Ciulla, M.M. et al. Left ventricular remodeling after experimental myocardial cryoinjury in rats. J. Surg. Res. 116, 91-97

University of Milan, Milano, Lombardy, Italy
Journal of Surgical Research (Impact Factor: 1.94). 02/2004; 116(1):91-7. DOI: 10.1016/j.jss.2003.08.238
Source: PubMed


The standard coronary ligation, the most studied model of experimental myocardial infarction in rats, is limited by high mortality and produces unpredictable areas of necrosis. To standardize the location and size of the infarct and to elucidate the mechanisms of myocardial remodeling and its progression to heart failure, we studied the functional, structural, and ultrastructural changes of myocardial infarction produced by experimental myocardial cryoinjury. The cryoinjury was successful in 24 (80%) of 30 male adult CD rats. A subepicardial infarct was documented on echocardiograms, with an average size of about 21%. Macroscopic examination reflected closely the stamp of the instrument used, without transition zones to viable myocardium. Histological examination, during the acute setting, revealed an extensive area of coagulation necrosis and hemorrhage in the subepicardium. An inflammatory infiltrate was evident since the 7th hour, whereas the reparative phase started within the first week, with proliferation of fibroblasts, endothelial cells, and myocytes. From the 7th day, deposition of collagen fibers was reported with a reparative scar completed at the 30th day. Ultrastructural study revealed vascular capillary damage and irreversible alterations of the myocytes in the acute setting and confirmed the histological findings of the later phases. The damage was associated with a progressive left ventricular (LV) remodeling, including thinning of the infarcted area, hypertrophy of the noninfarcted myocardium, and significant LV dilation. This process started from the 60th day and progressed over the subsequent 120 days period; at 180 days, a significant increase in LV filling pressure, indicative of heart failure, was found. In conclusion, myocardial cryodamage, although different in respect to ischemic damage, causes a standardized injury reproducing the cellular patterns of coagulation necrosis, early microvascular reperfusion, hemorrhage, inflammation, reparation, and scarring observed in myocardial infarction with a late evolution toward heart failure. This model is therefore suitable to study myocardial repair after injury.

