Closed-chest Models Research Articles

Open- vs. closed-chest pig models of donation after circulatory death

Open- vs. closed-chest pig models of donation after circulatory death

Novel Percutaneous Approach for Deployment of 3D Printed Coronary Stenosis Implants in Swine Models of Ischemic Heart Disease.

Minimally invasive methods for creating models of focal coronary narrowing in large animals are challenging. Rapid prototyping using three-dimensionally (3D) printed coronary implants can be employed to percutaneously create a focal coronary stenosis. However, reliable delivery of the implants can be difficult without the use of ancillary equipment. We describe the use of a mother-and-child coronary guide catheter for stabilization of the implant and for effective delivery of the 3D printed implant to any desired location along the length of the coronary vessel. The focal coronary narrowing was confirmed under coronary cineangiography and the functional significance of the coronary stenosis was assessed using gadolinium-enhanced first-pass cardiac perfusion MRI. We showed that reliable delivery of 3D printed coronary implants in swine models (n = 11) of ischemic heart disease can be achieved through repurposing mother-and-child coronary guide catheters. Our technique simplifies the percutaneous delivery of coronary implants to create closed-chest swine models of focal coronary artery stenosis and can be performed expeditiously, with a low procedural failure rate.

Altered hematological, biochemical and immunological parameters as predictive biomarkers of severity in experimental myocardial infarction

Preclinical studies in cardiovascular medicine are necessary to translate basic research to the clinic. The porcine model has been widely used to understand the biological mechanisms involved in cardiovascular disorders for which purpose different closed-chest models have been developed in the last years to mimic the pathophysiological events seen in human myocardial infarction.In this work, we studied hematological, biochemical and immunological parameters, as well as Magnetic resonance derived cardiac function measurements obtained from a swine myocardial infarction model. We identified some blood parameters which were significantly altered after myocardial infarction induction. More importantly, these parameters (gamma-glutamyl transferase, glutamic pyruvic transaminase, red blood cell counts, hemoglobin concentration, hematocrit, platelet count and plateletcrit) correlated positively with cardiac function, infarct size and/or cardiac enzymes (troponin I and creatine kinase-MB).Thus several blood-derived parameters have allowed us to predict the severity of myocardial infarction in a clinically relevant animal model. Therefore, here we provide a simple, affordable and reliable way that could prove useful in the follow up of myocardial infarction and in the evaluation of new therapeutic strategies in this animal model.

A critical appraisal of open- and closed-chest models of experimental myocardial ischemia

Myocardial ischemia is one of the most extensively studied topics in modern cardiovascular research. Early investigators first reported experimental myocardial ischemia (EMI) in 1862. The open-chest (surgical) approach is a well-developed model of EMI that enables researchers to directly access and observe the heart. With this approach, EMI is generally induced by surgical ligation of a coronary artery. A drawback of the open-chest model is the need for major surgery, which can result in local and systemic side effects. Alternative closed-chest models of EMI have been developed; most of these models involve endovascular catheterization with coronary artery embolization or thrombosis. Closed-chest techniques eliminate the need for invasive surgery, and the resultant model is more physiologically similar to clinical myocardial ischemia than is EMI produced by artery ligation. The authors present a review of open- and closed-chest models of EMI and discuss the advantages and disadvantages of each approach.

Ethanol Induction of Complete Heart Block in Swine

A method for the induction of complete heart block (CHB) by ethanol injection and its success rate in a pig model of acute right ventricular failure is reported. Additionally, a review of the literature for the induction of CHB in laboratory animals is detailed. The literature review was undertaken to both compare our rate of success with other methods and provide insight into our technique and refine its implementation. Animal models of CHB have facilitated the understanding of therapeutics for various cardiac pathologies in humans. In our laboratory, CHB in pigs is used for complete control of heart rhythm in studies of biventricular pacing. Experiments carried out on pigs in our laboratory that required the induction of CHB were reviewed retrospectively. In addition, review of the literature for creating CHB in animals was undertaken. Our success rate was compared to that of other groups. Our success rate (93%) is similar to other models of CHB, in general, and to those models that used the injection of caustic substances with thoracotomy. Review of the literature indicates that our success rate is comparable to other groups and that, although many approaches have been described in both open- and closed-chest models, success is likely dependent on the practice and skill of the experimenter. In addition, review of the literature has afforded us new perspectives on the experimental induction of CHB.

