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Biomedical subjects

E D Bennett

Publications and source records attributed to E D Bennett.

At least 55 records · Page 3Linked to original sources

Advantages of a narrow-range, medium molecular weight hydroxyethyl starch for volume maintenance in a porcine model of fecal peritonitis.

OBJECTIVE: To compare the effectiveness of two hydroxyethyl starch solutions of different molecular weight ranges for volume maintenance in a porcine model of fecal peritonitis. DESIGN: Randomized prospective trial. SETTING: Laboratory investigation. SUBJECTS: Adolescent female pigs weighing approximately 30 kg. INTERVENTIONS: We compared diafiltered 6% pentastarch with 6% high molecular weight hetastarch for volume maintenance in a porcine model of fecal peritonitis. The number average molecular weight of pentastarch is higher than hetastarch, although the weight average molecular weight is lower, i.e., a narrow range of medium weight molecules. The infusion rate of each agent was adjusted to maintain baseline arterial Hct for less than or equal to 7 hr after instrumentation and induction of fecal peritonitis. MAIN OUTCOME MEASUREMENTS: The volume of fluid required to maintain arterial Hct was compared along with comparisons of hemodynamic and histologic responses associated with the two agents. RESULTS: Significantly less pentastarch was required to prevent hemoconcentration than hetastarch (109 +/- 22.8 vs. 150 +/- 10.3 mL/kg; p less than .05) while hemodynamics, colloid osmotic pressure, and oxygen transport responses were similar. Capillary patency was greater (21.99 +/- 3.68 vs. 10.09 +/- 1.17%; p less than .05) and mean alveolar capillary barrier thickness was less (2.36 +/- 0.13 vs. 3.06 +/- 0.17 microns; p less than .05) with pentastarch than with hetastarch, as judged by electron microscopy. CONCLUSIONS: These data suggest that pentastarch is better retained in the circulation in capillary leak syndromes compared with hetastarch.

Animals↗

Noninvasive optimization of left ventricular filling using esophageal Doppler.

OBJECTIVE: To confirm whether the descending aortic blood flow velocity waveform variable of flow time corrected for heart rate, measured using an esophageal Doppler transducer, can be used for noninvasive optimization of left ventricular (LV) filling. SETTING: ICU and operating theater. SUBJECTS: Forty-three mechanistically ventilated patients in the ICU or undergoing cardiothoracic surgery in whom a pulmonary arterial catheter was in situ. INTERVENTIONS: LV preload was a) increased from hypovolemic states (pulmonary arterial occlusion pressure [PAOP] less than 8 mm Hg) by fluid challenge, b) decreased from normovolemic states (PAOP 10 to 15 mm Hg) by either iv nitrates or intravascular fluid loss, and c) decreased from heart failure or fluid overload states (PAOP greater than 20 mm Hg) by iv nitrates. No other maneuver was performed concurrently. MEASUREMENTS AND MAIN RESULTS: Descending aortic blood flow was measured by an esophageal Doppler transducer. Corrected flow time was calculated by dividing systolic flow time by the square root of the cycle time. PAOP and corrected flow time increased after fluid challenges in hypovolemic states, and decreased when LV preload was decreased from normovolemic states. However, when preload was decreased from overload states, PAOP always decreased, but the corrected flow time usually increased before any subsequent decrease. The greatest value of corrected flow time corresponded with the maximal stroke volume seen. CONCLUSIONS: Esophageal Doppler measurement of aortic blood flow can be used for rapid, noninvasive optimization of LV filling in mechanically ventilated patients.

Aorta↗

Effects of alterations in left ventricular filling, contractility, and systemic vascular resistance on the ascending aortic blood velocity waveform of normal subjects.

