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Circulatory benefits of diastolic counterpulsation in an ischemic heart failure model after aortomyoplasty

      Abstract

      Objective: Aortomyoplasty is an experimental surgical procedure in which the latissimus dorsi muscle is wrapped around the thoracic aorta and stimulated to contract during diastole, providing diastolic counterpulsation. We hypothesized that aortomyoplasty could improve cardiac function in a chronic ischemic heart failure model, similar to the improvement seen with the intra-aortic balloon pump. Methods: Six dogs (25-30 kg) successfully underwent aortomyoplasty followed by serial coronary microembolization. Ejection fraction decreased from 63.5% to 36.5%. Two weeks after the final microembolization, the muscle was conditioned for 4 months to achieve fatigue resistance. One year after aortomyoplasty, hemodynamic studies during 1 hour of aortomyoplasty and 1 hour of intra-aortic balloon counterpulsation determined mean diastolic aortic pressure, peak left ventricular pressure, and endocardial viability ratio for assisted and unassisted beats. Cardiac output, stroke volume, and parameters of cardiac function were also measured. Results: Endocardial viability ratio increased by 23.8% ± 7.9% (P =.001) with aortomyoplasty counterpulsation and by 22.7% ± 12.9% (P =.021) with the intra-aortic balloon pump. Both aortomyoplasty and the intra-aortic balloon pump significantly increased mean diastolic aortic pressure and reduced peak left ventricular pressure. Improvements in cardiac function with aortomyoplasty and the intra-aortic balloon pump were similar. Cardiac output increased from 2.61 ± 0.88 to 3.07 ± 1.06 L/min (P =.006), and index of afterload decreased from 5.4 ± 1.4 to 4.8 ± 1.4 mm Hg/mL (P =.02) during 1 hour of aortomyoplasty counterpulsation. Conclusion: One year after the procedure, aortomyoplasty counterpulsation provided diastolic augmentation and improved cardiac performance similar to the improvement provided by the intra-aortic balloon pump in a chronic ischemic heart failure model. Aortomyoplasty has the potential to benefit patients with ischemic heart disease refractory to current therapies.
      J Thorac Cardiovasc Surg 2002;123:1067-73
      Ischemic heart disease affects 26,000,000 Americans.
      American Heart Association
      2000 Heart and Stroke Statistical Update.
      Angioplasty and coronary artery bypass grafting have been the mainstay therapies, with 1.48 million procedures performed in 1998.
      American Heart Association
      2000 Heart and Stroke Statistical Update.
      Each year approximately 100,000 patients who are not candidates for revascularization continue to experience ischemic symptoms despite maximal medical therapy.
      • Mukherjee D
      • Ellis SG
      New options for untreatable coronary artery disease: angiogenesis and laser revascularization.
      As a result, there has been a growing interest in alternative therapies and assist devices for patients with ischemic heart failure who cannot be helped by pharmacologic treatment, are not candidates for revascularization, or are awaiting a heart transplant.
      Ischemia caused by compromised perfusion leads to myocardial hibernation, a state of left ventricular contractile dysfunction that is often reversed by revascularization and an improvement in myocardial oxygen supply.
      • Erbel R
      • Heusch G
      Coronary microembolization.
      • Ross Jr, J
      Myocardial perfusion-contraction matching: implications for coronary heart disease and hibernation.
      Diastolic counterpulsation can improve myocardial oxygen supply by increasing coronary perfusion and can decrease myocardial oxygen demand by reducing afterload. The most common form of diastolic counterpulsation is the intra-aortic balloon pump (IABP). The IABP continues to be beneficial for complications of myocardial infarction, end-stage cardiomyopathy, and postcardiotomy cardiogenic shock.
      • Quaal SJ
      Indications.
      • Torchiana DF
      • Hirsch G
      • Buckley MJ
      • Hahn C
      • Allyn JW
      • Akins CW
      • et al.
      Intraaortic balloon pumping for cardiac support: trends in practice and outcome, 1968 to 1995.
      • Eltchaninoff H
      • Dimas AP
      • Whitlow PL
      Complications associated with percutaneous placement and use of intraaortic balloon counterpulsation.
      Refractory unstable angina has also been treated with the IABP
      • Quaal SJ
      Indications.
      • Torchiana DF
      • Hirsch G
      • Buckley MJ
      • Hahn C
      • Allyn JW
      • Akins CW
      • et al.
      Intraaortic balloon pumping for cardiac support: trends in practice and outcome, 1968 to 1995.
      • Eltchaninoff H
      • Dimas AP
      • Whitlow PL
      Complications associated with percutaneous placement and use of intraaortic balloon counterpulsation.
      and the enhanced external counterpulsation device, which uses external compression of the lower extremities to augment diastole.
      • Lawson WE
      • Hui JCK
      • Cohn PF
      Long-term prognosis of patients with angina treated with enhanced external counterpulsation: five-year follow-up study.
      An experimental surgical procedure that generates autologous diastolic counterpulsation is aortomyoplasty, in which the latissimus dorsi muscle (LDM) is wrapped around the ascending or descending thoracic aorta and stimulated to contract during diastole. Aortomyoplasty can increase coronary blood flow through diastolic augmentation
      • Cmolik BL
      • Thompson DR
      • Sherwood JT
      • Geha AS
      • George DT
      Increased coronary artery blood flow with aortomyoplasty in chronic heart failure.
      • Bolotin G
      • Wolf T
      • van der Veen FH
      • Shofti R
      • Loruso R
      • Shreuder JJ
      • et al.
      Acute descending aortomyoplasty induces coronary blood flow augmentation.
      • Bolotin G
      • Wolf T
      • Shachner R
      • van der Veen FH
      • Shofti R
      • Lorusso R
      • et al.
      Hemodynamic evaluation of descending aortomyoplasty versus intra-aortic balloon pump performed in normal animals: an acute study.
      and can decrease left ventricular work through afterload reduction.
      • Lazzara RR
      • Trumble DR
      • Magovern JA
      Dynamic descending thoracic aortomyoplasty: comparison with intraaortic balloon pump in a model of heart failure.
      Although the application of skeletal muscle extra-aortic counterpulsation is not a new idea and has had limited success clinically, indications for its use have been diverse.
      • Chachques JC
      • Braunberger E
      • Lajos P
      • Argyriadis P
      • Shafy A
      • Latremouille C
      • et al.
      Biological counterpulsation with aortomyoplasty: experimental and clinical results.
      • Trainini J
      • Barisani J
      • Mouras J
      • Cabrera Fischer EI
      • Christen AI
      Chronic aortic counterpulsation with latissimus dorsi: clinical follow-up. Cardiomyoplasty comparison.
      We propose that the enhanced coronary perfusion of chronic aortomyoplasty counterpulsation may benefit patients with ischemic heart disease who have exhausted pharmacologic options and are not candidates for revascularization.
      Previous work in our laboratory involved optimizing aortomyoplasty muscle stimulation to cardiac cycle timing, showing an increase in coronary blood flow with aortomyoplasty counterpulsation, optimizing muscle wrap configuration to yield the greatest hemodynamic benefits, and demonstrating the integrity of the LDM 6 months after aortomyoplasty.
      • Cmolik BL
      • Thompson DR
      • Sherwood JT
      • Geha AS
      • George DT
      Increased coronary artery blood flow with aortomyoplasty in chronic heart failure.
      • Cmolik BL
      • Thompson DR
      • Sherwood JT
      • Rovner AL
      • Geha AS
      • George DT
      Optimizing muscle wrap configuration for aortomyoplasty.
      • Thompson DR
      • Cmolik BL
      • Cheever EA
      • Geha AS
      • George DT
      Optimizing muscle-to-cardiac timing for aortomyoplasty.
      • Sherwood JT
      • Thompson DR
      • Schomisch SJ
      • Stewart RW
      • George DT
      • Cmolik BL
      Long-term diastolic counterpulsation with aortomyoplasty: hemodynamic effectiveness at 6 months.
      The purpose of this investigation was to confirm the long-term stability of the aortomyoplasty muscle wrap and to evaluate the efficacy of acute aortomyoplasty counterpulsation in comparison with the IABP in a chronic ischemic heart failure model. We hypothesized that 1 year after the procedure, aortomyoplasty counterpulsation would provide cardiac benefits equivalent to the IABP in a chronically ischemic heart.

