# Inotropy

The term inotropy (also: inotropism, adjective : inotrop ; from ancient Greek ἡ ἴς he is, genitive ἰνός inos = tendon, fiber, muscle, nerve, power, strength; and τρέπειν trepein = turn, turn, change, change your mind; τρεπω trepo = turn, turn; ἡ τροπη e trope = turning, turning) describes in medicine the influence on the ability of the heart muscles to contract . In this context, inotropy describes the strength of the heart (impact force, myocardial contractility, contraction force , shortening speed , shortening fraction ( English : fractional shortening )). The inotropy forms the functional opposite of the lusitropia .

## Definitions

The inotropy is

• The cardiac contractility,
• the effect on the heart rate ,
• "the contractility of the heart muscle based on the comparable preload ( preload ) during the quiet before the twitch"
• influencing strength or speed of muscular contractility or
• the " influencing the ability of muscles to contract."

## physiology

The heart force is the product of the blood mass m (= weight of the stroke volume ) and its acceleration a. The formula F = ma with the SI unit Newton N = kgm / s 2 applies to cardiac force . The heart force in the small circuit is much smaller than the heart force in the large circuit .

The heart work (separately for both circuits) is now the product of heart force and arterial length with the unit joule (J = Nm), because work is defined as force times distance. In addition, the work of the heart is defined as the product of blood pressure and stroke volume; one speaks of the pressure-volume work of the heart.

The cardiac output (with the SI unit watt W = J / s) is firstly the quotient of cardiac work and the measured duration, and secondly the product of cardiac work and heart rate and thirdly the product of cardiac output and mean arterial pressure . Here, too, both cycles must be considered separately.

The cardiac output is approximately the square root of the quotient of cardiac output and peripheral resistance . In addition, cardiac output is the product of stroke volume and heart rate as well as the quotient of blood pressure and peripheral resistance. All three formulas apply independently of each other for both circuits.

## Medication

Medicinal substances that influence the inotropy by increasing the contraction force of the heart are called inotropics ( singular : inotropic ) or inotropic substances . A distinction is made between positive inotropy (increase in contractility) and negative inotropy (decrease in contractility).

With positive inotropics one wants to improve the symptoms of heart failure by increasing the cardiac output . With negative inotropics one wants to increase the individual life expectancy (life extension ) to relieve the heart ( cardiodepression , cardioprotection) while accepting a possible worsening of the heart failure.

## Positive inotropy

Positive inotropy is basically related to an increased supply of calcium ions in the muscle cell. It can be based on various mechanisms:

The binding of catecholamines ( noradrenaline from local sympathetic varicosities as well as noradrenaline and adrenaline from the adrenal medulla ) to β 1 -adrenoceptors sets the signal chain

G protein-coupled receptor → activated G α →  adenylyl cyclase →  cAMP →  protein kinase A (PKA)

in progress. The PKA phosphorylates calcium channels ( L-type calcium channel in the plasma membrane and ryanodine receptor of the sarcoplasmic reticulum ), which increases the calcium influx during the plateau phase of the action potential. Thus, catecholamines increase the maximum strength and the steepness of the increase in strength.

The binding of cardiac glycosides (such as digoxin , digitoxin or ouabain ) to the α-subunit of sodium-potassium-ATPase inhibits the active transport of sodium ions out of the cell. The cytosolic sodium concentration increases, which is thermodynamically unfavorable for the calcium outflow mediated by the sodium-calcium exchanger via the plasma membrane. The calcium ions thus increasingly absorbed into the sarcoplasmic reticulum are available for the contraction process: the contraction force increases.

By inhibiting phosphodiesterase, methylxanthines lead to an increased release of calcium and thus have a positive inotropic effect.

## Negative inotropy

Especially sympatholytic substances such as B. Beta blockers have a negative inotropic effect. Negative inotropy is also described as an undesirable side effect of antiarrhythmic drugs . Also, calcium antagonists have a negative inotropic; on the other hand, some calcium antagonists can significantly increase cardiac output.

Acetylcholine intervenes in the signaling pathway described above by binding to the M 2 receptor by inhibiting adenylyl cyclase by activating an inhibitory G protein . The parasympathetic innervation by the vagus nerve does not have a significant negative inotropic effect, however, since only the atrial myocardium and not the ventricles are innervated. (See also the article Parasympathetic, section: Heart .)

