Biomedical subjects

D J McCormick

Publications and source records attributed to D J McCormick.

At least 55 records · Page 3Linked to original sources

PubMed1996

Chimeric rat/human neurotensin receptors localize a region of the receptor sensitive to binding of a novel, species-specific, picomolar affinity peptide.

Recently, we reported the development of a species-specific neurotensin analog that displays selective binding affinity at the rat and human neurotensin (NT) receptor, L-[3,2'-Nal11]NT(8-13) (where Nal is naphthylalanine) (NT19). We have developed another neurotensin analog, L-[3,1'-Nal11]NT(8-13), (NT34), that exhibits a 126-fold difference in binding affinities between the rat and human receptors. This compound differs from our previous reported species-specific ligand in the steric positioning of the naphthyl ring on the L-alanine side chain. For NT34, the observed Kd values at the rat and human neurotensin receptors were 0.046 and 5.8 nM, respectively. In stimulating phosphatidylinositol turnover, the observed EC50 values were 2.8 nM and 130 nM in rat and human, respectively. We constructed a series of chimeric rat/human neurotensin receptor genes and expressed them by transient transfection into human embryonic kidney (HEK-293) cells. Radioligand binding assays were then performed using neurotensin and NT34. Our results led us to propose a region of the neurotensin receptor that may be involved in determining species specificity, i. e. the transmembrane VI, the third extracellular loop, and transmembrane VII regions of the neurotensin receptor.

Amino Acid Sequence↗

PubMed1996

Photoaffinity labeling of the lutropin receptor with synthetic peptide for carboxyl terminus of the human choriogonadotropin alpha subunit.

Human choriogonadotropin (hCG) consists of an alpha subunit and a beta subunit. The existing evidence from various studies using truncation, substitution, synthetic hormone peptides, and hCG crystals suggests that the C-terminal region of the alpha subunit contacts the luteinizing hormone/choriogonoadotropin (LH/CG) receptor and is involved in receptor activation. Despite a deluge of the speculation and the important role of the alpha C-terminal region, direct evidence for its interaction with the receptor has been elusive. Because of the significant biological activity, it is imperative to prove the interaction of the alpha C-terminal region. For this purpose, decamer peptides corresponding to the alpha subunit sequence from His83 to Ser92 (alpha 83-92) were derivatized with the N-hydroxysuccinimide ester of 4-azidobenzoylglycine (ABG) and radioiodinated. The resulting ABG-125I-alpha 83-92 was capable of binding and activating the LH/CG receptor. Furthermore, UV-sensitive ABG-125I-alpha 83-92 exclusively photoaffinity-labeled an approximately of 86-kDa molecule. This labeled molecule was shown to be the LH/CG receptor by various methods including immunoprecipitation by anti-LH/CG receptor antiserum. In addition, evidence is presented that the amino group of alpha Lys91 of alpha 83-92 is in such close proximity to a carboxyl group of the receptor that this pair is cross-linked to form an amide, a zero length cross-link. This low affinity contact of alpha 83-92 and the receptor is sufficient for receptor activation and is crucial for the full understanding of the mechanistics of the receptor activation steps.

Affinity Labels↗

PubMed1996

Phosphorylation of cholecystokinin receptors expressed on Chinese hamster ovary cells. Similarities and differences relative to native pancreatic acinar cell receptors.

Phosphorylation of G protein-coupled receptors is an established mechanism for desensitization in response to agonist stimulation. We previously reported phosphorylation of the pancreatic acinar cell cholecystokinin (CCK) receptor and the establishment of two-dimensional phosphopeptide mapping of its sites of phosphorylation (Ozcelebi, F., and Miller, L. J. (1995) J. Biol. Chem. 270, 3435-3441). Here, we use similar techniques to map sites of phosphorylation of the same receptor expressed on a stable receptor-bearing Chinese hamster ovary (CHO)-CCKR cell line. Like the native cell, the CHO-CCKR cell receptor was phosphorylated in response to agonist stimulation in a concentration-dependent manner; however, the time course was quite different. CHO-CCKR cell receptor phosphorylation increased progressively to a plateau after 15 min, while in the acinar cell it peaks within 2 min and returns to baseline over this interval. There were distinct qualitative and quantitative differences in the sites of phosphorylation of the two receptor systems. One site previously attributed to action of a staurosporine-insensitive kinase in the acinar cell was absent in the CHO-CCKR cell. Site-directed mutagenesis was utilized to eliminate predicted sites of protein kinase C action, but only two of four such sites affected the phosphopeptide map of this receptor. Chemical and radiochemical sequencing were performed on these and other phosphopeptides which were present in both the CHO-CCKR cells and agonist-stimulated pancreatic acinar cells to provide direct evidence for the phosphorylation sites actually utilized. Thus, these data support the usefulness and limitations of a model cell system in studying receptor phosphorylation and desensitization.

