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Biomedical subjects

J K Alexander

Publications and source records attributed to J K Alexander.

At least 19 recordsLinked to original sources
PubMed2001

Obesity and coronary heart disease.

Obesity is commonly cited as a risk factor for the development of coronary heart disease (CHD). Epidemiologic studies tend to support this contention, particularly those focusing on patients with central obesity. Such studies however, are imprecise and prone to misclassification bias. Angiographic and post mortem studies have demonstrated little or no correlation of total fat mass and coronary atherosclerosis except in those with abdominal obesity. There is a strong association of obesity, particularly central obesity, and traditional risk factors for CHD such as hypertension, type II diabetes mellitus, and dyslipidemia. There may also be an association between obesity and several nontraditional risk factors such as hyperhomocystinemia, elevated Lp(a) levels and factors that increase thrombogenesis. Obesity may also alter endothelial function. Weight loss, although associated with favorable modification of multiple risk factors for CHD, has not been shown to independently and definitively reduce CHD risk.

Adipose Tissue↗
PubMed1999

Cardiac arrhythmia at high altitude: the progressive effect of aging.

To evaluate the effects of aging on cardiac rhythm at high altitude, I wore a Holter monitor at age 75 during a climb to 5,100 m on Mt. Kilimanjaro, then compared findings with those from my climb to 5,895 m at age 65. Holter leads were placed to identify left or right ventricular source of ectopy, and on the 2nd ascent arterial oxygen saturation was monitored by finger oximetry. Sea-level testing revealed no evidence of cardiac disease. During ascent from 4,710 to 5,100 m, when arterial oxygen saturation reached 70%, heart rate was higher (123 vs 116 beats per minute), and frequency of left ventricular premature complexes was greater (56 vs 50 per hour) than on the earlier ascent. Nine 3- to 5-complex runs of left ventricular tachycardia were recorded during climbing, resting, or sleeping, and there was 1 run of 14 complexes at 250 beats per minute during the climb near 5,100 m. These observations suggest that aging increases sympathetic response or sensitivity, or both, to hypoxia during exercise, and even during sleep. Also, our focus should perhaps be on sympathetic stimulation rather than on pulmonary hypertension as a cause of arrhythmia in unacclimatized older persons at high altitude.

Aged↗
PubMed1995

Coronary problems associated with altitude and air travel.

Hypoxia accompanying acute exposure to high altitude engenders augmented sympathetic nervous activity, thus increasing heart rate and blood pressure and the risk of effort angina and dysrhythmia in coronary patients. This risk is highest during the first 1 to 3 days and diminishes in 5 to 7 days as sympathetic activity subsides. Protective effects may result from 1. Gradual ascent. 2. Attention to blood pressure control. 3. Limitation of activity to less than the symptom-limiting degree at sea level, especially during the first 1 to 3 days. 4. Preexisting exercise tolerance of modest-to-moderate degree. 5. Ability of patient to appraise heart rate and blood pressure. Ascent by high-risk patients can be recommended to no more than moderate altitude, where adequate facilities for cardiovascular care are proximate. The risk of acute mountain sickness is not increased in older coronary patients. Strong contraindications to air travel by coronary patients would appear to be 1. New-onset angina. 2. Unstable angina. 3. Frequent or high-grade ventricular ectopy. 4. Severe or poorly controlled hypertension. Myocardial infarction within several weeks or months constitutes a relative contraindication, with persistent angina, ventricular ectopy, and poor ventricular function as the factors of greatest concern.

Aerospace Medicine↗
PubMed1995

How well do older persons tolerate moderate altitude?

We studied the physiologic and clinical responses to moderate altitude in 97 older men and women (aged 59 to 83 years) over 5 days in Vail, Colorado, at an elevation of 2,500 m (8,200 ft). The incidence of acute mountain sickness was 16%, which is slightly lower than that reported for younger persons. The occurrence of symptoms of acute mountain sickness did not parallel arterial oxygen saturation or spirometric or blood pressure measurements. Chronic diseases were present in percentages typical for ambulatory elderly persons: 19 (20%) had coronary artery disease, 33 (34%) had hypertension, and 9 (9%) had lung disease. Despite this, no adverse signs or symptoms occurred in our subjects during their stay at this altitude. Our findings suggest that persons with preexisting, generally asymptomatic, cardiovascular or pulmonary disease can safely visit moderate altitudes.

