Systemic compliance: does it play a role in the genesis of essential hypertension?

Arterial compliance is part of the load faced by the heart. Decreased compliance increases this load. We have studied the cardiovascular consequences of decreased systemic compliance in six closed chest anaesthetised dogs where ascending aortic flow transducers and left ventricular crystals had previously been implanted. A stiff tube was put into the abdominal aorta from the left flank and moved to the ascending aorta. Inflation of a cuff on the proximal end of the tube forced the heart to eject into a non-compliant outflow conduit. The distal end of the tube was connected to the distal aorta and, via a pump, to a carotid artery where mean pressure was kept above 80 mmHg. We measured systemic pressures (catheter-tip manometer), cardiac output (electromagnetic flowmeter) and either left ventricular end-diastolic pressure (fluid filled catheter, Statham P23Db) or left ventricular diameter (ultrasound transit time method). From these variables we calculated systemic compliance and input impedance. A 35% decrease in compliance caused a 12% increase in systolic, and a 12% decrease in diastolic pressure while mean pressure and cardiac output did not change significantly. With a decrease in compliance of 63% systolic pressure increased by 18%, while diastolic pressure decreased by 24%. Mean pressure did not change significantly but cardiac output fell by 21%. In both groups of altered compliance peripheral resistance rose slightly but this was not significant. Decreased compliance mainly caused changes in the low frequency range of the input impedance: moduli increased and phase angles became more negative.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes of microsphere density with time in myocardial infarcts in dogs.

The density of microspheres injected before occlusion of a coronary artery, in the infarcted region [I], was compared with that of healthy, normal myocardium [N], from the same dog. The [I]/[N] ratio was measured at different days after infarction up to 2 weeks. The ratio was below unity before the ninth day and above that thereafter. The changes in microspheres density can be explained on the basis of microsphere loss from necrotic tissue and changes in infarct mass.

Reflection in the systemic arterial system: effects of aortic and carotid occlusion.

Experiments were performed in seven closed-chest anaesthetized male dogs to determine the role of pulse wave reflection in the pattern of flow and pressure in the ascending aorta. Ten days after implantation of an electromagnetic flow transducer around the ascending aorta a balloon catheter was placed in the descending aorta via the femoral arteries. At the same time a tip manometer was introduced into the ascending aorta. Aortic occlusions at three different sites caused pressure pulses with secondary systolic rises and flow pulses with biphasic deceleration. Secondary rises occurred 45 +/- 9.0 ms after the initial pressure rise for high aortic occlusion; this time was 75 +/- 8.5 ms for occlusion at the level of the diaphragm and 114 +/- 16.5 ms for occlusion near the level of the renal arteries. These times approximate the times in which the pulse travels from the tip manometer to the inflated balloons and back. Forward and reflected pressure and flow waves were calculated from reflection coefficients. Aortic occlusion caused larger reflected waves and the recorded wave forms were caused by the summation of forward and backward waves, the latter contributing the secondary pressure rise and the increased flow deceleration. Occlusion of both carotid arteries showed no specific reflection site but reflected waves were larger. This increased reflection can probably be explained as the result of greater total reflection from distributed sites under increased peripheral resistance.

Distribution of cardiac output, oxygen consumption and lactate production in canine endotoxin shock.

Endotoxin causes shock accompanied by compensatory changes such as redistribution of cardiac output and increased oxygen extraction. We studied these effects in anaesthetised dogs (etomidate: 4 mg X kg-1 X h-1, n = 14) randomly assigned to a control (n = 6) and a shock group (endotoxin 1.5 mg X kg-1; n = 8). We measured left ventricular pressure, LVEDP and LVdP/dt (Millar microtip), mean systemic, central venous and pulmonary artery pressure (Statham P23Db), cardiac output (thermodilution), organ flow (microspheres, 15 micron, 5 labels), bloodgases (PO2, PCO2), pH and lactate. All measurements were performed before and at 60, 90, 120 and 150 min after endotoxin or saline. Sixty minutes after endotoxin mean systemic pressure, LVdP/dt and cardiac output had decreased (by 60, 50 and 35%), while heart rate had increased (by 30%). Arterial PO2 was lower after endotoxin (-29%), haematocrit and mixed venous PCO2 were higher (+16 and +38%) and arterial pH had decreased from 7.34 to 7.14. After endotoxin perfusion of heart and adrenals did not change but muscle perfusion increased (by 33% at t = 90). Endotoxin caused vasoconstriction in spleen and kidneys: the percentage of cardiac output to these organs thus decreased (by 50 and 69%). Sixty minutes after endotoxin we found vasodilatation in the hepatic arterial, pancreatic, and gastrointestinal beds. Later the percentage of cardiac output to these beds decreased. Systemic arterio-venous shunting fell (from 6.5 to 0.7%). Systemic and splanchnic oxygen extraction increased (by 66 and 71% at t = 60): oxygen consumption hardly changed; 60 min after endotoxin it tended to decrease. During shock serum lactate rose (by 167% at t = 60) before oxygen consumption fell. Myocardial oxygen consumption did not alter during shock but the tension time index decreased.

