Biomedical subjects

F G Spinale

Publications and source records attributed to F G Spinale.

At least 163 records · Page 9Linked to original sources

PubMed1992

Use of a combined right ventricular ejection fraction-oximetry catheter system for coronary bypass surgery.

OBJECTIVE: To evaluate the reproducibility and accuracy of a new pulmonary artery catheter system that provides both right ventricular ejection fraction and continuous venous oxygen saturation monitoring. DESIGN: Criterion standard study. SETTING: University medical center. PATIENTS: A consecutive sample of ten patients undergoing elective coronary artery bypass surgery provided informed consent for the study. Exclusion criteria included emergency surgery or clinically important preoperative tricuspid regurgitation as assessed by echocardiography. None of the patient sample was excluded. MEASUREMENTS: Catheter-derived mixed venous and arterial oximetry data were compared with simultaneous values obtained using conventional laboratory cooximetry methods. Measurements were performed before cardiopulmonary bypass and intermittently up to 48 hrs after cardiopulmonary bypass. The variability of cardiac output and computed right ventricular ejection fraction was also assessed concurrently with the oximetry analysis. RESULTS: A significant correlation was observed for mixed venous oxygen saturation between catheter-derived and laboratory cooximetry data (r2 = .81, p < .01). Similarly, arterial oxygen saturation values obtained from pulse oximetry and laboratory values were significantly related (r2 = .81, p < .01). The coefficient of variation for each set of five repeated measurements for cardiac output was 8%, and for computed right ventricular ejection fraction, it was 16%. CONCLUSIONS: The combined catheter system provides the means to monitor both mixed venous oxygen saturation and right ventricular ejection fraction. These data provide a reliable and detailed assessment of cardiopulmonary function that should prove beneficial in the critical care setting.

Aged↗

PubMed1992

Changes in myocardial blood flow during development of and recovery from tachycardia-induced cardiomyopathy.

BACKGROUND: Chronic supraventricular tachycardia (SVT) causes a dilated cardiomyopathy and myocyte injury. Termination of SVT improves left ventricular (LV) function but is associated with LV hypertrophy. Changes in myocardial blood flow (MBF) that may accompany the development of and recovery from SVT cardiomyopathy might have a significant effect on LV function and myocyte structure. The goal of this study was to relate changes in LV function, myocyte composition, and coronary vascular structure to changes in MBF with the development and recovery of SVT cardiomyopathy. METHODS AND RESULTS: LV function and MBF were measured in three groups of conscious pigs: sham control (control; n = 8), after 3 weeks of atrial pacing (SVT, 240 beats per minute; n = 8), and after a 4-week recovery from SVT (post-SVT; n = 8) by echocardiography catheterization and microspheres. Measurements were made under three states: 1) at rest with a basal heart rate, 2) rapid atrial pacing (240 beats per minute), and 3) during adenosine infusion (1.5 mumol/l.kg-1.min-1) without pacing. LV myocyte, capillary, and arteriole morphometric studies were performed in five additional pigs from each group using histochemistry and electron microscopy. LV fractional shortening was lower and left atrial pressure was significantly higher in the SVT group compared with control at rest, during pacing, and with adenosine (p less than 0.05). In the post-SVT group, fractional shortening returned to control values at rest and with adenosine, but fell from control values with pacing (p less than 0.05). Left atrial pressure fell in the post-SVT but remained significantly higher than control (p less than 0.05). LV/body weight ratio was significantly increased in the post-SVT group (p less than 0.05). In all states, SVT LVMBF was significantly reduced from control values (rest, 0.8 +/- 0.3 versus 1.6 +/- 0.3 ml-min-1.g-1; pacing, 1.2 +/- 0.2 versus 3.1 +/- 0.3 ml.min-1.g-1; adenosine, 1.4 +/- 0.3 versus 4.4 +/- 0.4 ml.min-1.g-1, respectively, p less than 0.05). In the post-SVT group, LVMBF was similar to control at rest (1.3 +/- 0.2 ml.min-1.g-1) but was significantly lower than control with pacing and adenosine (2.0 +/- 0.4 and 2.5 +/- 0.5 ml.min-1.g-1, respectively, p less than 0.05). Myofibrillar content fell significantly with SVT compared with control (42 +/- 5 versus 61 +/- 3%, p less than 0.05) and returned to control values in the post-SVT group (64 +/- 3%). Capillary density remained unchanged in the SVT and post-SVT groups, but capillary luminal diameter decreased and arteriole diameter increased in the SVT group (p less than 0.05). CONCLUSIONS: The LV dysfunction and myocyte injury with SVT cardiomyopathy were associated with reduced MBF. Early recovery from SVT cardiomyopathy resulted in hypertrophy with normal MBF at rest, but significantly reduced coronary reserve.

