Pharmacological classification of adenosine receptors in the sinoatrial and atrioventricular nodes of the guinea-pig

Factors influencing the change in bone mineral after 3 mo of lactation were investigated in 47 breast-feeding mothers, 11 formula-feeding mothers, and 22 nonpregnant, nonlactating control subjects. At 6-8 wk postpartum, the breast-feeding group had a mean (+/-SD) calcium intake of 34.8+/-13.2 mmol/d and breast-milk volume, calcium concentration, and calcium output of 0.865+/-0.230 L/d, 7.41+/-1.25 mmol/L, and 6.41+/-2.00 mmol/d, respectively. There was no relation between calcium intake and any breast-milk variable. Dual-energy X-ray absorptiometry of the whole body, spine, hip, and forearm was performed at 0.5 and 3 mo. There were significant decreases in bone mineral content at the spine (3.96%; 95% CI: 4.86%, 3.06%), femoral neck (2.39%; 95% CI: 3.61%, 1.17%), total hip (1.51%; 95% CI: 2.45%, 0.60%), and whole body (0.86%; 95% CI: 1.29%, 0.43%) in breast-feeding mothers but not in formula-feeding mothers or nonpregnant, nonlactating women. These changes were not related to calcium intake, breast-milk calcium concentration, vitamin D-receptor genotype, postpartum weight change, or use of the progesterone-only contraceptive pill. After adjustment for bone area, breast-milk volume and height were identified as significant predictors at the spine, such that greater decreases were associated with taller mothers (P = 0.007) and those with greater breast-milk volume (P = 0.001). This finding suggests that the marked bone mineral changes observed in breast-feeding mothers represented a physiologic response to lactation that was independent of dietary calcium supply.     

An autocrine function for transforming growth factor (TGF)-beta3 in the transformation of atrioventricular canal endocardium into mesenchyme during chick heart development

Transformation of atrioventricular canal endocardium into invasive mesenchyme is a critical antecedent of cardiac septation and valvulogenesis. Previous studies by Potts et al. (Proc. Natl. Acad. Sci. USA 88, 1510-1520, 1991) showed that treatment of atrioventricular canal endocardial and myocardial cocultures with TGFbeta3 antisense oligodeoxynucleotides blocked mesenchyme formation. Based on this observation, we sought to: (i) identify the target tissue of TGFbeta3 antisense oligos in this transformation bioassay, and (ii) more clearly define the mechanism of TGFbeta3 function in atrioventricular canal mesenchyme formation. In situ hybridization and immunohistochemistry showed little or no TGFbeta3 mRNA or protein in the atrioventricular canal myocardium or endocardium prior to mesenchyme formation (stage 14; paraformaldehyde fixation). However, by stage 18 transforming atrioventricular canal endocardial cells and mesenchyme as well as myocardium were positive for both TGFbeta3 mRNA and protein. In culture bioassays, atrioventricular canal endocardial monolayers pretreated with antisense phosphorothioate oligodeoxynucleotides to TGFbeta3 did not transform into invasive mesenchyme in response to cardiocyte conditioned medium: the subsequent addition of exogenous TGFbeta3 protein relieved this inhibition. Control cultures without pretreatment or those receiving missense oligos generated similar numbers of invasive mesenchyme in response to cardiocyte conditioned medium. Direct addition of TGFbeta3 protein to atrioventricular canal endocardial monolayers in the absence of cardiocyte conditioned medium resulted in loss of cell:cell associations and stimulated cellular hypertrophy, but did not engender invasive mesenchyme formation or alter endocardial proliferation after 24 h of culture. Similar results were obtained with TGFbeta2 protein, either alone or in combination with TGFbeta3. The results of this study indicate that: (i) atrioventricular canal endocardium expresses TGFbeta3 in response to a myocardially derived signal other than TGFbeta3, (ii) atrioventricular canal endocardial TGFbeta3 functions in an autocrine fashion to elicit selected characteristics necessary for cushion tissue formation, and (iii) TGFbeta3 alone or in combination with TGFbeta2 is insufficient to transform atrioventricular canal endocardium into invasive mesenchyme in culture.     

