Salivary electrolytes and digitalis

The hypothesis that an increase in salivary concentration ofcertain electrolytes (Ca x K) is a sign of digitalis intoxicationwas tested in 16 untreated health volunteers, 29 digitalisedheart failure patients and four further healthy volunteers givendigoxin. Salivary electrolyte levels were raised in only abouthalf the digitalised patients and blood levels of digoxin werenot always higher in these patients than in those with normalelectrolyte concentrations. The salivary electrolyte levelsof the healthy volunteers given digoxin remained normal. Thesefindings would seem to rule out the possibility that digitalisis responsible for the changes in salivary electrolytes observedin certain cases of heart failure. A very marked correlation(P<0.00002 by Fisher's exact probability test) was found,however, between an increase in the product of salivary calciumand potassium (Ca_sal x K_sal) and the presence of clinical signsof poorly compensated heart failure. It is suggested that thismight be a result of adrenergic stimulation, which is knownto occur in heart failure, affecting the salivary glands.     

Circular dichroism (CD) studies on biological activity of mast cell degranulating (MCD) peptide analogs*

Analogs of MCD peptide were synthesized by solid-phase methods. Positive charges were deleted at the N-and/or C-terminus, including the helical portion of the molecule. Four peptides were prepared by removing residues 16–18 (Arg-Lys-Ile), 1–2 (Lys), 1–2 and 16–18 and by acetylation of the amino end (Ile). Analogs were tested on mast cells for histamine-releasing activity. Although the helicity of these derivatives, determined by circular dichroism (CD), was not significantly different from the native MCD peptide, two analogs with C-terminal deletions showed a 5- to 10-fold decrease in activity. These findings suggest that the C-terminus is more important than the N-terminus in determining bioactivity of MCD peptide.     

Characterization of the Factors that Determine the Effect of Sympathetic Stimulation on Heart Rate Variability

Heart rate variability analysis has been used to derive indices of sympathetic tone. As different sympathetic stimuli may give rise to divergent changes in heart rate variability, this study was designed to characterize the factors responsible for these divergent responses. Twelve healthy subjects (7 males, age 24.8 ±3.1 years) were evaluated. Five-minute electrocardiographic recordings were obtained at baseline, following upright tilt, and during isoproterenol infusion (25 ng/kg per min) under control conditions and following parasympathetic blockade. Data were acquired during spontaneous respiration and when breathing was timed with a metronome (15 breaths/min). Under control conditions, both upright tilt and isoproterenol infusion resulted in significant decreases in the SD and MSSD from baseline values of 69 ± 3 ms and 64 ± 5 ms to 48 ± 4 ms and 21 ± 5 ms during tilt and 44 ± 4 ms and 20 ± 5 ms during isoproterenol infusion, respectively. LF power also significantly increased from 0.47 ±0.17 In (beats/min)² at baseline to 1.90 ± 0.20. In (beats/min)² and 1.34 ± 0.18. In (beats/min)² during tilt and isoproterenoi infusion, respectively. No change in HF power was noted. Following parasympathetic blockade, all heart rate variability parameters were significantly decreased. No significant change from baseline in the SD, MSSD, or HF power was noted with either tilt or isoproterenol infusion. The LF power increased only with tilt from a baseline value of -3.17 ± 0.17 in (beats/min)² to -0.41 ± 0.19 in (beats/min)². Similar changes were noted during spontaneous respiration and metronome breathing. These findings demonstrate that the response of the sinus node to β–adrenergic stimulation depends on the mode of stimulation. In addition, the associated level of parasympathetic tone affects the observed changes in heart rate variability that are associated with sympathetic stimulation.     

The Monolithic Fetal Pacemaker:

DELL'ORFANO, J., et al .: The Monolithic Fetal Pacemaker: Prototype Lead Design for Closed Thorax Deployment. Prenatal sudden cardiac death and hydrops fetalis are often due to complete heart block. However, no pacing modality exists for intrauterine application for fetal bradycardia. A prototype lead for a novel fetal pacemaker has been developed and used in a direct pacing model. It has been demonstrated that the lead can be safely and successfully deployed using a hypochondriac and transdiaphragmatic or subxiphoid approach. Pacing with ventricular capture was evident with the widening of QRS duration from   50.2 ± 9.8   to   95.1 ± 12.8 ms (P = 0.0001)   . Further studies by echocardiogram revealed an increase in the pulse with pacing, confirming pacing. This study documents proof-of-concept for closed thorax over-the-wire deployment of a novel lead design applicable to fetal pacing. By combining the lead design with microcircuitry and a small power source, it is possible to create a monolithic fetal pacemaker system capable of being deployed in utero. (PACE 2003; 26[Pt. I]:805–811)     

