Summary The precise regulation of cerebral blood flow is critical for normal brain function and its disruption underlies many neuropathologies. The extent to which smooth muscle-covered arterioles or pericyte-covered capillaries control vasomotion during neurovascular coupling remains controversial. We found that capillary pericytes in mice and humans do not express smooth muscle actin and are morphologically and functionally distinct from adjacent precapillary smooth muscle cells (SMCs). Using optical imaging we investigated blood flow regulation at various sites on the vascular tree in living mice. Optogenetic, whisker stimulation or cortical spreading depolarization caused microvascular diameter or flow changes in SMC but not pericyte-covered microvessels. During early stages of brain ischemia, transient SMC but not pericyte constrictions were a major cause of hypoperfusion leading to thrombosis and distal microvascular occlusions. Thus, capillary pericytes are not contractile and regulation of cerebral blood flow in physiological and pathological conditions is mediated by arteriolar smooth muscle cells.

Occlusion of the microvasculature by blood clots, atheromatous fragments, or circulating debris is a frequent phenomenon in most human organs. Emboli are cleared from the microvasculature by hemodynamic pressure and the fibrinolytic system. An alternative mechanism of clearance is angiophagy, in which emboli are engulfed by the endothelium and translocate through the microvascular wall. We report that endothelial lamellipodia surround emboli within hours of occlusion, markedly reducing hemodynamic washout and tissue plasminogen activator-mediated fibrinolysis in mice. Over the next few days, emboli are completely engulfed by the endothelium and extravasated into the perivascular space, leading to vessel recanalization and blood flow reestablishment. We find that this mechanism is not limited to the brain, as previously thought, but also occurs in the heart, retina, kidney, and lung. In the lung, emboli cross into the alveolar space where they are degraded by macrophages, whereas in the kidney, they enter the renal tubules, constituting potential routes for permanent removal of circulating debris. Retina photography and angiography in patients with embolic occlusions provide indirect evidence suggesting that angiophagy may also occur in humans. Thus, angiophagy appears to be a ubiquitous mechanism that could be a therapeutic target with broad implications in vascular occlusive disorders. Given its biphasic nature-initially causing embolus retention, and subsequently driving embolus extravasation-it is likely that different therapeutic strategies will be required during these distinct post-occlusion time windows.

Objective:To compare the effectiveness of single bolus dose of esmolol or fentanyl in attenuating the hemodynamic responses during laryngoscopy and endotracheal intubation.Methods:Ninety adult ASA I and ASA II patients were included in the study who underwent elective surgical procedures. Patients were divided into three groups. Group C (control) receiving 10 ml normal saline, group E (esmolol) receiving bolus dose of esmolol 2 mg/kg and group F (fentanyl) receiving bolus dose of fentanyl 2 µg/kg intravenously slowly. Study drug was injected 3 min before induction of anesthesia. Heart rate, systemic arterial pressure and ECG were recorded as baseline and after administration of study drug at intubation and 15 min thereafter.Results:Reading of heart rate, blood pressure and rate pressure product were compared with baseline and among each group. The rise in heart rate was minimal in esmolol group and was highly significant. Also the rate pressure product at the time of intubation was minimal and was statistically significant rate 15 min thereafter in group E.Conclusion:Esmolol 2 mg/kg as a bolus done proved to be effective in attenuating rises in heart rate following laryngoscopy and intubation while the rise in blood pressure was suppressed but not abolished by bolus dose of esmolol.

Background:This study was undertaken to evaluate the analgesic effect of the combination of epidural Clonidine with Bupivacaine versus epidural Bupivacaine alone in patients undergone knee replacement surgery.Materials and Methods:A randomized double-blind design was used, and 60 adult patients (40-60 years) of ASA grade I and II scheduled for post-operative pain relief in total knee replacement surgeries by epidural Clonidine were studied. Patients received either an epidural Clonidine (1μg/kg) with Bupivacaine (1.5mg/kg) group CL (n=30) or Bupivacaine alone group CT (n=30) for Knee replacement surgeries. The pain score, blood pressure, heart rate, respiratory rate were measured at fixed times during the first 24 h after operation. Onset and duration of sensory and motor blockade, duration of analgesia, and analgesic requirement were compared.Results:The onset of sensory anesthesia was faster (493.8±31.66 in sec.) and the duration was significantly longer in Clonidine group (334.2 min). Requirement of supplementary analgesia (Inj. diclofenac) was markedly decreased in Clonidine group as evident from the findings that in control group 18 patients required 3 supplemental analgesic doses in first 24 hours as compared to only 3 patients in Clonidine group. Epidural Clonidine produced a significant decrease (P less than 0.05) in heart rate and blood pressure, whereas the respiratory rate was not affected. We also observed for side effects in both the groups. Incidence of significant hypotension was higher, 8 patients (26%) in Clonidine group compared to 2 patient (6%) in control group. Incidence of dryness of mouth was higher, 12 patients (48%) in Clonidine group compared to 5 (18%) in control group.Conclusion:The addition of Clonidine to Bupivacaine epiduraly prolongs motor and sensory block and analgesia, without an increased incidence of side effects.

Background:In this study, we compared the sedative effects of sublingual midazolam solution with the oral tablet as premedication. Sixty pediatric patients of ASA physical status I and II were randomly selected to receive either 0.5 mg/kg of tablet or 0.5 mg/kg of sublingual solution of midazolam as premedication, about 45 min before elective surgery.Materials and Methods:There were 30 patients in each group. In Group I, the patients received premedication in the form of oral midazolam tablet 0.5 mg/kg. In Group II, the patients received midazolam solution 0.5 mg/kg. The degree of sedation and ease of separation was assessed according to the Niall C. Wilton scale and the procedure of Davis Peter, respectively. The time for complete drug dissolution was noted in both the groups. Then, the patients were interviewed regarding their acceptance of taste.Results:The sedation scores in the sublingual group were higher than in the oral group at 30 and 45 min after drug administration (P=0.0134 and P=0.0157). 66.6% of the patients in the sublingual group found it satisfactory as compared to 53.3% in the case of group receiving tablet.Conclusion:Thus, from the present study, it is concluded that premedication with midazolam is more effective by the sublingual than the oral route in children.