Effects of gadolinium on cardiac mechanosensitivity in whole isolated swine hearts

Abstract

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.

Real-Time Deformability Cytometry Detects Leukocyte Stiffening After Gadolinium-Based Contrast Agent Exposure

“…Previous studies show that Gd is associated with strengthening of the F-actin cytoskeleton in fibroblasts 49 . Moreover, Gd is known to affect the mechanosensitivity of cardiac muscle cells 50 . Gd is frequently used as a blocker of stretch-activated ion channels 51 .…”

“…49 Moreover, Gd is known to affect the mechanosensitivity of cardiac muscle cells. 50 Gd is frequently used as a blocker of stretch-activated ion channels. 51 However, the mechanism of the mechanosensitive action of Gd3+ is not yet fully understood.…”

Dose-dependent suppression of tolaasin-induced hemolysis by gadolinium ion

“…Yang과 Sachs의 연구 [12]는 Xenopus oocytes에서 Gd 3+ 이 MSC를 세포 바깥쪽에서 완전히 가역적으 로 차단한다고 보고하였다. MSC의 저해는 1-100 μM Gd 3+ 농 도 범위에서 일어났다 [13]. MSC 저해에 관련된 Gd 3+ 의 작용기 작은 정확히 밝혀지지 않았으나, Lanthanides는 지질막이중층의 음 으로 하전된 인지질 등과 강하게 결합하며 [14], 막의 상전이 온도 를 높이고, 지질막의 유동성을 감소시키는 것이 밝혀졌다 [15,16].…”

Mechano‐electric and mechano‐chemo‐transduction in cardiomyocytes

“…GsMTx-4 shows good selectivity for SAC NS and is useful not only in cardiac cells, but also in native tissue (Bode et al 2001). This is not 'a given' and has led to false-negative observations with other, less suitable pharmacological agents such as gadolinium and streptomycin (Cooper & Kohl, 2005;Zhang et al 2018). A note of caution is warranted here for all cell culture studies: streptomycin, an obligatory component of most commercial culture media, is a formidable blocker of SAC NS and stretch-induced changes in Ca 2+ handling (Gannier et al 1994;Belus & White, 2003).…”