Name: tachycardia-induced cardiomyopathy as a chronic heart failure model in swine
Uploaded: 2018-02-17T15:00:00
Description: Watch this Scientific Journal Video about Tachycardia-Induced Cardiomyopathy As a Chronic Heart Failure Model in Swine at JoVE.com

This work was supported by Charles University research grants GA UK No. 538216 and GA UK No. 1114213.

This experimental protocol was reviewed and approved by the Institutional Animal Expert Committee at First Faculty of Medicine, Charles University, and was performed at the University experimental laboratory, Department of Physiology, First Faculty of Medicine, Charles University in Prague, Czech Republic, in accordance with Act No. 246/1992 Coll., on the protection of animals against cruelty. All animals were treated and cared for in accordance with the Guide for the Care and Use of Laboratory Animals, 8th edition, publ...

Chronic HF is a major health problem that contributes greatly to morbidity and mortality. The pathogenesis and progression of HF in humans is complex, so an appropriate animal model is critical to investigate the underlying mechanisms and to test novel therapeutics that aim to interfere with native severe disease progression. To study its pathogenesis, large animal models are being used for experimental testing.
In general, surgical models of chronic HF closely mimic this disease. When compare...

The variety of new treatment methods for heart failure (HF), especially the growing worldwide use of mechanical circulatory supports and extracorporeal membrane oxygenation (ECMO) in clinical practice, is reflecting in preclinical experimental testing. The main focus has been on hemodynamic changes caused by the examined treatment modalities, namely on systemic blood pressure1, myocardial contractility, pressure and volume changes in heart chambers and heart work2,3, arterial blood flow in systemic and peripheral arteries, along with metabolic compensation4 - regional tissue saturation, pulmonary perfusion, and blood gas analysis. Other studies are directed on long-term effects of the circulatory support5, concomitant inflammation, or occurrence of hemolysis. All these types of study need a stable biomodel of congestive HF.
Most of the published experiments on left ventricular (LV) performance and hemodynamics of mechanical circulatory support have been performed on experimental models of acute HF2,6,7,8,9,10, or even on completely intact hearts. On the other hand, in clinical practice, mechanical circulatory supports are often being applied in a status of circulatory decompensation that develops on the grounds of previously present chronic heart disease. In such situations, the adaptation mechanisms are fully developed and can play important roles in inconsistency of outcomes observed according to the &#34;acuteness or chronicity&#34; of underlying cardiac disease11. Therefore, a stable model of chronic HF can offer new insights into pathophysiological mechanisms and hemodynamics. Although there are reasons why the use of chronic HF models is scarce - time consuming preparation, instability of heart rhythm, ethical questions, and mortality rate - their advantages are clear, as they offer presence of long-term neurohumoral activation, general systemic adaptation, functional changes of cardiomyocytes, and structural alterations of heart muscle and valves12,13.
In general, the availability and variety of animal models used for hemodynamic studies is wide and offers choice for many specific needs. For these experiments, mostly porcine, canine, ovine, or with smaller settings murine models, are being chosen and offer a good simulation of expected human bodily reactions14. Furthermore, forms of single organ experiments are becoming more frequent15. To reliably mimic the pathophysiology of HF, circulation is being artificially deteriorated. Damage to the heart can be caused by various methods, often by either ischemia, arrhythmia, pressure overload, or cardiotoxic effects of drugs, with any of these leading to hemodynamic deterioration of the model. To produce a true model of chronic HF, time has to be provided for developing the long-term adaptation of the whole organism. Such a reliable and stable model is represented well by tachycardia-induced cardiomyopathy (TIC), which can be produced by rapid cardiac pacing in experimental animals.
It has been shown that in predisposed hearts, long-lasting incessant tachyarrhythmias can lead to systolic dysfunction and dilation with decreased cardiac output. The condition referred to as TIC was first described in 191316, widely used in experiments since 196217, and is now a well-recognized disorder. Its origin can lie in various types of arrhythmias - both supraventricular and ventricular tachycardia can lead to progressive deterioration of systolic function, biventricular dilation, and progressive clinical signs of HF including ascites, edemas, lethargy, and ultimately cardiac decompensation leading to terminal HF and, if not treated, death.
Similar effects of circulatory suppression were observed by introduction of high rate cardiac pacing in animal models. In a porcine model, an atrial or ventricular heart rate over 200 beats/minute is potent enough to induce end-stage HF in a period of 3 - 5 weeks (progressive phase) with characteristics of TIC, though interindividual differences do exist18,19. These findings correspond well to decompensated cardiomyopathy and are, importantly, preserved also after the cessation of pacing (chronic phase)19,20,21,22,23.
Porcine, canine, or ovine TIC models were repeatedly prepared to study the pathophysiology of HF14, as changes to the LV mimic the characteristics of dilated cardiomyopathy24. The hemodynamic characteristics are well described - increased ventricular end-diastolic pressures, decreased cardiac output, increased systemic vascular resistance, and dilation of both ventricles. In contrast, wall hypertrophy is not observed consistently, and even wall thinning was described by some researchers25,26. With progression of ventricular dimensions, regurgitation on atrioventricular valves develops26.
In this publication, we present a protocol to produce a TIC by long-term fast cardiac pacing in swine. This biomodel represents potent means to study decompensated dilated cardiomyopathy, hemodynamics of progressive chronic HF with low cardiac output, and effects of applied treatment.

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tachycardia-induced cardiomyopathy as a chronic heart failure model in swine

A stable and reliable model of chronic heart failure is required for many experiments to understand hemodynamics or to test effects of new treatment methods. Here, we present such a model by tachycardia-induced cardiomyopathy, which can be produced by rapid cardiac pacing in swine.
A single pacing lead is introduced transvenously into fully anaesthetized healthy swine, to the apex of the right ventricle, and fixated. Its other end is then tunneled dorsally to the paravertebral region. There, it is connected to an in-house modified heart pacemaker unit that is then implanted in a subcutaneous pocket. 
After 4 - 8 weeks of rapid ventricular pacing at rates of 200 - 240 beats/min, physical examination revealed signs of severe heart failure - tachypnea, spontaneous sinus tachycardia, and fatigue. Echocardiography and X-ray showed dilation of all heart chambers, effusions, and severe systolic dysfunction. These findings correspond well to decompensated dilated cardiomyopathy and are also preserved after the cessation of pacing.
This model of tachycardia-induced cardiomyopathy can be used for studying the pathophysiology of progressive chronic heart failure, especially hemodynamic changes caused by new treatment modalities like mechanical circulatory supports. This methodology is easy to perform and the results are robust and reproducible.

Testing the model: After signs of decompensated chronic HF became prominent, anesthesia and artificial ventilation were administered again following the principles described above, but dosing was adjusted due to low cardiac output27. Due to possible cardiodepressive effects of anesthetics, careful intensive monitoring of vital functions is necessary.
The animal was attached in the supine ...

Watch this Scientific Journal Video about Tachycardia-Induced Cardiomyopathy As a Chronic Heart Failure Model in Swine at JoVE.com

Tachycardia-Induced Cardiomyopathy As a Chronic Heart Failure Model in Swine

Here, we present a protocol to produce tachycardia-induced cardiomyopathy in swine. This model represents a potent way to study the hemodynamics of progressive chronic heart failure and the effects of applied treatment.

A stable and reliable model of chronic heart failure is required for many experiments to understand hemodynamics or to test effects of new treatment ...

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