Colloid volume loading does not mitigate decreases in central blood volume during simulated haemorrhage while heat stressed.

Heat stress results in profound reductions in the capacity to withstand a simulated haemorrhagic challenge; however, this capacity is normalized if the individual is volume loaded prior to the challenge. The present study tested the hypothesis that volume loading during passive heat stress attenuates the reduction in regional blood volumes during a simulated haemorrhagic challenge imposed via lower-body negative pressure (LBNP). Seven subjects underwent 30 mmHg LBNP while normothermic, during passive heat stress (increased internal temperature ∼1◦C), and while continuing to be heated after intravenous colloid volume loading (11 ml kg⁻¹). Relative changes in torso and regional blood volumes were determined by gamma camera imaging with technetium-99m labelled erythrocytes. Heat stress reduced blood volume in all regions (ranging from 7 to 16%), while subsequent volume loading returned those values to normothermic levels. While normothermic,LBNP reduced blood volume in all regions (torso: 22 ± 8%; heart: 18 ± 6%; spleen: 15 ± 8%). During LBNP while heat stressed, the reductions in blood volume in each region were markedly greater when compared to LBNP while normothermic (torso: 73 ± 2%; heart: 72 ± 3%; spleen: 72 ± 5%, all P<0.001 relative to normothermia). Volume loading during heat stress did not alter the extent of the reduction in these blood volumes to LBNP relative to heat stress alone (torso: 73 ± 1%; heart: 72 ± 2%; spleen: 74 ± 3%, all P>0.05 relative to heat stress alone). These data suggest that blood volume loading during passive heat stress (via 11 ml kg⁻¹ of a colloid solution) normalizes regional blood volumes in the torso, but does not mitigate the reduction in central blood volume during a simulated haemorrhagic challenge combined with heat stress.

Use of neural networks to improve quality control of interpretations in myocardial perfusion imaging.

BACKGROUND: The aim of this study was to explore the feasibility of using a technique based on artificial neural networks for quality assurance of image reporting. The networks were used to identify potentially suboptimal or erroneous interpretations of myocardial perfusion scintigrams (MPS). METHODS: Reversible perfusion defects (ischaemia) in each of five myocardial regions, as interpreted by one experienced nuclear medicine physician during his daily routine of clinical reporting, were assessed by artificial neural networks in 316 consecutive patients undergoing stress/rest 99mTc-sestamibi myocardial perfusion scintigraphy. After a training process, the networks were used to select the 20 cases in each region that were more likely to have a false clinical interpretation. These cases, together with 20 control cases in which the networks detected no likelihood of false clinical interpretation, were presented in random order to a group of three experienced physicians for a consensus re-interpretation; no information regarding clinical or neural network interpretations was provided to the re-evaluation panel. RESULTS: The clinical interpretation and the re-evaluation differed in 53 of the 200 cases. Forty-six of the 53 cases (87%) came from the group selected by the neural networks, and only seven (13%) were control cases (P < 0.001). The disagreements between clinical routine interpretation by an experienced nuclear medicine expert and artificial networks were related to small and mild perfusion defects and localization of defects. CONCLUSION: The results demonstrate that artificial neural networks can identify those myocardial perfusion scintigrams that may have suboptimal image interpretations. This is a potentially highly cost-effective technique, which could be of great value, both in daily practice as a clinical decision support tool and as a tool in quality assurance.

EANM/ESC guidelines for radionuclide imaging of cardiac function.

Radionuclide imaging of cardiac function represents a number of well-validated techniques for accurate determination of right (RV) and left ventricular (LV) ejection fraction (EF) and LV volumes. These first European guidelines give recommendations for how and when to use first-pass and equilibrium radionuclide ventriculography, gated myocardial perfusion scintigraphy, gated PET, and studies with non-imaging devices for the evaluation of cardiac function. The items covered are presented in 11 sections: clinical indications, radiopharmaceuticals and dosimetry, study acquisition, RV EF, LV EF, LV volumes, LV regional function, LV diastolic function, reports and image display and reference values from the literature of RVEF, LVEF and LV volumes. If specific recommendations given cannot be based on evidence from original, scientific studies, referral is given to "prevailing or general consensus". The guidelines are designed to assist in the practice of referral to, performance, interpretation and reporting of nuclear cardiology studies for the evaluation of cardiac performance.

