Acute hyperglycaemia is not associated with the development of atrial fibrillation in healthy pigs

Abstract

Development and progression of atrial fibrillation (AF) is driven by comorbidities such as arterial hypertension and diabetes mellitus. In animal models of chronic hyperglycaemia, progression of AF has been proposed to be triggered by oxidative stress, apoptosis and fibrosis. Acute glycosylation of CaMKII has been associated with increased susceptibility to arrhythmias in acute hyperglycaemia. However, the proarrhythmogenic effect of acute hyperglycaemia has not been investigated. Nine healthy, anesthetized pigs (54 ± 6 kg) were instrumented with electrophysiologic catheters and a multielectrode array on the epicardium of the left atrial anterior wall. Left and right atrial effective refractory periods (AERP), inducibility of AF and left atrial epicardial conduction velocities (CV) were measured at baseline (BL), increasing steps of blood glucose (200-500 mg/dL in steps of 100 mg/ dL by glucose infusion) and repeated after normalisation of blood glucose levels (recovery). Serum electrolytes were kept constant during measurements by means of sodium and potassium infusion. There were no significant differences in AERP, CV or AF inducibility between BL and recovery. Heart rate remained constant regardless of blood glucose levels (BL: 103 ± 18 bpm, 500 mg/dL: 103 ± 18 bpm, r = 0.02, p = 0.346). Mean left as well as right AERP increased with higher glucose levels. CV increased with glucose levels (1.25 (1.04, 1.67) m/s at BL vs. 1.53 (1.22, 2.15) m/s at 500 mg/dL, r = 0.85, p = 0.034). Rate of AF inducibility in the left atrium remained constant throughout the whole protocol (AF episodes > 10 s: mean inducibility of 80% at BL vs. 69% at 500 mg/dL, p = 0.32, episodes > 30 s: 0% at BL vs. 0% at 500 mg/dL, p = 0.17). Our data imply that acute hyperglycaemia is associated with lower arrhythmogenic substrate and does not promote AF inducibility.

WNT signaling in atrial fibrillation

“…[71][72][73] An excellent recent study demonstrated that acute hyperglycemia leads to a prolongation of conduction velocity and atrial effective refractory period (AERP) in healthy pigs. 74 This prolongation of the AERPs has rather protective effects with regard to AF inducibility. 74 The authors conclude that longerlasting hyperglycemia promotes AF by structural atrial remodeling, which is in full accordance with clinical observations and animal studies.…”

“…74 This prolongation of the AERPs has rather protective effects with regard to AF inducibility. 74 The authors conclude that longerlasting hyperglycemia promotes AF by structural atrial remodeling, which is in full accordance with clinical observations and animal studies. 75,76 The putative contribution of altered Wnt signaling pathway activity/expression to the AF-induced atrial structural remodeling in diabetic patients has not been specifically addressed so far.…”

CaMKII in Regulation of Cell Death During Myocardial Reperfusion Injury

“…Moreover, chronic hyperglycemia and CaMKII activation during diabetes downregulate K + channel expression and function, both of which increase sensitivity to arrhythmias possibly by O-GlcNAc glycosylation (Hegyi et al, 2020;Miura et al, 2020). However, when acute hyperglycemia was used to induce the glycosylation of CaMKII in animal experiments, only a low arrhythmic substrate was observed and atrial fibrillation was not induced (Manninger et al, 2020). Moreover, the most recent study showed that the locus of Ser280 in CaMKIIδ acts as phosphorylation rather than glycosylation in the model of AF (Mesubi et al, 2021), which should be further verified and explored in its change of conformation and function.…”