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Anesth Analg 2003;97:1230-1238
© 2003 International Anesthesia Research Society

CARDIOVASCULAR ANESTHESIA

Propofol Decreases Reperfusion-Induced Arrhythmias in a Model of "Border Zone" Between Normal and Ischemic-Reperfused Guinea Pig Myocardium

Jean-Luc Hanouz, MD PhD*, Alexandra Yvon, BSc{dagger}, Frédéric Flais, MD*, René Rouet, PhD{dagger}, Pierre Ducouret, PhD{dagger}, Henri Bricard, MD*, and Jean-Louis Gérard, MD PhD*,{dagger}

*Department of Anesthesiology, Centre Hospitalier Universitaire Caen, Caen, France; and {dagger}Laboratory of Experimental Anesthesiology and Cellular Physiology, Centre Hospitalier Universitaire Caen, Caen, France

Address correspondence and reprint requests to Jean-Luc Hanouz, MD, PhD, Département d’Anesthésie-Réanimation, CHU de Caen, Avenue Côte de Nacre, 14033 Caen Cedex, France. Address e-mail to hanouz-jl{at}chu-caen.fr


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
We examined the effect of propofol on the main mechanisms involved in ischemia/reperfusion-induced arrhythmias (i.e., spontaneous arrhythmias, conduction blocks, and dispersion of repolarization) in vitro. In a double-chamber bath, guinea pig right ventricular muscle strips were subjected to 30 min of simulated ischemia followed by 30 min of reperfusion (altered zone; AZ) and to standard conditions (normal zone; NZ). Action potential (AP) parameters were recorded in the NZ and AZ. We studied the effects of Intralipid® and of propofol at 10-6, 10-5, and 2 x 10-5 M on the occurrence of spontaneous sustained arrhythmias, conduction blocks, and the dispersion of repolarization. In NZ, Intralipid and propofol did not significantly modify the AP parameters. Propofol, but not Intralipid, lessened the ischemia-induced decrease in AP duration (APD) at 90% of repolarization (APD90) and attenuated the APD dispersion around the "border zone." Propofol did not modify the occurrence of ischemia-induced arrhythmias. Propofol 10-6 M, but not Intralipid or propofol at 10-5 and 2 x 10-5 M, decreased the occurrence of ischemia-induced conduction blocks. Propofol decreased the occurrence of reperfusion-induced spontaneous sustained arrhythmias. We conclude that, in vitro, propofol attenuated the ischemia-induced APD90 dispersion around the "border zone" and decreased the occurrence of spontaneous arrhythmias related to myocardial reperfusion injury.

IMPLICATIONS: In isolated guinea pig ventricular myocardium propofol, but not Intralipid®, attenuated the ischemia-induced shortening of action potential and, thus, the dispersion of repolarization and decreased the occurrence of spontaneous ventricular arrhythmia related to reperfusion injury. This result may be important for propofol-based anesthesia in patients at high risk for intraoperative ischemia.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Propofol is an IV anesthetic drug widely used during the induction and maintenance of anesthesia and during immediate postoperative sedation in patients undergoing coronary artery bypass surgery (1,2) and for prolonged sedation in critically ill patients (3). However, patients undergoing coronary artery bypass surgery are at high risk for perioperative myocardial ischemia, which is a major factor inducing ventricular dysrhythmias (4,5).

The cardioprotective effects of propofol on functional, metabolic, and histological changes caused by ischemia/reperfusion injury have been suggested by several experimental studies (6,7). However, in these experiments, supratherapeutic concentrations of propofol were administered only during a short period before myocardial ischemia or reperfusion, which is not representative of total IV propofol-based anesthesia. The mechanisms involved in the cardioprotective effects of propofol remain unclear but may involve an antioxidant effect and the attenuation of lipid peroxidation, as shown in in vitro as well as in vivo experiments (8,9).

The effect of propofol-based anesthesia on arrhythmias and conduction blocks related to myocardial ischemia/reperfusion injury remain unknown, despite its known clinical importance (4). Consequently, we examined the effects of propofol on ischemia- and reperfusion-induced arrhythmias, conduction blocks, and action potential (AP) parameter changes in an in vitro model of the "border zone" between normal and ischemic-reperfused myocardium.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
Care of the animals conformed to the recommendations of the Helsinki Declaration, and the study was performed in accordance with the official edict of French Ministry of Agriculture. The study did not require specific permission; it was required only that the laboratory be approved by the French Ministry of Agriculture.

