S. Mouren

Effects of Propofol and Thiopental on Coronary Blood Flow and Myocardial Performance in an Isolated Rabbit Heart

BackgroundSome clinical and experimental studies suggest that propofol decreases myocardial contractility and relaxation, whereas others report preserved cardiac function. To investigate the effects of propofol on intrinsic contractility and relaxation, increasing concentrations of propofol were infused in isolated blood-perfused rabbit hearts. Equimolar concentrations of thiopental were infused as a reference group. MethodsCoronary blood flow, left ventricular contractility and relaxation (as maximal positive and negative left ventricular pressure derivatives [dP/dtmax and dP/dtmin], respectively), and myocardial oxygen consumption (MvO2) were measured during infusion of 10–1,000 μM propofol in bloodperfused hearts. To determine whether the effects of propofol depend on the hearts perfusate, propofol also was infused in isolated buffer-perfused rabbit hearts. In addition, the effects of propofol solvent were investigated in blood- and buffer-perfused preparations. ResultsIn blood-perfused preparations, coronary blood flow increased with propofol concentrations greater than 30 μM and with 300 and 1,000 μM thiopental. Left ventricular dP/dtmax and dP/dtmin remained unchanged with propofol and decreased with concentrations of thiopental equal to or greater than 30 μM. MvO2 increased with 1,000 μM propofol, whereas coronary venous oxygen tension and content remained unchanged. MvO2 decreased with thiopental associated with a significant increase in coronary venous oxygen tension and content. In six buffer-perfused hearts, basal coronary blood flow was much greater and MvO2 less than in blood-perfused hearts. Left ventricular dP/dtmax and dP/dtmin decreased with 30, 100, and 300 μM propofol. Propofol vehicle did not change coronary blood flow, myocardial performance, or MvO2 of blood- or buffer-perfused hearts. ConclusionsWhen compared to a reference drug such as thiopental, propofol did not depress the myocardial performance of blood-perfused rabbit hearts. The type of the perfusate (blood vs. buffer), however, had a major influence on the myocardial effects of propofol.

Mechanisms of increased myocardial contractility with hypertonic saline solutions in isolated blood-perfused rabbit hearts

Hypertonic saline improves organ perfusion and animal survival during hemorrhagic shock because it expands plasma volume and increases tissue oxygenation.Because both decreased and increased myocardial performance have been reported with hypertonic saline, the effects of hyperosmolarity and the mechanism accounting for it were investigated in isolated blood-perfused rabbit hearts. Coronary blood flow (CBF), myocardial contractility, relaxation, and oxygen consumption were measured during administration of blood perfusates containing 140-180 mmol sodium concentrations ([Na+]). In two other series of experiments, the role of Na+-Ca2+ exchange in the inotropic effect of hyperosmolarity (160 mmol sodium concentration) and hypertonicity (sucrose) were also investigated. Hypertonic [Na+] induced a significant increase in contractility and relaxation, combined with a coronary vasodilation. Myocardial oxygen consumption (MvO2) increased at all hypertonic [Na+] without significant change in coronary venous oxygen tension (PvO2) and content (CvO2). Amiloride (0.3 mmol) inhibited the improved contractility observed with 160 mmol sodium. Similar Na+-Ca2+ exchanger blockade did not inhibit the inotropic effect of sucrose. These results confirm the positive inotropic effect of hypertonic [Na+]. The inhibition of this improvement by amiloride suggests that calcium influx through the sarcolemna could be the major mechanism of this effect. (Anesth Analg 1995;81:777-82)

Terlipressin-ephedrine versus ephedrine to treat hypotension at the induction of anesthesia in patients chronically treated with angiotensin converting-enzyme inhibitors: a prospective, randomized, double-blinded, crossover study.

