Pediococcus acidilactici UL5 and Lactococcus lactis ATCC 11454 are able to survive and express their bacteriocin genes under simulated gastrointestinal conditions.

AIMS: The aim of this work is to study the expression of stress genes and those involved in pediocin and nisin production in Pediococcus acidilactici UL5 and Lactococcus lactis ATCC11454 under simulated gastrointestinal (GI) physiological conditions. METHODS AND RESULTS: The two strains were fed to a dynamic GI model (TIM-1). Samples were taken from different compartments and analysed for strain survival as well as for the expression of pediocin PA-1 operon, nisin A production gene and stress genes using RT-qPCR. Ileal-delivered efflux showed a survival rate of 17 and 0·0007% for Ped. acidilactici and La. lactis, respectively. Pediocin operon genes from stressed cells were generally expressed at least at the same level as for unstressed cells. However, pedA is up-regulated in the effluent at 120 and 180 min. Nisin A genes were always up-regulated with particularly in the stomach after 70 min compared with control. CONCLUSIONS: Bacteriocin production of Ped. acidilactici UL5 and Lc. lactis ATCC 11454 are not affected by upper GI simulated conditions and thus could be considered as relevant probiotic candidates. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates the capacity of lactic acid bacteria to survive and express their bacteriocins genes under simulated GI conditions.

Electroarthrography: a novel method to assess articular cartilage and diagnose osteoarthritis by non-invasive measurement of load-induced electrical potentials at the surface of the knee.

OBJECTIVE: A new technique called electroarthrography (EAG) measures electrical potentials on the surface of the knee during joint loading. The objective of this study was to evaluate the effectiveness of EAG to assess joint cartilage degeneration. DESIGN: EAG recordings were performed on 20 asymptomatic subjects (Control group) and on 20 patients with bilateral knee osteoarthritis (OA) who had had a unilateral total knee replacement (TKR), both the TKR knee and the remaining knee were analyzed. EAG signals were recorded at eight electrode sites over one knee as the subjects shifted their weight from one leg to the other to achieve joint loading. The EAG signals were filtered, baseline-corrected and time-averaged. RESULTS: EAG repeatability was assessed with a test-retest protocol which showed statistically significant high intraclass correlation coefficients (ICC) for four electrode sites near the joint line. These sites also showed the highest mean EAG values. The mean EAG potentials of the Control group were significantly higher compared with the OA group for three sites overlying the joint line. The potentials overlying the TKR were statistically nul. In the Control group, no statistically significant correlation was found between the EAG amplitude and age, weight, height or body mass index (BMI); no statistical difference was found in mean EAG potentials between women and men. CONCLUSIONS: This study indicates that EAG signals arise from the streaming potentials in compressed articular cartilage which are known sensitive indicators of joint cartilage health. EAG is a promising new technique for the non-invasive assessment of cartilage degeneration and arthritis.

How clean is your ice machine? Revealing microbial amplification and presence of opportunistic pathogens in hospital ice-water machines.

BACKGROUND: Ice machines in healthcare facilities have been suspected and even linked to outbreaks and pseudo-outbreaks. Guidelines exist for maintenance of these devices but there is no clear independent infection control standard, and little is known about their microbial contamination. AIM: To evaluate the microbial contamination, amplification, and presence of opportunistic pathogens in ice-water machines in a healthcare facility. METHODS: Concentrations of general microbial indicators (heterotrophic plate counts (HPC), total and intact cells), faecal indicators (enterococci) and opportunistic pathogens (Pseudomonas aeruginosa, non-tuberculous mycobacteria (NTM), Candida spp.) were measured in 36 ice-water machines on patient wards of a 772-bed hospital. Profile sampling was performed on five ice-water machines and adjacent faucets to identify sites of microbial proliferation. FINDINGS: Candida spp. were found in half of ice-water samples while enterococci and P. aeruginosa were present in six and 11 drain inlets respectively. NTM were measured in all ice-water samples and 35 out of 36 biofilms. Pre-filters and ice machines are sites for additional amplification: NTM densities were on average 1.3 log10 higher in water of ice machine flushed 5 min compared to flushed adjacent tap water. CONCLUSION: Ice machine design needs to be adapted to reduce microbial proliferation. The absence of correlation between HPC densities (current microbial indicators) and NTM concentrations suggests a need for cleaning efficiency indicators better correlated with opportunistic pathogens. Cleaning and disinfection guidelines of ice machines in healthcare facilities need to be improved, especially when ice is given to the most vulnerable patients, and NTM may be an efficiency indicator.