Myocardial metabolic and morphometric changes during canine endotoxin shock before and after glucose-insulin-potassium.

Glucose-insulin-potassium (GIK) improves myocardial function during endotoxin shock but the mechanism of this action is not clear. We have studied in open chest dogs the effects of GIK (n = 9) on haemodynamics, myocardial biochemistry (repeated drill biopsies; glucose-6-phosphate, G-6-P; fructose-6-phosphate, F-6-P; adenosine triphosphate, ATP; creatinine phosphate, CP; glycogen) and myocardial histomorphometry. The animals were anaesthetised (etomidate 4 mg X kg-1 X h-1) and artificially ventilated (N2O:O2 = 2:1). After endotoxin (1.5 mg X kg-1) cardiac output (CO) and mean arterial pressure (MAP) fell rapidly, with a temporary recovery followed by gradual circulatory collapse. Coronary blood flow (cbf; radioactive microspheres) decreased, but this was not significant. G-6-P tended to fall, as did ATP levels while CP levels were unaltered. Histomorphometrical analysis showed myocardial cell swelling with compression of capillaries and decreased interstitial volume. GIK infusion (50% glucose, 2 g X kg-1bw, 8 mmol KCl and 3 U insulin kg-1bw) increased CO and coronary blood flow. Glycogen and G-6-P levels did not change, while F-6-P tended to increase. ATP levels were not influenced by ATP/CP ratio decreased. Myocardial cell swelling markedly decreased; average capillary cross-sectional area, as an index of capillary compression, returned to control value. In two dogs, which died before the end of the experiment, myocardial oedema, with disturbed capillary volume and reduced interstitial volume was unaltered after GIK. The initial effects of GIK are most likely due to restoration of myocardial perfusion. Improved perfusion, and the influence of elevated serum osmolality and insulin levels on excitation-contraction coupling may help to improve myocardial function.

Maldistribution of heterogeneous coronary blood flow during canine endotoxin shock.

STUDY OBJECTIVE - The aim was to investigate whether heterogeneous coronary blood flow is maldistributed during endotoxin shock. DESIGN - Variables were studied before (t = 0) and at t = 90 and t = 120 min after bolus injection of saline (n = 6) or endotoxin (n = 6). SUBJECTS - 12 anaesthetised mongrel dogs, weight 20-27 kg, were used. MEASUREMENTS AND MAIN RESULTS - We studied myocardial blood flows in small tissue sections (of about 1 g in left and 2 g in right ventricle) with radioactive microspheres, together with haemodynamic variables and global myocardial metabolism. At t = 0 min in controls, regional flows per 100 g were heterogeneous and ranged from a factor 0.2 to 2.7 and 0.6 to 1.6 of mean flow per 100 g to the left and right ventricle respectively; heterogeneity was unchanged at t = 90 and t = 120 min. Between t = 0, t = 90, and t = 120 min regional flows correlated: r = 0.78(SD 0.14), n = 18, for left ventricle, and r = 0.70(0.17) for right ventricle. In the endotoxin group, cardiac output and mean arterial pressure decreased by 44(7) and 48(11)% respectively, and lactate increased by 3.2(0.6) mmol.litre-1 at t = 120 min. Global left ventricle blood flow and delivery and metabolism of O2 were unchanged; lactate extraction and external work fell. The ratio between global right ventricular O2 delivery and external work also rose. Regional blood flows ranged from a factor 0.2 to 2.7 and 0.1 to 1.8 of mean flow to left and right ventricles respectively; heterogeneity did not differ from controls and did not change with time. Flow correlations with time were reduced: 0.45(0.24) for left ventricle and 0.45(0.26) for right ventricle (both n = 18, p less than 0.005 v controls). The left ventricular endocardial to epicardial flow ratio fell; flow was redistributed to both layers. CONCLUSIONS - Heterogeneous blood flow is redistributed throughout the heart during canine endotoxin shock so that, at unchanged global blood flow and flow heterogeneity, flow decreases in some but increases in other areas. Flow maldistribution may be associated with focal ischaemia, which may be masked by a rise in O2 uptake for a given workload (contractile inefficiency) in overperfused areas, and may thereby contribute to a fall in global myocardial external work for a given O2 delivery.

