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Biomedical subjects

Kingman P Strohl

Publications and source records attributed to Kingman P Strohl.

At least 19 recordsLinked to original sources
PubMed2006

Sleep apnea in acute coronary syndrome: high prevalence but low impact on 6-month outcome.

BACKGROUND AND PURPOSE: We postulate that the prevalence of sleep-disordered breathing (SDB) in subjects admitted with acute coronary syndrome (ACS) is high, self-report of SDB symptoms is helpful in identifying patients with ACS at risk for SDB, and prospective risk for adverse ACS outcomes is associated with SDB. PATIENTS AND METHODS: Consecutive patients admitted to the VA hospital with ACS over approximately 1 year were invited to participate. The Cleveland sleep habits questionnaire was administered, and a portable sleep study (Eden-trace, Level 3 monitoring) was performed within 72h of admission. RESULTS: Of 104 patients with complete and adequate sleep studies, 66.4% had an apnea-hypopnea index (AHI) >10/h, and 26.0%, an AHI>30 with the prevalent apnea pattern being obstructive (72.1%). Neither pre-test probability for sleep apnea per questionnaire (P=0.67) nor degree of subjective sleepiness (P=0.83) predicted SDB. Although symptoms of dyspnea and paroxysmal nocturnal dyspnea were significantly higher in SDB (AHI> or =10) compared to non-SDB (AHI<10) 6 months after admission for ACS, odds of readmission were not significantly different, and this lack of association persisted after covariate adjustment. The factors predicating readmission, but only at 1 month, were age and diabetes. CONCLUSIONS: In the setting of ACS, the prevalence of SDB was very high in this population and was not detected by self-reports of sleepiness or composite risk for SDB. The odds of adverse outcome for ACS up to 6 months were no different in patients with SDB compared to those without SDB, as compared to effects of an older age or presence of diabetes.

Acute Disease↗
PubMed2006

Graduate medical training, learning, relationships, and sleep loss.

An extensive literature exists regarding the potential effect of sleep loss on human performance and the recent regulatory changes that now limit the duty hours of resident-physicians. Recent studies and reviews emphasize the effects of sleepiness on medical errors of commission and to a lesser extent omission. This review focuses on an emerging literature on the effects of sleep loss on personal, social and professional growth and development of residents. As with the early literature on sleep loss and resident performance, this literature is largely at an observational level, but there is sufficient evidence from other professions to indicate that sleep loss will affect post-graduate career and life skills. A multi-dimensional approach is needed to counter the adverse outcomes of sleep loss and fatigue and might consist of education on healthy sleep habits, family outreach, personal alertness strategies, and reversal of bias if sleepiness is personally disclosed. The multi-dimensional approach might include not only resident physicians, but also residency program directors and attending physicians at their institutions.

Affect↗
PubMed2006

Domperidone and ventilatory behavior: Sprague-Dawley versus Brown Norway rats.

Domperidone, a dopamine D(2) receptor antagonist, is a tool for uncovering the tonic and dynamic effects of the peripheral dopaminergic system in unanesthestized animals. The hypothesis was that domperidone effects would vary between strains of the same species. Ventilatory behavior -- frequency and minute ventilation -- was measured by the plethysmographic method in unrestrained adult male Sprague-Dawley (SD: n=8) and Brown Norway (BN: n=8) rats before, during and after rapid transition to 100% O(2) after 5 min of 13% O(2)/3% CO(2). Tests were done 60 min after intraperitoneal injection of either vehicle (0.1% lactic acid in saline) or a dose of domperidone (0.1, 0.5, 1.0, or 5.0mg/kg) dissolved in vehicle, each on a separate day. Resting frequency and minute ventilation (mean+/-standard deviation) decreased after domperidone in the BN strain (e.g. 94.63/min+/-4.99 versus 87.37/min+/-9.59, p=0.42; 77.3 ml/min+/-9.25 versus 62.13 ml/min+/-11.5, p=0.019, respectively), but did not change in the SD. With increasing doses of domperidone the ventilatory response to hypoxia and reoxygenation became similar owing to a decrease in frequency and minute ventilation in the SD. At a dose altering SD hypoxic responses, the hypercapnic ventilatory response was not significantly affected. In conclusion, breathing frequency and minute ventilation over a challenge with hypoxia and reoxygenation differ with domperidone depending upon genetic background. We speculate that hypoxic ventilatory responses may be differently configured even among strains of the same species.

