Acute Myocardial Infarction In Rabbits Research Articles

Development of a new model for acute myocardial infarction in rabbits.

The rabbit left anterior descending coronary artery is not macroscopically apparent; this often leads to failure in creation of an acute myocardial infarction (AMI) model. In order to devise a simple method with good reproducibility and high success rate for use as a rabbit AMI model, a new surgical technique was developed, in which the obtuse marginal (OM) branch of the left circumflex coronary artery was coagulated with an electric knife using a left parasternal approach. Four weeks after OM branch coagulation, an electrocardiogram (ECG), blood biochemistry analysis, echocardiographic measurements and pathologic analysis were performed. The left parasternal approach provided the surgeon clear visualization of the targeted blood vessel to accurately identify the proper site to occlude. The successful development of AMI was confirmed by ST segment elevation on the ECG, by high levels of AMI-related markers in blood samples, by cardiac functional damage reflected on echocardiographic images and by changes in pathological sections. Furthermore, an acceptable success rate and low mortality were achieved. Hence, this surgical technique was suggested to be a highly reliable and reproducible method to induce AMI in rabbits for the assessment of new therapeutic interventions or regenerative approaches.

Reduced Apoptosis After Acute Myocardial Infarction by Simvastatin

To observe the effect of simvastatin in patients with acute myocardial infarction in rabbits against myocardial apoptosis, and to explore its possible mechanism. Male New Zealand white rabbits were randomized into three groups, including the myocardial infarction group (12 rabbits), the simvastatin treatment group (15 rabbits), and the sham group (12 rabbits). In the simvastatin treatment and myocardial infarction groups, the rabbits received myocardial infarction surgeries. While in the sham group, loose knots were tied in the left anterior descending coronary artery branches. The simvastatin treatment group was given simvastatin by oral gavage 24h after surgery. Parameters, which included left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left ventricular ejection fraction, and left ventricular mass index, were recorded in these three groups. Edge myocardial infarction and myocardial cell apoptosis were analyzed using TUNEL assay, and Bcl-2, Bax, and Caspase-3 protein levels were detected by Western blot. Acute myocardial infarction model was successfully established in rabbits by ligation of the left anterior descending coronary artery. Compared with the myocardial infarction group, left ventricular end-diastolic diameter (LVEDD) and left ventricular end systolic diameter (LVESD) were significantly reduced and left ventricular ejection fraction (LVEF) increased in the simvastatin treatment group. Compared with the sham group, LVEDD and LVESD were significantly increased and LVEF decreased in the simvastatin treatment group. All the differences were statistically significant (P<0.05). Left ventricular mass index in the simvastatin treatment group was statistically lower than the myocardial infarction group. Compared with the sham group, left ventricular mass index in both the simvastatin treatment and myocardial infarction groups was significantly increased. The differences of the above comparisons were statistically significant (P<0.05). Compared with the sham group, the apoptosis rate of the myocardial infarction group and the simvastatin treatment groups was significantly increased as shown by TUNEL assay, however, the apoptosis rate of the simvastatin treatment group was significantly lower than that of the myocardial infarction group. All the differences among above comparisons were statistically significant (P<0.05). Bcl-2 levels significantly increased in the simvastatin treatment group compared with the myocardial infarction group, but Bcl-2 levels in both groups were significantly lower than the sham group. However, Bax protein levels showed inverse expression with Bcl-2. Meanwhile, Caspase-3 protein expression showed similar trend with Bcl-2. Simvastatin can improve cardiac function after myocardial infarction and reduce apoptosis of myocardial cells, possibly by decreasing Bax and Caspase-3 expression and increasing the expression level of Bcl-2.

Non-invasive detection and quantification of acute myocardial infarction in rabbits using mono-[123I]iodohypericin SPECT

