Potentiation by hypokalemia of the effects of acetylcholine on the canine heart in situ

Abstract

In the heart in situ of vagotomized dogs, atrioventricular conduction was studied by the His bundle potential recording, sinus rate continuously registered and the effective refractory period (ERP) of the atrial muscle measured by the extrastimulus method. The modifications induced by the acute lowering of plasma potassium concentration from 3.5 to 2.0 mmol/l obtained by hemodialysis appeared to be similar to those due to parasympathetic stimulation and the effects of hypokalemia and acetylcholine (ACh) on the atrioventricular (A-V) and sinoatrial nodes as well as on the atrial contractile tissue gave rise to potentiation. Intraaortically injected near coronary ostia in a dose lower than liminal dose, ACh enhanced to a large extent all the phenomena elicited by hypokalemia, since the variations respectively observed under the influence of hypokalemia alone and the combination of hypokalemia and ACh were as follows: lengthening of conduction time in the A-V node by 100 and 180%, reduction of sinus rate by 10 and 20%, shortening of the atrial ERP by 20 and 40%.

An atrioventricular node model incorporating autonomic tone

“…Increased parasympathetic activity has been associated with an increased conduction delay ( Martin, 1977 ); studies in dogs reported an increased conduction delay with acetylcholine administration ( Priola et al, 1983 ; Bertrix et al, 1984 ) and vagal stimulation ( Spear and Moore, 1973 ; Martin, 1975 ; Pirola and Potter, 1990 ). Moreover, there are indications that an increased parasympathetic activity is associated with an increased refractory period ( Martin, 1977 ); experimental studies using rabbit hearts reported an increased AV-nodal refractory period ( West and Toda, 1967 ) and occurrences of 2:1 AV nodal block ( Cranefield et al, 1959 ) with acetylcholine administration, and studies in dogs reported occurrences of AV block with acetylcholine administration ( Hageman et al, 1985 ) and vagal stimulation ( Spear and Moore, 1973 ; Hageman et al, 1985 ).…”

Mechanisms of hypokalemia‐induced ventricular arrhythmogenicity

“…In fact, studies on isolated, perfused murine [65] guinea‐pig [66–68] and rabbit heart preparations [69,70] show that APD prolongation in hypokalemic setting may be associated with shortened rather than lengthened refractoriness. Likewise, hypokalemia reduces the ERP in atrial muscle [71–74], wherein it may also exaggerate acetylcholine‐induced shortening in refractoriness. These changes increase vulnerability to tachyarrhythmias because of reduced excitation wavelength [73–75], which enables to fit more re‐entrant circuits into available mass of cardiac tissue.…”

“…Low extracellular K + concentrations contribute to slowed conduction in various parts of cardiac conduction system as well as contractile muscle. Hypokalemia markedly slows atrioventricular (AV) nodal conduction in canine [71,72] and rabbit heart [78], both via direct effect on AV node and because of potentiation of acetylcholine‐induced negative dromotropic responses. Furthermore, hypokalemia has been found to reduce impulse propagation velocity in isolated rabbit atrium [74], sheep Purkinje fibers [92] and cat papillary muscle [93].…”