Duration of left ventricular assist device support: Effects on abnormal calcium cycling and functional recovery in the failing human heart.

BACKGROUND: Intracellular Ca(2+) handling is abnormal in human heart failure. Studies have demonstrated that left ventricular assist device (LVAD) support reverses phenotypic alterations, suggesting that, in select patients, LVAD support may be a bridge to recovery. Few studies have related support duration to phenotypic recovery. We hypothesized that reversal of impaired sarcoendoplasmic reticulum (SR) Ca(2+) cycling following LVAD implantation is duration-dependent. METHODS: We used post-rest potentiation to assess SR function, and Western blot analysis to measure Ca(2+)-cycling proteins. Left ventricular tissue from 10 non-failing hearts, 8 failing hearts and 10 LVAD-supported hearts was analyzed. Support ranged from 7 to 334 days. The median duration, 115 days, divided patients into short- and long-term support groups. RESULTS: Post-rest potentiation (PRP) response recovered after short-term LVAD support to a level (116.8 +/- 12.1%; n = 5) close to non-failing (123.4 +/- 12.0%; n = 10) hearts, but recovery after long-term support (23.5 +/- 7.0%; n = 5) remained closer to that of failing hearts (13.5 +/- 5.6%). We found a similar pattern of normalization for SR Ca(2+)-ATPase protein and the phospholamban/SR Ca(2+)-ATPase ratio (non-failing: 0.66 +/- 0.11; failing: 1.21 +/- 0.23; short-duration LVAD: 0.68 +/- 0.14; long-duration LVAD: 1.67 +/- 0.30; correlation p < 0.001; r = 0.93). The ratio also tended to correlate with the PRP response after unloading (p = 0.05; r = -0.65). CONCLUSIONS: SR Ca(2+) handling improved during early LVAD support, but long-term support was associated with abnormal Ca(2+) cycling. These findings cast doubt on strategies designed to wean patients after complete unloading with an LVAD.

Effects of remifentanil on the contractility of failing human heart muscle.

OBJECTIVE: The purpose of this study was to determine the direct effects of remifentanil on inotropy of human myocardial tissue removed from failing explanted hearts of cardiac transplant recipients. DESIGN: In vitro, prospective study with repeated measures. SETTING: Research laboratory in a tertiary referral center. INTERVENTIONS: The authors studied the effects of remifentanil on isometric myocardial contractile parameters in failing atrial and ventricular myocardial muscles. The authors also used 1 micromol/L of isoproterenol to test adrenergic responsiveness of failing myocardial tissues in the presence of supratherapeutic remifentanil concentrations. MEASUREMENTS AND MAIN RESULTS: Muscles were studied at 37 degrees C and 1 Hz, with concentrations of remifentanil covering a wide range of therapeutic as well as supratherapeutic concentrations (ie, between 0.001 and 100 microg/mL). After the dose-response curve was obtained, the author measured the inotropic response to 1 micromol/L of isoproterenol in the presence of the cumulative dose of remifentanil. Over the wide range of concentrations, remifentanil had no significant effect on contractile function. In the presence of supratherapeutic concentration of remifentanil, isoproterenol produced a 97% +/- 58% increase in developed tension in failing atrial muscles and a 91% +/- 40% increase in failing ventricular muscles, which did not significantly differ from control muscles. CONCLUSIONS: The authors showed that remifentanil had no significant negative inotropic effects in failing human heart muscle and that myocardial contractility remained fully responsive to beta-adrenergic stimulation at all remifentanil concentrations studied.