Partial meniscectomy changes fluid pressurization in articular cartilage in human knees.

Partial meniscectomy is believed to change the biomechanics of the knee joint through alterations in the contact of articular cartilages and menisci. Although fluid pressure plays an important role in the load support mechanism of the knee, the fluid pressurization in the cartilages and menisci has been ignored in the finite element studies of the mechanics of meniscectomy. In the present study, a 3D fibril-reinforced poromechanical model of the knee joint was used to explore the fluid flow dependent changes in articular cartilage following partial medial and lateral meniscectomies. Six partial longitudinal meniscectomies were considered under relaxation, simple creep, and combined creep loading conditions. In comparison to the intact knee, partial meniscectomy not only caused a substantial increase in the maximum fluid pressure but also shifted the location of this pressure in the femoral cartilage. Furthermore, these changes were positively correlated to the size of meniscal resection. While in the intact joint, the location of the maximum fluid pressure was dependent on the loading conditions, in the meniscectomized joint the location was predominantly determined by the site of meniscal resection. The partial meniscectomy also reduced the rate of the pressure dissipation, resulting in even larger difference between creep and relaxation times as compared to the case of the intact knee. The knee joint became stiffer after meniscectomy because of higher fluid pressure at knee compression followed by slower pressure dissipation. The present study indicated the role of fluid pressurization in the altered mechanics of meniscectomized knees.

Poly(adenosine diphosphoribose) polymerase activity and adenosine diphosphate ribosylation of proteins during pancreatic degeneration and regeneration.

The activity of poly(adenosine diphosphoribose) polymerase was measured in isolated rat pancreatic nuclei and was found to increase during pancreatic nuclei which follows an ethionine treatment, although a possible relationship of enzyme activity to the initial degenerative phase may also be considered. There is a 2-fold increase in the enzyme activity during the destruction process which remains high during the regeneration period. This increase of activity observed during regeneration is not related to a decrease of the polymer degradation. We have studied the adenosine diphosphate ribosylation of proteins during pancreatic regeneration, and we have found increases in the level of adenosine diphosphate ribosylations of these proteins just before regeneration and during the regeneration period. The in vivo adenosine diphosphate ribosylation of nuclear proteins does not correlate with synthetase activity measured in nuclei during the degeneration period but does correlate during the regeneration period and thereafter with the relative amount of enzymatic activity found in nuclei. Furthermore, as verified by autoradiography, labeling of the nuclei by polyadenosine diphosphoribose polymer shows a marked increase during regeneration.

Poly(ADP-ribose) polymerase activity in mouse cells which exhibit temperature-sensitive DNA synthesis.

The poly(ADP-ribose) polymerase activity of wild-type mouse L cells and of Balb/C-3T3 mouse fibroblasts remained relatively unchanged (at approx. 400 nmol substrate utilized/mg DNA per h) in actively-growing cells incubated at 34 degrees C or at 38.5 degrees C for at least 72 h. A similar result was obtained with the following temperature-sensitive cells grown at the permissive temperature (34 degrees C): ts A1S9 mouse L cells, ts C1 mouse L cells and Balb/C-3T3 ts mouse fibroblasts. The poly(ADP-ribose) polymerase activity of the temperature-sensitive cells was little affected during incubation for 20-24 h at the non-permissive temperature of 38.5 degrees C under which conditions temperature-inactivation of DNA replication was complete. Thereafter, this enzyme activity was found to increase some 2-fold, at a time when normal semi-conservative DNA synthesis was totally suppressed and replaced by repair replication (Sheinin, R. and Guttman, S. (1977) Biochim. Biophys. Acta 479, 105-118; Sheinin, R., Dardick, I. and Doane, F.W. (1980) Exp. Cell. Res., in the press).

New body surface isopotential map evaluation method to detect minor potential losses in non-Q-wave myocardial infarction.

