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Photodisruption in the human cornea as a function of laser pulse width.

BACKGROUND: We investigated the role of laser pulse width in determining fluence thresholds and efficiency for corneal photodisruption. METHODS: A laser system that delivers a wide range of pulse energies and pulse widths was used to produce ablations at pulse widths from 100 femtoseconds (fs) to 7 nanoseconds (ns). The laser-induced breakdown fluence threshold at each pulse width was determined by monitoring individual plasma emissions. Using multiple shots, the photodisruption threshold and cutting depth at each pulse width were determined histologically. RESULTS: Corneal breakdown thresholds decreased at a faster rate from 7 ns to approximately 10 picoseconds (ps), compared to further reductions in pulse width below 10 ps, where little variation was seen. Breakdown for pulse widths below 10 ps showed little intershot variability, resulting in highly reproducible fluence thresholds. Corneal tissue examined histologically showed similar fluence dependency. CONCLUSIONS: Corneal tissue photodisruption thresholds demonstrate pulse width dependence. At pulse widths less than 10 ps and with fluences near the breakdown threshold, ablations are maximally precise and efficient. These findings suggest optimal laser parameters for corneal surgery.

Cornea↗

Daily changes in oxygen saturation and pulse rate associated with particulate air pollution and barometric pressure.

Epidemiologic studies have linked fine particulate air pollution with increases in morbidity and mortality rates from cardiopulmonary complications. Although the underlying biologic mechanisms responsible for this increase remain largely unknown, potential pathways include transient declines in blood oxygenation and changes in pulse rate following exposures to particulate air pollution episodes. This study evaluated potential associations between daily measures of respirable particulate matter (PM) with pulse rate and oxygen saturation of the blood. Pulse rate and oxygen saturation (Spo2) using pulse oximetry were measured daily in 90 elderly subjects living near air pollution monitors during the winter of 1995-96 in Utah Valley. We also evaluated potential associations of oxygen saturation and pulse rate with barometric pressure. Small but statistically significant positive associations between day-to-day changes in Spo2 and barometric pressure were observed. Pulse rate was inversely associated with barometric pressure. Exposure to particulate pollution was not significantly associated with Spo2 except in male participants 80 years of age or older. Increased daily pulse rate, as well as the odds of having a pulse rate 5 or 10 beats per minute (bpm) above normal (normal is defined as the individual's mean pulse rate throughout the study period), were significantly associated with exposure to particulate pollution on the previous 1 to 5 days. The medical or biologic relevance of these increases in pulse rate following exposure to particulate air pollution requires further study.

Aged↗

Induction of natural killer cell activity and perforin and granzyme B gene expression following continuous culture of short pulse with interleukin-12 in young and old mice.

Anticancer immunotherapy with cytokines is often limited by the occurrence of severe toxicity, particularly in older age groups, which are characterized by a reduced tolerance to antineoplastic therapies. We, and others, have recently demonstrated the efficacy of pulsing procedures with IL-2 as a new therapeutic strategy to induce antitumor cytotoxic cells. The aim of this paper was to evaluate the effect of IL-12 on NK cell activity in young and old mice and to investigate the possibility of inducing NK cytotoxicity and perforin and granzyme B gene expression through a brief exposure of spleen lymphocytes from young and old mice to IL-12. Pulsed lymphocytes were compared with non-pulsed cells cultured continuously in IL-12. IL-12 was able to boost both endogenous and IL-2-induced NK cell activity in young and old mice; the levels of cytotoxicity were lower in old than in young animals although the relative increase of IL-12 plus IL-2 versus IL-2 alone was greater for old mice. Comparable levels of NK cell activity were obtained in pulsed (5 min-1 hour) and non-pulsed lymphocytes from both young and old mice after one or three days of culture. The efficacy of the pulsing procedure was evident in both endogenous and IL-2-induced NK cytotoxicity. The mRNA encoding perforin and granzyme B were markedly and similarly enhanced in both IL-12-pulsed and non-pulsed lymphocytes in comparison with control cells. The results demonstrate the effectiveness of IL-12 pulsing in inducing antitumor cytotoxic cells, suggesting the possibility of using IL-12 pulsing, alone or in combination with IL-2, in the immunotherapy of both young and old subjects.

Aging↗

Effects of delay on the type and velocity of travelling pulses in neuronal networks with spatially decaying connectivity.

