Question: 

In models of myocardial hibernation repetitive periods of ischemia are applied. We hypothesized that during the periods of low O₂ perfusion hypoxia inducible-factor 1a (HIF-1a) degradation may be reduced in the affected areas. This may activate resident leukocytes in the myocardium. As activated phagocytotic cells e.g. monocytes and macrophages take part in cardiac remodeling, fibrosis and cardiac function were taken as signs for their activity. Mice devoid of HIF-1a in myeloid cells offer an opportunity to investigate this hypothesis.

Methods: 

Deletion of myeloid cell HIF-1a was attained in LysMcre mice with an efficiency of 70%. For seven days LysMcre mice and their controls were subjected daily to 15 minutes of occlusion of the left anterior descending artery. 24 hours after the last reperfusion, hemodynamic measurements were performed by Millar catheter to evaluate cardiovascular function. Hearts were excised and histological sections were prepared for the calculation of fibrosis.

Results: 

Compared to controls, HIF-deficiency led to a significant increase of fibrosis (LysM: 30.7% vs. control 22.5%). This was consistent with an impaired cardiac function visible as increased diastolic intraventricular pressure (LysM: 10.98 mmHg vs. control: 2.47 mmHg), reduced contractility (LysM: 7407.48 mmHg/s vs. control: 10154.81 mmHg/s) and enhanced lung weight/body weight ratio (LysM: 6.33 vs. control: 5.29).

Conclusion: 

HIF-1a in myeloid cells seems to be an important regulator during myocardial hibernation. As its knockdown impaired myocardial function and increased cardiac injury.