Showing papers by "Francis G. Spinale published in 1990"

Changes in Left Ventricular Volume, Mass, and Function During the Development and Regression of Supraventricular Tachycardia-Induced Cardiomyopathy. Disparity Between Recovery of Systolic Versus Diastolic Function

Abstract: Chronic supraventricular tachycardia causes a dilated cardiomyopathy in man. Terminating this tachycardia appears to result in symptomatic improvement; however, its effects on left ventricular (LV) volume, mass, and function have not been fully examined. Accordingly, hemodynamic studies using simultaneous echocardiography and catheterization were performed in three groups of pigs: 1) those subjected to rapid left atrial pacing (240 beats/min) for 3 weeks (SVT, n = 8), 2) those subjected to supraventricular tachycardia for 3 weeks followed by termination of pacing and a 4-week recovery period (PSVT, n = 9), and 3) sham-operated controls (CTR, n = 10). Systolic pump function was assessed using fractional shortening (FS), peak ejection rate [peak (-)dD/dt], and maximum rate of pressure development [peak (+)dP/dt]. Diastolic function was assessed using the time constant of isovolumic pressure decline (tau), peak early diastolic filling rate [peak (+)dD/dt], the chamber stiffness constant (Kc), and the myocardial stiffness constant (Km). Supraventricular tachycardia caused LV dilation (end-diastolic dimension [EDD] increased from 3.5 +/- 0.4 cm in CTR to 4.9 +/- 0.5 cm in SVT, p less than 0.05) but no change in LV mass (LV weight-to-body weight ratio [LV/BW]) was 2.58 +/- 0.3 g/kg in CTR and 2.66 +/- 0.4 g/kg in SVT), all indexes of systolic function became abnormal (FS fell from 30 +/- 4% in CTR to 13 +/- 5% in SVT, p less than 0.05), and the indexes of relaxation and filling were slowed (tau increased from 36 +/- 3 msec in CTR to 51 +/- 13 msec in SVT, p less than 0.05). There were no significant changes in Kc or Km. After terminating the supraventricular tachycardia, LV volume fell but remained greater than that in CTR (EDD was 4.2 +/- 0.4 cm in PSVT, p less than 0.05 versus CTR) and substantial LV hypertrophy developed (LV/BW was 3.48 +/- 0.5 g/kg in PSVT, p less than 0.05 versus CTR). Systolic function returned to normal (FS was 31 +/- 5% in PSVT) but diastolic function remained abnormal. In PSVT, tau remained prolonged (49 +/- 12 msec, p less than 0.05 versus CTR), Kc increased from 3.7 +/- 1.0 in CTR to 7.4 +/- 1.2 (p less than 0.05), and Km increased from 4.4 +/- 1.5 in CTR to 13.9 +/- 9.7 (p less than 0.05). Thus, the improvement in systolic function that occurs after the termination of supraventricular tachycardia is associated with the development of LV hypertrophy and persistent diastolic dysfunction.

Chronic supraventricular tachycardia causes ventricular dysfunction and subendocardial injury in swine.

Abstract: Chronic supraventricular tachycardia has been associated with ventricular dysfunction in humans and animals. However, this ventricular failure is poorly characterized, and the ultrastructural consequences of supraventricular tachycardia are unknown. We serially examined right and left ventricular function, endomyocardial ultrastructure, and creatine kinase activity in eight pigs at base line and again at 1, 2, and 3 wk following rapid atrial pacing. Left and right ventricular ejection fractions fell significantly from base line after 1 wk of chronic tachycardia. Three weeks of chronic pacing resulted in further deterioration in ejection fractions. Significant biventricular chamber dilatation developed and was associated with a reduction in end-diastolic wall thickness after 2 wk of tachycardia. Mitochondrial injury and diminished mitochondrial cytochrome oxidase staining of subendocardial myocytes were observed after 2 wk of tachycardia. Endomyocardial creatine kinase activity fell from control levels following 2 wk of pacing. Postmortem examination revealed a reduction in left ventricular wall thickness compared with 14 control animals. Fibrosis occurred along the subendocardial layer in paced animals, and glycogen content was also reduced. In summary, chronic supraventricular tachycardia resulted in severe biventricular pump dysfunction and chamber dilatation that were associated with ultrastructural alterations and reduced enzyme activity of the subendocardial myocytes. These ultrastructural and metabolic changes may be potential mechanisms responsible for the ventricular dysfunction and dilatation observed in this model.

Relationship of bioimpedance to thermodilution and echocardiographic measurements of cardiac function.