Adenosine↗

PubMed1992

Relation between ventricular and myocyte function with tachycardia-induced cardiomyopathy.

Chronic supraventricular tachycardia (SVT) causes left ventricular (LV) dilatation and dysfunction. Changes in myocyte function and structure may be important factors in the development of SVT cardiomyopathy. Accordingly, LV function and isolated myocyte structure and function were examined in six pigs with pacing-induced SVT cardiomyopathy (3 weeks at 240 beats per minute) and six control pigs. LV function was examined by simultaneous echocardiography and catheterization, and isolated myocyte function was studied using computer-assisted video microscopy. Indexes of isolated myocyte contractile performance were examined in the unloaded, unattached state (31 control and 24 SVT cells) and after attachment to a basement membrane substrate (65 control and 45 SVT cells). LV fractional shortening and peak +dP/dt significantly decreased in SVT cells compared with control cells (12 +/- 2% versus 28 +/- 2%, and 842 +/- 61 versus 1,216 +/- 119 mm Hg/sec, respectively; p less than 0.05). Isolated myocyte percent shortening and normalized peak velocity of shortening of SVT myocytes adherent to a basement membrane were significantly lower than attached control myocytes (1.2 +/- 0.2% versus 4.3 +/- 0.3%, and 15 +/- 2 versus 37 +/- 5% resting cell length/sec, respectively; p less than 0.05). Similarly, in the unattached state, the extent and velocity of shortening of SVT myocytes were reduced by over 50% from control values. Contractile properties of attached and unattached cardiocytes were also examined in the presence of 2-8 mM extracellular Ca2+. For both attached and unattached SVT myocytes, responsiveness to increases in extracellular Ca2+ were significantly blunted from control values. Ultrastructural examination of SVT myocytes revealed that the percent volume of myofibrils within isolated myocytes was reduced from control values (46 +/- 7% versus 65 +/- 2%, p less than 0.05). In summary, SVT cardiomyopathy is probably due to a primary defect in isolated myocyte contractile performance. The reduced contractile function of SVT cardiomyopathic myocytes was associated with abnormalities in cytoarchitecture and Ca2+ responsiveness.

Animals↗

PubMed1992

The effects of valvular regurgitation on thermodilution ejection fraction measurements.

Through the use of thermodilution principles and rapid response thermistors, it is now possible to measure right ventricular ejection fractions serially in patients. However, to our knowledge, the extent to which tricuspid regurgitation affects the accuracy of thermodilution ejection fraction measurements has not been quantified. The purpose of this study was to compare actual and thermodilution ejection fraction measurements in an in vitro model of tricuspid regurgitation over a wide range of ejection fractions. Stepwise perforation of the inlet valve resulted in regurgitant fractions ranging from 4 to 40 percent. At each increment of inlet valve regurgitation, triplicate sets of thermodilution (EFthermo) ejection fraction measurements were obtained and compared with actual ejection fractions (EFactual). The mean difference between EFactual and EFthermo significantly increased with 8 percent regurgitation and significantly increased with greater increments of inlet valve regurgitation. EFthermo consistently underestimated EFactual over the entire range of regurgitant values. Linear regression analysis revealed a significant correlation between EFactual and EFthermo for all degrees of regurgitation; however, the correlation coefficient significantly declined from control valves with 13 percent regurgitation and declined further with 33 percent regurgitation. Qualitative classification of the inlet valve regurgitation into mild, moderate, and severe regurgitation was performed using pulsed Doppler echocardiography. Mild inlet valve regurgitation resulted in a significantly increased difference between EFactual and EFthermo from control values. A significant increase in the difference between EFactual and EFthermo was observed with both moderate and severe regurgitation. In summary, thermodilution underestimated actual ejection fraction in a direct linear relationship to the degree of inlet valve regurgitation. Thus, in the presence of tricuspid regurgitation, this method may still be useful in serially measuring changes in right ventricular ejection fraction.

