PubMed Health⌕ Search

Biomedical subjects

C Bondy

Publications and source records attributed to C Bondy.

At least 19 recordsLinked to original sources
PubMed1997

Aquaporin-1 water channel expression in human kidney.

The pattern of aquaporin-1 water channel protein (AQP1) expression in the human kidney was analyzed by immunocytochemistry using semi-thin and optimized high-resolution immunoelectron microscopy based on freeze-substituted and Lowicryl HM20 embedded tissue. In addition, in situ hybridization was used to determine AQP1 mRNA distribution. Immunoblots revealed a 28-kd band and a 35- to 45-kd band corresponding to unglycosylated and glycosylated AQP1. Glomerular capillary endothelium exhibited extensive AQP1 labeling, whereas glomerular podocytes and Bowman's capsule epithelium were unlabeled. AQP1 was localized in the proximal tubule, including the neck region directly connected to the glomerulus. However, there was a marked difference in the level of expression between cross-sections of the convoluted part and the proximal straight tubules, the latter displaying the most intense labeling. AQP1 labeling continued uninterrupted from the proximal straight tubule into descending thin limbs in outer medulla. Abrupt transitions from heavily labeled to unlabeled segments of thin limbs were observed, primarily in the inner medulla. This may represent the transition from the water-permeable thin descending limb to the water-impermeable thin ascending limb. In addition, heavy labeling of fenestrated endothelium was also observed in peritubular capillaries in cortex, outer medulla, and inner medulla. Immunolabeling controls were negative. In situ hybridization documented a marked difference in AQP1 mRNA levels within the proximal tubule, with the greatest AQP1 mRNA expression in straight proximal tubules. Glomeruli also showed marked signals, and descending thin limbs exhibited extensive expression in exact concordance with the immunocytochemical results. It was concluded that: (1) AQP1 is present in all proximal tubule segments, including segment 1 and the neck region, but there is a pronounced difference in expression levels with respect to both protein and mRNA levels; (2) AQP1 labeling is observed in the endothelium of fenestrated peritubular capillaries, as well as fenestrated glomerular capillaries; (3) AQP1 labeling continues directly from proximal tubules to descending thin limbs; and (4) abrupt transitions from labeled to unlabeled thin limb epithelium are noted.

Aquaporin 1↗
PubMed1996

Single lead VDD pacing: multicenter study.

Optimal treatment for patients with AV block and normal sinoatrial node (SA) function entails atrial sensing and ventricular pacing (VDD mode). Single-lead VDD pacing preserves AV synchrony, precludes the need to insert two leads, and makes the implanter's work simpler and quicker. Our objectives were to verify the performance of the Thera VDD pacing system (medtronic, Inc., Minneapolis, MN, USA), and evaluate the effectiveness of its atrial sensing and its ventricular sensing and pacing. In 165 patients, 150 adults (mean age 62 +/- 18 years) and 15 children (mean age 7 +/- 5 years) with 1 degree-3 degrees AV block and normal SA node function, a Thera VDD system (Models 8948 or 8968) was implanted. Intraoperative ventricular electrical measurements were not significantly different from those of VVI pacemakers. The mean amplitude of the atrial signal during implantation was 4.1 +/- 1.9 mV. Optimal atrial signals during implantation were usually obtained in the mid or lower part of the right atrium by using a special technique. Adequate atrial measurements remained stable throughout 24 months. There was no difference between serial measurements of atrial signal amplitudes at predischarge and during follow-up visits. Reposition of the lead was done in 2 patients (1.4%), and reprogramming to VVI in 7 patients: due to atrial fibrillation in 3 (1.8%) and due to atrial undersensing in 4 patients (2.4%). Thera VDD pacing is reliable and easy to manage with dependable atrial sensing and ventricular pacing. The survival rate of VDD pacing at 2 years was 96%.

Adolescent↗
PubMed1996

Effects of an Igf1 gene null mutation on mouse reproduction.