In patients chronically treated with angiotensin con-verting-enzyme inhibitors (ACEI), typically selected doses of ephedrine do not always restore arterial blood pressure when anesthesia-induced hypotension occurs. We postulated that the administration of terlipressin, an agonist of the vasopressin system, with ephedrine more effectively restores pressure in this setting than the administration of ephedrine alone. This prospective, randomized, cross-over, double-blinded study compared terlipressin combined with ephedrine (n = 19) with ephedrine alone (n = 21) in treating hypotension at the induction of anesthesia in 40 ACEI-treated patients undergoing hypotension (mean arterial blood pressure [MAP] <65 mm Hg or <30% of baseline value) after standardized anesthetic protocol (target-controlled IV anesthesia with propofol). Data are mean ± sd. Patient characteristics, MAP, and heart rate before and after the induction of anesthesia during hypotensive episodes were not significantly different between the two groups. After the first bolus, MAP was significantly greater in the Terlipressin-Ephedrine group (72 ± 12 mm Hg versus 65 ± 8 mm Hg, P < 0.05). The occurrence of a second hypotensive episode (5% versus 71%, P < 0.001), the duration (2 ± 1 min versus 3 ± 1 min, P < 0.01) of hypotensive episodes, and the median dose of ephedrine (3 versus 6 mg, P < 0.05) were significantly less in the Terlipressin-Ephedrine group. In conclusion, terlipressin combined with ephedrine is more effective than ephedrine alone for treating anesthesia-induced hypotension in ACEI-treated patients. We conclude that this patient population with a partially blocked endogenous response to hypotension may be good candidates for successful use of a vasopressin analog to counteract intraoperative refractory hypotension.

Treating anesthesia-induced hypotension by angiotensin II in patients chronically treated with angiotensin-converting enzyme inhibitors

Although angiotensin II bolus administration may be used to increase blood pressure in patients chronically treated with angiotensin-converting enzyme inhibitors (ACEI) who have severe hypotension on anesthetic induction, no data are available describing its time course and its effects on the left ventricular function. Fourteen patients chronically treated with ACEI for hypertension and scheduled for vascular surgery were prospectively studied. Patients with cardiac insufficiency were excluded. A transesophageal echocardiography probe was inserted to assess systolic left ventricular function. When hypotension was observed (systolic arterial pressure [SAP] <85 mm Hg), an IV bolus of 2.5 micro g of angiotensin II (AII) was given, and hemodynamic variables were recorded each 30 s over 5.5 min. Results are expressed as mean +/- SEM. Sixty seconds after the AII bolus injection, the SAP increased from 78 +/- 3 to 152 +/- 6 mm Hg. SAP remained higher than control until the 5th min. This was associated with significant increases in end-diastolic area (from 15.1 +/- 0.6 to 19.3 +/- 1.0 cm2, P <or=to 0.001), end-systolic area (from 6.6 +/- 0.4 to 10.7 +/- 0.7 cm2, P <or=to0.001), end-systolic wall stress (from 32 +/- 0.05 to 82 +/- 7 kdynes/cm2, P <or=to 0.001). In addition, a decrease in fiber-shortening velocity (from 1.1 +/- 0.05 to 0.76 +/- 0.04 circ/s, P <or=to 0.05) and in fractional area change (from 0.57 +/- 0.02 to 0.44 +/- 0.02, P <or=to 0.05) was observed. Heart rate did not significantly change during the study. Increases in preload and afterload were observed. However, the administration of AII causes a transient impairment in left ventricular function. We conclude that AII, given as an IV bolus of 2.5 micro g, is effective in restoring arterial blood pressure within 60 s in patients chronically treated with ACEI. Implications: Severe hypotension on anesthetic induction in patients chronically treated with angiotensin-converting enzyme inhibitors for hypertension could be treated with an IV bolus of 2.5 micro g of angiotensin II. (Anesth Analg 1998;86:259-63)

Comparison of isollurane with sodium nitroprusside for controlling hypertension during thoracic aortic cross-clamping☆

Abstract 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 isoflurane and sodium nitroprusside was stopped 2 minutes before unclamping. The same anesthetic technique using fentanyl, 6 μg/kg, flunitrazepsm, 0.02 mg/kg, pancuronium, 0.1 mg/kg, and 50% N 2 O was used for all patients. At the time of clamping, either isoflurane (maximal expired concentration, 2.6% ± 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, PvO 2 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. It is concluded that isoflurane added to fentanyl anesthesia is acceptable for thoracic aortic aneurysm surgery because it allows safe and effective control of hypertension during clamping without compromising hemodynamics and oxygen transport.

Myocardial and coronary effects of propofol in rabbits with compensated cardiac hypertrophy.

