Daniel W. Bergner

Persistent sympathoexcitation long after submaximal exercise in subjects with and without coronary artery disease

There is an increased risk of cardiac events after exercise, which may, in part, be mediated by the sympathoexcitation that accompanies exercise. The duration and extent of this sympathoexcitation following moderate exercise is unknown, particularly in those with coronary artery disease (CAD). Twenty control subjects (mean age, 51 years) and 89 subjects with CAD (mean age, 58 years) underwent two 16-min bicycle exercise sessions followed by 30-45 min of recovery. Session 1 was performed under physiological conditions to peak workloads of 50-100 W. In session 2, parasympathetic blockade with atropine (0.04 mg/kg) was achieved at end exercise at the same workload as session 1. RR interval was continually recorded, and plasma catecholamines were measured at rest and selected times during exercise and recovery. Parasympathetic effect, measured as the difference in RR interval with and without atropine, did not differ between controls and CAD subjects in recovery. At 30 and 45 min of recovery, RR intervals were 12% and 9%, respectively, shorter than at rest. At 30 and 45 min of recovery, plasma norepinephrine levels were 15% and 12%, respectively, higher than at rest. A brief period of moderate exercise is associated with a prolonged period of sympathoexcitation extending >45 min into recovery and is quantitatively similar among control subjects and subjects with CAD, with or without left ventricular dysfunction. Parasympathetic reactivation occurs early after exercise and is also surprisingly quantitatively similar in controls and subjects with CAD. The role of these autonomic changes in precipitating cardiac events requires further evaluation.

QT-RR hysteresis is caused by differential autonomic states during exercise and recovery

QT-RR hysteresis is characterized by longer QT intervals at a given RR interval while heart rates are increasing during exercise and shorter QT intervals at the same RR interval while heart rates are decreasing during recovery. It has been attributed to a lagging QT response to different directional changes in RR interval during exercise and recovery. Twenty control subjects (8 males, age 51 ± 6 yr), 16 subjects with type 2 diabetes (12 males, age 56 ± 8 yr), 71 subjects with coronary artery disease (CAD) and preserved left ventricular ejection fraction (LVEF) (≥50%) (51 males, age 59 ± 12 yr), and 17 CAD subjects with depressed LVEF (<50%) (13 males, age 57 ± 10 yr) underwent two 16-min exercise tests followed by recovery. In session 2, parasympathetic blockade with atropine (0.04 mg/kg) was achieved at end exercise. QT-RR hysteresis was quantified as: 1) the area bounded by the QT-RR relationships for exercise and recovery in the range of the minimum RR interval at peak exercise to the minimum RR interval + 100 ms and 2) the difference in QT interval duration between exercise and recovery at the minimum RR interval achieved during peak exercise plus 50 ms (ΔQT). The effect of parasympathetic blockade was assessed by substituting the QT-RR relationship after parasympathetic blockade. QT-RR hysteresis was positive in all groups at baseline and reversed by parasympathetic blockade (P < 0.01). We conclude that QT-RR hysteresis is not caused by different directional changes in RR interval during exercise and recovery. Instead, it is predominantly mediated by differential autonomic nervous system effects as the heart rate increases during exercise vs. as it decreases during recovery.

Effect of informed consent format on patient anxiety, knowledge, and satisfaction.

BACKGROUND Multiple formats have been used to deliver information needed for informed consent before a medical procedure, but data comparing formats are conflicting. METHODS Sixty-three patients (45 men, age 61 ± 16 years) undergoing an initial diagnostic cardiac electrophysiology study were randomly assigned to 1 of 3 groups: oral, written, or video informed consent using a standardized text for all 3 formats. Anxiety levels were assessed with the Spielberger State-Trait Anxiety Inventory (STAI), and questionnaires were used to assess patient comprehension and satisfaction with the informed consent process. Physician time needed to obtain informed consent was also measured. The effect of informed consent format on anxiety state was evaluated by comparing STAI before and after consent. Multivariable analysis was performed to assess the effects of baseline characteristics on the state anxiety scores. RESULTS For the oral, written, and video formats, the mean anxiety trait scores were 39 ± 9, 34 ± 8, and 31 ± 7, respectively (P = .005), and baseline anxiety state scores were 49 ± 12, 37 ± 12, and 36 ± 11, respectively (P = .0006). None of the formats had a significant effect on patient anxiety state after consent was obtained. After the procedure, anxiety state declined (P < .0001). There were no differences among the comprehension scores, and patient satisfaction was equivalent among formats. The oral format required the longest physician time (P = .06). CONCLUSION For electrophysiologic testing, all 3 formats have similar effects on anxiety and produce equivalent patient comprehension. The oral format requires more physician time. Given the standardization achievable with a written or video format, physicians may consider these options to facilitate obtaining informed consent.

