Patients with poor-grade subarachnoid hemorrhage (SAH) are often complicated with acute cardiopulmonary dysfunctions, particularly neurogenic pulmonary edema (NPE) and takotsubo-like cardiomyopathy (TCM). This study retrospectively investigated the incidence, demographics, clinical characteristics, and outcomes of patients with SAH complicated with both NPE and TCM (NPE-TCM). The effects of aneurysm location and other clinical variables on the incidence of NPE-TCM were also investigated. Among 234 SAH patients treated during 5-year period, 16 (7%) presented with NPE, and transthoracic ultrasonography revealed that 14 of these 16 patients (88%) also had TCM. All 14 patients with NPE-TCM had poor-grade SAH (World Federation of Neurosurgical Societies grades IV and V). Ruptured posterior circulation aneurysm was predictive of NPE-TCM, but other clinical variables were not. Eight of the 14 patients with NPE-TCM could undergo treatment for ruptured aneurysm. Long-term outcomes were favorable in 5 of the 8 patients. Grade IV SAH patients had significantly better outcomes than grade V patients. TCM develops frequently in SAH patients presenting with NPE, and transthoracic ultrasonography should be conducted routinely in that population. Patients with ruptured posterior circulation aneurysm may have elevated risk of developing NPE-TCM. Endovascular obliteration of the aneurysm may be preferable to open surgery, but the optimal treatment modality needs to be evaluated further. Considering the limited number of SAH patients complicated with NPE-TCM, a multi-center cooperative study may be required.
Activation of mitochondrial ATP-sensitive potassium (mitoK(ATP)) channels protects the brain against ischemic or chemical challenge. Unfortunately, the prototype mitoK(ATP) channel opener, diazoxide, has mitoK(ATP) channel-independent actions. We examined the effects of BMS-191095, a novel selective mitoK(ATP) channel opener, on transient ischemia induced by middle cerebral artery occlusion (MCAO) in rats. Male Wister rats were subjected to 90 mins of MCAO. BMS-191095 (25 microg; estimated brain concentration of 40 micromol/L) or vehicle was infused intraventricularly before the onset of ischemia. In addition, the effects of BMS-191095 on plasma and mitochondrial membrane potentials and reactive oxygen species (ROS) production in cultured neurons were examined. Finally, we determined the effects of BMS-191095 on cerebral blood flow (CBF) and potassium currents in cerebrovascular myocytes. Treatment with BMS-191095 24 h before the onset of ischemia reduced total infarct volume by 32% and cortical infarct volume by 38%. However, BMS-191095 administered 30 or 60 mins before MCAO had no effect. The protective effects of BMS-191095 were prevented by co-treatment with 5-hydroxydecanoate (5-HD), a mitoK(ATP) channel antagonist. In cultured neurons, BMS-191095 (40 micromol/L) depolarized the mitochondria without affecting ROS levels, and this effect was inhibited by 5-HD. BMS-191095, similar to the vehicle, caused an unexplained but modest reduction in the CBF. Importantly, BMS-191095 did not affect either the potassium currents in cerebrovascular myocytes or the plasma membrane potential of neurons. Thus, BMS-191095 afforded protection against cerebral ischemia by delayed preconditioning via selective opening of mitoK(ATP) channels and without ROS generation.
The purpose of this study was to investigate the short-term effects of rosuvastatin (RSV), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on transient, focal cerebral ischemia in C57BL/6J ob/ob mice with insulin resistance (IR). Male ob/ob, lean, or wild-type (WT) mice were treated with RSV (10 mg/kg per day, i.p.) or vehicle for 3 days. Ischemia was induced by 60 mins of middle cerebral artery occlusion (MCAO) and cortical blood flow (CBF) was monitored by laserDoppler flowmetry. Infarct volumes were measured 24 h after reperfusion. IR mice exhibited a higher infarct volume compared with Lean or WT mice, and RSV reduced infarct volume only in obese mice (40%±3% versus 32%±3%, P < 0.05). Blood cholesterol and insulin levels were elevated in ob/ob mice but were unaffected by RSV. The CBF reductions during MCAO were similar in all groups and were not affected by RSV. Although RSV did not increase cortical endothelial NO synthase (eNOS) levels in the ob/ob mice, it attenuated the increased cortical expression of intracellular adhesion molecule-1 (ICAM-1) after MCAO from ob/ob mice. Thus, RSV protects against stroke in IR mice by a mechanism independent of effects on the lipid profile, CBF, or eNOS but dependent on suppression of post-MCAO ICAM-1 expression.
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