We study a one-dimensional model of integrate-and-fire neurons that are allowed to fire only one spike, and are coupled by excitatory synapses with delay. At small delay values, this model describes a disinhibited cortical slice. At large delay values, the model is a reduction of a model of thalamic networks composed of excitatory and inhibitory neurons, in which the excitatory neurons show the post-inhibitory rebound mechanism. The velocity and stability of propagating continuous pulses are calculated analytically. Two pulses with different velocities exist if the synaptic coupling is larger than a minimal value; the pulse with the lower velocity is always unstable. Above a certain critical value of the constant delay, continuous pulses lose stability via a Hopf bifurcation, and lurching pulses emerge. The parameter regime for which lurching occurs is strongly affected by the synaptic footprint (connectivity) shape. A bistable regime, in which both continuous and lurching pulses can propagate. may occur with square or Gaussian footprint shapes but not with an exponential footprint shape. A perturbation calculation is used in order to calculate the spatial lurching period and the velocity of lurching pulses at large delay values. For strong synaptic coupling, the velocity of the lurching pulse is governed by the tail of the synaptic footprint shape. Moreover, the velocities of continuous and lurching pulses have the same functional dependencies on the strength of the synaptic coupling strength gsyn: they increase logarithmically with gsyn for an exponential footprint shape, they scale like (In gsyn)1/2 for a Gaussian footprint shape, and they are bounded for a square footprint shape or any shape with a finite support. We find analytically how the axonal propagation velocity reduces the velocity of continuous pulses; it does not affect the critical delay. We conclude that the differences in velocity and shape between the front of thalamic spindle waves in vitro and cortical paroxysmal discharges stem from their different effective delays.

Algorithms↗

Threshold determinations for selective retinal pigment epithelium damage with repetitive pulsed microsecond laser systems in rabbits.

BACKGROUND AND OBJECTIVE: In both clinical and animal studies, it has been shown that repetitive short laser pulses can cause selective retinal pigment epithelium damage (RPE) with sparing of photoreceptors. Our purpose was to determine the ophthalmoscopic and angiographic damage thresholds as a function of pulse durations by using different pulsed laser systems to optimize treatment modalities. MATERIALS AND METHODS: Chinchilla-breed rabbits were narcotized and placed in a special holding system. Laser lesions were applied using a commercial laser slit lamp, contact lens, and irradiation with a frequency-doubled Nd:YLF laser (wave-length: 527 nm; repetition rate: 500 Hz; number of pulses: 100; pulse duration: 5 micros, 1.7 micros, 200 ns) and an argon-ion laser (514 nm, 500 Hz, 100 pulses, 5 micros and 200 ms). In all eyes, spots with different energies were placed into the regio macularis with a diameter of 102 microm (tophat profile). After treatment, fundus photography and fluorescein angiography were performed and radiant exposure for ED50 damage determined. Speckle measurements at the fiber tips were performed to determine intensity peaks in the beam profile. RESULTS: Using the Nd:YLF laser system, the ophthalmoscopic ED50 threshold energies were 25.4 microJ (5 micros), 32 microJ (1.7 micros), and 30 microJ (200 ns). The angiographic ED50 thresholds were 13.4 microJ (5 micros), 9.2 microJ (1.7 micros), and 6.7 microJ (200 ns). With the argon laser, the angiographic threshold for 5 micros pulses was 5.5 microJ. The ophthalmoscopic threshold could not be determined because of a lack of power; however, it was > 12 microJ. For 200 ms, the ED50 radiant exposures were 20.4 mW ophthalmoscopically and 19.2 mW angiographically. Speckle factors were found to be 1.225 for the Nd:YLF and 3.180 for the argon laser. Thus, the maximal ED50 -threshold radiant exposures for the Nd:YLF were calculated to be 362 mJ/cM2 (5 micros), 478 mJ/cm2 (1.7 micros), and 438 mJ/cm2 (200 ns) ophthalmoscopically. Angiographically, the thresholds were 189 mJ/cm2 (5 micros), 143 mJ/cm2 (1.7 micros), and 97 mJ/cm2 (200 ns). For the argon laser, the maximal ED50 radiant exposure threshold was 170 mJ/cm2 angiographically. CONCLUSION: The gap between the angiographic and the ophthalmoscopic thresholds for the 200 ns regime (4.5 times above angiographic ED50) was wider than for the 1.7 micros regime (3.3 times above the angiographic ED50). This would suggest the appropriate treatment would be 200 ns pulses. However, histologies have yet to prove that nonvisible mechanical effects increase with shorter pulse durations and could reduce the "therapeutic window." When comparing the thresholds with 5 micros pulses from the argon and Nd:YLF laser, it demonstrates that intensity modulations in the beam profile must be considered.

