Translational Rabbit Model of Chronic Cardiac Pacing.

Animal models of cardiac pacing are beneficial for testing novel devices, studying the pathophysiology of artificially paced heart rhythms, and studying arrhythmia-induced cardiomyopathies and subsequent heart failure. Currently, only a few such models are available, and they mostly require extensive resources. We report a new experimental cardiac pacing model in small mammals with the potential to study arrhythmia-induced heart failure. In six New Zealand white rabbits (mean weight: 3.5 kg) under general inhalational anesthesia the jugular region was dissected and a single pacing lead was inserted via the right external jugular vein. Using fluoroscopic guidance, the lead was further advanced to the right ventricular apex, where it was stabilized using passive fixation. A cardiac pacemaker was then connected and buried in a subcutaneous pocket. The pacemaker implantation was successful with good healing; the rabbit anatomy is favorable for the lead placement. During 6 months of follow-up with intermittent pacing, the mean sensed myocardial potential was 6.3 mV (min: 2.8 mV, max: 12 mV), and the mean lead impedance measured was 744 Ω (min: 370 Ω, max: 1014 Ω). The pacing threshold was initially 0.8 V ± 0.2 V and stayed stable during the follow-up. This present study is the first to present successful transvenous cardiac pacing in a small-mammal model. Despite the size and tissue fragility, human-size instrumentation with adjustments can safely be used for chronic cardiac pacing, and thus, this innovative model is suitable for studying the development of arrhythmia-induced cardiomyopathy and consequent heart failure pathophysiology.

Aortic stenosis and mitral regurgitation modify the effect of venoarterial extracorporeal membrane oxygenation on left ventricular function in cardiogenic shock.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is widely used in the treatment of patients experiencing cardiogenic shock (CS). However, increased VA-ECMO blood flow (EBF) may significantly impair left ventricular (LV) performance. The objective of the present study was to assess the effect of VA-ECMO on LV function in acute CS with concomitant severe aortic stenosis (AS) or mitral regurgitation (MR) in a porcine model. Eight female swine (45 kg) underwent VA-ECMO implantation under general anaesthesia and mechanical ventilation. Acute CS was induced by global myocardial hypoxia. Subsequently, severe AS was simulated by obstruction of the aortic valve, while severe MR was induced by mechanical destruction of the mitral valve. Haemodynamic and LV performance variables were measured at different rates of EBF rates (ranging from 1 to 4 L/min), using arterial and venous catheters, a pulmonary artery catheter, and LV pressure-volume catheter. Data are expressed as median (interquartile range). Myocardial hypoxia resulted in declines in cardiac output to 2.7 (1.9-3.1) L/min and LV ejection fraction to 15.2% (10.5-19.3%). In severe AS, increasing EBF from 1 to 4 L/min was associated with a significant elevation in mean arterial pressure (MAP), from 33.5 (24.2-34.9) to 56.0 (51.9-73.3) mmHg (P ˂ 0.01). However, LV volumes (end-diastolic, end-systolic, stroke) remained unchanged, and LV end-diastolic pressure (LVEDP) significantly decreased from 24.9 (21.2-40.0) to 19.1 (15.2-29.0) mmHg (P ˂ 0.01). In severe MR, increasing EBF resulted in a significant elevation in MAP from 49.0 (28.0-53.4) to 72.5 (51.4-77.1) mmHg (P ˂ 0.01); LV volumes remained stable and LVEDP increased from 17.1 (13.7-19.1) to 20.8 (16.3-25.6) mmHg (P ˂ 0.01). Results of this study indicate that the presence of valvular heart disease may alleviate negative effect of VA-ECMO on LV performance in CS. Severe AS fully protected against LV overload, and partial protection was also detected with severe MR, although at the cost of increased LVEDP and, thus, higher risk for pulmonary oedema.

Acute Severe Heart Failure Reduces Heart Rate Variability: An Experimental Study in a Porcine Model.

There are substantial differences in autonomic nervous system activation among heart (cardiac) failure (CF) patients. The effect of acute CF on autonomic function has not been well explored. The aim of our study was to assess the effect of experimental acute CF on heart rate variability (HRV). Twenty-four female pigs with a mean body weight of 45 kg were used. Acute severe CF was induced by global myocardial hypoxia. In each subject, two 5-min electrocardiogram segments were analyzed and compared: before the induction of myocardial hypoxia and >60 min after the development of severe CF. HRV was assessed by time-domain, frequency-domain and nonlinear analytic methods. The induction of acute CF led to a significant decrease in cardiac output, left ventricular ejection fraction and an increase in heart rate. The development of acute CF was associated with a significant reduction in the standard deviation of intervals between normal beats (50.8 [20.5−88.1] ms versus 5.9 [2.4−11.7] ms, p < 0.001). Uniform HRV reduction was also observed in other time-domain and major nonlinear analytic methods. Similarly, frequency-domain HRV parameters were significantly changed. Acute severe CF induced by global myocardial hypoxia is associated with a significant reduction in HRV.