Amino Acid Sequence↗

PubMed1995

Primary hormonogenic sites as conserved autoepitopes on thyroglobulin in murine autoimmune thyroiditis. Secondary role of iodination.

We hypothesized earlier that conserved T cell epitopes and those unique to mouse thyroglobulin (MTg) contributed to its total thyroiditogenicity in murine autoimmune thyroiditis. Recent studies of synthetic peptides from human Tg (HTg) revealed no immunodominant epitopes. The role of iodine residues, considered by some to render Tg immunogenic, became unclear, since only one 12-mer peptide contained thyroxine (T4) positioned at hormonogenic site 2553. It primed T cells for thyroiditis transfer, but noniodinated peptide containing thyronine (T0) was not compared. To determine 1) whether other primary hormonogenic sites were likewise immunogenic and 2) whether iodination was requisite for this and other sites to be an autoepitope, we derivatized three pairs of 12-mer peptides, 1-12, 2549-2560, 2559-2570, containing T0 or T4 at positions 5, 2553, or 2567, respectively. The six peptides were used to stimulate MTg-primed cells in vitro and to immunize mice. None directly induced thyroiditis; peptide Abs were the lowest in mice given hT0(2567) or hT4(2567). Of the three T4-containing peptides, hT4(5) and hT4(2553), but not hT4(2567), stimulated MTg-primed or HTg-primed T cells in vitro, with hT4(2553) being the stronger. Comparing hT0(2553) with hT4(2553), both activated MTg-primed, or peptide-primed, T cells to transfer thyroiditis. The marked immunogenicity of noniodinated hT0(2553) and the poor antigenicity of hT4(5) and hT4(2567) demonstrate that immunogenicity of a conserved hormonogenic site is dependent more on its amino acid sequence than on T4 substitution. Iodination may enhance antigenicity and/or binding affinity, but it is not required for a Tg hormonogenic site to be an autoepitope.

Amino Acid Sequence↗

PubMed1995

Pharmacological and biochemical profiles of unique neurotensin 8-13 analogs exhibiting species selectivity, stereoselectivity, and superagonism.

Recently, the rat neurotensin receptor and the two human neurotensin receptor clones (differing by one amino acid residue) have been isolated. We present results with 33 newly synthesized neurotensin analogs. We have evaluated their binding potency at the three neurotensin receptor clones by determining equilibrium dissociation constants and coupling to phosphatidylinositol turnover. Our work focused on position 8 and 9 substitutions as well as position 11 of the neurotensin hexamer NT8-13. The results presented include: 1) the development of a compound that is species selective, with a binding potency at the rat receptor that is 20-fold more potent than at the human receptor; 2) the development of a pair of stereoselective compounds with the L-isomer exhibiting 190-700-fold more potency than the D-isomer; and 3) the development of an agonist that has a Kd of 0.3 and 0.2 nM at the human and rat neurotensin receptor, respectively, ranking it as among the most potent tested. Also, we present the first evidence that 1) the effect of pi electrons at position 11 (L-Tyr) are important for binding to the neurotensin receptor, and 2) the length of the side chain on position 9 (L-Arg) changes binding potency.

Amino Acid Sequence↗

PubMed1995

TSH receptor sequences recognized by CD4+ T cells in Graves' disease patients and healthy controls.

Twenty-nine overlapping synthetic peptides, twenty residues long, representing the entire extracellular sequence of the human thyroid stimulating hormone receptor (hTSHr), were used to test the epitope repertoire of CD4+ T lymphocytes from patients with Graves' disease and from healthy subjects. The peptides were used to propagate and test short term CD4+ T cell lines specific for hTSHr epitopes, and to directly test CD8+ depleted, CD4+ enriched peripheral blood lymphocytes. Analysis of the response of short-term CD4+ T cells lines and CD8+ depleted peripheral blood lymphocytes to the individual peptides revealed that 14 of the 15 patients and nine of the ten controls responded to at least one hTSHr peptide. There was no common response pattern, nor any region of the hTSHr sequence that was predominantly recognized. Several peptides were recognized by both patients and controls. These results support the notion that immunological tolerance to hTSHr is due to peripheral tolerance of potentially autoreactive CD4+ T cells, not their clonal deletion. The presence of self-reactive, hTSHr-specific CD4+ T cells in healthy individuals implies that these cells are not permanently anergized, since they can be activated in vitro.

