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Biomedical subjects

A Hoeft

Publications and source records attributed to A Hoeft.

At least 91 records · Page 5Linked to original sources

Effects of enoximone and R 80122, a new selective phosphodiesterase III inhibitor, on hemodynamics and myocardial energetics in patients with ischemic heart disease.

The present study was designed to compare the effects of enoximone and R 80122, a highly selective phosphodiesterase (PDE) III inhibitor, on left ventricular hemodynamics and myocardial blood flow and metabolism in patients with coronary artery disease. Twenty male, anesthetized patients, ASA physical status III, were studied before they underwent coronary artery bypass grafting (CABG) surgery. They were allocated randomly to receive either 0.3 mg/kg R 80122 (Group 1) or 1 mg/kg enoximone (Group 2) intravenously (IV). All patients were taking maintenance doses of either beta-receptor antagonists or calcium-channel-blocking drugs and nitrates. After receiving flunitrazepam, 2 mg orally, anesthesia was induced with fentanyl, midazolam, and pancuronium IV. Following control measurements after the induction of anesthesia, the PDE III inhibitor was infused over 2 min and measurements were repeated 5, 30, and 60 min after drug administration. There were no external stimuli to the patients during any of the measurement periods. R 80122 and enoximone decreased mean arterial pressure (MAP) by 20% and systemic vascular resistance (SVR) by 36% and 38%, respectively, while cardiac index (CI) increased by 27% and 30%, respectively. There were increases in heart rate (HR) by 10% and 19%, respectively, and in contractility (dp/dtmax) by 18% and 38%, respectively. Coronary perfusion pressure (CPP) decreased by 23% and 22%, respectively, and coronary vascular resistance (CVR) by 38% and 21%, respectively. Myocardial blood flow (MBF) and myocardial oxygen uptake (MVO2) increased in both groups, the increase in MBF being statistically significant (+34%) only in Group 1, whereas the changes in myocardial metabolism were not significant in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Regulation of local sweating in sleep-deprived exercising humans.

Thermoregulatory sweating [total body (msw,b), chest (msw,c) and thigh (msw,t) sweating], body temperatures [oesophageal (T(oes)) and mean skin temperature (Tsk)] and heart rate were investigated in five sleep-deprived subjects (kept awake for 27 h) while exercising on a cycle (45 min at approximately 50% maximal oxygen consumption) in moderate heat (T(air) and T(wall) at 35 degrees C). The msw,c and msw,t were measured under local thermal clamp (Tsk,l), set at 35.5 degrees C. After sleep deprivation, neither the levels of body temperatures (T(oes), Tsk) nor the levels of msw,b, msw,c or msw,t differed from control at rest or during exercise steady state. During the transient phase of exercise (when Tsk and Tsk,l were unvarying), the msw,c and msw,t changes were positively correlated with those of T(oes). The slopes of the msw,c versus T(oes) or msw,t versus T(oes) relationships remained unchanged between control and sleep-loss experiments. Thus the slopes of the local sweating versus T(oes) relationships (msw,c and msw,t sweating data pooled which reached 1.05 (SEM 0.14) mg.cm-2.min-1.degree C-1 and 1.14 (SEM 0.18) mg.cm-2.min-1.degree C-1 before and after sleep deprivation) respectively did not differ. However, in our experiment, sleep deprivation significantly increased the T(oes) threshold for the onset of both msw,c and msw,t (+0.3 degrees C, P < 0.001). From our investigations it would seem that the delayed core temperature for sweating onset in sleep-deprived humans, while exercising moderately in the heat, is likely to have been due to alterations occurring at the central level.

Adult↗

Qualitative assessment of thermal and evaporative adjustments of human scrotal skin in response to heat stress.

To study scrotal thermoregulation and its efficacy to work against heat accumulation, five subjects were exposed to four experimental conditions under which core and skin temperatures and sweat evaporative responses of various skin surfaces--chest, abdomen and scrotum--were compared. The temperature response of the scrotal area exhibited the largest inertia, and this observation is likely to be the consequence of heat exchange via the vascularization of testes and scrotum which is more efficient than in other parts of the body in limiting local heat storage, thus alleviating heat stress of the testis. The pulsatile nature and the synchronous pattern of the scrotal evaporative heat loss indicate that scrotal sweating takes place, although the gradient response appeared to be less marked than elsewhere in the body. Relatively low and inert scrotal temperature can partly explain this poor local drive for sweating.

Abdomen↗

Calculation of body transport function.

