Extrinsic compression of the left main coronary artery in pulmonary hypertension.

Compression of the left main coronary artery by a dilated pulmonary artery can be a life-threatening condition. It can present with angina, symptoms of left ventricular dysfunction, and sudden death. Diagnosis and treatment of this condition is very important. We demonstrate significant compression of the left main coronary artery on coronary angiography and thorax CT examinations.

Non-invasive detection of coronary artery disease by a newly developed high-frequency QRS electrocardiogram.

Compared to other non-invasive methods, the conventional 12-lead electrocardiogram (ECG) has low sensitivity and specificity for identifying coronary artery disease (CAD). We compared the newly developed high-frequency QRS electrocardiogram (HFQRS ECG, 150-250 Hz) with adenosine sestamibi myocardial perfusion study (MPI)-the most sensitive non-invasive study in cardiology practice. Using advanced 12-lead computer-based ECG software recently developed at NASA, criteria for a positive 12-lead HFQRS-ECG test for obstructive CAD were developed using 300 signal-averaged beats from patients undergoing elective coronary angiograms for evaluation of chest pain. These criteria, which rely strictly upon the presence or the absence of morphologic 'reduced amplitude zones' (RAZs) and not upon the 'root mean squared' (RMS) voltage amplitudes of the HFQRS complexes, were then applied prospectively to 18 patients undergoing MPI. Active CAD was considered present when reversible ischemic defects were present on MPI. Of the 18 patients, 9 had reversible defects on MPI (positive scan), whereas the other 9 had no reversible perfusion defects (negative scan). Patients with a positive nuclear study went on to coronary angiography confirming CAD, except in one patient who had nonobstructive coronary disease (<50% stenosis). Eight of the 18 subjects therefore had active CAD, whereas 10 were judged not to have active CAD. The 12-lead HFQRS-ECG result was consistent with nuclear scan results in 14 of 18 patients. The HFQRS-ECG and nuclear results differed in: (1) one patient who had a low score positive MPI, negative HFQRS-ECG and normal coronary angiogram; (2) one patient who had a small reversible anterior wall perfusion defect, 60% LAD lesion on angiogram but a negative HF-QRS result; and (3) two individuals who had positive HFQRS-ECG results in the face of negative nuclear scans but who did not undergo angiography. 12-lead HFQRS ECG had excellent sensitivity (87.5% based on 7/8 true positives correctly identified) and specificity (no worse than 80%, >8/10 true negatives correctly identified) for identifying CAD. 12-lead HFQRS ECG is an easily performed, inexpensive and potentially widely available technique that utilizes the same leads and electrodes as the conventional 12-lead ECG. It had accuracy comparable to MPI in this study. Resting 12-lead HFQRS ECG appears to be a very promising non-invasive technique for identifying CAD and may represent a viable alternative to many of the more expensive and time-consuming techniques presently utilized for non-invasively identifying CAD.

Adaptive responses of the cardiovascular system to prolonged spaceflight conditions: assessment with Holter monitoring.

This article presents selected findings obtained with Holter monitoring from two crew members of the expedition, performed during a 175-day space mission on board orbital space station "MIR." Using mathematical processing of daily cardiointervals files, 5-minute sections of records were analyzed consecutively. Then, the average daily values of indices, the average-per-every-eight-hours values (morning, evening, night) and mean values per hour were computed. The results of analysis showed that prolonged exposure of man to microgravity conditions leads to important functional alteration in human neuroautonomic regulatory mechanisms. Both crew members had significant increase of heart rate, the rise of stress index, the decrease in power of the spectrum in the range of respiratory sinus arrhythmia. These marked signs of activation of the sympathetic section of the vegetative nervous system showed individual variations. The analysis of the daily collection of cardiointervals with Holter monitoring allows us to understand and forecast the functional feasibilities of the human organism under a variety of stress conditions associated with acute and chronic microgravity exposure.

Effects of lower-body negative pressure on blood flow with applications to the human cardiovascular system.

The paper reports a theoretical investigation into the effects of lower-body negative pressure on blood flow through the human cardiovascular system. The human cardiovascular system is modelled as a closed network of arteries, arterioles, capillaries, venules and veins of different lengths and cross-sections. The pumping action is provided by the contraction of the ventricles. The model has been analysed using the finite-element method. The pertinent equations incorporating the effects of lower-body negative pressure for the pressures and flow velocities have been derived, and the quantitative results have been computed. Percentage changes in flow velocities, pressure drops and conductances under the application of lower-body negative pressure in the various segments and organs of the entire cardiovascular system are obtained. The lower-body negative pressure has no effect on the flow rates in carotid, ulnar and coronary arteries, nor on the supply of blood to the upper extremities, kidneys, spleen and liver. The major effects are found in the lower extremities.

