Frank-Starling Relationship Research Articles

Length-dependence of Cross-bridge Mediated Activation of the Cardiac Thin Filament

Length-dependent Ca2+activation of the thin filament plays a critical role in the steep force–length relationship of cardiac muscle (Frank-Starling relation). Recent evidence indicates that the increase in myofilament Ca2+sensitivity and Ca2+-troponin C affinity that occurs with increase in sarcomere length results from a cooperative activation of the thin filament by attached cross-bridges. At short sarcomere length the Ca2+sensitivity is lower because the access of cross-bridges for actin is reduced. The aim of this study was to determine the length-dependence of myosin-mediated thin filament activation in skinned bovine ventricular muscle, as assayed by the generation of force with progressive reduction of MgATP concentration in the absence of Ca2+. If the interaction between myosin and actin is weaker at short sarcomere length there should be a lower MgATP concentration needed to maintain the relaxed state. Contrary to expectation, the force–pMgATP relationship was not significantly influenced by change in sarcomere length. However this relationship became length-sensitive in the presence of phosphate analogs which stabilize weak-binding cross-bridges. We suggest that sarcomere length modulates Ca2+sensitivity by controlling the size of the population of thin filament regulatory units in the weakly-bound state.

Is titin the length sensor in cardiac muscle? Physiological and physiopathological perspectives.

One of the most salient physiological characteristics of cardiac muscle is that a dilated heart pumps more vigorously, a phenomenon known as the Frank-Starling relationship (see Allen and Kentish, 1985). At least two cellular mechanisms participate in this phenomenon: the reduction of the interfilament lattice spacing which favors the formation of cross-bridges (Wang and Fuchs, 1995) and the increased affinity of troponin C (TnC) for calcium (Ca2+) (Babu et al., 1988). In the latter case, it has been established that TnC itself is not the length sensor (Moss et al., 1991). The intracellular structure(s) able to sense changes in cell length has always been challenged and is still not known. We previously observed on intact isolated cardiac cells that active tension is more closely related to passive tension than to sarcomere length per se (Cazorla et al., 1997). This might have some physiological implications in the working heart since we found that sub-epicardial cells are more supple than sub-endocardial cells. In the present work on skinned cells, we studied the relationship between different levels of passive tension (modulated by a mild trypsin digestion) and the shift in pCa50 of tension-pCa relations induced by a stretch of cells from 1.9 to 2.3 microns sarcomere length. A significant correlation was obtained between passive tension and the stretch-induced shift in pCa50, or stretch-sensitivity of the active force. These observations led us to assume that titin might play a role in sensing cell length to modulate the contractile activity. Besides, it is known that myocardial infarcted cells are less sensitive to stretch. We propose that, in such a rat model, alterations of titin might participate in heart failure.

Using heart-lung interactions to assess fluid responsiveness during mechanical ventilation

According to the Frank-Starling relationship, a patient is a 'responder' to volume expansion only if both ventricles are preload dependent. Mechanical ventilation induces cyclic changes in left ventricular (LV) stroke volume, which are mainly related to the expiratory decrease in LV preload due to the inspiratory decrease in right ventricular (RV) filling and ejection. In the present review, we detail the mechanisms by which mechanical ventilation should result in greater cyclic changes in LV stroke volume when both ventricles are 'preload dependent'. We also address recent clinical data demonstrating that respiratory changes in arterial pulse (or systolic) pressure and in Doppler aortic velocity (as surrogates of respiratory changes in LV stroke volume) can be used to detect biventricular preload dependence, and hence fluid responsiveness in critically ill patients.

