Lauren J. Curtis

Load dependence of cardiac output in biventricular pacing

BACKGROUND The effect of biventricular pacing on stroke volume is believed to be dependent on right ventricular/left ventricular delay, but effects in individual patients are unpredictable. This variability may reflect relative right and left ventricular volume and/or pressure overloads. Accordingly, we tested the hypothesis that the relation of cardiac output to right ventricular/left ventricular delay is load dependent in a pig model of pulmonary stenosis. METHODS After median sternotomy in 6 anesthetized, domestic pigs, complete heart block was induced by ethanol ablation. During epicardial, atrial tracking DDD biventricular pacing, atrioventricular delay was varied between 60 and 180 ms in 30-ms increments. Right ventricular/left ventricular delay was varied at each atrioventricular delay from +80 ms (right ventricle first) to -80 ms (left ventricle first) in 20-ms increments. Aortic flow, right ventricular pressure, peripheral arterial pressure, and electrocardiogram were measured in the control state and during pulmonary stenosis, created by tightening a snare around the pulmonary artery until cardiac output decreased by 50%. RESULTS Atrioventricular and right ventricular/left ventricular delay had no effect on cardiac output during the control state, but during pulmonary stenosis there was a statistically significant (P =.0001, repeated-measures analysis of variance) right ventricular/left ventricular delay-related trend toward higher cardiac output with right ventricular pacing first. This effect was more pronounced when the optimal atrioventricular delay was determined first, resulting in a 20% increase in cardiac output when the optimal right ventricular/left ventricular delay was compared with simultaneous biventricular pacing. CONCLUSIONS Optimized biventricular pacing in swine is associated with increased cardiac output during acute pulmonary stenosis, but not during the control state. Further studies are needed to determine whether specific types of right ventricular and left ventricular overload predictably affect the relation between right ventricular/left ventricular delay and cardiac output.

Mechanisms of optimized biventricular pacing in pulmonary stenosis: effects on left ventricular geometry in swine.

We tested the hypothesis that optimized biventricular pacing (BiVP) enhances cardiac output (CO) during critical pulmonary stenosis (PS) by attenuating distortions in left ventricular (LV) geometry. Following median sternotomy in six anesthetized pigs, heart block was induced by ethanol ablation. During epicardial, DDD BiVP, atrioventricular delay (AVD) was varied from 60 ms to 180 ms in 30 ms increments. At the AVD with the highest CO right‐left delay (RLD) was varied from (+) 80 ms (RV first) to (−) 80 ms (LV first) in 20 ms increments. At each pacing setting, aortic flow, ECG, and LV diameter were measured in the control state (CON) and during PS, created by snaring the pulmonary artery until CO decreased 50%. Short axis LV echocardiograms were obtained at (+) and (−) 80 ms. In CON, RLD had no effect on function or geometry. During PS optimum BiVP resulted in significant increases in CO (1.12 L/min ± 0.13 SEM at RLD =+ 40 ms versus 0.92 ± 0.12 at RLD = 0 and 0.73 ± 0.08 at RLD =−80), and LV fractional shortening (8.97%± 0.51% at RLD =+ 40 ms versus 7.34%± 0.58% at RLD = 0 and 6.21%± 0.66% at RLD =−80). In addition, LV eccentricity with (−) RLD was significantly different versus CON at both end‐diastole (0.79 ± 0.07 vs 1.02 ± 0.03, P = 0.011 Students t‐test) and end‐systole (0.83 ± 0.05 vs 1.00 ± 0.02, P = 0.017). However, with (+) RLD differences versus CON were not significant at either end‐diastole (0.88 ± 0.06 vs 0.99 ± 0.03) or end‐systole (0.92 ± 0.03 vs 1.01 ± 0.03). In swine hearts with PS, optimized BiVP increases CO, fractional shortening, and LV symmetry. BiVP warrants further study as treatment for acute postoperative heart failure.

Validation of mean arterial pressure as an indicator of acute changes in cardiac output

Changes in mean arterial pressure (MAP) are often assumed to reflect changes in cardiac output (CO). A linear relationship is postulated to exist between these two quantities based upon the circuit model for systemic circulation. Previous studies have correlated changes in CO and MAP. However, to our knowledge, no studies have tested the relationship between CO and MAP in vivo without changes in systemic vascular resistance. Research on baroreceptor stimulation and vasomotor response has shown that vasomotor tone changes 15 to 60 seconds after an acute change in CO. Maximal activation of vasomotor response occurs after approximately 30 seconds. Thus MAP should correlate directly with CO during acute changes (<15 seconds). To test this, we examined the relationship between CO and MAP during 10 second occlusions of the inferior vena cava in anesthetized pigs. A linear relationship existed between CO and MAP in seven pigs (%MAP = 0.60[%CO] − 0.41, p = 0.0001). This study validates the use of MAP as an indicator of acute changes in CO. Fluctuations in MAP correlate well with acute changes in CO in the absence of changes in vascular tone.

Cariporide is cardioprotective after iatrogenic ventricular fibrillation in the intact swine heart

BACKGROUND We sought to introduce sodium-hydrogen exchange inhibition as prophylaxis against the development of ventricular dysfunction in the setting of implantable cardioverter defibrillator insertion in high-risk patients. Cariporide, shown to be safe in humans, was used to reproduce previous results in our laboratory that demonstrated that sodium-hydrogen exchange inhibition preserves left ventricular (LV) function after ventricular fibrillation (VF) and reperfusion. METHODS Twelve pigs (weight, 35 to 55 kg) were divided into two groups of six. Baseline ventricular function studies were based on echocardiography, conductance, aortic flow, and LV pressure. Animals were given vehicle (control) or cariporide (3 mg/kg intravenously). Ten minutes later, hearts underwent 80 seconds of VF. After reperfusion for 40 minutes, function studies were repeated. RESULTS Postmortem examination included measuring passive pressure-volume curves and myocardial water content. Systolic indices, including preload recruitable stroke work and ejection fraction, were significantly depressed from baseline after VF and reperfusion for control animals (preload recruitable stroke work, 30.13 +/- 0.59 [standard error of the mean] versus 43.85 +/- 2.60 mm Hg; ejection fraction, 25.7% +/- 2.4% versus 33.5% +/- 3.0%) but not for those in the cariporide group (preload recruitable stroke work, 38.36 +/- 1.87 versus 40.86 +/- 1.45 mm Hg; ejection fraction, 33.9% +/- 3.5% versus 32.8% +/- 3.9%). In vivo diastolic indices demonstrated trends toward diminished ventricular compliance in control animals but not in the cariporide group after VF and reperfusion. Control animals had significantly increased postmortem LV stiffness, myocardial water content, and normalized LV mass. CONCLUSIONS Cariporide preserves LV function after 80 seconds of VF and 40 minutes of reperfusion. Cariporide may prove useful in patients with severe LV dysfunction undergoing VF for implantable cardioverter defibrillator testing.