The Intact porcine bioprosthesis: early world-wide clinical experience and analysis of a single institution's experience.

The Intact porcine bioprosthesis is a new-generation valve fixed under stress-free conditions and subjected to a mineralization-inhibiting treatment. The valve is undergoing multi-centre prospective clinical evaluation sponsored by Medtronic, Inc., with 19 centres participating world wide. Since April 1986, 1465 valves have been implanted in the aortic position (AVR, n = 965), mitral position (MVR, n = 438), or both (n = 62), and followed up to 5 years. The data recorded at our participating centre, with 115 valves implanted (AVR n = 93, MVR n = 22) closely match the overall event and death rates in the prospective study. Early mortality in the overall study is 5.6% in AVR and 6.6% in MVR; 3-year actuarial survival rates are 88.5% in AVR and 85.6% in MVR; structural valve-failure-free rates at 3 years are 99.8% in AVR and 98.5% in MVR; 3-year freedom from valve-related reoperation is 97.3% in AVR and 95.8% in MVR. The preferential use of bioprosthetic valves in patients aged 70 years and older with no other indication for anticoagulant treatment entails the not infrequent occurrence of patient/prosthesis mismatch in AVR. Hence, when implanting bioprostheses in old patients, the acceptance of some mismatch has to be weighed against the freedom from anticoagulation treatment and the expected long-term freedom from structural valve failure. Further long-term follow-up will be required to demonstrate the greater durability expected from the stress-free fixation and the anti-mineralization treatment.

Clinical experience with an activity sensing pacemaker.

During clinical evaluation of the Medtronic Activitrax pacemaker in a worldwide multicenter study, implant and follow-up data were provided by 61 investigators on 222 patients. Pacing indications included two- and three-degree AV block in 149 and atrial arrhythmias in 174 patients; 16 patients received atrial pacing. Average and longest documented follow-up periods were 7.5 and 16 months respectively. Paired treadmill tests, one in Activity mode and one in VVI/AAI mode, were performed by 120 patients. At peak exercise, average heart rate was 95 bpm in VVI/AAI mode and 118 bpm in Activity mode (p less than 0.0001). Average exercise time was 9.4 minutes in VVI/AAI mode and 10.8 minutes in Activity mode (p less than 0.0001). In 54 patients who exclusively had paced rhythm during both treadmill tests, average heart rates and exercise times were 70 ppm and 8.1 minutes in VVI/AAI mode and 111 ppm and 10.3 minutes in Activity mode respectively (p less than 0.0001). 24-hour Holter recordings typically demonstrated pacing at or near basic rate during periods of rest and appropriate increase in pacing rate during daily activities. Patients had significantly fewer problems with physical effort in daily life during a week of Activity mode pacing than during a week of VVI/AAI mode pacing (p less than 0.05) as assessed from the symptom scores recorded by 62 patients in special diaries.

Estimation of regional pleural surface expansile forces in intact dogs.

Distances between percutaneously inserted apical and basal lung markers determined by biplane X-ray, computer-based videometry (J. Appl. Physiol. 34: 544, 1973) were calibrated against dependent percutaneously recorded pleural liquid pressures (J. Appl. Physiol. 31: 277, 1971) in five 10-12 kg mongrel dogs under morphine-pentobarbital anesthesia studied without thoracotomy. At the same apical pleural-liquid pressure values, the apical intermarker distances were uniformly greater when in the head-up rather than head-down position. This finding suggests that the expansile forces acting on the apical regions of the lung, in the head-up position, are greater (-30 +/- 2 cmH2O) than would be predicted from "pleural liquid" pressures (-15 +/- 1 cmH2O) measured at this nondependent site in the thorax, and much greater than the "pleural surface" pressures measured by the generally accepted balloon and counter-pressure techniques. In contrast, in the head-down body position, expansile forces acting on the nondependent basal regions of the lung estimated by the intermarker distance technique were variable to either side of the pressures measured by open-ended liquid-filled catheters, and thus were not significantly different. Mean values measured by the catheters and predicted by the markers were -14 +/- 1 and -10 +/- 3 cmH2O, respectively.

Topographical distribution of regional lung volume in anesthetized dogs.