As previously described (10), guinea pigs of either sex weighing 300–400 g were killed after anesthesia with ether, and the heart was quickly removed. A thin myocardial strip was carefully dissected from the free wall of the right ventricle and pinned, endocardial surface upward, in a special perfusion chamber (5 mL). As depicted in Figure 1, the perfusion chamber is bisected by a latex membrane containing a centrally located hole that allowed the myocardial strip to be passed through and divided into two compartments called the normal zone (NZ) and the altered zone (AZ). The two compartments were independently bubbled with carbogen (95% oxygen/5% CO2) and perfused at 2 mL/min with Tyrode’s solution (mM: 135 Na+, 4 K+, 1.8 Ca2+, 1.8 H2PO4-, 25 HCO3-, 117.8 Cl-, and 5.5 glucose) and bubbled with carbogen before perfusion. The pH of Tyrode’s solution was equilibrated at 7.35 ± 0.05, and the temperature was maintained at 36.5°C by a water-circulating thermostat-controlled bath (Polystat 5HP; Bioblock, Illkirch, France). At the end of each experiment, the absence of leak between the two compartments was tested by injection of methylene blue dye into one compartment.



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  		Figure 1. The double-chamber bath. In the normal zone (NZ), the myocardium was superfused with oxygenated Tyrode’s solution during the experiment. In the altered zone (AZ), the myocardium was superfused for 30 min with a modified Tyrode’s solution (i.e., hypoxia, hyperkalemia, acidosis, and lack of substrate) and 30 min with oxygenated Tyrode’s solution. Action potentials were recorded with intracellular microelectrodes. The myocardial strip could be stimulated by electrodes in NZ or AZ.

 
The preparations were stimulated at a frequency of 1 Hz by bipolar silicon-coated steel wire electrodes positioned on the muscle in the NZ and in the AZ. Thus, the preparation could be stimulated by one of the electrodes, either in the NZ or in the AZ. Stimuli were rectangular pulses of 1–2 V depolarizing voltage, 2 ms in duration, delivered by a programmable stimulator (Model SMP 310; Biologic, Grenoble, France). Preparations that needed pulses stronger than 5 V to elicit APs were discarded because there could be a conduction block at the level of the latex-separating membrane. During the protocol, stimulation was stopped whenever sustained spontaneous arrhythmias occurred. AP parameters were recorded simultaneously in both the NZ and AZ by using glass microelectrodes filled with KCl 3 M (tip resistance, 10–30 M{Omega}) and coupled with an Ag/AgCl microelectrode holder leading to a non-commercial high-impedance capacitance-neutralizing amplifier. A ball-shaped reference Ag/AgCl electrode was positioned in the superfusate of the compartments.

The following AP parameters were automatically stored and measured by a cardiac AP automatic acquisition system and processing device (Datapac; Biologic): resting membrane potential (RMP), maximal upstroke velocity (Vmax), AP amplitude (APA), AP duration (APD) at 50% of full repolarization (APD50), and APD at 90% of full repolarization (APD90). Cardiac APD is determined by a balance between inward and outward membrane currents. Inward currents during the plateau phase of AP are carried mainly through the L-type calcium current. As the major repolarizing current for cardiomyocytes, delayed rectifier potassium current (IK) activation initiates repolarization near the end of the AP plateau, which can be assessed by APD50. The late repolarization of the AP is mainly determined by the inward rectifier potassium current and the slow component of IK, namely, Iks, and is reflected by changes in APD90 (11).

Two types of electrical disturbance were recorded during the experiments: myocardial conduction blocks and spontaneous sustained arrhythmias. Myocardial conduction blocks between the AZ and the NZ were defined by the absence of AP detected in one zone after a stimulation applied in the other zone. Blocks were coded as present or absent. Spontaneous sustained arrhythmias (salvos >10 spontaneous APs) were recorded during ischemia and reperfusion periods and coded as present or absent.

The ratio of APD90 between the NZ and the AZ measured the dispersion of APD90 induced by ischemia and is an index of the dispersion of refractoriness periods. Ischemia dramatically shortens the repolarization phase but also induces the heterogeneity of the repolarization in the border zone between ischemic and nonischemic myocardium. The dispersion of the repolarization and, thus, of the refractoriness period sets the stage for reentry and is involved in ischemia-induced arrhythmias.