BACKGROUND: Potential losses caused by stable non-Q-wave myocardial infarction (MI) are too small to diagnose with the use of standard ECG. The aim of the present study was to obtain accurate diagnostic criteria for this prognostically important disease with the help of body surface mapping. METHODS AND RESULTS: Body surface potentials were recorded with the use of 63 unipolar leads in 45 patients with a non-Q-wave MI (41 to 75 years old); 24 healthy adults, 42 patients with unstable angina, and 70 patients with Q-wave MI served as reference groups. Qualitative pathological features of the isopotential maps, such as onset time and site and magnitude of the first right-anterior/anterior minimum, as well as pathological negativities at that time, were defined in non-Q-wave MI cases. These features, which account for the activation sequence and the body surface projections of specific cardiac regions (Selvester classification), showed a 91% sensitivity and an 88% specificity for the detection of non-Q-wave MI. In comparison, the different departure maps (first third QRS, QRS, and QRST isoarea) resulted in less favorable specificities (50% to 58%). Concordance between the isopotential maps and the acute-phase ECG (90%), hypokinesis (64%), fixed perfusion defects (59%), and significant stenosis of the infarct-related coronary artery (87%) supported the concept that these isopotential map changes correspond to the supposed sites of MI. There were pathological features in 69% of patients with unstable angina, with similar concordances as in non-Q-wave MI. CONCLUSIONS: Isopotential maps revealed characteristic features that were suitable for the detection and localization of non-Q-wave MI in the clinical setting of unstable coronary artery disease.

Markedly different effects on ventricular remodeling result in a decrease in inducibility of ventricular arrhythmias.

OBJECTIVES: The purpose of this study was to determine whether the type and extent of ventricular remodeling after infarction influence inducibility of ventricular arrhythmias after infarction. BACKGROUND: Although serious ventricular arrhythmias after infarction are related to ventricular dysfunction, the relation between inducibility of ventricular arrhythmias and ventricular remodeling remains incompletely understood. METHODS: Rats that survived ligation of the left anterior descending coronary artery (n = 218) were randomized to receive placebo (saline solution) or captopril or propranolol therapy and were followed up for 5 weeks. Hemodynamic and neurohumoral blood measurements were obtained, and therapy was stopped. Two days later, susceptibility to ventricular arrhythmias was assessed by programmed electrical stimulation, and hearts were prepared for pathologic studies. RESULTS: Placebo-treated rats with a large myocardial infarction had ventricular dysfunction, marked neurohumoral activation, ventricular enlargement (endocardial circumference 16 +/- 3 [mean +/- SD] to 20 +/- 4 mm, p < 0.05) and increased cardiac fibrosis (volume density of collagen 2.3 +/- 0.8% to 5.6 +/- 2.4%, p < 0.05). In many rats this resulted in easily inducible ventricular arrhythmias (inducibility quotient 4.9 +/- 2.2). Captopril attenuated the development of ventricular dysfunction, neurohumoral activation, ventricular hypertrophy and dilation (endocardial circumference 18 +/- 3 mm) and cardiac fibrosis (3.1 +/- 0.8%, p < 0.05). These modifications were accompanied by decreased inducibility of ventricular arrhythmias (inducibility quotient 1.1 +/- 2.0, p < 0.05). Propranolol did not prevent ventricular dysfunction, had variable effects on neurohumoral activation and led to increased ventricular dilation (endocardial circumference 25 +/- 4 mm, p < 0.05) and cardiac fibrosis (7.7 +/- 1.2%, p < 0.05). Nevertheless, these morphologic changes led to decreased inducibility of ventricular arrhythmias (inducibility quotient 2.2 +/- 2.5%, p < 0.05). CONCLUSIONS: This study indicates that the inducibility of ventricular arrhythmias can be reduced as a result of markedly different effects on ventricular remodeling, indicating that the relation between ventricular remodeling, arrhythmias and survival is more complex than previously thought.

Signal-averaged electrocardiography and detection of heart transplant rejection: comparison of time and frequency domain analyses.

