| Title |
Metformin prevents ischaemic ventricular fibrillation in metabolically normal pigs
|
|---|---|
| Published in |
Diabetologia, May 2017
|
| DOI | 10.1007/s00125-017-4287-2 |
| Pubmed ID | |
| Authors |
Li Lu, Shuyu Ye, Rebecca L. Scalzo, Jane E. B. Reusch, Clifford R. Greyson, Gregory G. Schwartz |
| Abstract |
Metformin is the drug most often used to treat type 2 diabetes. Evidence suggests that metformin may reduce mortality of individuals with type 2 diabetes, but the mechanism of such an effect is unknown and outcomes of metformin treatment in people without diabetes have not been determined. If metformin favourably affected mortality of non-diabetic individuals, it might have even broader therapeutic utility. We evaluated the effect of metformin on myocardial energetics and ischaemic ventricular fibrillation (VF) in metabolically normal pigs. Domestic farm pigs were treated with metformin (30 mg kg(-1) day(-1) orally for 2-3 weeks; n = 36) or received no treatment (n = 37). Under anaesthesia, pigs underwent up to 90 min low-flow regional myocardial ischaemia followed by 45 min of reperfusion. Pigs were monitored for arrhythmia, monophasic action potential morphology, haemodynamics and myocardial substrate utilisation, AMP-activated protein kinase (AMPK) phosphorylation activity and ATP concentration. Death due to VF occurred in 12% of pigs treated with metformin compared with 50% of untreated controls (p = 0.03). The anti-fibrillatory effect of metformin was associated with attenuation of action potential shortening in ischaemic myocardium (p = 0.02) and attenuation of the difference in action potential duration between ischaemic and non-ischaemic regions (p < 0.001) compared with untreated controls. Metformin had no effect on myocardial contractile function, oxygen consumption, or glucose or lactate utilisation. During ischaemia, however, metformin treatment amplified the activation of AMPK and preserved ATP concentration in myocardium compared with untreated controls (each p < 0.05). Chronic treatment of metabolically normal pigs with metformin at a clinically relevant dose reduces mortality from ischaemic VF. This protection is associated with preservation of myocardial energetics during ischaemia. Maintenance of myocardial ATP concentration during ischaemia is likely to prevent action potential shortening, heterogeneity of repolarisation, and propensity for lethal arrhythmia. The findings suggest that metformin might be protective in non-diabetic individuals with coronary heart disease. |
X Demographics
The data shown below were collected from the profiles of 11 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| India | 2 | 18% |
| Spain | 1 | 9% |
| United Kingdom | 1 | 9% |
| Germany | 1 | 9% |
| Brazil | 1 | 9% |
| United States | 1 | 9% |
| Unknown | 4 | 36% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 11 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 22 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 22 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 5 | 23% |
| Student > Master | 2 | 9% |
| Other | 2 | 9% |
| Professor | 2 | 9% |
| Student > Bachelor | 2 | 9% |
| Other | 2 | 9% |
| Unknown | 7 | 32% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 5 | 23% |
| Agricultural and Biological Sciences | 3 | 14% |
| Veterinary Science and Veterinary Medicine | 2 | 9% |
| Immunology and Microbiology | 2 | 9% |
| Linguistics | 1 | 5% |
| Other | 2 | 9% |
| Unknown | 7 | 32% |
Attention Score in Context
This research output has an Altmetric Attention Score of 7. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 July 2017.
All research outputs
#4,729,558
of 22,985,065 outputs
Outputs from Diabetologia
#2,032
of 5,085 outputs
Outputs of similar age
#83,064
of 310,857 outputs
Outputs of similar age from Diabetologia
#50
of 70 outputs
Altmetric has tracked 22,985,065 research outputs across all sources so far. Compared to these this one has done well and is in the 79th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 5,085 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 22.7. This one has gotten more attention than average, scoring higher than 60% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 310,857 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 73% of its contemporaries.
We're also able to compare this research output to 70 others from the same source and published within six weeks on either side of this one. This one is in the 28th percentile – i.e., 28% of its contemporaries scored the same or lower than it.