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    • "Cardiac cryolesion of the adult heart was first described in 1948 using dogs as the experimental model (Hass and Taylor, 1948). Similar methods have been described and applied to adult organisms from other species (Chablais et al., 2011; Ciulla et al., 2004; González-Rosa and Mercader, 2012; Van Amerongen et al., 2008). Cryolesions, however, have never been used to study vertebrate embryonic development. "
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    ABSTRACT: Tissue ablation is a classic experimental approach to study early embryo patterning. However, ablation methods are less frequently used to assess the reparative or regenerative properties of embryonic tissues during organogenesis. Surgical procedures based on the removal of a significant amount of tissue during organ formation very much depend on the skills of the researcher, are difficult to reproduce, and often result in extensive tissue disruption leading to embryonic death. In this paper, we present a new protocol to generate discrete, locally-restricted and highly reproducible wounds in the developing chick embryo using a liquid N2-cooled metallic probe. This in ovo procedure allows for the study of organ-specific tissue responses to damage, such as compensatory cell growth, cell differentiation, and reparative/regenerative mechanisms throughout the embryonic lifespan.
    Full-text · Article · Nov 2015 · Differentiation
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    • "From a historical perspective, except from LAD ligation with plain sutures [3,4,11], which has been the standard surgical technique of EMI ever since 1881 [12], there are also open-chest techniques where coronary blood flow restriction may be established by circumferential placement of an ameroid constrictor [13], a non-elastic Dacron stripe [14] or compression by an arterial puncture needle [15]. Moreover, induction of coronary artery occlusion by cryoinfarction [16] or electrolytic coronary injury and thrombosis [17] has been reported. Researchers have also established closed-chest techniques of EMI with the application of various different embolic materials like plugs [18], balloons [19], coils [20], beads [21], microspheres [22], or even gelatine sponges [23]. "
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    ABSTRACT: To date, most animal studies of myocardial ischemia have used open-chest models with direct surgical coronary artery ligation. We aimed to develop a novel, percutaneous, minimally-invasive, closed-chest model of experimental myocardial infarction (EMI) in the New Zealand White rabbit and compare it with the standard open-chest surgical model in order to minimize local and systemic side-effects of major surgery. New Zealand White rabbits were handled in conformity with the "Guide for the Care and Use of Laboratory Animals" and underwent EMI under intravenous anesthesia. Group A underwent EMI with an open-chest method involving surgical tracheostomy, a mini median sternotomy incision and left anterior descending (LAD) coronary artery ligation with a plain suture, whereas Group B underwent EMI with a closed-chest method involving fluoroscopy-guided percutaneous transauricular intra-arterial access, superselective LAD catheterization and distal coronary embolization with a micro-coil. Electrocardiography (ECG), cardiac enzymes and transcatheter left ventricular end-diastolic pressure (LVEDP) measurements were recorded. Surviving animals were euthanized after 4 weeks and the hearts were harvested for Hematoxylin-eosin and Masson-trichrome staining. In total, 38 subjects underwent EMI with a surgical (n = 17) or endovascular (n = 21) approach. ST-segment elevation (1.90 ± 0.71 mm) occurred sharply after surgical LAD ligation compared to progressive ST elevation (2.01 ± 0.84 mm;p = 0.68) within 15-20 min after LAD micro-coil embolization. Increase of troponin and other cardiac enzymes, abnormal ischemic Q waves and LVEDP changes were recorded in both groups without any significant differences (p > 0.05). Infarct area was similar in both models (0.86 ± 0.35 cm in the surgical group vs. 0.92 ± 0.54 cm in the percutaneous group;p = 0.68). The proposed model of transauricular coronary coil embolization avoids thoracotomy and major surgery and may be an equally reliable and reproducible platform for the experimental study of myocardial ischemia.
    Full-text · Article · Feb 2012 · Journal of Cardiothoracic Surgery
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    • "Indeed, it has been proven that this method is a valuable alternative to coronary occlusion-based methods when small animals were used such as mice [18] and [19], rats [20] and [21] and rabbits [22] and [23] because of the size and deeper location of their major coronary arteries. In larger animals, cryoinjury eliminates influence of variable extent of innate collateral coronary branches (e.g., in dogs) [6] which is a major determinant of ischemia and scar size in the occlusion models [7]. "
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    ABSTRACT: To investigate progression of cryoinjury in pigs using contrast-enhanced magnetic resonance imaging (MRI) as well as optical spectroscopy and imaging. Cryoinjury was produced in 16 pigs in vivo and investigated using Gd-and Mn-enhanced MRI, optical imaging/spectroscopy and histology in acute and chronic setting up to 4 weeks after the injury. (1) Acute cryoinjury resulted in formation of a lesion with a severely reduced rate of sub-epicardial indocyanine green (intravascular optical flow tracer) passage. In vivo late Gd-enhanced MRI showed a approximately 10 mm deep hypointense area that was surrounded by a hyperintense rim while ex vivo Mn-enhanced MRI (MEMRI) detected a homogenous hypointense zone. Histological and spectroscopic examination revealed embolic erythrocytes blockages within the cryolesion with a thin necrotic rim neighboring the normal myocardium. (2) Chronic 4-week cryoinjury was characterized by uniform Gd-enhancement, whereas MEMRI revealed reduced Mn(2+)enhancement. Histological examination showed replacement of the cryoinjured myocardium by scar tissue. Acute cryoinjury resulted in formation of a no-reflow core embolized by erythrocytes and surrounded by a rim of necrotic tissue. Upon injury progression, the no-reflow zone shrunk and was completely replaced with scar tissue by 4 weeks after injury.
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