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Nicardipine enhances diaphragmatic fatigue.

The effects of nicardipine, a calcium channel blocker, on diaphragmatic fatigue were studied in 20 anaesthetized, mechanically ventilated dogs divided into two groups: control group (Group C, n = 10) and nicardipine group (Group N, n = 10). Diaphragmatic fatigue was induced by intermittent supramaximal electric stimulation to bilateral phrenic nerves at a frequency of 20 Hz for 30 min. In Group N, 5 micrograms.kg-1.min-1 nicardipine iv was infused continuously during this fatigue-producing period. Transdiaphragmatic pressure (Pdi) produced by electrical stimulation (10-100 Hz) of the phrenic nerves was used as an index of diaphragmatic contractility. After a fatigue-producing period, the Pdi in both groups decreased at low frequency (10-30 Hz) stimulation compared with pre-fatigue values (P < 0.05), whereas no change in Pdi was observed at high-frequency (50-100 Hz) stimulation. The decrease of Pdi at low-frequency stimulation was larger in Group N (P < 0.05). The integrated diaphragmatic electric activity (Edi) in both groups did not change at any frequency of stimulation throughout the experiment. We conclude that nicardipine enhances diaphragmatic fatigue.

Animals↗

Taurine and pulmonary hemodynamics in sepsis.

This study has been performed to characterize the relationship between changes in plasma taurine (TAU) and hemodynamic patterns in sepsis. Analysis of 249 plasma aminoacidograms (AA-grams) and associated measurements in a group of critically ill, mechanically ventilated septic patients, showed that decreases in TAU were significantly correlated with increases in pulmonary artery pressure and pulmonary vascular resistance, and with worsening of pulmonary dysfunction. All cases requiring positive end-expiratory pressure greater than 10cmH2O had TAU lower than 50 microM/L. Low TAU was paralleled by decreases in other sulfur-containing AA, phosphoethanolamine, beta-alanine, glutamate and aspartate, within a pattern of greater metabolic dysregulation. These data provide evidence of a link between severity of pulmonary dysfunction and reduced TAU availability in clinical sepsis. The implications relate also to the need for specific investigations of the clinical effect of exogenous TAU on proinflammatory mediator-induced pulmonary dysfunction.

Adolescent↗

Left ventricular diastolic function in patients with left ventricular systolic dysfunction due to coronary artery disease and effect of nicardipine.

To assess the effect of nicardipine on left ventricular (LV) diastolic function independent of concurrent effects on loading conditions in patients with LV systolic dysfunction due to coronary artery disease, equihypotensive doses of intravenous nitroprusside and nicardipine were administered to 12 patients with congestive heart failure due to previous myocardial infarction (LV ejection fraction less than 0.40). LV micromanometer pressure and simultaneous radionuclide volume were obtained during a baseline period, during nitroprusside infusion, during a second baseline period and during nicardipine infusion. Mean systemic arterial pressure decreased an average of 21 mm Hg with nitroprusside and 19 mm Hg with nicardipine. A greater decrease in LV end-diastolic pressure was observed with nitroprusside (29 +/- 2 to 15 +/- 2 mm Hg, p less than 0.01) than with nicardipine (29 +/- 2 to 25 +/- 3 mm Hg, p less than 0.05). There was a decrease in the time constant of relaxation during nitroprusside but not during nicardipine infusion. There was enough overlap in LV volumes in the baseline and nitroprusside periods to compare diastolic pressure-volume relations over a common range of volumes in 4 patients, and enough overlap in the baseline and nicardipine periods in 11 patients. The relation was shifted downward in 3 of 4 patients taking nitroprusside and in 6 of 11 patients taking nicardipine. The relation between end-diastolic pressure and volume was not shifted with nicardipine.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Function, Right↗

Relationship between angiographic infarct size and left ventricular filling.

Infarct size may influence left ventricular filling after acute myocardial infarction. Pulsed Doppler transmitral flow velocities were compared in 47 patients at 7 +/- 6 days following acute myocardial infarction and 47 age-matched controls. Patients were stratified by angiographic infarct size into Groups I, II, III (corresponding angiographic hypokinetic scores less than 2; 2-2.99; greater than or equal to 3 SD/cord). Early diastolic transmitral Doppler flow velocities did not differ between infarct groups but atrial transmitral Doppler flow measurements did: peak A velocity (p = 0.001), A velocity time integral (p less than 0.001), and total velocity time integral (p = 0.001). Compared to controls atrial transmitral Doppler flow was augmented in Group I, whilst atrial and total transmitral Doppler flow were depressed in Group III. Peak A velocity and A velocity time integral were inversely related to infarct size (R = -0.44 to -0.54) and directly to left ventricular ejection fraction (R = 0.59 to 0.65). Large infarct size following myocardial infarction is associated with lower atrial and total transmitral Doppler flow velocities.

