Key result
Gadolinium at concentrations up to 100 μmol/L did not reliably suppress mechanically induced electrical activation or prolong the stimulation-activation delay in whole isolated swine hearts.
Why the study?
Does gadolinium suppress mechanically-induced electrical activation in isolated swine hearts?
Does gadolinium suppress mechanically-induced electrical activation in isolated swine hearts?
Gadolinium does not effectively suppress mechanosensitivity in intact whole-heart preparations, suggesting caution when using it as a stretch-activated ion channel blocker in this setting.
SAC blockers may aid experimental study of cardiac mechanosensitivity; leaves open therapeutic translation.
Mechanical stimulation can elicit electrical activation of the heart. This mechanosensitivity can start life-threatening arrhythmias (commotio cordis) or terminate them (precordial thump). Mechanosensitivity may also be involved in arrhythmogenesis in other settings. Stretch-activated ion channels (SACs) are thought to be important in mechanosensitivity and a number of agents that block them have been identified. Such agents could potentially be used as tools in experimental investigation of mechanosensitivity. However, studies using them in intact-heart preparations have yielded inconsistent results. In the present study, we used isolated, perfused hearts from 25-35 kg pigs and a computer-controlled device that repeatably delivered focal mechanical stimuli. The concentration-dependent ability of the SAC blocker gadolinium to suppress mechanical activation was assessed by the success rate of mechanical stimulation and by the delay between successful mechanical stimulation and electrical activation. In six hearts, perfusate was recirculated. In an additional six hearts, perfusate was not recirculated to prevent gadolinium from forming complexes with metabolic waste and possibly precipitating. Gadolinium did not suppress mechanically-induced activation. Although gadolinium has been shown to be an effective SAC blocker in isolated cells, using it to probe the role of mechanical stimulation in whole heart preparations should be done with great caution.
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Zhang et al. (2018) studied Cardiac mechanosensitivity (n=12). Gadolinium vs. 0 μmol/L (baseline) was evaluated on Success rate of mechanical stimulation (R) and stimulation-activation delay (D) (p=0.614). Gadolinium at concentrations up to 100 μmol/L did not reliably suppress mechanically induced electrical activation or prolong the stimulation-activation delay in whole isolated swine hearts.
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