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The Effects Of Fentanyl, Remifentanil On Myocardial Infarct Size And Mechanical Function Induced By Acute Myocardial Ischemia Reperfusion Injury In Rabbits

Posted on:2005-09-26Degree:MasterType:Thesis
Country:ChinaCandidate:X M ZhengFull Text:PDF
GTID:2144360125957616Subject:Anesthesia
Abstract/Summary:PDF Full Text Request
Objective: Single or mutiple brief episodes of sublethal cardiac ischemia-reperfusion produce a marked protection against subsequent prolonged ischemia.This phenomenon, which is termed ischemic preconditioning (IPC) , is one of the most powerful measures of minimizing myocardial damage in cytoprotection research (30%-90% reduction in infarct size) . Preconditioning can also be elicited by non-ischemia means, such as hypoxia and * drugs. Pharmacological preconditioning, compared with ischemia, may be a better choice to obtain cardialprotection, especially for the diseased and aged patients.Previous studies show that opiods, acting as triggar, can not only initiate thecardial protection of IPC, but also micmic the effectiveness of IPC. Fentanyl family are used widely in clinical practice, including the Alfentanil, Sulfentanil etc. The new synthetic Remifentanil, characterized by rapid onset, short duration of action, offers more stable and convenient anesthesia plat, especially in fast-track cardiac anesthesia, and will be expected to have broad prospects in future. Because the potential as cardioprotectors of fentanyl family is currently unknown, the aim of the present study was to investigate whether fentanyl and remifentanil, opioid receptor agonists, can protect the heart against myocardial ischemia-reperfusion injury, and if the protective effect of fentanyl can be abolished by naloxone. Also, we tried todetermine the possible mechanism involved in the beneficial effect of fentanyl. All work above may be of importance with respect to experimental as well as clinical medicine.Methods: 32 New Zealand White rabbits of either sex, were anesthetized with ketamine and ventilated with 100% oxygen via a positive pressure respirator . The respiratory rate and tidle volume were adijusted to keep the arterial blood pH in thephysiological range. The heart was exposed after the thorax was opened in the left 4intercostals space followed by pericardiotomy. Then, the rabbits were divided randomly into four groups (n=8 each) . All rabbits experienced 30 min of regional ischemia via the occlusion of the left anterior descending coronary artery (LAD) , followed by 120 min of reperfusion. The first group (control group) of rabbits was subjected only to the above ischemia/reperfusion sequence. Group F: iv fentanyl at dose of 0. 15mg-1 Kg-1, 10 min before the coronary occlusion. Group N-F: iv naloxone (3mg kg-1 ) followed by a 70 g-Kg-1 -min-1 infusion before feperfusion ,5 min before iv fentanyl as in Group F. Group REM: iv remifentanil (2.5 u g-Kg"1) , 10min before the coronary occlusion, followed by a continous infusion (1.6n g-Kg-1 min-1) throughout the- experiment. Under the monitering of hemodynamics, Measurements included HR, MAP, left ventricular systolic pressure (LVSP) , left ventricular end diastolic pressure (LVEDP) , left ventricular developed pressure (LVDP), maxium positive and minimum negative left ventricular pressure derivatives ( +dp/dt and -dp/dt ) and plasma malondialdehyde ( MDA ) , were obtained at baseline (To) , before ischemia (T0-1) , 30 min after ischemia (T1) , and 10 min (T2) , 30 min (T3) , 60niin (T4) , 120min (Ts) after reperfusion. At the end of the present experiment, the coronary artery was reoccluded and the 2% Evans blue was infused into the heart to determine the myocardial risk zone. Then the left ventricle was excised, weighed, frozen and cut into 2-mm slices which were incubated in 1% 2,3,5-triplenyltetrazolium chloride (TTC) to differentiate infarct size and risk zone. Infarct size was expressed as a percentage of the risk zone. The data were expressed as mean SEM( x s ). ANVOA ( repeated measures on a timefactor) was used to compare differences in indices at various time between groups and within groups. Statistical significance was assumed at P<0.05.Results:1 .General dataAll anaimals surived throughout the experiment. There were no significant differences in sex, weight etc.2. Changes in hemodynamicsThere were no significant differences in hemodynamic.
Keywords/Search Tags:myocardium, ischemia-reperfusion injury, fentanyl, remifentanil, preconditioning, cardiac function, ROS, rabbit
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