Adult↗

PubMed1994

Peptide-induced conformational changes in class I molecules. Direct detection by flow cytometry.

Activation of a T cell in response to peptide bound to class I MHC occurs by the sum of interactions across the area of contact between the TCR, the peptide, and class I MHC. It has been observed recently that substitution of the peptide residue at a position that is not accessible from the exterior of the class I molecule modulates T cell responses, raising the possibility that there may be indirect structural effects in the peptide-class I complex as a consequence of peptide binding. This report describes the use of mAbs to probe the conformation of the alpha 1 and alpha 2 domains of the mouse class I molecule Kb when bound to ovalbumin peptide and a panel of 19 peptide analogues that differ at position 2 (P2). By crystallographic data, side chains of this position are buried in the Ag binding cleft and have no direct access to the TCR. Substitution of position 2 results in a measurable change in conformation of the class I molecule, a change that correlates with the ability to stimulate T cells. This leads to a model that T cell activation by the peptide-class I complex may occur in three ways: 1) direct interaction of the TCR with the class I heavy chain, 2) direct interaction of the TCR with solvent-accessible peptide side chains, and 3) indirect interaction of peptide with TCR mediated via conformational perturbations in the class I complex.

Amino Acid Sequence↗

PubMed1994

Calmodulin interacts with amphiphilic peptides composed of all D-amino acids.

Calmodulin binds to amphiphilic, helical peptides of a variety of amino-acid sequences. These peptides are usually positively charged, although there is spectroscopic evidence that at least one neutral peptide binds. The complex between calmodulin and one of its natural target peptides, the binding site for calmodulin on smooth muscle myosin light-chain kinase (RS20), has been investigated by crystallography and NMR which have characterized the interactions between the ligand and the protein. From these data, it appears that the calmodulin-binding surface is sterically malleable and van der Waals forces probably dominate the binding. To explore further this apparently permissive binding, we investigated the chiral selectivity of calmodulin using synthesized analogues of melittin and RS20 that consisted of only D-amino acids. Fluorescence and NMR measurements show that D-melittin and D-RS20 both bind avidly to calmodulin, probably in the same general binding site as that for peptides having all L-amino acids. The calmodulin-peptide binding surface is therefore remarkably tolerant sterically. Our results suggest a potentially useful approach to the design of non-hydrolysable or slowly hydrolysable intracellular inhibitors of calmodulin.

Binding Sites↗

PubMed1994

The automated implantable cardiac defibrillator. Prophylaxis in cardiac sarcoidosis.

A patient with cardiac sarcoidosis proved by biopsy specimen and no history of sudden death or clinical sustained ventricular tachycardia prophylactically received an implantable cardioverter defibrillator (ICD) that later reversed an episode of near syncope. The patient was supported with the ICD until heart transplantation. The physiology and treatment of arrhythmias associated with cardiac sarcoidosis is described. Consideration for use of the ICD in asymptomatic patients and as bridge therapy until heart transplantation is discussed.

Cardiomyopathies↗

PubMed1993

Structure-function studies of the human thyrotropin receptor. Inhibition of binding of labeled thyrotropin (TSH) by synthetic human TSH receptor peptides.