Animals↗
PubMed2006

Medical therapy for obstructive sleep apnea: a review by the Medical Therapy for Obstructive Sleep Apnea Task Force of the Standards of Practice Committee of the American Academy of Sleep Medicine.

A significant number of patients with obstructive sleep apnea neither tolerate positive airway pressure (PAP) therapy nor achieve successful outcomes from either upper airway surgeries or use of an oral appliance. The purpose of this paper, therefore, was to systematically evaluate available peer-reviewed data on the effectiveness of adjunctive medical therapies and summarize findings from these studies. A review from 1985 to 2005 of the English literature reveals several practical findings. Weight loss has additional health benefits and should be routinely recommended to most overweight patients. Presently, there are no widely effective pharmacotherapies for individuals with sleep apnea, with the important exceptions of individuals with hypothyroidism or with acromegaly. Treating the underlying medical condition can have pronounced effects on the apnea/hypopnea index. Stimulant therapy leads to a small but statistically significant improvement in objective sleepiness. Nonetheless, residual sleepiness remains a significant health concern. Supplemental oxygen and positional therapy may benefit subsets of patients, but whether these therapies reduce morbidities as PAP therapy does will require rigorous randomized trials. PAP therapy has set the bar high for successful treatment of sleep apnea and its associated morbidities. Nonetheless, we should strive towards the development of universally effective pharmacotherapies for sleep apnea. To accomplish this, we require a greater knowledge of the neurochemical mechanisms underlying sleep apnea, and we must use this infrastructure of knowledge to design well-controlled, adequately powered studies that examine, not only effects on the apnea/hypopnea index, but also the effects of pharmacotherapies on all health related outcomes shown beneficial with PAP therapy.

Benzhydryl Compounds↗
PubMed2005

Nitric oxide and cardiopulmonary hemodynamics in Tibetan highlanders.

When O2 availability is reduced unavoidably, as it is at high altitude, a potential mechanism to improve O2 delivery to tissues is an increase in blood flow. Nitric oxide (NO) regulates blood vessel diameter and can influence blood flow. This field study of intrapopulation variation at high altitude tested the hypothesis that the level of exhaled NO (a summary measure of pulmonary synthesis, consumption, and transfer from cells in the airway) is directly proportional to pulmonary, and thus systemic, blood flow. Twenty Tibetan male and 37 female healthy, nonsmoking, native residents at 4,200 m (13,900 ft), with an average O2 saturation of hemoglobin of 85%, participated in the study. The geometric mean partial pressure of NO exhaled at a flow of 17 ml/s was 23.4 nmHg, significantly lower than that of a sea-level reference group. However, the rate of NO transfer out of the airway wall was seven times higher than at sea level, which implied the potential for vasodilation of the pulmonary blood vessels. Mean pulmonary blood flow (measured by cardiac index) was 2.7 +/- 0.1 (SE) l/min, and mean pulmonary artery systolic pressure was 31.4 +/- 0.9 (SE) mmHg. Higher exhaled NO was associated with higher pulmonary blood flow; yet there was no associated increase in pulmonary artery systolic pressure. The results suggest that NO in the lung may play a key beneficial role in allowing Tibetans at 4,200 m to compensate for ambient hypoxia with higher pulmonary blood flow and O2 delivery without the consequences of higher pulmonary arterial pressure.

Adaptation, Physiological↗
PubMed2005

Sleep symptoms and clinical markers of illness in patients with heart failure.