Mono-[(123)I]iodohypericin ([(123)I]MIH) has been reported to have high avidity for necrosis. In the present study, by using rabbit models of acute myocardial infarction, we explored the suitability of [(123)I]MIH micro single photon emission computed tomography (microSPECT) for non-invasive visualization of myocardial infarcts in comparison with [(13)N]ammonia micro positron emission tomography (microPET) imaging, postmortem histomorphometry, and [(123)I]MIH autoradiography. Fourteen rabbits were divided into four groups. The left circumflex coronary artery was permanently occluded in group A (n = 3), reperfused by releasing the ligature after 15 min in group B (n = 3) or 90 min in group C (n = 6), or not occluded in group D (n = 2). Animals received [(13)N]ammonia microPET perfusion imaging 18 h after infarct induction followed by microSPECT imaging at 2-3.5, 9-11, and 22-24 h post injection (p.i.) of [(123)I]MIH. The cardiac images were assembled into polar maps for assessment of tracer uptake. Animals were sacrificed and the excised heart was sliced for autoradiography, triphenyl tetrazolium chloride, and haematoxylin-eosin staining. Using [(123)I]MIH microSPECT, infarcts were well delineated at 9 h p.i. Mean microSPECT infarct size was 38.8 and 32.7% of left ventricular area for groups A and C, respectively, whereas group B showed low uptake of [(123)I]MIH. Highest mean infarct/viable tissue activity ratio of 61/1 was obtained by autoradiography in group C animals at 24 h p.i. The study indicates the suitability of [(123)I]MIH for in vivo visualization of myocardial infarcts.

Effects of angiotensin-( 1-7 ) on serum nitric oxide and myocardial microvascular integrity after reperfused acute myocardial infarction in rabbits

目的 探讨血管紧张素(1-7)[Ang-(1-7)]对急性心肌梗死再灌注血清一氧化氮(NO)水平及心肌微血管完整性的影响.方法 新西兰雄性大白兔30只,随机分成以下3组:假手术组、缺血再灌注(I-R)对照组和Ang-(1-7)治疗组,每组10只.Ang-(1-7)治疗组经置入式微量泵持续颈静脉给予Ang-(1-7)(25 μg·kg-1·h-1)3 d.假手术组和I-R对照组经微量泵只给予等量的生理盐水.每组均在3 d预处理后,冠状动脉左前降支结扎2 h,再灌注2 h.测定缺血前、后和再灌注2 h时血清NO含量及光镜下心肌灶性出血发生率的变化,并采用氯化三苯四唑(TTC)染色观察心肌梗死范围.结果 心肌缺血前Ang-(1-7)治疗组NO已显著升高(P＜0.01);心肌缺血后2 h时,各组NO均比缺血前显著降低(P＜0.01),但Ang-(1-7)治疗组比I-R对照组显著增高(P＜0.01);再灌注2 h后,各组NO均比缺血2 h时进一步降低,但Ang-(1-7)治疗组仍比I-R对照组显著增高(P＜0.01).心肌灶性出血发生率在I-R对照组为65.00%,而Ang-(1-7)治疗组为27.50%(P＜0.01).心肌梗死面积在I-R对照组为(28.70±5.45)%,而Ang-(1-7)治疗组为(15.46±4.32)%(P＜0.01).结论 静脉持续给予Ang-(1-7)能提高急性心肌梗死再灌注时血清NO水平,可保护心肌微血管的完整性。

Occlusive Acute Myocardial Infarct on 16 Multidetector-row Helical CT: An Experimental Study in Rabbits

Purpose: We wanted to evaluate the findings and diagnostic accuracy of MDCT for diagnosing occlusive acute myocardial infarction in rabbits. Materials and Methods: Myocardial infarction was induced in 14 rabbits. MDCT was performed in the early and delay phases at 1 minute and 6 minutes, respectively, after intravenous contrast injection. The rabbits were sacrificed after scanning. The cardiac specimens were sliced and then stained with triphenyltetrazolium chloride (TTC). The agreement in the transmural extent of infarction between the MDCT scans and the TTCstained specimens were analyzed by using kappa values. Results: Acute myocardial infarction was found in 9 of 14 rabbits on the TTC-stained specimens and MDCT. The infarcted myocardium was demonstrated as a low-attenuation area on the early phase and as a central low-attenuation area with rim-like enhancement along the endocardial and pericardial sides of the myocardial wall on the delay phase. There was excellent agreement in the scores of the transmural extent of myocardial infarction between the TTC-stained specimens and the early phase scan (kappa value = 0.882, p = 0.000), and there was fair to good agreement between the TTC-stained specimens and the delay phase scan (kappa value = 0.439, p = 0.000). Microscopic examination of the cardiac specimens revealed necrosis of myocardial cells in the central portion and granulation tissue along the endocardial and pericardial sides of the necrotic myocardium. Conclusion: 16 slice MDCT scan was useful for the diagnosis of acute myocardial infarction. The early phase scan was more accurate than the delay phase scan for evaluating the transmural extent of myocardial infarction. Histopathologic examination suggested that the low-attenuation area on the delay phase might correspond to necrotic myocardium and the enhanced area might correspond to granulation tissue.

