Christopher Rolfes

MRI Assessment of Pacing Induced Ventricular Dyssynchrony in an Isolated Human Heart

This study demonstrates the capabilities of MRI in the assessment of cardiac pacing induced ventricular dyssynchrony, and the findings support the need for employing more physiological pacing. A human donor heart deemed non‐viable for transplantation, was reanimated using an MR compatible, four‐chamber working perfusion system. The heart was imaged using a 1.5T MR scanner while being paced from the right ventricular apex (RVA) via an epicardial placed lead. Four‐chamber, short‐axis, and tagged short‐axis cines were acquired in order to track wall motion and intramyocardial strain during pacing. The results of this study revealed that the activation patterns of the left ventricle (LV) during RVA pacing demonstrated intraventricular dyssynchrony; as the left ventricular mechanical activation proceeded from the septum and anterior wall to the lateral wall, with the posterior wall being activated last. As such, the time difference to peak contraction between the septum and lateral wall was ∼125 msec. Likewise, interventricular dyssynchrony was demonstrated from the four‐chamber cine as the time difference between the peak LV and RV free wall motion was 180 msec. With the ongoing development of MR safe and MR compatible pacing systems, we can expect MRI to be added to the list of imaging modalities used to optimize cardiac resynchronization therapy (CRT) and/or alternate site pacing. J. Magn. Reson. Imaging 2010; 31: 466–469.

Design of a Novel Perfusion System to Perform MR Imaging of an Isolated Beating Heart

Isolated mammalian hearts have been used to study cardiac physiology, pharmacology, and biomedical devices in order to separate myocardial characteristics from the milieu of the intact animal and to allow for increased control over experimental conditions. Considering these benefits and that MRI is the “gold” standard for measuring myocardial function, it was considered desirable to have a system which would allow simultaneous MR imaging of an isolated beating heart. Here we describe a unique portable system, which enables physiologic perfusion of an isolated heart during simultaneous MR imaging. A two unit system was designed to physiologically support a large mammalian isolated heart during MR imaging were a modified Krebs-Henseleit perfusate was used as a blood substitute. The first unit, which resides in an adjacent support room next to the scanner, contains all electronically powered equipment and components (with ferromagnetic materials) which cannot operate safely near the magnet, including (1) a thermal module and custom tube in tube heat exchanger warming the perfusate to 38°C; (2) a carbogen tank (95% O2 5% CO2) and hollow fiber oxygenator; and (3) two centrifugal blood pumps which circulates and pressurizes the left and right atrial filling chambers. The second unit, which resides next to the magnet and is free of ferromagnetic materials, receives warmed, oxygenated perfusate from the first unit via PVC tubing. The isolated hearts were connected to the second unit via four cannulae sutured to the great vessels. A support system placed inside the scanner on the patient bed secured the hearts and cannulae in the correct anatomical position. To date, this system was tested in a 1.5 T Siemens scanner using swine hearts (n=2). The hearts were arrested with St. Thomas cardioplegia and removed via a medial sternotomy. After cannulation of the great vessels, reperfusion, and defibrillation, four-chamber and tagged short-axis cine loops were acquired using standard ECG gating. Tagged short-axis images obtained at the base, mid-ventricle, and apex were used to measure the following functional parameters for one heart: LV end-diastolic volume=38.84 ml, LV end-systolic volume=23.23 ml, LV stroke volume=15.6 ml, LV ejection fraction=40.18%, and peak LV circumferential strain=16%. The feasibility of MR imaging an isolated, four-chamber working large mammalian heart was demonstrated using a custom designed and built portable MRI compatible perfusion system. This system will be useful in studying in vitro cardiac function (including human hearts) and developing MRI safe biomedical devices and MRI guided therapies in a controlled setting.

Cardiac remodeling as a consequence of atrial fibrillation： An anatomical study of perfusion-fixed human heart specimens

Background Atrial fibrillation (AF) causes a continuum of atrial anatomical remodeling. Methods Using a library of perfusion-fixed human hearts, specimens with AF were compared to controls. During this preliminary assessment study, direct measurements were taken of atrial volume, pulmonary vein (PV) circumference, and left atrial (LA) wall thicknesses. Results Hearts with AF typically had larger atrial volumes, as well as a much larger variation in volume compared to controls (range of 59.6–227.1 mL in AF hearts compared to 65.1–115.9 mL in controls). For all hearts, right PVs were larger than left PVs (mean: 171.4 ± 84.6 mm[2] for right and 118.2 ± 50.1 mm[2] for left, P < 0.005). LA wall thicknesses ranged from 0.7 mm to 3.1 mm for both AF and control hearts. Conclusions Hearts with AF had a large range of sizes which is consistent with the progression of atrial remodeling during AF. The large range of thicknesses will influence the amount of energy needed to create transmural lesions during ablation procedures.