BackgroundMyocardial effects of propofol have been previously investigated but most studies have been performed in healthy hearts. This study compared the cardiac effects of propofol on isolated normal and hypertrophic rabbits hearts. MethodsThe effects of propofol (10–1,000 &mgr;m) on myocardial contractility, relaxation, coronary flow and oxygen consumption were investigated in hearts from rabbits with pressure overload–induced left ventricular hypertrophy (LVH group, n = 20) after aortic abdominal banding and from sham-operated control rabbits (SHAM group, n = 10), using an isolated and erythrocyte-perfused heart model. In addition, to assess the myocardial and coronary effects of propofol in more severe LVH, hearts with a degree of hypertrophy greater than 140% were selected (severe LVH group, n = 7). ResultsThe cardiac hypertrophy model induced significant left ventricular hypertrophy (136 ± 21%, P < 0.05). The pressure-volume relation showed normal systolic function but an altered diastolic compliance in hypertrophic hearts. Propofol only decreased myocardial contractility and relaxation at supratherapeutic concentrations (≥ 300 &mgr;m) in SHAM and LVH groups. The decrease in myocardial performances was not significantly different in SHAM and LVH groups. Propofol induced a significant increase in coronary blood flow which was not significantly different between groups. In severe LVH group, the degree of hypertrophy reached to 157 ± 23%. Similarly, the effects of concentrations of propofol were not significantly different from the SHAM group. ConclusionsPropofol only decreased myocardial function at supratherapeutic concentrations. The myocardial and coronary effects of propofol were not significantly modified in cardiac hypertrophy.

The continuous recording of blood pressure in patients undergoing carotid surgery under remifentanil versus sufentanil analgesia.

We compared the hemodynamic stability during carotid endarterectomy of remifentanil with that of sufentanil anesthesia. Fifty-six patients were randomly assigned into Remifentanil (n = 27) or Sufentanil (n = 29) groups. In the Remifentanil group, IV propacetamol (2 g) and morphine (0.1 mg/kg) were infused 30 min before skin closure. In the Sufentanil group, patients received 2 g propacetamol. Beat-to-beat recordings of systolic arterial blood pressure (SBP) and heart rate (HR) were stored on a computer. The maximum and minimum values of BP and HR after induction, at intubation, during the surgical procedure, and after the operation and the coefficients of variation of SBP and HR were used as indices of hemodynamic stability. The coefficients of variation of SBP and HR were similar in both groups during and after surgery. However, at intubation, maximal SBP was higher in the Sufentanil group (P < 0.05). Decreased propofol doses and isoflurane end-tidal concentrations were used in the Remifentanil group. At recovery, a similar profile of SBP and HR was found in both groups. We conclude that intra- and posthemodynamic stability was similar with remifentanil or sufentanil in patients undergoing carotid endarterectomy. However, remifentanil was more effective for blunting the increase in SBP at intubation without increasing the blood pressure-decreasing effect of induction. Intraoperative remifentanil use was associated with a decreased amount of hypnotic drug administered.

Crystalloid versus red blood cell-containing medium in the Langendorff-perfused isolated heart preparation.

Background The isolated heart model is widely used for the assessment of coronary vascular response under various experimental conditions. As medium perfusate influences oxygenation conditions, coronary vascular response and myocardial consumption performance may differ between isolated hearts perfused with from with Krebs-Henseleit solution or Krebs-Henseleit mixed with red blood cells (KH-RBC). Methods Coronary vascular response to endothelium-dependent and independent vasodilators as well as myocardial performance and oxygen consumption to isoproterenol infusion were compared in isolated rabbit hearts perfused with Krebs-Henseleit or KH-RBC. Krebs-Henseleit perfusate was equilibrated with 95% oxygen and 5% carbon dioxide, KH-RBC (haemoglobin 8.0 ± 1.1 g.dl−1) with 20% oxygen, 5% carbon dioxide, and 75% nitrogen. The perfusion pressure was kept constant so that coronary blood flow (CBF) varied with coronary resistance. Data are mean ± SD. Results Bradykinin induced a greater increase in CBF in KH-RBC-perfused hearts than in Krebs-Henseleit-perfused hearts (263 ± 78 versus 134 ± 35% of baseline, P < 0.001). Sodium nitroprusside induced a greater increase in CBF in KH-RBC-perfused than in Krebs-Henseleit-perfused hearts (257 ± 70 versus 174 ± 31% of baseline, P < 0.001). The increases in myocardial performance and in oxygen consumption induced by isoproterenol were greater with KH-RBC-perfused hearts than in Krebs-Henseleit-perfused hearts. A greater myoglobin release was observed in Krebs-Henseleit-perfused hearts. Conclusion Endothelium-dependent and independent coronary flow responses are increased in KH-RBC-perfused hearts. Moreover, metabolic control of CBF is altered in Krebs-Henseleit-perfused hearts. Such differences should be taken into account when pharmacologic responses of anaesthetic agents are studied.