Atrial Septostomy for Left Ventricular Unloading During Extracorporeal Membrane Oxygenation for Cardiogenic Shock: Animal Model.

OBJECTIVES: The aim of this study was to quantify and understand the unloading effect of percutaneous balloon atrial septostomy (BAS) in acute cardiogenic shock (CS) treated with venoarterial (VA) extracorporeal membranous oxygenation (ECMO). BACKGROUND: In CS treated with VA ECMO, increased left ventricular (LV) afterload is observed that commonly interferes with myocardial recovery or even promotes further LV deterioration. Several techniques for LV unloading exist, but the optimal strategy and the actual extent of such procedures have not been fully disclosed. METHODS: In a porcine model (n = 11; weight 56 kg [53-58 kg]), CS was induced by coronary artery balloon occlusion (57 minutes [53-64 minutes]). Then, a step-up VA ECMO protocol (40-80 mL/kg/min) was run before and after percutaneous BAS was performed. LV pressure-volume loops and multiple hemoglobin saturation data were evaluated. The Wilcoxon rank sum test was used to assess individual variable differences. RESULTS: Immediately after BAS while on VA ECMO support, LV work decreased significantly: pressure-volume area, end-diastolic pressure, and stroke volume to ∼78% and end-systolic pressure to ∼86%, while superior vena cava and tissue oximetry did not change. During elevating VA ECMO support (40-80 mL/kg/min) with BAS vs without BAS, we observed 1) significantly less mechanical work increase (122% vs 172%); 2) no end-diastolic volume increase (100% vs 111%); and 3) a considerable increase in end-systolic pressure (134% vs 144%). CONCLUSIONS: In acute CS supported by VA ECMO, atrial septostomy is an effective LV unloading tool. LV pressure is a key component of LV work load, so whenever LV work reduction is a priority, arterial pressure should carefully be titrated low while maintaining organ perfusion.

Vancomycin-releasing cross-linked collagen sponges as wound dressings.

The study presents a novel vancomycin-releasing collagen wound dressing derived from Cyprinus carpio collagen type I cross-linked with carbodiimide which retarded the degradation rate and increased the stability of the sponge. Following lyophilization, the dressings were subjected to gamma sterilization. The structure was evaluated via scanning electron microscopy images, micro-computed tomography, and infrared spectrometry. The structural stability and vancomycin release properties were evaluated in phosphate buffered saline. Microbiological testing and a rat model of a wound infected with methicillin-resistant Staphylococcus aureus (MRSA) were then employed to test the efficacy of the treatment of the infected wound. Following an initial mass loss due to the release of vancomycin, the sponges remained stable. After 7 days of exposure in phosphate buffered saline (37°C), 60% of the material remained with a preserved collagen secondary structure together with a high degree of open porosity (over 80%). The analysis of the release of vancomycin revealed homogeneous distribution of the antibiotic both across and between the sponges. The release of vancomycin was retarded as proved by in vitro testing and further confirmed by the animal model from which measurable concentrations were observed in blood samples 24 hours after the subcutaneous implantation of the sponge, which was more than observed following intraperitoneal administration. The sponge was also highly effective in terms of reducing the number of colony-forming units in biopsies extracted from the infected wounds 4 days following the inoculation of the wounds with the MRSA solution. The presented sponges have ideal properties to serve as wound dressing for prevention of surgical site infection or treatment of already infected wounds.

Transaortic or Pulmonary Artery Drainage for Left Ventricular Unloading in Venoarterial Extracorporeal Life Support: A Porcine Cardiogenic Shock Model.

The peripheral venoarterial extracorporeal life support (V-A ECLS) in cardiogenic shock (CS) may lead to LV overload. The transaortic suction device (Impella, ABIOMED Inc., Danvers, MA) was compared to the pulmonary artery (PA) drainage, for LV unloading efficacy during V-A ECLS in a porcine cardiogenic shock model. A dedicated CS model included 12 swine (21 ± 1.8-week-old and weighing 54.3 ± 4.6 kg) supported with V-A ECLS and randomized to Impella or PA-related LV drainage. LV unloading and end-organ perfusion were evaluated through the PA catheter and LV pressure/volume analysis. The LV end-diastolic volume sharply dropped with Impella (143.6 ± 67.4 vs 123 ± 75.7 mL) compared to a slight decrease in the PA cannula group (134.1 ± 39.9 vs 130.1 ± 34.7 mL), resulting in an overall stroke work and pressure-volume area reductions with both techniques. However, stroke work reduction was more significant in the Impella group (V-A ECLS 3998.8 ± 2027.6 vs V-A ECLS + Impella 1796.9 ± 1033.9 mm Hg × mL, P = 0.016), leading to a more consistent pressure-volume area reduction (Impella reduction 34.7% vs PA cannula reduction 9.7%) In terms of end organ perfusion, central and mixed O2 saturation improved with V-A ECLS, and subsequently, remaining unchanged with either Impella or PA cannula as unloading strategy (SVmO2: Impella 86.0 ± 5.8 vs 87.8 ± 5.8; PA cannula 82.5 ± 10.7 vs 82.5 ± 11.3 %). Transaortic suction and PA drainage provided effective LV unloading during V-A ECLS while maintaining adequate end-organ perfusion. Impella provides a greater LV unloading effect and reduces more effectively the total LV stroke work.