Acute Disease↗
PubMed1995

Age, altitude, and arrhythmia.

Continuous electrocardiographic recording by Holter monitor was carried out during a climb to 5,895 m by an unacclimatized 65-year-old man confirmed to be without cardiac disease on rigorous examination. During ascent, marked ventricular ectopy and multiple runs of left ventricular bigeminy developed in association with an increase in P-wave amplitude of lead V2, and unchanged QT interval. With the diminished aerobic stress of descent, bigeminy disappeared, although premature ventricular complexes, apparently of right ventricular origin, remained increased throughout the climb. Arrhythmogenic mechanisms activated by prolonged exercise under hypoxic conditions are reviewed in relation to age.

Aged↗
PubMed1994

Coronary heart disease at altitude.

In the past, it has been assumed that some basic physiologic responses to altitude, exposure in coronary patients are comparable to those in normal young subjects. In fact there are similar changes in sympathetic activation, heart rate, and blood pressure early after ascent, with decrements in plasma volume, cardiac output, and stroke volume as acclimatization proceeds. These responses are described, and experience with coronary patients is reviewed. During the 1st 2 to 3 days at altitude, coronary patients are at greatest risk of untoward events. Gradual rather than abrupt ascent, a moderate degree of physical conditioning, early limitation of activity to a level tolerated at low altitude for somewhat less), and attention to blood pressure control all appear to have protective effects. Ascent to moderate altitude appears to entail little risk in coronary patients who are asymptomatic or have moderate exercise tolerance, provided that the above precautions are observed and that activity does not exceed levels at lower altitude. If activity is to be increased, pre-ascent treadmill exercise testing or Holter monitor data secured under conditions comparable to those anticipated at altitude may provide reasonable guidelines. For coronary patients previously evaluated and known to be in a high-risk category, indications for ascent should be examined more critically, and precautionary measures should be more rigorous. Advice for patients with known coronary disease who may desire to trek at very high altitude must involve individual evaluation, and guidelines remain elusive.

Altitude↗
PubMed1992

Oxygen transport and cardiovascular function at extreme altitude: lessons from Operation Everest II.

Operation Everest II was designed to examine the physiological responses to gradual decompression simulating an ascent of Mt Everest (8,848 m) to an inspired PO2 of 43 mmHg. The principal studies conducted were cardiovascular, respiratory, muscular-skeletal and metabolic responses to exercise. Eight healthy males aged 21-31 years began the "ascent" and six successfully reached the "summit", where their resting arterial blood gases were PO2 = 30 mmHg and PCO2 = 11 mmHg, pH = 7.56. Their maximal oxygen uptake decreased from 3.98 +/- 0.2 L/min at sea level to 1.17 +/- 0.08 L/min at PIO2 43 mmHg. The principal factors responsible for oxygen transport from the atmosphere to tissues were (1) Alveolar ventilation--a four fold increase. (2) Diffusion from the alveolus to end capillary blood--unchanged. (3) Cardiac function (assessed by hemodynamics, echocardiography and electrocardiography)--normal--although maximum cardiac output and heart rate were reduced. (4) Oxygen extraction--maximal with PvO2 14.8 +/- 1 mmHg. With increasing altitude maximal blood and muscle lactate progressively declined although at any submaximal intensity blood and muscle lactate was higher at higher altitudes.

Adult↗
PubMed1987

Enhanced left ventricular systolic performance at high altitude during Operation Everest II.

Serial rest and upright cycle exercise 2-dimensional echocardiographic studies were performed in 7 healthy young men during acclimatization to a simulated altitude of 29,000 feet (barometric pressure [PB] 240 torr) in a chamber for 40 days. In all subjects left ventricular (LV) end-diastolic, end-systolic and stroke volumes progressively decreased, with mean reductions of 21%, 40% and 14%, respectively, on ascent to 25,000 feet (PB 282 torr) at rest, and reductions of 23%, 43% and 14% during 60-W exercise. At PB 282 torr, mean arterial blood O2 partial pressures were 37 torr (rest) and 32 torr (exercise), with corresponding O2 saturations of 68% and 59%. All 3 indexes of LV systolic function examined--ejection fraction, ratio of peak systolic pressure to end-systolic volume and mean normalized systolic ejection rate at rest--were sustained in all subjects at high altitude despite reduced preload, pulmonary hypertension and severe hypoxemia. Increases in ejection fraction of 6% at rest and 10% during exercise developed at PB 282 torr and a higher mean normalized systolic ejection rate in association with elevated circulating catecholamines reflecting enhanced sympathetic activity. LV systolic function is not a limiting factor in compromising the exercise capacity of normal humans on ascent to high altitude, even to the peak of Mt. Everest.