## Individual evidence

1. In many relevant specialist books, also in the latest editions of the standard works such as Harrison's internal medicine or Merck Manual as well as in the 3rd edition of the textbook of internal medicine by Walter Siegenthaler et alii, ISBN 3-13-624303-X , or in the manual of Internal diseases by Gerhard Brüschke in Volume 1, Part 1, Cardiovascular and vascular diseases by Bernd Heublein, Gustav Fischer Verlag , Stuttgart 1985, ISBN 3-437-10806-9 , the inotropy is neither mentioned nor defined. As shown below, the definitions cited are very inconsistent and even contradictory.
2. Ludwig August Kraus: Kritisch-etymologisches medicinisches Lexikon , 3rd edition, Verlag der Deuerlich- und Dieterichschen Buchhandlung, Göttingen 1844, pp. 541 and 1066.
3. So probably with the meaning of a change in force in the sense of an increase in cardiac muscle strength in the case of positive inotropy or a decrease in cardiac muscle strength in the case of negative inotropy. Today this is largely synonymous with increasing or decreasing contractility.
4. The cardiac output (as a measure of the severity or as a criterion for the presence of heart failure) is the product of stroke volume and heart rate , the quotient of cardiac output and blood pressure, the ratio of blood pressure and peripheral resistance, as well as the square root of the quotient of cardiac output and peripheral resistance . The stroke volume is the product of the end-diastolic cavity volume and the associated net ejection fraction, and the cardiac output is the product of cardiac work and heart rate .
5. Otto Martin Hess, Rüdiger WR Simon (ed.): Herzkatheter , Springer-Verlag, Berlin, Heidelberg 2000, ISBN 978-3-642-62957-0 , p. 171: "Impact force = impact work per expulsion time". - That's physically wrong. Work per time is performance and not strength. The definition of " stroke work = mean systolic blood pressure times stroke volume" (at the specified location) is, however, probably correct.
6. Maxim Zetkin , Herbert Schaldach (Ed.): Dictionary of Medicine , 1st edition, Verlag Volk und Gesundheit , Berlin 1956, p. 407.
7. Willibald Pschyrembel: Clinical Dictionary , 267th edition, de Gruyter , Berlin, Boston 2017, ISBN 978-3-11-049497-6 , p. 876.
8. Gerhard Brüschke (Ed.): Handbook of Internal Diseases , Volume 1, Part 1, Gustav Fischer Verlag , Stuttgart 1985, ISBN 3-437-10806-9 , pages 128 and 141.
9. ^ Robert HG Schwinger, Klara Brixius: The regulation of intracellular Ca 2+ homeostasis , in: Erland Erdmann : " Herzinsufficiency ", 4th edition, Wissenschaftliche Verlagsgesellschaft , Stuttgart 2005, ISBN 3-8047-2196-6 , p. 90.
10. ^ Wolfgang Trautwein , Otto Heinrich Gauer , Hans-Peter Koepchen : Heart and Circulation , Urban & Schwarzenberg , Munich, Berlin, Vienna 1972, ISBN 3-541-05411-5 , pp. 129-134.
11. ^ Lexicon Medicine , 4th edition, special edition, Naumann & Göbel Verlagsgesellschaft, Elsevier , Munich no year, ISBN 3-625-10768-6 , p. 840.
12. Maxim Zetkin , Herbert Schaldach (Ed.): Lexikon der Medizin , 16th edition, Ullstein Medical , Wiesbaden 1999, ISBN 3-86126-126-X , p. 966.
13. Otto Martin Hess, Rüdiger WR Simon (ed.): Herzkatheter , Springer-Verlag, Berlin, Heidelberg 2000, ISBN 978-3-642-62957-0 , p. 171: "Ability of the myocardial fibers to shorten and develop strength (= Contractility) ".
14. ^ Robert M. Youngson: Collins Dictionary of Medicine , Harper Collins, Glasgow 1992, ISBN 0-583-31591-7 [sic!], P. 316.
15. Duden : The Dictionary of Medical Terms , Bibliographisches Institut , 4th Edition, Georg Thieme Verlag , Stuttgart, New York 1985, ISBN 3-411-02426-7 , ISBN 3-13-437804-3 , p. 352.
16. ^ Willibald Pschyrembel: Clinical Dictionary , 85. – 99. Edition, de Gruyter Verlag, Berlin 1951, p. 391: "inotrop = influencing the heart contraction". - This is the first explanation in the "Clinical Dictionary"; In the previous edition from 1944, only a missing annex was referred to on page 335 for explanation.
17. Markwart Michler , Jost Benedum : Introduction to Medical Technical Language , 2nd edition, Springer-Verlag, Berlin, Heidelberg, New York 1981, ISBN 3-540-10667-7 , p. 187.
18. Gerd Harald Herold : Internal Medicine 2019 , self-published, Cologne 2018, ISBN 978-3-9814660-8-9 , p. 210: "The contractility (inotropy; strength and speed of the muscle fiber shortening) is the primary determinant of the ejection capacity of the heart" .