Both sexes of adult mice homozygous for a targeted mutation of the Igf1 gene, encoding insulin-like growth factor 1, are infertile dwarfs (approximately 30% of normal size). The testes are reduced in size less than expected from the degree of dwarfism but sustain spermatogenesis only at 18% of the normal level. The epididymides are overall nearly allometric to the reduced body weight, but the distal regions of the duct, vas deferens, seminal vesicles, and prostate are vestigial. Despite the mutational impact on the epididymis, capacitated sperm are able to fertilize wild type eggs in vitro. It is hypothesized that the infertility of male mutants is caused by failure of androgenization resulting in absence of mating behavior, due to drastically reduced levels of serum testosterone (18% of normal). This hormonal deficiency was correlated with an ultrastructural analysis of mutant Leydig cells revealing a significant developmental delay, while assays in organ culture showed that the basal and LH-stimulated production of testosterone by testicular parenchyma is reduced in comparison with wild type controls. The female mutants fail to ovulate even after administration of gonadotropins, which is apparently the primary cause of their infertility, and possess an infantile uterus that exhibits a dramatic hypoplasia especially in the myometrium. The phenotypic manifestations of the mutation were correlated with the localization of transcripts for insulin-like growth factor I and its cognate receptor in wild type reproductive tissues by in situ hybridization.

Animals↗
PubMed1995

Evaluation of a new rate adaptive ventricular pacemaker controlled by double sensors.

UNLABELLED: The LEGEND-PLUS, a new rate adaptive pacemaker that combines activity and minute ventilation sensing for automatic rate adaptation was implanted in the right ventricle (VVIR) in 11 patients (mean age 62 +/- 9 years). Initial programming was performed using the Programmer Exercise Protocol (a 3-minute walk). This programming was evaluated by treadmill tests, up-stairs and down-stairs walking, and Holter recordings. RESULTS: Following the final programming of LEGEND-PLUS, the mean upper activity rate was 102 +/- 7 beats/min (range 90-120 beats/min), while the mean upper minute ventilation rate was 125 +/- 16 beats/min (range 100-150 beats/min). The mean rate responses during the exercise protocol and the final programming in minute ventilation and activity sensing modes were 5.4 +/- 2.3 (range 1-9), versus 4 +/- 2.4 (range 1-8; P < 0.01) and 7.6 +/- 1.1 (range 5-9), versus 7.5 +/- 0.8 (range 6-9; P = 0.8), respectively. In the combined sensing mode, the acceleration rate was identical to the activity rate response and the deceleration rate mimicked the minute ventilation. CONCLUSION: Dual sensor VVIR pacemakers have the potential to improve rate adaptation to exercise. The rate response to exercise in patients fitted with activity and minute ventilation sensors, VVIR pacemakers closely mimics the physiological rate response.

Adult↗
PubMed1995

Astrocytes upregulate glial fibrillary acidic protein (GFAP), but not insulin-like growth factor-I (IGF-I) during experimental autoimmune neuritis (EAN).

T cell-mediated autoimmune neuritis produces rapid activation of spinal cord microglia. To determine whether this microglial response upregulates astrocytic expression of IGF-related proteins, we induced EAN and used in situ hybridization and immunocytochemistry to examine the mRNAs and peptides for glial fibrillary acidic protein (GFAP), insulin-like growth factor-I (IGF-I), IGF-I receptor (IGFR-I) and IGF binding protein-2 (IGFBP-2). Relative levels of GFAP mRNA and peptide were highest in the lumbar spinal cord 4-10 d following T cell transfer and significant GFAP elevations were still present after three weeks. The astrocytes expressing GFAP mRNA and peptide were localized around motoneurons which were related topographically to axons in peripheral nerve inflammatory lesions. In the nucleus gracilis, where terminals of dorsal root ganglion neurons are located, astrocytic levels of GFAP mRNA and peptide rose later and did not reach their highest levels until 21 d after T cell transfer. Even though microglia were activated in both locations 2-4 d after transfer, astrocytic levels of IGF-I, IGFR-I and IGFBP-2 mRNA and peptide did not differ significantly from those observed in controls. The dissociation of GFAP and IGF-I expression in EAN suggests that these astrocytic responses may be independently regulated. We also suggest that the type and severity of remote neuronal injury are probably more important inducers and regulators of these astrocytic responses than microglial cell activation.

Animals↗
PubMed1995

Expression of insulin-like growth factor binding proteins in the rat kidney: effects of long-term diabetes.