OBJECTIVES: To confirm the consistent effects on Doppler-measured aortic blood flow velocity waveform variables of alterations in left ventricular preload, afterload, and inotropy using pharmacologic and physiologic maneuvers. SETTING: Medical school laboratory. SUBJECTS: Healthy volunteers. INTERVENTIONS: Increasing infusion rates of dobutamine (1.25 to 5 micrograms/kg.min), esmolol (1.25 to 5 mg/min), phentolamine (1.25 to 5 mg/min), methoxamine (1.25 to 5 mg/min), metaraminol (1.25 to 5 mg/min), and placebo (1.25 to 5 mL of 0.9% saline/min) and increasing plasma removal (0.5 to 1 L) in awake, rested, supine subjects. MEASUREMENTS AND MAIN RESULTS: Ascending aortic blood flow was measured by the suprasternal Doppler approach allowing calculation of waveform variables of stroke distance and minute distance (linear measures of stroke volume and cardiac output), peak velocity, mean acceleration and flow time corrected for heart rate. An index of systemic vascular resistance was obtained by dividing mean systemic BP by the minute distance. Inotropic changes predominantly affected peak velocity and mean acceleration. Changes in preload mainly affected the flow time corrected for heart rate, whereas afterload changes had an intermediate effect. Unsuspected but subsequently confirmed hemodynamic effects were seen with esmolol and metaraminol. CONCLUSIONS: Aortic blood flow velocity waveform variables measured by Doppler ultrasound can be used to noninvasively follow changes in left ventricular preload, afterload, and inotropy.

Adrenergic beta-Antagonists↗

Baroreflex sensitivity and electrophysiological correlates in patients after acute myocardial infarction.

BACKGROUND: Several studies have identified transient disturbances of autonomic function during the acute and recovery phases of myocardial infarction, and it has recently been suggested that survivors of acute myocardial infarction with depressed vagal tone may be at increased risk of sudden or arrhythmic death. METHODS AND RESULTS: To investigate this hypothesis, parasympathetic function was assessed by arterial baroreflex sensitivity (BRS) testing (using the phenylephrine method) and by heart rate variability (HRV) analysis from 24-hour Holter recording in 68 patients at day 7-10 after infarction. The relation between autonomic tone and markers of arrhythmic propensity, including programmed ventricular stimulation (PVS) and late potentials in addition to other clinical variables, was examined. BRS for the whole group was 7.0 +/- 4.7 msec/mm Hg and was inversely correlated with age (r = 0.53, p less than 0.001) but not with left ventricular ejection fraction (r = 0.035, p = NS). In those patients in whom sustained monomorphic ventricular tachycardia (SMVT) was induced, BRS was significantly reduced (p = 0.001) as was HRV (p = 0.007) and left ventricular ejection fraction (p = 0.022). The strongest association between any variable (including HRV, BRS, late potentials, left ventricular ejection fraction, exercise testing, Q waves, and infarct site) and the induction of sustained monomorphic ventricular tachycardia was depressed BRS with a relative risk of 36.28 (95% confidence interval, 5-266). CONCLUSIONS: This study confirms that depressed BRS identifies a subgroup at high risk for arrhythmic events after myocardial infarction and that programmed ventricular stimulation may be safely limited to this group without any loss of predictive accuracy.

Arrhythmias, Cardiac↗

Goal directed therapy with dobutamine in a porcine model of septic shock: effects on systemic and renal oxygen transport.

Systemic and renal haemodynamic and functional indices were measured in 15 anaesthetised pigs during systemic sepsis induced by faecal peritonitis. Five animals were assigned to maintenance of cardiac output (CO) at baseline, pre-infection values throughout the study (controls n = 5). In the remaining 10 animals, CO was increased by 25% prior to induction of sepsis and maintained at this level for the duration of the study using volume expansion with intravenous colloid and an infusion of either 20 micrograms/kg/min dobutamine (n = 5) or placebo (n = 5). Hourly measurements were made of CO, left renal blood flow, arterial and renal venous oxygen saturation, urine output, creatinine clearance and arterial partial pressure of oxygen until the animal died or until termination 8 h. Systemic indices of oxygen transport did not reflect the behaviour of the renal vascular bed during the management of sepsis. In the dobutamine group systemic oxygen uptake (VO2) increased from 173 +/- 30 to 277 +/- 73 ml/min (P less than 0.05), however this resulted in a decrease in renal DO2 (20 +/- 9 to 10 +/- 2 ml/min P less than 0.05) and there was no equivalent rise in renal VO2 (3.3 +/- 1.6 to 3.2 +/- 1.5 ml/min). There was however no significant difference in the effect on renal function of the three management protocols. Agents used to increase cardiac output during systemic sepsis may result in significantly different effects on the renal vascular bed which are not revealed by the measurement of systemic indices alone.

