Cardiovascular reserve in idiopathic dilated cardiomyopathy as determined by exercise response during cardiac catheterization.

Simultaneous right- and left-sided cardiac high-fidelity hemodynamic measurements were obtained at rest and supine exercise during cardiac catheterization in 27 patients (mean age 32 +/- 10 years) with idiopathic dilated cardiomyopathy to investigate the hemodynamic exercise response and possible mechanisms for the wide variation in exercise tolerance observed clinically. There were no significant differences in other rest hemodynamic variables between group 1, patients with a normal exercise factor (more than 600, n = 10), and group 2, patients with an abnormal exercise factor (less than 600, n = 17). A greater increase in stoke volume index (12 +/- 6 vs 2 +/- 8 ml/beats/m2, mean +/- standard deviation) and a greater decrease in systemic vascular resistance with exercise occurred in group 1 than in group 2 (-614 +/- 304 vs -406 +/- 291 dynes cm-5). Elevation of right ventricular end-diastolic pressure with exercise was significantly greater in group 2 than in group 1 (7 +/- 5 vs 1 +/- 4 mm Hg, respectively, p less than 0.05). A maintained cardiac reserve in patients with idiopathic dilated cardiomyopathy appears to be largely dependent on 2 primary factors: preservation of normal right ventricular function during exercise; and preservation of systemic vasodilator capability sufficient to produce a significant degree of afterload reduction during exercise.

Aortic input impedance during Mueller maneuver: an evaluation of "effective length".

Aortic input impedance was calculated in seven subjects in the control state (normal reflection) and during the Mueller maneuver (increased reflection) to evaluate "effective arterial length" under altered physiological conditions. Regional foot-to-foot pulse wave velocities and pressure waveforms along the aorta were used to define an "apparent anatomic length" or distance to a dominant discrete site of reflection "seen" by the ejecting ventricle. Time of wave travel was taken to be one-half the interval from the foot of the incident wave to the midsystolic inflection point. Knowing the time of travel from the returning reflection and velocity, distances calculated to the "apparent anatomic length" were 35 +/- 2 and 34 +/- 2 during control and Mueller maneuver, respectively (P = NS). The frequency of the first minimum of the modulus (fmin) and the first zero crossing of the phase angle (f phi) were determined from the input impedance spectra. During baseline conditions, fmin (3.9 +/- 0.2 Hz) approximately equaled f phi (4.2 +/- 0.2 Hz), and the resulting "effective lengths" calculated using the quarter-wavelength formula were similar to the apparent anatomic length. These data suggested that the aortic region incorporating the renal arterial branches as a site of discrete reflection and that terminal load was not significantly frequency dependent. During Mueller maneuver, however, f min (3.3 +/- 0.2 Hz) and f phi (5.1 +/- 0.2 Hz) were significantly discordant, the terminal load became strongly frequency dependent, and effective length calculated from f min was dissimilar (P less than 0.05) from the unchanged apparent anatomic length.(ABSTRACT TRUNCATED AT 250 WORDS)

Doppler evaluation of cardiac filling and ejection properties in humans during parabolic flight.

The cardiac filling and ejection properties of seven normal human subjects were examined during microgravity created on a National Aeronautics and Space Administration aircraft during parabolic flight. Doppler echocardiography was used to measure intracardiac velocities in sitting and supine subjects during three phases of flight: hypergravity (phase I), early microgravity (phase III), and late microgravity (phase IV). Heart rate declined 6% (P < 0.001) and right ventricular inflow velocities rose (46%, early; 26%, mean; P < 0.01) between phase I and phases III or IV in the sitting position only. Peak left ventricular outflow velocities rose 12% and inflow velocities rose (13%, early; 20%, mean) between phases I and IV while subjects were in the supine position (P < 0.05). A 14% rise in early velocities alone was seen between phases I and IV while subjects were in the sitting position (P < 0.05). In subjects entering microgravity while sitting, right heart chambers can accept additional venous return. When microgravity was entered while subjects were supine, however, venous augmentation was not observed. Left heart filling was more prominently enhanced when microgravity was entered while subjects were supine, suggesting a shift of fluid within the pulmonary vasculature.