To evaluate the role of the signal-averaged electrocardiogram (ECG) in the detection of heart transplant rejection, findings on 277 ECGs were compared with those in 218 endomyocardial biopsy specimens in 25 patients followed up for a median duration of 5.2 months (range 7 days to 17.5 months). Signal-averaged ECGs obtained at intervals of 16.4 +/- 22.3 days were analyzed in the time domain before and after high pass filtering at 25 and 70 Hz. Frequency domain analysis was performed with use of a fast Fourier transform algorithm. Sixteen severe rejection episodes requiring treatment were observed. These episodes induced significant decreases in peak and root-mean-square voltages of both filtered and unfiltered QRS complexes, as well as in the total spectral area. Conversely, QRS duration and 50- to 250-Hz or 70- to 110-Hz spectral areas were not significantly altered. In 14 cases mild rejection episodes were observed that did not significantly alter any of the variables studied. The root-mean-square voltage of the 70-Hz high pass filtered QRS complex was found to be the most accurate variable in detecting rejection. Moreover, this variable was also the most reproducible in 10 healthy control subjects. The optimal rejection criterion was defined as an 11% decrease in voltage between two consecutive recordings. It provided 87.5% sensitivity with 78.4% specificity. In conclusion, the signal-averaged ECG is helpful in the management of heart transplant rejection. Frequency domain analysis of the QRS complex does not increase the accuracy of the technique compared with the time domain approach.

Myocardial infarction patients in the 1990s--their risk factors, stratification and survival in Canada: the Canadian Assessment of Myocardial Infarction (CAMI) Study.

OBJECTIVES: This study sought to evaluate the in-hospital and postdischarge mortality of patients with an acute myocardial infarction in the 1990s. BACKGROUND: The widespread implementation of therapeutic interventions that modify the natural history of coronary artery disease has led to changes in the profile and survival of patients with an acute myocardial infarction. Although data exist for selected subsets of patients with an acute myocardial infarction, at this time there is little recent prospective information on all patients presenting with an acute myocardial infarction, particularly for survival after hospital discharge. METHODS: All patients < or = 75 years old presenting with an acute myocardial infarction between July 1, 1990 and June 30, 1992 at nine Canadian hospitals were prospectively evaluated and followed up for 1 year. From November 1991, patients of all ages were included. In two centers, recruitment continued until December 31, 1992. A total of 3,178 patients were recruited. RESULTS: The in-hospital mortality rate of patients < or = 75 years old was 8.4%, and that at 1 year after hospital discharge was 5.3%. For patients of all ages recruited after November 1, 1991, the in-hospital mortality rate was 9.9% and 7.1% for 1 year after hospital discharge. For patients < or = 75 years old, age carried an independent in-hospital but no post discharge risk. Female patients had a twofold greater risk of dying in hospital. After hospital discharge, only 1.7% of patients < or = 75 years old and 1.9% of patients of all ages died of a presumed arrhythmic death. Premature ventricular contractions had no independent prognostic value. The relatively low in-hospital (5.3%) and postdischarge (6.1%) reinfarction rate may have contributed to improved survival. A greater reinfarction rate in patients >75 years old (17.4% vs. 9.6%, p < 0.001) may have contributed to their poorer outcome. CONCLUSIONS: One-year mortality after acute myocardial infarction continues to decrease, and changes in the prognostic value of traditional methods of risk stratification have occurred.

Differential regulation of Hox C6 in the appendages of adult urodeles and anurans.

Morphogenesis and pattern formation are biological processes that rely on the expression of positional determinants to divide the embryo into compartments. Hox genes are among the selector genes that direct the mechanism of positional information. Here we report the molecular structure and pattern of expression of a new Hox C6 transcript in the adult newt. Molecular analysis showed that the gene transcribes a long primary transcript in both limb and tail regeneration territories and subsequently uses maturation events to produce two RNAs that share the same DNA binding domain and differ in their 5' extremity. Both RNAs were found in the limb and showed a proximal-distal gradient of expression. The tail sample showed accumulation of only one Hox C6 transcript. These results suggest that both transcriptional and post-transcriptional regulations are involved in the appendage-specific expression of Hox C6 in the adult newt. Finally, the adult frog, which has lost its regeneration capacity, also post-transcriptionally regulates the expression of Hox C6 in its appendages.

Graded expression of Emx-2 in the adult newt limb and its corresponding regeneration blastema.

