A mechanical model of the human heart relating septal function to myocardial work and energy.

A thorough understanding of ventricular interaction and the effects of septal function on right and left ventricular performance in the human heart requires measurement of interventricular pressure gradients using high fidelity pressure transducers. The advent of newer echocardiographic techniques provides an opportunity to combine high resolution images with bi-ventricular catheterization data in the cardiac catheterization laboratory, and obtain the detailed hemodynamic and echocardiographic information necessary to more fully understand the clinical manifestations of normal and abnormal septal and free wall mechanical function. We have anticipated these developments and modified the description of heart mechanics in our integrated multi-scale model of the human cardio-respiratory system (H-CRS) to closely analyze how the mechanical properties of the inter-ventricular septum affect the work, energy utilization, and oxygen consumption of the atria, ventricles, septum, and each ventricular free wall. Combined with the H-CRS model, these modifications allow one to observe how tissue properties of the septum affect the entire heart and circulation. For example, the normal septum transfers energy from the left to the right ventricle, and assists the pre-load of both, acting as a third pump. Diseases that increase septal elastance cause abnormalities resembling left ventricular diastolic dysfunction (LVDD), including a decrease in cardiac output and an increase in pulmonary pressures despite a normal left ventricular ejection fraction. Similar applications of the H-CRS model to other regional disorders such as hypertrophic obstructive cardiomyopathy and myocardial infarction might likewise allow one to study their clinical implications in greater detail.

Using a human cardiopulmonary model to study and predict normal and diseased ventricular mechanics, septal interaction, and atrio-ventricular blood flow patterns.

We upgraded our human cardiopulmonary (CP) model with additional data that enables it to more accurately simulate normal physiology. We then tested its ability to explain human disease by changing two parameter values that decrease ventricular compliance, and found that it could predict many of the hemodynamic, gas exchange, and autonomic abnormalities found in patients with left ventricular diastolic dysfunction (LVDD). The newly incorporated information includes high-fidelity pressure tracings simultaneously recorded from the RV and LV of a normal human in a cardiac catheterization laboratory, Doppler echocardiographic inlet flow velocity patterns, measures of right and left ventricular impedance, and atrial volumes. The revised cardiovascular section details the hemodynamics of a normal subject to the extent that it can now explain the effects of septal compliance on ventricular interaction, the differences in left and right ventricular pressure development, and venous blood gas mixing in the right atrium. The model can isolate the highly interrelated features of normal and abnormal physiology, and simultaneously demonstrate their interaction in a manner that would be very difficult or impossible using an intact organism. It may therefore help physicians and scientists understand, diagnose, and improve their treatment of complicated cardiovascular and pulmonary diseases. It could also simulate the hemodynamic and respiratory effects of ventricular and pulmonary assist devices, and thus help with their development.

Cerebral autoregulation and gas exchange studied using a human cardiopulmonary model.

The goal of this work is to study the cerebral autoregulation, brain gas exchange, and their interaction by means of a mathematical model. We have previously developed a model of the human cardiopulmonary (CP) system, which included the whole body circulatory system, lung and peripheral tissue gas exchange, and the central nervous system control of arterial pressure and ventilation. In this study, we added a more detailed description of cerebral circulation, cerebrospinal fluid (CSF) dynamics, brain gas exchange, and cerebral blood flow (CBF) autoregulation. Two CBF regulatory mechanisms are included: autoregulation and CO(2) reactivity. Central chemoreceptor control of ventilation is also included. We first established nominal operating conditions for the cerebral model in an open-loop configuration using data generated by the CP model as inputs. The cerebral model was then integrated into the larger CP model to form a new integrated CP model, which was subsequently used to study cerebral hemodynamic and gas exchange responses to test protocols commonly used in the assessment of CBF autoregulation (e.g., carotid artery compression and the thigh-cuff deflation test). The model can closely mimic the experimental findings and provide biophysically based insights into the dynamics of cerebral autoregulation and brain tissue gas exchange as well as the mechanisms of their interaction during test protocols, which are aimed at assessing the degree of autoregulation. With further refinement, our CP model may be used on measured data associated with the clinical evaluation of the cerebral autoregulation and brain oxygenation in patients.

A human cardiopulmonary system model applied to the analysis of the Valsalva maneuver.