A new model for simulation of recirculation has been developed which describes the measured concentration-time course of a drug in the aorta. It is based on repetitive convolution of the injected input dilution curve with a body transport function plus the input dilution curve. If the basic shape of a body transport function, i.e. such as log-normal distribution, is known, it is possible to calculate the parameters of this function with a non-linear least-squares procedure from measured tracer dilution data. In the present investigation this algorithm is used to estimate the body transport function for experimental data, obtained in two experiments with sheep. Once the body transport function is known, the formula can be used to describe the dispersion of a drug. Intravascular concentration time curves at different places in the body can also be predicted or the blood volume can be estimated.

Algorithms↗

Temperature and sweating responses in one-legged and two-legged exercise.

In looking at the thermoregulatory responses resulting from symmetrical or asymmetrical exercise, this paper has focused on the effect of local skin temperature (Tsk,local) on local sweat rates (msw,local) during one-legged (W1) and two-legged (W2) exercise on an ergocycle. Five subjects underwent four 3-h tests at 36 degrees C, each consisting of six 25-min exercise periods alternating with 5-min rest periods. The subjects performed W1 and W2 at 45 and 90 W, respectively, either dehydrated or rehydrated. Body temperatures and total sweat rate were measured as well as four msw,local (on chest and thighs), assessed from sweat capsules under which Tsk,local was maintained at predetermined levels (37.0 degrees C and 35.5 degrees C). The combinations of Tsk,local levels, capsule locations, exercise intensity and hydration level chosen in our protocol led to the following results. The hydration level affected rectal temperature but not total or msw,local. No specific effect of muscle activity was found; msw,local on thighs of resting and working legs were similar. The msw,local were only influenced by exercise intensity, msw,local being more elevated during the higher intensity. No significant effect of Tsk,local on msw,local was found, whatever the experimental condition and/or the location. It was concluded that local thermal effects on msw,local could have been masked by the strong central drive for sweating which has been found to exist in subjects exercising in a warm environment.

Adult↗

Leg skin temperature and thigh sweat output: possible central influence of local thermal inputs.

To demonstrate whether or not the skin temperature of one lower limb can have an influence on the sweat rate of the contralateral leg, the two legs of five subjects were exposed inside leg-chambers to specific local thermal conditions while sweat rates were measured on both limbs. Three experiments (C I, II, III) of 3 h were carried out: each included two phases A and B. During A, the right leg was not ventilated, while the left leg was (C I) or was not (C II-III) ventilated. During B, the legs were either removed from the leg-chambers (C I) or ventilated inside the chambers at differently controlled levels of leg skin temperature (C II-III). At all times, sweat capsules on both legs measured the sweat rates of local areas of the thigh which were also temperature-controlled. Results showed that, at constant or slightly increased mean skin and core temperatures, the sweat output of one leg could be decreased at constant (C II) or higher local skin temperature (C III) probably due to a decrease in the temperature of the opposite leg. This finding is interpreted as a consequence of a central negative effect, originating from contralateral thermal inputs.

Adult↗

[Coronary circulation and myocardial oxygen balance in anesthesia].

It is generally believed that in patients with impaired coronary reserve an imbalance between myocardial O2-demand and O2-supply is the main cause of myocardial ischaemia. However, clinical experience as well as recent experimental results indicate that this global view may not always explain the occurrence of regional myocardial ischaemia. It was therefore investigated whether in patients before and after induction of anaesthesia as well as during sternotomy metabolic indices of ischaemia, i.e. lactate and/or hypoxanthine release into the coronary sinus, are related to global indices of myocardial O2-balance. It was found that neither myocardial O2-demand or O2-supply nor O2-balance correlated with myocardial ischaemic events. Conversely it was observed that in contrast to expectations lactate and/or hypoxanthine release occurred more often in conjunction with high values of coronary venous oxygen saturation than with low values. Since coronary venous oxygen saturation can be considered as a physiological index of global myocardial O2-balance, the data of the present investigation suggest that during anaesthesia a global imbalance between myocardial oxygen supply and demand is not the main cause of myocardial ischaemia. Thus, regional factors seem to be more important for initiation of myocardial ischaemic events than global O2-balance.

Anesthesia↗

Priming of cardiopulmonary bypass with human albumin or Ringer lactate: effect on colloid osmotic pressure and extravascular lung water.

