Male Sprague-Dawley rats weighing between 220 and 240 g were used. All animals were maintained in accordance with the Guidelines for the Care and Use of Laboratory Animals published by the US National Institutes of Health in 1996.

The animals received general anesthesia with an intramuscular injection of 50 mg/kg of ketamine (Ketamine Hcl®, Huons, Seoul, South Korea) and 3 mg/kg of zylazine (Rompun®, Bayer, Seoul, South Korea). The rats were judged to be awake from the anesthesia once their tails moved during the procedure, and then 25 mg/kg of ketamine and 1.5 mg/kg of zylazine were injected to maintain the level of anesthesia. After anesthesia was induced, a heparin-treated 24 G catheter was inserted into the femoral vein, and each drug was infused according to the protocol. The trachea was intubated, and the rats were ventilated mechanically (tidal volume: 8 ml/kg, respiratory rate: 80 strokes/min) with ambient air using a volume-controlled rodent ventilator (Harvard Rodent Ventilator Model 607, Harvard, Holliston, MA, USA). The arterial blood pH and gases were maintained within normal physiological limits (pH: 7.3-7.4, PaCO₂: 30-40 mmHg, PaO₂: 60-100 mmHg).

A paramedian sternotomy was performed, and the pericardium was opened to expose the heart. For the I/R experiments, a 4-0 black silk, nonabsorbable suture was passed around the left coronary artery (LCA) territory to induce regional myocardial ischemia. The coronary artery was occluded by pulling a snare through a small vinyl chloride tube and clamping it with a mosquito hemostat. Reperfusion was achieved by releasing the clamp. Myocardial ischemia was confirmed by the appearance of regional epicardial cyanosis over the myocardial surface and by arrhythmia. After 25 min of ischemia, the myocardium was reperfused by loosening the snare, which was maintained for 48 h of reperfusion. Successful reperfusion was confirmed by the disappearance of epicardial cyanosis and the production of epicardial hyperemia and arrhythmia after releasing the snare. The body temperature was monitored with a rectal thermometer and maintained at 36-38℃ using a heating pad.

Sixty-four rats were divided randomly into four groups. The sham group received a bolus infusion of 2.5 mg/kg of profopol (Fresofol® 2%, Fresenius Kabi, Homburg, Germany) followed by a continuous propofol infusion at a rate of 200 µg/kg/min, which was maintained until 30 min after the sham operation. The LCA was not occluded. The control group received 0.3 ml of normal saline intravenously followed by a continuous infusion of normal saline at a rate of 1.5 ml/h. The propofol group received a bolus infusion of 2.5 mg/kg of profopol followed by a continuous propofol infusion at a rate of 200 µg/kg/min. The intralipid group received a bolus infusion of 0.3 ml of 2% intralipid (20% Intralipid®, Fresenius Kabi, Sweden) followed by a continuous infusion of 2% intralipid at a rate of 1.5 ml/h. A 25 min LCA occlusion was produced followed by 48 h of reperfusion. Each drug was administered intravenously 5 min before the ischemic insult, and continuous drug infusion was maintained until 5 min after reperfusion.

An additional experiment was performed when a rat died during an experiment or during the postexperimental care period. An additional experiment was required for five, zero, six, and four rats in the control, sham, propofol, and intralipid groups, respectively. Two and four rats in the control and intralipid groups, respectively, required additional anesthesia. The hemodynamic function and infarct weight were checked in 10 rats of each group. The cardiac troponin-1 (cTn-I) level was also checked in six rats from each group.

After the 48 h reperfusion, the rats were anesthetized with 25 mg/kg of ketamine and 1.5 mg/kg of xylazine. The right common carotid artery was cannulated with a 2-Fr Millar catheter (Model SPR-407, Millar Instruments Inc., Houston, TX, USA) and advanced into the left ventricle (LV) to measure heart rate (HR), left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), the peak rate of intraventricular pressure increase (+dP/dt_max), and the peak rate of intraventricular pressure decrease (-dP/dt_max). The systolic and diastolic pressures were checked after repositioning the catheter to the ascending aorta.

After analyzing hemodynamic function, the LCA was occluded again, and 1 ml of 2% Evans blue dye was injected into the pulmonary artery to determine the areas at risk (AAR). The perfused myocardium was stained with Evans blue dye, whereas the occluded vascular bed was not. The atrium, right ventricle, and major vessels were removed from the heart, and the AAR was separated from the non-ischemic area. The AAR was cut into small pieces and incubated in 0.5% 2,3,5-triphenyltetrazolium chloride (TTC) at 37℃ for 15 min. The non-infarcted myocardium was stained a deep red color with TTC, and the infarcted area (IA) remained a pale yellow. The sections were fixed for 24 h in 2% formalin, and the LV, AAR, and IA weights were determined. The AAR and IA were expressed as a percentage of the LV and AAR weights, respectively.

Twenty-four rats were assigned to the four groups to measure cTn-I levels. The thoracic cavity was opened to expose the heart and collect a 2 ml blood sample from the right ventricle. The serum was collected and stored at -75℃ until analysis. The serum cTn-I level was determined using an enzyme linked immunosorbent assay kit from Life Diagnostics (cat. no. 2010-2-HS, West Chester, PA, USA). The cTn-I activity was detected by spectrophotometry (Infinite® F200, Tecan Group Ltd., Mönnedorf, Switzerland) at 460 nm after reacting the serum sample on a cTn-I antibody-coated plate.

All values are expressed as the mean ± SD. All statistical analyses were performed using SPSS software (ver. 12.0 for Windows, SPSS Inc., Chicago, IL, USA). The differences between groups were evaluated using a Friedman one-way analysis of variance and a post hoc Tukey's multiple comparison test. Statistical significance was defined as P < 0.05.

The hemodynamic measurements recorded after 48 h of reperfusion revealed LV dysfunction, as demonstrated by the increased LVEDP (P = 0.01) and decreased LVSP (P = 0.01), +dP/dt_max (P = 0.0001), and -dP/dt_max (P = 0.0001) in the control group compared to the sham group. Propofol significantly inhibited the decrease in +dP/dt_max compared to the control group (P = 0.002) and intralipid group (P = 0.01) (Table 1).

No significant differences between the three groups were observed in the AAR/LV induced by occluding the LCA territory. The IA weights in the control, propofol, and intralipid groups were 0.12 g, 0.08 g (P = 0.031 vs. control group), and 0.09 g, respectively. The IA/AAR in the control, propofol, and intralipid groups was 49.8%, 32.6% (P = 0.014 vs. control group), and 33.4% (P = 0.045 vs. control group), respectively. No significant differences in IA weight and IA/AAR were found between the propofol and intralipid groups (Table 2).

The serum cTn-I levels in the sham, control, propofol, and intralipid groups were 0.087 ng/ml, 12.2 ng/ml (P = 0.0001 vs. sham group), 6.7 ng/ml (P = 0.0001 vs. sham group, P = 0.0001 vs. control group), and 10.4 ng/ml (P = 0.0001 vs. sham group, P = 0.005 vs. intralipid group), respectively (Fig. 1). The I/R-induced serum cTn-I level was reduced by propofol infusion during the peri-ischemic period.