A conscious baboon model for evaluation of hemodynamics in altered gravity.

A model was developed for evaluation of cardiovascular parameters in conscious baboons exposed to altered gravitational environments. Baboons were trained to sit quietly in a confinement chair of unique design which allowed a range of normal physical activity. They were then instrumented with high-fidelity blood pressure transducers in the aorta and left ventricle, electromagnetic flow probes encircling the proximal ascending aorta, left and right atrial fluid catheters, left ventricular sonomicrometer crystals in a 3-axis configuration, and a hydraulic occluder cuff encircling the inferior vena cava. Catheters and transducer wires were exteriorized at the midscapular region of the back. Viability of percutaneous exit sites was enhanced by use of velour cuffs on the transducer wires, providing a scaffold for wound healing. Pressure transducers and flow probes were calibrated and balanced during postoperative cardiac catheterization procedures. This instrumentation allowed measurement of beat-to-beat stroke volume and cardiac output not reliant on thermodilution techniques. Postoperative longevity was from 1 to 10 months. Instrumentation failure included endocardial trapping of ventricular pressure transducers, corrosion of ventricular sonomicrometer crystals, and catheter tip thrombosis. Acquisition of high quality data was possible with this model in several different environments of altered gravitational stress, allowing characterization of aortic flow and ventricular performance.

A method for repeated high-fidelity micromanometer measurement of intracardiac pressures.

Dial-tipped, high-fidelity micromanometers were inserted through polyurethane catheters to acutely measure blood pressures within the chambers of the heart and the great vessels of baboons, rhesus monkeys, and goats. Repeated measurements of atrial, ventricular, aortic, and pulmonary artery pressure were possible with this method, with calibration of micromanometers accomplished immediately prior to and after pressure recordings to assure data accuracy. All attempts to pass micromanometers into the atria in all species were successful. Passage of micromanometers from the left ventricle across the aortic valve and into the aorta was successful in 97% of the attempts in baboons, 100% for rhesus monkeys, and 75% for goats; while insertions into the pulmonary artery from the right ventricle were successful in 64% of the baboons, 40% of the rhesus monkeys, and 75% of the goats. Advantages of this technique are that a permanent conduit for cardiac vascular access is available and that high-fidelity pressure signals may be acquired.

Evaluation of dual-tip micromanometers during 21-day implantation in goats.

Investigative research efforts using a cardiovascular model required the determination of central circulatory haemodynamic and arterial system parameters for the evaluation of cardiovascular performance. These calculations required continuous beat-to-beat measurement of pressure within the four chambers of the heart and great vessels. Sensitivity and offset drift, longevity, and sources of error for eight 3F dual-tipped micromanometers were determined during 21 days of implantation in goats. Subjects were instrumented with pairs of chronically implanted fluid-filled access catheters in the left and right ventricles, through which dual-tipped (test) micromanometers were chronically inserted and single-tip (standard) micromanometers were acutely inserted. Acutely inserted sensors were calibrated daily and measured pressures were compared in vivo to the chronically inserted sensors. Comparison of the pre- and post-gain calibration of the chronically inserted sensors showed a mean sensitivity drift of 1.0 +/- 0.4% (99% confidence, n = 9 sensors) and mean offset drift of 5.0 +/- 1.5 mmHg (99% confidence, n = 9 sensors). Potential sources of error for these drifts were identified, and included measurement system inaccuracies, temperature drift, hydrostatic column gradients, and dynamic pressure changes. Based upon these findings, we determined that these micromanometers may be chronically inserted in high-pressure chambers for up to 17 days with an acceptable error, but should be limited to acute (hours) insertions in low-pressure applications.

Central hemodynamics in a baboon model during microgravity induced by parabolic flight.