We have undertaken a randomized study on 20 patients undergoing coronary artery bypass surgery in order to determine the influence of cardiopulmonary pump prime solutions on colloid osmotic pressure and extravascular lung water. Crystalloid priming with Ringer lactate was compared with an albumin solution of nearly physiological colloid osmotic composition (4%). Measurements of extravascular lung water were performed by a modified, highly sensitive thermal dye technique, with additional detection of tracer signals in the pulmonary artery. In the Ringer lactate group, a significantly greater decrease in colloid osmotic pressure occurred immediately after onset of cardiopulmonary bypass. The more pronounced decrease in colloid osmotic pressure and in transcapillary gradient (difference between colloid osmotic pressure and pulmonary capillary wedge pressure) in the Ringer lactate group was associated with a significant increase in extravascular lung water (by 60%) in the postoperative period; the human albumin group, however, showed only a slight tendency to increased lung water. There were no differences in haemodynamic or respiratory states after operation.

Albumins↗

Validation of myocardial oxygen demand indices in patients awake and during anesthesia.

An important guideline for anesthesia in patients with ischemic heart disease is the effect on myocardial oxygen demand. Therefore, this investigation evaluated commonly used myocardial oxygen demand formulas for clinical application. The study was performed on patients undergoing coronary bypass surgery (n = 62). Measurements of standard hemodynamics were obtained before and after induction of anesthesia, as well as during sternotomy and after surgery. Coronary blood flow was determined by the argon wash-in technique. In 15 patients, a left ventricular tip manometer was used to accurately assess the first derivative of left ventricular pressure time course. The following indices of left ventricular oxygen demand were calculated: 1) rate pressure product (RPP); 2) tension time index (TTI); 3) pressure work index (PWI) according to the methods of Rooke; and 4) additive parameter (Eg), according to the methods of Bretschneider. All hemodynamic indices of myocardial oxygen demand showed moderate correlation with myocardial oxygen uptake (MVO2) (RPP: r = 0.77; TTI: r = 0.79; PWI: r = 0.79; Eg: r = 0.71). On the average, PWI and Eg led to an underestimation of MVO2 in patients. The constants of the PWI and Eg formulas, which have been developed based on animal experiments, therefore are not directly applicable to clinical conditions. New constants have been derived for PWI by multiple linear regression analysis of the data in the current investigation.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗

[The effect of sufentanil on cerebral blood flow, cerebral metabolism and the CO2 reactivity of the cerebral vessels in man].

Sufentanil, a synthetic opioid that is 5-10 times as potent as fentanyl, has been suggested for use during neurosurgical procedures because it maintains cardiovascular stability and produces hypnosis without the use of additional anesthetic agents. Doses as low as 2.5 micrograms.kg-1 are reported to create deep levels of anesthesia as demonstrated by EEG changes to high-amplitude delta-waves. However, there are no reports concerning the effects of sufentanil on blood flow and metabolism in the human brain. The present study was designed to investigate the influence of high-dose sufentanil-O2 anesthesia on the cerebral circulation, metabolism, and the cerebrovascular response to CO2 in man. METHODS. Nine male and 2 female patients between 41 and 60 years of age who were scheduled for coronary artery bypass surgery were studied. Premedication consisted of flunitrazepam 2 mg orally and piritramide 15 mg and promethazine 50 mg i.m. 1 h before arrival in the induction room. Measurements were performed with the patients awake (I), after sufentanil 10 micrograms.kg-1 as an induction dose followed by 0.15 micrograms.kg-1.min-1 as an infusion with normocapnia (pa CO2 42.1 +/- 2 mmHg) (II), during hypercapnia (pa CO2 53.7 +/- 3.5 mmHg) (III), and during hypocapnia (pa CO2 31.7 +/- 2 mmHg) (IV). Cerebral blood flow (CBF) was measured using the argon wash-in technique. Cerebral venous blood was obtained from a catheter in the superior bulb of the right internal jugular vein. Cerebral metabolic rates of oxygen (CMRO2) glucose (Mgluc) lactate (CMlac) were calculated by multiplying the arterial-cerebral venous oxygen and substrate differences by CBF. The Anaerobic Index was calculated from the equation avD lactate x 100/2 x avD glucose = ANI (%) Cerebral electrical activity was recorded by aperiodic analysis of the EEG (Lifescan). RESULTS AND DISCUSSION. In the EEG sufentanil anesthesia was characterized by a decrease in the number of high-frequency waves and an increase in the number and amplitude of delta-waves, a pattern that did not change throughout the study period. Concomitantly, under normocapnic conditions high-dose sufentanil led to the significant decrease in CBF by 29% accompanied by an 18% increase in cerebral vascular resistance (CVR). CMRO2 decreased by 22% while CMRgluc and CMRlac changed only insignificantly such that the ANI, which represents the percentage of anaerobically metabolized glucose, essentially remained unchanged. Mean perfusion pressure declined by 18% but stayed within the range of autoregulation. Hypoventilation (III) was followed by an 82% increase in CBF as a result of a 55% reduction in CVR, whereas cerebral metabolic parameters did not show important changes when compared to measurement II. Hyperventilation (IV), on the other hand, produced a distinct fall in CBF by 56% to a value that was 21% below the one obtained under normocapnia. This was due to an increase in CVR of the same magnitude. There was a 31% rise in CMRO2, resulting in a decrease in cerebral venous oxygen tension, but in no case did it fall below the critical value of 20 mmHg at which tissue hypoxia becomes severe. Although CMRlac increased and CMRgluc did not significantly change, the ANI remained essentially unchanged, which suggests a predominantly aerobic metabolism. The increase in metabolic activity with sufentanil during hypocapnia might be caused by an alkalosis-induced stimulation of glycolysis. It might also be related to a reduction in the depth of anesthesia, although neither the EEG nor the hemodynamic parameters indicated this. This study shows that the coupling between CBF and metabolism is well maintained and that the cerebrovascular response to CO2 is unimpaired during high-dose sufentanil anesthesia.

