Abstract
Introduction
Cardiotoxicity from excessive exposure to circulating cobalt ions is a debilitating side effect for many patients with metal-on-metal hip replacements and has been implicated in some extreme cases to lead to heart failure (HF). A key feature of HF is cardiac fibrosis which results from excessive collagen deposition by cardiac fibroblasts (CFs) and can contribute to compromised diastolic function. To date, extremely little is known about the effects of cobalt on CFs, which comprise up to two-thirds of the total heart cell population in humans and rats.
Methods
Here, we have examined the chronic effects of cobalt on cardiac diastolic function and fibrosis development in adult male rat hearts. In addition, we have studied the acute effects of cobalt on both human and rat ventricular CF growth, morphology, and viability. Following echocardiographic assessment of rats (180-220g) treated with vehicle (n≤10) or 1mg/kg CoCl2 (n≤14) for 28 days via daily intraperitoneal injections, hearts were removed and used for sectioning and analysis of fibrosis by picrosirius red staining. In separate experiments, primary ventricular rat or human CFs were treated acutely with up to 5mM CoCl2 in culture for 24h and 48h, followed by brightfield imaging and viability assessment by MTT.
Results
Echocardiography of vehicle (n=10) and cobalt-treated (n=14) animals showed only subtle differences across groups for left ventricular end-diastolic diameter (vehicle: 0.68±0.02mm; CoCl2: 0.68±0.01mm; NS), left ventricular end-systolic diameter (vehicle: 0.26±0.02mm; CoCl2: 0.32±0.01mm; pConclusion
In conclusion, while chronic (28-day) cobalt treatment (1mg/kg) of rats results in relatively subtle effects upon cardiac diastolic function, acute cobalt treatment (up to 5mM CoCl2) of either rat or human CFs appears to have direct effects on cell viability across both species. This cellular effect could have clinical implications on the pathogenesis of diastolic dysfunction in patients with chronically high circulating cobalt levels.
Cardiotoxicity from excessive exposure to circulating cobalt ions is a debilitating side effect for many patients with metal-on-metal hip replacements and has been implicated in some extreme cases to lead to heart failure (HF). A key feature of HF is cardiac fibrosis which results from excessive collagen deposition by cardiac fibroblasts (CFs) and can contribute to compromised diastolic function. To date, extremely little is known about the effects of cobalt on CFs, which comprise up to two-thirds of the total heart cell population in humans and rats.
Methods
Here, we have examined the chronic effects of cobalt on cardiac diastolic function and fibrosis development in adult male rat hearts. In addition, we have studied the acute effects of cobalt on both human and rat ventricular CF growth, morphology, and viability. Following echocardiographic assessment of rats (180-220g) treated with vehicle (n≤10) or 1mg/kg CoCl2 (n≤14) for 28 days via daily intraperitoneal injections, hearts were removed and used for sectioning and analysis of fibrosis by picrosirius red staining. In separate experiments, primary ventricular rat or human CFs were treated acutely with up to 5mM CoCl2 in culture for 24h and 48h, followed by brightfield imaging and viability assessment by MTT.
Results
Echocardiography of vehicle (n=10) and cobalt-treated (n=14) animals showed only subtle differences across groups for left ventricular end-diastolic diameter (vehicle: 0.68±0.02mm; CoCl2: 0.68±0.01mm; NS), left ventricular end-systolic diameter (vehicle: 0.26±0.02mm; CoCl2: 0.32±0.01mm; pConclusion
In conclusion, while chronic (28-day) cobalt treatment (1mg/kg) of rats results in relatively subtle effects upon cardiac diastolic function, acute cobalt treatment (up to 5mM CoCl2) of either rat or human CFs appears to have direct effects on cell viability across both species. This cellular effect could have clinical implications on the pathogenesis of diastolic dysfunction in patients with chronically high circulating cobalt levels.
| Original language | English |
|---|---|
| Pages (from-to) | 614 |
| Number of pages | 1 |
| Journal | Acta Physiologica |
| Volume | 236 |
| Issue number | S725 |
| DOIs | |
| Publication status | Published - 18 Sept 2022 |
| Event | Europhysiology 2022 - Tivoli Conference Centre, Copenhagen, Denmark Duration: 16 Sept 2022 → 18 Sept 2022 |
Keywords
- concentration
- time-dependent effects
- cobalt
- rat
- human
- ventricular cardiac fibroblasts