Effects of passive heating on central blood volume and ventricular dimensions in humans.

Mixed findings regarding the effects of whole-body heat stress on central blood volume have been reported. This study evaluated the hypothesis that heat stress reduces central blood volume and alters blood volume distribution. Ten healthy experimental and seven healthy time control (i.e. non-heat stressed) subjects participated in this protocol. Changes in regional blood volume during heat stress and time control were estimated using technetium-99m labelled autologous red blood cells and gamma camera imaging. Whole-body heating increased internal temperature (> 1.0 degrees C), cutaneous vascular conductance (approximately fivefold), and heart rate (52 +/- 2 to 93 +/- 4 beats min(-1)), while reducing central venous pressure (5.5 +/- 07 to 0.2 +/- 0.6 mmHg) accompanied by minor decreases in mean arterial pressure (all P < 0.05). The heat stress reduced the blood volume of the heart (18 +/- 2%), heart plus central vasculature (17 +/- 2%), thorax (14 +/- 2%), inferior vena cava (23 +/- 2%) and liver (23 +/- 2%) (all P

Propylthiouracil before 131I therapy of hyperthyroid diseases: effect on cure rate evaluated by a randomized clinical trial.

A randomized clinical trial was performed to clarify whether pretreatment with propylthiouracil (PTU) before radioiodine ((131)I) therapy influences the final outcome of this therapy, as has been indicated by retrospective studies. Untreated consecutive hyperthyroid patients with Graves' disease (n = 23) or a toxic nodular goiter (n = 57) were randomized to either PTU (+PTU; n = 39) or no pretreatment (-PTU; n = 41) before compensated (131)I therapy. The median PTU dose was 100 mg, which was discontinued 4 d before treatment. The median (131)I activity was 302 MBq (range, 87-600 MBq). After (131)I therapy, the serum free T(4) index increased in the +PTU group from 97.7 +/- 47.5(+/-sd) nmol/liter at the time of therapy to 152.3 +/- 77.6 nmol/liter at 3 wk (P < 0.001) and 140.4 +/- 75.9 nmol/liter at 6 wk (P < 0.001). In the -PTU group, the serum free T(4) index, which was initially 254.3 +/- 145.7 nmol/liter, decreased significantly to 212.0 +/- 113.0 nmol/liter at 3 wk (P < 0.05) and 165.8 +/- 110.0 nmol/liter at 6 wk (P < 0.005). After 1 yr of follow-up, the treatment failure rate in patients with a toxic nodular goiter was four times higher in the +PTU group than in the -PTU group (nine of 20 vs. three of 25 patients; P = 0.06), whereas the difference among patients with Graves' disease was less obvious (four of six vs. four of nine; P = 0.81). Patients in the +PTU group who were cured had higher serum TSH (s-TSH) levels at the time of (131)I therapy than those who were not cured. By adjusting for a possible interfactorial relationship through a regression analysis, including the s-TSH level and type of disease, only PTU pretreatment had a significant adverse effect on the cure rate (P = 0.03). In conclusion, this randomized trial demonstrates that PTU pretreatment reduces the cure rate of (131)I therapy in hyperthyroid diseases, although this adverse effect seems to be attenuated by the concomitant rise in s-TSH.

Myocardial perfusion imaging and coronary angiography in patients with known or suspected stable angina pectoris.

