A mouse model of heart failure with preserved ejection fraction due to chronic infusion of a low subpressor dose of angiotensin II.

Heart failure (HF) with preserved ejection fraction (HFpEF) is a clinical syndrome of HF symptoms associated with impaired diastolic function. Although it represents ∼50% of patients with HF, the mechanisms of disease are poorly understood, and therapies are generally ineffective in reducing HF progression. Animal models of HFpEF not due to pressure or volume overload are lacking, therefore limiting in-depth understanding of the pathophysiological mechanisms and the development of novel therapies. We hypothesize that a continuous infusion of low-dose angiotensin II (ATII) is sufficient to induce left ventricular (LV) diastolic dysfunction and HFpEF, without increasing blood pressure or inducing LV hypertrophy or dilatation. Osmotic pumps were implanted subcutaneously in 8-wk-old male mice assigned to the ATII (0.2 mg·kg(-1)·day(-1)) or volume-matched vehicle (N = 8/group) for 4 wk. We measured systolic and diastolic arterial blood pressures through a tail-cuff transducer, LV dimensions and ejection fraction through echocardiography, and LV relaxation through pulsed-wave Doppler and LV catheterization. Myocardial fibrosis and cardiomyocyte cross-sectional area were measured. ATII infusion had no effects on systemic arterial blood pressure. ATII induced significant impairment in LV diastolic function, as measured by an increase (worsening) in LV isovolumetric relaxation time, myocardial performance index, isovolumetric relaxation time constant, and LV end-diastolic pressure without altering LV dimensions, mass, or ejection fraction. Chronic infusion of low-dose ATII recapitulates the HFpEF phenotype in the mouse, without increasing systemic arterial blood pressure. This mouse model may provide insight into the mechanisms of HFpEF.

Remote ischemic preconditioning for myocardial protection: update on mechanisms and clinical relevance.

Ischemic heart disease is the leading cause of death for both men and women worldwide, accruing 7.4 million deaths in 2012. There has been a continued search for better cardioprotective modalities that would reduce myocardial ischemia-reperfusion injury. Among these attempts, a more convenient model of ischemic preconditioning, known as remote ischemic preconditioning (RIPC) was first introduced in 1993 by Przyklenk and colleagues who reported that brief regional occlusion-reperfusion episodes in one vascular bed of the heart render protection to remote myocardial tissue. Subsequently, major advances in myocardial RIPC came with the use of skeletal muscle as the ischemic stimulus. To date, numerous studies have revealed that RIPC applied to the kidney, liver, mesentery, and skeletal muscle, have all exhibited cardioprotective effects. The main purpose of this review article is to summarize the new advances in understanding the molecular mechanisms of RIPC during the past 5 years, including those related to capsaicin-activated C sensory fibers, hypoxia-inducible factor 1α, connexin 43, extracellular vesicles, microRNA-144, microRNA-1, and nitrite. In addition, we have discussed results from several recent human clinical trials with RIPC. Taken together, the emerging clinical evidence supports the concept that the effectiveness of RIPC paired with its low-cost and non-invasive features makes it an ideal treatment before reperfusion after sustained ischemia. More carefully designed studies are warranted to fully exploit the clinical benefits of RIPC and its potential implications in patients with cardiovascular disease.

The Ansa Hypoglossi: Quantifying Axonal Density of a Donor Nerve for Facial Reinnervation.

Background: There are a number of nerve grafting options for facial reanimation and the ansa hypoglossi (AH) may be considered in select situations. Objective: To compare axonal density, area, and diameter of AH with other nerves more usually used for facial reanimation. Methods: AH specimens from patients undergoing neck dissections were submitted in formalin. Proximal to distal cross sections, nerve diameters, and the number of axons per nerve, proximally and distally, were measured and counted. Results: Eighteen nerve specimens were analyzed. The average manual axon count for the distal and proximal nerve sections was 1378 ± 333 and 1506 ± 306, respectively. The average QuPath counts for the proximal and distal nerve sections were 1381 ± 325 and 1470 ± 334, respectively. The mean nerve area of the proximal and distal nerve sections was 0.206 ± 0.01 and 0.22 ± 0.064 mm2, respectively. The mean nerve diameter for the proximal and distal nerve sections were 0.498 ± 0.121 and 0.526 ± 0.75 mm, respectively. Conclusion: The histological characteristics of the AH support clinical examination of outcomes as a promising option in facial reanimation.