In conclusion, we have Metformin mouse shown that CBF was reduced in elderly males with mild to moderate CHF, and was independently associated with factors that represent the severity of CHF. Reduced CBF was associated with impaired physical performance, and deteriorated quality of life, as well. Future studies are now needed to tease out possible association of CBF with cerebral disorders known to be more potentiated in the population with heart failure as well as to investigate the possible underlying mechanisms. “
“Radiation vasculopathy affects patients with primary brain tumor and causes significant morbidity from

ischemia related to hemodynamic insufficiency [1] and [2]. In these patients, medical management for secondary stroke prevention commonly includes HMG-CoA reductase inhibitors, or statins. Previous studies have shown that statin use improves cerebrovascular reactivity [3]. We report a contradictory finding in a unique patient with radiation vasculopathy and suggest broader implications for patients with hemodynamic insufficiency. check details A 66 year old man who underwent surgery and radiation for glioblastoma multiforme presented 6 months post surgery with new onset left sided weakness. He was found with a right

middle cerebral artery infarct and placed on simvastatin along with aspirin. He underwent a baseline transcranial Doppler (TCD) and then had his statin withdrawn. He was then brought back to the clinic 6 weeks later for follow-up study. Initial TCD showed no significant stenoses by velocity criteria in the proximal vessels of the circle of Willis. Interestingly, however, there was flow diversion on the right with ACA > MCA velocity, suggesting distal stenosis. The breath holding index was 0.42. 6 weeks later, after statin withdraw, TCD showed persistent flow diversion, but significant improvement in the BHI to 0.78. The data from this patient suggests small arteriolar disease from radiation vasculopathy causing poor hemodynamic flow to the right hemisphere.

Although the precise means by which statins worsen the hemodynamic flow to the affected hemisphere is unknown, the mechanism we propose below for this finding is based on previous studies in which statins almost have been shown to improve cerebrovascular flow [3]. While these findings seem to be contradictory, the finding in radiation vasculopathy is actually a logical extension of the larger theory regarding statin effects on cerebral blood flow and in fact corroborates the other findings of flow augmentation. Statins have the effect of decreasing cholesterol synthesis, and do so by inhibiting the upstream enzyme HMG CoA reductase. The downstream effect of this inhibition is the decreased production of not only cholesterol, but also geranyl pyrophosphate, a constituent of the family of small GTPases known as Rho. In the absence of geranyl pyrophosphate, less of the Rho GTPases are active [4].