Of Mice and Dogs

Large animal models have provided much of the descriptive data regarding the cellular and molecular events in myocardial infarction and repair. The availability of genetically altered mice may provide a valuable tool for specific cellular and molecular dissection of these processes. In this report we compare closed chest models of canine and mouse infarction/reperfusion qualitatively and quantitatively for temporal, cellular, and spatial differences. Much like the canine model, reperfused mouse hearts are associated with marked induction of endothelial adhesion molecules, cytokines, and chemokines. Reperfused mouse infarcts show accelerated replacement of cardiomyocytes by granulation tissue leading to a thin mature scar at 14 days, when the canine infarction is still cellular and evolving. Infarcted mouse hearts demonstrate a robust but transient postreperfusion inflammatory reaction, associated with a rapid up-regulation of interleukin-10 and transforming growth factor-beta. Unlike canine infarcts, infarcted mouse hearts show only transient macrophage infiltration and no significant mast cell accumulation. In correlation, the growth factor for macrophages, M-CSF, shows modest and transient up-regulation in the early days of reperfusion; and the obligate growth factor for mast cells, stem cell factor, SCF, is not induced. In summary, the postinfarction inflammatory response and resultant repair in the mouse heart shares many common characteristics with large mammalian species, but has distinct temporal and qualitative features. These important species-specific differences should be considered when interpreting findings derived from studies using genetically altered mice.

Usefulness of percutaneous intracardiac administration of colored microspheres in measuring blood flow distribution to the brain in 7-day-old rats.

By using colored microsphere (CMS) technique in newborn rats, we explored the relationship between injection sites and blood flow distribution patterns in open-chest and in closed-chest models, with hopes that percutaneous left ventricle injection can be applicable to measure relative blood flow distribution to the brain. Seven-day-old Wistar rats were used. In open-chest models (n = 30), we exposed the heart and injected CMS (15 microm diameter, 125000 spheres in 0.05 mL) to left and right ventricles, respectively. In closed-chest models (n = 12), we percutaneously punctured the left ventricle to administer microspheres to see the difference in blood flow distribution between the right and left side of organs. Microsphere counts were compared between the left and right side of each organ by unpaired t-test (mean +/- SD). Open-chest showed that right ventricle injection resulted in exclusive entrapment in the lungs, while left ventricle injection resulted in systemic distribution. According to this, one of 12 injections in the closed-chest was judged as right ventricle injection. The other 11 showed insignificant differences between the right and left side in the cortex, lung, and kidney. Right ventricle injection is differentiated from left ventricle injection and microsphere counts are the same between right and left side of the organs, suggesting that percutaneous microsphere injection is applicable for relative blood flow distribution in 7-day-old rat models.

The effect of collateral flow and myocardial viability on the distribution of technetium-99m sestamibi in a closed-chest model of coronary occlusion and reperfusion.

Myocardial uptake of technetium-99m sestamibi at low coronary flow rates overestimates blood flow, but the relative impact of flow and viability on 99mTc-sestamibi kinetics is unclear. The objective of this study was to determine the effect of myocardial viability and the degree of collateral blood flow on the uptake and retention of 99mTc-sestamibi by examining three animal models of coronary occlusion and reperfusion, each reflecting a different state of viability and collateral blood flow. Three closed-chest animal models were studied: canine (high collateral flow, preserved viability), porcine (low collateral flow, absent viability) and porcine with slowly occlusive coronary stents producing infarction and enhanced collateral blood flow (high collateral flow, absent viability). There were seven dogs, seven pigs and six pigs, respectively, in each animal model. Animals from all three models were subjected to a 40-min total left anterior descending artery (LAD) occlusion followed by 2 h of reperfusion. 99mTc-sestamibi and radiolabelled microspheres were injected during LAD occlusion 10 min prior to reperfusion. Animals were sacrificed after 2 h of reperfusion flow. Ex situ heart slice imaging to determine risk area was followed by viability staining to determine infarct size. Slices were subsequently sectioned into equally sized radial segments and placed in a gamma well counter. Risk area as determined by ex situ 99mTc-sestamibi imaging was not significantly different by model. Pathological infarct size differed significantly by model [canine = 1%+/-1% of the left ventricle (LV); porcine = 13%+/-8% LV; porcine with stent = 14%+/-7% LV; P = 0.002)]. Collateral blood flow by microspheres during occlusion tended to differ among models (overall P = 0.08), with the canine and porcine with stent models having relatively high flow rates compared with the acute porcine model. 99mTc-sestamibi activity correlated with microsphere blood flow in all three models, with r values for individual animals (n = 20) ranging from 0.86 to 0.96 (all P<0.0001). There was a significant difference in the regression line intercepts (P<0.0001) and slopes (P<0.01) among the three models comparing 99mTc-sestamibi uptake with myocardial blood flow. 99mTc-sestamibi uptake overestimated blood flow to a greater extent in the canine model (high flow with viability) than in the porcine model (low flow, absent viability). Despite enhanced collateral flow, there was significantly less overestimation of flow in the porcine stent model (high flow, absent viability). In conclusion, at low flow rates 99mTc-sestamibi activity overestimates myocardial blood flow. This effect is most pronounced in myocardium with significant collateral flow and preserved viability, consistent with over-extraction or redistribution of the tracer. The effect is markedly decreased in non-viable myocardium regardless of blood flow.

