Effects of acute dynamic cardiomyoplasty in a goat model of chronic ventricular dilatation: part 1

BACKGROUND: The acute effects of cardiomyoplasty in an experimental model of chronic dilated heart have not been thoroughly investigated. Therefore, a model of chronic left ventricular (LV) dilatation was created to accurately determine actual changes shortly after passive and active wrapped skeletal muscle. METHODS: A carotid-jugular shunt model in 8 goats was used to induce progressive dilatation of the cardiac ventricles. Geometric modifications induced by the arteriovenous shunt were monitored by transthoracic echocardiography. After 8 weeks, cardiomyoplasty was performed, and the acute hemodynamic changes obtained with static cardiomyoplasty soon after the wrapping procedure were determined. Hence, hemodynamic variables recorded during assisted cardiac beats were then compared with data collected with unassisted cardiac beats using the conductance catheter method to generate pressure-volume loops. RESULTS: During electrical stimulation of the unconditioned skeletal muscle wrapped around the dilated left ventricle, a significant increase in stroke volume (117 +/- 48 mL versus 87 +/- 38 mL; p < 0.05) was observed. Early wrapped latissimus dorsi muscle activation also induced a reduction in LV end-systolic volume (from 51 +/- 28 mL to 27 +/- 14 mL; p < 0.05) when compared with unassisted LV contraction. CONCLUSIONS: In a chronic model of cardiac dilatation, acute dynamic cardiomyoplasty was shown to increase LV contractile performance and reduce LV volume. Further evaluation is necessary to show the effects of a conditioned wrapped muscle on LV systolic function and dimensions in the long-term.     

Dynamic cardiomyoplasty acutely impairs left ventricular diastolic function.

In patients with congestive heart failure, medical treatment has a high rate of mortality and morbidity, and transplantation is limited by the availability of donor hearts. Dynamic cardiomyoplasty is being investigated as surgical therapy to improve left ventricular function in these patients. To evaluate the early postoperative effects of this procedure on left ventricular diastolic function, we studied seven dogs through the use of sonomicrometry and micromanometry in a canine model of dynamic cardiomyoplasty. Left ventricular diastolic parameters were determined before wrapping the latissimus dorsi muscle (baseline), after latissimus dorsi muscle wrap but without stimulation, and with synchronous left ventricular contraction-latissimus dorsi muscle stimulation. End-diastolic pressure was increased in both conditions after latissimus dorsi muscle wrap (without stimulation, 5 +/- 1; with stimulation, 6 +/- 2 mm Hg; p < 0.05) compared with baseline (3 +/- 2 mm Hg). The peak rate of diastolic pressure decay was greater at baseline (1560 +/- 370 mm Hg/sec) than after latissimus dorsi muscle wrap, both without (1260 +/- 330 mm Hg/sec, p < 0.01) and with (1120 +/- 420 mm Hg/sec, p < 0.01) stimulation. The constant of pressure decay was prolonged both without (53 +/- 10 seconds, p < 0.05) and with (62 +/- 11 seconds, p < 0.01) latissimus dorsi muscle stimulation compared with the baseline (38 +/- 5 seconds). Compared with baseline (0.2 +/- 0.2 cm-2), the constant of passive chamber stiffness increased after the latissimus dorsi muscle was wrapped around the heart (1.6 +/- 0.7 cm-2, p < 0.05) and with stimulation (2.1 +/- 1.0 cm-2, p < 0.01). The maximal diastolic filling rate (baseline, 18.1 +/- 6.7; without stimulation, 16.6 +/- 8.9; with stimulation, 16.6 +/- 4.1 cm2/sec, not significant) and end-diastolic short-axis area (baseline, 7.3 +/- 2.3; without stimulation, 7.4 +/- 2.1; with stimulation, 7.5 +/- 2.3 cm2, not significant) were similar among the three conditions. The latissimus dorsi muscle wrap prolonged relaxation and increased left ventricular passive stiffness. Synchronous latissimus dorsi muscle stimulation with left ventricular contraction did not improve diastolic function in this model. The results suggest that in the early postoperative period, dynamic cardiomyoplasty impairs diastolic function.     