Detection of cardiovascular autonomic neuropathy using exercise testing in patients with type 2 diabetes mellitus

AIMS This study investigated autonomic nervous system function in subjects with diabetes during exercise and recovery. METHODS Eighteen type 2 diabetics (age 55±2 years) and twenty healthy controls (age 51±1 years) underwent two 16-min bicycle submaximal ECG stress tests followed by 45 min of recovery. During session #2, atropine (0.04 mg/kg) was administered at peak exercise, and the final two minutes of exercise and entire recovery occurred under parasympathetic blockade. Plasma catecholamines were measured throughout. Parasympathetic effect was defined as the difference between a measured parameter at baseline and after parasympathetic blockade. RESULTS The parasympathetic effect on the RR interval was blunted (P=.004) in diabetic subjects during recovery. Parasympathetic effect on QT-RR slope during early recovery was diminished in the diabetes group (diabetes 0.13±0.02, control 0.21±0.02, P=.03). Subjects with diabetes had a lower heart rate recovery at 1 min (diabetes 18.5±1.9 bpm, control 27.6±1.5 bpm, P<.001). CONCLUSIONS In subjects with well-controlled type 2 diabetes, even with minimal evidence of CAN using current methodology, altered cardiac autonomic balance is present and can be detected through an exercise-based assessment for CAN. The early post-exercise recovery period in diabetes was characterized by enhanced sympathoexcitation, diminished parasympathetic reactivation and delay in heart rate recovery.

Inhibition of Rotavirus Infectivity by a Neoglycolipid Receptor Mimetic

Group A rotaviruses are a major cause of diarrhea in the young of many mammalian species. In rotavirus infected piglets mortality can be as high as 60%. Previous research in this laboratory has identified a porcine intestinal GM3 ganglioside receptor that is required for sialic acid-dependent rotavirus recognition of host cells. In addition, we previously demonstrated exogenously added GM3 can competitively inhibit porcine rotavirus binding and infectivity of host cells in vitro. Sialyllactose, the carbohydrate moiety of GM3, is approximately 3 orders of magnitude less effective than GM3 at inhibiting rotavirus binding to cells. Furthermore, production of therapeutic quantities of GM3 ganglioside for use as an oral carbomimetic in swine is cost prohibitive. In an effort to circumvent these problems, a sialyllactose-containing neoglycolipid was synthesized and evaluated for its ability to inhibit rotavirus binding and infectivity of host cells. Sialyllactose was coupled to dipalmitoylphosphatidylethanolamine (PE) by reductive amination and the product (SLPE) purified by HPLC. Characterization of the product showed a single primulin (lipid) and resorcinol (sialic acid) positive band by thin layer chromatography and quantification of phosphate and sialic acid yielded a 1:1 molar ratio. Mass spectroscopy confirmed a molecular weight coinciding with SLPE. Concentration-dependent binding of rotavirus to SLPE was demonstrated using a thin-layer overlay assay. Using concentrations comparable to GM3, SLPE was also shown to inhibit rotavirus binding to host cells by 80%. Furthermore, SLPE was shown to decrease rotavirus infection of host cells by over 90%. Finally, preliminary results of in vivo animal challenge studies using newborn piglets in their natural environment, demonstrated SLPE afforded complete protection from rotavirus disease. The efficacy of SLPE in inhibiting rotavirus binding and infection in vitro and in vivo, coupled with its relatively low-cost, large-scale production capabilities make SLPE a promising candidate for further exploration as a possible prophylactic or therapeutic nutriceutical for combating rotavirus disease in animals. Most importantly, the results presented here provide proof of concept that the nutriceutical approach of providing natural or synthetic dietary receptor mimetics for protection against gastrointestinal virus infectious disease in all species is plausible.