INTRODUCTION: The patho-physiological cause of angina pectoris is myocardial ischaemia, which can be objectified by myocardial perfusion imaging (MPI). METHODOLOGY: MPI was undertaken prior to coronary angiography (CAG) in 86 randomly selected patients with known or suspected stable angina pectoris. RESULTS: Among 78 adequately stressed patients, MPI was normal in 28 (36%) and showed reversible and irreversible perfusion abnormalities in 30 (38%) and 20 patients (26%), respectively. Coronary angiograms were normal in 28 (36%) and revealed at least one > or = 50% stenosis in 50 patients (64%) (16 with single and 34 with multi vessel disease). Using angiography as a reference, the sensitivity and specificity of MPI in detecting coronary artery disease was 88% and 93%, respectively. DISCUSSION: MPI demonstrates regional hypoperfusion whereas CAG depicts anatomical stenosis in epicardial arteries. Both modalities are potentially relevant in patients with stable angina pectoris. The functional significance of coronary artery lesions is, however, variable and MPI can demonstrate normal myocardial perfusion in the presence of moderate lesions. MPI exhibited a high sensitivity and specificity regarding significant lesions. More than one third of the subjects had a normal MPI and a normal CAG. Patients with stable angina pectoris and a normal MPI have a very low risk of cardiac events and do usually not require further invasive investigation or therapy. Reversible ischaemia and irreversible ischaemia with demonstration of viable tissue call for coronary revascularisation.

[Myocardial scintigraphy and coronary arteriography in patients with known or suspected stable angina pectoris]. / Myokardiescintigrafi og koronararteriografi hos patienter med kendt eller formodet stabil angina pectoris.

INTRODUCTION: Myocardial perfusion imaging (MPI) demonstrates regional hypoperfusion, whereas coronary angiography shows anatomical stenoses in epicardial arteries. Both modalities are potentially relevant in patients with stable angina pectoris. MATERIALS AND METHODS: MPI was undertaken before angiography in 86 randomly selected patients with stable angina pectoris. RESULTS: Of 78 adequately stressed patients, MPI was normal in 28 (36%) and showed reversible and irreversible perfusion abnormalities in 30 (38%) and 20 patients (26%), respectively. Coronary angiograms were normal in 28 (36%) and revealed at least one > or = 50% stenosis in 50 patients (64%) (16 with single vessel and 34 with multivessel disease). With angiography as reference, the sensitivity and specificity of MPI in the detection of coronary artery disease were 88% and 93%, respectively. DISCUSSION: Patients with stable angina pectoris and a normal MPI have a very low risk of cardiac events and do not usually require invasive investigation and therapy. Reversible ischaemia and irreversible ischaemia with viable tissue call for coronary revascularisation.

Effect of a full bladder on urine production in humans.

OBJECTIVE: To demonstrate the reduction in urine production in healthy humans upon bladder distension and to identify the factors responsible for this reduction. MATERIALS AND METHODS: Twelve healthy females were investigated twice in a cross-over designed experiment: once with the urinary bladder empty at the start and once pre-filled to 60% of the maximum bladder capacity. Glomerular filtration rate, effective renal plasma flow, urine content of catecholamines, blood pressure, pulse rate, plasma arginine vasopressin (AVP) and plasma concentration of renine and electrolytes were analysed together with serum osmolality. RESULTS: Three subjects failed to reach maximum bladder capacity during the "full bladder" test and were excluded. The urine production in the "full-bladder" test was significantly lower than the "empty-bladder" test (p = 0.024). In the "full-bladder" test a significant increase in mean blood pressure was found (p=0.01). No further significant changes were demonstrated. CONCLUSIONS: Acute bladder distension causes a reduction in urine production or a "pooling of urine" in the upper urinary tract in healthy humans. The mechanism is unknown.

Vertebral artery flow and spinal manipulation: a randomized, controlled and observer-blinded study.

BACKGROUND: Several studies have been published on the effect of cervical rotation alone upon blood flow in the vertebral arteries. However, we have not found articles addressing the question of how spinal manipulative therapy per se affects the vertebral artery flow. OBJECTIVE: The aim of the present study was to investigate whether any changes occur in peak flow velocity in the vertebral artery after spinal manipulative therapy as measured using the latest Doppler ultrasound technology. DESIGN AND SETTING: A randomized, controlled and observer-blinded study at a university hospital vascular laboratory. PARTICIPANTS: Twenty university students with a "biomechanical dysfunction" in the cervical spine. RESULTS: We observed no change in peak flow velocity immediately after spinal manipulative therapy and found no correlation between peak flow velocity and systolic blood pressure. CONCLUSION: To the best of our knowledge, this is the first study comparing flow velocity in the vertebral artery before and after spinal manipulative therapy. We found no significant changes in otherwise healthy subjects with a biomechanical dysfunction of the cervical spine. Major changes in peak flow velocity might in theory explain the pathophysiology of cerebrovascular accidents after spinal manipulative therapy. However, in uncomplicated spinal manipulative therapy, this potential risk factor was not prevalent.