Animals↗

[Cell membrane electroporator with digital generation of random shaped pulses].

A Digital Poration System (DPS), a versatile device for electrotreatment of biological objects by electric field pulses; was designed, constructed, and implemented. A feature distinguishing DPS from the currently available electroporators based on capacitor discharge through the load is the use of a digital-to-analog converter card as a generator of pulses applied for electroporation of biological membranes, with further amplification of the pulse by both voltage and current. The shape of pulses, including bipolar pulses, is arbitrarily programmable in DPS unlike other electroporators providing exponentially decaying and square-wave pulses only. Thus, the application area of DPS is substantially extended. In DPS, many of the drawbacks inherent in capacitor electroporators are removed, including the need for an additional external pulse analyzer monitoring and logging the electroporation processes, the necessity to recharge the capacitor before any new pulse, a poor precision of setting and measuring the pulse parameters, the need for an additional generator of long-lasting low-voltage signals for electrophoresis of ions into the porated object, the need for additional AC generators for the alignment of cells before, after, and during electroporation, and the need for an additional microprocessor to control multi-pulse and/or repetitive protocols. DPS provides a slew rate of about 1 V/1 ns required for the electroporation of most mammalian somatic cells, with +/- 250 V output voltage and 500 Ohm load resistance. The application area of DPS is much wider than for the available porators. It includes electrochemotherapy, cell electrofusion, oocyte activation by mimicking calcium waves (the latter two are the crucial components of mammalian organism cloning technology), dielectrophoretic bunching and orientation ordering of cells, sorting of cells, and electrophoresis of charged species into the cells.

Cell Membrane↗

Abnormal delay in recovery of pulse rate in 9454 patients referred for treadmill exercise test to Cleveland Clinic, 1990-1997--an independent predictor of excess mortality.

OBJECTIVE: The objective of this article is to present results from the latest of 3 recent reports from the Cleveland Clinic on excess mortality associated with abnormal delay in the recovery of an elevated pulse rate produced in a treadmill exercise test. This is done in the context of a long-standing medical interest in this phenomenon and its prognostic significance (see Comment section). BACKGROUND: Delay in return of the pulse rate after exercise has long attracted medical interest as a potentially unfavorable prognostic factor. However, this has not become a factor in the interpretation of the treadmill exercise test. Cardiologist staff members of the Cleveland Clinic have recently studied the mortality predictive effect of delay in pulse recovery in 3 different cohorts of patients given a treadmill exercise test (modified Bruce protocol). The newest, largest and most complete of these studies is the source article for this report. STUDY DESIGN: This was an observational follow-up (FU) study with a median of 5.2 years (range 1.4-8.7 years). The patients were categorized as abnormal pulse recovery at 1 minute after peak exercise with decrease of only 12 beats per minute or less, and normal if >12 beats per minute. These classes were combined with dichotomous classes according to the exercise test result and with other associated risk factors. RESULTS: A good approximation of exposure was achieved for each of the 4 pulse recovery/exercise test groups. From numerical data in the article, it was possible to derive aggregate mean annual mortality rates for these groups and selected combinations of pulse recovery with other risk factors. Mortality was lowest (2.8 per 1000) in the group with pulse recovery and exercise test both normal (66% of the total patients screened), and this was used as the "expected" rate, without adjustment for any differences in age. On this basis the excess death rate (EDR) was about 7 per 1000 per year when either pulse recovery or exercise test was abnormal, and 28 per 1000 when both were abnormal. Similar levels of EDR were found in the combinations of pulse recovery with other risk factors. CONCLUSION: Abnormal pulse recovery after the treadmill exercise test is a powerful and independent predictor of significant excess mortality.

Exercise Test↗

Non-invasive assessment of arterial stiffness by pulse-wave velocity correlates with endothelial dysfunction.

