We have developed a mathematical model of the human atria myocyte based on averaged voltage-clamp data recorded from isolated single myocytes. Our model consists of a Hodgkin-Huxley-type equivalent circuit for the sarcolemma, coupled with a fluid compartment model, which accounts for changes in ionic concentrations in the cytoplasm as well as in the sarcoplasmic reticulum. This formulation can reconstruct action potential data that are representative of recordings from a majority of human atrial cells in our laboratory and therefore provides a biophysically based account of the underlying ionic currents. This work is based in part on a previous model of the rabbit atrial myocyte published by our group and was motivated by differences in some of the repolarizing currents between human and rabbit atrium. We have therefore given particular attention to the sustained outward K+ current (I[sus]), which putatively has a prominent role in determining the duration of the human atrial action potential. Our results demonstrate that the action potential shape during the peak and plateau phases is determined primarily by transient outward K+ current, I(sus) and L-type Ca2+ current (I[Ca,L]) and that the role of I(sus) in the human atrial action potential can be modulated by the baseline sizes of I(Ca,L), I(sus) and the rapid delayed rectifier K+ current. As a result, our simulations suggest that the functional role of I(sus) can depend on the physiological/disease state of the cell.

The electrophysiological properties of single ventricular myocytes from control rats and from rats made diabetic by streptozotocin (STZ) injection (100 mg/kg body weight) have been investigated using whole-cell voltage-clamp measurements. Our major goal was to define the effects of diabetes on rate-dependent changes in action potential duration and the underlying outward K' currents. As early as 4 to 6 days after STZ treatment, significant elevation of plasma glucose levels occurs, and the action potential duration increases. In both control and diabetic rats, when the stimulation rate is increased, the action potential is prolonged, but this lengthening is considerably more pronounced in myocytes from diabetic rats. In ventricular myocytes from diabetic rats, the Ca2`-independent transient outward K' current (It) is reduced in amplitude, and its reactivation kinetics are slowed. These changes result in a smaller It at physiological heart rates. The steady-state outward K' current (IK) also exhibits rate-T he cardiovascular complications of diabetes mellitus are well known.1,2 In addition to coronary vessel disease, there are significant derangements in the myocardium itself, including alterations in both mechanical and electrical activity.34 Changes in both the action potential configuration5,6 and the ECG of diabetic patients have been described and may be responsible for the increased propensity for cardiac arrhythmias.7Recent findings have provided important biochemical/electrophysiological evidence concerning the cellular mechanism(s) for the functional changes that occur in the heart in the diabetic state. Changes in the ionic currents that generate the action potential8 9 have been described, and the amounts of GTP-binding proteins that mediate hormonal and neurotransmitter transduction mechanisms10 are known to be altered significantly. In addition to well-known changes in membrane phospholipid composition," ion pump and exchange systems,12 and overall cellular metabolic activity,13.'4 there are alterations in the levels of various hormones that, in turn, may also affect cardiac function. For example, a hypothyroid state develops in diabetic animals and patients.5,15In most previous studies, an animal model of chemically induced diabetes has been used, and the effects of diabetes have been investigated after a period of no less Received April 30, 1993; accepted December 8, 1993 dependent attenuation, and this phenomenon is more pronounced in cells from diabetic rats. These STZ-induced changes in It and IK also develop when a lower dose (55 mg/kg) of STZ is used and measurements are made after 7 weeks of treatment. These electrophysiological effects are not related to the hypothyroid conditions that accompany the diabetic state, since they cannot be reversed by replacement of the hormone L-triiodothyronine to physiological levels. Direct effects of STZ could be ruled out, since preceding the STZ injection with a bolus injection of 3-O-methylglucose, which prevents development of hyperglycemia, pr...

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A b s t r a c tBackground: Structural heart disease, including valvular disease as well as congenital defects, causes important alterations in heart anatomy. As a result, individualised planning for both surgical and percutaneous procedures is crucial for procedural optimisation. Three dimensional (3D) rapid prototyping techniques are being utilised to aid operators in planning structural heart procedures. Aim:We intend to provide a description of 3D printing as a clinically applicable heart modelling technology for the planning of percutaneous structural heart procedures as well as to report our first clinical use of a 3D printed patient-specific heart model in preparation for a percutaneous mitral annuloplasty using the Mitralign percutaneous annuloplasty system. Methods:Retrospectively gated, contrast enhanced, multi-slice computed tomography (MSCT) scans were obtained. MSCT DICOM data was analysed using software that creates 3D surface files of the blood volume of specific regions of interest in the heart. The surface files are rendered using a software package that creates a solid model that can be printed using commercially available stereolithography machines. Results:The technique of direct percutaneous mitral annuloplasty requires advancement of a guiding catheter through the aorta, into the left ventricle, and requires the positioning of the tip of the catheter between the papillary muscles in close proximity to the mitral annulus. The 3D heart model was used to create a procedural plan to optimise potential device implantation. The size of the deflectable guiding catheter was selected on the basis of the patient's heart model. Target locations for annulus crossing wires were evaluated pre-procedurally using the individual patient's 3D heart model. In addition, the ability to position the Bident Catheter at the appropriate locations under the mitral annulus as well as the manoeuvrability between the papillary muscles were analysed on the heart model, enabling safe completion of the procedure, which resulted in a significant reduction in mitral regurgitation.Conclusions: 3D printing is a helpful tool in individualised planning for percutaneous structural interventions. Future studies are warranted to assess its role in preparing for percutaneous and surgical heart procedures.

These results provide additional information concerning the ionic mechanism(s) for early and late repolarization, and they allow findings from electrophysiologically viable human atrial cells to be related to recent information regarding the molecular biology of potassium currents in human heart.