The Use of Isolated Heart Models and Anatomic Specimens as Means to Enhance the Design and Testing of Cardiac Valve Therapies

In recent years the use of perfusion-fixed cadaveric specimens and isolated heart models has helped develop an improved understanding of the device-tissue interface and contributed to the rapid evolution of surgically and percutaneously delivered valve therapies. This chapter describes a novel series of techniques utilized within the Visible Heart® laboratory by engineers, scientists, and anatomists to visualize and analyze the form and function of the four cardiac valves and assess potential repair or replacement therapies. The study of reanimated large mammalian hearts (including human) and specially prepared anatomical specimens using various clinical and nonclinical imaging modalities has provided feedback for both design engineers and clinicians that seek to develop and/or employ valve repair approaches for patients with acquired or congenital heart valve defects.

Localized Drug Delivery for Cardiothoracic Surgery

It is noteworthy to consider that extensive bioavailability and bioequivalence studies are typically required before new drug therapies can be approved [1]. These studies include pharmacokinetic studies that take into account: 1) dosing, absorption, and elimination rates of the drug and its active metabolites, as well as 2) the potential effects of multiple doses, drug interactions, and the differences whether medications are taken with or without food. A major therapeutic factor that compounds the variations often seen from patient to patient is individual differences in absorption and elimination rates. This will also cause variations in the amount of drug that reaches the desired targeted tissue when used as a clinical therapy.

Cardiac Devices and Testing

From the earliest reported cardiac surgeries in the late 19th century, exponential improvements in surgical techniques and operating times have opened the door for the development of novel cardiac devices. The design and development of cardiac devices in the 21st century is driven by the innovation and resources of an industry forecast to be worth

A Device and Methodology for Continuous Hypothermic Perfusion of Explanted Large Mammalian Hearts, Followed by In Vitro Langendorff Reanimation: Pilot Studies

266 billion by 2012. This market growth is demonstrated by the many patent applications submitted each year to create novel devices or embellish existing products.

Visualization of Coronary Artery Bypass Grafts and Coronary Artery Stents in Re-Animated and Perfusion Fixed Human Hearts

The current methodologies of clinical heart transplantation limit the ischemic window to 4–6 h. Periods longer than this can induce dysfunction in the organ and can lead to increased patient morbidity and mortality. An alternative to the current methods of static cold storage (CS) is continuous hypothermic perfusion (CHP), where a hypothermic oxygenated crystalloid solution is mechanically perfused through the coronary arteries. This has been shown to preserve the function for up to 72 h, but the techniques have yet to be optimized. We have developed an apparatus and methodology for performing CHP on large mammalian hearts, followed by reanimation in our in vitro Langendorff apparatus (The Visible HeartTM ). We are also investigating the utility of the cardioprotective agents docosahexaenoic acid and [D-Ala2, D-Leu5] enkephalin, both of which have shown cardioprotective effects in our laboratory, and we believe that their addition to the preservation solution can further extend the transplant window. A series of pilot studies has been performed to date, with modestly successful results. Hearts preserved with CHP seem to show better functionality than CS hearts but far worse functionality than hearts reanimated immediately after explant. We hope to use this system to optimize CHP methodology and eventually develop a system for prolonging the window for heart transplantation.

Cardiac Responses to the Intrapericardial Delivery of Metoprolol: Targeted Delivery Compared to Intravenous Administration

Using Visible Heart® methodologies we imaged coronary artery bypass grafts (CABGs) and coronary stents in isolated beating human hearts and perfusion fixed human hearts. Due to the varying cardiac health of the donor hearts it has been possible to see progressive levels of stent endothelialization and vascular calcification. The isolated heart model uses a clear Krebs–Henseleit buffer in place of blood, allowing for the unique opportunity to image the coronary vessels. In the isolated human heart a fiberscope was inserted into either the native coronary artery or the CABG with the heart in sinus rhythm. In order to verify cardiac function during the imaging process the following measurements were read at a sampling rate of 5 kHz: ECG, aortic flow, and ventricular pressures. Perfusion fixed hearts were fixed in an end diastolic state achieved by applying pressures comparable to physiological conditions. This process causes the coronary arteries to fix in a dilated state. CABGs of human hearts were then imaged using fluoroscopy (angiograms) and fiberscopic techniques. The stented native coronary arteries of human hearts were imaged via fluoroscopy and by dissection. Through a variety of imaging techniques and using Visible Heart® methodologies we have obtained a unique visualization of a CABG and a coronary artery stent in a beating human heart during sinus rhythm. Investigative studies in perfusion fixed human hearts have provided a more complete anatomical imaging study of stent endothelialization in the native coronary arteries and vascular calcification in bypass grafts.