Study of the auriculo-ventricular conduction by means of the recording of bundle of His in deep hypothermal conditions

In a retrospective review of 440 pregnancies occurring in women over the age of 40, increased frequencies of both perinatal and maternal complications were noted. The perinatal mortality rate of the study group was three times greater than that of the general obstetric population. There were increased incidences of both low and high birthweight infants. Neonatal morbidity was increased. Congenital abnormalities were noted in 12 infants, including 2 infants with cytogenetic abnormalities. Hypertensive disorders complicated one-third of the pregnancies. Diabetes mellitus and abruptio placentae occurred with increased frequency. Cesarean section was required in 12.2% of the deliveries.     

Incorporation of (3H)uridine by the chromatoid body during rat spermatogenesis

The in vitro incorporation of tritiated uridine into RNA by the spermatogenic cells of the rat has been analyzed by high-resolution autoradiography. Special attention has been focused on the unique cytoplasmic organelle, the chromatoid body. After a short labeling time (2 h), this organelle remains unlabeled in the vast majority of the early spermatids although the nuclei are labeled. When the 2-h incubation with (3H)uridine is followed by a 14-h chase, the chromatoid body is seen distinctly labeled in all spermatids during early spermiogenesis from step 1 to step 8. Very few grains are seen elsewhere in the cytoplasm of these cells. When RNA synthesis in the spermatid ceases, the chromatoid body also remains unlabeled. It is likely that the chromatoid body contains RNA which is synthesized in the nuclei of the spermatids. The function of this RNA as a stable messenger RNA needed for the regulation of late spermiogenesis is discussed.     

Quantitative characteristics of the multiplication of muscle cells in the course of postnatal cardiogenesis in mice

Changes in the absolute number of muscle cells and nuclei in the ventricle during the 1st year of postnatal life were followed in males of the CC57BR mice. The counts were carried out in the cell suspension obtained from the fixed cardiac muscle by means of alkaline dissociation. The number of muscle cells and nuclei reliably increased during the 1st month of life and ceased to increase when the maturity was attained (2-3 months). The number of muscle cells increased twice and that of muscle nuclei almost 4 times. A comparative estimate was made of the role of proliferation and growth of muscle cells in the increase of ventricle weight with the age. The importance of individual variation of the number of muscle cells and nuclei during early postnatal ontogenesis for the study of the myocardium adaptive growth is discussed.     

Stereospecific effect of bupivacaine isomers on atrioventricular conduction in the isolated perfused guinea pig heart

BACKGROUND: The local anesthetic bupivacaine is an equal mixture of two optically active isomers known to exert different cardiotoxic profiles in vivo. Enantiomer-specific forms of bupivacaine may have differential effects on cardiovascular function, specifically on cardiac electrophysiology. The authors' aim was to determine if there were any direct functional differences in the cardiac effects of bupivacaine isomers. The isolated heart was used to avoid possible indirect cardiac effects of bupivacaine, such as autonomic nervous and hormonal influences, as well as preload and afterload factors. METHODS: The hearts of 12 ketamine-anesthetized guinea pigs were perfused with Krebs-Ringer's solution (97% oxygen, 3% carbon dioxide) at constant perfusion pressure using the Langendorff technique. Atrial and ventricular bipolar electrodes were placed to measure heart rate (HR) and atrioventricular (AV) conduction time. Left ventricular pressure (LVP), coronary flow, and inflow and outflow oxygen tensions were also measured. Oxygen delivery, oxygen consumption (MVO2), and percentage of oxygen extraction were calculated. Each heart was perfused with increasing randomized concentrations (0.5, 1, 5, 10 microM) of both isomers and the racemate of bupivacaine. RESULTS: Racemic and isomeric bupivacaine equally and dose dependently decreased cardiac function. At 10 microM bupivacaine these changes were HR, -17 +/- 2%; LVP, -50 +/- 3%; coronary flow, -20 +/- 4%; and MVO2, -46 +/- 4%. The (+) isomer significantly prolonged AV conduction compared with the racemate and the (-) isomer at all concentrations. At 10 microM, AV time was 54 +/- 6% longer with the (+) isomer and 30 +/- 4% longer with the (+/-) racemate than with the (-) isomer. The greater delay in AV time with the (+) than the racemate or (-) isomer led to a second-degree AV dissociation in 10 of 12 of hearts treated with (+) bupivacaine. CONCLUSIONS: This study shows that bupivacaine has an enatiomer-specific effect to delay AV conduction and to produce second-degree AV dissociation in the isolated perfused heart. This suggests that bupivacaine isomers probably have differential effects on one or more ion-specific channels regulating AV conduction. Other measured direct cardiac effects of bupivacaine appear to be independent of the isomeric form.     

