Platelet activation in major surgical stress: influence of combined epidural and general anaesthesia.

Platelets are activated in surgery releasing vasoactive substances such as serotonin and thromboxane. Platelets become temporarily hypoaggregable during surgery followed by a postoperative hyperaggregability. Local anaesthetics are known to inhibit platelet function but earlier reports are conflicting. In order to study the impact of the combined use of general and regional anaesthesia on platelet function during major surgery 16 otherwise healthy patients were randomised to either general anaesthesia (GA) (n = 8) or GA combined with epidural anaesthesia (GA+EPI) (n = 8) for elective upper abdominal surgery. Cyclic 3',5' adenosine monophosphate, plasma glucose, plasma cortisol and the rate pressure product (RPP) were markers of the stress response. ADP-induced platelet aggregation and the release products beta-thromboglobulin, serotonin and thromboxane 2 were measured in plasma before and during as well as for 3 days after surgery. A marked stress response was noted in both groups and epidural anaesthesia (EPI) only reduced the rate pressure product (RPP). Platelet aggregation was reduced during surgery, a little more so in the GA+EPI group. Postoperatively both groups showed significant hyperaggregability. The release products were not significantly influenced by regional anaesthesia. In conclusion epidural as combined with general anaesthesia affects platelet responses to major abdominal surgery only to a minor extent, although it may attenuate the haemodynamic response.

Hormonal and hemodynamic changes following single-dose felodipine treatment during mental stress.

Mental stress induces changes in hemodynamic variables and in the plasma level of many hormones and plasma peptides. These changes can be modulated by various drugs, eg, beta-blockers. In a double-blind, placebo-controlled crossover study, the authors evaluated the hormonal and hemodynamic changes during psychological stress and the effect of felodipine 10 mg (plain tablet). Eight male volunteers participated. Heart rate, blood pressures, and stroke volume were measured by ECG, mercury sphygmomanometer, and impedance cardiography. Catecholamines and atrial natriuretic factor in plasma were measured by electrochemical and radioimmunoassay techniques. A single dose of felodipine, 10 mg, exaggerates the heart rate decreases the left ventricular ejection time and augments the plasma level increment of noradrenaline. The stress-induced changes in other variables were not influenced by felodipine treatment. In conclusion, acute felodipine treatment influences the reflex activation of the sympathetic nervous system during psychological stress. In the treatment of patients, especially patients with heart disease, these findings could be important but further investigations in patients need to be done.

Platelet activation in mental stress.

Platelets are known to become activated in vivo by different stressful stimuli such as surgery and dynamic exercise. Mental stress has been shown to increase platelet aggregability. Platelet activation is thought to be of major importance in atherogenesis and cardiac fatalities. In order to clarify further stress-induced platelet activation with special reference to the period after the stress, we studied eight young, healthy volunteers during and for 1 h after a mental stress test (Stroops Colour Word Conflict Test). Using highly standardized techniques, we have measured platelet aggregability ex vivo and the platelet release products beta-thromboglobulin, platelet factor 4 and serotonin in plasma. As markers of the stress response we measured cyclic-AMP in plasma, heart rate, cardiac output and blood pressure. The stress test induced a significant cardiovascular response with increases in heart rate, blood pressure, and cardiac output and as a measure of adrenergic activity an increase in cyclic AMP in plasma during the test. Platelet aggregability was unaffected during the test but decreased following the stress. During the first hour following the test and release products beta-thromboglobulin and serotonin increased significantly in plasma. We conclude that platelets are activated during mental stress and that this activation involves a post-stress release of vasoactive compounds from platelets.

Differential effects of beta-adrenoceptor partial agonists in patients with postural hypotension.

The central haemodynamic effects of pindolol and xamoterol have been investigated in patients with postural hypotension. Pindolol is a non-selective beta-adrenoceptor partial agonist, whereas xamoterol is beta 1-selective and possesses a higher degree of agonist activity. The study comprised 16 patients with postural hypotension of different aetiologies. Blood pressure, heart rate and stroke volume were measured in the supine and head-up tilted positions. Left ventricular ejection fraction (LVEF) was measured in the supine position, and vascular resistance, left ventricular volume, and left ventricular contractility were derived. Pindolol and xamoterol were administered intravenously in incremental doses to reach total doses of 0.02 and 0.20 mg.kg-1, respectively. Pindolol showed beta-adrenoceptor antagonistic effects in the supine position through decrements in heart rate from 70 to 66 beats.min-1 and LVEF from 0.57 to 0.52, and reduced mean arterial blood pressure from 103 mm Hg to 93 mm Hg. Xamoterol showed beta-adrenoceptor agonistic effects in the supine position through increments in heart rate from 72 to 90 beats.min-1 and LVEF from 0.58 to 0.66, and raised mean arterial blood pressure from 108 to 123 mm Hg. It is concluded that the degree of agonist activity of a beta-adrenergic agent is of importance if it is given to a patient with postural hypotension.

