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Biomedical subjects

F A Gaffney

Publications and source records attributed to F A Gaffney.

At least 19 recordsLinked to original sources

Head-down tilt bedrest. HDT'88--an international collaborative effort in integrated systems physiology.

An international collaborative project, initiated by the DLR-NASA Life Sciences Working Group, led to the performance of a head-down tilt bedrest (HDT) study at the DLR Institute for Aerospace Medicine. Scientific and operational questions were addressed in preparation for the D-2 Spacelab mission. Principal areas of interest were cardiovascular regulation and fluid/electrolyte metabolism. The results are detailed in a series of 13 reports to which the present paper serves as an introduction.

Adaptation, Physiological

The effects of a 10-day period of head-down tilt on the cardiovascular responses to intravenous saline loading.

We tested the hypothesis that adaptation to microgravity, simulated by a 10-day period of head-down tilt (HDT), alters the responses to an intravenous fluid load by causing a larger fraction of the infused volume to be retained and magnifying the acute hemodynamic effects. HDT caused a significant (p less than 0.01) decrease in blood volume (-0.72 liters) and weight (-1.6 kg). Rapid infusion (22 ml/kg over 20 min.) of isotonic saline before, during, and after HDT produced a transient blood volume expansion with 18% of the infusate retained intravascularly after 2 hours. HDT had no effect on this response. Control hemodynamics were significantly different with lower cardiac output and higher total peripheral resistance (TPR) during and after HDT. Saline caused significant increases in cardiac output, heart rate, and stroke volume and a decrease in TPR. The magnitude and time course of these changes were not altered by HDT. The results refute the hypothesis and suggest that during HDT new set points or operating points were established for the control of intravascular volume and hemodynamic state.

Adult

Cardiovascular response to lower body negative pressure before, during, and after ten days head-down tilt bedrest.

The haemodynamic response to lower body negative pressure (LBNP) was studied in 6 test subjects before (baseline), during, and after (recovery) ten days of 6 degrees head-down bedrest. The LBNP protocol consisted of a 35 min control period, application of a staircase differential pressure profile (15 min at -15 mmHg; 5 min at -30 mmHg; 15 min at -40 mmHg), and a 10 min post-stress observation period. Cardiac output was measured by a foreign gas rebreathing technique. Finger plethysmographic arterial blood pressure (BP), ECG, and heart rate (HR), lower limb crossectional area, and the electrical impedance of three body segments were recorded continuously. As expected, HDT caused a decrease in plasma volume and total body fluid volume. Resting CO at the end of HDT was 16% below the baseline level and similar to CO in the upright position before HDT. Stroke volume (SV) was also reduced, but there were no significant changes in control HR or BP. Absolute changes in CO and SV during LBNP were similar at baseline and during HDT, but the relative changes were larger during HDT. HR and vasoconstriction responses were enhanced, but presyncope occurred in two subjects. Reduced cardiac filling with decreased stroke volume at rest is the apparent primary cause of the altered LBNP response during HDT.

Adult

Effects of head-down tilt for 10 days on the compliance of the leg.

The purpose of this investigation was to measure lower leg compliance before, during and after a 10-day period of bedrest at head-down tilt to test the hypothesis that leg compliance and the capacity for venous pooling is increased by the adaptation to stimulated microgravity. Venous occlusion plethysmography with multiple proximal occlusion pressures was used to obtain compliance measurements in six male subjects. Calf circumference decreased significantly during the tilt (corresponding to a decrease in cross sectional area of 7%) and had not returned to baseline seven days after the end of tilt. Compliance post-tilt was significantly greater than pre-tilt, probably mainly due to a reduction in muscle mass. This study supports the need for investigations to define: (a) the degree of protection against orthostatic hypotension that can be achieved by maintaining leg muscle mass and tone, and (b) efficient and specific exercise programs to prevent loss of muscle mass and function-particularly during spaceflight.

Adaptation, Physiological

Cardiovascular and metabolic responses to static contraction in man.