Metabolic vasodilatation with glucose-insulin-potassium does not change the heterogeneous distribution of coronary blood flow in the dog.

OBJECTIVE: The heterogeneous distribution of coronary blood flow could represent regional differences in demand, or mismatching of regional O2 supply to demand, caused by regionally exhausted vasodilatation (anatomical/mechanical factors) or by regional arteriovenous diffusional O2 shunting. Regional coronary blood flow and global myocardial oxygenation and metabolism were measured during metabolic vasodilatation with glucose-insulin-potassium (GIK). METHODS: Variables were studied before and 30 and 60 min after start of a 30 min infusion of GIK (50% glucose, 4 ml.kg-1, 8 mM KCl, and 3 U insulin.kg-1). Regional blood flows were measured by radioactive microsphere technique and cardiac output by thermodilution. Experimental subjects were six anaesthetised mongrel dogs, weighing 20-27 kg. RESULTS: GIK increased plasma osmolarity and lactate, decreased haemoglobin, and increased cardiac output by 67(29)% and systemic O2 supply by 32(13)%, at unchanged arterial and central venous pressures and heart rate. Coronary blood flow rose by 97(50)% and left ventricular O2 supply by 56(41)%. Although regional blood flows in small tissue samples of about 1 g in the left ventricle ranged from a factor 0.31 to 1.73 of mean flow, GIK did not change flow heterogeneity and regional flows significantly correlated in time. Left ventricular O2 uptake rose by 42(40)%, while venous PO2 increased and O2 extraction decreased. Global lactate uptake increased at unchanged extraction. Changes were reversed after GIK. CONCLUSIONS: GIK transiently increases myocardial O2 uptake following a raised cardiac output, caused by a hyperosmolarity induced rise in cardiac contractility rather than by haemodilution. Although myocardial O2 supply is distributed heterogeneously, the fractional rise with GIK is almost equal among regions. At constant lactate extraction, increased venous PO2 and decreased O2 extraction do not indicate overperfusion in some regions at the cost of underperfusion in others, are probably caused by a small, direct vasodilating effect of hyperosmolarity, and argue against diffusional O2 shunting. As for global O2 supply to demand, the increase in regional O2 supply is probably well adapted to regionally increased demand during GIK, so that the heterogeneous distribution of O2 supply can be explained by regional differences in demand and not by regionally exhausted vasodilatation or O2 shunting.

Skeletal muscle perfusion and metabolism during canine endotoxin shock.

Conflicting data exist in literature about the effects of endotoxin on skeletal muscle perfusion and metabolism during canine endotoxin shock. In 12 dogs we therefore studied (six control and six endotoxin treated, 1.5 mg X kg-1) under etomidate (4 mg X kg-1 X h-1) anaesthesia muscle blood flow (radioactive microspheres) in fore limb, thorax, diaphragm and hind limb (five different muscles) and skin blood flow before (t = 0) and 90 and 120 min after endotoxin. We also measured blood flow in the femoral artery and vein (electromagnetic flow transducers) and the arteriovenous differences of oxygen, lactate, glucose and FFA over the femoral vascular bed (at t = 0, 30, 90 and 120 min). Endotoxin administration caused a fall of flow in the femoral artery and vein (by 65 and 63%, respectively at t = 15). After t = 60 flow in the femoral artery and vein increased slowly but the flows were still below the preshock values at t = 20 (by 33 and 50%, respectively). Skeletal muscle and skin flow did not decrease or even increased after endotoxin but decreased in the control group. Percentage of cardiac output distributed to brachial, intercostal and hind limb muscle and skin increased after endotoxin (by 163, 167, 111 and 120%, respectively at t = 20). The five muscles of the hind limb did not respond differently to endotoxin. In spite of diminished arterial inflow, skeletal muscle perfusion was thus maintained in the hind limb, probably due to closing of shunts and redistribution of blood away from bone. Oxygen extraction but also lactate release by the femoral bed had increased during endotoxin shock. After endotoxin femoral glucose extraction was only elevated at t = 30 when arterial glucose concentration had also increased. The femoral bed produced free fatty acids (FFA) but during endotoxin shock the arteriovenous concentration difference of FFA decreased. Our data suggest that skeletal muscle flow nor oxygen consumption and glucose metabolism is affected during 2 h of canine endotoxin shock. Lactate production, however, tended to increase.