Survival of autotransfused red cells. 51Cr studies in 10 knee arthroplasty patients.

We determined the long-term survival of red blood cells collected postoperatively from the surgical drains, filtered and autotransfused with the Constavac Blood Conservation System. 10 patients with knee arthrosis were treated with cementless total knee arthroplasty and postoperatively connected to the autotransfusion system. Shed blood was collected for 6 hours postoperatively and then reinfused. Before reinfusion, a fraction of the blood shed was radiolabeled with chromium-51 (51Cr). For a postoperative minimum period of 40 days the activity of 51Cr was measured in frequent venous blood samples. The time from 100% to 50% activity of the isotope (T50Cr) was 21 days, equal to that reported for banked autologous blood.

Sarcoidosis causes abnormal seasonal variation in 1,25-dihydroxy-cholecalciferol.

OBJECTIVES: The spontaneous seasonal variations in the calcium regulating hormones 1,25-dihydroxy-cholecalciferol (1,25-DHCC) and parathyroid hormone (PTH) were investigated in patients with sarcoidosis. DESIGN: Controlled, prospective observational study with measurements in the winter and summer seasons, respectively. SUBJECTS: Twelve patients (age: median 33, range 21-54 years) with biopsy-verified (n = 8) sarcoidosis were included as well as 11 age-matched healthy control subjects. MAIN OUTCOME MEASURES: Serum values of calcium, ionized calcium, phosphate, chloride, bicarbonate, creatinine, albumin, angiotensin-converting enzyme, alkaline phosphatase, 1,25-DHCC, and PTH. Also, 24-h whole body retention of 99mTc methylene-diphosphonate was assessed. RESULTS: The patient group showed an increased level of 1,25-DHCC in the summer season (w:146 +/- 67, s:198 +/- 73 pmol L-1; P < 0.01) in contrast to the opposite finding among controls (w:161 +/- 34, s:144 +/- 43 pmol L-1; P < 0.05). Comparing the individual seasonal changes between the two groups, the difference was marked (P < 0.001). Compared with controls, total serum calcium was elevated in the summer season in the patient group (P < 0.05), in which the same parameter correlated positively with 1,25-DHCC (r = 0.658; P < 0.01). PTH was increased two to three times above the control values throughout the year (patients: w:0.37 +/- 0.13, s:0.24 +/- 0.08 micrograms L-1; controls: w:0.14 +/- 0.09, s:0.10 +/- 0.04 micrograms L-1; P < 0.001); although, the level of this hormone was still found within the reference interval. 24-h whole body bone scintigraphy failed to show any seasonal variation in bone metabolism. In contrast, serum alkaline phosphatase was found to be increased during the summer season compared with the control group (P < 0.001). Angiotensin-converting enzyme showed no seasonal variation. CONCLUSIONS: In sarcoidosis, 1,25-DHCC is abnormally regulated throughout the year, with a significantly higher serum level in the summer season. Uncontrolled production of 1,25-DHCC in sarcoid pulmonary alveolary macrophages is possibly responsible for hypercalcaemic episodes, and this parameter should be used as a marker of disease activity.

Left ventricle haemodynamics and vaso-active hormones during graded supine exercise in healthy male subjects.