Effect of Ionic Strength on Length-dependent Ca2+Activation in Skinned Cardiac Muscle

S. H. Smith and F. Fuchs. Effect of Ionic Strength on Length-dependent Ca2+Activation in Skinned Cardiac Muscle. Journal of Molecular and Cellular Cardiology (1999) 31, 2115–2125. The length-dependence of myofilament Ca2+sensitivity is considered to be an important component of the steep force–length relationship in cardiac muscle (Frank–Starling relation). Recent studies suggest that Ca2+sensitivity is a function of the number of strong-binding cross-bridge interactions formed at a given sarcomere length. However, the length-dependent step in the thin filament activation process is still unknown. This study was designed to test the hypothesis that sarcomere length influences the transition of the thin filament from the unattached (blocked) state to the weakly bound (closed) state. This hypothesis was tested by determining the length-dependence of Ca2+sensitivity as a function of ionic strength in skinned bovine ventricular muscle. Previous studies have shown that reduction in ionic strength below a critical level, in the absence of Ca2+, shifts the thin filament to the closed state. In this study normal Ca2+regulation was maintained at low ionic strength but the length-dependence of Ca2+sensitivity and the length-dependence of Ca2+binding were eliminated. These results are consistent with the hypothesis that the transition from the blocked to the closed state is a function of filament geometry as well as Ca2+and ionic strength.

Means for Load Variation During Echocardiographic Assessment of the Frank-Starling Relationship

Because minimally invasive methods of preload variation are not validated for load-insensitive indexes of cardiac performance, intravenous nitroglycerin (NTG), phenylephrine, and saline solution (VOL) boluses were used in blocked and intact autonomic states to alter load and were compared with vena caval occlusion in the assessment of preload recruitable stroke work relationships between stroke work and left ventricular end-diastolic volume in dogs. In both autonomic states NTG and VOL produced comparable linear relationships. NTG and saline solution were combined with noninvasive measurements of left ventricular pressure and volume to construct echocardiographic relationships between stroke work and left ventricular end-diastolic cross-sectional area; NTG produced linear relationships similar to vena caval occlusion. Therefore NTG and VOL reliably alter load in constructing preload recruitable stroke work relationships, and NTG may be used with noninvasive measurements to provide load-insensitive estimates of cardiac function in a minimally invasive manner. (J Am Soc Echocardiogr 1999;12:792-800.)

Length Modulation of Active Force in Rat Cardiac Myocytes: is Titin the Sensor?

The intrinsic cellular mechanisms by which length regulates myocardial contraction, the basis of the Frank–Starling relation, are uncertain. The aim of this work was to test the hypothesis that passive force, possibly via titin, participates in the modulation of Ca2+sensitivity of cardiac contractile proteins induced by stretch. Titin degradation by a mild trypsin digestion modulated passive force induced by increasing from 1.9 to 2.3 μ m sarcomere length in skinned rat cardiac cells. Force–pCa curves were established at these two sarcomere lengths after various durations of trypsin application that induced different passive force levels. They allowed us to evaluate myofilament Ca2+sensitivity by the pCa of half-maximal activation (pCa50). In control conditions, stretching cells from 1.9 to 2.3 μ m induced a leftward shift of pCa50(ΔpCa50) of 0.39±0.03 pCa units (mean±SEM, n=8 cells), reflecting an increase in Ca2+sensitivity of the contractile machinery. Passive force measured every 2 min decreased exponentially after the beginning of the trypsin application (t1/2@12 min). The first 30% decrease of passive force did not affect the stretch-induced variation in Ca2+sensitivity. Then, with further decrease in passive force, ΔpCa50decreased. At the lowest passive force investigated 20% of initial passive force, ΔpCa50decreased by approximately 55%. These effects were not accompanied by a significant modification of either maximal activated force at pCa 4.5 solution or pCa50at 1.9 μ m sarcomere length. This indicates that there was no major functional alteration of the contractile machinery during the protocol as also suggested by contractile and regulatory protein electrophoresis on 2.5–12% gradient and 15% SDS–PAGE gels. Thus, besides modulation induced by the reduced lattice spacing during enhanced heart refilling, Ca2+sensitivity of the cardiac contractile machinery may be controlled at least partially by internal passive load, which is known to be largely attributable to titin.