Animals↗

The effects of oral isosorbide 5-mononitrate on mortality following acute myocardial infarction: a multicentre study.

We have conducted a randomized, double-blind, placebo-controlled multicentre trial of oral isosorbide 5-mononitrate (ISMN) in 360 patients with suspected acute myocardial infarction. Patients were stratified prior to analysis according to the presence or absence of left ventricular failure on admission. ISMN caused a significant reduction in systolic and diastolic blood pressure during the first 12 h. There was no significant effect on heart rate. Overall mortality was 4.9% in the ISMN group compared with 4.0% in controls at 5 days, and 14.1% compared with 10.5% at 6 months (NS). A non-significant reduction in mortality in the ISMN group with heart failure (ISMN 7.9%, placebo 12.9%, at 5 days) contrasted with a non-significant increase in mortality in patients without heart failure treated with ISMN (ISMN 4.1%, placebo 2.1%, at 5 days). Lignocaine was used in twice as many patients in the ISMN group as in placebo group (P less than 0.01), both with and without heart failure. Diamorphine usage was similar in the ISMN and control groups. Oral ISMN has similar haemodynamic effects to intravenous nitroglycerin, and can be of benefit in acute myocardial infarction with heart failure. However, our results question the use of nitrates in acute myocardial infarction in the absence of heart failure.

Analysis of Variance↗

Pretreatment with pentoxifylline improves the hemodynamic and histologic changes and decreases neutrophil adhesiveness in a pig fecal peritonitis model.

We investigated pentoxifylline (PTF) as a pretreatment of septic syndrome in pigs with fecal peritonitis. In the untreated group there was a progressive decrease in mean arterial pressure (MAP), cardiac output, mean pulmonary artery wedge pressure (WP), and a progressive rise in mean pulmonary artery pressure (MPAP), pulmonary vascular resistance (PVR), systemic vascular resistance (SVR), heart rate (HR), and core temperature (T). In those pigs given PTF there was a significantly smaller increase in SVR throughout and in PVR after 270 min. No significant differences were seen in MAP, MPAP, WP, HR, and T. Neutrophil adhesiveness did not change in the untreated group. However, it decreased markedly with PTF, both before and after peritonitis induction. Electron microscopy of the lungs, liver, and spleen in the test group showed severe damage, with endothelial disruption, capillary or sinusoidal occlusion, leukostasis, and neutrophil degranulation. Pretreatment with PTF attenuated these changes.

Animals↗

Prediction of serious post-infarction cardiac arrhythmias.

Simple clinical findings suggestive of a large myocardial infarction identify most patients at risk from serious post-infarction arrhythmias (defined as sustained ventricular tachycardia and sudden death not associated with reinfarction). However, similar findings are seen in many other patients who remain free of complications. The presence of late potentials and frequent ventricular ectopics on long-term electrocardiographic monitoring add to prognostic accuracy in patients with clinical complications, with a predictive accuracy of nearly 90% when all three features are present.

Electrocardiography↗

High fat, low carbohydrate, enteral feeding lowers PaCO2 and reduces the period of ventilation in artificially ventilated patients.

The objective of this study was to compare the effect of a high fat, low carbohydrate enteral feed with a standard isocaloric, isonitrogenous enteral feed on PaCO2 and ventilation time in patients with acute respiratory failure requiring artificial ventilation. 20 clinically stable patients requiring enteral feeding were randomized to either feed in a double-blind fashion. Initial ventilator standard settings were adjusted according to clinical state. Measurements including minute volume and arterial blood gases were made twice daily. Weaning was carried out according to set criteria. During the feeding period, PaCO2 just prior to weaning fell by 16% in the high fat group but increased by 4% in the standard feed group (p = 0.003). The high fat group spent a mean of 62 h less time on the ventilator (p = 0.006). A high fat, low carbohydrate enteral feed appears to be beneficial in patients undergoing artificial ventilation.