When impalement of the microelectrode was lost, readjustment was attempted. If the readjusted AP parameters differed less than 10% from the previous ones, experiments were continued, otherwise data were included only in electrical disturbance recordings.

After a 2-h equilibration period, a 30-min simulated ischemia was induced in the AZ by superfusion with a modified Tyrode’s solution while the NZ remained perfused with oxygenated Tyrode’s solution. The modified Tyrode’s solution differed from the normal solution by an increased K+ concentration (from 4 to 12 mM); a decreased HCO3- concentration (from 25 to 9 mM), which led to a decrease in pH (from 7.35 ± 0.05 to 6.90 ± 0.05); a decrease in PO2 by bubbling with 95% nitrogen/5% CO2; and withdrawal of glucose. The combined hypoxia, hyperkalemia, acidosis, and lack of energy substrate reproduced, in vitro, the electrophysiologic abnormalities induced in vivo by ischemia (12). At the end of the simulated ischemia, a 30-min reperfusion period was simulated with normal Tyrode’s solution bubbled with 95% oxygen/5% CO2.

The following groups were studied: a control group (Tyrode’s solution alone; n = 12), an Intralipid group (Intralipid® solution containing soybean oil 100 mg/mL, glycerol 22.5 mg/mL, and egg lecithin in water 12 mg/mL; n = 6), a propofol 10-6 M group (n = 8), a propofol 10-5 M group (n = 8), and a propofol 2 x 10-5 M group (n = 8). After baseline parameters were recorded, propofol 10-6 M, propofol 10-5 M, propofol 2 x 10-5 M, Intralipid solution corresponding to the concentration obtained with propofol at 2 x 10-5 M, or Tyrode’s solution alone was randomly superfused in both NZ and AZ during the simulated ischemia and reperfusion periods. Propofol was obtained from the commercial solution containing Intralipid (Diprivan; Zeneca Pharmaceuticals, Cergy Pontoise, France).

Because of a loss of microelectrode impalements, AP parameters were analyzed from 8 preparations of 12 attempted in the control group, 6 preparations of 8 attempted in the propofol groups, and 6 preparations of 6 attempted in the Intralipid group. The occurrences of conduction blocks and spontaneous sustained arrhythmias were recorded in all experiments.

Data are expressed as mean ± SD. AP parameters at identical time points were compared among groups by an analysis of variance and, if significantly different, by a Student-Newman-Keuls post hoc test. Repeated-measures analysis of variance was used to test differences over time among groups for AP parameters. Differences were considered as significant when P < 0.05. Fischer’s exact test was used for comparison of categorical data.


   Results
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 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
In the control group, all AP parameters recorded in the NZ remained unchanged with time. None of the propofol concentrations modified the AP parameters measured in the NZ (Table 1). Although the APD90 values measured at baseline and 30 min in the Intralipid group were significantly smaller than those measured in the control group (Table 1), Intralipid had no effect on APD90 over time.


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  		Table 1. Effects of Propofol on the Action Potential Variables in the Normal Zone
 
Simulated ischemia-induced alterations of AP parameters within groups are summarized in Table 2. Thirty minutes of simulated ischemia induced a significant membrane depolarization (+38% ± 3%; P < 0.05), a significant decrease in Vmax (-74% ± 20%; P < 0.05) and APA (-36% ± 10%; P < 0.05), and a significant shortening of APD50 (-69% ± 14%; P < 0.05) and APD90 (-66% ± 9%; P < 0.05) in all groups. Reperfusion of the AZ was associated with a complete recovery of the AP parameters (Table 2).