We have probed the hormone binding regions of the entire putative extracellular domain of the human thyrotropin (TSH) receptor (hTSHr) using synthetic peptides. A series of 26 overlapping peptides comprising the complete sequence of the extracellular domain of hTSHr was synthesized. Each peptide (20 amino acid residues each) was tested for its ability to interact with TSH, as evidenced by inhibition of binding of labeled hormone to native, membrane bound TSH receptors. Four of the 26 peptides interacted with labeled TSH and inhibited its binding to thyroid membranes. The most potent of these peptides was 256-275, which inhibited 125I-bovine TSH binding with an IC50 of 31.7 +/- 1.3 microM. The remaining peptides were 16-35 (351 +/- 9.4 microM), 106-125 (282 +/- 20.5 microM), and 226-245 (951 +/- 245 microM). An additional peptide, 286-305, showed minimal activity, and the remaining 21 peptides showed no activity. Peptides 256-275, 106-125, and 16-35 also inhibited binding of 125I-human chorionic gonadotropin to ovarian membrane receptors, suggesting that those regions of the receptor are involved in binding of a common glycoprotein hormone structure such as the alpha-subunit. In contrast, peptides 226-245 and 286-305 did not inhibit human chorionic gonadotropin binding, suggesting that these two regions are involved in hormone-specific activity. Of interest is the finding that the latter two peptides are from regions of TSHr that are largely dis-homologous to the lutropin receptor, whereas the former three, with the exception of 16-35, are from regions that are largely homologous between the two receptors. The data suggest that multiple, discontinuous regions of the extracellular domain of hTSHr are involved in the binding of the hormone. Furthermore, the binding regions are localized to TSHr-specific sequences as well as to regions that are highly homologous to LHr. This suggests that homologous regions of the two receptors are likely to perform similar functions in the interaction with their specific hormone, suggesting that those regions may be involved in binding of the glycoprotein hormone common alpha-subunit.

Amino Acid Sequence↗

PubMed1993

Visualization of implantable defibrillator patches by two-dimensional echocardiography.

Implantable cardioverter defibrillators are being used with increasing frequency for the management of life-threatening ventricular arrhythmias. In order to determine whether the titanium mesh of the defibrillator patch causes ultrasonographic acoustical interference, 30 patients underwent prospective serial echocardiographic examination. In addition, studies were reviewed to determine whether the defibrillator patches could be visualized with standard two-dimensional echocardiography. In no patient did the anterior patch produce acoustical interference, and, unless specific measures were utilized (such as a standoff pad, a zoom feature, or a 5-MHz transducer), the patches were rarely visualized.

Adult↗

PubMed1993

A receptor binding site identified in the region 81-95 of the beta-subunit of human luteinizing hormone (LH) and chorionic gonadotropin (hCG).

Two series of overlapping peptides comprising the entire sequences of the beta-subunits of human lutropin (LH) and choriogonadotropin (hCG) were prepared by a comprehensive synthetic strategy in order to identify all linear regions of the subunit that may participate in binding of the hormone to its receptor. Each series of peptides (15 residues in length) spanned the entire amino acid sequences of the two beta-subunits. The peptides were tested for their ability to inhibit the binding of 125I-labeled hCG or LH to rat ovarian membranes and for their ability to inhibit hCG-stimulated progesterone production in a Leydig cell bioassay. The most potent inhibitor of LH/hCG binding was a peptide containing the sequence beta 81-95, a receptor binding site of the LH/hCG beta subunit not previously described. The concentration at which LH/hCG binding was inhibited at 50% (IC50) was 20 microM and 30 microM for hCGbeta 81-95 and LH beta 81-95, respectively. These peptides also inhibited the stimulation of progesterone production by hCG in Leydig cell bioassays. In order to determine important residues that inhibit binding within this region, a third set of peptides was synthesized in which each residue of hCG beta 81-95 was sequentially replaced with the residue L-alanine. Five residues (Leu-86, Cys-88, Cys-90, Arg-94, and Arg-95) were critical for maximal inhibition of hCG binding by CG beta 81-95. In addition to site beta 81-95, other sites that inhibited hCG/LH binding but with significantly lower potencies included hCG beta 1-15, LH beta 41-55, and LH beta 91-105.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1993

Nine residues influence the binding of alpha-bungarotoxin in alpha-subunit region 185-200 of human muscle acetylcholine receptor.

Identification of residues in the skeletal muscle nicotinic acetylcholine receptor (AChR) that bind snake venom alpha-neurotoxin antagonists of acetylcholine [e.g., alpha-bungarotoxin (alpha-BTx)] provides structural information about the neurotransmitter binding region of the receptor. Using synthetic peptides of the human AChR alpha-subunit region 177-208, we previously localized a pharmacologically specific binding site for alpha-BTx in segment 185-199. To define in more detail the residues that influence the binding of alpha-BTx to this region, we prepared 16 peptide analogues of the alpha-subunit segment 185-200, with the amino acid L-alanine sequentially replacing each native amino acid. Circular dichroism spectroscopy did not reveal changes in the secondary structure of the peptides except for the analogue in which Pro194 was substituted with alanine. This implies that any change in alpha-BTx binding could be attributed to replacement of the native residue's side chain by alanine's methyl group, rather than to a change in the structure of the peptide. The influence of each substitution with alanine was determined by comparing the analogue to the parental sequence alpha 185-200 in solution-phase competition with native human AChR for binding of 125I-labeled alpha-BTx. The binding of alpha-BTx by analogue peptides with alanine substituted for Tyr190, Cys192, or Cys193 was greatly diminished. Binding of alpha-BTx to peptides containing alanine replacements at Val188, Thr189, Pro194, Asp195, or Tyr198 was also reduced significantly (p < 0.003). An unanticipated finding was that substitution of alanine for Ser191 significantly increased alpha-BTx binding (p < 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1993