Echocardiograms during six hours of bedrest at head-down and head-up tilt and during space flight.

Left ventricular end-diastolic volume increased after 4 1/2 to 6 hours of space flight, but was significantly decreased after 5 to 6 days of space flight. To determine the role of acute gravitational effects in this phenomenon, responses to a 6-hour bedrest model of 0 gravity (G; 5 degrees head-down tilt) were compared with those of fractional gravity loads of 1/6 G, 1/3 G, and 2/3 G by using head-up tilts of 10 degrees, 20 degrees, and 42 degrees, respectively. On 4 different days, six healthy male subjects were tilted at one of the four angles for 6 hours. Cardiac dimensions and volumes were determined from two-dimensional and M-mode echocardiograms in the left lateral decubitus position at control (0), 2, 4, and 6 hours. Stroke volume decreased with time (P < .05) for all tilt angles when compared with control. Ejection fraction (EF) at -5 degrees was greater than at +20 degrees and +42 degrees (not significant); EF at +10 degrees was greater than at +42 degrees (not significant). For the tilt angles of -5 degrees, +10 degrees, and +20 degrees, mean heart rate decreased during the first 2 hours, and returned to control or was slightly elevated above control (+20 degrees) by 6 hours (not significant). At the +42 degrees angle of tilt, heart rate was increased above control at hours 2, 4, and 6. There were no significant differences in cardiac output at any time point for any tilt angle.(ABSTRACT TRUNCATED AT 250 WORDS)

Mathematical modelling of the human cardiovascular system in the presence of stenosis.

This paper reports a theoretical study on the distribution of blood flow in the human cardiovascular system when one or more blood vessels are affected by stenosis. The analysis employs a mathematical model of the entire system based on the finite element method. The arterial-venous network is represented by a large number of interconnected segments in the model. Values for the model parameters are based upon the published data on the physiological and rheological properties of blood. Computational results show how blood flow through various parts of the cardiovascular system is affected by stenosis in different blood vessels. No significant changes in the flow parameters of the cardiovascular system were found to occur when the reduction in the lumen diameter of the stenosed vessels was less than 65%.

Mathematical modelling of flow distribution in the human cardiovascular system.

The paper presents a detailed model of the entire human cardiovascular system which aims to study the changes in flow distribution caused by external stimuli, changes in internal parameters, or other factors. The arterial-venous network is represented by 325 interconnected elastic segments. The mathematical description of each segment is based on equations of hydrodynamics and those of stress/strain relationships in elastic materials. Appropriate input functions provide for the pumping of blood by the heart through the system. The analysis employs the finite-element technique which can accommodate any prescribed boundary conditions. Values of model parameters are from available data on physical and rheological properties of blood and blood vessels. As a representative example, simulation results on changes in flow distribution with changes in the elastic properties of blood vessels are discussed. They indicate that the errors in the calculated overall flow rates are not significant even in the extreme case of arteries and veins behaving as rigid tubes.

The effects of exercise on blood flow with reference to the human cardiovascular system: a finite element study.

This paper reports on a theoretical investigation into the effects of vasomotion on blood through the human cardiovascular system. The finite element method has been used to analyse the model. Vasoconstriction and vasodilation may be effected either through the action of the central nervous system or autoregulation. One of the conditions responsible for vasomotion is exercise. The proposed model has been solved and quantitative results of flows and pressures due to changing the conductances of specific networks of arterioles, capillaries and venules comprising the arms, legs, stomach and their combinations have been obtained.

Treatment of motion sickness in parabolic flight with buccal scopolamine.

Treatment of acute motion sickness induced by parabolic flight with a preparation of scopolamine placed in the buccal pouch was investigated. Twenty-one subjects flew aboard a KC-135 aircraft operated by the National Aeronautics and Space Administration (NASA) which performed parabolic maneuvers resulting in periods of 0-g, 1-g, and 1.8-g. Each subject flew once with a tablet containing scopolamine and once with a placebo in a random order, crossover design. Signs and symptoms of motion sickness were systematically recorded during each parabola by an investigator who was blind to the content of the tablet. Compared with flights using placebo, flights with buccal scopolamine resulted in significantly lower scores for nausea (31%-35% reduction) and vomiting (50% reduction in number of parabolas with vomiting). Side effects of the drug during flight were negligible. We conclude that buccal scopolamine is more effective than a placebo in treating ongoing motion sickness.

