Intraindividual Reproducibility of Heart Rate Variability

Heart rate variability was determined from three consecutive Holter recordings performed on days 1, 7, and 28 in 17 normal subjects, in 13 patients with angiographically normal coronary arteries, and in 9 patients with remote myocardial infarctions. Group data of several time and frequency domain measures of heart rate variability were highly reproducible (correlation coefficients 0.629–0.894). However, some individuals exhibited considerably larger day-to-day variations in heart rate variability. Single heart rate indices differed by up to 50% between two Holter recordings. Such potential differences must be considered when repeated heart rate variability determinations are used to assess changes in neurocardiac reflex regulation or effects of therapeutic interventions.     

Epicardial Mapping: Ventricular Epicardial Activation is Unaffected by Heart Position

Epicardial ventricular mapping was performed in five dogs during sinus rhythm with a sock array containing 41 bipolar electrodes. Maps were generated with a computer-assisted mapping system when the heart was in situ and when the heart was lifted by 44 degrees out of the chest. Times of earliest and latest epicardial activation in these two states did not differ. Despite a different frontal plane QRS axis, location of earliest activation was not affected by lifting the heart. In two of the five animals, the site of latest epicardial activation was minimally different from the heart in situ, but the general pattern of epicardial activation was unchanged. Therefore, the change in frontal plane QRS axis with lifting the heart was due to a change in heart position rather than a general change of heart activation.     

The relationship between the vascular manifestations of shock produced by endotoxin,trauma, and hemorrhage. I. Certain similarities between the reactions in normal and endotoxin-tolerant rats

The vascular effects of lethal doses of E. coli endotoxin, as observed in the mesentery of the rat, resemble the reactions of traumatic and hemorrhagic shock in the following respects: a profound inhibition of arteriolar and precapillary reactivity to topical epinephrine occurs after an initial stage of hyperreactivity; the small veins show failure to relax completely following constrictor doses of epinephrine; and the terminal vessels develop an unusual sensitivity to fluctuations in temperature of the fluid irrigating the tissue. Rats in which tolerance to bacterial endotoxin is induced, by repeated doses given daily, become highly resistant to the lethal effects of both drum trauma and hemorrhagic shock. However, rats in which the adaptation to traumatic shock is produced by repeated exposure to drum trauma, do not develop a significant degree of tolerance to lethal doses of endotoxin. The injection of small non-lethal doses of bacterial endotoxin during non-lethal episodes of trauma or hemorrhage, leads to the development of irreversible shock and death. The bearing of these findings on the problem of the relationship between endotoxin and traumatic shock is discussed.     

The relationship between the vascular manifestations of shock produced by endotoxin,trauma, and hemorrhage. II. The possible role of the reticulo-endothelial system in resistance to each type of shock

In studies designed to establish the interrelationship between bacterial endotoxins and the vascular sequelae of hemorrhagic and traumatic shock, the effect of factors known to influence the phagocytic behavior of the reticulo-endothelial system (RES) were investigated. Measures which induced a so called "blockade" of the RES were uniformly associated with an exacerbation of the vascular effects of the endotoxin of E. coli. Such pretreatment also counteracted the cross-tolerance induced by endotoxins against the lethal effects of hemorrhage or drum trauma. The vascular reactions characteristic of irreversible hemorrhagic shock could be simulated by a combination of pretreatment with carbon or proferrin and the infusion of small doses of E. coli endotoxin. An increase in the phagocytic activity of the RES, induced by repeated injections of certain colloids, was associated with an enhanced tolerance of shock. Measurement of carbon clearance values indicated that although an augmented phagocytic capacity was present in rats with induced tolerance to bacterial endotoxins, the development of resistance to trauma was not associated with a comparable change in the phagocytic function of the RES.     

Rapamycin‐mediated suppression of renal cyst expansion in del34 Pkd1−/− mutant mouse embryos: An investigation of the feasibility of renal cyst prevention in the foetus

Aim: Polycystic kidney disease (PKD) in humans involves kidney cyst expansion beginning in utero. Recessive PKD can result in end‐stage renal disease (ESRD) within the first decade, whereas autosomal dominant PKD (ADPKD), caused by mutations in the PKD1 or PKD2 gene, typically leads to ESRD by the fifth decade of life. Inhibition of mTOR signalling was recently found to halt cyst formation in adult ADPKD mice. In contrast, no studies have investigated potential treatments to prevent cyst formation in utero in recessive PKD. Given that homozygous Pkd1 mutant mice exhibit cyst formation in utero, we decided to investigate whether mTOR inhibition in utero ameliorates kidney cyst formation in foetal Pkd1 homozygous mutant mice. Methods: Pregnant Pkd1^+/? female mice (mated with Pkd1^+/? male mice) were treated with rapamycin from E14.5 to E17.5. Foetal kidneys were dissected, genotyped and evaluated by cyst size as well as expression of the developmental marker, Pax2. Results: Numerous cysts were present in Pkd1^?/? kidneys, which were twice the weight of wild‐type kidneys. Cyst size was reduced by a third in rapamycin‐treated Pkd1^?/? kidney sections and kidney mass was reduced to near wild‐type levels. However, total cyst number was not reduced compared with control embryos. Pax2 expression and kidney development were unaltered in rapamycin‐treated mice but some lethality was observed in Pkd1^?/? null embryos. Conclusion: Rapamycin treatment reduces cyst formation in Pkd1^?/? mutant mice; therefore, the prevention of kidney cyst expansion in utero by mTOR inhibition is feasible. However, selective rapamycin‐associated lethality limits its usefulness as a treatment in utero.