The fall of cardiac output in endotoxemic rats cannot explain all changes in organ blood flow: a comparison between endotoxin and low venous return shock.

During endotoxin shock mean arterial pressure (MAP) and cardiac output (CO) fall, and the latter is redistributed. To evaluate whether these changes are solely caused by the low output, or are also based on endotoxin itself, we compared regional hemodynamic changes during endotoxemia with those in a nonendotoxemic state of decreased CO in anesthetized rats. In group E (n = 10) endotoxin Escherichia coli O127:B8 (8 mg.kg-1) was infused from t = 0 till t = 60 min. In group B (n = 10) the same decrease of CO and MAP was obtained as in group E by inflating a balloon in the inferior caval vein, distal to the renal veins, from t = 0 till t = 60 min. We measured MAP, CO (thermodilution), central venous pressure, heart rate, organ blood flow, and redistribution of CO (microspheres), arterial lactate and glucose, and hematocrit. MAP and CO decreased (p < .05) in both groups (by 30 and 50%, respectively at t = 60). Heart rate, hematocrit, arterial lactate, and arterial glucose were significantly higher (p < .05) in group E (by 17, 12, 180, and 55%, respectively). Blood flow to most organs had similarly decreased in both groups. The decreased intestinal blood flow lead to macroscopic damage only in group E. Blood flows (absolute or as percentage of CO) to heart, hepatic artery, and diaphragm, however, had significantly increased in group E while blood flows to skin, skeletal muscle, and stomach had decreased more in group E. Except for the heart these differences could be explained by increased work load (detoxification: liver; hyperventilation: diaphragm, muscle) and thus to a more pronounced redistribution at the expense of skin and muscle blood flow. Regional hemodynamic changes during endotoxemia thus could largely be attributed to decrease of CO and redistribution of the circulating blood volume. In the heart, endotoxin seemed to exert effects independent of the hypodynamic state. This was also true for the intestinal damage and the rise in hematocrit and arterial lactate.

Laparotomy and renal function during endotoxin shock in rats.

Despite the wide use of laparotomy to study kidney function, the possible influence of this procedure on systemic and renal parameters in septic rats is unknown. We studied this in anesthetized Wistar rats with and without endotoxin shock (1 h Escherichia coli O 127.B8: 8 mg.kg-1 infusion). We also compared clearance of creatinine and inulin to measure glomerular filtration rate (GFR). Laparotomy attenuated the endotoxin-induced decrease in cardiac output and abolished the increase in systemic and renal vascular resistance, while renal plasma flow was maintained. Better perfusion in other organs as well was indicated by a more gradual increase in arterial lactate concentration and less intestinal damage. By contrast, GFR decreased considerably during endotoxemia, irrespective of laparotomy. This change in GFR could be reliably assessed using creatinine clearance. The ratio of creatinine-to-inulin clearance averaged between .5 and .75. Renal ATP content did not change and the endotoxin-induced increase in the number of granulocytes lodged in glomeruli was not affected by laparotomy. In conclusion, our study indicates that laparotomy significantly influences the vascular effects caused by endotoxin. Laparotomy also revealed an effect of endotoxin on GFR, independent of renal blood flow.

Gram-negative shock in rats depends on the presence of capsulated bacteria and is modified by laparotomy.

To develop a hyperdynamic sepsis model in rats, four Escherichia coli strains were used, which differed in the presence or absence of a capsule or K antigen (K1 and K-, respectively) and/or in O serogroup (O9 and O18). Of the two clinical isolates, O9K- did not survive in rat serum, whereas O18K1 and two isogenic laboratory strains (O18K1 and O18K-) were able to resist serum bacteriolysis. Pentobarbital-anesthetized rats (n = 21) received an intravenous bolus of 10(9) bacteria. In contrast to the two noncapsulated strains, both capsulated strains induced hyperdynamic shock; arterial lactate rose from a mean value of .91 to 3.09 mmol.L-1, systemic vascular resistance dropped from 1.15 to .78 mmHg.min.mL-1, and cardiac output transiently increased from 98 to 115 mL.min-1; renal plasma flow remained at 3-4 mL.min-1, whereas glomerular filtration rate decreased from 1.3 to .7 mL.min-1. Laparotomy, which is often performed to study kidney function, completely abolished the hyperdynamic condition, while glomerular filtration rate was still decreased. We conclude that in rats, in contrast to humans, capsulated bacteria are required to induce a hyperdynamic septic shock; the hyperdynamic characteristics of the shock do not occur in animals subjected to a laparotomy.