There is substantial controversy regarding muscle blood flow and its regulation during static exercises. Major issues include (1) the relationship between developed force and muscle blood flow, (2) the ability of metabolic vasodilation to overcome neurally mediated vasoconstriction, (3) the time course and magnitude of hyperaemic flow following static exercise and (4) blood flow to the contralateral inactive limb. At rest, 15, 25 and 50% maximal voluntary contractions (MVC) femoral venous flow in four healthy young men (LBF; mean +/- 1 SD) was 0.4 +/- 0.3, 1.76 +/- 0.65, 0.90 +/- 0.32 and 1.06 +/- 0.59 1 min-1, and mean arterial pressures (MAP) were 104 +/- 13, 140 +/- 14, 160 +/- 17 and 161 +/- 11 mmHg. Thus, LBF does not increase proportionally with increasing levels of MVC, despite increased arterial pressure. Further, during both 25 and 50% MVC, which were held to exhaustion, an elevated limb vascular resistance was encountered towards the end of contraction, which suggests that neurally mediated vasoconstrictor activity overrides local vasodilation. Femoral venous effluent documented perfusion of active muscle during contractions of 15 and 25% MVC, but less so at 50% MVC. Immediately in recovery LBF reached levels of 3-3.5 1 min-1, which corresponded to 150 ml 100 g-1 min-1. When both O2 uptake and lactate release during the contractions and in recovery were taken into account, a close correlation between rate of energy turnover and exerted force was found. When MAP was raised by static contraction of the opposite quadriceps, LBF in the inactive leg increased momentarily. Within 1 min vascular resistance became elevated and the blood flow became reduced.

Adult

Hemodynamic, ventilatory, and biochemical responses of panic patients and normal controls with sodium lactate infusion and spontaneous panic attacks.

Hemodynamic, ventilatory, and biochemical variables were measured in ten healthy adults and ten panic patients during infusion of 0.5 mol/L of sodium lactate. Physical activity, fitness level, and ambulatory electrocardiograms were also recorded. Lactate infusion doubled cardiac output, increased blood lactate levels by sixfold, and produced hypernatremia, hypocalcemia, and decreased serum bicarbonate levels in both groups but raised arterial pressure only in the patients. The patients hyperventilated before and during the infusion. Physiological responses and somatic complaints with the infusion differed little between the groups, but emotional complaints were six times more frequent among the panic patients. Eight patients but no control subjects interpreted their symptoms as a panic attack. Heart rate increased with only 14 of 31 recorded spontaneous outpatient panic attacks. Sodium lactate infusions appear to produce panic by mimicking the physiology of spontaneous panic. Treatment with cardioactive agents is not indicated in the absence of cardiopulmonary or autonomic nervous system abnormalities.

Adult

Cardiovascular effects of vasoactive intestinal peptide in healthy subjects.

Hypotension and flushing are occasionally observed in patients with pancreatic cholera syndrome. Similar effects are produced when vasoactive intestinal polypeptide (VIP) is administered to healthy subjects. To characterize further these responses, serial measurements of heart rate, blood pressure, cardiac output and forearm blood flow were made in 6 healthy subjects during constant VIP infusion (400 pmol/kg/hr for 100 minutes). VIP infusion caused sustained vasodilatation and decreased total peripheral resistance and mean arterial pressure by 30 and 12%, respectively. Forearm resistance decreased by 65%. The effects on cardiac output and stroke volume were biphasic. During the early phase of VIP infusion (0 to 70 minutes), heart rate and cardiac output increased with only minor changes in stroke volume. Later (71 to 100 minutes) the tachycardia persisted, but cardiac output decreased toward control levels due to decreased stroke volume. Echocardiograms during the infusion demonstrated increased left ventricular contractility as defined by the relation between end-systolic wall stress and shortening fraction. These data document potent vasodilatory and inotropic actions of VIP. It is likely that intravascular volume losses from increased intestinal secretion account for the decreased stroke volume seen late in the VIP infusion period and immediately thereafter. The tachycardia appears to be an appropriate compensatory mechanism to maintain blood pressure in the presence of vasodilatation and loss of intervascular volume. These observations provide an explanation for the cardiovascular findings in patients with sudden release of VIP from tumors.

Adult

Echocardiographic measurements of left ventricular mass by a non-geometric method.