Adult↗

Effects of bepridil, diltiazem and verapamil on atrial refractoriness and heart rate in the conscious dog: comparison with quinidine.

1. Bepridil at cumulative doses between 1.25 and 8.75 mg/kg and quinidine between 2.5 and 17.5 mg/kg given in conscious dogs with chronic atrioventricular block and implanted atrial pacing electrodes, dose-relatedly lengthened atrial effective refractory period (AERP), as reflected by the decrease in maximal atrial frequency determined by pacing. 2. Diltiazem shortened AERP at 0.25 mg/kg and lengthened it at 1.75 mg/kg, but both effects were very slight. 3. Verapamil between 0.06 and 0.435 mg/kg did not alter AERP at all. 4. Except for diltiazem at 0.75 and 1.75 mg/kg and bepridil at 8.75 mg/kg, each dose of each drug increased atrial rate. Each drug produced an increase in ventricular rate and a short-lasting lowering in mean blood pressure. 5. Thus, these results indicate that bepridil exhibits more marked antiarrhythmic potentialities than quinidine and that the atrial and ventricular tachycardic effects observed are mainly baroreceptor reflex effects.

Animals↗

Forced swim stress: supersensitivity of the isolated rat pacemaker to the chronotropic effect of isoprenaline and the role of corticosterone.

1. Forced swim (three daily sessions) resulted in an increased plasma corticosterone level and supersensitivity of the isolated rat pacemaker to the chronotropic effect of isoprenaline. 2. Bilateral adrenalectomy, performed 2 days before forced swim, abolished the development of pacemaker supersensitivity to isoprenaline. 3. Administration to rats of the antiglucorticoid compound RU-38486 prevented the development of pacemaker supersensitivity to isoprenaline. Pretreatment of rats not submitted to forced swim with the synthetic glucocorticoid RU-28362 causes pacemaker supersensitivity to isoprenaline. 4. Pretreatment of rats with diazepam or imipramine which block the forced swim-induced increase in the plasma level of corticosterone prevented the development of pacemaker supersensitivity to isoprenaline. 5. It is concluded that corticosterone plays a critical role in the modulation of the sensitivity to catecholamines of the pacemaker beta-adrenoceptors during adaptation to repeated stress.

Adrenal Glands↗

Comparison of isoflurane with sodium nitroprusside for controlling hypertension during thoracic aortic cross-clamping.

The aims of this randomized study were (1) to determine if isoflurane is effective in controlling blood pressure during thoracic aortic cross-clamping, and (2) to compare its effects on hemodynamics and oxygen transport to those of sodium nitroprusside. Sodium nitroprusside (SNP group, n = 10) or isoflurane (ISO group, n = 10) was started 2 minutes before cross-clamping and was adjusted to maintain systolic arterial pressure as near as possible to preinduction values. The duration of thoracic aortic cross-clamping was 26 +/- 4 minutes in the SNP group and 30 +/- 4 minutes in the ISO group. Administration of isoflurance and sodium nitroprusside was stopped 2 minutes before unclamping. The same anesthetic technique using fentanyl, 6 micrograms/kg, flunitrazepam, 0.02 mg/kg, pancuronium, 0.1 mg/kg, and 50% N2O was used for all patients. At the time of clamping, either isoflurance (maximal expired concentration, 2.5% +/- 0.3%) or sodium nitroprusside (cumulative dose, 11.1 +/- 1.0 mg) was effective in maintaining the systolic blood pressure below 160 mm Hg, whereas the pulmonary capillary wedge pressure did not change. However, only SNP was able to bring the arterial pressure above the cross-clamp back to postinduction levels. During clamping, stroke index values were similar in both groups, but cardiac index increased only in patients receiving SNP. In both groups, at clamping and unclamping, PvO2 was higher than postinduction values, indicating that throughout the study the oxygen needs of the perfused area were adequately met. There was no evidence of acute left ventricular decompensation because pulmonary capillary wedge pressures did not abruptly increase, nor did pulmonary edema occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Aorta, Abdominal↗

Integration of quantitative and qualitative reasoning: an expert system for cardiosurgical patients.

