Assessment of synchronized direct mechanical ventricular actuation in a canine model of left ventricular dysfunction.

Direct mechanical ventricular actuation (DMVA) is an experimental procedure that provides biventricular cardiac assistance by intracorporeal pneumatic compression of the heart. The advantages this technique has over other assist devices are biventricular assistance, no direct blood contact, pulsatile blood flow, and rapid, less complicated application. Prior studies of nonsynchronized DMVA support have demonstrated that a subject can be maintained for up to 7 days. The purpose of this study was to determine the acute hemodynamic effects of cardiac synchronized, partial DMVA support in a canine model (RVP) of left ventricular (LV) dysfunction. The study consisted of rapidly pacing seven dogs for 4 weeks to create LV dysfunction. At the conclusion of the pacing period, the DMVA device was positioned around the heart by means of a median sternotomy. The animals were then imaged in a 1.5 T whole body high speed clinical MR system, with simultaneous LV pressure recording. Left ventricular pressure-volume (PV) loops of the nonassisted and DMVA assisted heart were generated and demonstrated that DMVA assist shifted the loops leftward. In addition, assist significantly improved pressure dependent LV systolic parameters (left ventricular peak pressure and dp/dt max, p < 0.05), with no diastolic impairment. This study demonstrates that DMVA can provide synchronized partial assist, resulting in a decrease in the workload of the native heart, thus having a potential application for heart failure patients.

Dynamic cardiomyoplasty decreases myocardial workload as assessed by tissue tagged MRI.

The effects of dynamic cardiomyoplasty (CMP) on global and regional left ventricular (LV) function in end-stage heart failure still remain unclear. MRI with tissue-tagging is a novel tool for studying intramyocardial motion and mechanics. To date, no studies have attempted to use MRI to simultaneously study global and regional cardiac function in a model of CMP. In this study, we used MRI with tissue-tagging and a custom designed MR compatible muscle stimulating/pressure monitoring system to assess long axis regional strain and displacement variations, as well as changes in global LV function in a model of dynamic cardiomyoplasty. Three dogs underwent rapid ventricular pacing (RVP; 215 BPM) for 10 weeks; after 4 weeks of RVP, a left posterior CMP was performed. After 1 year of dynamic muscle stimulation, the dogs were imaged in a 1.5 T clinical MR scanner. Unstimulated and muscle stimulated tagged long axis images were acquired. Quantitative 2-D regional image analysis was performed by dividing the hearts into three regions: apical, septal, and lateral. Maximum and minimum principal strains (lambda, and lambda2) and displacement (D) were determined and pooled for each region. MR LV pressure-volume (PV) loops were also generated. Muscle stimulation produced a leftward shift of the PV loops in two of the three dogs, and an increase in the peak LV pressure, while stroke volume remained unchanged. With stimulation, lambda1 decreased significantly (p<0.05) in the lateral region, whereas lambda2 increased significantly (p<0.05) in both the lateral and apical regions, indicating a decrease in strain resulting from stimulation. D only increased significantly (p<0.05) in the apical region. The decrease in strain between unassisted and assisted states indicates the heart is performing less work, while maintaining stroke volume and increasing peak LV pressure. These findings demonstrate that the muscle wrap functions as an active assist, decreasing the workload of the heart, while preserving total pump performance.

Ten weeks of rapid ventricular pacing creates a long-term model of left ventricular dysfunction.

OBJECTIVE: Rapid ventricular pacing produces a reliable model of heart failure. Cessation after 4 weeks of rapid ventricular pacing results in rapid normalization of left ventricular function, but the left ventricle remains persistently dilated. We present novel data that show that prolonged rapid ventricular pacing (10 weeks) creates a model of chronic left ventricular dysfunction. METHODS: In 9 dogs undergoing 10 weeks of rapid ventricular pacing, left ventricular function and volumes were serially assessed by using 2-dimensional echocardiography and pressure-volume analysis for 12 weeks after cessation of pacing. RESULTS: Increased end-diastolic volume and decreased systolic and diastolic function were seen at the end of pacing. By 2 weeks of recovery from rapid ventricular pacing, end-diastolic volume and ejection fraction were partially recovered but did not improve further thereafter. Load-independent and load-sensitive indices of function obtained by pressure-volume analysis at 8 and 12 weeks of recovery confirmed a persistence of both systolic and diastolic dysfunction. In addition, left ventricular mass increased with pacing and remained elevated at 8 and 12 weeks of recovery. Four of these dogs studied at 6 months of recovery showed similar left ventricular abnormalities. CONCLUSION: Ten weeks of rapid ventricular pacing creates a long-term model of left ventricular dysfunction.

Cardiac-respiratory gating method for magnetic resonance imaging of the heart.

In studies of transmural myocardial function, acquisitions of high spatial and temporal resolution tagged cardiac images often exceed the practical time limit for breath-hold fast imaging techniques. Therefore, a dual cardiac-respiratory gating device has been constructed to acquire SPAMM-tagged cardiac MR images at or near end-expiration during spontaneous breathing, by providing an external trigger to a conventional MRI system. Combined cardiac and respiratory gating essentially eliminates the respiratory motion artifacts in tagged cardiac MR images. Compared to cardiac-gated images obtained during intermittent breath-holds, cardiac-respiratory gated images show improved tag-myocardium contrast due to magnetization recovery during inspiration.