The accuracy of a new non-geometric method for calculating left ventricular myocardial volumes from 2-D echocardiographic images was assessed in vitro using 20 formalin-fixed normal human hearts. Serial oblique short axis images were acquired from one point at 5 degree intervals, for a total of 10 to 12 cross sections. Echocardiographic myocardial volumes were calculated as the difference between the volumes defined by the epi- and endocardial surfaces. Actual myocardial volumes were determined by water displacement. Volumes ranged from 80 to 174 ml (mean 130.8 ml). Linear regression analysis demonstrated excellent agreement between echocardiographic (X) and direct measurements (Y) i.e., y = 0.98 X + 4.3 ml; r = 0.94; SEE = 8.4; p = 0.001. Comparison of 10 duplicate measurements by two independent observers yielded an r of 0.96. These in vitro results suggest that with this technique, quantitative analysis of a limited number of cross sectional echocardiographic views will provide accurate left ventricular mass estimates.

Echocardiography

Comparative efficacy of behavioral stress management versus propranolol in reducing psychophysiological reactivity in post-myocardial infarction patients.

The present study compared the relative efficacy of a behavioral stress-management procedure versus a pharmacologic method (the beta-blocker propranolol) in reducing psychophysiological reactivity in post-myocardial infarction (MI) patients. A pretreatment-posttreatment assessment design was used, with 10 patients participating in six separate sessions. The first session involved evaluating psychophysiological reactivity to an emotional stressor (a public-speaking task). The subsequent five sessions involved the administration of the respective treatments, either stress management or drug. The patients were randomly assigned to each treatment group. The public-speaking stressor was readministered after the last treatment session. Results demonstrated that behavioral stress management reduced psychophysiological reactivity to public speaking to the same level seen with propranolol. The findings suggest that this nonpharmacological approach could be of use when beta-blocker therapy is not desired, not practical, or medically contraindicated.

Adult

Cardiovascular deconditioning produced by 20 hours of bedrest with head-down tilt (-5 degrees) in middle-aged healthy men.

Cardiovascular deconditioning after prolonged bedrest has been attributed to inactivity. To examine the role of the altered distribution of body fluids, 5 healthy men, aged 41 to 48 years, were studied before, during and after a 20-hour period of bedrest with head-down tilt (-5 degrees). This intervention produces a marked central shift of intravascular and interstitial fluid, but the short duration minimizes the effects of inactivity. Central venous pressure, cardiac output and stroke volume all increased significantly (p less than 0.05) from supine baseline mean values; central venous pressure from 8.6 to 12.6 cm H2O, cardiac output from 6.9 to 7.9 liters/min, and stroke volume from 104 to 113 ml after 15 minutes of tilt, but all values returned to baseline within 20 hours. Supine central venous pressure after tilt was 7.4 cm H2O, cardiac output 5.7 liters/min and stroke volume 84 ml. Blood volume decreased 0.51 liters. After tilt, orthostatic stress produced a higher heart rate (90 +/- 18 vs 68 +/- 12 beats/min). Maximal oxygen consumption decreased (2.36 +/- 0.41 vs 2.62 +/- 0.48 liters/min), mainly owing to reduced stroke volume (87 +/- 22 vs 107 +/- 18 ml, p less than 0.05). Thus, tilt produced a transient increase in central venous pressure, stroke volume and cardiac output, but supine mean values were below baseline levels after 20 hours. The post-tilt state was qualitatively and quantitatively similar to that seen after 2 to 3 weeks of bedrest or several days of spaceflight. These results are also similar to those from a previously studied group of ten 20- to 30-year-old normal men.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological

Single and combined therapy for systemic hypertension with propranolol, hydralazine and hydrochlorothiazide: hemodynamic and neuroendocrine mechanisms of action.

