The Bowditch effect, also known as the Treppe phenomenon and the Treppe effect, is an autoregulation method by which myocardial tension increases with an increase in

heart rate Heart rate (or pulse rate) is the frequency of the heartbeat measured by the number of contractions (beats) of the heart per minute (bpm). The heart rate can vary according to the body's physical needs, including the need to absorb oxygen and e ...

. It was first observed by

Henry Pickering Bowditch Henry Pickering Bowditch (April 4, 1840 – March 13, 1911) was an American soldier, physician, physiologist, and dean of the Harvard Medical School. Following his teacher Carl Ludwig, he promoted the training of medical practitioners in a conte ...

in 1871.

Mechanism

The underlying cause of the Bowditch effect is an increase in the

calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar t ...

concentration in the

sarcoplasmic reticulum The sarcoplasmic reticulum (SR) is a membrane-bound structure found within muscle cells that is similar to the smooth endoplasmic reticulum in other cells. The main function of the SR is to store calcium ions (Ca2+). Calcium ion levels are kep ...

of cardiac muscle cells, and its increased release into

sarcoplasm Sarcoplasm is the cytoplasm of a muscle cell. It is comparable to the cytoplasm of other cells, but it contains unusually large amounts of glycogen (a polymer of glucose), myoglobin, a red-colored protein necessary for binding oxygen molecules tha ...

. One of the explanations for an increase in the intracellular calcium concentration is the inability of the Na⁺/K⁺-ATPase to keep up with influx of

sodium Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable ...

at higher

s. When a higher heart rate occurs, for example due to adrenergic stimulation, the

L-type calcium channel The L-type calcium channel (also known as the dihydropyridine channel, or DHP channel) is part of the high-voltage activated family of voltage-dependent calcium channel. "L" stands for long-lasting referring to the length of activation. This c ...

has increased activity. The

sodium-calcium exchanger The sodium-calcium exchanger (often denoted Na+/Ca2+ exchanger, exchange protein, or NCX) is an antiporter membrane protein that removes calcium from cells. It uses the energy that is stored in the electrochemical gradient of sodium (Na+) by al ...

(which allows 3 Na⁺ to flow down its

electrochemical gradient An electrochemical gradient is a gradient of electrochemical potential, usually for an ion that can move across a membrane. The gradient consists of two parts, the chemical gradient, or difference in solute concentration across a membrane, and t ...

in exchange for 1 Ca⁺⁺ ion to flow out of the cell) works to decrease the levels of intracellular calcium. As the heart rate becomes more robust, and the length of

diastole Diastole ( ) is the relaxed phase of the cardiac cycle when the chambers of the heart are re-filling with blood. The contrasting phase is systole when the heart chambers are contracting. Atrial diastole is the relaxing of the atria, and ventri ...

decreases, the Na⁺/K⁺-ATPase, which removes the Na⁺ brought into the cell by the Na⁺/Ca⁺⁺ exchanger, does not keep up with the rate of Na⁺ influx. This leads to a less efficient Na⁺/Ca⁺⁺ exchange, since the gradient is decreasing for sodium and the driving force behind calcium transport is actually the

concentration gradient Molecular diffusion, often simply called diffusion, is the thermal motion of all (liquid or gas) particles at temperatures above absolute zero. The rate of this movement is a function of temperature, viscosity of the fluid and the size (mass) o ...

of sodium, therefore Ca⁺⁺ builds up within the cell. This results in an accumulation of calcium in the myocardial cell via the sodium calcium exchanger and leads to a greater state of inotropism, a mechanism which is also seen with

cardiac glycoside Cardiac glycosides are a class of organic compounds that increase the output force of the heart and decrease its rate of contractions by inhibiting the cellular sodium-potassium ATPase pump. Their beneficial medical uses are as treatments for co ...

s. Alternatively, another mechanism is that the Na⁺-Ca⁺⁺ membrane exchanger, which operates continually, has less time to remove the Ca⁺⁺ that arrives in the cell. This occurs because of the decreased length of diastole with positive chronotropy. With an increased intracellular Ca⁺⁺ concentration, there follows a positive inotropy.''Physiology at a Glance'', Second Edition (2008) — Jeremy Ward & Roger Linden It has also been observed that increased heart rate stimulates SERCA2a, which increases the calcium inflow and content in the sarcoplasmic reticulum. This activation of SERCA2a is indirectly by the phosphorylation of

phospholamban Phospholamban, also known as PLN or PLB, is a micropeptide protein that in humans is encoded by the ''PLN'' gene. Phospholamban is a 52-amino acid integral membrane protein that regulates the calcium (Ca2+) pump in cardiac muscle cells. Func ...

(PLN) by calmodulin kinase II (

CAMK CAMK, also written as CaMK or CCaMK, is an abbreviation for the Ca2+/calmodulin-dependent protein kinase class of enzymes. CAMKs are activated by increases in the concentration of intracellular calcium ions (Ca2+) and calmodulin. When activated, t ...

Clinical significance

Positive Bowditch effect causes an increase in

cardiac output In cardiac physiology, cardiac output (CO), also known as heart output and often denoted by the symbols Q, \dot Q, or \dot Q_ , edited by Catherine E. Williamson, Phillip Bennett is the volumetric flow rate of the heart's pumping output: th ...

due to the increased force of contraction of heart muscles. This phenomenon is usually absent or even reversed (negative Bowditch effect) in

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, ...

and other diseases of heart, such as

cardiomyopathy Cardiomyopathy is a group of diseases that affect the heart muscle. Early on there may be few or no symptoms. As the disease worsens, shortness of breath, feeling tired, and swelling of the legs may occur, due to the onset of heart failure. ...

and

coronary artery disease Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves Ischemia, the reduction of blood flow to the myocardium, heart muscle due to build-up o ...

. This is termed as the null or inverse staircase phenomenon. The probable cause for this effect is attributed to mutations in SERCA2a.

History

The Bowditch effect was first observed by

in 1871, after whom it is named.

References

{{reflist Cardiovascular diseases