Identification of a 60-kilodalton stress-related protein, p60, which interacts with hsp90 and hsp70.

Immunoaffinity purification of hsp90 from chick oviduct cytosol reveals two major proteins, hsp70 and a 60-kDa protein (p60), copurifying with hsp90. A similar result is obtained when hsp90 is immunoaffinity purified from chick liver and brain cytosols, avian fibroblasts, and rabbit reticulocyte lysate. This p60 is the same protein previously identified in certain assembly complexes of chick progesterone receptor generated in a cell-free reconstitution system. Tryptic and cyanogen bromide peptide fragments were generated from gel-purified p60, and partial N-terminal sequences were determined from eight peptides. The sequences show a striking similarity to the sequence of a 63-kDa human protein (IEF SSP 3521) whose abundance is increased in MRC-5 fibroblasts following simian virus 40 transformation. A monoclonal antibody was prepared against avian p60; Western immunoblot analysis showed that p60 was present in each of eight chick tissues examined and in each of the human, rat, rabbit, and Xenopus tissues tested. Immunoaffinity purifications from both chick oviduct cytosol and rabbit reticulocyte lysate using anti-p60 and anti-hsp70 monoclonal antibodies confirm that there is a relatively abundant complex in these extracts containing hsp90, hsp70, and p60. This complex appears to comprise an important functional unit in the assembly of progesterone receptor complexes. However, judging from the abundance and widespread occurrence of this multiprotein complex, hsp90, hsp70, and p60 probably function interactively in other systems as well.

Amino Acid Sequence↗

PubMed1992

Synthetic analogs of the carboxyl-terminus of beta-thyrotropin: the importance of basic amino acids in receptor binding activity.

Previously, using a synthetic peptide strategy, we determined that four distinct regions of human beta-thyrotropin (beta TSH) were responsible for interaction of TSH with the TSH receptor. The most potent of these four regions was the carboxyl-terminus of the subunit, represented by the peptide sequence beta 101-112, which inhibited binding of radiolabeled beta TSH to receptor in radioreceptor assay with an IC50 of approximately 100 microM. In the current studies, we systematically substituted the native amino acids in region beta 101-112 with alanine, and we have determined which residues within this span are important to the binding activity of TSH to its receptor. Substitution of Lys101, Asn103, Tyr104, Cys105, Lys107, and Lys110 with alanine each caused a significant fall in activity as compared to the native sequence, whereas substitution at the remaining positions had little or no effect. Because three of these residues are positively charged at physiologic pH, we hypothesized that this charge may be important to the binding activity of the sequence. We modified the charge characteristics of the region by synthesizing two series of analogs in which the residues identified in the alanine substitution studies were substituted with Arg, D-Lys, and D-Arg at each position. In addition, a series of analogs containing basic residues, either added to or substituted for nonbasic residues in the sequence beta 101-112, was synthesized. Substitution of Arg, D-Lys, and D-Arg for Lys101, Lys107, and Lys110 had little effect on activity; however, inclusion of additional basic residues in the beta 101-112 sequence significantly enhanced the inhibitory activity of the region.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗

PubMed1992

Inhibition of TSH bio-activity by synthetic beta TSH peptides.