Cardiac Output↗

PubMed1992

Effects of chronic tachycardia-induced cardiomyopathy on the beta-adrenergic receptor system.

Chronic supraventricular (or ventricular) tachycardia causes a dilated cardiomyopathy. Effective treatment requires ablation of the tachycardia using antiarrhythmic agents, cryoablation, electroablation, or surgical interruption/excision. However, the underlying pathophysiologic mechanisms responsible for the development of supraventricular tachycardia-induced cardiomyopathy have not been fully identified. We hypothesized that chronic supraventricular tachycardia is associated with significant changes in the beta-adrenergic system that may have implications for the pathophysiology and treatment of supraventricular tachycardia-induced cardiomyopathy. Accordingly, we examined the relationship between left ventricular function, plasma norepinephrine level, beta-receptor number and affinity, and response to a beta-agonist (isoproterenol) infusion in eight control pigs and eight pigs subjected to supraventricular pacing-induced tachycardia (240 beats/min for 3 weeks). Left ventricular function was measured using simultaneous echocardiography and catheterization. Left ventricular end-diastolic dimension and pressure increased in pigs with supraventricular tachycardia (5.1 +/- 0.4 cm and 27 +/- 2 mm Hg) versus control pigs (3.8 +/- 0.3 cm and 8 +/- 2 mm Hg), p < 0.05. Left ventricular fractional shortening decreased in supraventricular tachycardia (10 +/- 1%) versus control pigs (34 +/- 1%), p < 0.05. In addition, in the pigs with supraventricular tachycardia the fractional shortening versus left ventricular end-systolic stress relationship fell below the control relationship. Plasma norepinephrine level (measured by high-performance liquid chromatography) increased in pigs with supraventricular tachycardia (3592 +/- 1606 pg/ml plasma) versus control pigs (323 +/- 74 pg/ml plasma), p < 0.05. beta-Receptor number and affinity (measured by [3H]dihydroalprenolol binding) did not change in supraventricular tachycardia (98.6 +/- 11.5 fmol/mg protein and 7.2 +/- 1.1 nmol) versus control pigs (99.1 +/- 9.4 fmol/mg protein and 6.8 +/- 0.5 nmol). The response to isoproterenol infusion (10 micrograms/kg) in supraventricular tachycardia was blunted: the absolute increase in left ventricular peak (+)dP/dt was reduced in supraventricular tachycardia (833 +/- 233 mm Hg/sec) versus control pigs (2180 +/- 139 mm Hg/sec), p < 0.05. Chronic supraventricular tachycardia caused a decreased contractile state, increased plasma norepinephrine level, and caused no change in beta-receptor number or affinity; however, the response to beta-agonist infusion was blunted. These results suggest that chronic supraventricular tachycardia is associated with uncoupling of the beta-receptor from subsequent intracellular components of the beta-adrenergic system. Therefore medical management of chronic supraventricular tachycardia-induced cardiomyopathy before and immediately after definitive ablation may require use of pharmacologic agents whose actions do not depend on an intact beta-adrenergic pathway.

Animals↗

PubMed1991

In vitro validation of a right ventricular thermodilution ejection fraction system.