The antihypertensive mechanisms of single and combined therapy with a beta-adrenergic antagonist (propranolol) and a vasodilator (hydralazine) were investigated in 9 patients with moderately severe hypertension, who were receiving maintenance diuretic (hydrochlorothiazide) treatment. Hemodynamic and neuroendocrine responses were determined at rest and during lower body negative pressure, and dynamic and static exercise stress after the chronic administration of propranolol and hydralazine, given alone or in combination. All 3 drug regimens, each administered for at least 10 weeks, reduced blood pressure (p less than 0.05) compared with diuretic-only therapy in patients at rest, in both the supine and standing position, and during lower body negative pressure and dynamic exercise. There was a significant additive antihypertensive effect when propranolol and hydralazine were combined. Only combination therapy effectively lowered pressure during static exercise. The regimens produced divergent effects on the supine cardiac output: a decrease with propranolol (p less than 0.05), no change with combination therapy and an increase with hydralazine (p less than 0.05). Both hydralazine and combination therapy significantly reduced supine total peripheral resistance (p less than 0.05), whereas propranolol produced no change. All 3 drug treatments significantly reduced total peripheral resistance during upright rest and dynamic exercise (p less than 0.05), without changing cardiac output or maximal exercise capacity. During exercise, cardiac output was maintained in patients treated with propranolol and in those treated with combined therapy by increases in stroke volume (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Electromechanical changes during electrically induced and maximal voluntary contractions: surface and intramuscular EMG responses during sustained maximal voluntary contraction.

Changes in the electrical activity of the human gastrocnemius and soleus muscles during fatiguing maximal plantar flexions were studied with computer-aided EMG frequency power spectral analysis and intramuscular spike amplitude-frequency histogram analysis. In some experiments, brief supramaximal nerve stimulations of 80 Hz were given at 15-s intervals during sustained maximal voluntary contractions (MVCs). Multiple muscle biopsy samples were also obtained from the gastrocnemius muscle for fiber type determination. The surface EMG frequency spectral analysis showed a highly significant reduction in mean power frequency and root mean square EMG amplitude during sustained MVCs. The intramuscular spike amplitude-frequency histograms showed that the gastrocnemius muscle had a progressive reduction in the motor unit discharge frequency, particularly those with a relatively high amplitude, whereas the soleus muscle hardly showed a reduction in motor unit activity. Reduction in motor unit activity was also found to be more pronounced in gastrocnemius muscles with higher proportions of type II fibers. Brief maximal tetanic stimulations initially matching the MVC failed to increase the contraction force. Similarly, the evoked compound mass action potentials showed little change in the amplitude in subjects with different muscle fiber compositions. Results of this study suggest that during sustained MVCs, force fatigue could not be attributed to a failure of muscle membrane electrical propagation; a progressive reduction in motor unit activation does not result in a functional disadvantage, but may optimize excitation-contraction coupling by avoiding a muscle electrical conduction failure; and the extent of the reduction in motor unit activation seems to be muscle-fiber-type-dependent which may account for the reduction in amplitude and frequency of the surface EMG.

Biomechanical Phenomena

Pathophysiologic mechanisms of cardiac tamponade and pulsus alternans shown by echocardiography.

A pericardial effusion is easily recognized by echocardiography, but the diagnosis of cardiac tamponade by echocardiography is controversial. Recently, several reports have indicated that right ventricular (RV) or right atrial (RA) diastolic collapse represent highly specific and sensitive signs of a hemodynamically significant pericardial effusion. This report evaluates the pathophysiologic significance of these findings in 3 patients. One patient had classic clinical and hemodynamic features of tamponade without typical echocardiographic features; 1 had typical echocardiographic features of tamponade without the characteristic clinical or hemodynamic features; and 1 had all the findings characteristic of tamponade, including mechanical and electrical alternans. The first patient had increased right-sided cardiac pressures and RV hypertrophy, which prevented RV or RA collapse. The second patient had low right-sided intracardiac pressures, which allowed RV and RA diastolic compression to occur during early and mid-diastole. In the third patient, severe holodiastolic impairment of right-sided filling, and presumed decreased pulmonary venous and pericardial compliance, in the setting of tamponade produced a beat-to-beat alternation of RV and left ventricular filling with associated electrical and mechanical alternans. RV or RA collapse during diastole occurs when intrapericardial pressure equals or exceeds intracardiac pressure. Increases in wall stiffness of chamber pressures may prevent diastolic collapse in the setting of tamponade. Conversely, extremely low intracardiac pressures may allow diastolic collapse to occur in the absence of overt cardiac tamponade. The extent and timing of the RA or RV collapse, rather than its mere occurrence, are important in the diagnosis of cardiac tamponade by echocardiography.

Adolescent