Recovery of cardiac function by long-term left ventricular support in patients with end-stage cardiomyopathy

Effects of long-term left ventricular (LV) support on end-stage cardiomyopathy patients is unclear. We applied our LV assist system (LVAS) to six heart transplant candidates, aged 17 to 49, with dilated cardiomyopathy, including one dilated phase hypertrophied cardiomyopathy. LVAS was installed between the left atrium and the ascending aorta, and the pump was positioned parecorporeally. In all patients, their general condition improved, and their pump flows were kept at 4 to 5 L/min. Exercise was started after stabilization of their general condition under constant pump flow. Natural heart size and function were examined by echocardiography. In the beginning of assist, all patients showed impaired cardiac function and LV dilation. During LV assist, systolic function measured by ejection time improved in all patients. Left ventricular end-diastolic dimension (LVDd), showed a remarkable decrease in two patients, who were weaned from LVAS after 3 months of support. They are doing well more than 1 year and 3 years after removal; peak VO2 levels (ml/min/kg) were 30 at 1.2 years and 27 at 2.7 years after removal. In the other four patients, however, LVDd had no remarkable changes, and three could not be weaned from LVAS. The last was discontinued from LVAS after 5 months of support because of infection and died 2 months after removal. From this experience, long-term LVAS may provide the chance for recovery of the natural heart in patients with end-stage cardiomyopathy. The patients whose hearts showed remodeling were able to be weaned from LVAS, and their heart function maintained in good condition for several years.     

State of the art: "diastology" research 1998

The performance of the left ventricle (LV) during diastole is defined by the pressure-volume relationship. Consequently, noninvasive techniques have been limited in the evaluation of diastolic function by their inability to evaluate intracardiac pressure, particularly LV filling pressure and end-diastolic pressure. Abnormalities of LV diastolic function play a major role in producing the clinical signs and symptoms of heart failure. Previous studies have demonstrated that the transmitral flow (TMF), pulmonary venous flow (PVF) and left atrial appendage flow (LAAF) velocity patterns determined by pulsed Doppler echocardiography are useful parameters for evaluating left atrial (LA) and LV hemodynamic events. However, these variables are influenced by loading conditions, particularly preload. Furthermore, it has become increasingly clear that abnormalities of LV diastolic function, such as relaxation and filling, can be assessed precisely using color Doppler M-mode echocardiography and pulsed tissue Doppler imaging irrespective of preload. This review presents a clinical approach to understanding the hemodynamic abnormalities of the LA and LV in a variety of cardiac diseases using these new modalities. In addition, the limitations of these techniques are discussed.     

Inhaled nitric oxide is not a myocardial depressant in a porcine model of heart failure

BACKGROUND: Inhaled nitric oxide has been shown to be a potent and selective pulmonary vasodilator. Reports of increases in left ventricular end-diastolic pressure and episodes of pulmonary edema during the clinical use of inhaled nitric oxide in patients with preexisting left ventricular dysfunction have raised concerns that this agent may have myocardial depressant effects. We therefore undertook a study of the effects of inhaled nitric oxide on myocardial contractility in a porcine model of ventricular failure and pulmonary hypertension. METHODS: After inducing heart failure in 10 pigs by rapid ventricular pacing, hemodynamic measurements and pressure-volume diagrams (by the conductance method) were obtained in six animals at baseline and during administration of inhaled nitric oxide at concentrations of 20 and 40 ppm. Myocardial contractile state was assessed by the end-systolic pressure-volume relationship and preload-recruitable stroke work, whereas diastolic function was measured in terms of the end-diastolic pressure-volume relationship and the pressure decay time constant T. RESULTS: Baseline hemodynamics reflected heart failure and pulmonary hypertension, and inhaled nitric oxide induced significant reductions in mean pulmonary artery pressure and pulmonary vascular resistance. Although left ventricular end-diastolic pressure increased during administration of inhaled nitric oxide, no changes were observed in measures of systolic or diastolic function. CONCLUSIONS: Inhaled nitric oxide reduced pulmonary vascular resistance but did not alter myocardial contractility or diastolic function. Increases in left ventricular end-diastolic pressure during inhaled nitric oxide therapy are therefore not due to myocardial depression and may be related to increases in volume delivery to the left side of the heart resulting from reduced pulmonary vascular resistance.     