The purpose of this study was to survey patients with heart failure (HF) for sleep symptoms using a standardized questionnaire and correlate symptoms with conventional markers of clinical status. A self-report paper questionnaire was offered to patients presenting to a tertiary care HF clinic. Symptoms were grouped according to "risk" categories and correlated with routine clinical information. One hundred six (52.7% of 201 with all data) respondents had a high pretest probability for sleep apnea syndrome. Sixty three (31.3%) reported symptoms suggesting the presence of chronic insomnia; seven (3.5%) and eight (4%) reported symptoms of narcolepsy and restless legs syndrome, respectively. High-risk respondents for sleep apnea had a higher body mass index (p<0.001), were younger (p<0.05), and had a higher ejection fraction (p<0.05). The odds ratio (confidence interval) for paroxysmal nocturnal dyspnea (PND) to a complaint of sleepiness was 1.99 (1.1-3.6) and to a complaint of insomnia was 3.5 (1.8-6.5). In men, complaints of sleepiness in patients with PND were correlated, 4.47 (1.9-10.3), as was a correlation to high pretest probability for sleep apnea, 2.47 (1.1-5.5). There were no correlation of New York Heart Association status classification to high risk for sleep apnea, but a complaint of insomnia tended to occur with worsening functional status (p<0.05). There was only modest correlation of self-reported symptoms as elicited by a questionnaire and risk for sleep disorders with common clinical assessments for HF. Such collection of symptoms might be useful in establishing guidelines for routine sleep testing or as an adjunct to clinical trials.

Adolescent↗
PubMed2004

Incidence of serious adverse events during nocturnal polysomnography.

OBJECTIVES: The purpose of the study was to verify whether minimal concern is warranted in regard to serious adverse effects in the sleep laboratory. DESIGN: A prospective multicenter study PARTICIPANTS: Three scoring teams for 17 sleep laboratories. METHODS: Reports of adverse events occurring during polysomnography or identified upon scoring a study were collected over an 18-month time period. Incidence of mortality and adverse events were evaluated using a binomial distribution based on the Bernoulli process. RESULTS: Of 16,084 studies, the mortality rate during or 2 weeks after an adverse event, as noted, was 0.006%, and the overall rate of adverse events was 0.35%. CONCLUSIONS: Adverse event rates are low; however, procedures for handling medical emergencies or adverse events during or after polysomnography are prudent, and those studies performed for research should include preparedness for the possibility of adverse events.

Adult↗
PubMed2004

The fa leptin receptor mutation and the heritability of respiratory frequency in a Brown Norway and Zucker intercross.

We sought to determine whether the fa (leptin receptor) mutation was a major determinant of the putative obesity effects on respiratory frequency in an intercross between the Brown Norway (low breathing frequency, nonobese strain) and the Zucker (moderately high breathing frequency, with the fa mutation) strains. The hypothesis was that rats bearing one (heterozygote) or two (homozygote) alleles of the Glu296Pro point mutation (fa) would have a uniformly high respiratory frequency in the second filial (F2) generation, compared with wild-type animals. In addition to breathing frequency, tidal volume and minute ventilation were assessed during baseline, acute hypoxic (10% O2-0% CO2-balance nitrogen), hypercapnic (93% O2-7% CO2), hyperoxic (100% O2-0% CO2), and combined (10% O2-3% CO2-balance nitrogen) challenges in fa homozygote (fa/fa; n = 24), fa heterozygote (fa/wt; n = 33), and wild-type (wt/wt; n = 19) animals. Phenotypes were adjusted with stepwise regression analyses for the effects of age, sex, length, and litter size. Broad-sense heritability was estimated by examining the variance of the traits in first filial and F2 generations. ANOVAs were used to determine the mode of inheritance of the fa allele in the F2 generation. As anticipated, weight demonstrated the greatest overall broad-sense heritability (77%) and was the result of the recessive mutation. Breathing parameters during the hypoxic, hypercapnic, and combined challenges demonstrated a wide range of heritability from 5 to 96%, with a very nonuniform proportion of heritability explained by the leptin receptor. At best, for frequency 4.5 min into the hypercapnic hypoxic challenge, approximately 20% of the total heritability (approximately 67%) could be attributed to an effect of the leptin receptor mutation. We conclude that, unlike its major effect on weight, the effect of the fa allele is not a major gene involved in the regulation of breathing frequency.

Animals↗
PubMed2004

Inspired oxygen concentrations during positive pressure therapy.