The distribution of regional lung volume during static deflation from total lung capacity to functional residual capacity was determined from the positions of intraparenchymal metallic markers ascertained by a biplane video roentgenographic technique in supine and prone anesthetized dogs. Regional lung volumes were linearly related to overall lung volume so that regional volume could be characterized by a ventilation index (VI), which is the ventilation per alveolus relative to the ventilation of the overall lung. For the supine position, there were vertical and cephalocaudal gradients in VI in both the upper and lower lobes. Mean VI was greater in the lower lobe than in the upper lobe, but VI was less than would be predicted from extrapolation of the upper lobe relationship. For the prone position, there was no consistent gradient in VI in any direction. The magnitude of the gradients in VI and the effects of body position suggest that, in the recumbent dog, the thoracic cavity shape is a more important determinant of regional lung volume than is the effect of gravity on the lung itself.

On relationship between bulk modulus and relative volume of lung during inflation-deflation maneuvers.

An equation of the form K=C/[1 - (V/V max)]n relating the bulk modulus K to the relative volume V/V max of lung region during inflation-deflation maneuvers is proposed. It well represents the observed fact that the bulk modulus becomes infinitely large when the regional volume approaches its maximum capacity V max. The parameter C describes the bulk modulus at low regional volume whereas the parameter n quantifies the rate at which the bulk modulus changes during the inflation-deflation maneuvers. The mathematical expressions for the regional pressure, P, and volume V , are obtained by integrating the equation K=VdP/dV. They fit exceedingly well with the experimental data recorded during inflation-deflation tests of six excised canine lung lobes.

Evaluation of ischemic heart disease with a prototype volume imaging computed tomographic (CT) scanner: preliminary experiments.

A prototype synchronous volumetric computed tomographic X-ray scanner was used to demonstrate, in individual experiments, the possibility of estimating percent coronary arterial stenosis, regional myocardial blood supply and regional myocardial wall dynamics. Scans were obtained during angiography in intact anesthetized dogs or in an isolated metabolically supported working left ventricular preparation. Percent arterial stenosis was quantitated using the percent change in brightness area product of successive cross-sectional images of contrast agent-filled Tygon tubing sutured to the epicardium. Myocardial blood supply was evaluated by the transmural and circumferential extent and th time rate of change of myocardial opacification during coronary angiography. The regional time rate of change of left ventricular wall thickening during the systolic phase of the cardiac cycle was demonstrated in the isolated ventricle preparation. The recently installed Dynamic Spatial Reconstructor high speed volumetric scanning system will be used to make these measurements from scan data obtained during a single angiogram in man.

Distribution of regional volumes and ventilation in excised canine lobes.

A linear elasticity solution for the gravitational deformation of excised lungs was obtained. The accuracy of our solution was examined by comparing predicted and measured displacements of markers glued to the surface of canine lower lobes. The equations describing the strains in a lobe were used to predict the distribution of regional volumes and the slope of phase III (S3) of a single-breath oxygen (SBO2) test. The analysis predicted a negative S3. However, S3 was found to be positive in the five lobes tested, suggesting that factors other than gravity were responsible for the observed pattern of ventilation. In SBO2 tests repeated with increasing delays at end inflation, S3 progressively decreased, became negative, and was eventually abolished. Our equations predicted the most negative observed S3 well. We conclude that continuum mechanics can be used to describe the gravitational deformation of lungs and the resulting effect on ventilation distribution.

Regional lung expansion at total lung capacity in intact vs. excised canine lungs.

A computer-based biplane videoroentgenographic recording technique that determines the spatial coordinates of radiopaque lung parenchymal markers was used to compare regional lung expansion at total lung capacity (TLC) in the intact dog (prone and supine) and after removal from the chest. The reproducibility of the technique was examined by repeated determinations of intermarker distances at various static lung volumes during stepwise inflation and deflation of the lungs. Most of the variability in repeated determinations of intermarker distances at any lung volume was due to cardiogenic motion. When marker positions were determined repeatedly at the same phase of the cardiac cycle, the maximum coefficient of variation was less than 3% for a marker pair separated by 16.5 mm. At TLC, distances between all intralobar marker pairs in the intact thorax (prone and supine) and excised were highly linearly related (r = 0.96-0.99), whereas distances between interlobar marker pairs did not correlate as well (r = 0.77-0.86). We conclude that at TLC 1) the intact thorax does not distort the shape of the individual lobes from the state of isotropic expansion, and 2) in different body positions, overall lung shape may be different due to displacementof lobes relative to each other, but individual lobes remain uniformly expanded.

Effect of gravitational and inertial forces on vertical distribution of pulmonary blood flow.

