Simple SummarySpinal anesthesia (application of local anesthetic into the subarachnoid space of spinal cord where cerebrospinal fluid circulates) is generally considered a simple, effective and safe procedure. Three rare incidents of patients who developed stroke after surgery under spinal anesthesia with bupivacaine prompted us to report these infrequent clinical cases. Their shared pathology of stenosis (abnormal narrowing of a blood vessel) or atheromatosis (abnormal accumulation of material in an artery) in the carotid or middle cerebral artery (key blood supply to brain), revealed postoperatively, formed the impetus to assess in a companion animal study whether spinal bupivacaine may compromise blood supply to the brain. We found in two-thirds of the rats studied that on application of bupivacaine into the subarachnoid space, blood pressure, blood flow in common carotid artery and baroreflex (responsible for maintained blood pressure) remained stable after a transient drop. However, the other third exhibited a secondary hypotension, depressed baroreflex, declined heart rate, reduced carotid blood flow and waning blood supply to and oxygen level in the cerebral cortex. Our animal study confirmed that blood supply to the brain can indeed be compromised (cause of stroke) after spinal anesthesia, and an impaired baroreflex, which leads to hypotension, plays a contributory role.Spinal anesthesia is generally accepted as an effective and safe practice. Three rare incidents of postoperative cerebral infarction after surgery under spinal anesthesia prompted us to assess whether spinal bupivacaine may compromise carotid or cerebral blood flow. Postoperative examination after the stroke incident revealed that all three patients shared a common pathology of stenosis or atheromatosis in the carotid or middle cerebral artery. In a companion study using 69 Sprague-Dawley rats, subarachnoid application of bupivacaine elicited an initial (Phase I) reduction in the mean arterial pressure, carotid blood flow (CBF) and baroreflex-mediated sympathetic vasomotor tone, all of which subsequently returned to baseline (Phase II). Whereas heart rate (HR) exhibited sustained reduction, cardiac vagal baroreflex, baroreflex efficiency index (BEI) and tissue perfusion and oxygen in the cerebral cortex remained unaltered. However, in one-third of the rats studied, Phase II gave way to Phase III characterized by secondary hypotension and depressed baroreflex-mediated sympathetic vasomotor tone, along with declined HR, sustained cardiac vagal baroreflex, decreased BEI, reduced CBF and waning tissue perfusion or oxygen in the cerebral cortex. We concluded that carotid and cerebral blood flow can indeed be compromised after spinal anesthesia, and an impaired baroreflex-mediated sympathetic vasomotor tone, which leads to hypotension, plays a contributory role.