Beneficial effects of intermittent suction and pressure treatment in intermittent claudication.

The present study reports on the effects of a physical treatment modality in patients with intermittent claudication. During this treatment a major part of the skin surface is subjected to intermittent suction and pressure. In a previous, preliminary study the authors found a beneficial effect of this treatment in intermittent claudication. The study included 34 patients with moderate, stable intermittent claudication. Twenty-two patients participated in a double-blinded, randomized trial comparing the effects of 25 treatments to 25 placebo applications given over a period of two months. Twelve patients participated in an open trial investigating the possible effects of the treatment on platelet aggregation and fibrinolysis. Pain-free and maximal walking distances were measured on a treadmill, and systolic blood pressure was measured on the upper limb, the ankle, and the first toe bilaterally. The threshold for adenosine diphosphate (ADP)-induced platelet aggregation was tested, and the fibrinolytic activity was estimated from the euglobulin clot lysis time. Active treatment resulted in significant improvements in pain-free and maximal walking distances, whereas no changes could be found during placebo administration. The treatment caused significant increments in the ADP thresholds for platelet aggregation, while the effects on fibrinolysis were uncertain. It is concluded that intermittent suction and pressure treatment offers a new approach for conservative treatment of intermittent claudication.

Xamoterol in severe congestive heart failure: long-term oral treatment, a double-blind randomised study.

Twelve patients in severe congestive heart failure were given placebo, 100 mg xamoterol (Corwin) twice daily and 200 mg xamoterol twice daily, respectively, in 3 two-week periods in a double-blind randomised study. At the end of each treatment period the patients were evaluated. No differences were found between placebo and xamoterol in the following parameters: New York Heart Association function group index, heart volume, body weight, exercise duration on bicycle and treadmill, heart rate and systolic and diastolic blood pressure at rest. However, during exercise we found significantly lower heart rate and rate-pressure product during xamoterol treatment. This reduction is probably indicating occupation of beta-adrenoreceptors with concomitant reduced oxygen consumption during exercise.

Reliability of impedance cardiography in measuring central haemodynamics.

The purpose of the study described here was to investigate the reliability of impedance cardiography (IC) in measuring cardiac output (CO) and central blood volume. Absolute values and changes in these variables obtained by impedance cardiography and by isotope- or thermodilution techniques were compared. The reproducibility of IC within the same day was compared with that of isotope dilution and the reproducibility in IC from day to day was derived. Finally, the effects of the readings of impedance tracings by different observers were quantified. The results are based on 270 measurements in 37 healthy subjects and in 25 unmedicated patients with ischaemic heart disease. We obtained significant correlations between absolute values (y = 0.68x + 1.48) and changes (y = 1.00x + 0.0003) in CO measured by IC and isotope- or thermodilution. IC significantly overestimated absolute values of CO (P less than 0.001). We found a qualitative but no quantitative correlation between thoracic fluid volume measured by IC and central blood volume measured by isotope dilution. IC was highly reproducible both when studies were repeated within the same day (SD on differences in CO = 0.36 1 min-1 for IC; SD on differences in CO = 0.30 1 min-1 for isotope dilution) and on different days (SD on differences in CO = 0.45 1 min-1). A low intra-observer variability was found (SD on differences in CO = 0.12 1 min-1). We conclude that impedance cardiography is reliable in measuring changes in cardiac output and thus suitable for repeated measurements in studies on the haemodynamic effects of physiological or pharmacological intervention. Impedance cardiography is sufficiently reliable for comparison of absolute values of CO between different groups of patients. We cannot recommend impedance cardiography for quantitative studies of central blood volume.

Central haemodynamics in patients with severe postural hypotension.