Soluble glucan protects against endotoxin shock in the rat: the role of the scavenger receptor.

Soluble carboxymethyl-b-1,3-glucan (CMG), a possible ligand for scavenger receptors, has macrophage-activating action but lacks the granulomatose inflammatory side effect: it is a promising immunomodulator that may mitigate the severity of sepsis. This motivated us to study in rats the effect of CMG (25 mg/kg), injected into the tail vein at 48 and 24 h prior to the administration of 5 mg/kg Escherichia coli 0127.B8 endotoxin on survival, hemodynamic condition, and, in vitro, on the chemiluminescence of PMNs and macrophages, and on macrophagal tumor necrosis factor (TNF) production. Acetylated low density lipoprotein (AcLDL) clearance in vivo and in vitro binding to macrophages was used to study scavenger receptor function. In the nonpretreated group 9 of 10 rats died during the first 24 h after endotoxin, but all CMG-pretreated rats survived. CMG-pretreatment prevented severe decreases in cardiac output and blood pressure after endotoxin. Chemiluminescence of macrophages and PMNs from CMG-pretreated rats was about two times less (p < .05) than that from nonpretreated ones; the endotoxin induced TNF production by macrophages also decreased. Pretreatment with CMG increased, but coinjection of CMG and AcLDL decreased the AcLDL clearance, while coinjection of endotoxin and AcLDL decreased the survival rate. In vitro AcLDL uptake by macrophages decreased after coinjection with CMG. Our results thus showed that CMG was protective in rat endotoxin shock, which seemed partly connected with enhancement of endotoxin clearance through scavenger receptors and to decreased TNF production.

Pump-induced platelet aggregation in albumin-coated extracorporeal systems.

OBJECTIVE: Coating of extracorporeal systems with heparin does not prevent platelet activation and subsequent bleeding disorders. We investigated whether this could be due to elevated shear stress caused by a roller pump. METHODS: Human or rat blood was made to flow through an uncoated or an albumin-coated medical polyvinyl chloride tube with or without a roller pump. Aggregation of platelets in the tubing was recorded continuously with a photometric device. RESULTS: Although in vitro gravitational flow in uncoated tubes caused immediate platelet aggregation and platelet loss, this remained absent in coated tubes. When the pump was started in experiments with a coated tube strong platelet aggregation was observed and platelet count fell within 5 minutes to 78% +/- 2% and 71% +/- 3% of control values in human and rat blood, respectively. In vivo, no aggregation was observed during spontaneous flow in rats with an albumin-coated tube running from the carotid artery to the femoral artery, but aggregation started as soon as the blood was pumped. Pump-induced platelet aggregation, both in vitro and in vivo, could be prevented with aurintricarboxylic acid, which specifically inhibits shear-induced platelet aggregation as has recently been shown. Pump perfusion of blood in an uncoated tube did not elicit platelet aggregation. CONCLUSIONS: Pump perfusion of blood in coated systems elicits shear-induced platelet aggregation, which may be prevented by administration of substances that block the binding of von Willebrand factor to glycoprotein Ib receptors on the platelets. The effects of pumping on platelets are masked in uncoated circuits because of the dominant influence of blood-material contact.

Increased systemic microvascular albumin flux in septic shock.

Lymph/plasma (L/P) albumin ratios were followed in a patient with a traumatic thoracic duct lymph fistula, during septic shock when lymph flow was high and at recovery when lymph flow was low. Higher albumin ratios were found during the former. On both occasions, the P-L difference of radioactive counts/min per gram was followed for 6 h after i.v. injection of 51Cr human serum albumin (HSA). Equilibration half times between plasma and lymph amounted to 0.85 h during septic shock and 2.49 h at recovery. The data indicate that systemic microvascular albumin flux had increased during shock in our patient. Increased permeability may have been responsible.

Influence of fluid resuscitation on renal function in bacteremic and endotoxemic rats.