We developed a chronically instrumented nonhuman primate model (baboon) to evaluate the central cardiovascular responses to transient microgravity induced by parabolic flight. Instrumentation provided simultaneous recording of high fidelity (Ao) and pulmonary artery (PA) pressures, right and left ventricular and atrial pressures, Ao and PA blood flow velocities and vessel dimensions, ECG and pleural pressures. Four daily flights in 1991 and five in 1992 were flown with forty parabola per flight. Animals flown in 1991 were not controlled for volume status. Animals flown in 1992 were studied in one of three conditions: 1) volume depleted by furosemide (DH), 2) volume expanded by saline infusion (VE), and 3) euvolemic (EU, no intervention, used for echo only). Mean right atrial pressures (RAP) during 1991 flights had a variable early microgravity response: increases in n=3 and decrease in n=3 (supine) and increases in n=5, decreases in n=2 (upright). In 1992 flights, DH, upright and supine, changed -10 +/- 4.1 mmHg, -3.2 +/- 2.2 mmHg, respectively (p < .05) compared to the pull-up phase. In contrast, VE changed (from pull-up to microgravity) +13 +/- 1.5 mmHg and +4.25 +/- 2.9 mmHg (upright and supine, respectively, p < .05). EU increased with microgravity +6.9 +/- .9 mmHg (upright only). LAP responses were similar, but more variable. Finally, heart chamber areas paralleled pressure changes. Thus, right and left heart filling pressure changes with sudden entry into microgravity conditions were dependent on initial circulatory volume status and somewhat modified by position (supine vs upright).

Beat-to-beat determination of peripheral resistance and arterial compliance during +Gz centrifugation.

This study focused on the problem of describing changes in total peripheral resistance (TPR) and systemic arterial compliance (SAC) under time-varying +Gz acceleration stress. Nonsteady-state measures of peripheral resistance can only be derived when arterial compliance is taken into account. We have developed a successful analytical model to track simultaneous changes in peripheral resistance and systemic arterial compliance during non-stationary periods of increased gravitational load on a beat-to-beat basis. Using a 2-element windkessel model, aortic flow into an input node was defined as equal to the sum of a capacitative (Cao) and a resistive (Rarterial) flow leaving the node such that: Iao = Caod(Pao - Ppleural)/dt + (Pao - Pra)/Rarterial We made the assumption that Cao and Rarterial were constant over a cardiac cycle, and divided the pressure and flow signals for each beat of a record into two different intervals, integrating this equation over each, giving two equations in two unknowns. Cao and Rarterial were then obtained from the matrix solutions. To test the model, we used recordings from chronically instrumented baboons subjected to a 10 s rapid onset +Gz (head-to-foot) stress. Beat-to-beat calculations of peripheral resistance and systemic arterial compliance from our model were compared to values obtained from a previously reported 3-element wind-kessel model.

An acute animal model that simulates the hemodynamic situations present during +Gz acceleration.

Air combat maneuver acceleration (G) profiles with onset/offset patterns that occur faster than the response characteristics of the human cardiovascular system may lead to regulatory instability and, ultimately, acceleration-induced loss of consciousness (G-LOC) incidents. We have developed an acute animal model that simulates the hemodynamic situations seen under acceleration to study the effects of complex G environments on individual reflexogenic areas. This preparation allowed us to individually isolate the effects of high gravity on venous return and cardiac preload, arterial baroreflexes and splanchnic capacity. This report describes the preparation and presents examples of the types of +Gz simulations possible and recordings of the responses of the animals. Further, we tested the hypothesis that the volume of blood displaced from the cephalic regions of the circulation and the rate of displacement into the splanchnic capacitance with G onset is affected by distending pressure at the carotid/aortic baroreceptor sites. Early results from 7 dogs show that resistance to flow into the splanchnic beds is affected by changes in distending pressure occurring at arterial baroreceptor sites. When pressure distending the carotid/aortic baroreceptors was increased, resistance to flow into the abdominal vascular beds was decreased. This result suggests that sudden increases in +Gz loads occurring during the overshoot phase from a previous G-peak may result in reduced tolerance.