Long-term dynamic cardiomyoplasty improves chronic and acute myocardial energetics in a model of left ventricular dysfunction.

BACKGROUND: We present the first long-term evaluation of myocardial energetics after dynamic cardiomyoplasty (CMP) in a model of left ventricular (LV) dysfunction. METHODS AND RESULTS: Seventeen dogs underwent rapid ventricular pacing (RVP) to create heart failure. Eight dogs were randomly selected to undergo cardiomyoplasty. All dogs continued RVP for 6 additional weeks, whereas the CMP dogs underwent a simultaneously delivered synchronized muscle wrap conditioning protocol. After termination of RVP at 10 weeks in all dogs, myoplasty dogs continued to receive muscle wrap stimulation until the terminal study. Pressure-volume analysis to assess LV energetics was conducted at baseline and 4 weeks and 3 months after termination of RVP (6 months after baseline). At 6 months, CMP dogs displayed enhanced contractility, lower volumes, and more optimal energetics compared with control animals. Acute muscle wrap stimulation further increased effective contractility and myocardial efficiency compared with unassisted beats. CONCLUSIONS: The decrease in NYHA functional class that occurs in patients after dynamic cardiomyoplasty may be secondary to its beneficial effects on long-term myocardial function, volume, and energetics.

Noninvasive measurement of the human brachial artery pressure-area relation in collapse and hypertension.

A noninvasive method to obtain pressure-lumen area (P-A) measurements of the human brachial artery is introduced. The data obtained from this method are analyzed using a mathematical model of the relationship between vessel pressure and lumen area including vessel collapse and hypertension. An occlusive arm cuff is applied to the brachial artery of ten normal subjects. The cuff compliance is determined continuously by means of a known external volume calibration pump. This permits the computation of the P-A curve of the brachial artery under the cuff. A model is applied to analyze the P-A relation of each subject. The results show that the lumen area varies considerably between subjects. The in vivo resting P-A curve of the brachial artery possesses features similar to that of in vitro measurements. A primary difference is that the buckling pressure is higher in vivo, presumably due to axial tension, as opposed to in vitro where it is near zero or negative. It is found that hypertension causes a shift in the P-A curve towards larger lumen areas. Also, the compliance-pressure curve is shown to shift towards higher transmural pressures. Increased lumen area provides an adaptive mechanism by which compliance can be maintained constant in the face of elevated blood pressure, in spite of diminished distensibility.

Modified rapid ventricular pacing: a chronic model of heart failure for evaluation of new surgical therapies.

Rapid ventricular pacing (RVP) in dogs creates a well characterized model of dilated cardiomyopathy. Standard pacing protocols use RVP at 240-260 beats/min for 2-4 weeks, and result in high mortality rates if continued longer. The authors describe a modification of RVP that results in significant heart failure by 4 weeks, but can be continued for up to 10 weeks with low mortality. Nineteen mongrels underwent RVP at 215 beats/min for 10 weeks. Serial pressure-volume analysis and echocardiography were performed in this model to assess longitudinally changes in left ventricular (LV) function and volumes. The mortality rate was 10%. Significant progressive LV dysfunction with concomitant LV enlargement was observed throughout the pacing period. Finally, norepinephrine levels were elevated at the end of pacing, consistent with an activated sympathetic system. This modified RVP protocol permits long-term pacing with a low mortality rate and results in progressive heart failure throughout the pacing period. This model would be useful in the long-term evaluation of newer surgical and medical therapies of the failing heart.

Determination of global function and regional mechanics of dynamic cardiomyoplasty using magnetic resonance imaging.

This study used tissue tagged magnetic resonance (MR) to assess regional strain and generate pressure-volume (PV) loops in a canine model of cardiomyoplasty (CMP). Three dogs with rapid ventricular pacing induced heart failure underwent dynamic CMP chronic cardiac assistance for 1 year. At the end of the study period, we performed a MR study with the myostimulator "on" and "off" and recording of left ventricular (LV) pressure. We determined the short axis displacement (D) and maximal and minimal principal strains (lambda1 and lambda2) by quantitative two-dimensional regional spatial modulation of magnetization visualization utility image analysis. LV PV loops were generated by combining the LV volume data from the MR images with the LV pressure recorded during imaging. Muscle stimulation produced a leftward shift of the LV PV loops in two of the three dogs, and an increase in LV peak pressure and dp/dt max. In contrast, short axis lambda1 and lambda2 did not change significantly (p = NS). D increased significantly in the anterolateral, posterolateral, and posteroseptal regions (p < 0.05) but did not change for the septal region (p = NS). Flap stimulation augments LV function in the absence of short axis strain change; this suggests that dynamic CMP exerts its main action along the long axis of the heart.

Stabilization of chronic remodeling by asynchronous cardiomyoplasty in dilated cardiomyopathy: effects of a conditioned muscle wrap.

