Bedside ultrasound of the internal jugular vein to assess fluid status and right ventricular function: The POCUS-JVD study.

BACKGROUND: Accurate estimation of fluid status is important in the management of heart failure patients, however, the current methods for bedside assessment can be unreliable or impractical for daily use. METHODS: Non-ventilated patients were enrolled immediately prior to scheduled right heart catheterization (RHC). Using M-mode, IJV maximum (Dmax) and minimum (Dmin) anteroposterior diameters were measured during normal breathing, while supine. Respiratory variation in diameter (RVD) was calculated as [(Dmax - Dmin)/Dmax] in percentage. Collapsibility with sniff maneuver (COS) was assessed. Lastly, inferior vena cava (IVC) was assessed. Pulmonary artery pulsatility index (PAPi) was calculated. Data was obtained by five investigators. RESULTS: Total 176 patients were enrolled. Mean BMI was 30.5 kg/m2, LVEF 14-69% (range), 38% with LVEF ≤35%. The POCUS of IJV could be performed in all patients in <5 min. Increasing RAP demonstrated progressive increase in IJV and IVC diameters. For high filling pressure (RAP ≥10 mmHg), an IJV Dmax ≥1.2 cm or IJV-RVD < 30% had specificity >70%. Combining the POCUS of IJV to physical examination improved the combined specificity to 97% for RAP ≥10 mmHg. Conversely, a finding of IJV-COS was 88% specific for normal RAP (<10 mmHg). An IJV-RVD <15% is suggested as a cutoff for RAP ≥15 mmHg. The performance of IJV POCUS was comparable to IVC. For RV function assessment, IJV-RVD < 30% had 76% sensitivity and 73% specificity for PAPi <3, while IJV-COS was 80% specific for PAPi ≥3. CONCLUSION: POCUS of IJV is an easy to perform, specific and reliable method for volume status estimation in daily practice. An IJV-RVD < 30% is suggested for estimation of RAP ≥10 mmHg and PAPi <3.

Sarcomere length affects Ca2+ sensitivity of contraction in ischemic but not non-ischemic myocardium.

In healthy hearts, myofilaments become more sensitive to Ca2+ as the myocardium is stretched. This effect is known as length-dependent activation and is an important cellular-level component of the Frank-Starling mechanism. Few studies have measured length-dependent activation in the myocardium from failing human hearts. We investigated whether ischemic and non-ischemic heart failure results in different length-dependent activation responses at physiological temperature (37°C). Myocardial strips from the left ventricular free wall were chemically permeabilized and Ca2+-activated at sarcomere lengths (SLs) of 1.9 and 2.3 µm. Data were acquired from 12 hearts that were explanted from patients receiving cardiac transplants; 6 had ischemic heart failure and 6 had non-ischemic heart failure. Another 6 hearts were obtained from organ donors. Maximal Ca2+-activated force increased at longer SL for all groups. Ca2+ sensitivity increased with SL in samples from donors (P < 0.001) and patients with ischemic heart failure (P = 0.003) but did not change with SL in samples from patients with non-ischemic heart failure. Compared with donors, troponin I phosphorylation decreased in ischemic samples and even more so in non-ischemic samples; cardiac myosin binding protein-C (cMyBP-C) phosphorylation also decreased with heart failure. These findings support the idea that troponin I and cMyBP-C phosphorylation promote length-dependent activation and show that length-dependent activation of contraction is blunted, yet extant, in the myocardium from patients with ischemic heart failure and further reduced in the myocardium from patients with non-ischemic heart failure. Patients who have a non-ischemic disease may exhibit a diminished contractile response to increased ventricular filling.

MgADP Promotes Myosin Head Movement toward Actin at Low [Ca2+] to Increase Force Production and Ca2+-Sensitivity of Contraction in Permeabilized Porcine Myocardial Strips.