An improved isolated, left ventricular ejecting, murine heart model. Functional and metabolic evaluation.

An improved, isolated, left ventricular-ejecting, murine heart model is described and evaluated. Special attention was paid to the design and impedance characteristics of the artificial aortic outflow tract and perfusate composition, which contained glucose (10 mM plus insulin) and pyruvate (1.5 mM) as substrates. Temperature of the isolated perfused hearts was maintained at 38.5 degrees C. During antegrade perfusion (preload 10 mm Hg, afterload 50 mm Hg, 2.5 mM Ca2+) proper design of the aortic outflow tract provided baseline values for cardiac output (CO), left ventricular developed pressure (LVDP) and the maximum first derivative of left ventricular pressure (LV dP/dtmax) of 11.1+/-1.7 ml min-1, 83+/-5 mm Hg and 6283+/-552 mm Hg s-1, respectively, resembling findings in the intact mouse. During 100 min normoxic antegrade perfusion CO declined non-significantly by less than 10%. Varying pre- and afterloads resulted in typical Frank-Starling relationships with maximal CO values of 18.6+/-1.8 ml min-1 at pre- and afterload pressures of 25 and 50 mm Hg, respectively. Left ventricular function curves were constructed at free [Ca2+] of 1.5 and 2.5 mM in the perfusion medium. Significantly higher values for CO, LVDP and LV dP/dtmax and LV dP/dtmin were obtained at 2.5 mM Ca2+ at all loading conditions investigated. Phosphocreatine and creatine levels remained stable throughout the perfusion period. Despite a small but significant decline in tissue ATP content, the sum of adenine nucleotides did not change during the normoxic perfusion period. The tissue content of glycogen increased significantly.

The Frank-Starling mechanism is not mediated by changes in rate of cross-bridge detachment

We tested the hypothesis that the Frank-Starling relationship is mediated by changes in the rate of cross-bridge detachment in cardiac muscle. We simultaneously measured isometric force development and the rate of ATP consumption at various levels of Ca2+ activation in skinned rat cardiac trabecular muscles at three sarcomere lengths (2.0, 2.1, and 2.2 microns). The maximum rate of ATP consumption was 1.5 nmol.s-1.microliter fiber vol-1, which represents an estimated adenosinetriphosphatase (ATPase) rate of approximately 10 s-1 per myosin head at 24 degrees C. The rate of ATP consumption was tightly and linearly coupled to the level of isometric force development, and changes in sarcomere length had no effect on the slope of the force-ATPase relationships. The average slope of the force-ATPase relationships was 15.5 pmol.mN-1.mm-1. These results suggest that the mechanisms that underlie the Frank-Starling relationship in cardiac muscle do not involve changes in the kinetics of the apparent detachment step in the cross-bridge cycle.

Hypoxia and ischaemia in buffer-perfused toad hearts.

Previous studies on the effects of ischaemia or hypoxia in ectothermic vertebrate hearts have generally used preparations that were not performing at physiological levels of pressure and flow. The conclusions that ischaemia or hypoxia are not stressful to these organisms were examined in another species, Bufo marinus, in which a buffer-perfused heart was performing physiological levels of work. The in situ preparation demonstrated the Frank-Starling relationship and mechanical characteristics similar to the hearts of intact animals. The hearts recovered from 60 min of ischaemia and reperfusion with no reduction in pressure, flow or heart rate parameters. Hearts exposed to 30 min of hypoxia at physiological filling and diastolic afterload pressures ceased generating a continuous cardiac output during the hypoxia. In most cases, there was a gradual reduction of cardiac output to zero, but in 27% of the hearts studied, intermittent beating was observed. During reoxygenation, the hearts recovered 50-90% of their prehypoxic function and were damaged. Hearts exposed to hypoxia with reduced filling and diastolic afterload continued to develop a cardiac output throughout the hypoxia and demonstrated an overshoot phenomena with the onset of reoxygenation. If demand is in the normal range at the onset of hypoxia, the hearts intrinsically reduce demand either by reducing pressure development or by conversion to intermittent beating. Toad hearts appear not to be damaged by ischaemia, a condition in which demand is low.