The role of arterial elastance in ventricular-arterial coupling in normal gravity and altered acceleration environments.

The role of physiological elastance (Ep) in maximizing external work (EW) transfer is not well understood and has not been investigated during microgravity and increased acceleration conditions. By better understanding this relationship, cardiovascular control mechanisms for meeting metabolic demands during normal gravity and altered acceleration stresses may be elucidated. Therefore, the objectives of this study were to determine the effect of Ep in maximizing EW of the left ventricle and to investigate this relationship during altered acceleration states. Ventricular and arterial parameters were estimated using established lumped parameter models from isolated beats of experimental data. These data were obtained during parabolic flight (0 and approximately 2 Gz) and centrifuge runs (approximately 1 to approximately 4 Gz) where acceleration was used to drive the cardiovascular system into a wide range of physiologic operating and coupling conditions. Parameter estimates at each Gz level were used in a series of computer simulations in which Ep was varied over a wide range to find the point of maximum EW for that coupling condition. Cardiac output and mean arterial pressure were maintained throughout the simulation process by adjusting heart rate. Results of the simulation showed that as arterial elastance decreased from its initially estimated (physiologic) value, external work increased slightly and as elastance increased, external work decreased. In particular, we found that the arterial elastance was set at a point near that which would produce maximal external work. In addition, it was found that altered Gz states may affect the Ep-EW relationship.

Effects of 12 days exposure to simulated microgravity on central circulatory hemodynamics in the rhesus monkey.

Central circulatory hemodynamic responses were measured before and during the initial 9 days of a 12-day 10 degrees head-down tilt (HDT) in 4 flight-sized juvenile rhesus monkeys who were surgically instrumented with a variety of intrathoracic catheters and blood flow sensors to assess the effects of simulated microgravity on central circulatory hemodynamics. Each subject underwent measurements of aortic and left ventricular pressures, and aortic flow before and during HDT as well as during a passive head-up postural test before and after HDT. Heart rate, stroke volume, cardiac output, and left ventricular end-diastolic pressure were measured, and dP/dt and left ventricular elastance was calculated from hemodynamic measurements. The postural test consisted of 5 min of supine baseline control followed by 5 minutes of 90 degrees upright tilt (HUT). Heart rate, stroke volume, cardiac output, and left ventricular end-diastolic pressure showed no consistent alterations during HDT. Left ventricular elastance was reduced in all animals throughout HDT, indicating that cardiac compliance was increased. HDT did not consistently alter left ventricular +dP/dt, indicating no change in cardiac contractility. Heart rate during the post-HDT HUT postural test was elevated compared to pre-HDT while post-HDT cardiac output was decreased by 52% as a result of a 54% reduction in stroke volume throughout HUT. Results from this study using an instrumented rhesus monkey suggest that exposure to microgravity may increase ventricular compliance without alternating cardiac contractility. Our project supported the notion that an invasively-instrumented animal model should be viable for use in spaceflight cardiovascular experiments to assess potential changes in myocardial function and cardiac compliance.

Body position and volume status as determinants of cardiovascular responses to transition into microgravity in parabolic flight.

The condition of microgravity during spaceflight imposes a new challenge to the cardiovascular system and to its homeostatic mechanisms. Initial fluids shifts from the dependent parts to the upper parts of the body are supposed to induce a plethora of effects which eventually lead to the well-known puffy faces and chicken legs' of astronauts. At the same time some 2-3 kgs. in fluid is lost in urine and by diminished uptake. For research into these longer-term effects of spaceflight extensive physiologic experiments are required in space. In view of the high cost and the logistic problems related to space-research much work is done in simulation experiments like bedrest or head down tilt studies. For the very initial effects of micro-G parabolic flight can be used. In parabolic flights we have addressed the question of immediate cardiovascular effects of the transition into microgravity. Since a parabola will last for not more than some 25 seconds, one may expect to observe mainly changes in the outflow of the autonomic nervous system, reflecting in blood pressure and heart rate as easily measurable parameters. Such changes can be expected to be caused by the sudden disappearance of hydrostatic effects and the shifts of fluid from pools where it is kept under the influence of gravity. Hydrostatic effects will play a role in the position of the baroreceptors with respect to the heart: in the upright position the carotid sinuses are some 25 cm above heart level, consequently they observe a lower pressure than that at the heart. When this effect disappears in micro-G a suddenly increased pressure will be observed and the baroreflex is called into action. On the venous side blood will rush to the right atrium when it is no longer pulled down in the compliant vessels of the abdomen and legs. This may be expected to lead to increased pressures on the low-pressure side of the heart. Apart from changes in filling of the left heart this may lead to autonomic nervous effects on systemic blood pressure and heart rate as well.