Right ventricular ejection fraction (RVEF) is used clinically as an index of right ventricular (RV) pump function. Clinical measurements of RVEF are complicated by the need for complex imaging equipment to compute RV volumes. Recently, the use of thermodilution (TD) methods have been suggested as a simplified means to measure RVEF (RVEFTD) in patients using rapid response thermistors. Validation, however, by comparison of RVEFTD and other methods in vivo, is difficult. Accordingly, thermodilution derived EF measurements (EFTD) were compared to known values using an in vitro system, with known ejection fractions (EF) set from 17-78% and stroke rates varying independently from 50-100 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 less than 0.001). Bias analysis showed that the points were within a 95% confidence interval of +/- 12%. Multivariate analysis showed that stroke rate did not significantly affect TD measurements (r = 0.03, p greater than 0.7). 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 RVEF in the clinical setting.

Algorithms↗

PubMed1991

The acute effects of flecainide in the swine heart failing from incessant supraventricular tachycardia.

The acute hemodynamic and electrophysiologic effects of flecainide in tachycardia-induced ventricular dysfunction were investigated using an animal model. Seven swine were initially (CON) evaluated by echocardiography and then by right heart catheterization and provocative electrical ventricular stimulation both before and after treatment with intravenous flecainide. Rapid atrial pacing at 210 to 240 beats/min (SVT) was then employed for 2 to 4 weeks until echocardiographic evidence of left ventricular dysfunction developed. Immediately upon termination of pacing, the above studies were repeated both before and after treatment with flecainide. Significant (p less than 0.0001) pacing-related hemodynamic effects on the cardiac output (CON:3.0 L/min versus SVT:1.6 L/min), right ventricular ejection fraction (CON:55% versus SVT:17%), and pulmonary wedge pressure (CON:8 mm Hg versus SVT:22 mm Hg) were observed. Pacing-related electrophysiologic effects included increases in the PR interval (CON:94 msec versus SVT:119 msec, p less than 0.001) and QTc interval (CON:418 msec versus SVT:450 msec, p = 0.016). With serum flecainide concentrations in the human therapeutic range, no significant effect on hemodynamic or electrophysiologic parameters in either the normal or failing heart were detected. Nonsustained ventricular tachycardia induced prior to pacing in one animal and after pacing in another animal was seen before but not following use of flecainide. No acute proarrhythmic effects were observed. In summary, intravenous flecainide had no significant acute adverse hemodynamic, electrophysiologic, or proarrhythmic effects in an animal model of tachycardia-induced ventricular dysfunction.

Animals↗

PubMed1991

Right ventricular pump dysfunction with acute experimental septic shock.

Right ventricular (RV) function has been poorly characterized at the onset of acute bacterial septic shock. Using a volumetric thermodilution catheter, previously validated in our laboratory, we serially measured RV function in a porcine model of acute septic shock. Six pigs (21.3 +/- 0.9 kg) were instrumented and Pseudomonas aeruginosa (3.4 x 10(8) cfu/ml, 0.3 ml/20 kg/min) was infused. RV ejection fraction, RV volumes, cardiac output, arterial pressure, central venous pressure, and pulmonary arterial pressure were measured at baseline and at 30, 60, 120, and 240 min after starting the bacterial infusion. RV ejection fraction and stroke volume were decreased at 30 min compared to baseline (21 +/- 5 vs 43 +/- 5% and 14 +/- 3 vs 23 +/- 3 ml, respectively; P less than 0.05) and remained depressed throughout the experiment. Mean arterial pressure was significantly reduced at 60, 120, and 240 min compared to baseline (P less than 0.05). There was a significant increase in pulmonary vascular resistance (1771 +/- 493 vs 301 +/- 99 dyn-sec-cm-5 at 30 min; P less than 0.05) and RV stroke work (5.7 +/- 1.1 vs 2.3 +/- 0.3 gm-m/beat at 30 min; P less than 0.05) while no significant change in RV end-diastolic volume or central venous pressure was observed. Thus, a decrease in RV pump performance was associated with an increase in afterload and no change in preload. These results suggest that severe RV pump dysfunction occurs early in acute septic shock. This was manifested by significant reductions in RV ejection fraction and increased in stroke work.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Ventricular function and Na+,K(+)-ATPase activity and distribution with chronic supraventricular tachycardia.