Vertical distribution of pulmonary blood flow (VDPBF) was studied, using radioactive microsphere emboli, in dogs without thoracotomy in the right decubitus position during exposure to lateral (--Gy) accelerations of 1, 2, 4, and 6 G. At all levels of force environment studied, an inverse linear relationship was observed between vertical height in the thorax and pulmonary blood flow (ml/min/ml lung tissue) with a decrease in flow to the most dependent region of the lung despite large increases in intravascular pressures at this site. Changes in blood flow were smallest at the mid-lung level, the hydrostatic "balance point" for vascular and pleural pressures. These force environment-dependent changes in VDPBF are not readily explainable by the Starling resistor analog. Gravity-dependent regional differences in pleural and associated interstitial pressures, plus possible changes in vascular tone resulting from inadequate aeration of blood in the most dependent regions of the lung, probably also affect VDPBF.

Spatial distribution of pulmonary blood flow in dogs in increased force environments.

Spatial distribution of pulmonary blood flow (SDPBF) during 2- to 3-min exposures to 6-8 Gy acceleration was studied, using radioactive microspheres in dogs, and compared to previously reported 1 Gy control distributions. Isotope distributions were measured by scintiscanning individual 1-cm-thick cross sections of excised, fixed lungs. Results indicate: 1) the fraction of cardiac output traversing left and right lungs did not change systematically with the duration and magnitude of acceleration; but 2) the fraction is strongly affected by the occurrence or absence of fast deep breaths, which cause an increase or decrease, respectively, in blood flow through the dependent lung; and 3) Gy acceleration caused a significant increase in relative pulmonary vascular resistance (PVR) in nondependent and dependent regions of the lung concurrent with a decrease in PVR in the midsagittal region of the thorax. Result 3 may be mediated primarily by changes in regional alveolar volume and geometry in the nondependent hemithorax conbined with hydrostatic effects of extravascular fluid and active hypoxic response in the dependent region and is superimposed on, and may override, hydrostatic effects of perfusion pressures on SDPBF during acceleration.

Effect of force environment on regional pulmonary displacements and volumes in dogs.

Regional displacements of lung parenchyma due to respiratory movements at 1 G and 7 Gy were studied in anesthetized dogs in the left decubitus position in a water-filled respirator that provided control of respiratory volumes and rate and minimized inertial shifts in position and shape of the thorax and abdominal contents and related effects on the lungs. Inspiratory movements at 1 G were relatively uniform, although regional volume increased more in the nondependent (right) lung than in the dependent (left) lung. Regional functional residual capacity (FRC) increased in the nondependent lung and decreased in the dependent lung during exposures to 7 Gy. The greatest inspiratory increase in volume occurred near the midlung, where regional FRC changed the least during acceleration. The decrease in dependent and increase in nondependent lung volumes during acceleration are attributed to the increased weight and consequent downward displacement of the higher specific gravity mediastinal contents concomitantly with upward displacement of pulmonary gas, producing an exaggeration of the dependent-to-nondependent gradient in alveolar size.

Quantitative imaging of the structure and function of the heart, lungs, and circulation.

A 28-x-ray-source, cylindrical-scanning, transaxial tomographic x-ray-imaging system is in the process of being fabricated. This system will scan synchronously up to 250 parallel transverse cross sections of the human body over an axial range of 25 cm within 0.01 second at a maximum rate of 60 scans per second. The system will provide numerous variations of scanning configurations to permit quantitative assessment of the relative importance of transverse section thickness, image contrast, spatial and temporal resolution, and related computerized algorithms and display techniques. Synchronous imaging at high temporal resolution of a three-dimensional volume--for example, the heart--eliminates the need for successive periods of breath-holding and gated imaging techniques and is essential for quantitation of cardiovascular and pulmonary function and structure in intact animals or humans. Initial clinical applications are expected to be in the early detection of lung cancer and the diagnosis of the nature and degree of congenital and acquired cardiovascular disabilities.

Biplane videoroentgenographic analysis of dynamic regional lung strains in dogs.

A method is described for determining the spatial distribution of pulmonary parenchymal strains in the intact canine thorax, using measurements of displacement of metallic (1-mm-diam)) markers percutaneously implanted throughout the parenchyma of the right lung. Dogs are supported head up or head down in a water-immersion respirator with the animal's airway connected to ambient air. Tracking of the parenchymal markers is accomplished by stereo biplane videoroentgenographic recordings, which allow high temporal (60/S) and spatial (+/- 1.5 mm) resolution measurements of the "tagged" lungs during various respiratory maneuvers. After transferring the video information to a stop-action video disc, an operator-interactive computer program is used to input the geometric coordinates of the markers into the computer. The true spatial coordinates are then determined after correction for pincushion and magnification distortions. Spatial and temporal distributions of regional parenchymal strains are obtained by determining the distance between markers on a frame-by-frame basis over the extent of the respiratory cycle. Data indicate nonuniformity in regional lung parenchymal strains.