The increase in Ca²⁺ sensitivity of isometric force development along with sarcomere length (SL) is considered as the basis of the Frank-Starling law of the heart, possibly involving the regulation of cross-bridge turnover kinetics. Therefore, the Ca²⁺ dependencies of isometric force production and of the cross-bridge-sensitive rate constant of force redevelopment ( k_tr) were determined at different SLs (1.9 and 2.3 μm) in isolated human, murine, and porcine permeabilized cardiomyocytes. k_tr was also determined in the presence of 10 mM inorganic phosphate (P_i), which interfered with the force-generating cross-bridge transitions. The increases in Ca²⁺ sensitivities of force with SL were very similar in human, murine, and porcine cardiomyocytes (ΔpCa₅₀: ∼0.11). k_tr was higher ( P < 0.05) in mice than in humans or pigs at all Ca²⁺ concentrations ([Ca²⁺]) [maximum k_tr ( k_tr,max) at a SL of 1.9 μm and pCa 4.75: 1.33 ± 0.11, 7.44 ± 0.15, and 1.02 ± 0.05 s⁻¹, in humans, mice, and pigs, respectively] but k_tr did not depend on SL in any species. Moreover, when the k_tr values for each species were expressed relative to their respective maxima, similar Ca²⁺ dependencies were obtained. Ten millimolar P_i decreased force to ∼60–65% and left ΔpCa₅₀ unaltered in all three species. P_i increased k_tr,max by a factor of ∼1.6 in humans and pigs and by a factor of ∼3 in mice, independent of SL. In conclusion, species differences exert a major influence on k_tr, but SL does not appear to modulate the cross-bridge turnover rates in human, murine, and porcine hearts.

Objectives: Our aim was to assess the procedural success and determine the clinical predictors of postprocedure mortality, following rotational atherectomy (RA) and stenting in high‐risk patients.Background: RA is mainly used to facilitate stenting in complex lesions. Outcomes involving RA and stenting have been investigated, yet high‐risk patients have not been adequately described.Methods: Data of 218 consecutive patients who underwent RA were evaluated in a prospective register. Primary endpoints were the angiographic success and long‐term mortality. Secondary endpoints were procedural success, consumption of the angioplasty equipment, and periprocedural major adverse cardiac events. The impact of the relevant angiographic and clinical characteristics on long‐term mortality was analyzed using uni‐ and multivariate Cox regression analysis.Results: Mean age of the patients was 70 ± 8.2 years, diabetes was present in 44%, and chronic renal failure in 29%. Prior myocardial infarction and three‐vessel disease amounted to 42.2% and 32.6%, respectively. Altogether, 52.8% of patients underwent RA after a failed, non‐RA intervention attempt, and 30.7% of cases presented as acute coronary syndromes. Angiographic success was 100%, and all patients received stents after RA. Periprocedural major adverse cardiac events occurred in five (2.3%) patients. Postprocedural death was investigated, with a mean follow‐up of 36 months. Mortality amounted to 37.2%. Multivariate analysis revealed that left ventricular ejection fraction < 50%, glomerular filtration rate < 60 ml/min, cardiogenic shock, and diabetes were the only independent mortality predictors.Conclusions: We have found that RA and stenting is feasible and viable in an elderly high‐risk population, with exceptional procedural success and acceptable long‐term results.

Summary: Effects of ischaemic preconditioning (IP) on the mobilisation and recruitment of haematopoietic (HSCs) and mesenchymal stem (MSC) cells were determined in porcine coronary occlusion/reperfusion. Thirtythree pigs underwent percutaneous occlusion of the left anterior descending coronary artery (LAD) for 90 minutes (min), followed by 120 min reperfusion. IP was performed in 16 of the 33 pigs by two cycles of 5 min balloon occlusion/reperfusion prior to the 90 min occlusion (group IP vs. group C). Peripheral blood and myocardial tissue concentration of bone marrow origin HSCs (characterised by coexpression of CD31+, CD90+, CD45+) and MSCs (characterised by coexpression of CD44+, CD90+, CD45-) were measured by flow cytometry in the early phase of IP. Plasma/serum levels of stem cell mobilisation factors (stromal cell-derived factor-1α [SDF-1α], vascular endothelial growth factor [VEGF], tumour necrosis factor α[TNF-α] and interleukin-8 [IL-8]) were measured. IP led to a significant increase in circulating HSCs as compared with the group C (475 ± 233 vs. 281 ± 264 /μl, p=0.032) in the early phase of IP. In contrast, a rapid and prolonged decrease in level of circulating MSCs was observed in group IP as compared with group C (19 ± 12 vs. 32 ± 17 /μl, p=0.015). The recruitment of HSCs and MSCs in infarct and border zone was significantly greater in IP group, indicating a faster homing of MSCs as compared with the rate of mobilisation. Rapid increase in VEGF, TNF-α and IL-8 levels was induced by IP, which, however, was not correlated with the levels of circulating SCs. In conclusion, IP resulted in differential mobilisation and recruitment of HSCs and MSCs in the early phase of cardioprotection.

