Acute pulmonary hypertension causes depression of left ventricular contractility and relaxation.

BACKGROUND AND OBJECTIVE: The haemodynamic effects of acute pulmonary hypertension can be largely attributed to ventricular interdependence during diastole. However, there is evidence that the two ventricles also interact during systole. The aim of the present study was to examine the effects of acute pulmonary hypertension on both components of left ventricular systole, i.e. contraction and relaxation, using load-independent indices. METHODS: Ten pigs were instrumented with biventricular conductance catheters, a pulmonary artery flow probe and a high-fidelity pulmonary pressure catheter. Haemodynamic measurements were performed in baseline conditions and during stable pulmonary vasoconstriction induced by the thromboxane analogue U46619. Contractility was quantified using the end-systolic pressure-volume and preload recruitable stroke work relationships. The tau-end-systolic pressure relationship was used to assess load-dependency of relaxation. RESULTS: Acute pulmonary hypertension caused a decrease in the slope of the left ventricular preload recruitable stroke work relationship (from 6.64 +/- 1.7 to 5.19 +/- 1.9, mean +/- SD; P < 0.05), a rightward shift of the end-systolic pressure-volume relationship (P < 0.05), and an increase in the slope of the tau-end-systolic pressure relationship (from -0.15 +/- 0.5 to 0.35 +/- 0.17; P < 0.05). The diastolic chamber stiffness constant of both ventricles increased during pulmonary hypertension (P < 0.05). CONCLUSIONS: In the present model, acute pulmonary hypertension impairs left ventricular contractile function and relaxing properties. The present study provides additional evidence that, besides the well-known diastolic ventricular cross talk, systolic ventricular interaction may play a significant role in the haemodynamic consequences of acute pulmonary hypertension.

Evaluation of a new continuous cardiac output monitor in off-pump coronary artery surgery.

We evaluated a new, ultra-fast response continuous cardiac output monitor in 34 adult patients undergoing off-pump coronary artery bypass graft surgery. Cardiac output was measured with the TruCCOMS continuous cardiac output monitor (Aortech International plc, Lanarkshire, UK), using triplicate cold bolus thermodilution as the criterion standard, at fixed time points during surgery and during dobutamine infusion. The two techniques were compared using linear regression and Bland-Altman analysis. Overall, the study device displayed a bias of 0.4 l.min(-1) with limits of agreement of +2.5 l.min(-1) and -1.7 l.min(-1). The study device failed to detect the change in cardiac output caused by dobutamine accurately (y = 0.18x + 0.45; r(2) = 0.13), with an error linearly related to the magnitude of the change measured. We conclude that the device's failure to detect changes in cardiac output could be a major limitation in its clinical use in its current form.

Effects of propofol on the systolic and diastolic performance of the postischaemic, reperfused myocardium in rabbits.

BACKGROUND AND OBJECTIVE: The effect of propofol on myocardial dysfunction during ischaemia and reperfusion is controversial yet important because of its frequent use in cardiac anaesthesia. Although animal studies suggest a free radical-scavenging potential, the cardioprotective properties of propofol have not been demonstrated consistently in vivo. Previous studies focused on systolic function while diastolic function may be a more sensitive marker of ischaemic injury. The main aim was to document the effect of propofol on diastolic function in isolated, blood perfused rabbit hearts subjected to moderate global ischaemia and reperfusion. METHODS: Propofol 168 micromol L(-1), or the equivalent of its vehicle, Intralipid, was administered to 34 paced parabiotic Langendorff blood-perfused isolated rabbit hearts before and after 30 min of global normothermic ischaemia. Recovery of systolic function was quantified with the maximum rate of rise of left ventricular pressure. Diastolic performance was assessed using the time constant of the decline in left ventricular pressure (tau) and chamber stiffness (VdP/dV at 12 mmHg). RESULTS: Recovery of systolic function during reperfusion was comparable in the two groups. There was no difference in left ventricular pressure between the two groups at any time during the experiments. Chamber stiffness increased significantly during ischaemia and reperfusion in the control group (from 34 +/- 9 to 54 +/- 8 mmHg during ischaemia, and 43 +/- 5 mmHg after 30 min reperfusion; mean +/-95% confidence interval) but not in the propofol-treated group (29 +/- 5, 36 +/- 8 and 30 +/- 8 at baseline, ischaemia and 30 min reperfusion, respectively). CONCLUSIONS: Propofol has no protective effect on active relaxation or on systolic function in the present model, but it reduces ischaemic and postischaemic chamber stiffness.

Oesophageal Doppler monitoring overestimates cardiac output during lumbar epidural anaesthesia.

Oesophageal Doppler monitoring (ODM) has been advocated as a non-invasive means of measuring cardiac output (CO). However, its reliance upon blood flow measurement in the descending aorta to estimate CO is susceptible to error if blood flow is redistributed between the upper and lower body. We hypothesize that lumbar epidural anesthesia (LEA), which causes blood flow redistribution, causes errors in CO estimates. We compared ODM with thermodilution (TD) measurements in fourteen patients under general anaesthesia for radical prostatectomy, who had received an epidural catheter at the intervertebral level L2-L3. Coupled measurements of CO by means of the TD and ODM techniques were performed at baseline (general anaesthetic only) and after epidural administration of 10 ml of 0.25% bupivacaine. The two methods were compared using Bland-Altman analysis: before LEA there was a bias of -0.89 litre min(-1) with limits of agreement ranging between -2.67 and +0.88 litre min(-1). Following lumbar sympathetic block, bias became positive (+0.55 litre min(-1)) and limits of agreement increased to -3.21 and +4.30 litre min(-1). ODM measured a greater increase in CO after LEA (delta=+1.71 (1.19) litre min(-1) (mean (SD)) compared with TD (delta=+0.51 (0.70) litre min(-1)). We conclude that following LEA, measurements with the Oesophageal Doppler Monitor II overestimate CO and show unacceptably high variability. Blood flow redistribution may limit the value of ODM.