In this work the possibility of building an expert system to reason on the status of post-operative cardiac patients in intensive care units is analysed. The long-term knowledge consists of causal network which describes the main relationships between hemodynamic and metabolic quantities involved in the evolution after cardiac surgery. The inference engine uses an original hybrid formalism, which integrates numerical simulation and qualitative methods. If available, the numerical values of quantities and their exact mathematical relationships are employed; otherwise, the inference engine reasons by using a discrete qualitative representation of quantities. Simulations performed using real data indicate that integration of quantitative and qualitative methods reduces the number of diagnostic scenarios compatible with patient data, and constitutes a valid tool for reasoning about physiological disorders in terms of deep causal knowledge.

Atrial Function, Right↗

High-dose alfentanil for myocardial revascularization: a hemodynamic and pharmacokinetic study.

It has been suggested that high plasma levels of alfentanil are required in order to control hemodynamic responses to noxious stimuli in patients undergoing myocardial revascularization. The present study was designed to determine the hemodynamic profile in 10 patients and the time course of alfentanil plasma concentrations and pharmacokinetics (7 patients) during and following coronary artery surgery using alfentanil administration based on an overdosage principle. Premedication consisted of lorazepam, 0.07 mg/kg, given 2 hours before surgery. Ten milligrams of alfentanil was given over 5 minutes for anesthesia induction, followed by an infusion of 60 mg/h until sternotomy and 30 mg/h up to skin closure. Additional 5-mg boluses were given prior to noxious intraoperative events. Hemodynamic measurements were performed prior to cardiopulmonary bypass. Blood was sampled simultaneously prebypass and then during the postbypass period for determination of alfentanil plasma levels. The very high alfentanil plasma concentrations achieved provided satisfactory intraoperative conditions in most, but not all, patients. Recovery time was short, despite the large amounts of narcotic used. It is concluded that very high doses of alfentanil associated with lorazepam premedication resulted in hemodynamic stability and markedly elevated narcotic plasma concentrations in most patients. Such plasma levels seem to provide satisfactory anesthetic conditions.

Alfentanil↗

Hemodynamic responses to pancuronium and vecuronium during high-dose fentanyl anesthesia for coronary artery bypass grafting.

The hemodynamic and electrocardiographic (ECG) effects of pancuronium and vecuronium were compared during high-dose fentanyl anesthesia for coronary artery bypass grafting (CABG) surgery. Forty-eight morphine-scopolamine premedicated patients scheduled for elective CABG were anesthetized with fentanyl (100 micrograms/kg) in divided doses, and either of two muscle relaxants, pancuronium (n = 26; 0.10 mg/kg) or vecuronium (n = 22; 0.09 mg/kg). Hemodynamic data, blood gas samples, and ECG tracings were obtained at the following intervals: (1) control; (2) prior to intubation; (3) 1 minute after intubation; (4) prior to sternotomy; and (5) 1 minute after sternotomy. In the pancuronium group, heart rate (HR), cardiac index (CI), and rate-pressure product (RPP) were increased after induction of anesthesia and following intubation. Eleven patients (42.3%) displayed ischemic ST segment changes. Four patients in this group developed tachycardia and hypertension to an extent requiring pharmacological intervention. Vecuronium-treated patients displayed no increases in HR, MAP, and RPP, and a decrease in CI. Only one patient (5.6%) developed evidence of ischemic ECG changes. Four patients in the vecuronium group, all receiving preoperative beta-blocker therapy, became hypotensive and bradycardic after the induction of anesthesia. The present investigation confirms the increased incidence of myocardial ischemia during high-dose fentanyl-pancuronium anesthesia. Although vecuronium was associated with fewer myocardial ischemic changes, the occurrence of bradycardia and hypotension in some patients receiving preoperative beta-adrenergic blocking drugs remains a concern.

Anesthesia, Intravenous↗

Blood pressure management during aortic surgery: urapidil compared to isosorbide dinitrate.

The efficacy and hemodynamic effects of urapidil, an arteriolar vasodilator, and isosorbide dinitrate, a venodilator, were compared, when used for blood pressure control during abdominal aortic surgery. Urapidil is an alpha-adrenergic receptor antagonist with serotonin-1A receptor-agonist activity in the central nervous system. Hemodynamic profiles were recorded before and after the administration of the study drug (+/- 10 minutes before aortic clamping), 3 and 10 minutes following aortic clamping, and before and 3 and 10 minutes following the removal of the aortic clamp. Arterial and mixed venous oxygen contents were compared. Both groups of 18 patients were similar with respect to demographic profiles, anesthetic technique, and perioperative fluid therapy. Identical heart rate and blood pressure profiles were obtained. In contrast to isosorbide dinitrate, urapidil produced a 17% (P < 0.05) increase in cardiac index as a result of a 30% (P < 0.001) decrease in systemic vascular resistance before placement of the aortic clamp. In patients treated with urapidil, cardiac index was higher (P < 0.05) 10 minutes after aortic clamping, before removal of the clamp, and 10 minutes later. The arterio-venous oxygen content difference decreased from 3.2 +/- 0.8 mL O2/dL to 2.4 +/- 1.0 mL O2/dL (P < 0.01) following urapidil, but did not change during the administration of isosorbide dinitrate. It is concluded that urapidil is an effective and safe drug for the prevention of the hemodynamic consequences of aortic clamping. Compared to a venodilator (isosorbide dinitrate), urapidil offers the advantage of improving cardiac output and oxygen delivery.