Complete unloading alone may not adequately protect the left ventricle

BACKGROUND: The benefit of left ventricular (LV) unloading for preserving LV function is commonly accepted, but its efficacy remains incompletely defined. METHODS: We studied the influence of complete LV unloading on LV systolic and diastolic mechanics using an in situ isovolumic preparation with two different coronary perfusion pressures (CPPs) in 12 dogs during prolonged normothermic cardiopulmonary bypass. RESULTS: Multivariate analysis of covariance with time as a covariate revealed that a high CPP (143 +/- 36 mm Hg; n = 6) was associated with better preservation of systolic LV function over time as assessed by LV end-systolic elastance (p < 0.001) and the end-systolic pressure-volume relation physiologic intercept (p < 0.001) compared with a moderate CPP (107 +/- 18 mm Hg; p < 0.005 versus a high CPP by t-test; n = 6). Dobutamine (2 micrograms.kg-1.min-1) improved LV end-systolic elastance (p < 0.005) and LV physiologic intercept (p < 0.01) only in the high-CPP group. Conversely, impaired LV diastolic function (as measured by LV stiffness) was observed (p < 0.001) with a high CPP, but did not change with a moderate CPP. CONCLUSIONS: These observations in canine hearts suggest that complete LV unloading may not preserve LV systolic function adequately over time when CPP is maintained in the accepted clinical range. A higher CPP is required to prevent deterioration over prolonged cardiopulmonary bypass times, but diastolic dysfunction still occurs.     

A novel monoclonal antibody permitting recognition of NKT cells in various mouse strains

OBJECTIVES: The purpose of this study was to determine whether restrictive left ventricular (LV) filling patterns are associated with diastolic ventricular interaction in patients with chronic heart failure. BACKGROUND: We recently demonstrated a diastolic ventricular interaction in approximately 50% of a series of patients with chronic heart failure, as evidenced by paradoxic increases in LV end-diastolic volume despite reductions in right ventricular end-diastolic volume during volume unloading achieved by lower body negative pressure (LBNP). We reasoned that such an interaction would impede LV filling in mid and late diastole, but would be minimal in early diastole, resulting in a restrictive LV filling pattern. METHODS: Transmitral flow was assessed using pulsed wave Doppler echocardiography in 30 patients with chronic heart failure and an LV ejection fraction < or = 35%. Peak early (E) and atrial (A) filling velocities and E wave deceleration time were measured. Left ventricular end-diastolic volume was measured using radionuclide ventriculography before and during -30-mm Hg LBNP. RESULTS: Nine of the 11 patients with and 2 of the 16 patients without restrictive LV filling patterns (E/A > 2 or E/A 1 to 2 and E wave deceleration time < or = 140 ms) increased LV end-diastolic volume during LBNP (p = 0.001). The change in LV end-diastolic volume during LBNP was correlated with the baseline A wave velocity (r = -0.52, p = 0.005) and E/A ratio (r = 0.50, p = 0.01). CONCLUSIONS: Restrictive LV filling patterns are associated with diastolic ventricular interaction in patients with chronic heart failure. Volume unloading in the setting of diastolic ventricular interaction allows for increased LV filling. Identifying patients with chronic heart failure and restrictive filling patterns may therefore indicate a group likely to benefit from additional vasodilator therapy.     

Desflurane, sevoflurane, and isoflurane impair canine left ventricular-arterial coupling and mechanical efficiency