Recent studies have shown that the renal synthesis of insulin-like growth factor binding proteins (IGFBPs) is altered in insulin-deficient diabetes mellitus, suggesting that these changes may be implicated in the alterations in renal function and morphology that accompany diabetes. To investigate the time course and the precise cellular distribution of changes in IGFBP expression, we used quantitative in situ hybridization to analyze renal IGF-I and IGFBP-1 to -5 messenger RNA (mRNA) localization and levels from 2 days to 6 months after the onset of streptozotocin-induced diabetes. There was an immediate sharp decline in IGF-I mRNA levels in the outer medulla that persisted for up to 3 months and a much smaller reduction in IGF-I mRNA levels in the medullary thick ascending limbs (MTALs). In nondiabetic animals, IGFBP-1 mRNA is most abundant in the MTALs. Immediately after the induction of diabetes, however, there was a greater than 2-fold increase in cortical IGFBP-1 mRNA and a 75% decrease in IGFBP-1 mRNA in MTALs. These changes persisted for up to 6 months in the diabetic animals. In contrast, IGFBP-5 mRNA levels were increased in the outer medulla and decreased in the cortex of diabetic kidneys. No significant changes in renal IG-FBP-2 mRNA levels or distribution were noted, and changes in IG-FBP-3 and -4 mRNA levels were subtle. In summary, streptozotocin-induced diabetes is associated with very prominent and complex alterations in renal IGF system gene expression, including robust increases in cortical IGFBP-1 and profound decreases in cortical IG-FBP-5 mRNA and medullary IGF-I mRNA levels. The divergent changes in IGFBP-1 and -5 mRNA levels in cortex vs. outer medulla indicate that regulation of IGFBP mRNA levels is quite complex.

Albuminuria↗
PubMed1995

Granulosa cell DNA synthesis is strictly correlated with the presence of insulin-like growth factor I and absence of c-fos/c-jun expression.

Insulin-like growth factor I (IGF-I) mRNA is selectively expressed by a subset of rat ovarian follicles. To elucidate the biological role and regulation of follicular IGF-I, we have analyzed individual follicles with respect to IGF-I production, DNA synthesis, and c-fos and c-jun expression, since AP-1 complex components have been implicated both in regulation of IGF-I gene expression and cell proliferation. IGF-I mRNA localization, bromodeoxyuridine (BRDU) incorporation, and c-fos and c-jun immunoreactivity were compared in serial sections from prepubertal and mature rat ovaries. BRDU incorporation is exclusively concentrated in IGF-I-expressing follicles in both prepubertal and mature rats, with further intrafollicular correlation between local concentrations of BRDU-positive granulosa cells and IGF-I mRNA. Furthermore, there is a striking negative correlation between IGF-I mRNA localization and follicular fos/jun immunoreactivity. Both c-fos and c-jun are readily detected in granulosa cells of luteinized follicles where IGF-I mRNA is never found. Immunoreactive c-jun but not c-fos is detected in granulosa cells of atretic follicles, while neither c-fos nor c-jun is detected in IGF-I mRNA-positive granulosa cells. These data implicate IGF-I in granulosa cell proliferation and the fos/jun heterodimer in granulosa cell luteinization, while expression of c-jun in the absence of c-fos may be implicated in programmed granulosa cell death.

Animals↗
PubMed1994

The effect of overdrive pacing rate and duration on ventricular escape rhythms in patients with chronic complete atrioventricular block.

The effect of overdrive (OD) pacing rate and duration on subsidiary pacemakers was evaluated in 54 patients with third-degree AV block. They had a permanent pacemaker implanted 61 +/- 56 months earlier because of complete AV block in 38 patients and, in 16 patients because of second-degree AV block, which in the interim advanced to complete AV block. The patients had a reliable infranodal escape rhythm, with a mean cycle length of 2,022 +/- 603 msec, upon discontinuation of the ventricular OD pacing, at a rate of 40 beats/min. The escape interval and escape rhythm cycle length was evaluated after OD pacing at 40, 50, 60, 70, 90, and 100 beats/min for 30 seconds, at each rate. In 100% of the patients the subsidiary pacemaker recovered after OD pacing at 40 and 50 beats/min and the number decreased to 59% at a rate of 100 beats/min. The escape interval prolonged gradually between OD pacing at 40 and 100 beats/min, by 56%. The effect of OD pacing duration at 50 and 70 beats/min was evaluated. At an OD pacing rate of 70 beats/min there was a significant effect of the pacing duration on the escape interval. There were significant differences in the escape interval duration and escape rhythm cycle length between males and females, patients with or without coronary artery disease, and patients with narrow or wide QRS escape. However, the increase in the OD pacing rate had a similar effect on the escape interval in the above mentioned groups. There was no effect on the paced QRS duration and sinus cycle length at each OD pacing rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Clinical evaluation of a new single pass lead VDD pacing system.