BACKGROUND: Dynamic cardiomyoplasty is a promising new therapy for dilated cardiomyopathy. The girdling effects of a conditioned muscle wrap alone have recently been postulated to partly explain its mechanism. We investigated this effect in a canine model of chronic dilated cardiomyopathy. METHODS AND RESULTS: Twenty dogs underwent rapid ventricular pacing (RVP) for 4 weeks to create a model of dilated cardiomyopathy. Seven dogs were then randomly selected to undergo subsequent cardiomyoplasty, and all dogs had 6 weeks of additional RVP. The cardiomyoplasty group also received 6 weeks of concurrent skeletal muscle stimulation consisting of single twitches delivered asynchronously at 2 Hz to transform the wrap without active assistance. All dogs were studied by pressure-volume analysis and echocardiography at baseline and after 4 and 10 weeks of pacing. Systolic indices, including ejection fraction (EF), end-systolic elastance (Ees), and preload-recruitable stroke work (PRSW) were all increased at 10 weeks in the wrap versus controls (EF, 34.0 versus 27.1, P=.008; Ees, 1.65 versus 1.26, P=.09; PRSW, 35.9 versus 25.5, P=.001). Ventricular volumes, diastolic relaxation, and left ventricular end-diastolic pressures stabilized in the cardiomyoplasty group but continued to deteriorate in controls. Both the end-systolic and end-diastolic pressure-volume relationships shifted farther rightward in controls but remained stable in the cardiomyoplasty group. CONCLUSIONS: In addition to potential benefits from active systolic assistance, benefits from dynamic cardiomyoplasty appear to be partially accounted for by the presence of a conditioned muscle wrap alone. This conditioned wrap stabilizes the remodeling process of heart failure, arresting progressive deterioration of systolic and diastolic function.

Dynamic cardiomyoplasty: its chronic and acute effects on the failing heart.

OBJECTIVES: Dynamic cardiomyoplasty is an alternative therapy for end-stage heart failure. We investigated the mechanisms, both acute and chronic, by which a synchronously stimulated conditioned muscle wrap affects left ventricular function in a chronic canine model of dilated cardiomyopathy. METHODS: Nineteen dogs underwent rapid ventricular pacing at a rate of 215 beats/min for 4 weeks to create a model of heart failure. Eight dogs were then randomly selected to undergo cardiomyoplasty, and all dogs received 6 additional weeks of rapid ventricular pacing. The cardiomyoplasty group also received a graded muscle conditioning protocol of synchronized burst stimulation to transform the muscle wrap. All dogs were studied with pressure-volume analysis and echocardiography at baseline and after 4 and 10 weeks of rapid ventricular pacing. Data in the cardiomyoplasty group were analyzed with the stimulator off, with it augmenting every beat (1:1), and with it augmenting only every other beat (1:2). RESULTS: Stimulator "of" data at 10 weeks of rapid pacing demonstrated chronic effects by enhanced ventricular function (end-systolic elastance = 1.80 after myoplasty vs 1.17 for controls, p = 0.005) and a stabilization of volumes and composite end-systolic and end-diastolic pressure-volume relations in the cardiomyoplasty group when compared with controls. Myoplasty stimulation increased apparent contractility (preload recruitable stroke work = 31.3 for stimulator "of" vs 40.6 for stimulator 1:2 assisted beats [p < 0.05] and vs 45.4 for stimulator 1:1 [p < 0.05]). CONCLUSIONS: Benefits from dynamic cardiomyoplasty are by at least two mechanisms: (1) the girdling effects of a conditioned muscle wrap, which halts the chronic remodeling of heart failure, and (2) active systolic assistance, which augments the apparent contractility of the failing heart.

Design and control of the atrio-aortic left ventricular assist device based on O2 consumption.

The left ventricular assist device (LVAD) is used in parallel with the left ventricle to temporarily assist patients with diminished cardiac function for the purpose of minimizing heart workload and to maintain systemic arterial perfusion. The proper adjustment and timing of the pneumatic LVAD is important such that this goal is achieved. Previous investigations into the left ventricular assist device are inconclusive regarding the optimal utilization of this device. This paper documents a protocol for optimal timing of the LVAD. Timing is studied using a closed-loop analog model of the heart, vascular system, and the LVAD. The model is tested for basic representation of the physiological system. The LVAD is incorporated into the model to discover its interaction with cardiac preload and afterload. Heart workload is computed via the pressure-volume-area method. The normal and impaired heart are modeled, in each case the pump control variables are adjusted. A protocol for adjustment of the LVAD is proposed based on reduced heart oxygen consumption. It was found that the pump should begin ejection immediately after the close of the aortic valve and that the pump filling pressure should be set to a value which produces maximum filling of the pump. Although aortic pressure and flow could be improved at pump rates above the heart rate, oxygen utilization of the heart could only be minimized for synchronous pumping. The adjustment of the pump ejection pressure is a tradeoff between d/dt (LVO2) and stroke volume and mean arterial pressure. The LVAD should be designed to minimize inflow and outflow resistance and to maximize pump compliance. The process of weaning the patient from the LVAD is considered. The overall results provide quantitative guidance for the use of the AA-LVAD.