Central haemodynamics in the supine and head-up tilted positions were studied in 24 patients with severe postural hypotension with and without supine hypertension. Results were compared with those obtained in eight normotensive and eight untreated hypertensive controls. In the supine position the patients had higher vascular resistances, lower stroke volumes and longer left ventricular ejection time indexes compared to controls, whereas left ventricular ejection fractions did not differ significantly. The patients with supine hypertension had significantly higher vascular resistance compared to those with supine normotension. The highest supine blood pressure levels were found in patients with multiple system atrophy. During tilt, vascular resistance and heart rates were increased and stroke volumes and left ventricular ejection time indexes were decreased in the controls. The patients were unable to increase their vascular resistance, but increased their heart rate and decreased their left ventricular ejection time indexes to a degree similar to the controls. The reductions in stroke volume were smaller in the patients compared to the controls. Changes in haemodynamics in response to head-up tilting did not differ significantly between patients with supine hypertension and supine normotension. It is concluded that patients with postural hypotension have higher supine vascular resistance and are unable to contract peripheral arteries and arterioles during head-up tilting. Contractility of the left ventricle is preserved and the baroreceptors are partially intact. Postural hypotensive patients with supine hypertension differ from those with supine normotension only with respect to supine vascular resistances.

[Captopril renography in the diagnosis of renovascular hypertension]. / Captopril-renografi ved diagnosticering af renovaskulaer hypertension.

The value of renography before and after angiotensin converting enzyme inhibition with captopril (captopril renography) as a test for renovascular hypertension was studied in fourteen hypertensive patients. The captopril renography was performed with 99mTc-DTPA by means of a gammacamera, allowing determination of single kidney glomerular filtration rate (SKGFR). In all patients determination of renal vein plasma renin concentration and renal angiography were carried out. Eleven patients showed an elevated unilateral renin secretion. All of these had a significant decrease of SKGFR in one or both kidneys after captopril. Three patients without a lateralized renal renin secretion showed no change in SKGFR. In five patients with presumed essential hypertension there was no change in SKGFR during captopril renography. Captopril renography with 99mTc-DTPA gammacamera renography is a promising tool for identification of unilateral increased renin secretion in hypertensive patients suspected of renovascular hypertension.

Effects of vacusac in intermittent claudication: a controlled cross-over study.

The effect of a new physical treatment modality, Vacusac, was tested on a group of patients with stable intermittent claudication. Twenty-two patients with a median age of 65 years and a median duration of intermittent claudication of 5 years were randomized to either active or placebo treatments. Seventeen patients completed the study. The effect of treatment was quantified by measurements of systemic and peripheral systolic blood pressures and by measurements of the pain-free and the maximal walking distance on a treadmill. The ankle pressure index (ankle systolic pressure/arm systolic pressure) and toe pressure index (toe systolic pressure/arm systolic pressure) were calculated. After 25 active treatments, administered over a period of 2 months, the patients allocated to this group attained a significant increase in the pain-free walking distance from 54 m (24-107 m) to 99 m (30-420 m) (P less than 0.05) and in the maximal walking distance from 99 m (36-182 m) to 185 m (68-591 m) (P less than 0.05). The patient group receiving 25 placebo treatments did not show any significant changes in either the pain-free or the maximal walking distance. This group then received 25 active treatments over a period of 2 months. This active treatment resulted in a significant increase in the pain-free walking distance from 51 m (14-100 m) to 86 m (18-1000 m) (P less than 0.05) and in the maximal walking distance from 98 m (40-199 m) to 175 m (51-1000 m) (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Post-exercise platelet activation--aggregation and release in relation to dynamic exercise.

Relatively scarce information is found on the period immediately following physical stress, with special reference to human platelet activity. This, in connection with earlier observations of an increase in platelet release products and hyperaggregability following surgical stress, has initiated the present study. We studied platelet function in eight healthy non-mediated volunteers during and 1 h after cycle exercise of submaximal intensity. ADP-induced platelet aggregability was enhanced in the last minute of exercise followed by a decreased aggregability 1 h after. Adrenaline-induced platelet aggregation showed the same attenuation after exercise but no change during work. The release products beta-thromboglobulin and serotonin in plasma showed significant increases after exercise. This is taken as evidence of an enhanced platelet activity following exercise. A normal stress-response, measured as increase in cyclic AMP in plasma, was observed. In conclusion, platelets are activated following moderate exercise and it seems valid to include the post-exercise period in future studies.

Haemodynamics in postural hypotension--effects of the beta-adrenoceptor partial agonist xamoterol, and pindolol.