The effect of basic fibroblast growth factor on acute myocardial infarction in rabbits

The effect of basic fibroblast growth factor on acute myocardial infarction in rabbits

Failure of AICA Riboside to Limit Infarct Size During Acute Myocardial Infarction in Rabbits

This study examined whether the adenosine potentiator, 5-aminoimidazole-4-carboxamide riboside (AICAr), could limit tissue necrosis during acute myocardial infarction in rabbit hearts with minimal coronary collateral flow. Forty-four rabbits underwent 45 min of ischemia with or without coronary reperfusion for 180 min. Five groups were studied. Saline or AICAr (20 mg/kg, i.v.) was administered as a bolus either 10 min before coronary occlusion or 10 min before the onset of coronary reperfusion. The anatomic risk zone size was assessed by radiolabeled microsphere autoradiography and the area of tissue necrosis was defined using the tetrazolium staining method. Coronary collateral flow in the central ischemic zone was assessed using the radiolabeled microsphere technique. No differences were observed for tissue necrosis (normalized to risk zone size) for saline- and AICAr-treated rabbits (66.2 +/- 10.9% vs. 70.8 +/- 19.9%, p = NS) subjected to 45 min of coronary occlusion without reperfusion. Similarly, tissue necrosis in rabbit hearts with 45 min of coronary occlusion followed by 180 min of reperfusion was not significantly reduced when AICAr was administered either 10 min before ischemia or 10 min before reperfusion (79.8 +/- 17.5 and 76.4 +/- 8.1%, respectively) compared to saline-treated controls (68.1 +/- 22.7%). Coronary collateral flow in these hearts was almost nonexistent. The risk zone size and cardiac hemodynamics were similar between the treatment groups. These results demonstrate that AICAr was unable to limit myocyte necrosis when administered either before ischemia or before coronary reperfusion in this experimental preparation of acute myocardial infarction.

Inability of dimethylthiourea to limit tissue necrosis during acute myocardial infarction in rabbits

This study examined the effect of treatment of with dimethylthiourea (DMTU), a highly cell-permeable scavenger of hydroxyl radicals, on tissue necrosis in rabbit hearts during myocardial ischemia and reperfusion. Sixty-two rabbits underwent 45 minutes of coronary occlusion with, or without, coronary reperfusion for 3 hours. A saline vehicle, or DMTU (500 mg.kg intravenously [iv]) was administered over 45 minutes starting either 10 minutes before or 10 minutes after coronary occlusion, or 10 minutes before coronary reperfusion. Anatomic risk zone size was assessed using microsphere autoradiography, and the area of necrosis was determined using tetrazolium staining. Cardiac hemodynamics and risk zone sie were similar for all treatment groups. No differences were observed in the extent of tissue necrosis (normalized to risk zone size) for saline- and DMTU-treated rabbits subjected to 45 minutes (61.2 ± 23.1% vs. 70.6 ± 16.5%) or 225 minutes (82.8 ± 5.4% vs. 78.3 ± 5.9%) of permanent coronary occlusion without reperfusion. Similarly, tissue necrosis in rabbits with 45 minutes coronary occlusion followed by 3 hours reperfusion was not significantly reduced when DMTU was administered either 10 minutes before coronary occlusion, 10 minutes after coronary occlusion, or 10 minutes before coronary reperfusion (67.0 ± 9.9%; 57.6 ± 10.6%; 68.3 ± 13.3%) compared to saline-treated controls (76.6 ± 10.5%). These results demonstrate that the hydroxyl radical scavenger DMTU does not appear to influence the progression of myocyte injury in this experimental model of acute myocardial infarction. These findings suggest that oxygen-derived free radical species may not play as important a role in myocyte injury as originally assumed, or that hydroxyl radical scavengers, such as DMTU, do not influence tissue necrosis in this model of myocardial injury.

The effects of trapidil and propranolol on platelet aggregation and prostacyclin-thromboxane balance following acute myocardial infarction in rabbits.

Changes in infarct size, platelet aggregation, and plasma 6-k-PGF1 α and thromboxane B2 levels in the coronary sinus and arterial blood were observed in rabbits following acute myocardial infarction with or without trapidil or propranolol treatment. It was found that platelet aggregation, thromboxane B2 and 6-k-PGF1 α were elevated significantly in the control group 6 h after coronary ligation. These changes were inhibited by trapidil as well as propranolol, either of which could limit infarct size remarkably.