BACKGROUND: The effects of desflurane, sevoflurane, and isoflurane on left ventricular-arterial coupling and mechanical efficiency were examined and compared in acutely instrumented dogs. METHODS: Twenty-four open-chest, barbiturate-anesthetized dogs were instrumented for measurement of aortic and left ventricular (LV) pressure (micromanometer-tipped catheter), dP/dtmax, and LV volume (conductance catheter). Myocardial contractility was assessed with the end-systolic pressure-volume relation (Ees) and preload recruitable stroke work (Msw) generated from a series of LV pressure-volume diagrams. Left ventricular-arterial coupling and mechanical efficiency were determined by the ratio of Ees to effective arterial elastance (Ea; the ratio of end-systolic arterial pressure to stroke volume) and the ratio of stroke work (SW) to pressure-volume area (PVA), respectively. RESULTS: Desflurane, sevoflurane, and isoflurane reduced heart rate, mean arterial pressure, and left ventricular systolic pressure. All three anesthetics caused similar decreases in myocardial contractility and left ventricular afterload, as indicated by reductions in Ees, Msw, and dP/dtmax and Ea, respectively. Despite causing simultaneous declines in Ees and Ea, desflurane decreased Ees/Ea (1.02 +/- 0.16 during control to 0.62 +/- 0.14 at 1.2 minimum alveolar concentration) and SW/PVA (0.51 +/- 0.04 during control to 0.43 +/- 0.05 at 1.2 minimum alveolar concentration). Similar results were observed with sevoflurane and isoflurane. CONCLUSIONS: The present findings indicate that volatile anesthetics preserve optimum left ventricular-arterial coupling and efficiency at low anesthetic concentrations (< 0.9 minimum alveolar concentration); however, mechanical matching of energy transfer from the left ventricle to the arterial circulation degenerates at higher end-tidal concentrations. These detrimental alterations in left ventricular-arterial coupling produced by desflurane, sevoflurane, and isoflurane contribute to reductions in overall cardiac performance observed with these agents in vivo.     

A comparison of cathepsin B processing and distribution during neuronal death in rats following global ischemia or decapitation necrosis

OBJECTIVE: The relationship between the left ventricular (LV) relaxation time constant and early diastolic filling is not fully defined. This study provides additional evidence that LV isovolumic pressure fall in the normal intact heart in response to certain interventions is not adequately described by a model of monoexponential decay and that its relationship to filling is complex. METHODS AND RESULTS: To gain further insight into the relationship between LV relaxation and early rapid filling we measured LV isovolumic relaxation rate, peak early filling velocity (E), LV volumes, and transmitral pressures at baseline and in the first postextrasystolic beat after a short-coupled extrasystole in 9 anesthetized dogs. Postextrasystolic isovolumic relaxation rate was slowed as measured by 3 commonly used time constants, while E was increased 32%. LV contractility and peak pressure were also increased, while LV end-systolic volume was decreased. LV minimum pressure was deceased, while the early diastolic transmitral pressure gradient was increased. Although all relaxation time constants measured over the entire isovolumic relaxation phase indicated slowed relaxation, direct measurement of isovolumic relaxation time indicated no change in relaxation rate. Calculation of the time constants and direct measurement of isovolumic relaxation time during early isovolumic pressure decay indicated slowed postextrasystolic pressure decay rate compared with baseline, while calculation of time constants and direct measurement of isovolumic relaxation time during late isovolumic relaxation indicated augmented postextrasystolic pressure decay rate versus baseline. CONCLUSIONS: This non-exponential behavior of LV isovolumic pressure decay in postextrasystolic beats after short-coupled extrasystoles provides further evidence that the relationship that exists between ventricular relaxation and early filling is not simple. The results are interpreted in terms of current theoretical formulations that attribute control of myocardial relaxation to the interaction between inactivation-dependent and load-dependent mechanisms.     

Effect of shape on pressure-volume relationships of ellipsoidal shells

Previous theoretical procedures for determining the slope and intercept of the stiffness-stress relationship of the passive myocardium from diastolic pressure-volume (P-V) data assume that the eccentricity of the left ventricle (LV) is invariant. In this study a mathematical model for an ellipsoidal membrane was developed that does not contain that constraint. The model predicts a small (less than 10%) but significant decrease in eccentricity as transmural pressure increases. This result was confirmed by the use of a thick-wall finite element model. The implications of this result are as follows. 1) The slope and intercept of the stiffness-stress relationship of unconstrained ellipsodial shells can be determined by fitting a spherical model to the P-V relationships exhibited by the shells. 2) An ellipsoidal model that assumes that the eccentricity of such shells is invariant for all pressures would predict erroneous intercepts. 3) If the eccentricity of the diastolic LV initially decreases relative to its value at zero transmural pressure, then a thick-wall spherical model may be adequate for determining the slope and intercept of the myocardial stiffness-stress relationship.     

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.     