BACKGROUND: Pulse-wave velocity is the speed of the blood pressure wave to travel a given distance between two sites of the arterial system and is determined by the elasticity, wall thickness and blood density. Pulse-wave velocity correlates well with arterial distensibility and stiffness and is a useful non-invasive index to assess arteriosclerosis. Arterial endothelial dysfunction is one of the key early events in atherogenesis, preceding structural atherosclerotic changes. This study sought to establish the correlation of non-invasive estimation of arterial wall stiffness by pulse-wave velocity and its association with endothelial dysfunction in subjects at higher risk for atherosclerosis. METHODS AND RESULTS: A total of 102 subjects (60 males and 42 females, mean age 51 years), including those with hypertension (n = 39), type 2 diabetes mellitus (n = 26), concomitant type 2 diabetes mellitus and hypertension (n = 29) and primary dyslipidemia without diabetes mellitus and hypertension (n = 8). Pulse-wave velocity was measured by the Vascular Profiler 1000 (VP-1000) waveform analysis and vascular evaluation system, an automated, non-invasive, screening device. Endothelial function was assessed by flow-mediated dilation of the brachial artery. The brachial-artery diameter was measured on B-mode ultrasound images, with the use of a 7.0 MHz linear-array transducer. Mean brachial artery pulse-wave velocity on the right extremity was 1699 cm/s and on the left 1694 cm/s. Mean flow-mediated dilation in the study subjects was 3.6 +/- 8.4%. Mean brachial artery pulse-wave velocity in the right and left extremities and the higher value of brachial artery pulse-wave velocity of the two extremities showed a negative and significant correlation with flow-mediated dilation of the brachial artery (correlation coefficient r = -0.32, p = 0.001; r = -0.40 p < 0.0001; r = -0.37, p = 0.001, respectively). Mean heart-brachial pulse-wave velocity also showed a negative and significant correlation with flow-mediated dilation of the brachial artery (r = -0.23, p = 0.022). Mean arterial stiffness was 36.2 +/- 22%. Arterial stiffness in the right extremity and the higher value of the two extremities showed a negative and significant correlation with flow-mediated dilation of the brachial artery (correlation coefficient r = -0.31, p = 0.002; r = -0.32, p = 0.001, respectively). CONCLUSIONS: Increased values of pulse-wave velocity reflecting upon arterial stiffness show an excellent correlation with reduced values of brachial artery flow-mediated dilation. We propose that the non-invasive modalities of estimation of the pulse-wave velocity and endothelial function estimation by flow-mediated dilation of brachial artery be used in clinical practice in assessment of pre-clinical atherosclerosis.

Aged↗

Sequential pulse defibrillation for implantable defibrillators.

A technique is described that reduces defibrillation threshold for automatic implantable defibrillators, permits either reducing the size of the pulse generator or increasing the effectiveness of the pulse generator, and provides an increased safety factor. Defibrillation threshold was compared in 12 anesthetized dogs with mean (+/- SD) body weight of 21.6 +/- 3.4 kg for two defibrillating modalities: 1) single pulse technique with current flowing from electrodes in the right ventricle to electrodes either in the superior vena cava or on the left ventricular epicardium, and 2) sequential pulse technique. The sequential pulse technique tested uses two pulses and three or four electrodes. Current of the first 5-ms pulse flows from the superior vena caval electrode to an electrode in the right ventricle, and after a 1-ms interval, current of the second pulse flows from electrodes on the left ventricular epicardium to the right ventricular electrode. Ventricular defibrillation threshold was reduced by 56% to 6.3 +/- 1.03 joules (mean +/- SEM) (P less than 0.01). Because defibrillation threshold is less for sequential pulse defibrillation than for conventional techniques, sequential pulse defibrillators can be smaller and more effective than previously available devices.

Animals↗

Optimization of epicardial electrode size and implant site for reduced sequential pulse defibrillation thresholds.

The influence of epicardial electrode surface area and implant site on sequential pulse defibrillation threshold was investigated in four isolated heart preparations. Electrodes with surface areas of 2.5, 5.0, and 10.0 cm2 were each sutured, in random order, to the epicardial surface of the isolated heart at each of four sites: mid-ventral left ventricle (LV); mid-dorsal LV; lateral-apical LV; and lateral-basal LV. The epicardial electrode is one of the electrodes in a three-electrode, two-current pathway, sequential pulse system. The first two electrodes, which are catheter-mounted, are located in the right ventricular apex (RVA) and superior vena cava (SVC). In sequential pulse defibrillation, one shock is delivered from the SVC to the RVA, followed 1 msec later by a second shock delivered from the third electrode to the RVA. Sequential pulse defibrillation threshold was obtained with each epicardial electrode used at each site. A single-pulse (SVC to RVA) catheter threshold was also obtained in each heart. The overall mean sequential pulse threshold was 47 per cent less than the mean single-pulse threshold (P less than 0.001). Increasing patch size reduced sequential pulse threshold (P less than 0.03), but no significant effect of patch location could be demonstrated. It is concluded that sequential pulse defibrillation is superior to single-pulse catheter defibrillation and that increasing epicardial patch size is advantageous, although patch location does not influence thresholds in the isolated heart.

