Background—The failing myocardium is characterized by decreased force production, slowed relaxation, and depressed responses to β-adrenergic stimulation. In some heart failure patients, heart function is so poor that a left ventricular assist device (LVAD) is inserted as a bridge to transplantation. In the present research, we investigated whether circulatory support with an LVAD influenced the functional properties of myocytes from the failing heart.Methods and Results—Myocytes were isolated from human explanted failing hearts (HF-myocytes) and failing hearts with antecedent LVAD support (HF-LVAD-myocytes). Studies of myocyte function indicated that the magnitude of contraction was greater (9.6±0.7% versus 6.9±0.5% shortening), the time to peak contraction was significantly abbreviated (0.37±0.01 versus 0.75±0.04 seconds), and the time to 50% relaxation was reduced (0.55±0.02 versus 1.45±0.11 seconds) in the HF-LVAD-myocytes compared with the HF-myocytes (P<0.05). The HF-LVAD-myocytes had larger contractions than the HF-myocytes at all frequencies of stimulation tested. The negative force-frequency relationship of the HF-myocytes was improved in HF-LVAD-myocytes but was not reversed. Responses to β-adrenergic stimulation (by isoproterenol) were greater in HF-LVAD-myocytes versus HF-myocytes.Conclusions—The results of the study strongly support the idea that circulatory support with an LVAD improves myocyte contractile properties and increases β-adrenergic responsiveness.

—Our objective was to determine the respective roles of the sarcoplasmic reticulum (SR) and the Na ⁺ /Ca ²⁺ exchanger in the small, slowly decaying Ca ²⁺ transients of failing human ventricular myocytes. Left ventricular myocytes were isolated from explanted hearts of patients with severe heart failure (n=18). Cytosolic Ca ²⁺ , contraction, and action potentials were measured by using indo-1, edge detection, and patch pipettes, respectively. Selective inhibitors of SR Ca ²⁺ transport (thapsigargin) and reverse-mode Na ⁺ /Ca ²⁺ exchange activity (No. 7943, Kanebo Ltd) were used to define the respective contribution of these processes to the Ca ²⁺ transient. Ca ²⁺ transients and contractions induced by action potentials (AP transients) at 0.5 Hz exhibited phasic and tonic components. The duration of the tonic component was determined by the action potential duration. Ca ²⁺ transients induced by caffeine (Caf transients) exhibited only a phasic component with a rapid rate of decay that was dependent on extracellular Na ⁺ . The SR Ca ²⁺ -ATPase inhibitor thapsigargin abolished the phasic component of the AP Ca ²⁺ transient and of the Caf transient but had no significant effect on the tonic component of the AP transient. The Na ⁺ /Ca ²⁺ exchange inhibitor No. 7943 eliminated the tonic component of the AP transient and reduced the magnitude of the phasic component. In failing human myocytes, Ca ²⁺ transients and contractions exhibit an SR-related, phasic component and a slow, reverse-mode Na ⁺ /Ca ²⁺ exchange–related tonic component. These findings suggest that Ca ²⁺ influx via reverse-mode Na ⁺ /Ca ²⁺ exchange during the action potential may contribute to the slow decay of the Ca ²⁺ transient in failing human myocytes.

The aim of this study was to assess the effect of the level of adherence to the DASH diet on hypertension risk by conducting a systematic review and meta-analysis. A systematic literature search was performed. Two independent investigators performed the study selection, data abstraction, and assessment of the included studies. The meta-analysis was performed separately with the adjusted hazard (HR) or incident rate ratios (IRR) and the odds ratios (OR) of the highest compared to the lowest DASH diet adherence scores using a random effects model. A total of 12 studies were included in the qualitative and quantitative synthesis. When cohort studies reporting HR were pooled together, high adherence to the DASH diet was associated with a lower risk of hypertension (HR: 0.81, 95% CI 0.73–0.90, I² = 69%, PI 0.61–1.08) compared to the low adherence. When cross-sectional studies reporting OR were combined, high adherence to the DASH diet was also related to a lower risk of hypertension (OR: 0.80, 95% CI 0.70–0.91, I² = 81%, PI 0.46–1.39). The findings suggest that high adherence to the DASH diet has a positive effect on reducing hypertension risk compared to low adherence. These data strengthen and are in line with all hypertension guidelines, indicating that lifestyle changes should start early even in populations with normal blood pressure.