OBJECTIVES: This study examined the effects of various factors that might influence the fraction of oxygen in inspired air (FiO (2)) in a human and in a model system during nasal positive pressure treatments. DESIGN AND METHODS: A healthy male volunteer and a mannequin head were each outfitted with a nasal continuous positive air pressure mask and pressure source (BiPAP S, Respironics, Murrysville, PA). Oxygen was added through either a side port in the mask or a port near the machine. Flow and FiO (2) were measured while varying inspiratory and expiratory pressures. Measurements were repeated with a leak added to the system and using different sites of oxygen administration. RESULTS: In both the human and in the model system, increasing inspiratory pressure, thereby increasing flow, decreased FiO (2) inside the mask. In the model system, addition of a fixed leak caused an increase in flow and decrease in FiO (2) at any given level of inspiratory and expiratory pressure. CONCLUSION: In patients using nasal positive pressure therapy, variables of pressure, leak around the mask, and the site of oxygen delivery determine the inspired oxygen concentration when giving oxygen supplementation.

Continuous Positive Airway Pressure↗
PubMed2004

The effects of sleep loss and fatigue on resident-physicians: a multi-institutional, mixed-method study.

PURPOSE: To identify and model the effects of sleep loss and fatigue on resident-physicians' professional lives and personal well-being. METHOD: In 2001-02, 149 residents at five U.S. academic health centers and from six specialties (obstetrics-gynecology, emergency medicine, family medicine, internal medicine, pediatrics, surgery) were recruited for the study. Residents were all in good standing in their programs. In a mixed-methods design, focus groups consisted of an average of seven (range, three to 14) individuals in the same year of training and residency program, for a total of 60 interns and 89 senior residents. Trained moderators conducted focus groups using a standardized, semistructured discussion guide. Participants also completed a 30-item quantitative questionnaire assessing sleepiness and workplace sleep attitudes that included the Epworth Sleepiness Scale (ESS). RESULTS: Residents described multiple adverse effects of sleep loss and fatigue on learning and cognition; job performance, including professionalism and task performance; and personal life, including personal well-being and relationships with spouse or significant other and family. Only 16% of the sample scored within the "normal" range on the ESS; 84% scored in the range for which clinical intervention is indicated. Sleepiness was consistent across institution, specialty, years of training, age, gender, marital status, and having children. CONCLUSIONS: More residents perceived that sleep loss and fatigue had major impact on their personal lives during residency, leaving many personal and social activities and meaningful personal pleasures deferred or postponed. Sleep loss and fatigue also had major impact on residents' abilities to perform their work. This finding further substantiates the growing concern about the potential impact on professional development. These observations should be taken into account in developing new training guidelines and educational interventions for housestaff.

Adult↗
PubMed2004

Strain differences in murine ventilatory behavior persist after urethane anesthesia.

Differences in breathing pattern between awake C57BL/6J (B6) and A/J mice are such that A/J mice breathe slower, deeper, and with greater variability than B6. We theorized that urethane anesthesia, by affecting cortical and subcortical function, would test the hypothesis that strain differences require a fully functional neuroaxis. We anesthetized B6 and A/J mice with urethane, placed them in a whole-body plethysmograph, and measured the durations of inspiration and expiration, respiratory frequency (Fr), and peak amplitude during exposure to room air (21% O2), hyperoxia (5 min, 100% O2), hypoxia (5 min, 8% O2), and posthypoxic reoxygenation (5 min, 100% O2). Breathing variability was assessed by calculating the coefficient of variation (CV) and by applying spatial statistics to Poincaré plots constructed from the timing and amplitude data. Even though Fr in anesthetized B6 and A/J mice was greater than that for unanesthetized animals, anesthetized A/J mice still breathed slower, deeper, and with greater variability than B6 mice at rest and during hyperoxia. During the fourth minute of hypoxia, Fr and its CV were not significantly different between strains. Even though Fr was similar between strains immediately after hypoxia, its CV was significantly greater for B6 than A/J mice. Posthypoxic Fr was significantly less than baseline Fr in B6 but not A/J mice, and the CV for posthypoxic Fr was greater for B6 but less for AJ mice compared with baseline CV. This difference in patterning was confirmed by spatial statistical analysis. We conclude that strain-specific differences in respiratory pattern and its variability are robust genetic traits. The neural substrate for these differences, at least partially, exists within subcortical structures generating the breathing pattern.