Amputation of a newt limb causes stump cells to organize the reformation of the missing structures. The phenomenon is remarkably precise in that the regeneration is perfect. During the first few days following amputation, the tissue proximal to the plane of amputation gives rise to the blastema, an area of growth composed of mesenchymal cells covered by a single epithelium. The blastema possesses a morphogenetic potential characteristic of the structures that have been amputated. Looking for control genes putatively involved in regeneration, we cloned the newt version of the mouse and human Emx-2. Its expression is restricted to the skin of the regeneration territories and is graded along the proximal-distal axis of both forelimb and hindlimb, with higher levels in distal regions. The regeneration blastema also show this proximal-distal graded level of expression with distal blastemas (mid-radius and ulna) showing higher levels of expression when compared to blastemas of more proximal origin (mid-humerus). Finally, retinoic acid proximalizes both the level of Emx-2 expression and the positional memory of the blastema suggesting Emx-2 may participate in pattern formation by specifying positional information.

Characterisation of unipolar waveform alternation in acutely ischaemic porcine myocardium.

The relation between electrical alternans recorded in acutely ischaemic myocardium, ventricular arrhythmias, and changes in the activation sequence was studied. Sixty three unipolar electrograms, simultaneously recorded from the epicardial surface of the in situ porcine heart during 6 min periods of coronary occlusion, were converted to a digital format and analysed by computer. The time integrals of the electrograms during their QRS complex, ST segment, and T wave were measured. Unipolar waveform alternation was then quantified by subtracting the values obtained for two consecutive beats showing alternans. The spatial distribution of unipolar waveform alternation was illustrated by isoarea difference maps. Isochronal maps of the local excitation detected on each electrogram were constructed. Of 52 occlusions in 27 preparations, unipolar waveform alternation was detected in 42 and was promptly followed by ventricular arrhythmias in 37. The magnitude of unipolar waveform alternation increased from the margin to the inner portion of the ischaemic zone but its correlation with activation delay was poor, and there was no change in the activation sequence. These results suggest that beat to beat alternation of the unipolar waveform is related to changes in the action potential configuration rather than to changes in the activation sequence. Furthermore, unipolar waveform alternation appears to be associated with the development of early post-occlusion ventricular arrhythmias.

Expression of Hox A11 in the limb and the regeneration blastema of adult newt.

Homeoproteins are functionally involved in pattern formation of developing systems and are potentially good candidates to regulate positional information during limb regeneration in the newt. Here we report the molecular structure of Hox A11 and its pattern of expression during the regeneration of adult newt appendages. The transcriptional unit of the gene is composed of two exons separated by an intron. Northern blots revealed two major transcripts; a size difference would result from using two different polyadenylation signals. Therefore, the gene would encode a single protein that is very homologous to other vertebrate counterparts. The pattern of expression of Hox A11 in the adult newt shows interesting findings in relation to limb regeneration. First, expression is found in both intact limb and tail, showing maintenance of expression of an important regulator of development in the appendages of the adult newt. Second, Hox A11 is expressed mainly in the muscle and the bone of intact limbs, two tissue fractions known to participate in blastemal fate determination. Third, the level of Hox A11 expression increases drastically in both limb and tail regeneration blastemas, suggesting that the population of expressing cells is preferentially recruited during blastemal formation. Finally, proximal blastemas (mid-humerus) significantly express higher levels of transcript compared with distal ones (mid-radius and ulna). These features of expression suggest that Hox A11 may participate in limb pattern formation by specifying positional information to the progenitor cells of the regenerate.

Homeobox-containing genes in the newt are organized in clusters similar to other vertebrates.

In vertebrates, the majority of homeobox (HBox) genes are found in four clusters and this structural organization is believed to be of functional importance. Many HBox genes sustain their expression in the appendages of the adult newt. To further understand their regulation, the genomic loci of four newt HBox genes (two from the human HBox (HOX)-2 complex and two from the HOX-3 complex) were analysed and compared with homologous loci in other vertebrates. Notophthalmus viridescens HBox (NvHBox) genes were selected from a lambda EMBL3 library and analysed by restriction mapping and nucleotide (nt) sequencing. The nt sequences of the NvHBox genes have a very high degree of homology (more than 90%) with the human and mouse HBox genes, HOX-3.3, HOX-3.4, HOX-2.7 and HOX-2.8. The sequences flanking the HBox are also very homologous to their human and mouse counterparts. Moreover, the size of the DNA spacer separating NvHBox-3.3 from NvHBox-3.4, and NvHBox-2.7 from NvHBox-2.8 in the newt is similar in the homologous regions of the mouse and human, despite there being a C value ten times greater in the newt genome. Finally, three of these NvHBox genes are expressed in the limbs of the adult newt.