Functional recovery of the native heart after cardiomyoplasty in sheep with heart failure: passive and dynamic effects of volume loading

BACKGROUND: Dynamic cardiomyoplasty (d-CMP) encourages reverse remodeling and improved contractility and stroke work (SW) efficiency of the failing native heart. This contrasts with passive cardiomyoplasty (p-CMP), which provides "passive girdling." To further evaluate pump recovery we assessed native left ventricular performance (without assist) 6 months after dynamic and passive CMP in sheep with heart failure with acute volume loading. METHODS: Heart failure (left ventricular ejection fraction 26%+/-8%) induced by coronary microembolization was followed by CMP in 11 sheep. After 8 weeks of muscle "training," paced cardiac assist was undertaken in the d-CMP group (n = 6). Five sheep with heart failure served as controls. Six months later the pressure-volume relationship was derived before and after volume loading by colloid solution. Latissimus dorsi muscle pacing was previously ceased in the d-CMP group. RESULTS: Volume loading increased left ventricular end-diastolic volume and pressure in all groups. After volume loading in d-CMP, the SW and pressure-volume area were increased, and SW efficiency remained unchanged. In p-CMP neither variable changed, whereas in control heart failure SW efficiency decreased due to a rise in pressure-volume area with stable SW. CONCLUSIONS: Based on response to volume loading, the failing native heart after 6 months of d-CMP showed functional recovery from "active girdling," whereas p-CMP prevented functional deterioration through passive girdling. The failing control heart progressively deteriorated.     

Ventricular remodeling after cardiomyoplasty in heart failure sheep: passive and dynamic effects

Background. Recent reports claim that cardiomyoplasty (CMP) has a girdling effect on the left ventricle, to prevent dilatation and functional deterioration, but the mechanism of its long-term effects on the native heart is not known. We compared the relative role of CMP’s active squeezing and passive girdling in chronically failing hearts.

Methods. After induction of stable heart failure (left ventricular ejection FRACTION = 27% ± 7%) by staged coronary microembolization, CMP was performed in 11 of 18 sheep. After 8 weeks pacing training of the latissimus dorsi muscle (LDM), cardiac assist was begun with 1:2 synchronous bursts in 6 sheep (d-CMP, N = 6), and the LDM in the passive group (p-CMP, N = 5) remained unstimulated. Four (base line) and 30 weeks after induction of heart failure, the pressure-volume relationship was derived.

Results. After 30 weeks in d-CMP the slope (E_max) of the end-systolic pressure-volume relationship increased by 66% ± 55% (p < 0.05) and external work efficiency by 48% ± 41% (p < 0.01). In the passive CMP and control groups, slope and external work efficiency were unchanged. Conversely, left ventricular end-diastolic volume decreased (−14% ± 12%, p < 0.05) in the dynamic CMP group compared with a static course in the passive CMP group (3% ± 10%, p > 0.05) and an increase (18% ± 15%, p < 0.05) in controls.

Conclusions. Dynamic CMP improved native heart’s contractility and external work efficiency. In addition, whereas passive CMP has simply a girdling effect, dynamic CMP also induces reverse left ventricular chamber remodeling.     

Effects of dynamic cardiomyoplasty on indices of left ventricular systolic and diastolic function in a canine model of chronic heart failure.

The effects of cardiomyoplasty were evaluated with multiple-gated equilibrium radionuclide angiocardiography and catheterization in a canine model of chronic heart failure. Doxorubicin was administered to 12 dogs at a dose of 1 mg/kg/wk intravenously for 10 weeks. Left ventricular ejection fraction was reduced from a mean of 53.6% +/- 3.4% to 33.5% +/- 2.3% preoperatively. Two dogs died of presumed arrhythmia during this period. Cardiomyoplasty with the left latissimus dorsi muscle was performed on 10 dogs. The muscle was wrapped around both the left and right ventricles. Five dogs died of infection or arrhythmia after the operation. Postoperatively the muscle remained unstimulated for 2 weeks to allow adhesion to the heart. After this period, the latissimus dorsi muscle was conditioned by a progressive stimulation protocol. After the muscle was conditioned, multiple-gated equilibrium radionuclide angiocardiography studies showed that left ventricular global ejection fraction was 18.4% +/- 7.2% at 0 volts (nonstimulation), 26.2% +/- 3.7% at 5-volt stimulation (p less than 0.05), and 31.0% +/- 5.4% at 10-volt stimulation (p less than 0.05). Regional ejection fractions in low lateral, apical, and low septal regions at 5 volts and 10 volts were higher than those at 0 volts (p less than 0.05). Regional wall motion (percent radial shortening) of the low lateral region was higher than that during nonstimulation (p less than 0.05). Peak emptying rate was 2.07 +/- 0.95 end-diastolic counts per second at 0-volt, 3.10 +/- 0.67 at 5-volt, and 3.34 +/- 0.89 at 10-volt stimulation (p less than 0.05). Peak filling rate was 1.81 +/- 0.52 end-diastolic counts per second at 0-volt, 2.67 +/- 1.18 at 5-volt, and 3.11 +/- 0.65 at 10-volt stimulation (p less than 0.05). Cardiac catheterization data showed a nonsignificant increase in left ventricular rate of pressure rise with increasing voltage (1302 +/- 355 mm Hg/sec at 0 volts, 1450 +/- 413 mm Hg/sec at 5 volts, and 1568 +/- 455 mm Hg/sec at 10 volts). Left ventricular systolic pressures were unchanged. End-diastolic pressures decreased (11.2 +/- 1.48 mm Hg at 0 volts, 10.4 +/- 2.30 mm Hg at 5 volts, and 9.6 +/- 1.52 at 10 volts; p less than 0.05). These data show that cardiomyoplasty can improve indices of systolic and diastolic function in a canine model of chronic heart failure.     