Abstract: Bioimpedance cardiography has been suggested as a noninvasive means to monitor cardiac function. However, this method has not been compared to more conventional techniques such as echocardiography. This study compared simultaneously obtained thermodilution cardiac output and right ventricular ejection fraction (RVEF), and echocardiographic left ventricular fractional shortening (LVFS), to bioimpedance cardiac output and the maximum first derivative of the bioimpedance signal (dZ/dtmax) during positive inotropic stimulation and preload reduction. Eight pigs were instrumented with a rapid response thermistor (positioned in the pulmonary artery) and bioimpedance electrodes. Simultaneous thermodilution, echocardiographic, and bioimpedance measurements were performed at baseline and after 5, 10, and 15 min of isoproterenol infusion (0.5 microgram/kg.min). In six pigs, measurements were also performed after balloon occlusion of the inferior vena cava. A significant correlation was observed between LVFS and dZ/dtmax (r = .88, n = 35) over all time points. Thermodilution and bioimpedance cardiac output were in close agreement (r = .92, n = 35). However, bioimpedance overestimated cardiac output in the very low and high output states. The mean difference between thermodilution and bioimpedance cardiac outputs was -0.02 +/- 0.37 L/min. There was a positive relationship between RVEF and dZ/dtmax (r = .54, n = 35). In summary, bioimpedance was significantly correlated with thermodilution cardiac output over a wide hemodynamic range. The peak first derivative of the bioimpedance signal dZ/dtmax may provide a noninvasive index of ventricular pump performance. Further studies are required to evaluate the diagnostic value of bioimpedance cardiography in the clinical setting.

Cardiac function and morphology of Hanford miniature swine and Yucatan miniature and micro swine.

Abstract: The use of miniature swine in biomedical research is increasing; however, a comparison of cardiac function and morphology between strains has yet to be characterized The purpose of this project was to examine comprehensive hemodynamics and cardiac morphology of three groups of ten normal, 4 months old, age-matched Yucatan miniature (MINI) pigs, Yucatan micropigs (MICRO) and Hanford (HAN) miniature pigs, 5 males and five females per group Closed chest cardiac catheterization under equivalent conditions was performed followed by post mortem cardiac morphometry Mean arterial pressure was significantly greater in the Hanford group when compared to both the minipig and micropig pigs (HAN: 89 +/- 4; MINI: 48 +/- 3; MICRO: 53 +/- 2 mmHg) Pulmonary vascular resistance was significantly different between the three groups (HAN: 9 +/- 1; MINI: 60 +/- 12; MICRO: 111 +/- 29 dyne x sec/cm x m2) The Hanford strain had a significantly smaller heart weight to body weight ratio than the other two groups (HAN: 46 +/- 10; MINI: 57 +/- 01; MICRO: 55 +/- 10) Variations in cardiovascular parameters occur among these strains and should be considered when constructing experimental designs

The pig as a model of tachycardia and dilated cardiomyopathy.

Abstract: Chronic Supraventricular Tachycardia (SVT) can produce a dilated cardiomyopathy which has a poorly understood association with ventricular dysfunction in humans and animals. The purpose of this study was to produce a model of chronic SVT and dilated cardiomyopathy using swine, which have a cardiac anatomy similar to man. Eight pigs were implanted with chronic atrial catheters and a pacemaker, with four additional sham-operated pigs serving as controls. We examined ventricular function and morphology at baseline (120 +/- 3 bpm), pacing baseline (240 bpm), and at 1, 2 and 3 weeks of rapid atrial pacing (240 bpm). Ventricular ejection fractions fell significantly from baseline following 1 week (left: 38 +/- 3% vs baseline 61 +/- 1%; right: 31 +/- 5% vs baseline 56 +/- 1%; p less than 0.05) and deteriorated further by 3 weeks of SVT (left: 26 +/- 4%, right: 19 +/- 3%; p less than 0.05). Significant biventricular chamber dilation developed by 2 weeks of SVT (left: 50 +/- 5 cc vs paced baseline 27 +/- 2 cc; right: 67 +/- 6 cc vs paced baseline 28 +/- 3 cc; p less than 0.05) and continued to increase by week 3 of SVT (left: 66 +/- 11 cc; right: 78 +/- 8 cc; p less than 0.05). Five additional paced pigs, without chronic atrial catheters, were followed using echocardiography.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between bioimpedance, thermodilution, and ventriculographic measurements in experimental congestive heart failure

Abstract: Purpose of investigation – Bioimpedance cardiography has been suggested as a non-invasive means to monitor cardiac function but has not been tested in cases of severe ventricular dysfunction. This study compared thermodilution stroke volume, ventriculographic left ventricular ejection fraction, bioimpedance stroke volume, and the maximum first derivative of the bioimpedance signal dZ/dtmax, during the development of experimental congestive heart failure. Design – Simultaneous thermodilution stroke volume, ventriculography, and bioimpedance measurements were serially measured in pigs following acute pacing, and after 1, 2, and 3 weeks of tachycardia. Thermodilution stroke volume measurements were obtained by positioning a thermistor tipped catheter into the pulmonary artery and integrating the thermodilution curve with respect to heart rate. Left ventricular stroke volume and ejection fractions were measured from single plane ventriculograms using the area-length method. Using a series of electrodes positioned on the thoracic segment and a low level current (2.5 ma), the bioimpedance waveform was recorded and stroke volume and dZ/dtmax computed. Subjects – The subjects were eight pigs (23-30 kg) with developing ventricular dysfunction due to chronic rapid atrial pacing (240 beats·min−1) and four controls. Measurements and main results – Left ventricular ejection fraction decreased significantly from acutely paced values following 7 d tachycardia [60(SEM 1)% v 41(3)% respectively, p<0.01] and continued to decline with longer durations of tachycardia. A significant correlation was observed between ejection fraction and dZ/dtmax (r = 0.74, n = 32). Thermodilution and bioimpedance stroke volumes fell significantly from acutely paced values after week 2 of tachycardia [thermodilution: 13.8(0.9) v 8.5(1.4) ml; bioimpedance: 13.6(1.1) v 11.2(1.5) ml respectively, p<0.05] and were highly correlated throughout the study period (r = 0.90, n = 32). However, bioimpedance overestimated thermodilution values at week 2 (p<0.05) and at week 3 of tachycardia [thermodilution: 8.4(0.8) ml v bioimpedance: 9.6(1.0) ml, NS]. Conclusion – In a tachycardia induced model of heart failure, bioimpedance was significantly correlated with thermodilution stroke volume. The peak first derivative of the bioimpedance signal dZ/dtmaxmay provide a non-invasive index of ventricular pump performance. While these results are promising, further studies are required to evaluate the diagnostic value of bioimpedance cardiography in the clinical setting.