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  		Table 2. Effects of Propofol on the Action Potential Variables During Simulated Ischemia and Reperfusion in the Altered Zone
 
Intralipid and propofol 10-6, 10-5, and 2 x 10-5 M did not modify the simulated ischemia-induced change in RMP, Vmax, and APA (Table 2). The simulated ischemia-induced shortening of APD50 was significantly attenuated by propofol 10-5 M (-40% ± 15% versus -69% ± 14%; P < 0.05) but not by Intralipid (-57% ± 8% versus -69% ± 14%; not significant). Although there was a trend toward a lower simulated ischemia-induced shortening in APD50 with propofol 10-6 M (-50% ± 15% versus -69% ± 14%; P = 0.09) and 2 x 10-5 M (-51% ± 16% versus -69% ± 14%; P = 0.09), this effect was not significant. The simulated ischemia-induced shortening of APD90 was significantly attenuated by propofol 10-6 M (-39% ± 10% versus -66% ± 9%; P < 0.05), propofol 10-5 M (-35% ± 11% versus -66% ± 9%; P < 0.05), and propofol 2 x 10-5 M (-40% ± 20% versus -66% ± 9%; P < 0.05) but not by Intralipid (-63% ± 4% versus -66% ± 9%; not significant).

During the reperfusion period, the recovery of RMP, APA, Vmax, APD50, and APD90 in the AZ was similar in the control and treated groups and returned to baseline values (Table 2). The ratio of APD90 between NZ and AZ reflects the dispersion of APD90 around the border zone and, thus, the dispersion of the refractoriness period. As shown in Figure 2, the dispersion of APD90 after 30 min of simulated ischemia was significantly reduced by all propofol concentrations.



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  		Figure 2. Effects of simulated ischemia (control; n = 8), Intralipid (n = 6), propofol 10-6 M (n = 6), propofol 10-5 M (n = 6), and propofol 2 x 10-5 M (n = 6) on the dispersion of APD90 between normal (NZ) and ischemic (AZ) myocardial zones. The dispersion of APD90 is represented by the ratio of APD90 in NZ/APD90 in AZ. Data are mean ± SD. APD90 = action potential duration at 90% of repolarization; NZ = normal zone; AZ = altered zone; NS = not significant.

 
Figure 3 shows, every 2 min, the number of preparations that exhibited spontaneous arrhythmias during simulated ischemia and reperfusion periods. Figure 4 shows the percentage of preparations that exhibited spontaneous sustained arrhythmias during the 30-min simulated ischemia and the 30-min reperfusion periods. In the control group, 25% (3 of 12) of the preparations exhibited spontaneous arrhythmias during 30 min of simulated ischemia. The occurrences of ischemia-induced spontaneous sustained arrhythmias were not significantly modified by Intralipid and propofol at any concentration tested (Fig. 4).



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  		Figure 3. Time course of the effect of Intralipid (n = 6), propofol 10-6 M (n = 8), propofol 10-5 M (n = 8), and propofol 2 x 10-5 M (n = 8) on the occurrence of spontaneous sustained arrhythmias (salvos >10 spontaneous action potentials) during the 30 min of simulated ischemia (left) and during the 30 min of reperfusion (right). Data, measured every 2 min, are the number of preparations presenting spontaneous sustained arrhythmias between the normal zone and the altered zone.

 


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  		Figure 4. Time course of the effect of Intralipid (n = 6), propofol 10-6 M (n = 8), propofol 10-5 M (n = 8), and propofol 2 x 10-5 M (n = 8) on the occurrence of conduction block during 30 min of simulated ischemia (left) and during 30 min of reperfusion (right). Data, measured every 2 min, are the number of preparations presenting conduction blocks between the normal zone and the altered zone. NS = not significant.

 
Figure 3 shows that, in the control group, reperfusion-induced arrhythmias started within 2 min of reperfusion and persisted during the 30 min of reperfusion. In the control group, 92% of the preparations (11 of 12) exhibited spontaneous arrhythmias during the reperfusion phase (Fig. 4). Propofol at each concentration tested, but not Intralipid, significantly decreased the incidence of reperfusion-induced arrhythmia (Figs. 3 and 4).

In the control group, 67% of the preparations exhibited conduction blocks between NZ and AZ during the 30 min of simulated ischemia (Fig. 4). Propofol at 10-6 M, but not Intralipid or propofol at 10-5 and 2 x 10-5 M, significantly reduced the conduction blocks observed during ischemia (Figs. 4 and 5).



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  		Figure 5. Global incidence (percentage of preparations with disturbances in each group) of spontaneous sustained arrhythmias (salvos >10 spontaneous action potentials) and conduction block during 30 min of simulated ischemia and reperfusion. The number at the top of each column indicates the ratio between the number of preparations presenting the disturbance and the total number of preparations in each group: control (n = 12), Intralipid (n = 6), propofol 10-6 M (n = 8), propofol 10-5 M (n = 8), and propofol 2 x 10-5 M (n = 8).