Animals↗

[Pulsed Doppler in the diagnosis of tricuspid insufficiency].

Forty-eight patients underwent M-Mode, 2D and pulsed Doppler echocardiography with systematic apical and subcostal examination of the mitral and tricuspid orifices to determine the value of pulsed Doppler echo in the detection of tricuspid regurgitation. The fourty-eight patients, aged 12 to 69 years, were divided into 2 groups: Group I: 27 patients referred for cardiac catheterisation usually with a view to surgery. The majority of patients had rheumatic valvular, congenital heart disease or cardiomyopathies. All of these patients had phonocardiography, right and left heart catheterisation, right ventricular angiography and measurement od cardiac output. Group II: 21 control patients with no auscultatory, radiological or electrocardiographic changes. This group was studied to determine the specificity of pulsed Doppler examination of the tricuspid valve and the patients only underwent echocardiography. Selective right ventricular angiography was selected as the reference. The sensitivity, specificity and predictive value of pulsed Doppler echocardiography in the positive diagnosis of tricuspid regurgitation were determined. Its value in quantifying tricuspid regurgitation was also analysed. The sensitivity of pulsed Doppler was 93 p. 100 in this series: all but one case of angiographically proven tricuspid regurgitation were detected by the finding of unequivocal systolic turbulence in the right atrium. The specificity of pulsed Doppler was 91 p. 100. The positive predictive value of systolic turbulence in the right atrium was 81 p. 100. The only reliable criteria for quantifying the regurgitation were the intensity of the acoustic signal and the spatial extension of intraatrial turbulent flow: all patients with turbulent flow propagating as far as the superior wall of the right atrium or the inferior vena cava had angiographically severe tricuspid regurgitation. A comparison with other paraclinical methods of detecting tricuspid regurgitation showed that pulsed Doppler echocardiography is the most sensitive tool at the clinician's disposal for diagnosing this lesion: the sensitivity of auscultation and phonocardiography was 50 p. 100, jugular pulse tracings 54 p. 100, right heart catheterisation 50 p. 100, and pulsed Doppler echocardiography 93 p. 100. Pulsed Doppler echocardiography may even be superior to angiography which has, until now, been the method of reference for diagnosing tricuspid regurgitation.

Adolescent↗

Proximal and distal pulse pressure after acute antihypertensive vasodilating drugs in Wistar-Kyoto and spontaneously hypertensive rats.

OBJECTIVE: In a previous study (J Hypertens 1993, 11:135-139) our group showed that in anaesthetized rats, although pulse pressure increased from the proximal (common carotid artery) to the distal (terminal aorta) portion of the aorta in normotensive Wistar-Kyoto (WKY) rats, such a pulse pressure gradient was not observed in spontaneously hypertensive rats (SHR) which had identical values of proximal and distal pulse pressure. The purpose of the present study was to show, in awake SHR, in comparison with awake WKY rats, that the lack of pulse pressure gradient might be functionally reversed after acute administration of vasodilating agents. METHODS: The drugs (administered intra-arterially) were an angiotensin converting enzyme inhibitor (perindoprilat; 2 mg/kg), a calcium antagonist (nicardipine; 30 micrograms/kg), a peripheral vasodilator (hydralazine; 200 micrograms/kg) and placebo (isotonic saline). Blood pressure was evaluated invasively. RESULTS: In untreated rats it was noticed that pulse pressure increased physiologically from the proximal to the distal part of the aorta for the same mean arterial pressure in WKY rats, whereas no pulse pressure gradient was observed in SHR. With acute drug administration, marginal modifications were observed in WKY rats, but mean arterial pressure was reduced significantly in SHR (hydralazine > perindoprilat > nicardipine). Proximal pulse pressure was decreased significantly with perindoprilat or nicardipine but was unchanged with hydralazine. Distal pulse pressure was unchanged, except for an increase in the nicardipine-treated group. Heart rate was increased significantly by hydralazine. CONCLUSION: The results show that, although all of the drugs studied decreased mean arterial pressure in SHR, only the calcium antagonist nicardipine and the angiotensin converting enzyme inhibitor perindoprilat reduced proximal pulse pressure. This dissociation between the effects on mean arterial pressure and proximal and distal pulse pressure can be explained by the preferential action of the different antihypertensive agents on large arteries and wave reflections, producing different patterns in the pulsatile component of the heart load.