Left ventricle systolic and diastolic functional parameters were measured by gated equilibrium radionuclide cardiography in 12 healthy men (age 33-51 years) at rest and during graded supine exercise. The leftventricle end-diastolic volume showed an initial small (11%) increase during low submaximal exercise [from mean 163 (SD 40) at rest to mean 181 (SD 48) ml], while left ventricle end-systolic volume decreased successively [from mean 59 (SD 19) to mean 39 (SD 21) ml] with increasing exercise. Stroke volume was therefore elevated at all exercise levels compared with rest [mean 104 (SD 23) ml], and the peak value [mean 128 (SD 33) ml] was found at the lowest exercise level, contributing 40% to the initial increase in cardiac output. Cardiac output increased from mean 6.2 (SD 1.4) at rest to mean 20.2 (SD 5.0) l.min-1 at maximum. Left ventricle peak ejection and peak filling rates increased from mean 449 (SD 89) and mean 442 (SD 85) ml.s-1 at rest to mean 996 (SD 227) and mean 1255 (SD 333) ml.s-1, respectively, at maximum. The myocardium oxygen consumption, assumed to be proportional to the sum of the stroke work and the potential energy, increased fourfold, but absolute values were twice as high as expected, indicating that extrapolation from data obtained in dog hearts (as we have done) cannot be directly applied to humans. Selected vaso-active hormones were measured at all exercise intensities. Noradrenaline (NA), adrenaline (A) and angiotensin II (AII) concentrations showed a very pronounced increase at maximal exercise compared with the preceding lower intensites, while atrial natriuretic factor (ANF) and cyclic guanosinemonophosphate (cGMP) concentrations showed a more continuous increase, and dopamine (DA) remained almost unchanged. This speaks in favour of a crucial role for NA, A and AII in preserving blood pressure at maximum exercise, while DA probably has no importance for the cardiovascular homeostasis during exercise. Increases in concentrations of ANF and cGMP were highly correlated (r = 0.86). Our data supported the opinion that there is a cardiac limitation to maximal performance connected to the cardiac pumping capacity.

Angiotensin converting enzyme inhibition at rest and during exercise in congestive heart failure.

The haemodynamic effects of the sulfhydryl-containing angiotensin converting enzyme inhibitor, zofenopril, were studied in patients in New York Heart Association functional class II and III. Twenty-one clinically stable patients with coronary artery disease or cardiomyopathy completed a randomized double-blind treatment period of 2 months with either 15 mg zofenopril once daily or placebo. Regular therapy with digoxin and diuretic drugs was continued. Left ventricular volumes were measured by radionuclide angiography at rest and during submaximal bicycle exercise. Zofenopril significantly increased mean stroke volume at rest from 59 to 67 ml (48 vs 48 ml in the control group, 95% confidence interval of the difference 1 to 16 ml) and left ventricular ejection fraction at rest from 39 to 43% (30 vs 30% in the control group, 95% confidence interval of the difference 1 to 8%). No significant changes occurred in heart rate, cardiac output, and blood pressure at rest, and zofenopril did not result in haemodynamic alterations during exercise. Thus, 15 mg of the sulfhydryl-containing angiotensin converting enzyme inhibitor, zofenopril, administered once daily to patients with moderate heart failure increases left ventricular function at rest, but not during exercise.

Acute plasma expansion: left ventricular hemodynamics and endocrine function during exercise.

In 11 healthy subjects (8 males and 3 females, age 21-59 yr) left ventricular end-diastolic (LVEDV) and end-systolic (LVESV) volumes were measured in the supine position by isotope cardiography at rest and during two submaximal one-legged exercise loads before and 1 h after acute plasma expansion (PE) by use of a 6% dextran solution (500-750 ml). After PE, blood volume increased from 5.22 +/- 0.92 to 5.71 +/- 1.02 (SD) liters (P < 0.01). At rest, cardiac output increased 30% (5.3 +/- 1.0 to 6.9 +/- 1.6 l/min; P < 0.01), stroke volume increased from 90 +/- 20 to 100 +/- 28 ml (P < 0.05), and LVEDV increased from 134 +/- 29 to 142 +/- 40 ml (NS). LVESV was unchanged (44 +/- 11 and 42 +/- 14 ml). Heart rate rose from 60 +/- 7 to 71 +/- 10 beats/min (P < 0.01). The cardiac preload [central venous pressure (CVP)] was insignificantly elevated (4.9 +/- 2.1 and 5.3 +/- 3.0 mmHg); systemic vascular resistance and arterial pressures were significantly reduced (mean pressure fell from 91 +/- 11 to 85 +/- 11 mmHg, P < 0.01). Left ventricular peak filling and peak ejection rates both increased (19 and 14%, respectively; P < 0.05). During exercise, cardiac output remained elevated after PE compared with the control situation, predominantly due to a 10- to 14-ml rise in stroke volume caused by an increased LVEDV, whereas LVESV was unchanged. CVP increased after PE by 2.1 and 3.0 mmHg, respectively (P < 0.05).2+ remained unchanged during exercise compared with rest after PE in