Transesophageal echocardiographic evaluation of baboons during microgravity induced by parabolic flight.

The central cardiovascular responses to transient microgravity are not well understood. Theoretically, entrance into microgravity results in the loss of the hydrostatic pressure head and an increase in central venous pressure (CVP) as a consequence of augmented venous return. However, controversy exists regarding the time course and magnitude of cephalad blood volume shifts and its relationship to central atrial filling pressures. On the June 1991 STS 40 shuttle mission, pre-launch echocardiograms suggested changes in cardiac dimensions occurred while the astronauts were in the supine, feet-up position. Furthermore, a CVP line in an astronaut (n=1) demonstrated an unexpected abrupt decrease in CVP during orbital insertion. In April 1991, our laboratory performed Doppler echocardiography in 6 normal human volunteers during parabolic flight. Increases in right ventricular velocities reflecting a central shift of blood volume was demonstrated in subjects examined in the sitting position. However, test subjects examined in the horizontal positions had no significant rise in Doppler velocities. In addition, Latham et al noted variable central cardiovascular responses in chronically instrumented baboons during early microgravity. Transthoracic echocardiography (TTE) is a feasible method to noninvasively examine cardiac anatomy during parabolic flight. However, transducer placement on the chest wall is very difficult to maintain during transition to microgravity. In addition, TTE requires the use of low frequency transducers (2.5 MHz) which limits resolution. Transesophageal echocardiography (TEE) is an established imaging technique which obtains echocardiographic information from the esophagus. It is a safe procedure and provides higher quality images of cardiac structures than obtained with TTE. Since there are no interposed structures between the esophagus and the heart, higher frequency transducers can be used and resolution is enhanced. With TEE, a flexible transducer tip permits contact with the esophageal mucosa, allowing for consistent imaging. This study was designed to determine whether TEE was feasible to perform during parabolic flight and to determine whether acute central volume responses occur in acute transition to zero gravity (0G) by direct visualization of the cardiac chambers.

Circulatory filling pressures during transient microgravity induced by parabolic flight.

Theoretical concepts hold that blood in the gravity-dependent portion of the body would relocate to more cephalad compartments under microgravity conditions. The result is an increase in blood volume in the thoracic and cardiac chambers. This increase in central volume shift should result in an increase in central atrial filling pressures. However, experimental data has been somewhat contradictory and nonconclusive to date. Early investigations of peripheral venous pressure and estimates of central venous pressure (CVP) from these data did not show an increase in CVP in the microgravity condition. However, CVP recorded in human volunteers during the parabolic flight by Norsk revealed an increase in CVP during the microgravity state. On the June 1991 STS 40 shuttle mission, a payload specialist wore a fluid line that recorded CVP during the first few hours of orbital insertion. These data revealed decreased CVP. When this CVP catheter was tested during parabolic flight in four subjects, two subjects had increased CVP recordings and two other subjects had decreased CVP measurements. In April 1991, our laboratory performed parabolic flight studies in several chronic-instrumented baboon subjects. It was again noted that centrally recorded right atrial pressure varied with exposure to microgravity, some animals having an increase and others having a decrease. Thus, data presently available has demonstrated a variable response in the mechanism not clearly defined. In April 1992, we determined a test hypothesis relating the possible mechanism of these variable pressure responses to venous pressure-volume relationships.