures and the function of heart valves.
Diastole: The Relaxation Phase
During diastole, all four heart chambers relax. The atrioventricular (AV) valves open, and the semilunar valves close. This phase sees the lowest chamber pressures, promoting ventricular filling. Venous blood enters the heart through the...

The normal cardiac rhythm is a synchronized electrical activity that facilitates the regular and coordinated contraction of the heart muscle. This process is essential for efficient blood circulation throughout the body. The fundamental elements involved in establishing and maintaining this rhythm include the unique electrical properties of cardiac muscle cells, the sinoatrial (SA) node's pacemaker function, the specialized conducting system, and the ionic mechanisms underlying each phase of...

The electrical signals recorded on an electrocardiogram (ECG) occur before the mechanical processes of contraction and relaxation during the cardiac cycle.
A cardiac action potential originates in the SA node and spreads throughout the atria and the AV node in approximately 0.03 seconds. This results in the P wave in an ECG and triggers atrial contraction. The action potential is then briefly slowed at the AV node, allowing the atria to contract and fill the ventricles with blood before...

Typical heart performance is influenced by heart rate, rhythm, myocardial contraction, and metabolism or blood flow. The cardiac muscle exhibits distinct electrophysiological features, including pacemaker activity and calcium channel control, which play a vital role in the heart's response to various drugs. The autonomic nervous system, comprising the sympathetic and parasympathetic branches, regulates heart rate. Sympathetic activation increases heart rate, while parasympathetic activation...