Effect of inferior vena cava occlusion on left ventricular end-systolic pressure-volume relations in intact canine hearts--modulation by the autonomic nervous system

The effect of inferior vena cava occlusion (IVCO) on end-systolic pressure-volume relations (ESPVR) of the left ventricle was studied in intact canine hearts. In 12 anesthetized open-chest dogs, left ventricular (LV) pressure and volume were measured simultaneously using a microtip catheter and a conductance catheter, respectively. ESPVR was constructed from LV pressure-volume loops during IVCO (10 sec) and subsequent IVCO release under 5 conditions: control, after righ or left cardiac sympathetic nerve (CSN) stimulation, bilateral vagotomy (VAT), and both VAT and bilateral CSN resection. Emax in IVCO release was significantly greater than that in IVCO in the control state. Following right or left CSN stimulation, Emax was increased increased in both IVCO and IVCO release, with the same hysteretic change in Emax. With VAT, however, no hysteretic change was observed because Emax was the same in IVCO and IVCO release. After VAT and CSN resection, Emax was decreased in both IVCO and IVCO release, and again no hysteretic change was observed. These data imply that a sudden decrease in venous return into the heart induces a decrease in afferent vagal nerve activity, and thus increases efferent CSN activity, resulting in enhanced myocardial contractility.     

Immediate reproducibility of upper limit of vulnerability measurements in patients undergoing transvenous implantable cardioverter defibrillator implantation

BACKGROUND: Asynchronous electrical activation, induced by ventricular pacing, causes regional differences in workload, which is lower in early- than in late-activated regions. Because the myocardium usually adapts its mass and structure to altered workload, we investigated whether ventricular pacing leads to inhomogeneous hypertrophy and whether such adaptation, if any, affects global left ventricular (LV) pump function. METHODS AND RESULTS: Eight dogs were paced at physiological heart rate for 6 months (AV sequential, AV interval 25 ms, ventricular electrode at the base of the LV free wall). Five dogs were sham operated and served as controls. Ventricular pacing increased QRS duration from 47.2+/-10.6 to 113+/-16.5 ms acutely and to 133.8+/-25.2 ms after 6 months. Two-dimensional echocardiographic measurements showed that LV cavity and wall volume increased significantly by 27+/-15% and 15+/-17%, respectively. The early-activated LV free wall became significantly (17+/-17%) thinner, whereas the late-activated septum thickened significantly (23+/-12%). Calculated sector volume did not change in the LV free wall but increased significantly in the septum by 39+/-13%. In paced animals, cardiomyocyte diameter was significantly (18+/-7%) larger in septum than in LV free wall, whereas myocardial collagen fraction was unchanged in both areas. LV pressure-volume analysis showed that ventricular pacing reduced LV function to a similar extent after 15 minutes and 6 months of pacing. CONCLUSIONS: Asynchronous activation induces asymmetrical hypertrophy and LV dilatation. Cardiac pump function is not affected by the adaptational processes. These data indicate that local cardiac load regulates local cardiac mass of both myocytes and collagen.     

Importance of pre-treatment radiation absorbed dose estimation for radioimmunotherapy of non-Hodgkin''s lymphoma

We have been developing a new type of centrifugal pump for long-term use. The magnetically suspended centrifugal pump (MSCP) contains no shaft and seal so that long life expectancy is predicted. Paracorporeal left ventricular (LV) assist circulation between the left atrium and the descending aorta was instituted using sheep. The flow rates ranged from 2.5-5.5 L/min. The sheep that lived the longest (46 days) died of an embolism as a result of the thrombus in the pump. No thrombus formation was observed in other pumps. Plasma free hemoglobin levels ranged from 9 to 18 mg/dl, which led to the conclusion that the hemolysis level remained within an acceptable range. Two driving modes were compared. The slope of the pressure-flow relationship plot under a constant motor current mode was steeper than that under a constant rotational speed mode, and thus, the flow fluctuation decreased. In conclusion, the MSCP is durable for more than a month at the current stage of development and is a promising device for long-term ventricular assist.     

Analysis of mumps vaccine failure by means of avidity testing for mumps virus-specific immunoglobulin G

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.     