Discussion

w x We recently reported in this journal 1 that intravenous administration of adenosine, given immediately prior to and continuing for 2.5 h into reperfusion, failed to limit infarct size in an open-chest canine model of regional myocardial infarction. Our study was designed to investigate the ability of adenosine, one putative inhibitor of lethal reperfusion injury, to limit myocardial necrosis following a regional ischemic insult. Both lethal and nonlethal reperfusion injury have been hypothesized to exist. There is strong evidence that myocardial stunning occurs, at least in part, through oxygen-derived free radicals generated upon the onset of arterial reperfusion and therefore stunning is generally accepted to be a form of non-lethal w x reperfusion injury 2 . However, the existence of lethal reperfusion injury is more controversial. The experimental protocol used in our study included therapy with adenosine, based on the dose, route, and timing of administration used in the study of Pitarys et al. w x Ž 3 . These investigators had reported a positive effect i.e., . limitation of infarct size of therapy in a closed-chest canine model. In addition, our experimental protocol was designed to reproduce the results previously reported by Homeister et al. who showed that adenosine plus bolus administration of lidocaine, but not adenosine alone, resulted in cardioprotection in a canine model of regional w x infarction 4 . We were unable to show any limitation of infarct size as a result of intravenous adenosine administration, with or without lidocaine, in our open-chest model. Our negative results were discordant with the reports of marked limitation of infarct size in studies by Forman and w x colleagues 3 . Both openand closed-chest models have been used successfully in many different experimental laboratories to w x study the pathophysiology of ischemia and reperfusion 5 .

Pulmonary and systemic hemodynamics during hemorrhagic shock in baboons.

The pulmonary and systemic hemodynamic response to four hours of hemorrhagic shock and resuscitation has been studied in 17 baboons using both open and closed chest models. No pulmonary artery (PA) hypertension occurred during shock or resuscitation except for an increase in lft ventricular end diastolic pressure (LVEDP) secondary to intravascular volumee overload with Dextran. Pulmonary vascular resistance (PVR) increased during shock but returned to control levels with reinfusion of shed blood and correction of acidosis. PVR was moderately elevated following reinfusion of shed blood if acidosis was not corrected or if volum resuscitation was inadequate. No increase in gradients occurred between PA pressure and left atrial (LA) pressure or LVEDP and there was no gradients between small pulmonary vein and LA pressure. Arterial PO2 uniformly increased during shock and remained at or above control levels of reinfusion. Gross or histologic evidence of "congestive atelectasis" or "shock lung" was not observed. These observations suggest that in the subhuman primate, hemorrhage alone does not produce significant injury to the lung during shock or the immediate postresuscitation interval. Hemorrhage alone did not produce changes in the lung which would result in increased pulmonary microvascular hydrostatic pressure following appropriate resuscitation.

Reduction of exercise-induced regional myocardial dysfunction by propranolol. Studies in a canine model of chronic coronary artery stenosis.

Reduction of exercise-induced regional myocardial dysfunction by propranolol. Studies in a canine model of chronic coronary artery stenosis.