Combined Arterial Hypertension and Ischemic Stroke Exaggerate Anesthesia-Related Hypotension and Cerebral Oxygenation Deficits: A Preclinical Study.

BACKGROUND: Intraoperative arterial hypotension (IOH) is a common side effect of general anesthesia (GA), associated with poor outcomes in ischemic stroke. While IOH is more prevalent with hypertension, it is unknown whether IOH may differ when GA is induced during ischemic stroke, versus other clinical settings. This is important given that many stroke patients receive GA for endovascular thrombectomy. METHODS: We evaluate the cardiovascular responses to volatile GA (isoflurane in 100% o2 ) before and during middle cerebral artery occlusion stroke in rats instrumented to record blood pressure (BP) and cerebral tissue oxygenation (p o2 ) in the projected penumbra, in clinically relevant cohorts of normotensive (Wistar rat, n = 10), treated hypertensive (spontaneously hypertensive [SH] + enalapril, n = 12), and untreated hypertensive (SH rat, n = 12). RESULTS: During baseline induction of GA, IOH was similar in normotensive, treated hypertensive, and untreated hypertensive rats during the induction phase (first 10 minutes) (-24 ± 15 vs -28 ± 22 vs -48 ± 24 mm Hg; P > .05) and across the procedure (-24 ± 13 vs -30 ± 35 vs -39 ± 27 mm Hg; P > .05). Despite the BP reduction, cerebral p o2 increased by ~50% in all groups during the procedure. When inducing GA after 2 hours, all stroke groups showed a greater magnitude IOH compared to baseline GA induction, with larger falls in treated (-79 ± 24 mm Hg; P = .0202) and untreated(-105 ± 43 mm Hg; P < .001) hypertensive rats versus normotensives (-49 ± 21 mm Hg). This was accompanied by smaller increases in cerebral p o2 in normotensive rats (19% ± 32%; P = .0144 versus no-stroke); but a decrease in cerebral p o2 in treated (-11% ± 19%; P = .0048) and untreated (-12% ± 15%; P = .0003) hypertensive rats. Sham animals (normotensive and hypertensive) showed similar magnitude and pattern of IOH when induced with GA before and after sham procedure. CONCLUSIONS: Our findings are the first demonstration that ischemic stroke per se increases the severity of IOH, particularly when combined with a prior history of hypertension; this combination appears to compromise penumbral perfusion.

Protocol for the MAnagement of Systolic blood pressure during Thrombectomy by Endovascular Route for acute ischemic STROKE randomized clinical trial: The MASTERSTROKE trial.

REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12619001274167p. RATIONALE: Cerebral blood flow is blood pressure-dependent when cerebral autoregulation is impaired. Cerebral ischemia and anesthetic drugs impair cerebral autoregulation. In ischemic stroke patients treated with endovascular thrombectomy, induced hypertension is a plausible intervention to increase blood flow in the ischemic penumbra until reperfusion is achieved. This could potentially reduce final infarct size and improve functional recovery. AIM: To test if patients with large vessel occlusion stroke treated with endovascular thrombectomy will benefit from induced hypertension. DESIGN: Prospective, randomized, parallel group, open label, multicenter clinical trial with blinded assessment of outcomes. PROCEDURES: Patients with anterior circulation stroke treated with endovascular thrombectomy with general anesthesia within 6 h of symptom onset, and patients with 'wake up' stroke or presenting within 6 to 24 h with potentially salvageable tissue on computed tomography perfusion scanning, are included. Participants are randomized to a systolic blood pressure target of 140 mmHg or 170 mmHg from procedure initiation until recanalization. Methods to maintain the blood pressure are at the discretion of the procedural anesthesiologist. STUDY OUTCOMES: The primary efficacy outcome is improvement in disability measured by modified Rankin Scale score at 90 days. The primary safety outcome is all-cause mortality at 90 days. ANALYSIS: The Mann-Whitney U test will be used to test the ordinal shift in the seven-category modified Rankin Scale score. All-cause mortality will be estimated using the Kaplan-Meier method and compared using a log-rank test.

Effects of pallidotomy on motor symptoms in an animal model of Parkinson's disease.

The present study was designed to evaluate the motor effects of lesioning the internal globus pallidus in an animal model of Parkinson's disease. Fourty rats were divided into four groups (each of 10 rats) which received either unilateral 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle (mfb) plus sham surgery to the pallidum, sham surgery of mfb plus N-methyl-D-aspartate (NMDA) induced pallidal lesions, combined 6-OHDA mfb + NMDA pallidal lesions or sham surgery to both structures. Animals with 6-OHDA lesions developed significant ipsilateral biases in head position, body axis and circling after amphetamine challenge (all P < 0.05). Prominent contralateral deficits were present in sensorimotor response latency and contralateral circling was induced by apomorphine challenge (both P < 0.05). The addition of an NMDA pallidal lesion, improved the head position and body axis biases, as well as dopamine-agonist induced rotation and contralateral reaction time in a sensorimotor task (all P < 0.05). There was, however, a slight worsening of sensorimotor response on the ipsilateral side (P < 0.05). Pallidal lesions in the absence of 6-OHDA lesions produced contralateral head position and body axis biases (both P < 0.05). These data indicate that pallidotomy improves some, but not all aspects of parkinsonian motor dysfunction in an animal model of Parkinson's disease (PD).

Implanted telemetry transmitters alter the noradrenergic response in vas deferens from mice.

Implantable telemetry devices are widely used in experimental animals. We investigated the potential for such implants to induce stress in mice. Changes in body weight and post-mortem responses of the vas deferens to noradrenaline (as a measure of sympathetic activation) were measured 28 days after transmitter implantation. We examined the influence of the anaesthetic used during implantation (pentobarbitone or fentanyl/fluanisone/midazolam), the strain (Balb/c and CBA) and the body weight at the time of implantation (small = 19-24g; large = 27-30g). A sham-implantation procedure did not significantly affect the responses to noradrenaline. When telemetry transmitters were implanted in small mice of both strains, there was a significant increase in the maximum response to noradrenaline compared to that obtained in tissues from large mice. The anaesthetic used during implantation did not affect the responses to noradrenaline obtained post mortem. Mice of both strains had a significant post-operative weight loss and this was maintained for the experimental period. The results show that implantation of telemetry transmitters has a significant impact in mice that weigh < 25g.