Alfentanil↗

A comparison of fenoldopam and nitroprusside in the control of hypertension following coronary artery surgery.

A prospective trial to compare the effects of the synthetic dopaminergic (DA1) agonist, fenoldopam (FEN), with sodium nitroprusside (SNP) for control of blood pressure following coronary artery bypass graft surgery was carried out in 20 patients. Patients were randomly allocated to receive either FEN or SNP when the systolic arterial blood pressure (SAP) rose above 130 mmHg. The goal of therapy was to achieve a stable control of blood pressure below 130 mmHg at a level at least 25 mmHg below the pretreatment value. Treatment was then continued for 2 hours. Hemodynamic measurements were made before treatment, after stable control of blood pressure had been achieved, and thereafter at 30, 60, and 120 minutes. Urine output, sodium, potassium, and creatinine clearance were also measured during the study. Both SNP and FEN caused a rapid and significant fall in SAP (P < 0.001) and a fall in systemic vascular resistance (P < 0.001). FEN caused an increase in cardiac index (P < 0.001) and in stroke volume (P < 0.001) in contrast to SNP. Urine output and potassium clearance fell with SNP (P < 0.05) in contrast to FEN. Thus, FEN would appear to control SAP as effectively as SNP, but may have more beneficial effects on cardiac output and some aspects of renal function.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Isoflurane versus fentanyl: hemodynamic effects in cancer patients treated with anthracyclines.

Cancer patients treated with anthracycline derivatives are at risk for perioperative cardiovascular decompensation. The authors studied hemodynamic performance before, during, and after laparotomy in 14 anthracycline-treated patients with ovarian carcinoma. General anesthesia was maintained with 70% N2O in O2, and patients were randomized to receive supplementation with either isoflurane, 0.59% end-tidal +/- 0.04 (mean +/- SE), or fentanyl, 2.67 micrograms/kg +/- 0.49 as a loading dose, and a total dose of 7.16 micrograms/kg +/- 0.71. The degree of hemodynamic stability relative to the baseline was assessed. There was no obvious superiority of either technique prior to the skin incision. However, during and immediately after surgery, a clearer tendency for isoflurane-N2O to result in better hemodynamic stability was found. Isoflurane-N2O demonstrated significantly smaller change scores in systemic vascular resistance (SVR) and cardiac index (CI). At the start of surgery, the isoflurane-N2O change in SVR was 228.08 dyne.sec.cm-5 compared to 479.58 for the fentanyl patients, (P = 0.002); at the end of surgery the corresponding means were -12.09 and 703.14 dyne.sec.cm-5, respectively, (P = 0.002). Isoflurane-N2O was associated with significantly greater CI stability in the early postoperative period: the isoflurane-N2O mean change was -0.081 L/min/m2, versus -0.993 for the fentanyl-N2O patients, (P = 0.005). The authors conclude that anthracycline-treated patients who do not have overt evidence of cardiomyopathy can be safely anesthetized with either anesthetic technique. However, during surgery and in the early postoperative period, an isoflurane-N2O technique appears to offer better hemodynamic stability.

Acid-Base Imbalance↗

Transesophageal pulsed-Doppler echocardiographic evaluation of transmitral and pulmonary venous flow during ventilation with positive end-expiratory pressure.