Anesthetics, Intravenous↗
PubMed2004

Ventilatory behavior during sleep among A/J and C57BL/6J mouse strains.

The pattern of breathing during sleep could be a heritable trait. Our intent was to test this genetic hypothesis in inbred mouse strains known to vary in breathing patterns during wakefulness (Han F, Subramanian S, Dick TE, Dreshaj IA, and Strohl KP. J Appl Physiol 91: 1962-1970, 2001; Han F, Subramanian S, Price ER, Nadeau J, and Strohl KP, J Appl Physiol 92: 1133-1140, 2002) to determine whether such differences persisted into non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Measures assessed in C57BL/6J (B6; Jackson Laboratory) and two A/J strains (A/J Jackson and A/J Harlan) included ventilatory behavior [respiratory frequency, tidal volume, minute ventilation, mean inspiratory flow, and duty cycle (inspiratory time/total breath time)], and metabolism, as performed by the plethsmography method with animals instrumented to record EEG, electromyogram, and heart rate. In all strains, there were reductions in minute ventilation and CO2 production in NREM compared with wakefulness (P < 0.001) and a further reduction in REM compared with NREM (P < 0.001), but no state-by-stain interactions. Frequency showed strain (P < 0.0001) and state-by-strain interactions (P < 0.0001). The A/J Jackson did not change frequency in REM vs. NREM [141 +/- 15 (SD) vs. 139 +/- 14 breaths/min; P = 0.92], whereas, in the A/J Harlan, it was lower in REM vs. NREM (168 +/- 14 vs. 179 +/- 12 breaths/min; P = 0.0005), and, in the B6, it was higher in REM vs. NREM (209 +/- 12 vs. 188 +/- 13 breaths/min; P < 0.0001). Heart rate exhibited strain (P = 0.003), state (P < 0.0001), and state-by-strain interaction (P = 0.017) and was lower in NREM sleep in the A/J Harlan (P = 0.035) and B6 (P < 0.0001). We conclude that genetic background affects features of breathing during NREM and REM sleep, despite broad changes in state, metabolism, and heart rate.

Animals↗
PubMed2003

Periodic breathing and genetics.

The episodic waxing and waning of ventilation is a fundamental event in sleep apnea syndromes. Post-hypoxic frequency decline (PHFD) and periodic breathing (PB) are evoked by brief hypoxic exposures in unanaesthetized and unrestrained inbred C57BL/6J mice, but not in A/J mice; and expression of PHFD differs not only among these mice strains but in among rat strains as well. These observations along with the current literature on genetic factors that operate on ventilatory behavior at rest and with chemosensory drive lead to the hypothesis that genetic factors infer some proportion of risk for the ventilatory instability observed in human sleep apnea syndromes.

Animals↗
PubMed2003

Competency-based goals for sleep and chronobiology in undergraduate medical education.

STUDY OBJECTIVES: Sleep and circadian rhythms are biologic processes operative in health and disease, but as yet there is no articulated curriculum for undergraduate medical education. DESIGN: A multidisciplinary expert-opinion approach was utilized to assess and define education objectives and the potential for implementation. SETTING: N/A. PATIENTS OR PARTICIPANTS: National Institutes of Health Sleep Academic Awardees. INTERVENTIONS: N/A. RESULTS: Four competencies with examples of instruction objectives were identified relating to sleep processes and sleep need, the impact of sleep and sleep disorders on human illness, the sleep history, and the application of sleep physiology and pathophysiology to patent care. Various strategies and tools are currently available for implementation and assessment of learning objectives for these knowledge and skills. CONCLUSION: The core competencies can be designed to improve physician knowledge and skills in recognizing and intervening in sleep problems and disorders. Learning objectives can be immediately incorporated into most medical school curricula. At the same time, these competencies serve as an important bridge across multiple medical content areas and disciplines and between undergraduate and postgraduate training.

Chronobiology Phenomena↗