Purpose
We are reporting in the first study that daily atorvastatin treatment in SHRSPs demonstrated stroke protection and decreasing mortality. In the second study, to reveal the protective mechanism from the aspect of cerebral blood circulation, SHRSPs were treated daily with atorvastatin, and rCBF were measured by autoradiography at premorbid period of stroke.
Methods
Male 8 weeks SHRSPs were treated daily orally with atorvastatin suspension at a dose of 20 mg/kg (n=5, A group). Vehicle male 8 weeks SHRSPs were treated daily orally with same amount of suspension without atorvastatin (n=5, V group). RCBF were measured by autoradiography (Sakurada et al) at age of 13 weeks, which was considered at premorbid period of stroke from the result of the first study. Briefly, rats were anesthetized with a mixture of halothane, oxygen and balance of nitrous oxide. Catheters were placed into femoral artery and vein, and physiological variables were monitored, such as blood pressure and arterial blood gas. After recovered from anesthesia, 150 μCu/kg of [14C]-iodoantipyrine (IAP) was infused into the vein, and 10 blood samples were obtained from the arterial catheter. RCBF were calculated from brain sample and blood samples. Region of interest was set for 15 sites bilaterally (cingulate, frontal, temporal, parietal, occipital, rhinal and entorhinal cortex, caudoputamen, globus pallidus, thalamus, hypothalamus, substantia nigra, CA1 and CA3 hippocampus and dentate gyrus). Averages of both hemispheres from each regions were used for rCBF, and values were indicated as mean±SD. Differences between A and V groups were tested for statistical significance using unpaired t-test. A P value less than 0.05 was considered statistically significant.
Results
There were no significant differences in physiologic variables between A and V groups. RCBF was significant larger in A group in cingulate cortex (A:128±14, V:96±21), and there were larger tendency in the other cortex, caudoputamen and grobus pallidus. There were no significant difference between A and V groups in thalamus, hypothalamus, substantia nigra, CA1 and CA3 hippocampus and dentate gyrus.
Conclusions
Atorvastatin treatment increased rCBF in many region of interest especially cingulate cortex at premorbid period of stroke without changing physiologic variables. It was considered that higher cerebral blood flow at premorbid period contribute to stroke prevention.