UNLABELLED: Twenty-five patients with second- to third-degree AV block and normal sinus function (16 males, mean age 60 +/- 18; range 15-78 years) underwent implantation of VVD pacemakers (THERA VDD, Medtronic, Inc.) with a single pass (SP) lead. RESULTS: During implantation the mean amplitude of the atrial (A) signal was 3.9 +/- 1.4 mV (range 2.0-7.8 mV). Stable, acceptable A-signals during implantation were usually observed in the mid- or lower part of the right atrium. The lead tip electrical parameters were not compromised in any patient in order to obtain an acceptable A-signal. To verify VDD device function, patients underwent pacing system analysis on the second day and again 1, 3, and 6 months after implantation. Acute and chronic electrical measurements in the ventricle were similar to those with regular steroid leads. During follow-up tests, stable atrial sensing (A > or = 0.7 mV) was found in all but one patient (in whom A was 0.25-0.5 mV and an intermittent loss of atrial sensing occurred). There was no difference between serial measurements of A-signal amplitudes on the second day or 1, 3, and 6 months after implantation: 1.9 +/- 1.3 mV, 1.5 +/- 0.6 mV, 1.3 +/- 0.8 mV, and 1.5 +/- 1.1 mV, respectively. The mean implantation time was 54.0 +/- 17 minutes and the mean fluoroscopy time was 3.2 +/- 1.3 minutes. CONCLUSIONS: SP lead VDD pacing is reliable and easy to manage with dependable atrial sensing and ventricular pacing.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Initial experience with a new algorithm for automatic mode switching from DDDR to DDIR mode.

UNLABELLED: Implantation of dual chamber devices in patients with paroxysmal atrial tachyarrhythmias who require permanent pacemakers may lead to significant complications due to an inappropriately triggered ventricular response. VVI/VVIR units cause loss of AV synchrony in the presence of sinus activity. A new DDDR device (THERA DR, model 7940), with an automatic mode switching (AMS) algorithm, was evaluated. When the mean atrial rate is > 182 beats/min, atrial tachyarrhythmia is detected, and AMS is activated. Twenty-three patients (12 males, mean age 71 +/- 7 years) underwent implantation of a THERA DDDR device with the AMS algorithm. Seventeen patients had AV block and/or sick sinus syndrome (SSS) and atrial arrhythmias, and 6 patients (2 with hypertrophic obstructive cardiomyopathy) had SSS and paroxysmal atrial fibrillation (PAF). The follow-up period was from 1-9 months. During follow-up, Holter monitoring and treadmill tests were performed. RESULTS: Eighty-seven episodes of AMS were recorded. Telemetered AMS recordings demonstrated episodes in which the DDDR mode switched to the DDIR mode in the presence of PAF, and reverted to DDDR when sinus rhythm returned. Paroxysmal supraventricular arrhythmias with a heart rate < 182 beats/min did not activate the mode switch. CONCLUSIONS: This early, short-term clinical experience with a DDDR device capable of AMS from DDDR to DDIR demonstrated appropriate clinical function and response to PAF. These preliminary results suggest that DDDR pacemakers with AMS to DDIR may significantly extend the current indications for dual chamber pacing.

Aged↗
PubMed1993

Developmental gene expression and tissue distribution of the CHIP28 water-channel protein.