 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
This study showed that 1) propofol did not modify baseline AP parameters but attenuated the ischemia-induced decrease in APD90 and decreased the APD90 dispersion between NZ and AZ after 30 min of simulated ischemia; 2) propofol decreased conduction blocks during 30 minutes of simulated ischemia; and 3) propofol decreased the occurrence of arrhythmias during myocardial reperfusion.

Our results show that propofol and Intralipid did not modify the AP parameters recorded in NZ (Table 1). This is consistent with previous results showing that propofol up to 10-4 M did not modify the AP parameters of isolated guinea pig myocardium (13). In contrast, Puttick and Terrar (14) and Sakai et al. (15) showed that propofol shortened the APD90 in isolated ventricular myocytes. Similarly, it has been shown in guinea pig myocytes that propofol at 10-6 and 10-5 M decreased IK but did not modify the inward rectifier potassium current, which is the main determinant of APD90 (16). However, alterations of membrane components by enzymatic dissociation and the effect of temperature on the whole-cell voltage-clamp technique cannot entirely be excluded (17). Finally, it has been recently shown that large concentrations of propofol blocked the slow component of IK, namely, IKs, which would prolong APD90 (18). These controversial results may be explained by the observation that various concentrations of propofol may differentially modulate the currents involved in AP, and drug-induced changes in APD reflect the net effect on several different individual currents.

This is the first study showing that propofol, but not Intralipid, attenuated the ischemia-induced decrease in APD90 (Table 2). The ischemia-induced AP shortening is related, in large part, to an increase in membrane K+ conductance via the activation of an adenosine triphosphate (ATP)-dependent potassium (KATP) channel (19). However, it has been shown that clinically relevant concentrations of propofol had no effect on the sarcolemmal and mitochondrial KATP channels in isolated ventricular myocytes (20). Numerous outward potassium currents have been implicated in the repolarizing phase of AP. Thus, it has been shown that propofol decreased IK mainly by blocking its slow component (16,18). Although propofol blocks IKs at concentrations larger than those tested in our study (18), effects of ischemia on the sensitivity and the functional properties of membrane potassium channels could not be excluded. In addition to the KATP channels, potassium channels activated by arachidonic acid (KAA) (21) and direct effects of fatty acid peroxidation products (22) may contribute to APD shortening during myocardial ischemia. Because of the antioxidant properties of propofol (23) and its ability to inhibit lipid peroxidation induced by oxidative stress (24), the effects of propofol on ischemia-induced changes in APD may result, at least in part, from the modulation of KAA currents. Nevertheless, the precise mechanisms underlying the effect of propofol on ischemia-induced changes in APD and on potassium channels involved in ischemia need further specifically designed studies.

The attenuation of ischemia-induced changes in APD reported in the presence of propofol in our study resulted in a decrease in the dispersion of APD90 around the border zone between normal and ischemic myocardium during the late phase of ischemia (Fig. 2). Increased dispersion of refractoriness to conduction between ischemic and nonischemic zones sets the stage for reentrant arrhythmias, and the dispersion of repolarization has been implicated in the generation of ventricular arrhythmias (25,26). Nevertheless, our study does not show any antiarrhythmic effect of propofol during the 30 minutes of simulated ischemia. This may be because we measured only spontaneous arrhythmia and not triggered or automatic activities. It has been suggested that ischemia-induced arrhythmias measured in this model are mainly triggered activities favored by conduction blocks around the border zone (27). Our results also show that propofol at 10-6 M significantly reduced the occurrence of conduction blocks during the simulated ischemia. Although our study shows only a trend toward a decrease in the occurrence of conduction block at larger concentrations of propofol, one should consider that conduction block in our control group was lower than that reported previously in the same model (13). Taken together, the decrease in APD dispersion and conduction blocks during the simulated ischemia would be expected to decrease ischemia-induced arrhythmias. Four processes are considered basic to the genesis of ischemia-induced arrhythmias: 1) increased automaticity; 2) slowing of conduction in specific areas, with resultant reentry and reexcitation; 3) dispersion of refractoriness between the ischemic and nonischemic zones; and 4) early and delayed afterdepolarizations. Our experimental model enabled us to show that propofol may have beneficial effects on two ischemia-induced electrophysiological changes related to ventricular arrhythmias (i.e., conduction blocks and dispersion of repolarization). In addition, previous experimental studies have reported that propofol slows atrial rate and depresses atrioventricular nodal conduction (28). Nevertheless, specifically-designed experiments are required to determine the effects of propofol on ischemia-induced early and delayed afterdepolarizations and increased automaticity.

