Vascular responses in forearm and calf to contralateral static exercises

Ten normal subjects performed a 90-s isometric exercise [20, 30, and 40% of maximal voluntary contraction (MVC)] of the flexor muscle of the right index finger or quadriceps muscle of the right leg. Contralateral forearm and calf blood flows (strain gauge plethysmography) and arterial blood pressure (auscultation) were measured simultaneously. Each exercise caused a decrease in forearm vascular resistance and a progressive increase in calf resistance. These changes were greatest with the 40% MVC. With finger exercise at 20 and 40% MVC, the percentage decreases in forearm vascular resistance from control were 12.3 and 22.7%, respectively (P < 0.01). Similar decreases (9.5 and 24.9%, respectively; P < 0.01) were noted with exercise of the quadriceps muscle. By contrast, the corresponding increases in calf vascular resistance were greater (P < 0.01) with quadriceps exercise (13.3 and 55.4%, respectively) than with finger exercise (6.0 and 36.0%). Arrest of the circulation to the exercising muscles just before the exercise ended caused an abrupt increase in forearm vascular resistance and a decrease in calf resistance. These studies provide further evidence of the heterogeneity of responses of forearm and calf resistance vessels to certain cardiovascular stimuli.link_to_subscribed_fulltex

Differential effects of lower body negative pressure on forearm and calf blood flow

Modest degrees of lower body negative pressure (<20 mmHg) cause a reflex constriction of forearm resistance vessels attributable to a decrease in activity of cardiopulmonary mechanoreceptors. In the present study, we sought to determine whether the calf vessels respond similarly. Left forearm and right calf blood flows were measured simultaneously by strain-gauge plethysmography in 10 healthy volunteers. Forearm flows decreased significantly from control during negative pressures of 10, 15, or 20 mmHg, whereas calf flows did not increase significantly until 20 mmHg; at 10, 15, and 20 mmHg, decreases in forearm flow were significantly greater than those of the calf. Similar results were obtained in a second series of experiments in which venous pooling in the right leg during lower body negative pressure was prevented by enclosing it in a boot. At 40 mmHg, or after a Valsalva maneuver, both forearm and calf vessels constricted markedly and to the same degree. It appears that the reflex reduction in blood flow to the skeletal muscles of the limbs resulting from deactivation of the low-pressure intrathoracic mechanoreceptors is directed primarily to the arm.link_to_subscribed_fulltex

Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients

Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin- kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. METHODS In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10 months. RESULTS At 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of -56.0% in the bococizumab group and +2.9% in the placebo group, for a between-group difference of -59.0 percentage points (P<0.001) and a median reduction from baseline of 64.2% (P<0.001). In the lower-risk, shorter-duration trial (in which the patients had a baseline LDL cholesterol level of ≥70 mg per deciliter [1.8 mmol per liter] and the median follow-up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval [CI], 0.80 to 1.22; P = 0.94). In the higher-risk, longer-duration trial (in which the patients had a baseline LDL cholesterol level of ≥100 mg per deciliter [2.6 mmol per liter] and the median follow-up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P = 0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P = 0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P<0.001). CONCLUSIONS In two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococizumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower-risk patients but did have a significant benefit in the trial involving higher-risk patients