Previous models combining the human cardiovascular and pulmonary systems have not addressed their strong dynamic interaction. They are primarily cardiovascular or pulmonary in their orientation and do not permit a full exploration of how the combined cardiopulmonary system responds to large amplitude forcing (e.g., by the Valsalva maneuver). To address this issue, we developed a new model that represents the important components of the cardiopulmonary system and their coupled interaction. Included in the model are descriptions of atrial and ventricular mechanics, hemodynamics of the systemic and pulmonic circulations, baroreflex control of arterial pressure, airway and lung mechanics, and gas transport at the alveolar-capillary membrane. Parameters of this combined model were adjusted to fit nominal data, yielding accurate and realistic pressure, volume, and flow waveforms. With the same set of parameters, the nominal model predicted the hemodynamic responses to the markedly increased intrathoracic (pleural) pressures during the Valsalva maneuver. In summary, this model accurately represents the cardiopulmonary system and can explain how the heart, lung, and autonomic tone interact during the Valsalva maneuver. It is likely that with further refinement it could describe various physiological states and help investigators to better understand the biophysics of cardiopulmonary disease.

Focal elastic obstruction of the inferior vena cava.

Obstruction of the supra-hepatic inferior vena cava (IVC) is a common cause of hepatic venous hypertension and the most common cause of Budd-Chiari Syndrome. Because most cases of IVC obstruction go undiagnosed until Budd-Chiari Syndrome develops, the natural history of IVC obstruction is not well defined. We report a case of a focal, elastic, non-membranous obstruction of the IVC causing hepatic venous hypertension and elevated serum transaminases in a 36-year-old man. The obstruction was successfully treated with placement of a self-expanding metallic stent with normalization of hepatic transaminases.

Ventricular arrhythmias following thermal damage of epicardial tissue: possible causes and clinical implications.

Epicardial heating may be used for ventricular tachycardia (VT) ablation and transmyocardial revascularization. However, the potential risks of thermal epicardial injury, including arrhythmia, have not been fully explored. This study relates the pathologic and arrhythmic sequellae of epicardial heating when applied with a diode laser at varying doses. Acute pathology and dosimetry were determined in a group of normal dogs using 2-3 W over 30-90 seconds. Another group received a similar dose range before undergoing 24-hour monitoring, and electrophysiological testing was done at 4 weeks. In this group, four dogs each received 12 lesions (90-180 J) according to a randomized block design. Another dog received nine lower dose lesions (30-120 J). Acute lesions measured 2.5-8.0-mm wide by 4-8.5-mm deep. Charring and vaporization were common when 3 W were applied over 45 seconds. Within 24 hours, VT with features of abnormal automaticity occurred in all dogs receiving this dose. The dog in whom lower doses induced coagulation only had no VT. Four weeks later, electrophysiological study induced no VT. At this time fibrosis and granulation tissue were organizing the contraction band necrosis seen acutely, and some lesion borders were becoming calcified. No major vessels had been damaged. Abnormal automaticity and VT may occur if thermal damage of the epicardium exceeds coagulation. This could be related to tissue injury caused by sudden water vaporization, and may have clinical relevance given the growing indications for myocardial heating.

Slow intramural heating with diffused laser light: A unique method for deep myocardial coagulation.

BACKGROUND: Catheter ablation of postinfarction ventricular tachycardia (VT) may be limited by insufficient myocardial coagulation or excessive endocardial or epicardial damage. We propose that volumetric heating restricted to intramural sites may improve the outcome and safety of this procedure, especially if delivered at rates that enhance heat conduction and forestall adverse tissue changes. METHODS AND RESULTS: A novel optical fiber with a diffusing tip for direct intramural, volumetric laser heating was tested via thoracotomy and percutaneously in normal dogs. Low-power (2.0- to 4.5-W) diode laser light (805 nm) diffused within tissue induced large lesions but no visible surface damage, mural thrombi, or transmural perforation. Mean lesion depth approximated tip length (10 mm). Mean lesion widths in the thoracotomy and percutaneous groups were 5.8+/-0.5 to 9.1+/-0.84 mm and 5.2+/-0.85 to 7.9+/-1.1 mm, respectively, depending on the light dose. Mean volumes in the percutaneous group were 1006+/-245 to 2471+/-934 mm. ST-segment depression, appearing in unfiltered bipolar electrograms recorded from the guiding catheter, was specific for lesion induction. All dogs survived the protocol, which included a 1-hour observation period. In cross section, lesions were elliptical to spherical and characterized by extensive contraction-band necrosis abruptly bordering viable tissue. No platelets or fibrin adhered to the endocardium. CONCLUSIONS: Slow, volumetric, and direct intramyocardial heating induces large, deep lesions without hazardous tissue damage. Such heating might cure postinfarction VT more successfully and safely than present techniques. Further testing and development of this method seem warranted.

Ventricular defibrillation in canines with chronic infarction, and effects of lidocaine and procainamide.