Effects of Wrapping Tightness on Acute Cardiac Function in Dynamic Cardiomyoplasty

Background. It has not been clarified how tightly the heart should be wrapped for maximal augmentation of cardiac function in cardiomyoplasty.

Methods. Hearts in acute failure induced by propranolol were wrapped with the left latissimus dorsi muscle, loosely (loose CMP), moderately (moderate CMP), and tightly (tight CMP) in each of 5 pigs. To measure the pressure between the latissimus dorsi muscle and the left ventricle (LV), a Millar pressure catheter with a latex balloon was placed on the anterior wall of the LV. Left ventricular wall tension was calculated according to Laplace's law, using the difference between the LV pressure and the balloon pressure.

Results. In the loose CMP, moderate CMP, and tight CMP groups, the mean balloon pressures during unassisted beats were 8.2, 10.4, and 13.2 mm Hg, respectively. During unassisted beats, the mean LV wall tension values were 38,683, 29,938 (p < 0.05 versus loose CMP), and 26,652 (p < 0.05 versus loose CMP) dynes/cm, respectively, the peak LV pressures were 76.8, 73.8, and 65 (p < 0.05 versus loose CMP) mm Hg, respectively, and the stroke volumes were 12.8, 9.2, and 8.5 (p < 0.05 versus loose CMP) mL, respectively. During assisted beats, the mean LV wall tension values were 20,059, 11,290, and 7,893 (p < 0.05 versus loose CMP) dynes/cm, respectively, the peak LV pressures were 94.1, 98.1, and 92.0 mm Hg, respectively, and the stroke volumes were 13.8, 11.6, and 9.4 (p < 0.05 versus loose CMP) mL, respectively.

Conclusions. During unassisted beats, tight CMP (13 mm Hg) had the advantage of diminishing LV wall tension, but the disadvantage of diminishing LV pressure and stroke volume, compared with loose CMP (8 mm Hg). Moderate CMP (10 mm Hg), however, had the advantage of diminishing LV wall tension without a decrease in LV pressure and stroke volume.     

Increased coronary artery blood flow with aortomyoplasty in chronic heart failure

BACKGROUND: We hypothesized that diastolic counter-pulsation using aortomyoplasty will increase coronary blood flow. METHODS: In dogs (n = 6, 20 to 25 kg), the left latissimus dorsi muscle was isolated, wrapped around the descending thoracic aorta, and conditioned by chronic electrical stimulation. Heart failure was induced by rapid ventricular pacing. In a terminal study, left ventricular and aortic pressures, and blood flow in the left anterior descending coronary artery and descending aorta were measured. The endocardial-viability ratio was calculated. RESULTS: Aortomyoplasty increased mean diastolic aortic pressure (70 +/- 5 to 75 +/- 5 mm Hg, p < 0.05) and reduced peak left ventricular pressure (86 +/- 4 to 84 +/- 4 mm Hg, p < 0.05), leading to a 16% increase in endocardial-viability ratio (1.29 +/- 0.05 to 1.49 +/- 0.05, p < 0.05). Coronary blood flow was increased by 15% (8.2 +/- 1.5 to 9.4 +/- 1.6 mL/min, p < 0.05). During muscle contraction, 2.7 +/- 0.5 mL was ejected from the wrapped aortic segment. CONCLUSIONS: These data demonstrate that aortomyoplasty provides successful diastolic counterpulsation after muscle conditioning and heart failure.     