Function of the heart conduction system in Wolff-Parkinson-White syndrome

A study of the functional state of the heart conduction system by means of electrophysiologic testing of 46 patients with the Wolff-Parkinson-White syndrome has shown that the peculiarities of atrioventricular conduction and the development of an electrocardiographic picture in this disease are determined by the functions of anomalous accessory atrioventricular pathways--more frequently of the Kent's bundle and more infrequently of the Macheim's bundle. In addition, the degree of manifestations of the ventricular pre-excitation on the ECG depends on the correlation between impulse conduction times along the anomalous and normal pathways. The slow conduction along the Kent bundle form the basis of the latent WPW syndrome not recorded by the ECG.     

The effect of Ro 11-1781, a calciumantagonist, on atrioventricular conduction (author's transl)

The effect of an intravenous bolus of 1 mg/kg Ro 11-1781, a new calciumantagonist, on sinus node automaticity and intracardiac conduction was studied by His-bundle electrography and atrial stimulation. During sinus rhythm, no significant action of Ro 11-1781 on rate, P-A-interval, A-H interval, and H-V-interval was observed. The sinus node recovery time remained unaltered. On atrial stimulation, the St-H-interval was significantly (p less than 0.001) prolonged after Ro 11-1781. Wenckebach Periods occurred at lower stimulation rates in all patients after Ro 11-1781. It is concluded that Ro 11-1781 prolongs av nodal conduction and may be of therapeutic value in the treatment of supraventricular arrhythmias.     

Circadian rhythms of atrioventricular conduction properties in chronic atrial fibrillation with and without heart failure

Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are members of the immunoglobulin superfamily adhesion molecules on vascular endothelium and important in the development of eosinophil (EOS) accumulation in allergic inflammation. To define the role of these adhesion proteins in EOS inflammation, peripheral blood EOS from allergic donors were incubated in either buffer (control)-, recombinant human (rh)-VCAM-1-, or rh-ICAM-1-coated plates, and the effects of these adhesion proteins on EOS effector functions were determined. VCAM-1 induced spontaneous EOS adhesion whereas EOS adhesion to ICAM-1 required a second signal, such as granulocyte macrophage colony-stimulating factor (GM-CSF). Although only VCAM-1 stimulated EOS superoxide anion (O2-) generation, the addition of GM-CSF (100 pM) to the reactions resulted in a greater and equivalent production of O2- with VCAM-1 and ICAM-1. In the presence of GM-CSF, ICAM-1 and VCAM-1 caused significant release of EOS-derived neurotoxin (EDN). Moreover, only ICAM-1 (no GM-CSF) promoted calcium ionophore A23187 (0.2 microM)-induced EOS leukotriene C4 (LTC4). Enhanced O2- generation, EDN release, and LTC4 generation observed with ICAM-1 and VCAM-1 were significantly inhibited by anti-beta2-integrin antibody. These results suggest that ICAM-1 and VCAM-1 are important in determining the eventual function of airway EOS.     