Our results showing that propofol may have beneficial antiarrhythmic effects during myocardial ischemia/reperfusion (Fig. 4) confirm and extend previous experimental results suggesting a cardioprotective effect of propofol on contractile function and metabolic and histological changes related to ischemia. In isolated rat hearts, the administration of propofol before and during ischemia increases recovery of contractile function, decreases lactate dehydrogenase release, and decreases histological injury during reperfusion (6). Moreover, Kokita et al. (8) have shown that propofol-enhanced recovery of contractile dysfunction after myocardial ischemia was associated with an improved energy state and decreased lipid peroxidation during postischemic reperfusion. Finally, Mathur et al. (29) have shown that a 15-minute administration of propofol before a 60-minute period of ischemia preconditions isolated rat hearts independently of the activation of KATP channels. Furthermore, because propofol had no effect on flavoprotein oxidation, which indirectly reflects mitochondrial KATP currents (30), the cardioprotective effect of propofol against ischemia/reperfusion would not be related to the activation of mitochondrial KATP channels. Although we did not study the mechanisms underlying the antiarrhythmic effect of propofol during myocardial reperfusion injury, increasing evidence suggests that the beneficial effects of propofol on ischemia/reperfusion injury could be related to its antioxidant action (9,22), its ability to inhibit lipid peroxidation induced by oxidative stress (23), and its oxygen-derived free radical-scavenging properties (31). Finally, because it has been suggested that the ischemia-induced increase in sarcolemmal {alpha}1-receptor density is related to long-chain acylcarnitine release (32), a direct effect of propofol on the {alpha}-adrenoceptor cannot be totally discarded (33).

The clinical implications of our results should be interpreted with the increasing use of propofol during anesthesia and postoperative sedation in high-risk patients (1–3). Although clinical studies are lacking, De Hert et al. (34) recently suggested that sevoflurane protected against the transient myocardial dysfunction related to coronary surgery, whereas propofol did not. However, many confounding parameters could have interfered, suggesting that these results could not be interpreted as the net effect of propofol or sevoflurane on cardiac function after cardiopulmonary bypass. Finally, further clinical studies are required to evaluate the effects of propofol-based anesthesia on the incidence and severity of postoperative arrhythmias in patients.

The following points must be considered when the clinical relevance of our study is assessed. First, the study was performed on isolated right ventricular guinea pig myocardium, which differs from the whole heart and from human heart. Second, we studied isolated guinea pig myocardium at a low frequency of stimulation as compared with the physiological heart rate of the guinea pig. However, because of the difficulty of maintaining intracellular impalements and appropriate stimulus-AP latencies at a higher frequency of stimulation, a 1-Hz stimulation is mandatory for recording AP parameters, conduction blocks, and sustained arrhythmias. Third, we studied only conduction blocks and spontaneous arrhythmia and did not evaluate triggered activity and early or delayed afterdepolarizations that require specific experimental conditions (lower stimulation frequency and pharmacologically induced prolonged APD). Fourth, we studied anoxia rather than ischemia, which strictly refers to reduced myocardial blood flow and also involves endothelial dysfunction. Our model of ischemia/reperfusion led to reversible myocardial injury, as suggested by the recovery of AP parameters to baseline values at the end of reperfusion. Nevertheless, reversible ischemic injury is the most commonly encountered situation during the perioperative period. Finally, it should be noted that we tested concentrations of propofol close to those measured in human pharmacokinetic studies (35), considering the protein binding of propofol.

In conclusion, in isolated guinea pig ventricular myocardium, propofol, but not Intralipid, attenuated the ischemia-induced shortening of AP and APD90 dispersion around the "border zone" and decreased the occurrence of ischemia-induced conduction blocks and reperfusion-induced ventricular arrhythmias.


   Acknowledgments
 
Supported by the University of Caen.


   References
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

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Accepted for publication June 24, 2003.





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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press