Adult↗

[The energetics and economics of the cardiac pump function].

In anesthesiology and intensive care medicine it is often necessary to treat disorders involving cardiac failure or low-output syndrome. However, in patients who are endangered by ischemic heart disease, any pharmacologic therapy with positive inotropic agents should improve cardiac output without increasing myocardial oxygen demand significantly: the heart should perform its task as efficiently as possible. In the present study a mathematical model of myocardial efficiency was developed. The implications of this theoretical concept of myocardial efficiency were evaluated in animal experiments. THEORETICAL MODEL. Cardiac efficiency is predominantly dependent on preload, afterload, and inotropic state. Quantitatively, it can be calculated from end-diastolic volume, left ventricular systolic pressure (Psyst), stroke volume (SV), and ejection time. The implications of the theoretical analysis are: (1) the inotropic state, which leads to optimal myocardial efficiency, is specifically determined by preload and afterload: for each preload and afterload one matched inotropic state is necessary to achieve optimal efficiency; (2) an increase in blood pressure leads to a decrease in myocardial efficiency even if the inotropic state is optimally matched to preload and afterload; and (3) an increase in end-diastolic volume improves the efficiency of myocardial pump work. ANIMAL EXPERIMENTS. The validity of the theoretical model was studied in animal experiments with emphasis on the following items: (1) is theoretically optimal efficiency of myocardial pump work achieved by physiologic regulation of myocardial performance? (2) how does sympathetic stimulation influence myocardial efficiency? and (3) how do cardiodepressive agents such as beta-blockers or volatile anesthetics influence myocardial efficiency? METHODS. Experiments were performed on nine mongrel dogs after induction of piritramide--nitrous oxide anesthesia. Standard hemodynamics: heart rate, Psyst, maximum left ventricular pressure rise (dP/dtmax), and SV (thermodilution) as well as coronary blood flow (pressure difference catheter) and myocardial oxygen consumption (Fick principle) were measured. In order to create a broad range of different hemodynamic settings, blood withdrawal and retransfusion of blood and/or colloid osmotic solutions were used to modify intravascular volume. Additionally, the inotropic state was varied by infusion of catecholamines (isoproterenol 0.4-0.8 microgram.kg-1.min-1 or norepinephrine 1-2 micrograms.kg-1.min-1). Experimental myocardial failure was induced by adding halothane (0.8-1.5 MAC) to the basic anesthesia, beta-blockade with propranolol (125-250 micrograms.kg-1), and combination of beta-blockade with a pressure load imposed on the myocardium (propranolol 125-250 micrograms.kg-1 + norepinephrine 1-2 micrograms.kg-1.min-1). RESULTS. During variation of the intravascular blood volume by normo-, hypo-, and hypervolemia, the myocardial efficiency very closely matched the theoretically predicted values of optimal efficiency: the average observed efficiency was 98.8% of predicted optimal efficiency. Increasing afterload with norepinephrine did not alter this close relationship, although absolute values of efficiency decreased as predicted by the theoretical model. Application of isoproterenol resulted in SVs that exceeded optimal values by 41.5%. In contrast, during experimental myocardial failure SVs were too small to achieve the necessary values for optimal pump work; observed myocardial efficiency was therefore significantly lower than optimal efficiency. CONCLUSIONS. For pharmacological interventions, it can be concluded that maximal efficiency of cardiac pump work requires maximal end-diastolic filling in combination with minimal afterload. (ABSTRACT TRUNCATED AT 400 WORDS)

Anesthesia, Inhalation↗

Heterogeneity of myocardial blood flow under normal conditions and its dependence on arterial PO2.