Effects of eltanolone on myocardial performance and coronary flow in intact and catecholamine-depleted isolated rabbit hearts

Background Experimental studies suggest that the new short-acting intravenous anesthetic agent eltanolone does not markedly alter hemodynamics or cardiac function. However, because its intrinsic effects on myocardial performance and coronary blood flow are not yet known, they were examined in isolated blood-perfused rabbit hearts. Methods Coronary blood flow, myocardial contractility, relaxation, and oxygen consumption were measured during perfusion of hearts with 0.1 to 10 micro gram/ml eltanolone (n = 7) or its vehicle (n = 7). To determine whether the cardiac effects of eltanolone are mediated by indirect sympathetic activation, the same dose-response curve was studied in another group of five hearts depleted of catecholamine with reserpine treatment. Results Coronary blood flow significantly increased with 10 micro gram/ml eltanolone and significantly decreased with 10 micro gram/ml eltanolone vehicle. At eltanolone concentrations less than 10 micro gram/ml, myocardial contractility and relaxation remained unchanged but decreased at 10 micro gram/ml. Myocardial contractility and relaxation were not affected by perfusion of eltanolone vehicle alone. In eltanolone-perfused hearts, unchanged myocardial oxygen consumption was associated with significant increases in coronary venous oxygen content and tension, but in vehicle-perfused hearts, it was associated with reduced coronary venous oxygen content and tension. In catecholamine-depleted hearts, the variations in myocardial performance and coronary blood flow induced by eltanolone were similar to those observed in intact hearts. Conclusions Eltanolone (0.1 to 3 micro gram/ml) did not alter myocardial performance or coronary blood flow in isolated blood-perfused rabbit hearts. These effects were not due to an eltanolone-induced indirect sympathetic activation. Cardiac depression and coronary vasodilatation were only observed at concentrations of eltanolone far greater than those in clinical range.

Etude de l'activité baroréflexe lors de l'endartériectomie carotidienne sous anesthésie générale

The baroreceptor reflex was studied in eleven patients, aged 69 ± 6 years, scheduled for carotid endarterectomy under general anaesthesia. Nine were hypertensive. The anaesthetic protocol was the same for all the patients : premedication with morphine and scopolamine, induction with 5 mg · kg−1 thiopentone, 6 μg · kg−1 fentanyl and 0.01 mg · kg−1 pancuronium bromide. All the patients were intubated and ventilated with a mixture of nitrous oxide and oxygen. Fentanyl, 100 μg, was routinely given at the time of incision. Baroreflex sensitivity was tested using Smyths method, with a bolus of 75 μg trinitrin and plotting changes in heart rate against those in systolic blood pressure. Electrocardiogramme, invasive arterial blood pressure and airway pressure were simultaneously recorded. Paco2 and Pao2 were measured during arterial clamping. The tests were carried out before clamping, 2 min later and 10 to 20 min after the last injection of fentanyl. In the seven patients for whom clamping lasted more than 15 min, a further test was carried out after administration of 0.4 ± 0.05 vol % halothane (Datex analyser) for 5 min. During anaesthesia, baroreflex sensitivity was low (1.8 ± 0.3 ms · mmHg−1). After clamping, there was only a significant change in Pasys, with no changes in heart rate or blood gas values (129 ± 8 mmHg before clamping ; 167 ± 12 mmHg after clamping ; n = 8 ; p < 0.01). After halothane administration, the sensitivity slope decreased, but not significantly. Moreover, halothane decreased the R-R intervals (1140 ± 84 after clamping ; 963 ± 76 under halothane ; n = 6 ; p < 0.05). In patients undergoing carotid endarterectomy under general anaesthesia, baroreflex sensitivity was reduced ; this was probably mainly due, not only to the various anaesthetic drugs used, but also to the chronic hypertension, the age of the patients and the atheromatous disease.