enalaprilat-anhydrous and Burns

Autophagy plays a major role in myocardial ischemia and hypoxia injury. The present study investigated the effects of autophagy on cardiac dysfunction in rats after severe burn.. Protein expression of the autophagy markers LC3 and Beclin 1 were determined at 0, 1, 3, 6, and 12 h post-burn in Sprague Dawley rats subjected to 30% total body surface area 3rd degree burns. Autophagic, apoptotic, and oncotic cell death were evaluated in the myocardium at each time point by immunofluorescence. Changes of cardiac function were measured in a Langendorff model of isolated heart at 6 h post-burn, and the autophagic response was measured following activation by Rapamycin and inhibition by 3-methyladenine (3-MA). The angiotensin converting enzyme inhibitor enalaprilat, the angiotensin receptor I blocker losartan, and the reactive oxygen species inhibitor diphenylene iodonium (DPI) were also applied to the ex vivo heart model to examine the roles of these factors in post-burn cardiac function.. Autophagic cell death was first observed in the myocardium at 3 h post-burn, occurring in 0.008 ± 0.001% of total cardiomyocytes, and continued to increase to a level of 0.022 ± 0.005% by 12 h post-burn. No autophagic cell death was observed in control hearts. Compared with apoptosis, autophagic cell death occurred earlier and in larger quantities. Rapamycin enhanced autophagy and decreased cardiac function in isolated hearts 6 h post-burn, while 3-MA exerted the opposite response. Enalaprilat, losartan, and DPI all inhibited autophagy and enhanced heart function.. Myocardial autophagy is enhanced in severe burns and autophagic cell death occurred early at 3 h post-burn, which may contribute to post-burn cardiac dysfunction. Angiotensin II and reactive oxygen species may play important roles in this process by regulating cell signaling transduction.

Topics: Animals; Apoptosis; Apoptosis Regulatory Proteins; Autophagy; Beclin-1; Biomarkers; Biphenyl Compounds; Burns; Enalaprilat; Fluorescent Antibody Technique; Heart Function Tests; In Vitro Techniques; Losartan; Male; Microtubule-Associated Proteins; Myocardium; Onium Compounds; Rats; Rats, Sprague-Dawley

Topics: Animals; Burns; Disease Models, Animal; Enalaprilat; Humans; Hypoxia; Mitogen-Activated Protein Kinases; Nitric Oxide Synthase; Protoporphyrins; Sepsis; Shock

To investigate effects of angiotensin (1-7) [Ang (1-7)] and enalaprilat on function of isolated rat heart perfused by burn serum.. Eighty SD rats were used to prepare burn serum. Hearts of another 24 SD rats were isolated to reproduce Langendorff perfusion model. The rat hearts were divided into different groups with different perfusion fluids as K-H buffer group, K-H buffer containing 20% burn serum group (burn serum group), K-H buffer containing 20% burn serum and 2 microg/mL enalaprilat group (enalaprilat group), and K-H buffer containing 20% burn serum and 1 nmol/mL Ang (1-7) group [Ang(1-7) group]. The rat hearts were perfused for 30 mins with each of above-mentioned fluids in different groups. Then left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), +/- dp/dt max, coronary flow(CF), level of creatine kinase (CK) and lactate dehydrogenase (LDH) in respective coronary effluent were determined.. Compared with LVSP (11.2 +/- 1.0 kPa, 1 kPa = 7.5 mm Hg), +dp/dt max (642 +/- 53 kPa/s), -dp/dt max (380 +/- 61 kPa/s) and CF level in K-H buffer group, CF, LVSP (5.9 +/- 0.8, 8.0 +/- 1.1, 8.9 +/- 1.3 kPa, respectively), +dp/dt max (275 +/- 37, 454 +/- 48, 479 +/- 63 kPa/s, respectively), -dp/dt max (135 +/- 35, 219 +/- 47, 277 +/- 58 kPa/s, respectively) of burn serum group, those levels in Ang (1-7) group, and enalaprilat group were decreased obviously (P < 0.05 or P < 0.01), but LVEDP, level of CK and LDH in coronary effluent were increased. Compared with those parameters in burn serum group, CF, LVSP, +/- dp/dt max of Ang (1-7) group and enalaprilat group were increased obviously (P < 0.05 or P < 0.01), and LVEDP, level of CK and LDH in coronary effluent were decreased obviously (P < 0.01).. Ang (1-7) and enalaprilat can effectively improve left ventricular function of isolated rat heart perfused by burn serum and mitigate myocardial injury.

Topics: Angiotensin I; Animals; Burns; Enalaprilat; Male; Myocardial Reperfusion Injury; Peptide Fragments; Rats; Rats, Sprague-Dawley; Serum; Ventricular Function, Left