Beta-andrenoceptor agents have been used in the treatment of postural hypotension and agonist activity found to be important. The effects of xamoterol and pindolol on standing haemodynamics were compared in this study. Xamoterol was found to be of significant benefit, but pindolol was ineffective. Xamoterol may therefore be useful in the treatment of postural hypotension.

A comparison of systolic time intervals measured by impedance cardiography and carotid pulse tracing.

The purpose of this study was to compare the systolic time intervals (STI) obtained by impedance cardiography and by the conventional carotid technique. This comparison was done with respect to: 1) correlations between variables obtained by the two methods, 2) ability to reflect drug-induced changes, 3) reliability in terms of reproducibility and 4) heart rate dependency of the variables measured. The study included 25 unmedicated patients with ischaemic heart disease and 36 healthy subjects. We obtained significant correlations between STI-variables measured by the two methods (p less than 0.001) and found that left ventricular ejection times were longer when determined by the carotid technique (p less than 0.01). We found a significant correlation between drug-induced changes in STI-variables measured by the two methods (p less than 0.001). Both methods had a high degree of reproducibility and this parameter was significantly better within the same day, when impedance cardiography was used (p less than 0.01). The error due to the reading of STI-tracings obtained by impedance cardiography was very small when performed by the same observer. We found the pre-ejection period to be independent upon heart rate, while the left ventricular ejection time depended upon this parameter. We conclude that impedance cardiography and carotid technique differ with respect to the measurement of left ventricular ejection times, but not with respect to the measurement of other STI-variables. We furthermore conclude that both methods are reliable, but we recommend the use of impedance cardiography because it is easier to apply, it may be more precise and it can be used for simultaneous measurements of other haemodynamic variables.

Plasma concentrations of adrenaline, noradrenaline and dopamine during forearm dynamic exercise.

In six healthy volunteers plasma concentrations of adrenaline, noradrenaline and dopamine were measured at rest and during dynamic forearm exercise at submaximal and maximal intensities. Arterial and venous concentrations of adrenaline and noradrenaline increased with forearm exercise at all workloads. Dopamine concentrations did not change. The increases in adrenaline and noradrenaline were almost linearly related to the increase in heart rate with no levelling off at maximal exercise intensities. It is concluded that dynamic exercise with the forearm muscle group causes a small but significant activation of the sympatho-adrenal system as reflected by increases in plasma concentrations of adrenaline and noradrenaline.

Disposition kinetics of disopyramide in human healthy volunteers described by an open three compartment model.

Disposition kinetics of disopyramide was examined in an open randomised cross-over study in 8 healthy volunteers. Disopyramide was randomly administered as a single bolus injection (150 mg) over a period of 5 min. and as an infusion (28.2) mg/h to steady state. Disposition kinetics of disopyramide were most precisely described by an open three compartment model according to Akaike's information criteria. Significant positive correlations (0.909 +/- 0.04, P less than 0.05 (injection study); 0.787 +/- 0.11, P less than 0.05 (infusion study] were observed between total serum concentrations of disopyramide and renal clearance while no significant correlation could be demonstrated between free serum concentrations and renal clearance. This implies a constant value of unbound renal clearance. The results are consistent with non linear kinetics (mainly caused by the variable free fraction of the drug), when based on total serum concentrations. The disposition of unbound disopyramide, however seems to be linear (i.e. the kinetic parameters are independent of dose) in the bolus injection study. Total elimination clearance (free and total), volume of distribution and elimination half-life were significantly higher in the steady state experiment than in the bolus injection study.

Forearm oxygen uptake during maximal forearm dynamic exercise.

This study was undertaken in an attempt to determine the maximal oxygen uptake in a small muscle group by measuring directly the oxygen expenditure of the forearm. Five healthy medical students volunteered. The subjects' maximal forearm work capacity was determined on a spring-loaded hand ergometer. Exercise was continued until exhaustion by pain or fatigue. Two weeks later intra-arterial and intravenous catheters were placed in the dominant arm. Blood samples for measurement of oxygen concentration were collected via the catheters. Forearm blood flow was measured by means of the indicator dilution technique. Oxygen uptake was determined according to the Fick principle. The forearm oxygen uptake attained at maximal work loads was a mean of 201 (SD +/- 56) mumol.min-1.100 ml-1. It was impossible at maximal exercise to discern a plateau of the oxygen uptake curve in relation to work output. It is suggested that a plateau in the oxygen uptake curve is not a useful criterion for maximal oxygen uptake in a small muscle group. Skeletal muscle may have an unused capacity for oxygen consumption even at maximal exercise intensity where muscle work cannot be continued due to muscle pain and fatigue.