Heart reduction surgery: An analysis of the impact on cardiac function

Objectives: Reports of improved ejection fraction, coupled with decreased filling pressures, have prompted a number of centers to begin evaluating the efficacy of heart reduction surgery to ameliorate symptoms of heart failure. However, the impact of this operation on cardiac mechanics is unknown. We applied a multiple compartment elastance model to simulate the effects of excising cardiac mass on heart function. Methods: The left ventricle was divided into two functional compartments to simulate excision of part of the wall. At multiple increments of mass reduction, the resulting end-systolic elastance, ejection fraction, stroke volume, end-diastolic pressure and volume, and diastolic stiffness were determined. Results: Changes in systolic function were accompanied by offsetting changes in diastolic function; consequently, overall pump function (the Frank-Starling Relationship) was found to be depressed. The geometric rearrangement associated with this operation leads to a reduction in wall stress for a given level of pressure generation, thus implying an increase in the efficiency with which wall stress is transduced into intraventricular pressure. Conclusions: Overall pump function is depressed in the short run after heart reduction surgery. However, on the basis of theoretic arguments, heart reduction surgery may have long-term beneficial implications. Importantly, this analysis revealed that changes in parameters of ventricular function have different implications during heart reduction surgery than when such changes are observed with inotropism caused by acute pharmacologic therapy. (J Thorac Cardiovasc Surg 1997;113:1032-40)

Effects of epinephrine on right ventricular function in patients with severe septic shock and right ventricular failure: a preliminary descriptive study.

To recognize patients with unresponsive septic shock and right ventricular (RV) failure and to evaluate the effects of epinephrine on RV performance in these patients. Prospective descriptive study. Medical intensive care unit. 14 consecutive patients in septic shock unresponsive to fluid loading, dopamine, and dobutamine. Evaluation of RV function by thermodilution with a pulmonary artery catheter equipped with a rapid-response thermistor. Measurements were obtained before and during epinephrine infusion to achieve a systolic arterial pressure > or = 90 mmHg or a mean arterial pressure (MAP) > or = 70 mmHg. At the time of inclusion in the study the hemodynamic pattern in the 14 patients was as follows: (MAP) 58 +/- 14 mmHg, systemic vascular resistance (SVR) 1046 +/- 437 dyne.s.cm-5.m-2, pulmonary artery occlusion pressure (PAOP) 14 +/- 4 mmHg, mean pulmonary artery pressure (MPAP) 24 +/- 4 mmHg, right arterial pressure (RAP) 11 +/- 4 mmHg, cardiac index (CI) 4 +/- 1.7 l/min per m2. During epinephrine infusion, MAP, CI and stroke volume index (SVI) were increased (27%, p < 0.01; 20%, p < 0.01; 15%, p < 0.05, respectively). There was no change in PAOP, SVR or heart rate. Seven patients (group A) had marked RV failure defined by both RV dilation [RV end-diastolic volume index (RVEDVI) > 92 ml/m2] and low RV ejection factor (RVEF) (< 52%) and 7 did not (group B). Group A had a lower baseline RVEF than group B (24 +/- 7 vs 45 +/- 9%, p < 0.05), a higher RVEDVI (134 +/- 28 vs 79 +/- 17 ml/ m2, p < 0.01), and a higher RVES (systolic) VI (103 +/- 30 vs 43 +/- 11 ml/ m2, p < 0.01). The other hemodynamics, especially RAP and RV stroke work index (RVSWI) were no different in the two groups and did not predict RV dysfunction. In group A, epinephrine infusion improved RVEF (25%, p < 0.05) by a reduction in RVESVI (-8%, p < 0.05) without any change in RVEDVI or in RAP, in spite of a rise in MPAP (11%, p < 0.05). A rise in RVSWI (76%, p < 0.05), SVI (23%, p < 0.05), and CI (24%, p < 0.05) was also achieved. An upward vertical shift of the Frank-Starling relationship RVSWI/ RVEDVI and an upward shift to the left of the pressure volume relationship pulmonary artery peak pressure/RVESVI was observed only in the group with RV failure following treatment with epinephrine. In group B (without RV failure), RV parameters were not modified by epinephrine. In patients with severe septic shock, RV dysfunction was identified by the use of an RVEF pulmonary artery catheter and was improved by epinephrine by means of an improvement in RV contractility.