Adult↗

In vitro colloid osmotic pressure of commonly used plasma expanders and substitutes: a study of the diffusibility of colloid molecules.

The rational choice of a plasma substitute for states of hypovolaemia depends partly on its colloid osmotic pressure (COP). We have measured the COP of 108 samples of plasma substitute across selectively permeable membranes which retain molecules greater than 10,000 dalton (COP10) and 50,000 dalton (COP50) the ratio COP50/COP10 providing a potential index of diffusibility of the smaller molecules across capillary membranes. 6% Hespan solution showed a particularly favourable COP50/COP10 ratio at 0.58 indicating a potential for good retention in the circulation whilst 3.5% Haemaccel showed a COP50/COP10 ratio of 0.18 indicating a potential for marked transcapillary diffusion, especially in states of capillary leak. In patients with normal capillary permeability both Gelofusine and Dextran 110 are likely to show adequate retention in the circulation with a COP50/COP10 ratio of 0.37 and 0.39 respectively. These are comparable to the retention of 4.5% human albumin (0.36) but all of the plasma substitutes tested, with the exception of Haemaccel, provided a higher COP across both membranes than 4.5% human albumin solution. An in vivo comparison of these plasma substitutes is required to confirm the advantages of macromolecular colloids in states of capillary leak.

Colloids↗

Inducibility of sustained monomorphic ventricular tachycardia as a prognostic indicator in survivors of recent myocardial infarction: a prospective evaluation in relation to other prognostic variables.

The prognostic significance of sustained monomorphic ventricular tachycardia inducible with up to three extrastimuli was assessed in relation to other prognostic markers, including clinical assessment, signal-average electrocardiogram (ECG), Holter monitoring, ejection fraction measurement and exercise testing, in 75 patients after recent myocardial infarction. Among eight patients with inducible sustained monomorphic ventricular tachycardia, six suffered arrhythmic events during a median follow-up period of 16 months. No patient without inducible sustained monomorphic ventricular tachycardia suffered an arrhythmic event. Multivariate analysis showed that of all the variables examined, inducible sustained monomorphic ventricular tachycardia was the only independent predictor of arrhythmic events during the follow-up period. The sensitivity for predicting arrhythmic events by this response was 100%, the specificity 97% and the positive predictive accuracy 75%. Individually, the other prognostic variables were less sensitive and much less accurate predictors of arrhythmic events, but the combination of the occurrence of acute phase complications or frequent ectopic activity with an abnormal signal-averaged ECG approached the sensitivity and accuracy of inducible sustained monomorphic ventricular tachycardia. The prognostic utility of programmed ventricular stimulation in patients with recent myocardial infarction is limited because comparable information can be obtained less invasively. However, the test may have a role in selecting therapy in patients judged to be at risk from arrhythmias on the basis of noninvasive assessment.

Adult↗

Multi-organ damage resulting from experimental faecal peritonitis.

1. Using specific-pathogen-free New Zealand White rabbits, we have compared the effects of faecal peritonitis over a period of 5 h in eight test animals with eight controls in which a sham operation was performed. 2. There was morphological damage to lungs, liver and spleen of test animals. Lung capillaries and sinusoids of the liver showed occlusion by cell debris and leucocytes, with endothelial damage. The lungs also showed alveolar epithelial disruption, basement membrane exposure and type II pneumocytes lacking lamellar bodies. In the liver there was fibrin deposition and swollen Kupffer cells. The spleen showed degranulating neutrophils, fibrin deposits, platelet aggregates and activated macrophages, with no damage to the endothelium. 3. There was no morphological damage to the kidney or heart of test animals or to any organs of sham-operated animals. 4. There were mixed anaerobes and aerobes in faecal material used to induce peritonitis. Cultures of liver, spleen and kidney isolated four different types of micro-organisms. Blood cultures showed two types of micro-organisms. Cultures of lung and heart showed one type of micro-organism. 5. The presence of micro-organisms in an organ could not be correlated with the degree of histological damage to that organ. 6. In test animals an early significant reduction in circulating leucocytes and platelets was sustained for the duration of the experiment with significant diffuse intravascular coagulation. 7. There was no change in test animal neutrophil adhesiveness until 120 min, when significant reduction was observed. 8. Serum phospholipase A2 (EC 3.1.1.4) activity in the test group showed a threefold increase at 300 min.

