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Biomedical subjects

C G Blomqvist

Publications and source records attributed to C G Blomqvist.

At least 19 recordsLinked to original sources

Role of atrial natriuretic peptide in systemic responses to acute isotonic volume expansion.

Atrial natriuretic peptide (ANP) may activate multiple mechanisms that protect against circulatory volume overload. We hypothesized that a temporal relationship exists between increases in cardiac filling pressure and plasma ANP concentration and also between ANP elevation and vasodilation, fluid movement from plasma to interstitium, and increased urine volume (UV). We infused 30 ml/kg isotonic saline at 100 ml/min in seven supine male subjects and monitored responses for 3 h postinfusion. Right atrial pressure (RAP) was measured via a central catheter. ANP (pmol/l) was measured by radioimmunoassay. Transcapillary fluid transport (TFT) equaled infused volume minus UV, insensible fluid loss, and change in plasma volume (PV, measured with Evan's blue). Systemic vascular resistance (SVR) was calculated as (mean arterial pressure-RAP)/cardiac output (determined by acetylene rebreathing). Plasma oncotic pressure (OP) was measured directly. During infusion, mean TFT (+/- SE) increased from net reabsorption during control of 111 +/- 27 ml/h to net filtration of 1,219 +/- 143 ml/h (P < 0.01). At end infusion, mean RAP, heart rate, and PV exhibited peak increases of 146, 23, and 27%, respectively. Concurrently, SVR and OP achieved nadirs 29 and 31% below control, respectively. Mean plasma ANP and UV peaked (45 and 390%, respectively) at 30 min postinfusion. Systemic vasodilation and capillary filtration resulted from and compensated for infusion-induced circulatory pressure increases and hemodilution. By 1 h postinfusion, most cardiovascular variables had returned toward control levels, and net reabsorption of extravascular fluid ensued.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Diuresis and natriuresis following isotonic saline infusion in healthy young volunteers before, during, and after HDT.

In the present study the response to acute saline loading was investigated. During a 24-day study period six male subjects followed a standardized diet including a daily intake of 40 ml water and 125 mg NaCl per kg body weight. Before, during, and after a ten-day period of 6 degrees head down tilt (HDT) each volunteer received an intravenous 0.9% saline infusion of 22 ml/kg body weight over 20 minutes. HDT produced significant losses in body weight and in blood volume, but the responses to saline loading were similar during all phases of the study. Plasma levels of atrial natriuretic peptide (ANP) did not increase, while plasma levels of cyclic GMP increased by about 40% 90 minutes after each infusion. Urine flow nearly doubled during second hour post-infusion. Sodium excretion showed a 3-fold increase and remained elevated during the third hour, while potassium excretion was significantly reduced. Urinary excretion of cyclic GMP reached a peak during the second hour post-infusion. At the end of these short-term periods the cumulative water- and sodium-balance data disclosed that only about 20% of the infused water and less than 15% of the infused sodium was excreted during each experiment. In addition to the short-term renal response, urine flow and sodium excretion remained significantly elevated for more than 48 hours after each saline load. The long-term renal response was paralleled by an increased excretion of urinary cyclic GMP. HDT produced significant changes in body fluid distribution, but only minor changes in the regulatory responses to an acute saline load. We conclude from these data that the excretion of an acute isotonic saline load requires several days and that the renal response appears to be independent of the secretion of ANP from the heart.

Adult

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

Effect of head-down bedrest on blood/plasma density after intravenous fluid load.

