Noninvasive Recording of His-Purkinje System (HPS) Activity in Man on Beat-To-Beat Basis

Since 1969 His bundle electrography has been used for diagnosis and for the study of cardiac electrophysiology. This method has employed the catheterization technique and has allowed the continuous recording of electrical activity of the specialized cardiac conduction system in every beat. Such investigation, because of its invasive nature, cannot be considered a routine test; it requires expensive instrumentation, it has physiological and technical limitations that include discomfort, a slight morbidity risk and a rather limited recorded area within the heart. In 1973 a method was developed for a noninvasive recording of the electrical activity within the P-R segment of the electrocardiogram measured from the body surface. This method which employs the signal averaging technique delivers even less medical information than intracardiac measurement. The shortcomings of this averaging method include inability to detect beat-to-beat changes in the true signal. Such a method is not useful in transient arrhythmia detection and a "short acting" drug influence examination. The technical approach to the beat-to-beat noninvasive recording of the HPS activation signal as measured from the body surface has been proposed. Using a specially positioned electrode system, a low noise multiple parallel input amplifier and a computer for sampling, processing and plotting of the measured signal, we have obtained an output curve corresponding to the continuous beat-to-beat HPS activity.     

Modulation of Vascular O2 Responses by Cytochrome 450‐4A ω‐Hydroxylase Metabolites In Dahl Salt‐Sensitive Rats

Objective: This study evaluated the role of the 20‐HETE/cytochrome P450‐4A ω‐hydroxylase (CYP450‐4A) system in microvascular regulation in the skeletal muscle circulation following short‐term (three‐day) exposure to a high‐salt (HS) diet in Dahl salt‐sensitive (SS) rats. Methods: The effects of inhibiting CYP450‐4A on resting diameter, O₂‐induced constriction, and vasodilator responses to acetylcholine (ACh) and the nitric oxide (NO) donor, sodium nitroprusside (SNP), were evaluated in cremasteric arterioles of SS rats fed a low‐ (LS; 0.4% NaCl) or high‐salt (HS; 4% NaCl) diet for three days. Results: The HS diet upregulated CYP450‐4A mRNA expression and led to an enhanced constriction of arterioles in response to elevated PO₂ in SS rats, which could be blocked by inhibiting CYP450‐4A enzymes with dibromododecenyl methylsulfimide (DDMS). DDMS also inhibited resting tone significantly in SS rats fed the HS, but not the LS, diet, despite similar resting diameters and active tone in the two groups. Arteriolar dilations in response to ACh and SNP were similar in SS rats fed the LS vs. the HS diet and were unaffected by DDMS. Conclusions: These findings suggest that CYP450‐4A enzymes contribute to resting tone and to an enhanced response to elevated PO₂ in arterioles of Dahl‐SS rats fed the HS diet.     

Prognostic value of the ankle‐brachial index in elderly patients with a stable chronic cardiovascular event

Summary. Background and Objectives: Patients with polyvascular arterial disease have a greater risk of suffering a new atherothrombotic episode than those with involvement of only one vascular territory. We have studied the predictive prognostic value of the detection of non‐diagnosed peripheral arterial disease, determined by measuring the ankle‐brachial index in a population of elderly patients with stable chronic cardiac or cerebrovascular disease. Methods: This was a multicenter, prospective cohort study with consecutive inclusion of patients between 65 and 85 years of age with a previous atherothrombotic event, but without previously established peripheral arterial disease. Results: A total of 1096 patients were evaluated during 11.7 (± 2.2) months of follow‐up. An ankle‐brachial index of < 0.9 was observed in 29.9% and > 1.4 in 6.9%. The detection of an ankle‐brachial index < 0.9 was clearly associated with the presence of a combined primary event of cardiovascular death and non‐fatal cardiovascular event [HR 1.99 (95% CI, 1.49–2.66; P < 0.001)]. There was also a significant relationship between ankle‐brachial index > 1.4 and total (P = 0.001) or cardiovascular (P = 0.020) deaths. The predictive value of both ranges of the ankle‐brachial index was maintained after adjusting for age, sex, diabetes mellitus, vascular territory, macroalbuminuria or glomerular filtration rate. Conclusions: The detection of non‐diagnosed peripheral arterial disease in patients with stable coronary or cerebrovascular events identifies a very high risk population that might benefit from more intensive treatment.     

Relaxation by Calcium Antagonists of Potassium-contracted Trachea from Normal and Sensitized Guinea-pigs: Influence of Epithelium and the Surface of Drug Entry

Abstract— A technique by which drug access was restricted to either the mucosal or the adventitial surface of tracheal rings, isolated from normal (unsensitized) or sensitized guinea-pigs, was used to study the role of the epithelium in the relaxation produced by calcium antagonists (verapamil, nifedipine, cinnarizine and flunarizine) of K⁺-induced contraction. In trachea from normal guinea-pigs, the relaxation to verapamil for unrestricted or mucosal drug entry was reduced in the absence of epithelium, whereas the relaxation produced by nifedipine, cinnarizine or flunarizine was unchanged. In sensitized trachea, the relaxation elicited by the calcium antagonists tested was similar in intact and epithelium-denuded tracheal rings irrespective of the surface of drug entry. These results confirm that the epithelium influences the relaxation to verapamil. This modulatory effect is absent in sensitized trachea and is not shared by other calcium antagonists.     

Subthreshold response to white-noise current input in a tapering cable model of a neuron

^* Author to whom all correspondence should be addressed The expectation (mean) and variance of the depolarization inthe absence of a threshold for action-potential generation isobtained in a neuron model represented by a tapering equivalentcable with a random (white noise) synaptic input current ata point along the dendrites. The results show that the introductionof a taper in the equivalent-cable representation of the neuronproduces larger values for both the expectation and variancewhich are neither insensitive nor symmetrical with respect tothe location of the input. It is also shown that taper extendsthe invariance of the variability in the steady-state somaticresponse to proximally located random inputs, implying thatonly small changes in the noisiness of the somatic responseoccur for a random input located in the dendrites.