Abstract P024: Pharmacological Treatment of Hypertension and Lv Dysfunction Predictors in ESRD Patients With AV Fistula

Background: Effects of anti-hypertensive medications on left ventricular dimensions and systolic function in patients with arterio-venous (AV) fistulas have not been well investigated. Material and Methods: Medical charts and echocardiograms of 346 patients with AV fistula were reviewed. Of 346, 149 patients had TTE prior to the AV fistula surgery, 197 had TTE after the AV fistula surgery, and 76 patients had TTE before and after the AV fistula surgery. Data on medication use was available in 314 patients. ANOVA, chi-square, and logistic regression tests were employed. Results: In patients scheduled for AV fistula placement, 20% (31/149) patients had systolic dysfunction and 15% (22/142) had increased LV end-diastolic dimensions (LVEDD). Moderate systolic LV dysfunction was observed in 6% (9/149) and additional 8% (12/149) had severe LV dysfunction. Increased LVEDD with some LV dysfunction was noted in 27% (38/142).Following the AV fistula placement, 18% (36/197) of patients had systolic dysfunction and 12% (22/187) had increased LV end-diastolic dimensions (LVEDD). Moderate or severe systolic LV dysfunction was observed in 6% (5/197). LV systolic dysfunction or dilatation was noted in 23% (43/187). Of 314 patients, 63% were on beta-blockers (BB), 25% were on ACE inhibitor or an ARB , 43% on calcium-channel blocker , and 15% on alpha-antagonist . BB, ACEi-ARB, or AA were not associated with increased LVEDD or systolic dysfunction before or after the AV fistula placement. Prior to AV fistula, CCB treatment was not related to LV dilatation (36% in each group, p=0.981) Post AV fistula, CCB treatment was associated with increased LV dimensions (71% vs. 46%, p=0.029) but not LV systolic dysfunction (49% in LV dysfunction vs. 38% in the rest, p=0.446) . This association persisted after adjustment for co-morbidities and demographic parameters. Conclusions: LV systolic dysfunction and/or dilatation are common in patients undergoing AV fistula surgery. Despite decreased use of Ca-channel blockers in patients with LV dysfunction prior to AV fistula, Ca-channel blockers are associated with increased LV dimensions post AV fistula, and probably should be avoided in this vulnerable patient population.

Graded Inhibitory Synaptic Transmission Between Leech Interneurons: Assessing the Roles of Two Kinetically Distinct Low-Threshold Ca Currents

In leeches, two pairs of reciprocally inhibitory heart interneurons that form the core oscillators of the pattern-generating network for heartbeat possess both high- and low-threshold (HVA and LVA) Ca channels. LVA Ca current has two kinetically distinct components (one rapidly activating/inactivating, ICaF, and another slowly activating/inactivating, ICaS) that mediate graded transmission, generate plateau potentials driving burst formation, and modulate spike-mediated transmission between heart interneurons. Here we used different stimulating protocols and inorganic Ca channel blockers to separate the effects of ICaF and ICaS on graded synaptic transmission and determine their interaction and relative efficacy. Ca2+ entering by ICaF channels is more efficacious in mediating release than that entering by ICaS channels. The rate of Ca2+ entry by LVA Ca channels appears to be as critical as the amount of delivered Ca2+ for synaptic transmission. LVA Ca currents and associated graded transmission were selectively blocked by 1 mM Ni2+, leaving spike-mediated transmission unaffected. Nevertheless, 1 mM Ni2+ affected homosynaptic enhancement of spike-mediated transmission that depends on background Ca2+ provided by LVA Ca channels. Ca2+ provided by both ICaF and ICaS depletes a common pool of readily releasable synaptic vesicles. The balance between availability of vesicles and Ca2+ concentration and its time course determine the strength of inhibitory transmission between heart interneurons. We argue that Ca2+ from multichannel domains arising from ICaF channels, clustered near but not directly associated with the release trigger, and Ca2+ radially diffusing from generally distributed ICaS channels interact at common release sites to mediate graded transmission.