Using the mechanical oscillator technique, the mass density of antecubital venous blood and plasma samples was measured in 6 men before and after infusion of 22 ml/kg isotonic NaCl solution before, on day 7 during, and on day 3 after ten days of 6 degrees head-down bedrest. We studied 1) the distribution volumes of the infused NaCl solution, 2) the magnitude and time-course of induced fluid shifts to the extravascular spaces after rapid volume expansion, and 3) the protein concentration of the translocated fluid. The NaCl distribution volume was 16.7 +/- 2.9% body weight (BW) before, 15.0 +/- 3.0% BW during (P less than 0.05) and 13.0 +/- 1.3% BW after the head-down tilt (HDT) period (P less than 0.01). The volume of fluid shifted 120 min after infusion was not different in the control (12.9 +/- 7.4% plasma volume and 8.3 +/- 3.2% blood volume), during HDT (14.7 +/- 3.8% plasma volume and 7.4 +/- 5.6% blood volume), during HDT HDT conditions (14.6 +/- 2.2% plasma volume, and 8.2 +/- 1.3% blood volume, respectively). The density of the shifted fluid which reflects protein concentration was also unchanged (1004.2 +/- 4.2 g/l, 1002.6 +/- 4.3 g/l and 1003.9 +/- 8.2 g/l in the control, during, and after HDT periods, respectively). The mass density of red cells did not change with any condition. It is concluded that the distribution volume of isotonic saline solution decreases with diminished body mass. Densitometry provides a means of monitoring volume changes and protein shifts under the circumstances of our study.

Adult

Effects of head-down tilt and saline loading on body weight, fluid, and electrolyte homeostasis in man.

We studied the effects of head-down tilt bedrest (HDT) on body weight, fluid and sodium homeostasis. A fluid load session with rapid intravenous infusion of 22 ml/kg body weight (BW) isotonic saline was performed before, during and after HDT. During the pre- and post HDT periods the test subjects were given a diet containing 2600 kcal/day. The energy intake was reduced to 2000 kcal/day during HDT. Water intake was kept constant at 40 ml/kg BW, sodium intake was 2.2 mmol/kg BW and protein intake was 1.4 g/kg BW, while the daily fat and carbohydrate intake was reduced during the HDT period. As expected plasma volume and BW changed rapidly in the beginning of HDT and during early recovery. A total body water loss of 0.6 l was observed within the second day after tilting. Plasma volume was reduced by 16% during HDT-bedrest. The time course of the body fluid loss paralleled a decrease in body sodium that then remained fairly constant during the HDT-bedrest period (except for the interference caused by the fluid loading on day S06). A restoration of body fluid and body sodium content occurred early in the recovery period. Fluid loading caused a negative fluid balance of 0.6-0.9 l over a 48 hr period following infusion regardless of the phase of the HDT study. These results demonstrate that under our strictly controlled conditions 1) HDT alters body fluid and sodium balances, 2) a standard fluid loading causes a net negative 3-day fluid balance during all phases of the study.

Adult

Pulmonary responses to lower body negative pressure and fluid loading during head-down tilt bedrest.

Exposure to microgravity redistributes body fluids with important secondary effects on cardiovascular function. We tested the hypothesis that the fluid shifts also affect pulmonary gas exchange. Microgravity was simulated in six male volunteers by a 10-day period of bedrest at 6 degrees head-down tilt (HDT). Lower body negative pressure (LBNP) and intravenous saline loading superimposed acute changes in fluid distribution on the prolonged effects of HDT. HDT produced relative dehydration and hypovolemia with decreased pulmonary blood flow and diffusing capacity. Before bedrest, pulmonary blood flow decreased by 24% during LBNP and diffusing capacity by 7%, while functional residual capacity increased by 14% (p less than 0.05). Intravenous saline loading caused a 24% increase in pulmonary blood-flow (p less than 0.05). Functional residual capacity decreased by 10% and diffusing capacity by 6% (p less than 0.05). Lung tissue volume did not change significantly. Head-down tilt had only minor effects on the responses to LBNP and saline loading. We conclude that LBNP and intravenous saline loading produce major changes in pulmonary blood-flow and minor effects on pulmonary gas exchange, and that the response to acute changes in fluid distribution is not significantly altered during simulated microgravity.

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

Repeated plasma volume determination with the Evans Blue dye dilution technique: the method and a computer program.

This paper describes a reliable multiple sample Evans Blue dye dilution technique and a Pascal program which computes plasma and blood volume on the basis of this technique. The program performs needed corrections and dye disappearance curve fitting. It provides menu-driven facilities for data correction, graphic display of the dye disappearance curve, and print-out of all the involved data. Means +/- S.E.M. for three plasma volume determinations in each of six resting subjects were: 3239 +/- 96 ml, 3189 +/- 81 ml, and 3187 +/- 102 ml. The differences were not statistically significant.

