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Ischemia-reperfusion injury leads to distinct temporal cardiac remodeling in normal versus diabetic mice.

Eguchi M, Kim YH, Kang KW, Shim CY, Jang Y, Dorval T, Kim KJ, Sweeney G - PLoS ONE (2012)

Bottom Line: We first evaluated changes in cardiac function using echocardiography after 24 hours reperfusion and observed IR injury significantly decreased the systolic function, such as ejection fraction, fractional shortening and end systolic left ventricular volume (LVESV) in both control and diabetic mice.However, a reduced ability to metabolize glucose was observed in the diabetic animals as determined by PET-CT scanning using 2-deoxy-2-((18)F)fluoro-D-glucose.This was associated with marked increases in fibrosis, indicted by Masson trichrome staining, of heart sections in diabetic IR group.

View Article: PubMed Central - PubMed

Affiliation: Institut Pasteur Korea, Seoul, South Korea.

ABSTRACT
Diabetes is associated with higher incidence of myocardial infarction (MI) and increased propensity for subsequent events post-MI. Here we conducted a temporal analysis of the influence of diabetes on cardiac dysfunction and remodeling after ischemia reperfusion (IR) injury in mice. Diabetes was induced using streptozotocin and IR performed by ligating the left anterior descending coronary artery for 30 min followed by reperfusion for up to 42 days. We first evaluated changes in cardiac function using echocardiography after 24 hours reperfusion and observed IR injury significantly decreased the systolic function, such as ejection fraction, fractional shortening and end systolic left ventricular volume (LVESV) in both control and diabetic mice. The longitudinal systolic and diastolic strain rate were altered after IR, but there were no significant differences between diabetic mice and controls. However, a reduced ability to metabolize glucose was observed in the diabetic animals as determined by PET-CT scanning using 2-deoxy-2-((18)F)fluoro-D-glucose. Interestingly, after 24 hours reperfusion diabetic mice showed a reduced infarct size and less apoptosis indicated by TUNEL analysis in heart sections. This may be explained by increased levels of autophagy detected in diabetic mice hearts. Similar increases in IR-induced macrophage infiltration detected by CD68 staining indicated no change in inflammation between control and diabetic mice. Over time, control mice subjected to IR developed mild left ventricular dilation whereas diabetic mice exhibited a decrease in both end diastolic left ventricular volume and LVESV with a decreased intraventricular space and thicker left ventricular wall, indicating concentric hypertrophy. This was associated with marked increases in fibrosis, indicted by Masson trichrome staining, of heart sections in diabetic IR group. In summary, we demonstrate that diabetes principally influences distinct IR-induced chronic changes in cardiac function and remodeling, while a smaller infarct size and elevated levels of autophagy with similar cardiac function are observed in acute phase.

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Schematic diagram describing the time span of the experiment with summary of observations made at each time point.Changes in cardiac remodeling events were observed either at acute time point (24 hr reperfusion) or chronic time point (up to 6 weeks reperfusion) after 30 min of ischemia.
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pone-0030450-g007: Schematic diagram describing the time span of the experiment with summary of observations made at each time point.Changes in cardiac remodeling events were observed either at acute time point (24 hr reperfusion) or chronic time point (up to 6 weeks reperfusion) after 30 min of ischemia.

Mentions: In conclusion, we have demonstrated here that STZ-diabetes confers differential effects on cardiac remodeling events after IR injury (figure 7). Diabetic mice show a smaller infarct area post-MI, which may be the result of upregulated autophagy in the heart of these animals. However, in diabetic mice glucose metabolism is compromised at this time. Long term follow up studies indicated that diabetic mice heart develop severe fibrosis and concentric hypertophy leading to detrimental effects on functional performance.


Ischemia-reperfusion injury leads to distinct temporal cardiac remodeling in normal versus diabetic mice.

Eguchi M, Kim YH, Kang KW, Shim CY, Jang Y, Dorval T, Kim KJ, Sweeney G - PLoS ONE (2012)

Schematic diagram describing the time span of the experiment with summary of observations made at each time point.Changes in cardiac remodeling events were observed either at acute time point (24 hr reperfusion) or chronic time point (up to 6 weeks reperfusion) after 30 min of ischemia.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3275560&req=5

pone-0030450-g007: Schematic diagram describing the time span of the experiment with summary of observations made at each time point.Changes in cardiac remodeling events were observed either at acute time point (24 hr reperfusion) or chronic time point (up to 6 weeks reperfusion) after 30 min of ischemia.
Mentions: In conclusion, we have demonstrated here that STZ-diabetes confers differential effects on cardiac remodeling events after IR injury (figure 7). Diabetic mice show a smaller infarct area post-MI, which may be the result of upregulated autophagy in the heart of these animals. However, in diabetic mice glucose metabolism is compromised at this time. Long term follow up studies indicated that diabetic mice heart develop severe fibrosis and concentric hypertophy leading to detrimental effects on functional performance.

Bottom Line: We first evaluated changes in cardiac function using echocardiography after 24 hours reperfusion and observed IR injury significantly decreased the systolic function, such as ejection fraction, fractional shortening and end systolic left ventricular volume (LVESV) in both control and diabetic mice.However, a reduced ability to metabolize glucose was observed in the diabetic animals as determined by PET-CT scanning using 2-deoxy-2-((18)F)fluoro-D-glucose.This was associated with marked increases in fibrosis, indicted by Masson trichrome staining, of heart sections in diabetic IR group.

View Article: PubMed Central - PubMed

Affiliation: Institut Pasteur Korea, Seoul, South Korea.

ABSTRACT
Diabetes is associated with higher incidence of myocardial infarction (MI) and increased propensity for subsequent events post-MI. Here we conducted a temporal analysis of the influence of diabetes on cardiac dysfunction and remodeling after ischemia reperfusion (IR) injury in mice. Diabetes was induced using streptozotocin and IR performed by ligating the left anterior descending coronary artery for 30 min followed by reperfusion for up to 42 days. We first evaluated changes in cardiac function using echocardiography after 24 hours reperfusion and observed IR injury significantly decreased the systolic function, such as ejection fraction, fractional shortening and end systolic left ventricular volume (LVESV) in both control and diabetic mice. The longitudinal systolic and diastolic strain rate were altered after IR, but there were no significant differences between diabetic mice and controls. However, a reduced ability to metabolize glucose was observed in the diabetic animals as determined by PET-CT scanning using 2-deoxy-2-((18)F)fluoro-D-glucose. Interestingly, after 24 hours reperfusion diabetic mice showed a reduced infarct size and less apoptosis indicated by TUNEL analysis in heart sections. This may be explained by increased levels of autophagy detected in diabetic mice hearts. Similar increases in IR-induced macrophage infiltration detected by CD68 staining indicated no change in inflammation between control and diabetic mice. Over time, control mice subjected to IR developed mild left ventricular dilation whereas diabetic mice exhibited a decrease in both end diastolic left ventricular volume and LVESV with a decreased intraventricular space and thicker left ventricular wall, indicating concentric hypertrophy. This was associated with marked increases in fibrosis, indicted by Masson trichrome staining, of heart sections in diabetic IR group. In summary, we demonstrate that diabetes principally influences distinct IR-induced chronic changes in cardiac function and remodeling, while a smaller infarct size and elevated levels of autophagy with similar cardiac function are observed in acute phase.

Show MeSH
Related in: MedlinePlus