Angiotensin-Converting Enzyme Inhibitors↗

Optimal truncation of defibrillation pulses.

The statement that the optimal pulse for defibrillation has not yet been discovered implies that an ideal pulse exists, but that it is different in shape, duration, and energy as compared to pulses of today. The optimum pulse is that which can defibrillate with lowest energy. Reduction of energy can be reached twofold: by looking for a pulse duration with lowest energy threshold, and by finding the optimal truncation with lowest refibrillating effect. Assuming that there is also a rheobase in defibrillation below which no defibrillating but probably a refibrillating effect exists, the exponential pulse should be truncated if it intersects with the rheobase. Combining the fundamental law of electrostimulation with this boundary condition allows for the mathematical solution of the above problem of optimal energy. Defibrillation can be optimized with respect to pulse duration or tilt and to energy efficiency. The most important parameter in determining other optimized parameters such as output capacitor is the chronaxie. The calculations reveal that the "concept of constant energy" does not accurately describe defibrillation, that today's implantable cardioverter defibrillator devices possess refibrillating tilts, that pulse durations should be programmed to values between 4 and 10 msec, and that smaller output capacitors around 30 microF would minimize the energy requirements. Whether optimized monophasic pulses are inferior or equal to biphasic pulses needs further experimental studies.

Animals↗

Responses of bat inferior collicular and auditory cortical neurons to pulsatile amplitude modulated sound pulses.

Under free field stimulation conditions, this study examined the responses of inferior collicular and cortical neurons of the big brown bat, Eptesicus fuscus, to pulsatile amplitude modulated sound pulses by means of temporally patterned pulse trains. When the pulse trains were delivered at different pulse repetition rates between 1 and 100 pps, inferior collicular neurons can follow pulse repetition at a higher rate than can auditory cortical neurons. 85% of 40 inferior collicular neurons studied always discharged impulses to each presented pulse delivered at repetition rates of up to 40 pps and 20% of these neurons could follow the repetition rate throughout the entire range of repetition rates tested. In contrast, only 60% of 56 auditory cortical neurons could follow a repetition rate up to 10 pps. At higher repetition rates, they only discharged impulses to the first pulse of each pulse train. According to variation in number of impulses, filtering properties of responses of inferior collicular and auditory cortical neurons to pulse repetition rate can be described as low-pass, high-pass, or band-pass. Most (63%) inferior collicular neurons behaved like band-pass filters to pulse repetition rate while most auditory cortical neurons behaved like all-pass (52%) or low-pass (37%) filters. Possible mechanisms underlying the different filtering properties between the inferior collicular and auditory cortical neurons are discussed.

Acoustic Stimulation↗

Short-term changes in the Ca2+-exocytosis relationship during repetitive pulse protocols in bovine adrenal chromaffin cells.

Stimulus-secretion coupling was monitored with capacitance detection in bovine chromaffin cells recorded in perforated patch mode and stimulated with trains of depolarizing pulses. A subset of stimulus trains evoked a response with a Ca2+-exocytosis relationship identical to that obtained for single depolarizing pulses (Engisch and Nowycky, 1996). Other trains evoked responses with enhanced or diminished Ca2+ efficacy relative to this input-output function. The probability of obtaining a particular Ca2+-exocytosis relationship was correlated with the amount of Ca2+ entry per pulse, such that shorter pulses or smaller currents were associated with the greatest efficacy, and longer pulses and larger currents with the lowest efficacy. Apparent enhancements in Ca2+ efficacy were not caused by residual Ca2+ summing between pulses, because decreasing the interval between pulses usually reduced efficacy in the same cell; conversely, increasing the interval between pulses did not prevent an enhanced Ca2+-exocytosis relationship. Apparent decreases in Ca2+ efficacy were not caused by depletion of an available pool of release-ready vesicles, because an equivalent amount of total Ca2+ entry during a single long depolarizing pulse usually evoked a much larger secretory response in the same cell. Finally, there were no striking differences in global Ca2+ levels monitored with the fluorescent indicator Fura Red that could account for apparent changes in Ca2+ efficacy during repetitive stimulus protocols. It appears that in chromaffin cells, the Ca2+-exocytosis relationship is subject to activity-dependent changes during a stimulus train and can be modulated up or down from a basal state accessed by single pulse stimulations.