19. Günter Thiele (Ed.): Handlexikon der Medizin , Volume 2 (F – K), Urban & Schwarzenberg , Munich, Vienna, Baltimore without year, p. 1198: "Inotrop = with change in muscle strength " of the heart muscle.
20. Note: Strictly speaking, also the part of the cardiac work acceleration work W using the formula W = mv 2 /2 of the mass m of the stroke volume and the maximum velocity v of the blood flow. It is about 10% of the heart's work and can be estimated using the formula W = mv 2 , because the heart has two chambers.
21. Explanation : Pressure is force per area. So force is pressure times area. Work is power times away. So work is pressure times area times distance. Area times distance is volume. So work is pressure times volume.
22. "Inotropic = with an effect on the contractility ( performance ) of the heart muscle." Source: Roche Lexicon Medicine , 5th edition, Urban & Fischer , Munich, Jena 2003, ISBN 978-3-437-15156-9 , p. 929.
23. ^ Hexal Taschenlexikon Medizin , Urban & Fischer , 2nd edition, Munich, Jena 2000, ISBN 978-3-437-15010-4 , p. 353.
24. If one measures the cardiac output CO in m 3 / s, the cardiac output L in W = J / s and the peripheral resistance R in Pas / m 3 = Ns / m 5 , it is easy to see that the SI units of the CO equation 2 = L / R are correct. - The dimensions can also be calculated for control purposes. The cardiac output has the dimension L 3 T −1 . The cardiac output has the dimension ML 2 T −3 . The dimension of the peripheral resistance is the quotient of the dimensions of pressure and volume flow; thus (ML −1 T −2 ): (L 3 T −1 ) = ML −4 T −1 . Now for the definition formula HZV 2 = L / R the calculation of dimensions (L 3 T −1 ) 2 = L 6 T −2 = (ML 2 T −3 ): (ML −4 T −1 ) with L = length, T = Time and M = mass.
25. Gudrun Späth: Heart failure , de Gruyter , Berlin, New York 1988, ISBN 3-11-011801-7 , pp. 61 and 81-87.
26. ^ Franz Gross (ed.): The importance of calcium antagonists for high pressure therapy, MMV Medizin-Verlag, Munich 1984, ISBN 3-8208-1038-2 , p. 41.
27. M. Boeckh, T. Böckers: Original examination questions with commentary GK 2 (General Pharmacology and Toxicology). Thieme Verlag, Stuttgart 2002, ISBN 3-13-112535-7 , p. 181. ( online )
28. ^ Joachim Girndt: Cardiovascular diseases caused by arteriosclerosis , Wissenschaftliche Verlagsgesellschaft , Stuttgart 1994, ISBN 3-8047-1340-8 , p. 191.
29. ^ Felix Anschütz : Heart failure , Aesopus-Verlag, Basel, Wiesbaden 1984, ISBN 3-87949-095-3 , p. 157 f.
30. ^ Felix Anschütz : The chronic heart failure , Aesopus-Verlag, Basel 1988, ISBN 3-905031-12-4 , p. 162 f.
31. Hubert Mörl: Vascular Diseases in Practice , 2nd Edition, Edition Medicine, Weinheim, Deerfield Beach , Basel 1984, ISBN 3-527-15096-X , p. 99.
32. Berndt Lüderitz (Ed.): Arrhythmia treatment and hemodynamics , Springer-Verlag, Berlin, Heidelberg, New York 1990, ISBN 3-540-52056-2 , ISBN 0-387-52056-2 , p. 147.
33. Berndt Lüderitz: Therapy of cardiac arrhythmias , 2nd edition, Springer-Verlag, Berlin, Heidelberg , New York, Tokyo 1984, ISBN 3-540-13090-X , ISBN 0-387-13090-X , pp. 42 and 209.
34. Heinz Losse et al. (Ed.): Rational therapy in internal medicine , 2nd edition, Thieme-Verlag , Stuttgart, New York 1980, ISBN 3-13-512902-0 , p. 33.
35. Georg Schmidt: Antiarrhythmic Therapy: Cardiodepressive Side Effects , Schattauer , Stuttgart, New York 1989, ISBN 3-7945-1317-7 , 128 pages.
36. ^ Franz Gross (ed.): The importance of calcium antagonists for high pressure therapy, MMV Medizin-Verlag, Munich 1984, ISBN 3-8208-1038-2 , p. 41.
37. Another view: the contractility is not affected. Source: Ulrich Borchard: Kalziumantagonisten , de Gruyter , Berlin, New York 1993, ISBN 3-11-013167-6 , pp. 74–79.
38. ^ Hermann Eichstädt, Steven F. Horowitz: Nuklearkardiologie , Hoechst Aktiengesellschaft 1984, p. 68.
39. Erwin-Josef Speckmann, Jürgen Hescheler, Rüdiger Köhling (eds.): Physiologie , 5th edition, Elsevier / Urban & Fischer , Munich a. Jena 2008, ISBN 978-3-437-41318-6 : “In contrast, a clear negative inotropic effect of the vagus can only be found on the atrial myocardium of the warm-blooded animal . A weakening of the heart force via the vagus is not possible. "