Comparison of the effects of potential parenteral vehicles for poorly water soluble anticancer drugs (organic cosolvents and cyclodextrin solutions) on cultured endothelial cells (HUV-EC)

Left atrial (LA) adaptation during the development of left ventricular (LV) dysfunction is not fully understood. We performed echocardiographic assessment of LA volumes simultaneously with recordings of pulmonary wedge pressures in 60 patients. Twenty patients had no structural or functional LV abnormalities, 20 had a recent myocardial infarction with LV dysfunction, and 20 suffered from congestive heart failure (CHF). Pressure-volume loops were obtained at baseline and during increases in LA pressure produced by normal saline infusion. LA afterload was estimated by the effective LV elastance (E(LV)). Atrioventricular coupling was calculated by the E(LV)/E(es) ratio (where E(es) is the end-systolic elastance). E(es) increased in patients with myocardial infarction (0.80 +/- 0.09 mm Hg/ml, p <0.001), whereas it decreased in patients with CHF (0.22 +/- 0.05 mm Hg/ml, p <0.001) compared with controls (0.61 +/- 0.07 mm Hg/ml). Similarly, stroke workload increased in patients with myocardial infarction (60.7 +/- 7.3 mm Hg x ml, p <0.001), whereas it decreased in patients with CHF (25.4 +/- 2.2 mm Hg x ml, p <0.001) compared with controls (44.8 +/- 5.5 mm Hg x ml). In all patients LA stiffness (slope of the relation of the filling portion of the pressure-volume loop) was increased compared with controls (controls: 0.13 +/- 0.04, patients with myocardial infarction: 0.22 +/- 0.05, and patients with CHF: 0.27 +/- 0.05 mm Hg/ml, p <0.001 for both comparisons). Moreover, the E(LV)/E(es) ratio increased gradually as LV function deteriorated (controls: 1.06 +/- 0.10, patients with myocardial infarction: 1.35 +/- 0.16, and patients with CHF: 6.90 +/- 0.84, p <0.001). Thus, early in heart failure, LA pump function is augmented but LA stiffness increases and work mismatch occurs. With further progression of LV dysfunction, LA pump function decreases as a result of increased afterload imposed on the LA myocardium.     

Hematopoietic effects and clinical uses of granulocyte-macrophage colony-stimulating factor and PIXY321

We tested the influence of in vivo volume resuscitation on intrinsic contractile properties of left ventricular (LV) preparations of endotoxemic guinea pigs. Escherichia coli endotoxin (LPS)-injected animals were divided into nonresuscitated and resuscitated groups. Volume resuscitation improved cardiac output and stroke volume, increased arterial pH and body temperature, and decreased mortality. In isovolumetric LV preparations isolated 4 h after LPS injection, LV systolic pressures (in mmHg) preparations isolated 4 h after LPS injection, LV systolic pressures (in mmHg) of LPS with (42 +/- 3) and without (42 +/- 2) fluid resuscitation were consistently less than control values (70 +/- 3). LV end-diastolic pressure-volume (compliance) decreased in LPS-nonresuscitated hearts, while LV compliance of LPS-resuscitated hearts was similar to control. Thus, intravascular volume expansion selectively improved LV diastolic compliance of LPS hearts without affecting LV systolic function. These findings suggest that LV systolic and diastolic dysfunctions associated with endotoxemia and Gram-negative sepsis may involve separate pathogenic mechanisms.     

Analysis of right ventricular function during bypass of the left side of the heart by afterload alterations in both normal and failing hearts