Action Potentials↗

The use of papaverine in arterial sheaths to prevent loss of femoral artery pulse in pediatric cardiac catheterization.

This study evaluated the efficacy of intraarterial papaverine infusion after pediatric cardiac catheterization in reducing the incidence of lost pulse. This study was conducted at a teaching pediatric hospital and was designed as a randomized, prospective, double-blind, placebo-controlled study. Patients were children 5 years old or less undergoing antegrade and retrograde heart catheterization. The intervention used was an intraarterial infusion of placebo or 1.5 mg/kg papaverine after catheterization. Bilateral femoral artery ultrasound study was performed pre- and postcatheterization, including two-dimensional, color, spectral, and pulsatility index analysis. Outcome measures included clinical loss of pulse, ultrasound findings, plus other clinical factors. Fifty-six patients participated in the study (28 per group). Six patients clinically lost the pulse in the catheterized arteries [four in the papaverine and two in the placebo groups (p > 0.64)]. Clinical loss of pulse correlated with diminished pulsatility index (p < 0.035). The use of papaverine did not prevent decreased pulse or pulsatility index (p > 0.79). Increased arterial time was the only clinical factor associated with lost pulse (p < 0.0004). Pulsatility index <3.34 correlated with loss of pulse in the catheterized artery. The results indicated that intraarterial papaverine infusion after femoral artery catheterization does not prevent loss of pulse in the catheterized artery, and decreased pulsatility index correlates with diminished pulse and represents a good noninvasive method of evaluating femoral artery patency and flow.

Cardiac Catheterization↗

Pulse rate, coronary heart disease, and death: the NHANES I Epidemiologic Follow-up Study.

To determine whether associations of elevated resting pulse rate with CHD incidence or death in white men are independent of other risk factors and whether such associations exist for women and blacks, data were examined from the NHANES I Epidemiologic Follow-up Study. Over a follow-up period of 6 to 13 years, elevated RR for CHD incidence were found for older white men with baseline pulse greater than 84 beats/min compared with less than 74 beats/min after controlling multiple risk factors (RR = 1.37, 95% CL 1.02, 1.84). Risks of death from all causes, cardiovascular diseases, and noncardiovascular diseases were also elevated for white men with elevated pulse rate independent of other risk factors. CHD incidence was increased in white women with elevated pulse rate. Risks of death from all causes, cardiovascular diseases, and noncardiovascular diseases, were also elevated for white men with elevated pulse rate independent of other risk factors. CHD incidence was increased in white women with elevated pulse rate. Risk of death from all causes and cardiovascular diseases was elevated in black men and women with elevated pulse rate. Risk of death from noncardiovascular disease was elevated in black men with elevated pulse rate. The association with cardiovascular death was particularly striking in black women, even after adjusting for baseline risk factors (RR 3.03, 95% CL 1.46, 6.28). Further studies are needed to assess associations of pulse rate with CHD in blacks and to elucidate mechanisms in all groups.

Aged↗

Determinants of weak femoral artery pulse in dogs with mitral valve prolapse.

In three substudies encompassing 247 dogs from two breeds predisposed to myxomatous mitral valve disease (MMVD), femoral artery pulse strength was palpated and related to potential explanatory factors, including quantitative echocardiographic measures of MMVD, aortic and femoral artery diameter and wall thickness and blood pressure. In addition, in 109 Cavalier King Charles Spaniels (of which 61 were included in the three substudies mentioned above), the relation between femoral artery pulse strength and presence of thrombocytopenia was investigated. In 26% of the dogs, a pulse </=50% of normal strength was detected; six dogs (2.0%) had an absent pulse unilaterally or bilaterally. Mitral valve prolapse severity, degree of obesity, heart rate and age all influenced femoral artery pulse strength negatively. Weak femoral artery pulses were not related to clinical signs or to decreased pulse pressure or stroke volume. A weak femoral artery pulse reflected reduced artery diameter and/or distension rather than occlusion. In conclusion, weak femoral artery pulses in dogs with MMVD seem to be associated with regional/local reductions in blood flow and not arteriosclerosis or platelet count.

Animals↗