Rifampin-Releasing Triple-Layer Cross-Linked Fresh Water Fish Collagen Sponges as Wound Dressings.

OBJECTIVES: Surgical wounds resulting from biofilm-producing microorganisms represent a major healthcare problem that requires new and innovative treatment methods. Rifampin is one of a small number of antibiotics that is able to penetrate such biofilms, and its local administration has the potential to serve as an ideal surgical site infection protection and/or treatment agent. This paper presents two types (homogeneous and sandwich structured) of rifampin-releasing carbodiimide-cross-linked fresh water fish collagen wound dressings. METHODS: The dressings were prepared by means of the double-lyophilization method and sterilized via gamma irradiation so as to allow for testing in a form that is able to serve for direct clinical use. The mechanical properties were studied via the uniaxial tensile testing method. The in vivo rifampin-release properties were tested by means of a series of incubations in phosphate-buffered saline. The microbiological activity was tested against methicillin-resistant staphylococcus aureus (MRSA) employing disc diffusion tests, and the in vivo pharmacokinetics was tested using a rat model. A histological examination was conducted for the study of the biocompatibility of the dressings. RESULTS: The sandwich-structured dressing demonstrated better mechanical properties due to its exhibiting ability to bear a higher load than the homogeneous sponges, a property that was further improved via the addition of rifampin. The sponges retarded the release of rifampin in vitro, which translated into at least 22 hours of rifampin release in the rat model. This was significantly longer than was achieved via the administration of a subcutaneous rifampin solution. Microbiological activity was proven by the results of the disc diffusion tests. Both sponges exhibited excellent biocompatibility as the cells penetrated into the scaffold, and virtually no signs of local irritation were observed. CONCLUSIONS: We present a novel rifampin-releasing sandwich-structured fresh water fish collagen wound dressing that has the potential to serve as an ideal surgical site infection protection and/or treatment agent.

Increasing venoarterial extracorporeal membrane oxygenation flow puts higher demands on left ventricular work in a porcine model of chronic heart failure.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA ECMO) is widely used in the treatment of circulatory failure, but repeatedly, its negative effects on the left ventricle (LV) have been observed. The purpose of this study is to assess the influence of increasing extracorporeal blood flow (EBF) on LV performance during VA ECMO therapy of decompensated chronic heart failure. METHODS: A porcine model of low-output chronic heart failure was developed by long-term fast cardiac pacing. Subsequently, under total anesthesia and artificial ventilation, VA ECMO was introduced to a total of five swine with profound signs of chronic cardiac decompensation. LV performance and organ specific parameters were recorded at different levels of EBF using a pulmonary artery catheter, a pressure-volume loop catheter positioned in the LV, and arterial flow probes on systemic arteries. RESULTS: Tachycardia-induced cardiomyopathy led to decompensated chronic heart failure with mean cardiac output of 2.9 ± 0.4 L/min, severe LV dilation, and systemic hypoperfusion. By increasing the EBF from minimal flow to 5 L/min, we observed a gradual increase of LV peak pressure from 49 ± 15 to 73 ± 11 mmHg (P = 0.001) and an improvement in organ perfusion. On the other hand, cardiac performance parameters revealed higher demands put on LV function: LV end-diastolic pressure increased from 7 ± 2 to 15 ± 3 mmHg, end-diastolic volume increased from 189 ± 26 to 218 ± 30 mL, end-systolic volume increased from 139 ± 17 to 167 ± 15 mL (all P < 0.001), and stroke work increased from 1434 ± 941 to 1892 ± 1036 mmHg*mL (P < 0.05). LV ejection fraction and isovolumetric contractility index did not change significantly. CONCLUSIONS: In decompensated chronic heart failure, excessive VA ECMO flow increases demands and has negative effects on the workload of LV. To protect the myocardium from harm, VA ECMO flow should be adjusted with respect to not only systemic perfusion, but also to LV parameters.

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.