STUDY OBJECTIVE: The molecular and cellular mechanisms responsible for the dilated cardiomyopathy associated with chronic supraventricular tachycardia are not well understood. The purpose of this study was to examine Na+,K(+)-ATPase activity and distribution in a pacing induced model of dilated cardiomyopathy. DESIGN: Left ventricular function and Na+,K(+)-ATPase activity and distribution were examined in two groups of pigs: (1) atrially paced for 3 weeks (supraventricular tachycardia, 240 beats.min-1); (2) sham operated controls. SUBJECTS: 10 Yorkshire male swine (23-25 kg) were randomly assigned to the control group or the supraventricular tachycardia group. MEASUREMENTS AND MAIN RESULTS: Left ventricular function was examined using simultaneous pressure echocardiography. Na+,K(+)-ATPase activity was determined in tissue homogenates by measuring the rate of p-nitrophenol-phosphate (pNPP) hydrolysis. Changes in content and distribution of Na+,K(+)-ATPase were examined immuno-histochemically in tissue sections. Left ventricular fractional shortening decreased significantly with supraventricular tachycardia as compared to controls, at 15 (SEM 3)% v 31(3)%, respectively p less than 0.05. Supraventricular tachycardia resulted in a significant increase in end diastolic dimension [5.0(0.3) cm v 3.5(0.2) cm, respectively p less than 0.05] and pressure [22(4)mm Hg v 6(2)mm Hg, respectively p less than 0.05]. Maximal Na+,K(+)-ATPase activity (microgram pNPP.mg-1 protein.h-1) was significantly lower with supraventricular tachycardia than in controls, at 0.45(0.12) v 0.64(0.06), respectively p less than 0.05. In the presence of 7 microM digitalis, Na+,K(+)-ATPase activity was inhibited by 68% in control and by 45% in supraventricular tachycardia homogenates (p less than 0.05). In control sections all left ventricular myocytes showed a uniform immunostaining pattern along the sarcolemma for Na+,K(+)-ATPase, whereas a focal loss of staining was observed in myocytes from the supraventricular tachycardia group. CONCLUSIONS: The congestive cardiomyopathy produced by supraventricular tachycardia was associated with a reduction in sarcolemmal Na+,K(+)-ATPase activity and changes in enzyme distribution. The findings also suggest a reduction in digitalis sensitivity with chronic supraventricular tachycardia. These alterations in Na+,K(+)-ATPase activity may be one potential mechanism responsible for the depressed left ventricular function associated with chronic supraventricular tachycardia.

Animals↗

PubMed1991

Placement considerations for measuring thermodilution right ventricular ejection fractions.

BACKGROUND AND METHODS: Clinical examination of right ventricular (RV) performance has been hampered by the inability to measure easily RV volumes and ejection fraction. This study was performed to examine the effects of catheter position on thermodilution RVEF measurements. Six pigs (80 to 100 kg) were instrumented with an RV thermodilution catheter in the pulmonary artery, an injectate catheter in the right atrium, an atrial pacing electrode, and a systemic arterial catheter. RVEF measurements were determined using thermodilution in two ways: a) with incremental increases in pulmonary valve to thermistor distance; and b) with incremental increases in injectate port to tricuspid valve distance. These measurements were obtained at a paced rate of 102 +/- 2 beats/min and then repeated with pacing-induced tachycardia (140 beats/min). RESULTS: There was no significant difference in thermodilution RVEF measurements with the thermistor positioned 0 to 10 cm from the pulmonary valve at either heart rate. A significant reduction in RVEF occurred with the injection port located 5 to 7 cm proximal to the tricuspid valve, with this decrease becoming more pronounced during tachycardia. CONCLUSIONS: These results demonstrate that RVEF measurements can be reliably obtained using thermodilution. In these large hearts, thermodilution RVEF measurements appear to be independent of thermistor position within the pulmonary artery. However, large distances from injectate port to tricuspid valve reduced RVEF measurements.

Animals↗

PubMed1991

Tachycardia-induced cardiomyopathy: effects on blood flow and capillary structure.