The CHIP28 water channel is a major component of red cell and renal tubule membranes; however, its ontogeny and tissue distribution remain undefined. Three patterns of expression were identified when CHIP28 mRNA was surveyed by in situ hybridization histochemistry in rats between embryonic day 14 and maturity. (i) CHIP28 mRNA and protein were very abundant in hematopoietic tissue and kidneys of mature rats, but strong expression did not occur until after birth, when it appeared in renal proximal tubules and descending thin limbs, red pulp of the spleen, and membranes of circulating red cells. (ii) CHIP28 mRNA was abundant in choroid plexus epithelium throughout fetal development and maturity. (iii) CHIP28 mRNA was transiently observed in periosteum, heart, vascular endothelium, and cornea during fetal development. The ontogeny of kidney and red cell CHIP28 expression coincides with the ability of kidneys to concentrate urine, suggesting that CHIP28 promotes water reabsorption in the proximal nephron and provides red cell osmoregulation needed for passage through the hypertonic medulla. Its presence in the choroid plexus suggests that CHIP28-mediated water transport contributes to secretion of cerebrospinal fluid. The functional role of CHIP28 in developing bone, heart, and eye is unclear. These findings further establish the general physiologic role of CHIP28 as a water channel involved in reabsorption, osmoregulation, and secretion. The studies also suggest other possible functions during fetal development and predict that complex mechanisms will be needed for regulation of CHIP28 gene expression in diverse tissues at distinct points in development.

Animals↗
PubMed1993

Measurements of cardiac output by impedance cardiography in pacemaker patients at rest: effects of various atrioventricular delays.

OBJECTIVES: The purpose of this study was to evaluate the ability of impedance cardiography to determine the change in cardiac output caused by modifications in the atrioventricular (AV) delay in DDD (dual-chamber) pacing mode while pacing the atrium and ventricle at different programmed rates. BACKGROUND: Impedance cardiography permits continuous noninvasive monitoring of hemodynamic variables on a beat to beat basis. METHODS: Eleven patients with a DDD pacemaker were evaluated by impedance cardiography. Stroke volume, cardiac output and total peripheral resistance were assessed in the supine rest position during both DDD and ventricular (VVI) pacing. Hemodynamic variables were measured during DDD pacing at rates ranging from 60 to 110 beats/min in 10-beats/min increments with programmed AV delay varying from 50 to 250 ms in 50-ms increments. When the pacemaker was reprogrammed to the VVI pacing mode, these measurements were repeated at the same pacing rates. RESULTS: Cardiac output measurements during programmed conditions were found to be highly reproducible. The mean coefficient of variation was 3% during DDD pacing; it was 6% in the VVI pacing mode. A large decrease in cardiac output (approximately 30%) was found when a pacemaker was reprogrammed from the DDD to the VVI pacing mode. At DDD pacing rates between 70 to 110 beats/min, the highest cardiac output occurred at an average AV delay of < 120 ms from atrial stimulus to ventricular stimulus. At an average AV delay of > or = 200 ms, the cardiac output in the DDD and VVI pacing modes was similar. CONCLUSIONS: 1) Impedance cardiography allows highly reproducible noninvasive assessments of cardiac output in pacemaker patients; 2) inappropriate programming of the AV interval in patients with atrial and ventricular pacing can decrease cardiac output significantly, and the extent of the decrease is similar to or less than that observed in ventricular pacing; 3) hemodynamic measurements obtained with impedance cardiography can facilitate optimal programming of pacemaker variables.

Cardiac Output↗
PubMed1993

Anatomy of the insulin-like growth factor system in the human testis.

OBJECTIVE: To study the cellular patterns of gene expression for insulin-like growth factors I and II (IGF-I and IGF-II), their receptors and specific high-affinity binding proteins (IGFBPs) in the human testis. DESIGN: In situ hybridization histochemistry was used to localize messenger ribonucleic acids (mRNAs) for IGF-I and IGF-II, the IGF-I and IGF-II receptors and IGFBP-1 to 6 in fresh-frozen testis sections from healthy young men who died of trauma. RESULTS: Insulin-like growth factor I mRNA was not detected. Insulin-like growth factors II mRNA was abundant in testicular blood vessels and peritubular connective tissue. Both IGF-I and IGF-II receptor mRNAs were most abundant in the germinal epithelium. Insulin-like growth factor binding protein 1 mRNA was not detected. Binding protein-2 mRNA was expressed in both Leydig and Sertoli cells. Binding protein-3 mRNA was detected only in the endothelium of testicular blood vessels. Binding protein-4 mRNA was also localized in endothelium but, in addition, was present in Leydig cells and interstitial connective tissue. Binding protein-5 mRNA was abundant in connective tissue and was detected at low levels in Leydig cells. Binding protein-6 mRNA was present in some of the peritubular cells and in some cells of the interstitial compartment. CONCLUSION: Our results suggest that IGFs may play significant roles in testicular function and germ cell development.