This study investigated the mechanism of right ventricular failure during bypass of the left side of the heart by precisely assessing right ventricular function with use of a conductance catheter. Bypass of the left side of the heart was established with a centrifugal pump in 10 mongrel dogs weighing 11 to 19 kg. Right ventricular function during left heart bypass was evaluated by two parameters that were both derived from measurement of relative change in right ventricular volume by the conductance catheter technique. One parameter was the right ventricular end-systolic pressure-volume relationship as a load-independent index, and the other was the peak right ventricular pressure-right ventricular stroke volume relationship as a "force-velocity relationship." These parameters were measured in both normal and failing hearts while afterload was increased by bilateral intrapulmonary balloon inflation. Moreover, changes in these relationships were observed by varying assist ratios of left heart bypass from 0% to 100%. Failing heart models were induced by normothermic aortic clamping for 20 minutes. The right ventricular end-systolic pressure-volume relationship in normal hearts did not change, irrespective of the assist ratio of left heart bypass, whereas that in failing hearts decreased from 4.25 +/- 1.41 mm Hg/ml without bypass of the left side of the heart to 3.53 +/- 1.30 mm Hg/ml after 100% assist of left heart bypass (p < 0.05). In the peak right ventricular pressure-right ventricular stroke volume relationship, right ventricular stroke volume was almost constant in normal hearts when afterload was increased regardless of the assist ratio of left heart bypass. Moreover, right ventricular stroke volume was maintained at a higher level during bypass of the left side of the heart compared with that without left heart bypass. However, that slope of the relationship in failing hearts was inversely linear and became significantly steeper after 100% assist of bypass of the left side of the heart compared with that without left heart bypass (-0.131 +/- 0.042 versus -0.051 +/- 0.038, p < 0.005). Therefore ++these two slopes of the relationship intersected at a point that was considered the critical point of afterload during bypass of the left side of the heart. In other words, right ventricular stroke volume was decreased by 100% left heart bypass above the critical point of afterload. In conclusion, this study demonstrates not only that bypass of the left side of the heart results in an increase in right ventricular stroke volume in both normal and failing hearts at the physiologic range of afterload, but also that right ventricular function against higher afterload is impaired by 100% assist of bypass of the left side of the heart in failing hearts.     

Function of the residual myocardium after infarct and prognostic significance

Changes of the left ventricle after myocardial infarction are characterized by geometric, structural, and vascular alterations, which have been summarized under the term "remodeling". This process takes place in the infarct region as well as in the surviving myocardium. Depending on to the size of infarction and the degree of neurohumoral activation, the left ventricle demonstrates diastolic dysfunction which may finally lead to systolic failure. The residual myocardium develops progressive myocyte hypertrophy and interstitial fibrosis. These structural alterations are due to changes in loading conditions and stimulation of the neurohumoral system with an activation of local paracrine and autocrine factors. Myocardial function can be assessed by different non-invasive (echocardiography, radionuclide ventriculography, magnetic resonance imaging, etc.) or invasive methods (e.g., simultaneous pressure-volume measurements). "Myocardial tagging" based on magnetic resonance imaging allows the assessment of 3D-motion of the left ventricle by labelling specific myocardial regions with a rectangular grid. A systolic "wringing" motion with clock-wise rotation at the base and counter-clockwise rotation at the apex has been described in normal subjects. In the ischemic myocardium, delayed relaxation with a prolonged back-rotation (untwisting) has been reported during early diastole, whereas decreased systolic contraction with delayed diastolic rotation has been observed in non-Q-wave infarction. In patients with anterolateral aneurysms, a complete loss of systolic rotation has been demonstrated. The prognostic significance of LV "remodeling" has been emphasized by several authors: The size of infarction, LV volume, LV ejection fraction, as well as the degree of neurohumoral activation have been identified as being associated with an unfavorable clinical outcome. Yearly mortality rates have been reported to range between 15 and 17% in patients with large infarcts and marked LV dilatation and between 3 and 7% in patients with small to medium-sized infarcts.     

Early effects of coronary artery bypass surgery and cold cardioplegic ischemia on left ventricular diastolic function: evaluation by computer-assisted transesophageal echocardiography

OBJECTIVE: Although left ventricular (LV) systolic function undergoes a temporary decrease after cardiopulmonary bypass (CPB) in patients undergoing coronary artery bypass grafting (CABG), data on the effects of CABG and cardioplegic arrest on LV diastolic function are contradictory. The objective of the present study was to further evaluate the effects of CABG and CPB on LV diastolic function. DESIGN: A prospective study. SETTING: A multi-institutional investigation at a university hospital. PARTICIPANTS: 20 patients on beta-receptor antagonists, scheduled for CABG and with a preoperative ejection fraction over 0.5. INTERVENTIONS: Central hemodynamic measurements, transesophageal LV short-axis images, and mitral Doppler flow profiles were obtained before and after volume loading that in turn was performed both before surgical incision and after weaning from CPB. MEASUREMENTS AND MAIN RESULTS: Heart rate, cardiac output, and peak atrial filling velocity increased; systemic vascular resistance decreased; whereas stroke volume, LV area ejection fraction, deceleration rate and slope of early diastolic filling, time-velocity integral of early diastolic filling, and the ratio between early and atrial peak filling velocity were unchanged post-CPB compared with pre-CPB. LV end-diastolic stiffness that was calculated for each patient pre-CPB and post-CPB using the formula: P = B*eS*A), where P is the LV filling pressure and A is the end-diastolic short-axis area, was unchanged post-CPB compared with pre-CPB. CONCLUSIONS: Both the active and passive components of LV diastolic function are well maintained shortly after CABG and cardioplegic arrest in patients with a good preoperative systolic LV function.     

