Blood circulation is a periodic process, caused by a cyclic activity of the heart. Its unit of measurement is one heart cycle. A heart period (HP) is a length of the heart cycle. Heart rate (HR) is inversely proportional to the heart period. Both of indexes are the fundamental characteristics of circulation.

Sometimes HR does not change from cycle to cycle. In that case the heart works as stably as a pendulum. This negative clinical sign is called embriocardia or pendulum-like rhythm. Fortunately, it is rarely observed. In most cases HP is changing with every other cycle. The variability of periodic processes in circulation is a result of integrative neurohumoral influences. So its indexes are fundamental characteristics of the human regulatory systems.

The effects of neurohumoral regulation are realized in different ways. The most developed and quickest way is autonomic nervous system (ANS). It controls functioning of visceral organs, blood and lymphatic vessels, smooth muscles and partly cross-striated muscles. It has multilevel hierarchical organization with nonlinear polydirectional direct and indirect bonds. It interacts with somatic nervous system and is under the control of central nervous system.

The highest ANS level consists of the highest autonomic centers situated in the cortex of cerebral hemispheres and accomplish exceptionally important function of autonomic, somatic and motivational integration. ANS has representatives in pre - central, post - central convolutions and orbital zones of the cerebral cortex.

Hypothalamus is the underlying level. It is associated with cerebral cortex and autonomic centers in the brainstem and spinal cord. It controls the unconditional and conditional reflexes of vitally important functions such as breathing, circulation, metabolism etc.

Autonomic representation in the brainstem consists of mesencephalic and bulbar centers. The bulbar centers give origin to vagus nerve, which is a part of the parasympathetic nervous system (PSNS). The autonomic centers of the spinal cord consist of thoraco - lumbar and sacral parts. The heart is innervated by vagus nerve originating in the bulbar center and by sympathetic fibers coming from thoraco - lumbar autonomic centers. Autonomic centers of thoraco - lumbar and sacral parts of the spinal cord are situated in its medial horns and are forming the initial part of the sympathetic nervous system (SNS) and sacral part of PSNS correspondently. The fibers originated in these centers leave the spinal cord with the anterior spinal rootlets.

Motor impulses from the autonomic centers of the brainstem and spinal cord reach the effector organs by a two-neuron circuit. First-order neurons are located within the centers; second-order ones are situated in the peripheral autonomic nodes. The axons of the first neurons i.e. preganglionic ones terminate at the second neurons. The axons of the second neurons i.e. postganglionic course to effector organs. Peripheral autonomic nodes of PSNS lie very close to or within the visceral organs. Peripheral autonomic nodes of SNS are represented by the ganglion chains, which run down both sides of vertebral column, forming right and left sympathetic trunks. Those trunks are the beginning of the visceral organs sympathetic innervation.

The sympathetic innervation is more widely spread than the parasympathetic one. Most of the visceral organs are exposed to double i.e. sympathetic and parasympathetic innervation and some of the organs possess the sympathetic fibers only.

SNS together with the medullar stratum of suprarenal glands and other APUD - cells accumulations form the sympatho - adrenal system. The medullar stratum of the suprarenal glands possesses epinephrine - and norepinephrine - producing cells.

Sympathetic stimulation gives rise to positive inotropic and chronotropic effects, it also results in acceleration of the conductivity, hypertension, heart vessels dilation and constriction of the blood vessels in other tissues. Parasympathetic stimulation results in opposite effects.

The sympathetic influence on heart rate is mediated by release of epinephrine and norepinephrine. Activation of beta - adrenergic receptors result in cyclic AMP mediated phosphorilation of membrane proteins and increases in ICaL and in If. The end result is an acceleration of the slow diastolic depolarization. The parasympathetic influence on heart rate is mediated via release of acetylcholine by the vagus nerve. Muscarinic acetylcholine receptors respond to this release mostly by an increase in cell membrane K⁺ conductance. Acetylcholine also inhibits the hyperpolarization - activated pacemaker current If. The Ik decay hypothesis proposes that pacemaker depolarization results from slow deactivation of the delayed rectifier current, Ik, which, due to a time - independent background inward current, causes diastolic depolarization. Conversely, the If activation hypothesis suggest that following action potential termination, If provides a slowly activating inward current predominating over decaying Ik, thus initiating slow diastolic depolarization.

Under resting conditions, vagal tone prevails and variations in heart period are largely dependent on vagal modulation. The vagal and sympathetic activity constantly interact. As the sinus node is rich in acetylcholinesterase, the effect of any vagal impulse is brief because the acetilcholine is rapidly hydrolysed. Parasympathetic influences exceed sympathetic effects probably via two independent mechanisms: a cholinergically induced reduction of norepinephrine release in response to sympathetic activity, and a cholinergic attenuation of the response to an adrenergic stimulus.

Blood vessels possess sympathetic fibers only. PSNS does not influence them directly but multilevel structural bonds within ANS provide indirect parasympathetic effects on blood pressure and vessel tone. ANS is connected with fast variations of the heart rate with a cyclic period around seconds and minutes.

The most studied among the humoral factors altering the heart rate are the renin - angiotensine - aldosterone system and hormones. Those influences give origin to heart rate oscillation with a longer period (minutes and hours).