Chronic supraventricular tachycardia (SVT) causes a dilated cardiomyopathy. A potential factor contributing to the development of SVT-induced cardiomyopathy is abnormal myocardial blood flow (MBF). The purpose of this study was to relate changes in left ventricular (LV) function, MBF, and capillary structure with the development of SVT-induced cardiomyopathy. LV function and MBF were measured in two groups of conscious pigs: sham control (CON; n = 8) and after 3 wk of atrial pacing (SVT; 240 beats/min; n = 8) using echocardiography-catheterization and microspheres. Measurements were made under three states: 1) at rest with a basal heart rate, 2) during rapid atrial pacing (240 beats/min), and 3) during adenosine infusion (1.5 microM.kg-1.min-1) without pacing. LV capillary density, diameter, wall thickness, and capillary-myocyte distance were measured in four additional pigs from each group. LV fractional shortening was lower, and left atrial pressure was significantly higher in the SVT group compared with CON at rest, during pacing, and with adenosine (P less than 0.05). In the CON group, average LV-MBF at rest was 2.0 +/- 0.2 ml.min-1.g-1, increased with pacing to 3.0 +/- 0.2 ml.min-1.g-1 (P less than 0.05), and increased further with adenosine to 4.1 +/- 0.3 ml.min-1.g-1 (P less than 0.05). In all states, SVT LV-MBF was significantly reduced vs. CON (P less than 0.05); SVT LV-MBF was 0.8 +/- 0.2 ml.min-1.g-1 at rest, increased to 1.3 +/- 0.3 ml.min-1.g-1 with rapid pacing (P less than 0.05), and remained unchanged during adenosine (1.3 +/- 0.4 ml.min-1.g-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

PubMed1991

Collagen remodeling and changes in LV function during development and recovery from supraventricular tachycardia.

Chronic supraventricular tachycardia (SVT) causes left ventricular (LV) dYsfunction and dilatation. Termination of SVT appears to improve symptoms of congestive heart failure. However, the structural events that occur during development and regression of SVT-induced cardiomyopathy are unknown. Accordingly, LV function (simultaneous echocardiogram-catheterization) and collagen content and distribution were measured in pigs (23-25 kg) assigned to three groups: 1) rapid atrial pacing (240 beats/min) for 3 wk (SVT, n = 10); 2) SVT for 3 wk, followed by deactivation of the pacemaker and a 4-wk recovery period (PST, n = 9); and 3) sham-operated controls (CON, n = 10). LV fractional shortening was 30 +/- 2% in CON, fell to 13 +/- 2% with SVT (P less than 0.05), and returned to CON values with PST (31 +/- 2%). SVT resulted in significantly increased LV end-diastolic dimension compared with CON (4.9 +/- 0.3 vs. 3.5 +/- 0.2 cm, P less than 0.05) and no change in LV wt/body wt (2.7 +/- 0.2 vs. 2.6 +/- 0.2 g/kg, P = 0.85). Termination of SVT (PST) resulted in development of hypertrophy, LV mass increased to 3.50 +/- 0.3 g/kg (P less than 0.05 vs. CON). With the use of pressure-dimension-thickness relations during diastole, the regional chamber stiffness constant (Kc) was computed. Kc was unchanged by SVT compared with CON (5.3 +/- 1.4 vs. 3.7 +/- 0.5, P greater than 0.35) but increased with PST (7.4 +/- 0.6, P less than 0.05). LV hydroxyproline content significantly fell with SVT compared with CON (2.24 +/- 0.58 vs. 2.68 +/- 0.45 mg/g dry wt, P less than 0.05, respectively) and significantly increased with PST (3.68 +/- 0.85 mg/g dry wt, P less than 0.05). With the use of transmission electron microscopy, collagen fibril diameter was reduced with SVT compared with CON (1.45 +/- 0.5 vs. 1.7 +/- 0.5 microns, P less than 0.05) and increased with PST (3.3 +/- 1.4 microns, P less than 0.05). Scanning electron microscopy revealed disruption of collagen struts between adjacent SVT myocytes and a thickened collagen weave with PST. Thus chronic SVT resulted in systolic and diastolic dysfunction and reduced collagen support of adjoining myocytes. Early recovery from SVT was associated with LV hypertrophy, increased collagen, and increased LV stiffness.