Does alfentanil preserve left ventricular pump function during rapid sequence induction of anaesthesia?

A double-blind, randomised trial was conducted in 24 patients without cardiopulmonary disorders (20-43 years), to assess the effect of an intravenous bolus of alfentanil on the circulatory and catecholamine responses to rapid sequence induction of general anaesthesia. Induction included injection of thiopentone 5 mg/kg and suxamethonium 1.5 mg/kg in rapid succession, followed by laryngoscopy and intubation. Half of the patients received alfentanil 100 micrograms/kg immediately before thiopentone. The other half received saline. Blood pressure, heart rate, and plasma catecholamine concentrations were measured repeatedly, together with left ventricular ejection fraction assessed by radionuclide angiocardiography. The responses following laryngoscopy and intubation were completely different in the saline vs. the alfentanil group: rate pressure product +76% vs. -32%, mean arterial blood pressure +46% vs. -25%, heart +46% vs. no change, noradrenaline +117% vs. -25%, adrenaline +50% vs. -53%, and left ventricular ejection fraction -32% vs. no change. In conclusion, during rapid sequence induction of anaesthesia with thiopentone and suxamethonium, an intravenous bolus of alfentanil 100 micrograms/kg 1 min before laryngoscopy and intubation completely prevents hypertension, tachycardia, decrease in left ventricular ejection fraction, and activation of plasma catecholamines, though at the expense of moderate hypotension.

Effects of atropine on left ventricular volumes and ejection and filling rates at rest and during exercise.

1. The influence of the parasympathetic nervous system on left ventricular function including ejection and filling rates was studied by radionuclide cardiography in eight healthy young men at rest and during upright exercise. 2. After parasympathetic blockade induced by atropine, the mean heart rate (HR) at upright rest increased from 67 to 114 beats min-1, cardiac output (CO) from 4.05 to 5.17 1 min-1 (both P less than 0.001), and the diastolic blood pressure by 13 mm Hg (P less than 0.01). 3. Stroke volume (SV), left ventricular end diastolic and end systolic volume all decreased significantly after atropine. The relative ejection time increased from 0.33 to 0.51 of the cardiac cycle length (P less than 0.001), and the appropriate ejection and filling rates increased by 13% (P less than 0.05) and 147% (P less than 0.001), respectively. Haemodynamic changes in the supine position were virtually the same. 4. During exercise atropine increased HR from 115 to 146 beats min-1 (P less than 0.001) and CO by 12% (P less than 0.05), whereas SV decreased by 12% (P less than 0.05) and the systolic blood pressure by 16 mm Hg (P less than 0.001). Changes in ejection and filling rate of the left ventricle were of the same nature as those found at rest. 5. Thus apart from its HR limiting properties, secondary effects of parasympathetic nervous tone are dilatation of the left ventricle and enhancement of ejection, effects that are counteracted by atropine.

Left-ventricular performance, volumes, and catecholamine responses during anaesthesia induction--monitoring by combined radionuclide cardiography and right heart catheterization.