Myosin cross-bridges dissociate from actin following Mg2+-adenosine triphosphate (MgATP) binding. Myosin hydrolyses MgATP into inorganic phosphate (Pi) and Mg2+-adenosine diphosphate (ADP), and release of these hydrolysis products drives chemo-mechanical energy transitions within the cross-bridge cycle to power muscle contraction. Some forms of heart disease are associated with metabolic or enzymatic dysregulation of the MgATP-MgADP nucleotide pool, resulting in elevated cytosolic [MgADP] and impaired muscle relaxation. We investigated the mechanical and structural effects of increasing [MgADP] in permeabilized myocardial strips from porcine left ventricle samples. Sarcomere length was set to 2.0 µm at 28 °C, and all solutions contained 3% dextran T-500 to compress myofilament lattice spacing to near-physiological values. Under relaxing low [Ca2+] conditions (pCa 8.0, where pCa = -log10[Ca2+]), tension increased as [MgADP] increased from 0-5 mM. Complementary small-angle X-ray diffraction measurements show that the equatorial intensity ratio, I1,1/I1,0, also increased as [MgADP] increased from 0 to 5 mM, indicating myosin head movement away from the thick-filament backbone towards the thin-filament. Ca2+-activated force-pCa measurements show that Ca2+-sensitivity of contraction increased with 5 mM MgADP, compared to 0 mM MgADP. These data show that MgADP augments tension at low [Ca2+] and Ca2+-sensitivity of contraction, suggesting that MgADP destabilizes the quasi-helically ordered myosin OFF state, thereby shifting the cross-bridge population towards the disordered myosin ON state. Together, these results indicate that MgADP enhances the probability of cross-bridge binding to actin due to enhancement of both thick and thin filament-based activation mechanisms.

Prior Freezing Has Minimal Impact on the Contractile Properties of Permeabilized Human Myocardium.

Background Experiments measuring the contractile properties of human myocardium are important for translational research but complicated by the logistical difficulties of acquiring specimens. Accordingly, many groups perform contractile assays using samples that are acquired from patients at one institution and shipped to another institution for experiments. This necessitates freezing the samples and performing subsequent assays using chemically permeabilized preparations. It is unknown how prior freezing affects the contractile function of these preparations. Methods and Results To examine the effects of freezing we measured the contractile function of never-frozen and previously frozen myocardial samples. Samples of left ventricular tissue were obtained from 7 patients who were having a ventricular assist device implanted. Half of each sample was chemically permeabilized and used immediately for contractile assays. The other half of the sample was snap frozen in liquid nitrogen and maintained at -180 °C for at least 6 months before being thawed and tested in a second series of experiments. Maximum isometric force measured in pCa 4.5 solution, passive force measured in pCa 9.0 solution, and Hill coefficients were not influenced by prior freezing (P=0.07, P=0.14, and P=0.27 respectively). pCa50 in never-frozen samples (6.11±0.04) was statistically greater (P<0.001) than that measured after prior freezing (5.99±0.04) but the magnitude of the effect was only ≈0.1 pCa units. Conclusions We conclude that prior freezing has minimal impact on the contractile properties that can be measured using chemically permeabilized human myocardium.

Retail 101: ringing up hospital sales.

Healthcare organizations can recapture lost revenue by offering healthcare products in on-site retail outlets. Healthcare organizations should look for retail opportunities inside the facility, customizing products to the subspecialty services offered. The products should meet the needs of their captive audience of patients, visitors, and employees. The retail outlets should be located in easily accessible areas where traffic flow is heaviest.

Growth and fertility rates in the offspring of pregnant rats treated with L-omega nitro-L-arginine methyl ester (L-NAME), a nitric oxide inhibitor.

OBJECTIVE: The objective of this study was to determine neonatal growth, fertility, and blood pressure for offspring of pregnant rats following in utero exposure to L-omega nitro-L-arginine methyl ester (L-NAME). STUDY DESIGN: Osmotic mini-pumps were inserted on day 14 of gestation during the index pregnancy to deliver L-NAME (50 mg/day/rat) or a placebo control continuously. Pup weights were obtained longitudinally until postnatal day 76. Systolic blood pressures were measured on postnatal days 29 and 44. At 11 weeks of age, groups of females and males (control and L-NAME-exposed in utero) were housed in pairs for 14 days; females were assessed for mating with a sperm positive vaginal flush and subsequent establishment of pregnancy. Pup weight and systolic blood pressure are expressed as mean +/- standard error of the mean and compared by using the unpaired t test. P <.05 was considered statistically significant. RESULTS: Pups born to L-NAME-treated mothers were significantly smaller than controls (5.2 +/- 0.2 g and 6.5 +/- 0.1 g, respectively; P <.0001)). These differences persisted even at postnatal day 76. There was no difference in systolic blood pressure between control and L-NAME-exposed pups. Successful mating rates were as follows: 90% (9/10) in control females with control males, 67% (8/12) in control females with L-NAME males, 47% (7/15) in L-NAME females with control males, and 31% (4/13) in L-NAME females with L-NAME males, P =.007 (control versus L-NAME females). CONCLUSION: The offspring of pregnant rats with in utero exposure to L-NAME (prolonged nitric oxide inhibition) exhibited decreased neonatal weight, postnatal growth, and fertility.