Effects of thyroid state on serotonin, 5-hydroxyindoleacetic acid and substance P contents in discrete brain nuclei of adult rats.

The effects of chemical thyroidectomy produced by propylthiouracil treatment or hyperthyroidism produced by daily injections of thyroxine on the content of serotonin, its metabolite 5-hydroxyindoleacetic acid and of substance P in discrete brain nuclei of adult rats have been studied. Brain nuclei were removed by punches of frozen brain slices. The serotonin and 5-hydroxyindoleacetic acid contents were measured by high performance liquid chromatography with electrochemical detection while substance P was assayed by radioimmunoassay. The serotonin level was significantly increased in 11 nuclei of the hypothyroid and in 12 nuclei of the hyperthyroid rats. The 5-hydroxyindoleacetic acid levels were higher in 16 nuclei of the hypothyroid and 7 nuclei of the hyperthyroid animals. The state of the thyroid gland in adult rats also affected the substance P system but less consistently than the serotonin pathway. Thus, the substance P content in the brain of propylthiouracil-treated animals increased significantly in 4 nuclei while it decreased in the septum lateralis and the striae terminalis. Following the chronic thyroxine injections, the substance P level was increased in the nucleus caudatus putamen and the tractus diagonalis and was decreased in the area ventralis tegmenti. We previously reported that neonatal thyroidectomy caused a general increase of the substance P and serotonin contents in many brain nuclei of young rats. It appears that the effects of chemical thyroidectomy on mature and immature rat brain are different for the substance P system, suggesting that thyroxine plays an important role in the maturation of substance P-containing neurons.

Mapping of septal ventricular tachycardia: clinical and experimental correlations.

In patients with chronic myocardial infarction, ventricular tachycardia originating in the interventricular septum may account for a significant number of arrhythmia recurrences after direct ablative operations. We used total computer-assisted cardiac mapping (epicardial sock, left and right ventricular endocardial balloon electrode arrays) to assess whether tachycardia originating in deep or right-sided layers of the interventricular septum is associated with a specific pattern of epicardial activation sequence. We performed these studies during operations in 18 patients and during experiments in 12 dogs in which a septal myocardial infarction was produced by ligating the anterior septal coronary artery. Intraseptal needle electrodes were plunged into the septum of all animal preparations to generate pace-mapping data and to obtain intraseptal recordings (six preparations) during reentrant ventricular tachycardia induced by programmed stimulation. In addition, pace-mapping data of infarcted canine heart preparations were compared with those of nine healthy heart preparations. In the clinical study, 31 ventricular tachycardias with a septal site of origin were analyzed. Twenty tachycardias displayed an epicardial breakthrough in the area of the interventricular groove, whereas 11 had an epicardial breakthrough in the right ventricular free wall. Biventricular endocardial mapping revealed that left septal endocardial activation preceded right septal activation in the former and that right septal activation occurred earlier in the latter. In the experimental study, 14 ventricular tachycardias (cycle length 146 +/- 34 msec) were induced by programmed stimulation in 11 infarcted heart preparations. Eight tachycardias displaying an epicardial breakthrough on the right ventricle were found to originate in the right ventricular septal subendocardial layers, whereas six tachycardias in which the epicardial breakthrough occurred on the anterior interventricular groove originated in the left ventricular septal subendocardial layers. The epicardial breakthrough preceded the left ventricular endocardial breakthrough in six tachycardias (85.7%) originating in intermediate or right ventricular septal layers, but in only one of five tachycardias originating in the left ventricular septal layers. In the pace-mapping study, the epicardial breakthrough shifted progressively from the right ventricular free wall toward the interventricular groove area in response to pacing from the right, intermediate, and left ventricular thirds of the basal septum. This relationship was similar for infarcted and noninfarcted hearts, although transseptal conduction time was prolonged in infarcted hearts (45 +/- 10 msec vs 33 +/- 7 msec, p < 0.01). Therefore the information integrated from the localization of the epicardial breakthrough and the relative timing between the epicardial and the left ventricular endocardial breakthroughs can be used to estimate the depth of the site of origin of septal ventricular tachycardias. This study confirms that a three-dimensional view of the substratum of ventricular tachycardia can be derived from simultaneous epicardial and left ventricular endocardial mapping and can provide a superior basis for therapeutic interventions.