Sequential radionuclide imaging and continuous recording of arterial and right heart pressures were carried out during anaesthesia with midazolam 0.2 mg kg-1, pancuronium 0.15 mg kg-1 and fentanyl 10 micrograms kg-1 in eight patients with normal cardiopulmonary status scheduled for craniotomy. The aim was to examine how a stress-free anaesthetic induction tailored to protect against the hypertension and tachycardia provoked by laryngoscopy and intubation influenced left-ventricular performance, left-ventricular loading conditions and plasma catecholamine concentrations. During the 20-min study period no significant changes were observed in heart rate, left-ventricular ejection fraction, ratio of peak systolic pressure to left-ventricular end-systolic volume, pulmonary capillary wedge pressure, left-ventricular end-systolic volume, cardiac output, dopamine and noradrenaline concentrations. Except for a minor increase in mean arterial pressure after laryngoscopy and intubation, mean arterial pressure decreased 24%, left-ventricular end-diastolic volume decreased 15%, and left-ventricular stroke volume decreased 21%. Central venous pressure increased by 75% but there was no parallel increase in pulmonary wedge pressure, which in turn did not reflect the alterations in ventricular end-diastolic volume. Plasma adrenaline concentrations decreased significantly (66%). The chosen induction regimen preserved global left-ventricular pump function during laryngoscopy and intubation without any activation of the sympathetic nervous system. Central venous and pulmonary wedge pressures were unreliable in the assessment of ventricular preload during induction of general anaesthesia.

Left ventricular peak filling rate, heart failure and 1-year survival in patients with acute myocardial infarction.

Radionuclide left ventricular (LV) peak filling rate (PFR) was determined in 185 survivors of acute myocardial infarction (AMI) and expressed in units of (1) end-diastolic volume per second (EDV s-1). (2) stroke volume per second (SV s-1), or (3) actual millilitres of blood filled into the left ventricle per second (ml s-1). The purpose of the study was to assess the interrelationship between the three expressions of PFR, and to analyse their significance with regard to signs of congestive heart failure and 1-year survival in patients with AMI. PFR EDV s-1, PFR SV s-1 and PFR ml s-1 had a poor relationship to each other, were all influenced by LV volumes and ejection fraction, and supplied contradictory information with regard to LV filling in patients with heart failure. None of the three expressions of LV peak filling rate had an association to heart failure that was independent of LV volume and ejection fraction. A low PFR EDV s-1 in contrast to a high PFR SV s-1 was associated with a high 1-year cardiac mortality, suggesting that these 'normalized' indices of LV peak filling rate signalled LV size and stroke volume rather than actual LV filling behaviour. No association was present between PFR ml s-1 and 1-year mortality. We conclude that the clinical use of radionuclide LV PFR in patients with AMI may lead to spurious results, unless the influence of LV size and ejection fraction is taken into consideration.

Does the decrease in heart rate prevent a detrimental decrease of the end-systolic volume during central hypovolemia in man?

Central hypovolemia occurring with epidural anesthesia was investigated by measurement of hemodynamic and endocrine variables in 10 patients. Responses fell into two categories. Four patients experienced a hypotensive bradycardic episode after seventeen +/- four minutes. In this group epidural anesthesia initially induced a tendency toward an increase in heart rate from 65 +/- 4 to 73 +/- 5 beats/min concomitantly with decreases in end-diastolic (172 +/- 22 to 138 +/- 16 mL), end-systolic (67 +/- 12 to 51 +/- 9 mL), and stroke (105 +/- 10 to 85 +/- 7 mL) volumes (radionuclide cardiography). A subsequent decrease in mean arterial pressure from 76 +/- 3 to 67 +/- 4 mmHg was associated with a decrease in venous return as reflected by the decrease in cardiac output from 6.1 +/- 0.4 to 4.7 +/- 0.7 L/min. In this situation when the venous return was critically reduced, the heart rate was 49 +/- 4 beats/min and no further reduction in end-diastolic and end-systolic volumes was observed. The observed endocrine changes were compatible with a response to central hypovolemia. In the other 6 patients the reaction to epidural anesthesia did not induce statistically significant changes in hemodynamic and endocrine variables. It is concluded (1) that the decrease in heart rate associated with central hypovolemia during epidural anesthesia seems to be elicited when the left ventricular end-systolic volume is decreased by about 25% and (2) that a further decrease in end-systolic volume during progressive central hypovolemia is avoided possibly as a direct consequence of the slowing of the heart.