Heritable ventricular septal defect in Yucatan miniature swine.

Abstract: A heritable ventricular septal defect (VSD) was found in a strain of Yucatan miniature swine. The defect was determined to be a high membranous VSD analogous in anatomic location to the most common from of VSD in humans. Eighteen animals were studied clinically, hemodynamically and at necropsy to characterize the defect. Three mature animals developed pulmonary hypertension. Three animals were found to have a patent foramen ovale (PFO) in addition to the VSD. VSD is heritable probably due to polygenic factors. VSD in Yucatan miniature swine may be a suitable model of the human disease syndrome.

Right ventricular function and three-dimensional modeling using computer-aided design.

Abstract: Right ventricular (RV) volumetric and morphological analysis is complicated by the trabeculations and geometric configuration of the RV chamber. To improve RV analysis, custom computer-aided design programs were employed to obtain RV volumes and three-dimensional models from biplane ventriculograms. Biplane RV ventriculograms were analyzed from 14 anesthetized dogs and 22 RV casts. Computed volumes were highly correlated with reference RV volumes (r = 0.98, n = 36, P less than 0.01) with a range of 5-73 ml. Three-dimensional wire-frame and solid models constructed from the ventriculographic images provided excellent detail and a new perspective in chamber shape. This modeling technique was then used to examine RV volumes, geometric conformation, and regional shortening in 10 pigs during inotropic stimulation and preload reduction. Changes in RV volumes, ejection fraction, and regional motion were detected as well as alterations in chamber conformation. In summary 1) computer-aided design offers an accurate and simplified means to compute RV volumes using basic microcomputer equipment, and 2) three-dimensional reconstruction provided a unique view of RV geometry and a means to examine regional RV function.

Wavefront myocyte injury and relationship to function in right ventricular ischemia.

Abstract: Past studies of acute canine right ventricular (RV) ischemia have failed to demonstrate early irreversible injury or decreased function. However, the dog frequently has an extensive collateral circulation not found in all humans. The aim of this study was to measure RV global and regional function after right coronary occlusion in 32 closed-chest pigs. RV function was assessed by biplane ventriculography, and myocardial injury was examined by immunohistochemical localization of creatine kinase (CK) and by electron microscopy. Global RV ejection fraction and apical and midventricular regional function declined significantly after 10 min of occlusion. Injury to the myocardium progressed from the endocardium to the epicardium. Significant injury was observed in myocytes of the endocardium, midmyocardium, and epicardium at 10, 30, and 60 min of occlusion, respectively. Regional RV function and the extent of myocardial injury showed a high correlation (r = 0.96, P less than 0.01). The strong CK immunostaining seen in control hearts was diminished in myocytes along the endocardium at 15 min of occlusion. Depletion of immunoreactive CK in myocytes progressed toward the epicardium with longer ischemic times. These findings demonstrate that RV ischemic injury progresses in a wavefront fashion in the pig, which has similar coronary anatomy to humans, and irreversible myocardial injury occurred after 15-30 min of ischemia.

Rapid Response Thermistors To Measure Ventricular Ejection Fraction: In Vitro Validation

Abstract: Ejection fraction (EF) is used clinically as an index of ventricular pump function. Clinical measurements of EF are complicated by the need for complex imaging equipment to compute ventricular volumes. Recently, the use of thermodilution (TD) methods have been suggested as a simplified means to measure EF (EFTD) in patients using rapid response thermistors. However, comparisons of EFTD and other methods in vivo are difficult. Accordingly, EFTD'S were compared to known values using an in vitro system, with known EF's set from 17 to 78% and stroke rate varied independently from SO to 100 strokes/min. EFTD was computed by fitting the downslope of the TD curve to a monoexponential function and computing the time constant of thermal decay. A significant correlation existed between EFTD and actual EF over the entire study (r=0.96, p 0.8). This study demonstrates that TD accurately predicts EF using an in vitro system and appears to be independent of stroke rate. Thus, TD methods may provide an accurate, simple and reliable means to serially measure EF.