We conclude that pacing simultaneously at two right and two left ventricular sites significantly improves cardiac function compared with single RVA pacing, with or without sequential AV synchrony, in dogs with rapid ventricular pacing-induced heart failure and no BBB.

The purpose of this study was to characterize the transport mechanisms in endometrial epithelial cells that are responsible for regulation of Na and K concentrations in uterine luminal fluid. Porcine endometrial tissues were mounted in Ussing chambers and bathed in plasmalike Ringer solution. The mean basal short-circuit current (Isc) was 40 microA/cm2, and the mean tissue conductance was 3.6 mS/cm2. Addition of amiloride to the luminal solution inhibited 86% of the basal Isc. Concentration-response experiments using amiloride analogues showed a rank order of potency of benzamil > amiloride > 5-(N-methyl-N-isobutyl)-amiloride in blocking the Isc, with no response to ethylisopropylamiloride. Na channel immunoreactivity was localized to the apical membrane of surface epithelial cells. The Na-to-K selectivity ratio of the amiloride-sensitive Na channel was calculated to be 6.4:1. Prostaglandin (PG) F2 alpha or 8-(chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (CPT-cAMP) added to the luminal solution stimulated a twofold increase in Isc that was inhibited by pretreatment with amiloride. Experiments using both amphotericin B-permeabilized tissues and intact tissues showed that PGF2 alpha and cAMP increased Na absorption by activation of basolateral K channels. Treatment of the luminal solution with 4-aminopyridine produced an effect on Isc that was consistent with block of K secretion and a subsequent decrease in Na absorption. These experiments showed that Na and K transport are tightly coupled processes occurring under basal conditions in surface endometrial epithelial cells and that these processes are regulated by PGF2 alpha and cAMP.

transport were coupled under basal and cAMP stimulated conditions and basal anion transport decreased with age and during molting.

Previous studies in our laboratory have shown that Na absorption across the porcine endometrium is stimulated by PGF2alpha and cAMP-dependent activation of a barium-sensitive K channel located in the basolateral membrane of surface epithelial cells. In this study, we identify and characterize this basolateral, barium-sensitive K conductance. Porcine uterine tissues were mounted in Ussing chambers and bathed with KMeSO4 Ringer solution. Amphotericin B (70 microM) was added to the luminal solution to permeabilize the apical membrane and determine the current-voltage relationship of the basolateral K conductance after activation by 100 microM CPT-cAMP. An inwardly rectifying current was identified which possessed a reversal potential of -53 mV when standard Ringer solution was used to bathe the serosal surface. The K:Na selectivity ratio was calculated to be 12:1. Administration of 5 mM barium to the serosal solution completely inhibited the current activated by cAMP under these conditions. In addition to these experiments, amphotericin-perforated whole cell patch clamp recordings were obtained from primary cultures of porcine surface endometrial cells. The isolated cells displayed an inwardly rectifying current under basal conditions. This current was significantly stimulated by CPT-cAMP and blocked by barium. These results together with our previous studies demonstrate that cAMP increases Na absorption in porcine endometrial epithelial cells by activating an inwardly rectifying K channel present in the basolateral membrane. Similar patch clamp experiments were conducted using cells from a human endometrial epithelial cell line, RL95-2. An inwardly rectifying current was also identified in these cells which possessed a reversal potential of -56 mV when the cells were bathed in standard Ringer solution. This current was blocked by barium as well as cesium. However, the current from the human cells did not appear to be activated by cAMP, indicating that distinct subtypes of inwardly rectifying K channels are present in endometrial epithelial cells from different species.

The purpose of this study was to investigate the regulation of electrolyte transport across the porcine endometrium by gastrin-releasing peptide (GRP) and substance P (SP). Luminal addition of GRP, neuromedin B (NMB), SP, or neurokinin A(NKA) to mucosal tissues mounted in Ussing chambers produced a multiphasic change in short-circuit current (Isc) characterized by an initial rapid increase and subsequent decrease in current. A similar response was obtained after addition of ionomycin or thapsigargin to the tissues. The Isc response to the peptides or Ca ionophore was inhibited by pretreatment of the tissues with luminal amiloride or benzamil. GRP and SP were more potent [50% effective concentration (EC50) of 3 nM] than NMB or NKA (EC50 values of 46 and 26 nM, respectively) in producing the decrease in Isc. Pretreatment with the GRP receptor antagonist 3-Phe-His-Trp-Ala-Val-D-Ala-His-D-Pro-psi Phe-NH2 blocked the Isc response to GRP and NMB but not to SP or NKA, whereas the NMB receptor antagonist D-Nal-[Cys-Try-D-Trp-Orn-Val-Cys]-Nal-NH2 was ineffective in inhibiting the Isc response to any of the peptides. In contrast, pretreatment of the tissue with the nonpeptide SP receptor antagonist CP-99,994 blocked the Isc response to SP and NKA but not to GRP or NMB. Experiments with amphotericin B-permeabilized tissues showed that GRP, SP, ionomycin, and thapsigargin increased current through an outwardly rectifying K conductance located on the apical membrane of the cells. The K-to-Na selectivity ratio of this conductance was calculated to be 2.5:1. These experiments showed that GRP and SP, acting through different receptors, produced an increase in K efflux through a Ca-dependent K conductance present in the apical membrane of surface endometrial epithelial cells. In addition, immunohistochemistry data showed that GRP-like immunoreactivity was localized to surface and glandular epithelial cells, whereas GRP receptor antibody labeling was observed in both epithelial and stromal cells. These results suggest that GRP functions as both an autocrine and paracrine regulatory peptide in the endometrium.