Blood Volume

Physical fitness and cardiovascular regulation: mechanisms of orthostatic intolerance.

We studied three groups of eight men each--high, mid, and low fit (peak O2 consumption 60.0 +/- 0.8, 48.9 +/- 1.0, and 35.7 +/- 0.9 ml.min-1.kg-1)--to determine the mechanism of orthostatic intolerance in endurance athletes. Tolerance was defined by progressive lower body negative pressure (LBNP) to presyncope. Maximal calf vascular conductance (Gmax) was measured. The carotid baroreflex was characterized using both stepwise R-wave-triggered and sustained (2 min) changes in neck chamber pressure. High-fit subjects tended to have lower LBNP tolerance than mid- and low-fit subjects but similar baroreflex responses. Subjects with poor LBNP tolerance had larger stroke volumes (SV) (120 +/- 6 vs. 103 +/- 3 ml) and greater decline in SV with LBNP to -40 mmHg (40 +/- 2 vs. 26 +/- 4%). Stepwise multiple linear regression analysis revealed that Gmax and steady-state gain of the carotid baroreflex contributed significantly toward explaining interindividual variations in LBNP tolerance. Thus endurance athletes may have decreased LBNP tolerance, but apparently not as a simple linear function of aerobic fitness. Orthostatic tolerance depends on complex interactions among functional characteristics that appear both related (Gmax and SV) and unrelated (baroreflex function) to fitness or exercise training.

Adult

Left ventricular pressure-volume and Frank-Starling relations in endurance athletes. Implications for orthostatic tolerance and exercise performance.

BACKGROUND: Endurance athletes have a high incidence of orthostatic intolerance. We hypothesized that this is related to an abnormally large decrease in left ventricular end-diastolic volume (LVEDV) and stroke volume (SV) for any given decrease in filling pressure. METHODS AND RESULTS: We measured pulmonary capillary wedge (PCW) pressure (Swan-Ganz catheter), LVEDV (two-dimensional echocardiography), and cardiac output (C2H2 rebreathing) during lower body negative pressure (LBNP, -15 and -30 mm Hg) and rapid saline infusion (15 and 30 ml/kg) in seven athletes and six controls (VO2max, 68 +/- 7 and 41 +/- 4 ml/kg/min). Orthostatic tolerance was determined by progressive LBNP to presyncope. Athletes had steeper slopes of their SV/PCW pressure curves than nonathletes (5.5 +/- 2.7 versus 2.7 +/- 1.5 ml/mm Hg, p less than 0.05). The slope of the steep, linear portion of this curve correlated significantly with the duration of LBNP tolerance (r = 0.58, p = 0.04). The athletes also had reduced chamber stiffness (increased chamber compliance) expressed as the slope (k) of the dP/dV versus P relation (chamber stiffness, k = 0.008 +/- 0.004 versus 0.031 +/- 0.004, p less than 0.005; chamber compliance, 1/k = 449.8 +/- 283.8 versus 35.3 +/- 4.3). This resulted in larger absolute and relative changes in end-diastolic volume over an equivalent range of filling pressures. CONCLUSIONS: Endurance athletes have greater ventricular diastolic chamber compliance and distensibility than nonathletes and thus operate on the steep portion of their Starling curve. This may be a mechanical, nonautonomic cause of orthostatic intolerance.

Adult

Deficiency of skeletal muscle succinate dehydrogenase and aconitase. Pathophysiology of exercise in a novel human muscle oxidative defect.

