Novel Targets of Metformin in Cardioprotection: Beyond the Effects Mediated by AMPK.

Ischemic heart disease is the main cause of death globally. In the heart, the ischemia/reperfusion injury gives rise to a complex cascade of molecular signals, called cardiac remodeling, which generates harmful consequences for the contractile function of the myocardium and consequently heart failure. Metformin is the drug of choice in the treatment of type 2 diabetes mellitus. Clinical data suggest the direct effects of this drug on cardiac metabolism and studies in animal models showed that metformin activates the classical pathway of AMP-activated protein kinase (AMPK), generating cardioprotective effects during cardiac remodeling, hypertrophy and fibrosis. Furthermore, new studies have emerged about other targets of metformin with a potential role in cardioprotection. This state of the art review shows the available scientific evidence of the cardioprotective potential of metformin and its possible effects beyond AMPK. Targeting of autophagy, mitochondrial function and miRNAs are also explored as cardioprotective approaches along with a therapeutic potential. Further advances related to the biological effects of metformin and cardioprotective approaches may provide new therapies to protect the heart and prevent cardiac remodeling and heart failure.

The Impact of Head-of-Bed Positioning and Transducer Location on Cerebral Perfusion Pressure Measurement.

INTRODUCTION: Head-of-bed (HOB) elevation is the standard of care for patients with intracranial pressure monitoring at risk for intracranial hypertension. Measurement of cerebral perfusion pressure (CPP) based on HOB elevation and arterial transducer position has not been adequately studied. METHODS: This is a planned secondary analysis of prospectively collected data in which paired, serial arterial blood pressure (ABP), intracranial pressure, and CPP measures were obtained once per day for 3 days, with measures leveled at the tragus (Tg) and the phlebostatic axis (PA). The HOB position was recorded for all paired readings. RESULTS: From 136 subjects, ABP and CPP values were lower when the transducer was leveled at the Tg, compared with the PA (P < .001); these differences persisted regardless of HOB position. CONCLUSION: The difference in CPP when ABP is referenced at the Tg versus PA is not consistently attributed to HOB elevation.