To investigate the therapeutic effects of Enalaprilat on the myocardial kinetics in rats at early stage of severe scald.. Eighty-four SD rats were inflicted with 30% TBSA full-thickness scald, and randomly divided into scald (S, with intraperitoneal injection of isotonic saline according to Parkland formula, n=30), L (n=30), M (n=12) and H (n=12) groups. The rats in L,M,H groups were intraperitoneally injected with 1,2,4 mg/kg Enalaprilat. Other 6 healthy rats were enrolled into study as control (C group). The myocardial kinetic parameters including left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), +/- dp/dt max and the levels of A II in myocardium were observed at 1,3,6,12 and 24 post scald hour (PBH) in L and S groups,and at 6,12 PBH in M and H groups. The above indices in C group were also examined.. The levels of LVSP, LVEDP, +/- dp/dt max in C group were higher than those in other groups during 3-24 PBH (P < 0.05 or P < 0.01), while those in L,M,H groups were obviously higher than those in S group (P < 0.05 or P < 0.01). The level of +/- dp/dt max in H group at 6,12 PBH were obviously lower than those in L and M groups. The level of A II in S group at 1 PBH was (53.0 +/- 2.6) pg/200 mg, which was significantly higher than thatin C group [(14.8 +/- 0.7) pg/200 mg, P < 0.05 or P < 0.01]; it peaked at6 PBH and lowered afterwards, and they were significantly higher than that in C group at 24 PBH (P < 0.01). The levels of A II in L group during 3-24 PBH were obviously higher than those in C group (P < 0.01), which were also lower than those in S group. The level of A II in S group was significantly higher than in L,M,H groups at 6 PBH [(145.2 +/- 14.5) pg/200 mg. vs. (65.1 +/- 0.9) pg/200 mg, (53.6 +/- 1.1) pg/200 mg, (34.2 +/- 0.9) pg/200 mg, respectively, P < 0.01].. Myocardium can be obviously damaged at early stage after severe scald,cardiac function is impaired. Enalaprilat injection (especially at low dose) can significantly ameliorate the myocardial kinetics indices, and it seems to exert a protective effect on cardiac function.

Topics: Animals; Burns; Dose-Response Relationship, Drug; Enalaprilat; Myocardium; Rats; Rats, Sprague-Dawley; Ventricular Remodeling

To investigate the dose-effect relationship of enalaprilat (ENA) injection on the organ damage following early burn injury in rats.. A total of 54 SD rats were subjected to 30% total body surface area III scald injury, and were randomly divided into simple scald group (B group, with conventional fluid transfusion after scald), ENA treated group (E1, E2, E3 group, with intraperitoneal enalaprilat injection of 1, 2, 4 mg/kg after scald respectively). Other 6 rats were taken as normal control. Aortic systolic pressure (AOSP), aortic diastolic blood pressure (AODP), mean arterial pressure (MAP), angiotensin 1, blood urea nitrogen (Bun), creatinine (Cr), creatinine kinase (CK), alanine aminotransferase (ALT), aspartate aminotransferase (AST) of the simple scald group, E1 group, E2 group and E3 group were investigated at 6 h and 12 h post burn.. Ang II, Bun, Cr, CK, ALT, AST levels in ENA treated group after 6 h and 12 hours were significantly lower than those of simple scald group (all P < 0.05). AOSP, AODP, MAP in ENA treated group after 6 and 12 hours were significantly higher than those of simple scald group (all P < 0.05).. Low-dose enalaprilat, injection (1 mg/kg) could alleviate organ damage in post-burned rats, but has little effect on AOSP and AODP.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Burns; Disease Models, Animal; Dose-Response Relationship, Drug; Enalaprilat; Female; Male; Random Allocation; Rats; Rats, Sprague-Dawley; Viscera

To investigate the effects of single or combined administration of cedilanid and small-dose of enalaprilat on heart, liver, kidney and intestine damages at early stage of severe scald in rats.. Forty healthy male Wistar rats were enrolled in the study and randomly divided into: sham, burn control, cedilanid, enalaprilat, cedilanid + enalaprilat groups, with 8 rats in each group. Rats, except that of sham group (simulated scald with 37 degrees C water) were inflicted with 30% TBSA full-thickness scald, and were injected with Ringer's lactate solution (4 mLxkg(-1)x1% TBSA(-1)) intraperitoneally 30 minutes after burn. Then rats in cedilanid group were given cedilanid injection (0.2 mg/kg) intravenously, and those in enalaprilat group were given enalaprilat (1 mg/kg), and cedilanid + enalaprilat group with cedilanid and enalapril in the same dosage. At 6 post burn hour (PBH) or sham injury, parameters of myocardiac mechanics were recorded with the Multiple Channel Physiological Signal Collecting and Processing System. The blood flow of the liver, kidney and intestine was respectively detected with the Laser Doppler Flowmetry at 6 PBH. Serum contents of cTnI, TBA, beta2-MG and DAO were determined at 6 PBH to reflect visceral damages.. Compared with those in sham group, the parameters of myocardiac mechanics and blood flow of liver, kidney, intestine (158 +/- 32, 156 +/- 46, 119 +/- 30 PU, respectively) in burn control group were obviously decreased (P < 0.05), and the serum contents of cTnI, TBA, beta2-MG, DAO (5.0 +/- 0.3 microg/L, 82 +/- 23 micromol/L, 2.55 +/- 0.15 mg/L, 1.52 +/- 0.08 kU/L, respectively) in burn control group were obviously increased (P < 0.05). Compared with those in burn control group, the parameters of myocardiac mechanics and blood flow of liver, kidney, intestine in the cedilanid or enalaprilat groups increased markedly, and their serum contents of cTnI, TBA, beta2-MG, DAO decreased significantly (P < 0.05). Compared with those in burn control group, the parameters of myocardiac mechanics and blood flow of liver, kidney, intestine (240 +/- 49, 239 +/- 75, 194 +/- 55 PU, respectively) in cedilanid + enalaprilat group increased significantly (P < 0.05), and the serum contents of cTnI, TBA, beta2-MG, DAO (3.43 +/- 0.21 microg/L, 47 +/- 8 micromol/L, 2.01 +/- 0.16 mg/L, 1.17 +/- 0.15 kU/L, respectively) were decreased (P < 0.05).. Single administration of cedilanid or small-dose enalaprilat can ameliorate impairment of cardiac functions, prevent damages to liver, kidney and intestine in early stage of severe scald in rats. Combined administration of cedilanid and small-dose enalaprilat seems to be more effective.

Topics: Animals; Burns; Deslanoside; Disease Models, Animal; Drug Therapy, Combination; Enalaprilat; Male; Random Allocation; Rats; Rats, Wistar; Viscera