We evaluated a 22-yr-old Swedish man with lifelong exercise intolerance marked by premature exertional muscle fatigue, dyspnea, and cardiac palpitations with superimposed episodes lasting days to weeks of increased muscle fatigability and weakness associated with painful muscle swelling and pigmenturia. Cycle exercise testing revealed low maximal oxygen uptake (12 ml/min per kg; healthy sedentary men = 39 +/- 5) with exaggerated increases in venous lactate and pyruvate in relation to oxygen uptake (VO2) but low lactate/pyruvate ratios in maximal exercise. The severe oxidative limitation was characterized by impaired muscle oxygen extraction indicated by subnormal systemic arteriovenous oxygen difference (a-v O2 diff) in maximal exercise (patient = 4.0 ml/dl, normal men = 16.7 +/- 2.1) despite normal oxygen carrying capacity and Hgb-O2 P50. In contrast maximal oxygen delivery (cardiac output, Q) was high compared to sedentary healthy men (Qmax, patient = 303 ml/min per kg, normal men 238 +/- 36) and the slope of increase in Q relative to VO2 (i.e., delta Q/delta VO2) from rest to exercise was exaggerated (delta Q/delta VO2, patient = 29, normal men = 4.7 +/- 0.6) indicating uncoupling of the normal approximately 1:1 relationship between oxygen delivery and utilization in dynamic exercise. Studies of isolated skeletal muscle mitochondria in our patient revealed markedly impaired succinate oxidation with normal glutamate oxidation implying a metabolic defect at the level of complex II of the mitochondrial respiratory chain. A defect in Complex II in skeletal muscle was confirmed by the finding of deficiency of succinate dehydrogenase as determined histochemically and biochemically. Immunoblot analysis showed low amounts of the 30-kD (iron-sulfur) and 13.5-kD proteins with near normal levels of the 70-kD protein of complex II. Deficiency of succinate dehydrogenase was associated with decreased levels of mitochondrial aconitase assessed enzymatically and immunologically whereas activities of other tricarboxylic acid cycle enzymes were increased compared to normal subjects. The exercise findings are consistent with the hypothesis that this defect impairs muscle oxidative metabolism by limiting the rate of NADH production by the tricarboxylic acid cycle.

Aconitate Hydratase

Determination of left ventricular volumes with use of a new nongeometric echocardiographic method: clinical validation and potential application.

A new nongeometric echocardiographic technique for measurement of right and left ventricular volumes was recently validated in vitro. With this method, all images are taken from one point on the chest wall as the transducer is tilted through the ventricle. This approach offers several advantages. No geometric assumptions about ventricular shape are made. All images are acquired from the best echocardiographic window. Furthermore, the digitized points can be used to make a three-dimensional reconstruction of the ventricle. The present study addresses the clinical feasibility of imaging the heart from a single pivoting point in short axis and compares the accuracy of the method in determining left ventricular volumes with that of biplane cineangiography. Twenty-four patients underwent echocardiographic studies within 2 h before angiography. At catheterization, volumes determined by the biplane area-length method ranged between 95 and 368 ml at end-diastole and between 15 and 303 ml at end-systole. A good correlation was observed between ventricular volumes by angiography and echocardiography at end-diastole and end-systole (r = 0.92 and 0.96, respectively). Correlations between volumes by the two techniques were equally good in patients with wall motion abnormalities (n = 13; r = 0.97). Ventricular ejection fraction ranged between 18% and 84% at angiography and correlated well with echocardiographic measurements (r = 0.82). Thus, the echocardiographic tilt method provides accurate determination of left ventricular volume and ejection fraction. This nongeometric method offers the potential for the determination of right ventricular volume and three-dimensional display of the heart.

Adult

Effects of active muscle mass size on cardiopulmonary responses to exercise in congestive heart failure.

Previous studies from this laboratory demonstrated that in healthy young men, cardiac output is closely coupled to oxygen uptake during dynamic exercise, regardless of its mode or relative intensity, whereas other physiologic responses such as heart rate, blood pressure and ventilation are inversely related to the size of the active muscle mass when expressed as functions of oxygen uptake. The purpose of the current investigation was to determine whether congestive heart failure alters the pattern of physiologic responses to various modes of arm and leg exercise in proportion to the size of the active muscle mass. Cardiopulmonary responses to four modes of dynamic work (one arm curl, one arm cycle ergometry, one leg cycle ergometry and two leg cycle ergometry) were characterized in terms of absolute and relative intensities (oxygen uptake and mode-specific percent of peak oxygen uptake, respectively) in middle-aged men with congestive heart failure and control groups of healthy subjects and patients after myocardial infarction without heart failure. Peak oxygen uptake was reduced to the greatest extent in patients with heart failure for large muscle mass work (-13% for curl, -32% for one arm and one leg cycle ergometry and -37% for two leg cycle ergometry; p less than 0.05 versus the normal group for the three modes of ergometry). This finding was paralleled by a markedly blunted slope for the cardiac output-oxygen uptake relation for leg but not arm exercise that was only partially compensated for by a widened arteriovenous oxygen difference. Blood pressure expressed as a function of oxygen uptake remained inversely related to active muscle mass size in all groups of subjects despite attenuation of systolic pressure for heavy large muscle mass effort in the group with heart failure. Pulmonary ventilation at a given metabolic rate was not influenced by active muscle mass size. Thus, saturation of capacity for systemic oxygen transport occurs in conjunction with blunted cardiac output reserve in patients with heart failure during exercise involving a smaller muscle mass than in healthy subjects. The basic inverse relation between size of the active muscle mass and blood pressure at a given metabolic rate is not altered by aging or reduced cardiac reserve. The muscle mass effect on ventilation seen in young healthy subjects disappears with aging.

