What is Anrep effect?

What is Anrep effect?

Anrep effect was described by von Anrep in 1912 [1]. von Anrep showed that after clamping the aorta in a canine, which acutely decreases outflow and increases intraventricular pressure, heart dilates initially. This was followed by a progressive fall in end diastolic volume over minutes, towards the initial volume. At that time, it was thought to be due to the positive inotropic effect of adrenaline released by the adrenal gland in response to lowered blood supply [2].

The role of adrenal gland was ruled out by Rosenblueth in 1959 by reporting the same phenomenon in an isolated cardiac preparation [3]. Corresponding effect in isolated strips of ventricular myocardium was demonstrated by Parmley et al. They described both rapid and slow increase in the force developed after muscle is stretched [4]. The initial rapid increase in force of contraction is the well known Frank-Starling mechanism caused by an increase in responsiveness of the myofilament to calcium ions. The slow force response to the change in myocardial fiber length corresponds to the Anrep phenomenon or effect.

Anrep effect is a powerful mechanism by which heart adapts to an abrupt increase in after load after the initial Frank-Starling mechanism [2]. It is due to a progressive increase in calcium ion transient amplitude. Stretch triggers the release of angiotensin II, which in turn releases endothelin and activates sodium/hydrogen exchanger through endothelin type A receptors. Calcium ion transient is secondary to increased sodium ions [5]. The increase in contractility induced by the Anrep effect can be detected by changes in the ventricular pressure-volume loops. It occurs in response to an acute increase in afterload.

References

1. von Anrep G. On the part played by the suprarenals in the normal vascular reactions of the body. J Physiol. 1912 Dec 9;45(5):307-17. doi: 10.1113/jphysiol.1912.sp001553. PMID: 16993158; PMCID: PMC1512890.
2. Cingolani HE, Pérez NG, Cingolani OH, Ennis IL. The Anrep effect: 100 years later. Am J Physiol Heart Circ Physiol. 2013 Jan 15;304(2):H175-82. doi: 10.1152/ajpheart.00508.2012. Epub 2012 Nov 16. PMID: 23161880.
3. Rosenblueth A , Alanis J , Lopez E , Rubio R. The adaptation of ventricular muscle to different circulatory conditions. Arch Int Physiol Biochim. 1959 Jun;67(3):358-73. doi: 10.3109/13813455909072295. PMID: 13670663.
4. Parmley WW, Chuck L. Length-dependent changes in myocardial contractile state. Am J Physiol. 1973 May;224(5):1195-9. doi: 10.1152/ajplegacy.1973.224.5.1195. PMID: 4700639.
5. Alvarez BV, Pérez NG, Ennis IL, Camilión de Hurtado MC, Cingolani HE. Mechanisms underlying the increase in force and Ca(2+) transient that follow stretch of cardiac muscle: a possible explanation of the Anrep effect. Circ Res. 1999 Oct 15;85(8):716-22. doi: 10.1161/01.res.85.8.716. PMID: 10521245.