Cardiomyoplasty Benefits in Experimental Myocardial Dysfunction

Beneficial effects of cardiomyoplasty have been documented and the use of this technique in the treatment of dilated cardiomyopathy have been suggested. This study was undertaken to evaluate the effectiveness of stimulated preconditioned latissimus dorsi muscle flaps wrapped around the heart in order to restore ventricular contractility in six adult mongrel dogs with induced myocardial dysfunction by administration of beta blockers and volume loading. Hemodynamic and two-dimensional echocardiographic evaluation were performed 1 week after the surgical procedure and immediately after heart failure induction. With synchronous pulse train electrical stimulation, cardiac output increased from 1.46 +/- 0.13 (+/- SD) to 2.01 +/- 0.16 L/min (p less than 0.01), pulmonary wedge pressure decreased from 15.5 +/- 1.2 to 11.3 +/- 1.6 mmHg (p less than 0.01) and left ventricular end-diastolic pressure from 18.3 +/- 2.4 to 13.5 +/- 1.4 mmHg (p less than 0.04). Echo derived left ventricular ejection fraction increased from 39.3 +/- 2.4 to 59.6 +/- 2.9% (p less than 0.01) and segmental wall shortening from 15.4 +/- 1.2 to 26.3 +/- 1.7% (p less than 0.01), inclusive when the muscle flap was wrapped only around the left ventricle. In conclusion, this study suggests that cardiomyoplasty may be an alternative method of treatment for irreversible cardiomyopathy, including in patients with a great cardiac enlargement in which muscle flap may only be wrapped partially around the heart.     

Girdling effect of adynamic cardiomyoplasty in a model of dilated cardiomyopathy

OBJECTIVE: The potential benefits of adynamic cardiomyoplasty remain unclear. We determined whether unstimulated skeletal muscle wrap alone prevents or attenuates progressive left ventricular dilation in a canine model of congestive heart failure produced by repeated intracoronary infusions of doxorubicin. SUBJECTS AND METHODS: 14 dogs were randomized in to 2 groups, 1 undergoing cardiomyoplasty (CMP group) and 1 that did not (CONT group). Intracoronary doxorubicin was administered weekly for 5 weeks to induce heart failure. Hemodynamic data was obtained before infusion and 5 weeks afterward. Echocardiography was done weekly. RESULTS: Significant left ventricular dilation was observed in the CONT group--left ventricular end-diastolic diameter increased from 28.9 +/- 2.7 to 38.5 +/- 3.3 mm (p < 0.05). Significant left ventricular dilation was also observed in the CMP group--left ventricular end-diastolic diameter increased from 28.9 +/- 3.3 to 38.0 +/- 4.2 mm (p < 0.05). Dilation was slower in the CMP group than in the CONT group, however. Ejection fraction decreased from 58.0 +/- 13.8 to 29.9 +/- 13.7% in the CONT group, but was preserved from 56.0 +/- 8.8 to 51.9 +/- 10.3% in the CMP group. CONCLUSIONS: Adynamic cardiomyoplasty reduces ventricular dilation associated with heart failure without exacerbating left ventricular dysfunction.     

Latissimus dorsi dynamic cardiomyoplasty of the right ventricle. Potential for use as a partial myocardial substitute

Full-thickness right ventricular latissimus dorsi dynamic cardiomyoplasty with the Medtronic Cardiomyostimulator (Medtronic, Inc., Minneapolis, Minn.) was performed in a chronic canine model. In one group (n = 2) the latissimus dorsi was electrically preconditioned before cardiomyoplasty. In a second group (n = 3) cardiomyoplasty was performed and the muscle was progressively stimulated, with conditioning accomplished while the latissimus dorsi was functioning on the ventricle. The contribution of the stimulated latissimus dorsi to global ventricular function was assessed, and the effects of varying muscle stimulation parameters on latissimus dorsi function and hemodynamics were examined. Right ventricular systolic pressure increased 8%, from 23.2 +/- 0.95 to 25.1 +/- 1.5 mm Hg. The rate of pressure rise increased 37% from 226 +/- 13 to 309 +/- 12 mm Hg/sec. Right ventricular ejection fraction was measured in two dogs and increased 29% with latissimus dorsi stimulation, from 51.5% +/- 13.5% to 66.5% +/- 14.5%. Although the sample size was small, there was no difference observed between the preconditioned and nonpreconditioned groups. Right ventricular systolic pressure, rate of pressure rise, and percent latissimus dorsi fiber shortening increased as voltage and burst frequency of the muscle stimulus increased, whereas increasing the burst duration had little effect in two dogs so studied. Latissimus dorsi dynamic cardiomyoplasty can function as a partial myocardial replacement in a chronic canine model, apparently without preconditioning of the muscle. The degree of cardiac assist obtained with cardiomyoplasty appears to be influenced by the voltage and frequency of the stimulus applied to the muscle. Although it is unclear whether these results can be extrapolated to the left ventricle, this technique may find application in the treatment of ventricular aneurysm or ventricular tumor.     

Changes in mitral annular and left ventricular dimensions and left ventricular pressure-volume relations after off-pump treatment of mitral regurgitation with the Coapsys device.