Left ventricular adaptation to aortic regurgitation in conscious dogs

Objective: Cardiac failure as a result of valvular heart disease remains a major clinical problem that frequently leads to ventricular dysfunction, myocardial failure, and even death. The development of irreversible myocardial damage may be especially insidious in volume overload as a result of aortic or mitral regurgitation. Methods and results: Left ventricular wall volume, ventricular function, and myocardial performance were assessed in 10 chronically instrumented conscious dogs before and after creation of aortic regurgitation. Left ventricular wall volume was measured by serial echocardiography. Left ventricular function was assessed by total cardiac output, stroke work, the slope of the Frank-Starling relationship, and the slope of the end-systolic pressure-volume relationship. Myocardial performance was assessed by the slope of the myocardial power output versus end-diastolic strain relationship. End-diastolic wall stress and volume both increased acutely and remained elevated after creation of aortic regurgitation. Peak systolic wall stress increased initially (1 to 3 weeks) from 336 ± 30 to 369 ± 55 mm Hg but returned to control values as left ventricular wall volume increased from 78 ± 13 to 88 ± 16 ml after development of compensatory hypertrophy. Left ventricular systolic function remained constant or increased and was maintained initially by increased myocardial performance, which returned to baseline levels after the development of compensatory hypertrophy. Conclusions: Myocardial performance and ventricular function vary independently in aortic regurgitation. Measures of myocardial performance such as the myocardial power output versus end-diastolic strain relationship may be useful in clinical assessment of aortic regurgitation. (J Thorac Cardiovasc Surg 1997;113:149-58)

Development of cardiovascular responses to hypoxia in larvae of the frog Xenopus laevis.

Cardiovascular responses (blood pressure, heart rate, stroke volume, cardiac output, and peripheral vascular resistance) to acute hypoxia (Po2 = 70 mmHg) in developing larvae of Xenopus laevis from Nieuwkoop-Faber (NF) stage 45 and up to newly metamorphosed froglets were investigated. The results revealed two distinct response patterns to acute hypoxia in "early" (NF stages 45-48 and 49-51) and "late" (NF stages 52-53, 54-57, and 58-62) larval Xenopus. The early larvae responded to acute hypoxia with a significantly decreased stroke volume, cardiac output, and blood pressure. Peripheral resistance increased, whereas no change in heart rate occurred. In late larvae, stroke volume and blood pressure increased during acute hypoxia, but an offsetting bradycardia prevented major changes in cardiac output. We conclude that, up to stage 51 of development, hypoxia exerts a direct inhibitory effect on the heart and smooth muscle of the blood vessels, with no Frank-Starling relationship apparent. Older larvae show evidence of both intrinsic and extrinsic regulation of the cardiovascular system in response to acute hypoxia, suggesting that there is a specific point in larval development when cardiovascular regulation during hypoxia is expressed.

Alterations in hemodynamics and left ventricular contractility during carbon dioxide pneumoperitoneum.