Influence of inhaled nitric oxide on systemic flow and ventricular filling pressure in patients receiving mechanical circulatory assistance

BACKGROUND: In patients with left ventricular (LV) dysfunction, inhaled nitric oxide (NO) decreases pulmonary vascular resistance (PVR) but causes a potentially clinically significant increase in left atrial pressure (LAP). This has led to the suggestion that inhaled NO may reach the coronary circulation and have a negative inotropic effect. This study tested an alternative hypothesis that LAP increases because of volume shifts to the pulmonary venous compartment caused by NO-induced selective pulmonary vasodilation. METHODS AND RESULTS: The Thermo Cardiosystems Heartmate is an LV assist device (LVAD) that can be set (by controlling pump rate) to deliver fixed or variable systemic blood flow. Eight patients (between 1 and 11 days after LVAD implantation) were administered inhaled NO (20 and 40 ppm for 10 minutes), and LAP, systemic flow, and pulmonary arterial pressure were measured in both fixed and variable pump flow modes. In both modes, inhaled NO lowered PVR (by 25 +/- 6% in the fixed mode, P < .001, and by 21 +/- 5% in the variable mode, P < .003). With fixed pump flow, LAP rose from 12.5 +/- 1.2 to 15.1 +/- 1.4 mm Hg (P < .008). In the variable flow mode, LAP did not increase and the assist device output rose from 5.3 +/- 0.3 to 5.7 +/- 0.3 L/min (P < .008). CONCLUSIONS: A selective reduction in PVR by inhaled NO can increase LAP if systemic flow cannot increase. These data support the hypothesis that with LV failure, inhaled NO increases LAP by increasing pulmonary venous volume and demonstrate that inhaled NO has beneficial hemodynamic effects in LVAD patients.     

Dynamic cardiac compression improves contractile efficiency of the heart

The effect of dynamic cardiac compression on left ventricular contractile efficiency was assessed in terms of the pressure-volume relationship and myocardial oxygen consumption. In 11 excised cross-circulated dog hearts, the ventricle was directly compressed during systole (dynamic cardiac compression). Measurements for pressure-volume area (a measure of total mechanical energy), external work, and myocardial oxygen consumption were done before and during dynamic cardiac compression. Dynamic cardiac compression increased pressure-volume area by 28% +/- 17% (mean plus or minus the standard deviation) and external work by 24% +/- 20% (p = 0.0000185 and 0.0000212, respectively) at given end-diastolic and stroke volumes without affecting myocardial oxygen consumption. As a result, the oxygen cost of pressure-volume area, that is, the slope of the myocardial oxygen consumption-pressure-volume area relationship, significantly decreased by 16% +/- 13% (p = 0.0000135) whereas the pressure-volume area-independent myocardial oxygen consumption was unchanged. Then, contractile efficiency, that is, the reciprocal of the slope of the myocardial oxygen consumption-pressure-volume area relationship in joules significantly improved from 45% +/- 8% to 53% +/- 13% (p = 0.0000437). When the native myocardial oxygen consumption-pressure-volume area relationship was assessed by subtracting the dynamic cardiac compression pressure applied to the heart, the slope of the myocardial oxygen comsumption-pressure-volume area relationship returned to the control level. This indicates that the contractile efficiency of the native heart was not affected by dynamic cardiac compression. We conclude that dynamic cardiac compression enhances left ventricular pump function by improving the contractile efficiency of the overall heart leaving the energetics of the native heart unchanged.