OBJECTIVE: The objective of this study was to evaluate the changes in mitral annular and left ventricular dimensions and left ventricular pressure-volume relations produced by the Myocor Coapsys device that has been developed to treat functional mitral regurgitation (MR) off-pump. METHODS: The Coapsys device, which consists of anterior and posterior epicardial pads connected by a sub-valvular chord, was implanted in seven dogs with functional MR resulting from pacing induced cardiomyopathy. The Coapsys device was then sized by drawing the posterior leaflet and annulus toward the anterior leaflet. During sizing, MR grade was assessed using color flow Doppler echocardiography. Final device size was selected when MR was eliminated or minimized. Following implantation, heart failure was maintained by continued pacing for a period of 8 weeks. Mitral annular and left ventricular dimensions and left ventricular pressure-volume relations were evaluated by two-dimensional echocardiography and a conductance catheter, respectively, at pre-sizing, post-sizing, and after 8 weeks. RESULTS: All implants were performed on beating hearts without cardiopulmonary bypass. Mean MR grade was reduced from 2.9+/-0.7 at pre-sizing to 0.7+/-0.8 at post-sizing (P<0.001), and was maintained at 0.8+/-0.8 after 8 weeks (P<0.01). The septal-lateral dimensions were significantly reduced at both mitral annular level [2.4+/-0.2 cm at pre-sizing, 1.5+/-0.3 cm at post-sizing (P<0.001) and 1.8+/-0.3 cm after 8 weeks (P<0.05)] and mid-papillary level [4.1+/-0.4 cm at pre-sizing, 2.4+/-0.2 cm at post-sizing (P<0.001) and 3.3+/-0.4 cm after 8 weeks (P<0.001)]. The end-systolic pressure-volume relation shifted leftward at post-sizing with a significantly steeper slope (P=0.03). There was a significant (P=0.03) leftward shift of the end-diastolic pressure-volume relation at post-sizing. After 8 weeks, these changes in pressure-volume relations tended to return to pre-sizing relations. CONCLUSIONS: The Coapsys device significantly reduced MR by treating both the mitral annular dilatation and the papillary muscle displacement. Despite these significant dimensional changes, the Coapsys device did not negatively affect the left ventricular pressure-volume relations.     

Skeletal muscle ventricle aortic counterpulsation: function during chronic heart failure

BACKGROUND: Skeletal muscle ventricles (SMVs) are pumping chambers formed from latissimus dorsi muscle. The SMV aortic counterpulsator model has been proven to be stable in the long term and provide effective diastolic pressure augmentation in normal dogs. This study seeks to prove that the aortic counterpulsator model can function effectively in chronic heart failure. METHODS: In 6 dogs, pericardium-lined SMVs were created from latissimus dorsi muscle and electrically conditioned for fatigue resistance. Each SMV was attached to the descending thoracic aorta with a two-limb bifurcated graft and the aorta ligated between the limbs. The SMV was stimulated to contract during cardiac diastole at 1:2 to 1:3 ratio. Rapid ventricular pacing was initiated at 220 to 230 beats/min for 7 weeks to induce chronic heart failure. RESULTS: SMV contraction resulted in augmentation of the diastolic pressure time-index by 12.1% (32.8+/-15.4 versus 36.1+/-14.7 mm Hg-s, p < 0.05) at baseline, then by 33.6% (12.9+/-4.4 versus 16.8+/-4.3 mm Hg-s, p < 0.05) after 7 weeks of rapid ventricular pacing. After 7 weeks of rapid ventricular pacing, SMV counterpulsation provided significant afterload reduction with increases in peak left ventricular ejection velocity and stroke volume of 22.7% (142+/-55 versus 168+/-45 mL/s, p < 0.05) and 6.2% (13.0+/-5.1 versus 13.7+/-5.2 mL, p < 0.05), respectively. Coronary blood flow was measured in 3 animals at the 7-week measurement; augmentation averaged 47.6% (0.357+/-0.29 versus 0.432+/-0.26 mL/beat, p < 0.05). CONCLUSIONS: The SMV aortic counterpulsator provides improved cardiac assistance relative to the failing heart.     

Techniques to enhance extramyocardial collateral blood flow after a cardiomyoplasty.

OBJECTIVE: Chronic stimulation of a cardiomyoplasty was combined with low-dose infusion of heparin into the arterial supply of the cardiomyoplasty in order to determine if latissimus-derived collateral blood flow could be further enhanced. SUMMARY BACKGROUND DATA: Acute and chronic stimulation of a latissimus dorsi cardiomyoplasty increased extramyocardial collateral blood flow to 35 +/- 9% and 27 +/- 5%, respectively, of normal myocardial blood flow. METHODS: A model of coronary artery disease was created with an ameroid constrictor in goats, and a cardiomyoplasty was performed. Heparin (15 to 50 U/h) was delivered into the left subclavian artery for a period of 4 weeks. Simultaneously, the latissimus dorsi was chronically stimulated at 2 Hz. RESULTS: Chronic ischemic myocardium received a collateral flow per gram from the skeletal muscle equivalent to 11.8 +/- 5.2% of the blood flow to normal myocardium. The extramyocardial collateral flow correlated with the latissimus muscle flow (r = 0.72). CONCLUSIONS: Enhancement of extramyocardial collateral flow was not found with heparin treatment. In view of the correlation of extra-coronary collateral flow with latissimus muscle flow, the lack of a heparin effect may have been due to low latissimus blood flow. These results suggest that extramyocardial collateral blood flow to the myocardium is highest if the blood flow to the latissimus dorsi muscle is maintained.     