We studied the heterogeneity of myocardial blood flow in nine anesthetized closed-chest dogs using an indicator-dilution technique that allows the stochastic description of transport characteristics for three inert gases (helium, argon, and xenon) from the coronary inflow to outflow. The results show that under normal conditions the transcoronary transport of the tracers is spatially heterogeneous. Heterogeneity is strongly dependent on the arterial oxygen tension over a range of 40-200 Torr. This could be similarly observed with each tracer gas despite different physicochemical properties and was largely independent from the magnitude of coronary blood flow. The results are interpreted to mean that the arteriolar or intratissue PO2 influences myocardial blood flow over a broad range and possibly acts as an important integrating factor in the local regulation of coronary blood flow and flow reserve.

Animals↗

Transport of inert gases in mammalian myocardium: comparison with a convection-diffusion model.

Because tracer techniques are gaining an increasing importance for imaging flow (and metabolism) in the heart, experimental evidence is needed on the role of convection and diffusion in the transcoronary transport of solutes. In the present work, the transport of four different inert gases through the coronary system is studied in five closed-chest dog experiments and is compared with a digital multicapillary convection-diffusion model. Transport may be defined as flow dependent, as judged by the gross similarity of shape of the time-normalized dilution curves. However, the results show that the transcoronary transport of helium and xenon is more dispersed than that of argon and krypton, probably because of differences in diffusibility and solubility. A comparison of the animal and model experiments emphasizes the importance of diffusive transport of the gases. It is suggested that there is a diffusion shunt that is mainly located within the capillary network itself rather than between conduit vessels. Only for helium (which has the highest diffusivity) was a small arteriovenous shunt fraction seen that is thought to bypass the capillary exchange region. The conclusion is that although there is evidence of diffusional shunting at a capillary level, the inert gas kinetics in the heart are compatible with a basically flow-limited transport.

Animals↗

[Continuous measurement of cardiac output based on the Fick principle in cardiac anesthesia].

With the development of fiberoptic and pulse oximetry, as well as the development of the more modern methods of oxygen consumption measurements, the online monitoring of Fick cardiac (FCO) output has become possible in the clinical treatment routine. The aim of this study was to compare fiberoptically measured mixed venous oxygen saturation with values from blood samples and continuously determined Fick cardiac output with intermittent thermodilution cardiac output (TCO). Ten patients undergoing coronary artery bypass grafting were measured during the perioperative period. Total body oxygen consumption was determined with a metabolic monitor (Deltatrac Datex) from respiratory gases. Arterial oxygen saturation was assessed by pulse oximetry (Nellcor). Mixed venous oxygen saturation was measured by a balloon tipped pulmonary artery fiberoptic catheter (Opticath) attached to an electronic device based on three wavelengths (Oximetrix cardiac output monitor). Hemoglobin, Methemoglobin and CO-hemoglobin were determined from intermittent blood samples by in vitro analysis. FCO was calculated from corresponding differences in arterial mixed venous oxygen and total body oxygen consumption. TDCO values were calculated from microcomputer recordings of the thermodilution data by monoexponential curve-fitting with respect to baseline drift. A significant systematic difference between FCO and TCO was observed. FCO exceeded TCO on average by 0.42 +/- 0.12 l/min. The limits of confidence (95%) were 0.18 to 0.66 l/min. There was no systematic difference between mixed venous saturation measurements with the fiberoptic system and from blood samples. The cardiac output values derived from fiberoptic and pulse oximetry can be considered sufficiently reliable for clinical purposes.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

Characteristics of the pulmonary transport functions for heat and dye in pulmonary edema and orthostasis.

The aim of this study was to investigate whether changes in the distribution of pulmonary blood flow and disturbances of the pulmonary microcirculation can be detected by use of inflow-outflow indicator-dilution measurements. In 18 anesthetized (N2O-piritramide) mongrel dogs 221 thermal-indocyanine green dye indicator dilution kinetics were recorded in the pulmonary artery and aorta after central venous indicator injection. The lagged normal density function was used as a model for the pulmonary transport functions for heat and dye. The parameters of the lagged normal density function were computed by a non-linear least squares procedure by iterative convolution. After baseline measurements, in nine dogs, pulmonary edema was induced by central venous application of oleic acid. In nine other dogs, measurements were performed before and after postural changes. Our data show that both the microvascular injury caused by oleic acid edema and the perfusion heterogeneity caused by orthostasis can be detected by the indicator dilution technique since the both relative dispersion and skewness of the transport functions for heat and dye were significantly increased after these interventions.

Animals↗