Acclimatization↗
PubMed1987

Oxygen transport during exercise at extreme altitude: Operation Everest II.

Eight male volunteers had rest and exercise measurement to determine the mechanisms of oxygen transport during a 40-day chamber decompression simulating high-altitude exposure equivalent to the summit of Mt Everest. Five subjects completing the study decreased their maximum oxygen uptake by 72%. During maximal or near-maximal exercise, arterial PCO2 fell as low as 8 mm Hg, defending the alveolar PO2 and confirming marked hyperventilation. Alveolar-arterial diffusion did not improve and V/Q worsened. Cardiac function was unimpaired. Circulatory oxygen transport resembled that at sea level. The decrease in mixed venous PO2 was not enough to preserve fractional oxygen utilization "on the summit." The PO2 gradients from atmosphere to alveolus, alveolus to arterial blood, arterial to venous blood, and from venous (capillary) blood to mitochondria all decreased. However, hyperventilation appeared to be the primary adaptation that defended the maximum oxygen uptake.

Adult↗
PubMed1986

Effects of cholesterol and lipoproteins on endocytosis by a monocyte-like cell line.

The human monocyte/macrophage-like cell line U937 is a cholesterol auxotroph. Incubation of these cells in the growth medium in which delipidated fetal calf serum has been substituted for fetal calf serum depletes cellular cholesterol and inhibits growth. The cholesterol requirement of these cells for growth can be satisfied by human low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL), but not by high-density lipoprotein (HDL). U937 cells can bind and degrade LDL via a high-affinity site and this recognition is altered by acetylation of LDL. This indicates that these cells express relatively high LDL receptor activity and low levels of the acetyl-LDL receptor. The cells were used to study the role of cholesterol in lectin-mediated and fluid-phase endocytosis. Growth of the cells in the medium containing delipidated fetal calf serum results in impairment of both concanavalin A-mediated endocytosis of horseradish peroxidase and concanavalin A-independent endocytosis of Lucifer Yellow. Supplementation of the medium with cholesterol prevents cellular cholesterol depletion, supports growth and stimulates Lucifer Yellow endocytosis but fails to restore horseradish peroxidase endocytosis. However, if the cells are incubated in the presence of no less than 40 micrograms LDL protein/ml to maintain normal cell cholesterol levels, concanavalin A-mediated endocytosis of horseradish peroxidase is activated. The effect of LDL is specific since neither VLDL nor HDL3 at the same protein concentration activates horseradish peroxidase uptake by the cells. Furthermore, the activation of endocytosis by LDL is not inhibited by the inclusion of heparin or acetylation of the LDL indicating that binding of LDL to the LDL receptor is not required for these effects. The mediation of activation of horseradish peroxidase endocytosis by the lectin is presumed to involve binding of LDL to concanavalin A associated with the cell surface which in turn stimulates horseradish peroxidase binding and uptake by adsorptive endocytosis. The rate of fluid endocytosis and endosome formation seems to depend on cellular cholesterol content presumably because cholesterol is involved in maintaining the appropriate plasma membrane structure and fluidity.

Cell Division↗
PubMed1984

Increased metabolism contributes to increased resting ventilation at high altitude.