Animals↗

PubMed1991

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.

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.

Animals↗

PubMed1991

Alterations in myocyte shape and basement membrane attachment with tachycardia-induced heart failure.

Chronic supraventricular tachycardia (SVT) results in left ventricular (LV) dilatation and dysfunction. However, the underlying mechanisms responsible for LV failure in this setting are not known. LV force production is dependent on the coupling of myocytes to the extracellular matrix, which is mediated through the basement membrane. This study was designed to determine whether alterations in myocyte geometry and basement membrane attachment are associated with LV failure in a pacing-induced model of cardiomyopathy. Echocardiographic measurement of LV function was performed in six pigs after 3 weeks of pacing-induced SVT (240 beats/min) and in eight sham-operated controls. Myocytes from these hearts were isolated, and attachment studies to specific components of the basement membrane were performed using laminin, fibronectin, and collagen IV. The SVT group when compared with the control group showed a significant reduction of LV fractional shortening (14 +/- 2% versus 31 +/- 2%, respectively; p less than 0.05), increased end-diastolic dimension (50 +/- 1 versus 35 +/- 1 mm, respectively; p less than 0.05), and lengthening of isolated myocytes (196 +/- 18 versus 142 +/- 9 microns, respectively; p less than 0.05). Myocyte attachment to laminin (50 micrograms/ml) was significantly decreased at 60 minutes in the SVT group compared with the control group (18.2 +/- 4.5 versus 60.9 +/- 4.5 cells/mm2, respectively; p less than 0.05). Similar reductions in myocyte attachment to fibronectin and collagen IV were observed. Ultrastructural examination of LV sections revealed focal disruptions of the basement membrane-sarcolemmal interface and a reduced number of sarcolemmal festoons in SVT hearts compared with control hearts (0.8 +/- 0.6 versus 2.8 +/- 0.8/4 microns, respectively; p less than 0.05). These alterations in myocyte morphology and basement membrane attachment may contribute to the LV failure associated with chronic SVT. Further, these structural changes may play a significant role in the progression of ventricular dysfunction as well as recovery from chronic SVT.

Animals↗

PubMed1991

Relation between ventricular and myocyte remodeling with the development and regression of supraventricular tachycardia-induced cardiomyopathy.

Chronic supraventricular tachycardia (SVT) causes left ventricular (LV) dilatation and dysfunction. Termination of SVT appears to reduce LV size and improve function. However, changes in myocyte structure and morphology that accompany the development and regression of SVT-induced cardiomyopathy have not been studied. Accordingly, we measured LV function using echocardiography and catheterization in three groups of six pigs each: 3 weeks of atrial pacing (SVT; 240 beats/min), 4-week recovery from SVT (PST), and sham-operated controls. At each of these three end points, isolated myocyte dimensions and nuclear number were measured using fluorescence, and the volume percent of myocytes and myofibrils was computed from tissue sections using stereological techniques. SVT resulted in reduced LV fractional shortening (15 +/- 3% versus 31 +/- 2%, p less than 0.05), increased end-diastolic dimension (5.6 +/- 0.8 versus 3.8 +/- 0.2 cm, p less than 0.05), and no change in mass (2.6 +/- 0.1 versus 2.6 +/- 0.2 g/kg, p = NS) compared with controls. Myocyte length significantly increased with SVT (171 +/- 9 versus 109 +/- 11 microns, p less than 0.05), without significant changes in cell width (28 +/- 2 versus 26 +/- 2 microns). Nuclear number did not change with SVT; however, nuclear area/myocyte area significantly increased compared with controls (9.5 +/- 0.8 versus 8.7 +/- 0.8 x 10(-2), p less than 0.05). The volume percent of myocytes within the ventricular wall and the volume percent of myofibrils within myocytes decreased with SVT compared with controls (72 +/- 3% versus 80 +/- 3% and 45 +/- 5% versus 63 +/- 4%, respectively, p less than 0.05), with no change in total myocyte volume (54.2 +/- 2.7 versus 54.3 +/- 1.8 microns3 x 10(12)). In the PST group, LV fractional shortening returned to control values; however, there was persistent dilatation (end-diastolic dimension: 4.2 +/- 0.1 cm, p less than 0.05), and LV hypertrophy developed (3.3 +/- 0.3 g/kg, p less than 0.05). Increased myocyte length (158 +/- 5 microns, p less than 0.05) and width (33 +/- 2 microns, p less than 0.05) were observed in the PST group. The volume percent of myocytes and myofibrils returned to control values, with total myocyte volume significantly increased in the PST group compared with the control and SVT groups (74.5 +/- 2.6 microns3 x 10(12), p less than 0.05). In addition, the number of nuclei per myocyte in the PST group significantly increased from control values (5.1 +/- 0.1 versus 4.0 +/- 0.1, p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1991