Effects of lipids on the functional and metabolic recovery from global myocardial stunning in isolated rabbit hearts.

OBJECTIVES: High concentrations of free fatty acids may increase myocardial ischaemic damage. However, the administration of lipid emulsions during reperfusion improves the functional recovery of stunned myocardium. From this apparent controversy we hypothesise that the effect of lipids is related to the time of its administration: we compared the effects of pre- and post-ischaemic administration of Intralipid((R)) on stunned myocardium. We also examined the role of fatty acids and phospholipids, respectively, in the effect of lipid emulsions on stunned myocardium. METHODS: Myocardial stunning was produced by 15 min of ischaemia and 90 min of reperfusion in isolated blood perfused rabbit hearts. Intralipid((R)) was administered either prior to ischaemia or during reperfusion. Left ventricular pressure (LVP) and its first derivative (LVdP/dt) were measured to assess functional recovery. High energy phosphates were measured with HPLC. The effects of linoleic acid, phosphatidylcholine and their combination were also studied. RESULTS: Only when Intralipid((R)) was administered during reperfusion, it improved recovery from contractile function and increased high energy phosphate content in globally stunned myocardium. Both linoleic acid and phosphatidylcholine significantly improved myocardial function in stunned myocardium. CONCLUSIONS: The effect of lipids on the contractile performance and metabolic state of stunned myocardium depends mainly on the timing of its administration with regard to the ischaemia/reperfusion event. Both free fatty acids and phospholipids contribute to the beneficial effect of lipid emulsions on functional recovery of stunned myocardium.

Effect of clevidipine, an ultra-short acting 1,4-dihydropyridine calcium channel blocking drug, on the potency of isoflurane in rats and dogs.

Clevidipine is a new lipophilic, ultra-short acting 1, 4-dihydropyridine calcium channel antagonist for intraoperative use. Because sarcolemnal calcium currents are involved in the mechanism of action of anaesthetics we questioned whether clevidipine alters the potency of volatile anaesthetics. We studied the effects of clevidipine on minimal alveolar concentration and the time to awaken from isoflurane anaesthesia. Sprague-Dawley rats were anaesthetized with isoflurane, and were allocated to one of four treatments prior to minimal alveolar concentration determination: (a) saline control; (b) clevidipine 20 nmol kg-1 min-1; (c) clevidipine 40 nmol kg-1 min-1; (d) clonidine 1 microg kg-1 - positive control. Ten mongrel dogs were anaesthetized with isoflurane and received a continuous infusion of clevidipine 6 nmol kg-1 min-1 or the solvent (Intralipid 20% - control). After 2 h of steady-state anaesthesia, minimal alveolar concentration awake and the time to awakening were recorded. Clevidipine reduced minimal alveolar concentration to a small but statistically significant extent (from 1.40 +/- 0.16 control to 1.23 +/- 0.13 vol % with 20 nmol kg-1 min-1 and to 1.27 +/- 0.12 vol % with 40 nmol kg-1 min-1; mean +/- SD; P < 0.05) in rats. Clonidine reduced minimal alveolar concentration to 0.90 +/- 0.17 vol % (mean +/- SD; P < 0.05). Minimal alveolar concentration awake and the duration of sleep were not affected by clevidipine in dogs. Clevidipine mildly reduces minimal alveolar concentration of isoflurane but does not prolong the duration of sleep and does not affect minimal alveolar concentration awake after a 2-h steady-state isoflurane anaesthesia.

Effects of tramadol on minimum alveolar concentration (MAC) of isoflurane in rats.

It has been suggested previously that tramadol increases central nervous system activity and 'lightens' anaesthesia with volatile agents. We assessed the effects of tramadol on the minimum alveolar concentration (MAC) of isoflurane in 56 Wistar rats, instrumented chronically with an arterial and central venous catheter. The MAC of isoflurane was determined using the tail clamp method under three conditions: (1) after injection of saline (control); (2) after administration of tramadol 10 mg kg-1 i.v.; and (3) after administration of morphine 1 mg kg-1 i.v. The studies were repeated after treatment with the antagonists naloxone or yohimbine. Tramadol and morphine both reduced the MAC of isoflurane from mean 1.38 (SEM 0.05)% to 1.22 (0.06)% and 1.17 (0.06)%, respectively (P < 0.05). Concomitant administration of yohimbine did not abolish this reduction in MAC. In contrast, after pretreatment with naloxone, tramadol (1.47 (0.04)%) or morphine (1.38 (0.07)%) did not cause a reduction in the MAC of isoflurane compared with controls (1.39 (0.06)%). We conclude that tramadol and morphine reduced the MAC of isoflurane to a small but significant extent. For both drugs, this effect was related to their action at opioid receptors.