Animals↗

Effects of atrial natriuretic peptide on systemic haemodynamics and cardiac function in normal man.

Atrial natriuretic peptides (ANP) reduce blood pressure. Animal experiments suggest that this depressor action results from a reduction in cardiac output rather than peripheral vascular resistance but it is unresolved whether this is wholly due to their effect of reducing left ventricular filling or whether they have a negatively inotropic effect. We have therefore investigated the effects of ANP in normal man using Doppler measurements of ascending aortic blood flow. Six normal volunteers underwent infusions of placebo and incremental doses of ANP in the range 0.25 to 12 micrograms.min-1. Each infusion was given for 15 min and measurements made both in the supine and erect positions (passive tilt). In both positions ANP had dose dependent effects of increasing heart rate (HR) and maximal acceleration whilst lowering an index of systemic vascular resistance (ISVR). In the erect position ANP also lowered systolic blood pressure. In the 30 min after completion of the infusions there were significant decreases in peak velocity and cardiac output with increases in ISVR in both positions, but HR fell and diastolic pressure increased only when supine. During the course of the experiment mean haematocrit (SEM) increased from 43.9 (1.2) to 46.7 (1.0), indicating a mean reduction in plasma volume of 10.5%. This occurred despite a negative fluid balance of only 31(7) ml over the 2 h. These data suggest that ANP is not negatively inotropic and that, at pharmacological doses, it is an arteriolar dilator of rapid offset and reduces cardiac filling pressures by a mechanism of slower offset.

Adult↗

Continuous hemodynamic monitoring by esophageal Doppler.

A new 5.1-mHz continuous wave esophageal Doppler system is described for continuous hemodynamic monitoring in ventilated patients. Information is obtained from the size, shape, and changes in shape of the velocity waveforms of descending aortic blood flow. Minute distance, the product of waveform area (stroke distance) and heart rate, provides a measure of cardiac output. Good agreement between this technique and thermodilution was shown for cardiac output changes with 238 paired measurements made in 38 patients. The coefficient of variation was lower for Doppler (3.8%) than for simultaneous thermodilution measurements (6.2%). Seventy-eight changes in left ventricular filling, systemic vascular resistance, or inotropic state produced consistent alterations in waveform shape with a narrow-based waveform being indicative of hypovolemia. This development marks a significant advance in the technique and provides a useful alternative to invasive hemodynamic monitoring, both in the ICU and perioperatively.

Adult↗

Invasive hemodynamic monitoring in the United Kingdom. Enough or too little?

In response to a questionnaire regarding use of invasive hemodynamic monitoring techniques in the United Kingdom, 211 replies were received from 276 hospitals (76.4 percent). Over one fifth of Intensive Care or combined Intensive/Coronary Care Units did not use pulmonary artery catheters (PAC); of those that did, two thirds used no more than two/month, and only two units used more than ten/month. Nearly a quarter did not possess a cardiac output computer. Only 18 complications occurring in the preceding year were reported, which suggests underrecognition. Clinical indications and lack of expertise were the main reasons proferred for limited use; however, cost (which was generally underestimated) and clinical value also were mentioned. The majority of CCUs did not use PACs, and only 10 percent used more than two/month. Only 10 percent of hospitals have used them perioperatively and most cardiothoracic units used no more than two PACs/month. In view of the large difference in numbers used between the United Kingdom and the United States, a large-scale study is warranted to determine the actual value of PACs in reducing mortality and morbidity.

Catheterization, Peripheral↗