Anesthetic and postoperative protocols for a canine model of reversible left ventricular volume overload.

The purpose of this study was to develop anesthetic and postoperative methods that could be used in a canine model of reversible left ventricular volume overload (LVVO). LVVO was created by inducing mitral regurgitation (MR) in adult conditioned dogs. Using fluoroscopy, MR was induced by passing urologic grasping forceps into the left ventricle through a carotid artery and rupturing one or more chordae tendinea. Cardiac catheterization was performed after significant cardiac dysfunction developed (3 months after creation of MR) in order to collect data to confirm reduced contractile function. The MR was repaired by replacing the damaged valve with a bovine pericardial xenograft. Dogs were followed with sequential cardiac catheterizations to determine if the valvular replacement reversed the cardiac dysfunction. To develop this model, unique anesthetic and post-operative care protocols had to be instituted. In order not to exacerbate the existing cardiac dysfunction, a high dose narcotic anesthetic regimen using a sufentanil infusion at 9-13 microgram/kg h-1 was developed in association with cardiopulmonary bypass and hypothermia for the mitral valve replacement surgery. Intensive postoperative care protocols that involved major personnel and pharmaceutic interventions were necessary. Using our methods 11/17 dogs survived the procedure and were included in the protocol for study of mechanisms involved in reversal of cardiac dysfunction.

Anesthesia↗

PubMed1991

Sedative and cardiovascular effects of midazolam in swine.

The ability to reliably produce sedation in swine is hampered by the paucity of agents available. This project examined the use of a new water soluble benzodiazepine, midazolam, as a sedative in swine. Echocardiographic studies were performed on thirty 23 to 30 kg Yorkshire swine before and 20 minutes after each animal received a single intramuscular dose of 100 micrograms/kg midazolam. Heart rate and respiratory rate decreased significantly compared to nonsedated values (93 +/- 7 versus 117 +/- 2 bpm and 10 +/- 1 versus 20 +/- 1 breaths/min, respectively [p less than 0.05]). However, there was no effect on left ventricular fractional shortening (29.9 greater than 0.05 versus 29.5 +/- 0.05% [p greater than 0.05]). An additional five pigs were instrumented for a dose response study in order to collect hemodynamic data and blood gas values at baseline, and 15 min after the intravenous administration of incremental doses of midazolam (100 to 1,000 micrograms/kg). Despite a significant decrease in heart rate and respiratory rate, cardiac output, blood gases, and pH remained within normal ranges at all dosage levels. Both routes of administration produced sedation for 20 min in all animals. Midazolam is an effective swine sedative that is associated with stable cardiac function.

Animals↗

PubMed1991

DAPI as a useful stain for nuclear quantitation.

A simple-to-use fluorescent stain, 4',6-diamidino-2-phenylindole (DAPI), visualizes nuclear DNA in both living and fixed cells. DAPI staining was used to determine the number of nuclei and to assess gross cell morphology. Following light microscopic analyses, the stained cells were processed for electron microscopy. Cells stained with DAPI showed no ultrastructural changes compared to the appearance of cells not stained with DAPI. DAPI staining allows multiple use of cells eliminating the need for duplicate samples.

Animals↗