Hemodynamic Effects in Acute Cardiomyoplasty of Different Wrapped Muscle Activation Times as Measured by Pressure-Volume Relations

A bstract Background : Correct timing of mechanical interaction between wrapped latissimus dorsi muscle (LDM) and the heart during cardiac systole has been poorly understood and remains a controversial issue. Therefore, left ventricular pressure-volume relations were analyzed in acute cardiomyoplasty while changing the synchronization delays. Methods : Effects of different delays between the sensed cardiac R wave and wrapped muscle contraction were studied in goats submitted to acute left cardiomyoplasty. Conductance and micromanometer catheters were used to evaluate hemodynamics. Systolic contribution of the wrapped muscle was studied in preassisted and assisted beats, whereas diastolic effects were studied in assisted and postassisted beats. Results : At best settings, cardiomyoplasty resulted in a significant (p < 0.05) increase in left ventricular ejection fraction (from 42.2 ± 9.2 to 56.7%± 13%), in stroke work (from 2769 ± 1140 to 4271 ± 1717 gm/m²), in dP/dt (from 1185 ± 342 to 1510 ± 285 mmHg/sec), in end-systolic pressure (from 93.5 ± 22.5 mmHg to 97.3 ± 22.3 mmHg), and in peak ejection rate (from 282 ± 64 to 533 ± 241 mL/sec). Stroke volume showed a mean increase of 35% (from 42.2 ± 9.9 mL to 56.9 ± 20.1 mL) during assisted beats. Diastolic function was not substantially impaired at optimal stimulation delay. Incorrect timing of LD contraction resulted in suboptimal improvement or no change in comparison with unassisted hemodynamics. Conclusions : Our study documents support of cardiac performance by LDM. Incorrect timing of heart/wrapped muscle interaction led to suboptimal hemodynamic results. Muscle contraction timing is an important factor in cardiomyoplasty outcome.     

Physiologic and pathologic evaluation of chronic extra-aortic counterpulsation with latissimus dorsi flap. Preliminary results

This study attempted to evaluate the efficacy of chronic extra-aortic counterpulsation with a latissimus dorsi neuro vascular flap. Five dogs had a preliminary procedure consisting of the creation of a latissimus dorsi flap and a thoracotomy in which the flap was wrapped around the descending aorta just distal to the left subclavian artery. An epicardial lead was placed on the left ventricle and a nerve stimulating lead placed around the thoraco-dorsal nerve. Three weeks later, both leads were connected to a cardiomyostimulator programmed to function in a counterpulsation mode with a 1:2 assist frequency. Hemodynamic measurements were made at 6 and 8 and 10 and 12 weeks and the dogs were sacrificed. Three dogs had all sets of hemodynamic measurements made. Two of the three dogs demonstrated diastolic augmentation at 6 and 8 and 10 and 12 weeks average 20 to 25 mmHg. The third dog failed to demonstrate any change. All dogs were sacrificed at 12 weeks and specimens were submitted for histologic evaluation. The muscle flap was preserved in all animals. The aorta subjacent to the flap showed, (1) normal intima with no evidence of disruption or thrombus in all animals, (2) in the animals in whom counterpulsation was observed, there appeared to be thinning of the media in the aorta subjacent to the muscle flap, and (3) no evidence of distal emboli. This study demonstrated that chronic counterpulsation can be obtained with a latissimus dorsi flap. The actual hemodynamic benefits are not determined from this study. The medial thinning in the aortic wall may limit the long-term benefit of this procedure.     

Left ventricular mechanics and energetics in the dilated canine heart: acute versus chronic mitral regurgitation.