Blood Pressure

ST isopotential precordial surface maps in patients with acute myocardial infarction.

ST amplitude distributions were studied in 41 patients with acute myocardial infarction by deriving isopotential maps from a 5 x 7 electrode precordial matrix. Independent data on infarct size and localization were obtained utilizing the technetium 99m stannous pyrophosphate scintigraphic method. The locus of maximal ST elevation was stable for at least two days in 86% of 27 patients with anterior infarction. A single maximum or maximum-minimum was found in 88% but 22% of the patients had multiple maxima and/or minima in at least two maps. Areas of significant ST elevation were often excluded from the precordial matrix. The site of maximal ST elevation correlated with scintigraphic infarct site but was displaced medially in lateral infarction. The relation between infarct size and sigmaST elevation was significant and curvilinear. sigmaST underestimated size in large anterior infarction. The correlation of the size and the number of sites with ST elevation greater than or equal to 1.5 mm was weak (r = 0.56). The degree of ST abnormality in 14 patients with inferior infarction decreased significantly during the initial 24 hours. The isopotential maps were similar to those obtained in anterior infarction but the polarity was reversed. The results provide limited support for the continued exploration of ST analysis as a clinical method but suggest that sizing methods should be based on total body surface mapping, taking into account the geometry and electrical properties of the torso.

Action Potentials

Exercise testing in men with significant left main coronary disease.

The exercise tests of 26 male patients with significant left main disease were compared with those of 51 patients with three-vessel disease and 38 patients with two-vessel disease. Exercise-induced ischaemia (chest pain and/or greater than 1 mm ST segment change) occurred in 100 per cent of left main, 69 per cent of three-vessel, and 45 per cent of two-vessel disease patients. Though the mean peak work load was significantly higher in the two-vessel disease group than in those with three-vessel of left main disease, there was a wide overlap between groups. No intergroup differences were found in mean peak heart rates. In patients taking propranolol, no differences in mean peak work loads and heart rates were seen. The study showed that the absence of an exercise-induced abnormal electrocardiographic response virtually excludes left main disease. As judged by exercise performance, the presence of left main disease did not correlate with the severity of the patient's symptomatology. Propranolol did not influence the frequency of an ischaemic response in patients with left main or three-vessel disease.

Coronary Disease

Autonomic dysfunction in women with mitral valve prolapse syndrome.

Autonomic cardiovascular regulation was evaluated in 35 women, 19 with mitral valve prolapse and 16 healthy controls. Heart rate responses to the diving reflex and to phenylephrine infusion were diminished in patients. Noninvasive measures of cardiac output, heart rate, blood pressure, forearm flow and leg volume during lower body negative pressure (LBNP) showed that patients had less lower extremity pooling of blood and had lower forearm conductance. Blood pressures during LBNP rose or remained unchanged despite decreases in cardiac output of 20--25%. These data indicate that mitral valve prolapse patients have an increased venous and arterial vasoconstrictor activity. Cardiac output at rest and echocardiographic indices of contractility were normal. Patients with a history of significant ventricular arrhythmias had higher heart rates and lower forward stroke volumes than the other patients or controls. The combined data demonstrate autonomic dysfunction in women with the mitral valve prolapse syndrome and suggest decreased parasympathetic, increased alpha- and normal beta-adrenergic tone and responsiveness.

Adult