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Biomedical subjects

F A Gaffney

Publications and source records attributed to F A Gaffney.

At least 37 records · Page 2Linked to original sources

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↗

Spacelab Life Sciences flight experiments: an integrated approach to the study of cardiovascular deconditioning and orthostatic hypotension.

The microgravity environment of spaceflight produces rapid cardiovascular changes which are adaptive and appropriate in that setting, but are associated with significant deconditioning and orthostatic hypotension on return to Earth's gravity. The rapidity with which these space flight induced changes appear and disappear provides an ideal model for studying the underlying pathophysiological mechanisms of deconditioning and orthostatic hypotension, regardless of etiology. Since significant deconditioning is seen after flights of very short duration, muscle atrophy due to inactivity plays, at most, a small role. These changes in circulatory control associated with cephalad fluid shifts, rather than inactivity per se, are probably more important factors. In order to test this hypothesis in a systematic way, a multidisciplinary approach which defines and integrates inputs and responses from a wide variety of circulatory sub-systems is required. The cardiovascular experiments selected for Spacelab Life Sciences flights 1 and 2 provide such an approach. Both human and animal models will be utilized. Pre- and post-flight characterization of the payload crew includes determination of maximal exercise capacity (bicycle ergometry), orthostatic tolerance (lower body negative pressure), alpha and beta adrenergic sensitivity (isoproterenol and phenylephrine infusions), baroreflex sensitivity (ECG-gated, stepwise changes in carotid artery transmural pressure with a pneumatic neck collar), and responses to a 24 h period of 5 deg head-down tilt. Measurements of cardiac output (CO2 and C2H2 rebreathing), cardiac chamber dimensions (phased-array 2-dimensional echocardiography), direct central venous pressure, leg volume (Thornton sock), limb blood flow and venous compliance (occlusion plethysmography), blood and plasma volumes, renal plasma flow and glomerular filtration rates, and various hormonal levels including catecholamines and atrial natriuretic factor will also be obtained. The central venous catheter will be inserted immediately pre-launch and monitored with heart rate and blood pressure in-flight until cardiac output, respiratory gas exchange and quantitative 2D echocardiography measurements can be performed. In-flight hemodynamic measurements will be repeated at rest and during submaximal exercise daily and also during maximal exercise midway through the flight to document the timecourse and extent of cardiovascular changes in the payload crew. Parallel studies are planned for the animals. In addition to measurements of right atrial and aortic pressures and cardiac output, a dorsal micro-circulatory chamber will allow determinations of changes in capillary and venular architecture and function in six of the rats. The techniques and findings from many of the SLS-1 and 2 supporting studies have already yielded significant information about circulatory regulation in patients with both hypo- and hypertension. The flight experiments themselves will provide new data to test the validity of both animal and human models currently used for simulating the fluid shifts of a micro-gravity environment. The development of effective countermeasures, not only for short and long duration space travellers, but also for Earth-bound medical patients can then be physiologically based on experimental data rather than anecdote.

Animals↗

Right and left ventricular volumes in vitro by a new nongeometric method.

We present an evaluation of a new nongeometric technique for calculating right and left ventricular volumes. This method calculates ventricular chamber volumes from multiple cross-sectional echocardiographic views taken from a single point as the echo beam is tilted progressively through the ventricle. Right and left ventricular volumes are calculated from both the approximate short axis and approximate apical position on 20 in vitro human hearts and compared with the actual chamber volumes. The results for both ventricles from both positions are excellent. Correlation coefficients are > 0.95 for all positions; the standard errors are in the range of 5 to 7 mL and the slopes and intercepts for the regression lines are not significantly different from 1 and 0, respectively (except for the left ventricular short-axis intercept). For all positions, approximately 6 to 8 views are needed for peak accuracy (7.5 degrees to 10 degrees separation). This approach offers several advantages. No geometric assumptions about ventricular shape are made. All images are acquired from a single point (or window), and the digitized points can be used to make a three-dimensional reconstruction of the ventricle. Also, during the calculations a volume distribution curve for the ventricle is produced. The shape of this curve can be characteristic for certain situations (ie, right ventricle, short axis) and can be used to make new simple equations for calculating volume. We conclude that this is an accurate nongeometric method for determining both right and left ventricular volumes in vitro.

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↗

Stroke volume in-vivo using multiple 2D echo views from one echo window.

We recently validated in-vitro a new mathematical approach to echocardiographic volume calculation. With this method all echo views are acquired from one point as the transducer is tilted. The angle of tilt of the transducer must be measured. A tilt frame was designed for use in-vivo that does not interfere with imaging. The method was then tested in-vivo by comparing echocardiographic stroke volume with stroke volume determined by the acetylene rebreathing technique. Normal subjects were studied with either lower body negative pressure or continuous isoproterenol infusion. The regression line was Echo SV=-19.7 + 1.2*Acet SV, with R=0.80, SEE=17.1, MPE=17%. We conclude that this is an accurate, non-geometric method for ventricular volume calculation.

Acetylene↗