Ventilatory acclimation to high altitude results in an increase in total or minute ventilation, and is associated with a fall in alveolar PCO2, i.e. alveolar hyperventilation. However, the extent to which the increase in total ventilation is matched by a greater metabolic rate (VO2, VCO2) vs alveolar hyperventilation is unclear. We sought to determine the contribution of changes in metabolic rate to the increase in minute ventilation observed during exposure to high altitude. In 12 healthy male subjects taken from Denver, Colorado (1600 m) to Pikes Peak, Colorado (4300 m) for 5 days, resting minute ventilation increased from low to high altitude (+ 26% for the 5 days) and arterialized PCO2 fell. Resting metabolic rate increased 16% for the 5 days and could account for more than half of the increase in minute ventilation. Among subjects the increases in ventilation on days 1, 2 and 4 were positively correlated with increased CO2 production; they were not correlated with arterial oxygen saturation on any day. During exercise at high altitude, PCO2 values were not different from those at rest and minute ventilation rose above low altitude values (+ 58% by day 5), but the increase could not be accounted for by an increased CO2 production. Thus at rest but not during exercise a substantial portion of the rise in minute ventilation could be attributed to increased metabolic rate.

Acclimatization↗
PubMed1984

Variable inhibition by falling CO2 of hypoxic ventilatory response in humans.

Acute hypoxia stimulates an increase in ventilation but the resulting hypocapnia limits the magnitude of the increase. Thus the hypoxic ventilatory response is usually measured during isocapnia, but this may not reflect events at high altitude. We hypothesized that the degree of inhibition by hypocapnia might depend on individual ventilatory response to CO2 and thus vary between persons. To test this hypothesis we compared the isocapnic hypoxic ventilatory response (end-tidal PCO2 maintained by CO2 addition) with the response in which CO2 was not added and the end-tidal PCO2 fell to a variable extent (poikilocapnic hypoxia). In 14 healthy persons we found that the poikilocapnic hypoxic ventilatory response was determined by two factors: sensitivity to isocapnic hypoxia acting to increase ventilation and sensitivity to CO2 acting to decrease the hypoxic ventilatory response. The ventilatory response to poikilocapnic hypoxia correlated with but was generally less than the isocapnic hypoxic response. The magnitude of the difference between them related to the hypercapnic response. Further, the results suggested that the CO2 response in the high CO2 range related to ventilatory events in the low CO2 range. Thus the magnitude of ventilatory inhibition by hypocapnia may depend on individual ventilatory responsiveness to CO2.

Adult↗
PubMed1984

Hypocapnia and sustained hypoxia blunt ventilation on arrival at high altitude.

Hypoxia at high altitude stimulates ventilation, but inhibitory influences in the first days after arrival limit the ventilatory response. Possible inhibitory influences include hypocapnia and depression of ventilation during sustained hypoxia. Our approach was to compare hypoxic ventilatory responses at low altitude with ventilation at high altitude. In 12 subjects we compared responses both to isocapnic hypoxia and poikilocapnic (no CO2 added) hypoxia during acute (less than 10 min) and sustained (30 min) hypoxia in Denver (1,600 m) with ventilations measured on each of 5 days on Pikes Peak (4,300 m). On Pikes Peak, day 1 ventilation [minute ventilation = 10.0 1/min, BTPS; arterial O2 saturation (Sao2) = 82%] was less than predicted by either acute isocapnic or poikilocapnic tests. However, sustained poikilocapnic hypoxia (Sao2 approximately = 82%) in Denver yielded ventilation similar to that on Pikes Peak on day 1. By Pikes Peak days 4 and 5, endtidal PCO2, pHa, and Sao2 approached plateaus, and ventilation (12.4 1/min, BTPS) on these days was as predicted by the acute isocapnic test. Thus the combination of hypocapnia and sustained hypoxia may have blunted the ventilatory increase on Pikes Peak day 1 but apparently not after 4 or 5 days of acclimatization.

Adult↗
PubMed1983

Mechanism of reduced cardiac stroke volume at high altitude.

Two postulates have been advanced to account for reduced stroke at high altitude: (1) diminished venous return secondary to contracted plasma volume and (2) left ventricular (LV) dysfunction secondary to hypoxia. To test these hypotheses, we assessed LV dimensions and contractility indices by M-mode echocardiography and systolic time intervals in 11 young men at sealevel and serially for 10 days at 3100 m altitude. Mean LV end-diastolic dimension fell 16% after 6-8 days, with a 20% decrease in plasma volume reflected by hematocrit rise. Pre-ejection period to LV ejection time (PEP/LVET) ratio was increased after 1-2 days. All indices of contractility were unchanged at rest, and slightly enhanced during exercise. Thus stroke volume falls and PEP/LVET ratio rises at 3100 m because of diminished venous return despite preservation of LV systolic performance.

Altitude↗