Regional distribution of atrial electrical changes induced by stimulation of extracardiac and intracardiac neural elements.

UNLABELLED: Autonomic nerves and intrinsic cardiac neural elements are known to influence the electrophysiologic and dynamic properties of the heart. This study describes the regional distribution in the canine atria of electrophysiologic effects induced by stimulation of the right and left cervical vagosympathetic complexes, the right atrial ganglionated plexus, and the right and left stellate ganglia. Local atrial effects were determined from changes in QRST area of unipolar electrograms recorded from multiple sites with plaque electrodes sewn onto the atria in 16 anesthetized dogs. RESULTS: (1) Although being very consistent in any given preparation, atrial changes varied between animals when similar neural structures were stimulated. (2) Among the common features identified between preparations, consistent effects were induced by neural stimulation in the region of the sinus node, indicating that this atrial region is the most richly innervated. (3) All other regions of the atria could be affected by stimulation of either right-sided or left-sided efferent nerves. (4) Responses to right atrial ganglionated plexus stimulation after atropine administration indicated that the corresponding fat pad contains both sympathetic and parasympathetic neural elements. CONCLUSION: This study demonstrates that there is considerable overlapping of atrial innervation affecting all regions of the atria, as well as the sinus node region.

The effects of p-chlorophenylalanine (PCPA) treatment on the substance P content measured in discrete brain nuclei of normal and neonatally-induced hypothyroid rats.

Neonatal hypothyroidism is known to induce the accumulation of substance P and serotonin in many discrete brain nuclei of the rat. In this work, we have studied the effects of p-chlorophenylalanine (PCPA), a serotonin (5-HT) depleting drug, on the regional distribution of substance P in the brains of neonatally-induced hypothyroid and euthyroid rats. PCPA injections were given 48 and 24 h before sacrifice and the peptide content of discrete brain nuclei, removed by punches of frozen brain slices, was measured by radioimmunoassay. In hypothyroid animals, substance P levels were significantly increased in the n. paraventricularis, n. medialis thalami, n. arcuatus. n. mamillaris medialis, substantia nigra, area ventralis tegmenti, n. interpeduncularis, substantia grisea and n. dorsalis raphes. This hypothyroid-induced accumulation of substance P was completely abolished, and even reversed in some nuclei, by PCPA treatment. Interestingly, in normal rats, following PCPA treatment, the substance P level was increased in n. paraventricularis pars magnocellularis, n. ventromedialis (hypothalami), n. dorsomedialis pars dorsalis (hypothalami), n. amygdaloideus centralis, area ventralis tegmenti, substantia grisea, n. medianus raphes and n. dorsalis raphes. These results lend support to the existence of a physiological relationship between both substance P and serotonergic systems.

Comparative effects of neonatal hypothyroidism and euthyroidism on TRH and substance P content of lumbar spinal cord in saline and PCPA-treated rats.

The effects of neonatal thyroidectomy and thyroid hormone replacement therapy on the content of substance P and TRH in the lumbar segment of the rat spinal cord were studied. The peptide content of discrete spinal cord regions removed by punches of frozen serial slices was measured by RIA. Animals receiving T4 replacement therapy were indistinguishable from normal littermates. In hypothyroid animals without PCPA-treatment, levels of TRH and substance P were significantly increased by 100% in the ventral and the dorsal lumbar spinal cord, respectively. Inhibition of serotonin biosynthesis by PCPA increased by 90% the substance P content in the dorsal horn of euthyroid rats and abolished completely the stimulatory effect of hypothyroidism on the TRH content of the ventral horn. These findings suggest the existence of a physiological relationship between substance P and TRH with the serotoninergic system in the rat spinal cord and that thyroid hormone is implicated in the normal development of the peptide-containing neurons in the rat spinal cord.