Blood and urine responses to ingesting fluids of various salt and glucose concentrations.

Several hours before returning to Earth, Space Shuttle astronauts consume fluid and salt tablets equivalent to a liter of 0.9% saline as a countermeasure to postflight orthostatic intolerance. This countermeasure is not completely successful. Therefore, in search of a countermeasure that would protect against orthostatic intolerance better and for a longer duration, the authors compared the blood and urine responses of five men (21-41 yr) after they drank 1 L of 0.9% saline to their responses after drinking five other solutions: distilled water, 1% glucose, 0.74% saline with 1% glucose, 0.9% saline with 1% glucose, and 1.07% saline. Each subject ingested a different solution on 6 different days and remained seated for the ensuing 4 hours. Heart rate, blood pressures, and urine variables were measured before ingestion of the fluids and every 30 minutes thereafter; blood samples were drawn before, immediately after, and every 60 minutes after ingestion. Change in plasma volume, which was estimated from hemoglobin and hematocrit, was considered the most critical variable. Data for all solutions were compared by analysis of variance. Since plasma volume was increased most after ingestion of 1.07% saline, all variables (at 2 hours, at 3 hours and at 4 hours) were compared between 1.07% saline and 0.9% saline, the current countermeasure. Plasma volume was increased more after 1.07% saline than after 0.9% saline, and this difference was most significant at 4 hours after ingestion (P = .056). Diuresis occurred promptly after ingestion of the two saline-free solutions, water and 1% glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Orthostatic function during a stand test before and after head-up or head-down bedrest.

Astronauts may exhibit orthostatic dysfunction upon returning to 1 g after space flight. Understanding cardiovascular changes at 0 G will provide insights into the mechanisms of the loss of orthostatic tolerance, whether due to space flight or bedrest. Bedrest is one model used to produce cardiovascular changes that are associated with space flight. In the current study, young male adults were placed at -5 degrees, +10, +20, or +42 degrees bedrest (0, 1/6, 1/3, and 2/3g, respectively) for 6 hours on 4 different days. This was preceded and followed by a stand test: 5 minutes in the supine position, and then 5 minutes in the standing position, with the feet 9 inches apart and 6 inches from the wall. Cardiovascular values were measured at 1-minute intervals. Systolic and diastolic pressures were measured using an automated blood pressure device; mean arterial pressure (MAP; mm Hg) was calculated. Heart rate (bpm) and cardiac parameters were measured with a thoracic impedance device. Minute 3, 4, and 5 values were used to determine whether there were time or angle effects. Of six subjects, one reported nausea upon 3 minutes of standing after 6 hours of bedrest at -5 degrees. The same subject was lightheaded in the first minute of standing after 6 hours of bedrest at +10 degrees. Mean heart rate pre-bedrest in the supine position was 63 and increased by 24 bpm on standing. Heart rate post-bedrest in the supine position was 65 and increased by 35 bpm on standing; standing heart rate increased 11 bpm after -5 degrees bedrest. The increases after +10 degrees, +20 degrees, and +42 degrees tilts were 4, 3, and 4 bpm, respectively. Changes in the mean arterial blood pressure were minimal. Results from the stand test pre- and post- 6 hours of bedrest at -5 degrees but not at +10 degrees, +20 degrees, or +42 degrees are similar to those after space flight.

Pharmacologic considerations for Shuttle astronauts.

Medication usage by crewmembers in the preflight and inflight mission periods is common in the Shuttle Program. The most common medical reports for which medication is used are: space motion sickness (SMS), sleeplessness, headache, and backache. A number of medications are available in the Shuttle Medical Kit to treat these problems. Currently, astronauts test all frequently used medications before mission assignment to identify potential side-effects, problems related to performance, personal likes/dislikes, and individual therapeutic effect. However, microgravity-induced changes in drug pharmacokinetics, in combination with multiple operational factors, may significantly alter crew-member responses inflight. This article discusses those factors that may impact pharmacologic efficacy during Shuttle missions.

Reversal of cisplatin resistance with amphotericin B in a non-small cell lung cancer cell line.