Prior studies in dogs with normal hearts have demonstrated that lidocaine increases but procainamide does not change the energy required for successful defibrillation. Because many postinfarct patients receiving implantable cardioverter defibrillator devices require adjunctive antiarrhythmic therapy, we have studied the effects of lidocaine and procainamide on the relationship between delivered voltage and defibrillation success in mongrel dogs 21 +/- 3 days following ligation of the left anterior descending and first diagonal coronary arteries. Internal defibrillation testing using a patch-patch electrode configuration was performed before and during the administration of saline controls (n = 10), lidocaine (n = 10) and procainamide (n = 10). The mean infarct size as determined by staining with tetrazolium was 13.4% +/- 8.3% of right and left ventricles, and did not differ significantly between groups. The 50% effective defibrillation (ED50) voltage increased with infusions of saline (16% +/- 15%), lidocaine (40% +/- 22%), and procainamide (13% +/- 15%) and the ED50 energy increased 41% +/- 44%, 104% +/- 62%, and 35% +/- 36%, respectively. However, the increase in ED50 voltages and energies were significantly greater in animals receiving lidocaine compared to those receiving either saline control or procainamide (P < 0.01). There were trends toward change of hemodynamic parameters in all animals following baseline defibrillation testing; stroke volume declined 21% +/- 16%; and mean pulmonary artery and aortic pressure increased by 22% +/- 25% and 11% +/- 15%, respectively. In conclusion, unlike our previous studies in dogs with normal hearts, in this model hemodynamic deterioration occurred with repeated fibrillation and defibrillation, and defibrillation voltage requirements increased in the control series. Taking into consideration the increase in defibrillation voltage requirements over the duration of the experiments, lidocaine increases and procainamide does not change ED50; thus, their effects are similar in normal and infarcted canine hearts.

Recent advances in clinical cardiac electrophysiology.

Management of patients presenting with significant cardiac arrhythmias depends greatly on the initial clinical assessment; underlying cardiovascular disorders must be evaluated because they often are the substrate or trigger of arrhythmias. Electrophysiologic testing may be used to guide therapy with antiarrhythmic drugs or with devices such as the automatic implantable cardioverter/defibrillator; in selected patients, arrhythmias may be ablated surgically or with percutaneous catheter techniques. Advances in clinical cardiac electrophysiology have resulted in successful therapy or cure of many patients with symptomatic or life-threatening cardiac arrhythmias.

Intravenous 3-methoxy-O-desmethyl-encainide in reentrant supraventricular tachycardia: a randomized double-blind placebo-controlled trial in patients undergoing EP study.

Encainide is an agent effective in atrioventricular and atrioventricular nodal reentrant tachycardia. The metabolites O-desmethyl encainide and 3-methoxy-O-desmethyl encainide (MODE) are responsible for the clinical effects of encainide in most patients. In this study, intravenous MODE was evaluated in eight patients with reentrant supraventricular tachycardia undergoing electrophysiological testing. After tachycardia was induced at least twice to ensure reproducibility, MODE (30 micrograms/kg/min x 15 min, then 7.5 micrograms/kg/min) or placebo was administered in a double-blind fashion. If tachycardia remained inducible, the infusion was unblinded; in nonresponding subjects who received placebo, MODE was then administered. Placebo was ineffective in 3/3 patients. MODE prevented tachycardia induction in 5/8 patients and increased the tachycardia cycle length from 302 +/- 38 to 413 +/- 67 msec in the other three. At a mean concentration of 774 +/- 229 ng/ml, MODE prolonged PR, AH, HV, QRS, and QT intervals, right ventricular and accessory pathway effective refractory periods, and slowed or blocked antegrade accessory pathway conduction. Changes in intracardiac conduction were rate independent between cycle lengths 400 to 600 msec, while changes in ventricular effective refractory periods were most pronounced at rapid pacing rates. No adverse effects, hemodynamic changes, or conduction disturbances occurred. Thus, MODE can modify or suppress induction of reentrant atrioventricular or atrioventricular nodal tachycardia. The study design used here is well suited for the evaluation of newer antiarrhythmic agents by electrophysiological testing.

An unusual case of cardiac tamponade.

A 29-year-old woman with Ebstein's anomaly on anticoagulant therapy presented with chest pain. A diagnosis of pericarditis was made once a myocardial infarction and pulmonary embolus had been excluded. She was discharged but returned shortly thereafter with fever, tachypnea and tachycardia. A repeat chest film disclosed that the cardiac silhouette had enlarged greatly since prior admission. Despite the absence of pulsus paradoxus, right heart catheterization confirmed the clinical suspicion of pericardial tamponade.