Sex-Mediated Response to the Beta-Blocker Landiolol in Sepsis: An Experimental, Randomized Study

OBJECTIVES: To investigate any gender effect of the beta-1 adrenergic blocker, landiolol, on cardiac performance and energy metabolism in septic rats, and to explore the expression of genes and proteins involved in this process. DESIGN: Randomized animal study. SETTING: University research laboratory. SUBJECTS: Male and female Wistar rats. INTERVENTIONS: One hour after cecal ligation and puncture, male and female rats were randomly allocated to the following groups: sham male, cecal ligation and puncture male, cecal ligation and puncture + landiolol male, sham female, cecal ligation and puncture female, and cecal ligation and puncture + landiolol female. Cardiac MRI was carried out 18 hours after cecal ligation and puncture to assess in vivo cardiac function. Ex vivo cardiac function measurement and P magnetic resonance spectroscopy were subsequently performed using an isovolumic isolated heart preparation. Finally, we assessed cardiac gene and protein expression. MEASUREMENTS AND MAIN RESULTS: In males, landiolol increased indexed stroke volume by reversing the indexed end-diastolic volume reduction without affecting left ventricle ejection fraction. In females, landiolol did not increase indexed stroke volume and indexed end-diastolic volume but decreased left ventricle ejection fraction. Landiolol had no effect on ex vivo cardiac function and on high-energy phosphate compounds. The effect of landiolol on the gene expression of natriuretic peptide receptor 3 and on protein expression of phosphorylated-AKT:AKT ratio and endothelial nitric oxide synthase was different in males and females. CONCLUSIONS: Landiolol improved the in vivo cardiac performance of septic male rats while deleterious effects were reported in females. Expression of natriuretic peptide receptor 3, phosphorylated-AKT:AKT, and endothelial nitric oxide synthase are signaling pathways to investigate to better understand the sex differences in sepsis

Biomechanical Characteristics of Unconditioned and Conditioned Latissimus Dorsi Muscles Used for Cardiocirculatory Assistance

An understanding of the biomechanical characteristics of striated skeletal muscles involved in cardiocirculatory assistance is a prerequisite to assess their efficacy and to evaluate their haemodynamic benefits. Six goats had their latissimus dorsi muscles evaluated by isometric strain gauge testing. Total tension, and both active and passive force development at different preloads were measured. The relationship between muscle impedance and starting length was also studied. Four additional muscles were submitted to isometric and isotonic strain gauge testing after 3 months of chronic electrical stimulation (Broussais Hospital protocol) with the contralateral muscle serving as a control. In isometric testing, both conditioned and unconditioned goat latissimus dorsi displayed a Frank-Starling length-tension curve, and a linear relationship between muscle impedance and starting length was found. Chronic stimulation preserved muscle mass and isometric force. Transformed muscles showed a mean 59% reduction of maximal shortening velocity; means (s.d.) residual shortening velocity at maximal work and power output was 0.17(0.07) m/s. The work and power output were both reduced 65% after stimulation, and the residual maximal power at optimal preload varied from approximately 7.7 and 9.6 W/kg. It is concluded that, following the Broussais protocol, the goat latissimus dorsi muscle retained mass and most of its isometric force-generating capacity, but lost significant work and power potential. The residual power output did not, however, preclude the possibility of a significant cardiocirculatory contribution, providing that the conditions for optimal energy transduction are adequately delineated

Giant Cell Arteritis (Horton's Disease) of the Axillary Artery--Case Reports

The authors recently observed 2 elderly female patients with ischemic pain of the upper extremity as the first manifestation of giant cell arteritis. They presented with rest pain of both upper extremities and even gangrene of the thumb in 1 case. Subclavian and radial pulses were absent while peripheral pulses in the lower limbs were preserved. The angiography was so typical that the diagnosis of inflammatory arteritis was made, despite negative temporal artery biopsy. The patient with thumb gangrene was successfully operated on, the occlusive axillary lesions being bypassed by a long venous carotid humeral bypass graft. A biopsy of the axillary artery showed a granulomatous lymphoplasmocellular infiltration. A high-dose corticotherapy (24 mg daily) was begun in both cases, with dramatic improvements of general state, lowering of the erythrocyte sedimentation rate, and even reapparition of a reduced radial pulse in 1 patient. The authors discuss the incidence, symptoms, diagnosis, and treatment of systemic giant cell arteritis, with special attention to extracranial involvement. These case reports may broaden the knowledge of the diverse manifestations of giant cell arteritis and of its systemic character with widespread vascular involvement