The effects of volume overload associated with mitral regurgitation on left ventricular systolic mechanics, energetics, mechanical to external stroke work efficiency, and ventriculoarterial coupling were examined in 11 conscious, closed-chest dogs. Miniature radiopaque tantalum markers were implanted into the myocardium to measure left ventricular volume, and biplane cinefluoroscopic images were obtained 1 week and 3 months after creation of mitral regurgitation. Echocardiographically determined left ventricular mass increased from 116 +/- 28 to 152 +/- 29 gm (p less than 0.001). Left ventricular end-diastolic and end-ejection volumes increased by 24% and 27%, respectively. Global left ventricular systolic performance was assessed by the slopes (linear regression) of the end-systolic pressure-volume and end-systolic stress-volume relationships corrected for change in end-diastolic volume; normalized end-systolic pressure-volume relationships fell by 36% (p less than 0.001), and normalized end-systolic stress-volume relationships declined by 21% (p less than 0.005). The normalized end-systolic volume at 100 mm Hg end-systolic left ventricular pressure increased from 0.63 to 0.75 (p less than 0.05). Similar results were observed based on a nonlinear (quadratic) fit of the end-systolic pressure-volume data. In terms of energetics, the slopes of the stroke volume-end-diastolic volume and pressure-volume area-end-diastolic volume relationships fell significantly, indicating reduced external stroke work and mechanical energy at any given level of preload. Additionally, the efficiency of energy transfer from pressure-volume area to external pressure-volume work at matched end-diastolic volume was 25% lower (p = 0.006) at 3 months compared with the 1-week measurements. While overall effective arterial (or total vascular) elastance tended to decrease after a period of time, the effective ventriculovascular coupling ratio increased from 1.6 +/- 0.6 to 2.7 +/- 1.1 (p less than 0.005), indicating a greater degree of mismatch between the left ventricle and the total (forward and regurgitant) vascular load. Therefore the low pressure-volume overload of mitral regurgitation not only resulted in depressed left ventricular systolic mechanics but also was associated with deterioration of global left ventricular energetics and efficiency and exacerbated mismatch in coupling between the left ventricle and the systemic arterial bed and left atrium.     

Cardiovascular effects of inhaled nitric oxide in a canine model of cardiomyopathy.

BACKGROUND: The inhalation of nitric oxide (NO) in patients with heart failure decreases pulmonary vascular resistance (PVR) and is associated with an increase in pulmonary artery wedge pressure (PAWP). The mechanism for this effect remains unclear. METHODS: In dogs rapid-paced for 8 weeks to induce cardiac dysfunction, we performed left ventricular pressure-volume analysis of unpaced hearts in situ to determine whether during NO inhalation (80 ppm), the mechanism for the rise in PAWP is due to: 1) primary pulmonary vasodilation; 2) a direct negative inotropic effect; or 3) impairment of ventricular relaxation. RESULTS: Inhalation of NO decreased PVR by 51%+/-3.8% (257+/-25 vs 127+/-18 dynes x sec x cm(-5) [NO 80 ppm]; p < 0.001) and increased PAWP (15.4+/-2.4 vs 18.1+/-2.6 mm Hg [NO 80 ppm]; p < 0.001). Calculated systemic vascular resistance remained unchanged. Left ventricular (LV) end-diastolic pressure rose (16.4+/-1.9 vs 19.1+/-1.8 mm Hg [NO 80 ppm]; p < 0.001), as did LV end-diastolic volume (83.5+/-4.0 vs 77.0+/-3.4 mL [NO 80 ppm]; p = 0.006). LV peak +dP/dt was unchanged by NO (1,082+/-105 vs 1,142+/-111 mm Hg/sec [NO 80 ppm]; p = NS). There was a trend toward a stroke volume increase (17.4+/-1.2 vs 18.8+/-1.3 mL; p = NS), but the relaxation time constant and end-diastolic pressure-volume relation were both unchanged. CONCLUSIONS: In this canine model of cardiomyopathy, inhaled NO decreases pulmonary vascular resistance. The associated increase in left ventricular filling pressure appears to be secondary to a primary pulmonary vasodilator effect of NO without primary effects on the contractile or relaxation properties of the left ventricle.     

Vascular delay of the latissimus dorsi provides an early hemodynamic benefit in dynamic cardiomyoplasty.