The effect of exercise on platelet beta-adrenoceptor function and platelet aggregation in healthy human volunteers.

UNLABELLED: Plasma levels of adrenaline and noradrenaline, platelet cyclic-AMP (cAMP) content, platelet aggregation, platelet release of beta-thromboglobulin, and platelet factor 4 and serum content of thromboxane B2(TXB2) and 6-keto-PGF1 alpha were measured in 12 healthy male volunteers (age 38-72, mean 54.2 years) who were tested at rest and immediately after five min light cycle exercise. The plasma levels of adrenaline and noradrenaline increased significantly after exercise (P less than 0.01). The platelet cAMP level was not changed by exercise. The functional capacity of platelet beta-adrenoceptors, determined as cAMP production after beta-adrenoceptor stimulation in vitro, decreased highly significantly after exercise in all 12 volunteers (P less than 0.01). No alteration was observed in platelet aggregation induced by adrenaline or in platelet release of beta-thromboglobulin or platelet factor 4. No change was observed in the serum levels of TXB2 and 6-keto-PGF1 alpha. IN CONCLUSION: light cycle exercise results in a decreased functional capacity of platelet beta-adrenoceptors, but has no effect on platelet aggregation or platelet release. This might indicate a concomitant and equal decreased functional capacity of platelet alpha-adrenoceptors.

Prenalterol in severe congestive heart failure. II. Long-term oral treatment. Results with comments on the methods for evaluation of drugs in congestive heart failure.

Nine patients with severe congestive heart failure were treated with a partial beta-1-agonist prenalterol for 9.6 months on average. Five of the nine patients improved with an increase in NYHA-functional capacity of one class. In four of these patients, the improvement was maintained for 12 months. Upon discontinuation, deterioration occurred only in one case; in the latter, improvement reoccurred on reinstitution of prenalterol treatment. Significant improvement on exercise testing, however, occurred only in two patients. Prediction as to which patients would benefit from oral prenalterol was not possible from the pretreatment haemodynamic variables; similarly, the effect of oral prenalterol treatment could not be predicted from the response to prenalterol given intravenously. A critical review of the methods for evaluation of therapeutic intervention in congestive heart failure concludes the article.

Prenalterol in severe congestive heart failure. I. The immediate haemodynamic effects as compared to nitroglycerine.

The immediate haemodynamic effects of prenalterol and nitroglycerine were examined in 15 patients, with severe chronic heart failure. Prenalterol was given intravenously in increasing doses of 2, 4, and 8 mg. Cardiac index increased significantly by 16%, 24%, and 32%, respectively. Heart rate increased by 16%, 19%, and 24%. Stroke volume index, systemic artery pressure, pulmonary artery pressure, and right atrial pressure did not change. Prenalterol reduced systemic vascular resistance by 15%, 17%, and 24%, respectively. Forearm blood flow and forearm vascular resistance was unchanged. Cardiac index and heart rate were not changed by 0.5 mg nitroglycerine, administered sublingually. Systolic and diastolic blood pressure were on average reduced by 14% and 12%, respectively. Systolic and diastolic pulmonary artery pressure and right atrial pressure were similarly reduced by 17%, 31%, and 39%, respectively. Nitroglycerine lowered calculated systemic vascular resistance by 11%, whereas forearm blood flow and forearm vascular resistance was unchanged. The conclusion is that prenalterol acutely increased cardiac index and improved haemodynamics in 14 out of 15 patients, mainly due to an increased heart rate. Nitroglycerine did not change cardiac index in the same group of patients.

Acute unilateral obstruction of ureter. Disparity in divided renal function calculated from 131I-hippuran and 99mTc-DTPA renography.

Fifteen patients with acute unilateral obstruction of ureter and 30 control patients were studied with simultaneous 131I-Hippuran and 99mTc-DTPA gamma camera renography. In severe outflow obstruction the relative function of the obstructed kidney was higher when calculated with Hippuran than with DTPA. No difference was found in the control subjects. This means that the glomerular filtration rate of an obstructed kidney may be relatively more reduced than the renal blood flow. Therefore, measurement of the single kidney fraction of total glomerular filtration rate has to be calculated with a glomerular filtered tracer, e.g., 99mTc-DTPA.