During mechanical ventilation with high levels of positive end-expiratory pressure (PEEP) several hemodynamic changes occur, the mechanism of which has been the subject of various previous studies. The effects of increasing levels of PEEP during mechanical ventilation were measured on left atrial and left ventricular filling dynamics, as assessed by pulmonary venous and transmitral flow velocities, respectively. Using transesophageal echocardiography in 12 patients, Doppler flow velocities of pulmonary venous and transmitral flow were studied at baseline (0 cmH2O PEEP) and at 5, 10, 15, and 20 cm H2O with 10-minute intervals, and once more after removal of PEEP. In 2 of the 12 patients, PEEP could not be increased beyond 15 cmH2O, because cardiac index fell below 2.0 L/min/m2. Pulmonary venous flow velocity and velocity time integral during systole significantly decreased from 48 +/- 7 cm/s and 10.3 +/- 2.2 cm at baseline to 35 +/- 6 cm/s and 5.7 +/- 2.5 cm at 20 cmH2O PEEP, respectively (P < 0.01). In contrast, early and late diastolic velocities and velocity time integrals did not change. In regard to transmitral flow, both early and late diastolic velocities significantly decreased from 51 +/- 7 cm/s and 50 +/- 9 cm/s at baseline to 38 +/- 7 cm/s at 20 cmH2O PEEP, respectively (P < 0.01). Early and late diastolic velocity time integrals decreased from 6.1 +/- 1.8 cm and 4.7 +/- 1.0 cm to 4.5 +/- 1.0 cm (NS) and 3.4 +/- 0.7 cm (P < 0.05), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Modelling in the study of interaction of Hemopump device and artificial ventilation.

The aim of this work is to evaluate in different ventricular conditions the influence of joint mechanical ventilation (MV) and Hemopump assistance. To perform this study, we used a computer simulator of human cardiovascular system where the influence of MV was introduced changing thoracic pressure to positive values. The simulation confirmed that haemodynamic variables are highly sensitive to thoracic pressure changes. On the other hand, Hemopump assistance raises, among the others, mean aortic pressure, total cardiac output (left ventricular output flow plus Hemopump flow) and coronary flow. The simulation showed that the joint action of Hemopump and positive thoracic pressure diminishes these effects.

Air Pressure↗

Physiologic changes after brain death.

Although hemodynamic instability and cardiac dysfunction after brain death are reported in the potential organ donor, the underlying mechanisms, such as neuro-humoral changes, myocardial injury, and altered loading conditions, are discussed contrarily. The physiologic regulatory mechanisms that may contribute to the reduction of cardiac function after brain death are reviewed. Special emphasis is focused on the framework of pre- and afterload conditions and coronary perfusion as main determinants of myocardial contractility. On the basis of recent experimental and clinical data, the reduced myocardial contractility after brain death might be seen as a physiologic response to decreased pre- and afterload and coronary perfusion.

Atrial Function, Right↗

Effects of graded exercise on bronchial blood flow and airway dimensions in sheep.

Exercise stimulus-response relationships for airway blood supply and dimensions have not been described in mammalian species. These relationships are vital for postulates concerning integrated reflex factors normally controlling the airways and which may underlie the asthma syndromes of exercise. This study defines airways stimulus-response relationships in exercising sheep. Ewes between 35 and 40kg were instrumented at left thoracotomy under thiopentone/isoflurane general anaesthesia. Pulsed Doppler ultrasonic transducers were mounted on the bronchial artery, and transit-time plus single-crystal sonomicrometers on the left main bronchus. These recorded simultaneously and continuously bronchial blood flow (Q(br)) and conductance (C(br)), bronchial circumference (Circ(br)) and wall thickness (Th(br)). In Protocol 1 (P1), four sheep ran duplicate 5min protocols on a horizontal treadmill at continuous step-up-and-down speeds of 1min duration, namely, 0.8, 1.6, 2.2, 1.6 and 0.8mph (moderate exercise), followed by 10min recovery. In P2, four sheep ran duplicate 2min protocols at constant 4mph (strenuous exercise), and in P3, one sheep ran duplicate protocols each of 3min at 2.2, 4.4 and 6mph (severe exercise). Regression analysis and repeated measures ANOVA were used to assess differences between times, runs and exercise intensity. In P1, airway effects were directly related to graded exercise effort sustained over 5min. Peak effects occurred at 2.2mph, except for Th(br). Heart rate and P(a) rose (to 156% and 111% of resting, respectively), and Q(br) and C(br) fell (to 83% and 75%; both P<0.001). Circ(br) fell to 96% (P=0.02), and Th(br) rose at low speeds early and late, and thinned at the highest speed. In P2 and P3 for all variables the steady-state effects were systematically greater than for P1 (4.4mph: C(br) to 43%, Circ(br) to 93%; 6.6mph: C(br) to 25%, Circ(br) to 82%). There was no significant recovery hyperaemia, but there was residual post-exercise bronchoconstriction. The exercise stimulus-response relationships from rest to a maximal 6mph for sheep airway circumference and its bronchial circulation are inverse and functionally constrictor.

Animals↗