Carbon dioxide (CO2) pneumoperitoneum has been shown to adversely affect hemodynamics in patients. This study specifically examines the potential contribution of altered left ventricular contractility (LVC) to hemodynamic changes observed during CO2 pneumoperitoneum. In a canine model, LV volumes, LV pressure, and intrathoracic and central venous pressures were recorded both at basal intra-abdominal pressure (IAP) and after CO2 insufflation to produce IAPs of 5-25 mmHg. At IAPs greater than 15 mmHg, cardiac output and LV end-diastolic volume decreased. Mean arterial pressure and heart rate were unchanged. LVC, quantified using the linear Frank-Starling relationship, was not affected by increases in IAP. This study is the first to quantify LVC during CO2 pneumoperitoneum and demonstrates no changes in contractility over IAPs from 5 to 25 mmHg. In the dog model, any hemodynamic alterations induced by CO2 pneumoperitoneum are secondary to altered LV preload and not alterations in contractility or LV afterload.

Functional effects of EMD-57033 in isovolumically beating isolated rabbit hearts.

The results of isolated myocyte and cardiac muscle experiments indicate that inotropic agents that increase responsiveness of myofilaments to Ca2+ (so-called Ca2+ sensitizers) may prolong myocardial contraction and increase diastolic tone, but the importance of these effects in the whole heart is unclear. Therefore, we studied the effects of the Ca2+ sensitizer EMD-57033 (EMD) on left ventricular (LV) contractile events and passive properties in isovolumically beating isolated rabbit hearts that were buffer perfused at 30 degrees C. Several LV pressure and timing variables were evaluated, including the passive pressure-volume relationship, the Frank-Starling relationship, and the wall stress dependence of the duration of relaxation during perfusion with 0, 2, and 4 microM EMD. EMD (2 microM) increased average peak developed pressure of the Frank-Starling relationship by approximately 18%. In contrast, the peak developed pressure of the Frank-Starling relationship decreased toward control with 4 microM EMD, and therefore all the results presented pertain to 2 microM EMD. The maximum developed pressure at baseline volume was increased by approximately 19% by 2 microM EMD, and this was accompanied by an increase in contraction duration of approximately 13%, due exclusively to slowed relaxation. The relative contributions of maximal wall stress (sigma max) versus an independent negative lusitropic effect of EMD were determined at three LV volumes. At baseline volume, just less than one-half of the effect to slow relaxation was ascribable to an increase in sigma max, whereas the remainder was due to an independent EMD effect. LV passive properties were unchanged by perfusion with 2 microM EMD. We conclude that EMD is a potent inotrope in our isolated rabbit heart preparation, which has no effect on diastolic tone and causes a modest prolongation of contraction duration due to slowed relaxation. At baseline volume, approximately 50% of the slowed relaxation was ascribable to positive inotropy leading to increased sigma max, whereas the remaining approximately 50% was ascribable to a direct negative lusitropic effect of EMD. We discuss our results in terms of the current hypotheses regarding the mechanism of action of the Ca2+ sensitizers.

Length-dependent activation in intact ferret hearts: study of steady-state Ca(2+)-stress-strain interrelations.

We examined the steady-state stress-strain relationships and the steady-state stress-intracellular calcium concentration ([Ca2+]i) relationship in intact ferret hearts and compared these to previously published analogous relationships in skinned and intact muscle. Langendorff-perfused ferret hearts were treated with ryanodine and tetanized by rapid stimulation to create steady-state conditions. [Ca2+]i was measured concurrently by macroinjected aequorin. Over a range of volumes corresponding to strains between 1.0 and 0.75, steady-state stress decreased by 33% when saturating levels of perfusate calcium were used, indicating the degree to which physical factors contribute to the Frank-Starling relationship. The steady-state stress-[Ca2+]i relationship was sigmoidal with a mean Hill coefficient (nH) of 4.91 +/- 0.29 at a strain of 1.0, and the [Ca2+]i required for half-maximal activation (K1/2) was 0.41 +/- 0.03 microM. K1/2 increased and nH decreased with decreasing strains. These results are similar to those observed in intact muscle but differ quantitatively from results obtained in isolated, skinned preparations. Based on these results, we suggest that whole heart function can be related to average sarcomere function without the need for complex models of ventricular structure.