Effect of Graded Increases in Parasympathetic Tone on Heart Rate Variability

Parasympathetic Effects on Heart Rate Variability. Introduction : Time- and frequency-domain measurements of heart rate variability have been used as indices of parasympathetic tone. However, studies of the effect of parasympathetic stimulation on these indices in humans have yielded conflicting results.
Methods and Results : This study evaluated the effects of parasympathetic stimulation on heart rate variability. Twelve normal subjects (7 males, 5 females; age 24.8 ± 3.4 years) were evaluated in the Clinical Research Center. Five-minute ECG recordings were obtained at baseline and during graded phenylephrine infusions (0.3 and 0.6 μg/kg per min). Recordings were made during spontaneous respiration and when breathing was timed with a metronome at 15 cycles/min. Heart rate variability analysis was performed using standard time- and frequency-domain parameters. Graded phenylephrine infusion resulted in a progressive increase in blood pressure and RR interval but no consistent changes in heart rate variability for the group. The results during normal versus metronome breathing were similar. Stepwise linear regression analysis revealed that the phenylephrine-induced changes in heart rate variability were inversely correlated with the baseline heart rate variability and not related to the baseline KR interval or the phenylephrine-induced change in RR interval.
Conclusion : These findings suggest that the respiratory variation in "parasympathetic effect" typically observed at the sinus node can be either increased or decreased by parasympathetic stimulation, depending on the initial level of parasympathetic tone and the intensity of stimulation. This resolves the previously conflicting data. Thus, evaluation of parasympathetic tone using heart rate variability techniques should be cautiously undertaken.     

Hepatotoxicity of Salicylazosulfapyridine

A case report of a patient with biopsy-proven hepatitis which occurred while that patient was receiving Azulfidine which recurred after a rechallenge is presented. Toxic hepatitis, an apparent drug hypersensitivity reaction can result from Azulfidine therapy and must be considered in the differential diagnosis of hepatic abnormalities in patients with inflammatory bowel disease who are taking this drug. The literature concerning toxic reactions to the drug is reviewed.     

CIRCULATING ANTICOAGULANT IN CREST SYNDROME

We report the discovery of a circulating anticoagulant in apatient suffering from CREST syndrome. The patient was firstseen with a microangiopathic haemolytic anaemia which led tothe diagnosis of the CREST syndrome. Several months later, priorto a cataract operation, a routine coagulation screen (prothrombintime and partial thromboplastin time) was abnormal. Investigationshowed the presence of a circulating anticoagulant as well asa decrease in several clotting factors, principally factor VIIIC. KEY WORDS: CREST syndrome, Circulating anticoagulant     

Autonomic Effects on Noise Recorded During Signal-Averaged Electrocardiography

The purpose of this study was to assess the effects of autonomic stimulation and blockade on noise levels and to compare the noise measurements in the ST and TP segments of the signal-averaged ECG. Five-minute electrocardiographic data were recorded in 14 normal volunteers (8 males and 6 females; mean age 28.5 ± 5.0 years) on two separate days (day 1—baseline, epinephrine infusion, isoproterenol infusion, β-blockade, and combined adrenergic and parasympathetic blockade; day 2—baseline, phenylephrine infusion, parasympathetic blockade, and during phenylephrine infusion following atropine). Signal averaging was done off-line on 100 beats and noise was measured in both the ST and TP segments as the standard deviation of voltage in the segment of interest. For all conditions tested, the mean noise level measured in the ST segment (0.46 ± 0.16 μV) was significantly less than that measured in the TP segment (0.52 ± 0.24 μV; P = 0.0003). but there was good correlation between the noise measured in the STand the TP segment (R²= 0.62, P < 0.0001). Noise increased with isoproterenol infusion and decreased following adrenergic blockade. In addition, day 2 baseline noise was less than baseline noise on day 1. Finally, neither parasympathetic stimulation or blockade nor α-adrenergic stimulation significantly affected signal-averaged electrocardiography (SAECG) noise levels. Thus, the data support the notion that enhanced sympathetic tone increases noise levels and β-adrenergic blockade may decrease noise levels, likely due to effects from muscle sympathetic nerve activity. These findings are important since the target population for the SAECG are patients with myocardial infarction and congestive heart failure, conditions associated with increased sympathetic tone, which may in turn impact on the reproducibility or technical aspects of the SAECG. In addition, because noise in the ST and TP segments are highly correlated and the noise measured in the ST segment is less than that in the TP segment, uniform adoption of noise measurement in the ST segment seems most appropriate.