Table 2 Potential strategies for modulation of cerebral collateral flow in acute ischemic stroke
From: Cerebral collateral circulation in experimental ischemic stroke
Strategies | Risks | Cost | Results in preclinical stroke models | Results and feasibility in human stroke | |
|---|---|---|---|---|---|
Pressure load | |||||
Induced hypertension | Haemorrhagic transformation, cardiac arrhythmias, myocardial ischemia | Low | Core and penumbra CBF augmentation through LMAs after distal MCAO in mice [43] | Preliminary results indicate efficacy (small clinical studies) [44, 45]. High feasibility | |
Intravascular volume load | |||||
Dextran and hydroxyethyl starch | Anaphylaxis, pulmonary edema, platelet dysfunction | Low | CBF augmentation and improved outcome in various stroke models [46] | No benefit in early clinical trials (before the introduction of recanalization therapies) [47]. High feasibility | |
Albumin | Pulmonary edema, allergic reactions | Moderate | Cerebral perfusion enhancement through LMAs after distal MCAO in mice [48, 49] | No benefit in a large RCT (administered after recanalization therapy) [50]. High feasibility | |
Cerebral vasodilation | |||||
Nitric oxide inhalation | Pulmonary irritation | Moderate | Selective arteriolar vasodilation in the penumbra and cortical CBF enhancement after MCAO in mice [52] | No results available in human stroke. Moderate feasibility (inhalation delivery equipment needed) | |
Sphenopalatine ganglion stimulation | Invasive (minor surgery) | High | Cortical arterioles vasodilation and CBF augmentation after photothrombosis [53] | Ongoing clinical trial [54]. Moderate feasibility (surgery needed) | |
Sensory-induced vasodilation | No risks known | Low | Gradual reperfusion through collaterals after MCAO in rats [56] | No results available in human stroke. High feasibility | |
Acetazolamide | Paraesthesia, nausea, metabolic acidosis | Low | Negative effect on outcome if administered 48-54 h after the onset of permanent MCAO [59] | No results available in human acute stroke. Clinically used as diagnostic tool in chronic stroke. High feasibility | |
Cerebral flow diversion | |||||
Head down tilt | Increase in intracranial venous pressure | Low | Cerebral perfusion augmentation after bilateral CCAO in mice [62] | Increase in cerebral perfusion and blood flow velocity by flat head positioning (case series) [60, 61]. High feasibility | |
Partial aortic occlusion | Invasive (endovascular surgery) | High | Blood flow enhancement through LMAs after thromboembolic MCAO in rats [63] | Clinical trial suggest efficacy in post hoc subgroup analysis (further confirmation required) [64]. Moderate feasibility (endovascular procedure needed) | |