OBJECTIVES: Dynamic cardiomyoplasty (CMP) as a surgical treatment for chronic heart failure improves functional class status for most patients. However, significant hemodynamic improvement with latissimus dorsi muscle (LDM) stimulation has not been consistent. The current protocols do not allow early LDM stimulation after CMP surgery. We hypothesized that vascular delay of LDM would increase myocardial assistance after CMP and allow early (48-h) LDM stimulation after CMP. METHODS: Mongrel dogs (n = 24) were divided in four groups: 1) controls (n = 6), single-stage CMP; 2) Group ES (n = 6), single-stage CMP with early LDM stimulation beginning 48 h, postoperatively; 3) Group VD (n = 6), vascular delay of the LDM followed by CMP without early LDM stimulation, and 4) Group VDES (n = 6), vascular delay of LDM (14-18 days), followed by CMP with early stimulation (48 h postoperatively). Two weeks after CMP, global cardiac dysfunction was induced by injecting microspheres into the left coronary artery. LDM-assisted (S) beats were compared with nonstimulated beats (NS) by measuring aortic pressure (AoP), LV pressure, aortic flow, and by calculating first derivative of LV contraction (+/-dP/dt), stroke volume (SV), and stroke work (SW). RESULTS: In ES, LDM stimulation had no effect on the hemodynamic parameters. In the other groups, LDM stimulation significantly (p < 0.05) increased AoP, LVP, dP/dt, SV, and SW. However, these increases were much larger in VD and VDES. In VD, LDM stimulation increased peak AoP by 21.5+/-3.8 mm Hg, LVP by 22.1+/-4.1 mm Hg, dP/dt by 512+/-163 mm Hg/sec, SV by 10.4+/-2.3 mL, and SW by 22.1+/-5.4 g/m(-1). Similarly, in VDES, LDM stimulation increased peak AoP by 24.1+/-4.7 mm Hg, LVP by 26.2+/-4.3 mm Hg, dP/dt by 619+/-47 mm Hg/sec, SV by 6.5+/-0.7 mL, and SW by 16.7+/-4.1 g/m(-1). CONCLUSIONS: In dogs with global LV dysfunction, CMP after vascular delay resulted in a significant improvement in hemodynamic function measured 2 weeks after surgery. This improvement was not provided by single-stage CMP with or without early stimulation. Vascular delay of the LDM before surgery may play an important role for early benefit after CMP, shorten the overall muscle training period, as well as increase hemodynamic response to LDM stimulation.     

Changes in cardiac dynamics by opening an interventricular shunt in dogs

Changes in right and left ventricular (RV, LV) dynamics caused by an interventricular shunt were examined in open-chest dogs. At a pulmonary to systemic blood flow ratio of 1.7 +/- 0.2 pulmonary flow increased by 53 +/- 13%, whereas aortic flow decreased by 9 +/- 2%. Shunt flow was continuous from the left to the right ventricle throughout the cardiac cycle, but 72 +/- 4% took place during the LV ejection phase. Peak systolic LV pressure declined by 6 +/- 3 mm Hg, LV end-diastolic segment length (SL) rose, and systolic shortening of the SL increased. Peak systolic RV pressure rose from 28 +/- 3 to 36 +/- 3 mm Hg and RV end-diastolic and end-systolic SL rose almost equally. Accordingly, RV systolic SL shortening did not rise despite the substantial augmentation in RV outflow. The transseptal end-diastolic pressure gradient did not rise, while the transseptal peak systolic gradient decreased when the shunt was opened. Similarly directed alterations were observed when the shunt was opened at different preloads and when the shunt flow was varied. Local work in the anterior wall of the right ventricle (calculated from the RV pressure SL loop) rose by 26 +/- 4%, whereas RV stroke work (product of mean systolic right ventricular pressure and pulmonary flow) rose by 57 +/- 12%; difference, P less than 0.05. LV stroke work and local work in anterior LV free wall rose in proportion when the shunt was opened.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-Term Results of Right Latissimus Dorsi Cardiomyoplasty

A bstract Background : Initial experimental and clinical studies have shown that cardiomyoplasty using the right latissimus dorsi can improve left ventricular (LV) function early after operation. Methods : This study presents the long-term clinical results of this procedure. Between March 1991 and November 1992, 16 patients (12 men, 4 women; mean age 57; range 33–77 years) underwent operation. Survivors were evaluated at 6-month intervals for 2 years with right heart catheterization, radionuclide scans, exercise testing, and quality of life questionnaires. Results : The operative mortality was 6% (1/16), but 3 additional patients experienced sudden death within 6 months of operation. Survival was 63% (10/16) at 12 months and 50% (8/16) at 24 months. There were no significant changes in hemodynamic variables at 12 or 24 months after surgery. Left ventricular ejection fraction increased from 26.1 ± 5.3 to 33.4 ± 10.3 (p < 0.05) 6 weeks after operation, but was not different from baseline thereafter. The LV end-diastolic volume decreased significantly at 6 months from 306.1 ± 71 to 249.4 ± 69 mL (p < 0.01), and remained lower than the preoperative value in subsequent follow-up. Comparison of preoperative LV ejection fraction and LV stroke work index in 24-month survivors (7) and nonsurvivors (9) showed that survivors had better LV function before surgery. Functional status and quality of life were improved. Conclusions : Long-term results of right latissimus dorsi cardiomyoplasty are comparable to results using the left latissimus dorsi. Overall survival was limited by late sudden death, but survivors had improved functional capacity and stable LV function and size.