Assessment of the Frank-Starling relationship by two-dimensional echocardiography

The Frank-Starling relationship between left ventricular stroke work and end-diastolic minor-axis cross-sectional area was evaluated as a load-insensitive measure of inotropic state by two-dimensional echocardiography in 10 conscious dogs. Stroke work was calculated as the product of systolic change in cross-sectional area and either (1) beat-to-beat mean arterial pressure or (2) initial systolic blood pressure. Both Frank-Starling relationships were highly linear during preload variation (mean r = 0.96), sensitive to the inotropic state (slope increase with calcium 51% ± 43% and 62% ± 53%, respectively), and insensitive to afterload ( r < 0.4, slope or x intercept versus afterload). Thus the Frank-Starling relationships derived from two-dimensional echocardiographic images and peripheral arterial pressure may be a useful and practical means of assessing inotropic state with minimally invasive measurements.

Noninvasive methods of preload variation in assessment of the frank-starling relationship

Noninvasive methods of preload variation in assessment of the frank-starling relationship

OPTIMAL PREOPERATIVE TITRATED DOSAGE OF HYPERTONIC-HYPERONCOTIC SOLUTIONS IN CARDIAC RISK PATIENTS

Hypertonic-iso/hyperoncotic solutions have been the subject of numerous studies, mostly used in a fixed dosage (4 mL/kg bw or 250 mL). Nearly no study exists to prove whether this is the appropriate dosage especially in cardiac risk patients with accompanying diseases. We have compared preoperative volume loading with either 10% hydroxyethyl-starch/7.5% NaCl (HHT-HES) or 10% hydroxyethyl-starch/.9% NaCl (HES) in 50 mL bolus infusions. Volume loading was done with either HES or HHT-HES in 2 x 20 patients before aortic aneurysmectomy. The endpoint of stepwise infusion represented the highest cardiac index (CI) at the lowest possible wedge pressure (PCWP) (turning point of each individual Frank Starling relation). 167.5 mL (+/- 45.5 mL = 2.41 mL/kg bw) of HHT-HES and 440 mL (+/- 26.15 mL = 6.33 mL/kg bw) of HES were necessary. We observed a significant higher increase of the CI in the HHT-HES group. Significant increases of PCWP, pulmonary artery pressure, and central venous pressure occurred within the groups without any significant differences between the groups (p < .05). Results of the study showed: 1) The commonly used fixed dosage of 4 mL/kg bw of HHT-HES is too high in cardiac risk patients with slight hypovolemia. 2) HHT-HES should be given in an individual titration. 3) In the HHT-HES group we observed a positive inotropic effect (higher CI). 4) With the individual titration of HHT-HES no negative side effects occurred (especially no hypotension).

EFFECTS OF HYPERTONIC-HYPERONCOTIC INFUSION ON THE HUMAN ATRIAL NATRIURETIC FACTOR IN A STANDARDIZED CLINICAL TRIAL

Hypertonic-hyperoncotic solutions (HHT) are presently being utilized to resuscitate patients in shock. However, so far, the effects of HHT on human atrial natriuretic factor (hANF) have not yet been investigated in a clinical trial. The effects of HHT on hANF were studied in a standardized preoperative and clinical setting in patients undergoing aneurysmectomy. Twenty-three conscious patients were included in two groups: 11 HHT and 12 HES (HHT: 7.5% NaCl/10% HES 200; HES: .9% NaCl/10% HES 200). Stepwise infusion of 50 mL was titrated preoperatively according to individual Frank-Starling relationships. Central venous pressure (CVP) and pulmonary capillary wedge pressure (PCWP) were determined before, during and after volume application. hANF, cGMP were also measured before and 1, 10, 30, 60, and 120 min after administration. The volumes necessary to produce the same volume status were: 213.6 +/- 63.6 mL of HHT, 409.9 +/- 136.2 mL of HES (p < .001). The sodium load was 273.9 +/- 81.5 mmol of [HHT], 63.1 +/- 21.0 mmol of [HES] (p < .001).(ABSTRACT TRUNCATED AT 250 WORDS)