The potentiation of anticancer agents by non-anticancer drugs is one of the possible strategies for overcoming cellular resistance to chemotherapy. In order to overcome cis-diamminedichloroplatinum(II) (CDDP) resistance, we evaluated the sensitizing effect on CDDP-induced cytotoxicity of various non-anticancer agents which might alter membrane transport, by means of a colorimetric [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay. Drugs which have previously been demonstrated to modify multidrug resistance did not show a sensitizing effect to cisplatin. Only amphotericin B (AmB) selectively conquered CDDP resistance in the CDDP-resistant cell line. A drug accumulation study done by the atomic absorption method demonstrated that the accumulation of CDDP in the resistant cell line recovered to the level of the parental cell line after treatment with AmB. Thus, AmB might overcome CDDP resistance by increasing the accumulation of CDDP.

[A case of second-degree atrioventricular block caused by high dose cisplatin treatment].

A 56-year-old man was admitted to our hospital because of stage IV squamous cell carcinoma of the lung. He was treated with two courses of high dose cisplatin (40 mg/m2/day, day 1-5). On day 4 of each course, a second-degree atrioventricular block was observed, which disappeared after cisplatin treatment. This case suggests that, although the cardiotoxicity caused by cisplatin is believed to be rare, one should take special care in high dose usage.

[Adriamycin, cisplatin and etoposide combination chemotherapy in non-small cell lung cancer].

Nineteen patients with non-small cell lung cancer (eight patients with adenocarcinoma, nine patients with squamous cell carcinoma, one patient with large cell carcinoma and one patient with sarcoma) who had not received previous chemotherapy were treated with a combination of adriamycin (30 mg/m2, i.v., on day 1), cisplatin (80 mg/m2, i.v., on day 1) and etoposide (70 mg/m2, i.v., on day 1-5). This chemotherapy regimen was repeated as long as possible for patients in whom PR was induced. Among all patients, CR was induced in none and 6 showed a PR (response rate 32%). However, 4 (56%) squamous cell carcinoma patients also showed PR. The median response duration in 6 PR patients was 28 weeks, and the median survival time in all patients was also 28 weeks. Mild to severe hematologic toxicities were induced and one patient died during myelosuppression. However almost all cases were reversible. Other toxicities included alopecia, nausea/vomiting, diarrhea, stomatitis, peripheral neuropathy and myocardial infarction which were reversible and manageable. The APVp therapy may be a valuable regimen for non-small cell lung cancer, especially squamous cell carcinoma.

Cardiovascular physiology in space flight.

The effects of space flight on the cardiovascular system have been studied since the first manned flights. In several instances, the results from these investigations have directly contradicted the predictions based on established models. Results suggest associations between space flight's effects on other organ systems and those on the cardiovascular system. Such findings provide new insights into normal human physiology. They must also be considered when planning for the safety and efficiency of space flight crewmembers.

Cardiovascular function in space flight.

Changes in orthostatic heart rate have been noted universally in Soviet and U.S. crewmembers post space flight. The magnitude of these changes appears to be influenced by mission duration, with increasing orthostatic intolerance for the first 7-10 days of flight and then a partial recovery in the orthostatic heart rate response. Fluid loading has been used as a countermeasure to this postflight orthostatic intolerance. Previous reports have documented the effectiveness of this technique, but it has also been noted that the effectiveness of volume expansion diminishes as flight duration exceeds one week. The response of carotid baroreceptor function was investigated utilizing a commercially available neck collar which could apply positive and negative pressure to effect receptor stimulation. Bedrest studies had validated the usefulness and validity of the device. In these studies it was shown that carotid baroreceptor function curves demonstrated less responsiveness to orthostatic stimulation than control individuals. Twelve Space Shuttle crewmembers were examined pre- and postflight from flights lasting from 4-5 days. Plots of baroreceptor function were constructed and plotted as change in R-R interval vs. carotid distending pressure (an orthostatic stimulus). Typical sigmoidal curves were obtained. Postflight the resting heart rate was higher (smaller R-R interval) and the range of R-R value and the slope of the carotid sigmoidal response were both depressed. These changes were not significant immediately postflight (L + O), but did become significant by the second day postflight (L + 2), and remained suppressed for several days thereafter. It is hypothesized that the early adaptation to space flight involves a central fluid shift during the initial days of flight, but subsequent alterations in neural controlling mechanisms (such as carotid baroreceptor function) contribute to orthostatic intolerance.