Adult↗
PubMed1993

Anatomy of the human ovarian insulin-like growth factor system.

In situ hybridization was used to map insulin-like growth factor (IGF) system gene expression in ovaries from an anencephalic infant and several young women. Growing oocytes in infant and mature ovaries expressed transcripts for IGF-I and IGF-II, respectively, and all oocytes expressed abundant IGF-I receptor transcripts, raising the possibility of autocrine IGF function in oocyte maturation. IGF-I mRNA was not detected in the mature ovary, but IGF-II mRNA was localized in follicular blood vessels and in granulosa cells (GC) and was especially abundant in the GC of atretic as opposed to young follicles. IGF-I receptor mRNA was abundant in GC of antral and atretic follicles, and was expressed at low levels in the thecal and interstitial compartments. IGF-binding protein (IGFBP) 1 mRNA was not detected, but IGFBPs 2-5 mRNAs each demonstrated a unique ovarian distribution. IGFBP2 mRNA was abundant in GC and thecal cells at all stages of development. IGFBP3 mRNA was detected only in the endothelium of ovarian blood vessels. IGFBP4 mRNA was also localized in endothelium, but in addition was present in stromal connective tissue and in GC of the one Graafian follicle detected in this study, but not consistently in atretic follicles. IGFBP5 mRNA was expressed by luminal or cumulus GC in virtually all follicles and was highly abundant in stromal interstitial cells of the mature ovary.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Wilms' tumor (WT1) gene expression in rat decidual differentiation.

The Wilm's tumor suppressor gene (WT1) encodes a zinc-finger containing transcription factor that is selectively expressed in the developing urogenital tract, where it is thought to play a role in the differentiation of these tissues. We have used immunocytochemistry and in situ hybridization to study WT1 expression in the rat uterus during normal development and pregnancy from 0 to 20 days post coitum (p.c.). WT1 mRNA was abundant in uterine stroma from juvenile rats, but was much less abundant in uterine tissue from sexually mature rats; WT1 expression is not affected by ovariectomy or by treatment with estradiol or estradiol plus progesterone. WT1 gene was highly expressed, however, in the endometrial cells of early pregnancy. On day 6 p.c. WT1 mRNA was detected in anti-mesometrial decidual cells, and WT1 immunoreactivity was concentrated in the nuclei of these cells. All cells of fully-developed deciduoma at 7-8 days p.c. demonstrated WT1 expression. WT1 was not detected in trophoblast/placental tissues but remained abundant in the decidua basalis until parturition. The expression of WT1 was compared with insulin-like growth factor-II (IGF-II) and its receptor in the decidual since it has been shown that IGF-II gene transcription is repressed by WT1 in vitro. However, no spatiotemporal correlation in the expression of these three genes was found in differentiation of the rat decidua. In summary, these data suggest a role for WT1 in decidualization, since its expression is activated during the differentiation of uterine stromal cells into decidual cells.

Animals↗
PubMed1993

Comparison between patients with and without reliable ventricular escape rhythm in the presence of long standing complete atrioventricular block.

The underlying heart rhythm was evaluated in 74 patients with complete atrioventricular block and had a permanent pacemaker implantation. The pacing was inhibited for 10 seconds or until the patient developed symptoms of presyncope or syncope. Fifty-six patients (74%) had a reliable escape with a mean cycle length of 2010 +/- 596 msec and a mean escape interval of 2335 +/- 971 msec. In 93% of these patients the escape interval was < 4 seconds. The patients without reliable escape (24%), developed symptoms only after a mean of 7153 +/- 1875 msec. The duration of the conduction disorder was longer in the patients without escape and the intraventricular conduction was slower. More patients without escape were treated and antiarrhythmic agents. Forty-eight patients were followed for 1 year and underwent at least two different studies and 13% had different results at different tests. In conclusion, patients without reliable escape have a longer history of conduction disorder, a slower intraventricular conduction, and are frequently treated with antiarrhythmic agents. Even patients with reliable escape occasionally may show a greater pacemaker dependence; therefore, they should also be considered as pacemaker dependent.

Aged↗