The in vitro bioactivity of the human beta TSH subunit was investigated utilizing eleven overlapping synthetic peptides representing the entire 112 residue sequence. The peptides were tested for both stimulatory and inhibitory activity in two sensitive bioassay systems: the first based on cAMP production in FRTL-5 rat thyroid cells, and the second based on stimulation of iodine trapping by the same continuous cell line. Peptides from three distinct regions of the beta-subunit showed concentration dependent inhibition of TSH bio-activity, including beta 1-15, beta 11-25, beta 31-45, beta 81-95, and beta 91-105 with IC50 values ranging from 150 to 304 microM. An additional peptide representing the entire sequence of the "intercysteine loop" region of beta TSH, beta 31-52, also inhibited TSH activity with somewhat higher potency than its fragment peptide beta 31-45 (IC50 of 87.5 +/- 14.7 microM for beta 31-52 versus 207 +/- 92.4 microM for beta 31-45). Three of these, beta 1-15, beta 31-45, and beta 31-52, also inhibited binding of TSH to the receptor in a radio-receptor assay, as previously reported (1), supporting their importance in receptor interaction. None of the synthetic peptides stimulated either cAMP production or iodine trapping. Two other overlapping peptides, beta 81-95 and beta 91-105, possessed bio-inhibitory activity but did not inhibit binding of labeled TSH. Computer analysis of this sequence predicted an extended turn structure for this region. This region has been referred to as the "determinant loop" as it is bounded by cysteine residues at positions 88 and 95 that many believe form a disulfide bond in the native subunit. The current data suggests the beta 88-95 region may play a role in receptor activation after initial binding of hormone to receptor.

Amino Acid Sequence↗

PubMed1992

Programmable external automatic antitachycardia pacing as a bridge to definitive therapy in patients with recurrent sustained ventricular tachycardia.

The efficacy and safety of external programmable automatic antitachycardia pacemakers (ATPs) used in the critical care setting for recurrent sustained monomorphic ventricular tachycardia (VT) was evaluated. Ten patients who had failed a mean of 4.0 +/- 1.4 antiarrhythmic medications (range 2-7) and who had previously required electrical cardioversion for VT were enrolled. Prior to ATP use, successful overdrive pacing termination of VT was demonstrated in all patients. Intertach (Intermedics, Inc.; n = 9) and Orthocor II (Cordis, Inc.; n = 1) ATPs were attached to temporary bipolar transvenous or epicardial pacing leads. Mean patient age was 66.4 +/- 11.5 years, and mean left ventricular ejection fraction was 22 +/- 7.5%. At the time of initial ATP use, mean VT cycle length was 347 +/- 88 msec (range 280-550 msec). A burst scanning antitachycardia pacing algorithm was used in each patient; one patient was also treated with a fixed rate burst adapted to VT cycle length. The duration of ATP use ranged from 2-25 days (median 5), successfully terminating greater than 3,369 VT episodes (median 3, range 0 to greater than 3,103 episodes per-patient). Two episodes of ATP induced rate acceleration occurred, each successfully terminated by the ATP. Only two patients required external cardioversion during ATP use, one for primary ventricular fibrillation and one for rapid polymorphic VT associated with antiarrhythmic drug withdrawal. ATPs also provided antibradycardia pacing and allowed for serial programmed ventricular stimulation. No complications were associated with transvenous catheter or ATP use.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Incidence and timing of activity parameter changes in activity responsive pacing systems.

The incidence and timing of rate response parameter reprogramming in activity responsive pacing systems during the year after implantation was evaluated in two groups of patients: 24 patients in whom a VVI,R system was implanted (Activitrax, Medtronic, Inc.), and 21 patients in whom a DDD,R system was implanted (Synchrony, Siemens Pacesetter, Inc.). Activity parameter changes in Activitrax patients were made based on the presence of symptoms, while in Synchrony patients, changes were based on objective data obtained using a sensor indicated rate histogram with a slow and fast walk protocol. No significant difference in the incidence of activity parameter reprogramming was noted at various time intervals during the first year in Activitrax patients; in Synchrony patients a greater incidence of reprogramming changes was noted at the 1-month follow-up visit compared to later follow-up visits (P less than 0.02). Further, the incidence of changes at 1 month was greater for Synchrony compared to Activitrax patients (P less than 0.001), while no difference was detected between groups at subsequent follow-up intervals. Use of the slow and fast walk protocol, by permitting serial evaluation of sensor response, demonstrated alterations in sensor drive rates with similar levels of activity over the initial 4 to 6 postimplant weeks. This may result from postoperative changes at the pacemaker insertion site. Based on this experience, predischarge programming may not predict long-term rate response requirements. We recommend evaluation of sensor function using an exercise protocol performed at 4 to 6 postimplant weeks in all rate responsive pacing systems that utilize a piezoelectric crystal.

Aged↗