Applicability to abrasion material of in vitro autoradiography, using 3H-thymidine (author's transl)

The applicability of in vitro autoradiography, using 3H-thymidine, was tested on material obtained from gynaecological abrasion. Included were 161 abrasion samples obtained from 151 patients, and 88 per cent of them proved evaluable by autoradiography. The use of in vitro autoradiography was found to give no additional gain in information for biological assessment. Index testing by means of in vitro autoradiography failed to prove worthwhile unless it came to examination of polyps or of glandular-cystic hyperplasia or of effects exerted on the endometrium by ovarian tumours with sizeable hormonal activity. Endometrium was found to be a kind of tissue characterised in both intact and pathological condition by pronounced individual age-dependent and cycledependent variations of its marking indices.     

Preceding His-atrial interval as a determinant of atrioventricular nodal conduction time in the human and rabbit heart

This investigation shows that atrioventricular (A-V) nodal conduction time (A-H interval), both in the human and in the isolated rabbit heart, is determined mainly by the length of the preceding His-atrial (H-A) interval. The A-H intervals obtained during atrial extrasystolic stimulation at different basic rates, during Wenckebach cycles and during both transient and steady state responses to stepwise increases in stimulation frequency were plotted against the corresponding H-A intervals. The A-H intervals were found to have nearly the same duration provided they were preceded by the same H-A interval. The only important difference appeared in the short H-A interval range as a shortening of the A-H interval at faster basic rates. This facilitating effect of frequency, which was found in the majority of cases, is compatible with the similarly frequency-dependent shortening of the functional refractory period of the A-V node.     

Selective functional properties of dual atrioventricular nodal inputs. Role in nodal conduction, refractoriness, summation, and rate-dependent function in rabbit heart

BACKGROUND: The atrioventricular node receives its activation signal from the low crista terminalis and low interatrial septum, the summation of which is believed to favor conduction. A functional asymmetry between the inputs is also believed to be involved in nodal reentrant rhythms. We studied the selective functional characteristics of nodal inputs and determined their role in nodal conduction, refractoriness, summation, and rate-dependent function. METHODS AND RESULTS: The nodal properties of recovery, facilitation, and fatigue were characterized with stimulation protocols applied with varying phases between the two inputs in isolated rabbit heart preparations. The effects of the input phase, nodal functional state, and input reference on the nodal conduction time, recovery time, and refractory periods were assessed with multifactorial ANOVAs. It was found that the phase of stimulation significantly affected nodal conduction time but not the refractory periods or the time constant of the recovery. Each input could show longer and shorter conduction time than the other depending on the stimulation phase, input reference, and coupling interval. These effects were similar for different nodal functional states. However, pacing and recording from the low crista resulted in similar conduction and refractory values than did pacing and recording from the low septum. Input summation did not increase the otherwise equal efficacy of individual input in activating the node. Nodal surface recordings confirmed this functional symmetry and equivalent efficacy of the inputs and showed that input effects were confined to the proximal node. CONCLUSIONS: The two nodal inputs have equivalent functional properties and are equally effective in activating the rate-dependent portion of the node. Input interaction affects perinodal activation but not the rate-dependent nodal function.     

Automatic activity of pacemaker cells in the atrioventricular valves of the rabbit heart

The microelectrode technique applied revealed an automatic activity of the pacemaker cells with slow diastolic depolarization in the cusps of the atrioventricular valves obtained from 34 rabbit hearts. Electrophysiological characteristics of the action potentials of these cells were investigated. Inhibitors of slow sodium-calcium canal (Mn++, Co++, and Mg++ ions) proved to eliminate the automatic activity of the pacemaker cells. When the content of potassium ions was elevated in the perfusion solution, no suppression occurred. It is suggested that the automatic activity of the pacemaker cells in the atrioventricular values depended mainly on the functioning of the slow sodium-calcium canal.