PURPOSE: Fluid resuscitation, which is the most important primary therapy in sepsis, is not always able to prevent acute renal failure. In this study, we investigated in two different rat models of distributive shock whether fluid resuscitation would increase renal plasma flow (RPF) and subsequently glomerular filtration rate (GFR). MATERIALS AND METHODS: In pentobarbital anesthetized wistar rats Haemaccel (Behring Pharma, Hoechst, the Netherlands) infusion (1.2 mL/100 g/h for 3 hours) was started immediately during either bacteremia (bolus of living Escherichia coli bacteria, 10(9) or endotoxemia (1 hour infusion of E. coli endotoxin, 8 mg/kg), as well as in time-matched healthy controls. RESULTS: After 3 hours, this treatment had increased RPF (clearance of 131I-hippurate) above normal in control (+67%) and bacteremic rats (+75%), whereas in endotoxemic animals, the significantly decreased RPF was normalized. On the other hand, in bacteremic animals, the lowered GFR (clearance of creatinine; x44%) was normalized, whereas in endotoxemic animals GFR remained depressed (x30%). The lack of improvement in GFR during endotoxemia was also indicated by a profound fall in urine flow, which by contrast steadily increased in control and bacteremic rats owing to volume loading. In both shocked groups, the decreased renal oxygen delivery was normalized, but the higher renal oxygen consumption than expected on the basis of the work needed for sodium reabsorption was not influenced by Haemaccel treatment, despite the fact that it caused this work load to rise in bacteremic but not in endotoxemic rats. In both shock models, renal cortical adenosine triphosphate content did not differ from healthy controls and was not influenced by volume loading. CONCLUSIONS: In conclusion, our study suggests that a decrease in GFR caused by live bacteria in the circulation may benefit from fluid resuscitation, while during endotoxemia this therapy could not prevent acute renal failure.

Organ blood flow and distribution of cardiac output in dopexamine- or dobutamine-treated endotoxemic rats.

Endotoxemia causes a decrease of blood flow to most organs. If this could be prevented, chances of survival might improve. In endotoxemic rats, we studied the effect of a therapeutic infusion of dopexamine (dopaminergic, beta 2-adrenergic) on blood flow and percentage of the cardiac output distributed to heart, brain, hepatic artery, stomach, intestines, spleen, pancreas, kidneys, adrenals, diaphragm, skeletal muscle, and skin. Dopexamine action was compared with that of dobutamine (beta 1-adrenergic). Endotoxin shock was induced in 28 rats with infusion of 8 mg/kg Escherichia coli O127:B8 endotoxin from 0 to 60 minutes; the rats were then divided into 3 groups, which received from 60 to 135 minutes of an infusion of saline (ES; n = 10), dopexamine hydrochloride (DX, 3 x 10(-8) mol/kg.min; n = 10) or dobutamine (DB, 10(-7) mol/kg.min; n = 8). A fourth group served as time-matched controls (C, saline from 0 to 135 minutes; n = 8). In the untreated endotexemic rats, cardiac output decreased and organ blood flow decreased except in the diaphragm, heart, and brain; the percentage of the cardiac output to those organs increased. Dopexamine and dobutamine similarly improved cardiac output in endotoxemic rats. All organs benefitted to the same extent from the increased cardiac output. Therapeutic infusion of dopexamine during endotoxemia did not favor flow to any particular organ; redistribution of cardiac output changed little after administration of dopexamine, and its effects were not significantly different from those of dobutamine.

Reliability of stroke volume to pulse pressure ratio for estimating and detecting changes in arterial compliance.

Total arterial compliance is an important haemodynamic variable which is difficult to measure in vivo. Using a Windkessel model, it can be determined from the ratio of the diastolic-decay time constant (tau) of the arterial system and the peripheral resistance. Using this technique, paired estimates of arterial compliance were determined in control and in mechanically produced low-compliance steady states. Since determination of compliance based on the three-element Windkessel model is tedious the same data were retrospectively analysed to evaluate the reliability of the stroke volume to pulse pressure ratio (SV:PP) for estimating and predicting changes in compliance. The linear correlation coefficient for 148 paired values of compliance determined by the two methods was r = 0.85, P less than 0.001. Both methods indicated similar values (mean +/- s.e.m.) for compliance in the control steady state: 0.35 +/- 0.01 ml/mmHg (using tau/R) versus 0.36 +/- 0.01 ml/mmHg (using SV:PP), P was NS, and both methods detected a significant decrease in compliance, P less than 0.001, in the low-compliance steady state: 0.18 +/- 0.01 ml/mmHg (using tau/R) and 0.21 +/- 0.01 ml/mmHg (using SV:PP). Thus, SV:PP compared with (tau/R) was a good index of compliance and changes in compliance and may prove to be a useful index for estimating compliance clinically.