Background: Serum angiotensin-converting enzyme (ACE) activity determination can aid the early diagnosis of sarcoidosis. We aimed to optimize a fluorescent kinetic assay for ACE activity by screening the confounding effects of endogenous ACE inhibitors and interfering factors. Genotype-dependent and genotype-independent reference values of ACE activity were established, and their diagnostic accuracies were validated in a clinical study.Methods: Internally quenched fluorescent substrate, Abz-FRK(Dnp)P-OH was used for ACE-activity measurements. A total of 201 healthy individuals and 59 presumably sarcoidotic patients were enrolled into this study. ACE activity and insertion/deletion (I/D) genotype of theACEgene were determined.Results: Here we report that serum samples should be diluted at least 35-fold to eliminate the endogenous inhibitor effect of albumin. No significant interferences were detected: up to a triglyceride concentration of 16 mM, a hemoglobin concentration of 0.71 g/L and a bilirubin concentration of 150 μM. Genotype-dependent reference intervals were considered as 3.76–11.25 U/L, 5.22–11.59 U/L, 7.19–14.84 U/L forII,IDandDDgenotypes, respectively.I/Dgenotype-independent reference interval was established as 4.85–13.79 U/L. An ACE activity value was considered positive for sarcoidosis when it exceeded the upper limit of the reference interval. The optimized assay with genotype-dependent reference ranges resulted in 42.5% sensitivity, 100% specificity, 100% positive predictive value and 32.4% negative predictive value in the clinical study, whereas the genotype-independent reference range proved to have inferior diagnostic efficiency.Conclusions: An optimized fluorescent kinetic assay of serum ACE activity combined withACE I/Dgenotype determination is an alternative to invasive biopsy for confirming the diagnosis of sarcoidosis in a significant percentage of patients.

Purpose: Our aim was to evaluate the acute success and complication rates of the transradial and transulnar access for iliac artery stenting using sheathless guiding systems.Methods: Clinical and angiographic data from 156 consecutive patients with symptomatic iliac artery stenosis who were treated with transradial or transulnar access were evaluated. All patients underwent Duplex ultrasound before and after the intervention. The primary endpoints were the procedural success rate, major adverse events, and access site complication rates. The secondary endpoints were the angiographic result of the iliac artery intervention, fluoroscopy time, X‐ray dose, procedure length, crossover rate to another puncture site and hospitalization duration. The impact of the learning curve was also investigated, along with right or left radial access.Results: The indication for the intervention was intermittent claudication in 109 patients (69.9%), critical limb ischemia in 44 (28.2%) subjects and acute limb ischemia in three individuals (1.9%). Technical success was achieved in 155 patients (99.4%), with a crossover rate of 3.8%. Radial and ulnar artery access was used in 151 (96.8%) and 7 (4.5%) patients, respectively. The Ankle‐brachial index increased from 0.69 [0.65–0.72] to 0.91 [0.88–0.95] as a result of the procedures (P < 0.001). The cumulative incidence of major adverse events was 3.8% at the 2‐month follow‐up (0% in patients with intermittent claudication and 13.8% in patients with critical limb ischemia). Radial artery access site complications were encountered in eight patients (5.1%). We documented decreased X‐ray doses (1742.0 [783.9–2701] vs. 1435 [991.1–1879] vs. 692.8 [275.3–1110] Gy cm⁻² P < 0.05) over time; however, the fluoroscopy time, procedure time, and contrast consumption were not significantly different. Left hand access was not associated with significantly better results than right radial artery access.Conclusions: Iliac artery stenting can be safely and effectively performed using radial or ulnar artery access and sheathless guiding catheters, with acceptable complication rates and high levels of technical success. The physician learning curve plays an important role in decreasing the X‐ray dose. © 2016 The Authors. Catheterization and Cardiovascular Interventions Published by Wiley Periodicals, Inc.