      Material and methods

      Six male mongrel dogs (25-30 kg) completed the study. The procedures were performed in compliance with the “Principles of Laboratory Animal Care” of the National Society for Medical Research and the “Guide for the Care and Use of Laboratory Animals” prepared by the Institute of Laboratory Animal Resources, National Research Council, and published by the National Academy Press, revised 1996. The Case Western Reserve University Institutional Animal Care and Usage Committee also approved the protocol.

      Descending aortomyoplasty

      Ten mongrel dogs underwent aortomyoplasty. General anesthesia was induced with buprenorphine (0.3 mg subcutaneously) and sodium thiopental (25 mg/kg intravenously). After endotracheal intubation, anesthesia was maintained with isoflurane (1%-2%). Prophylactic cefazolin (1 g) and fluids were administered intravenously. The animal was monitored by continuous electrocardiography (ECG) and pulse oximetry. In the left thoracotomy position, an axillary incision extending to midthorax was made for the left LDM to be mobilized. The neurovascular bundle was preserved, and intramuscular pacing electrodes were implanted near the thoracodorsal nerve. The electrodes were tunneled subcutaneously to exit between the scapulae, where they were later attached to a portable stimulator. Through a left fifth interspace thoracotomy, the descending thoracic aorta was exposed, and several intercostal arteries were ligated as needed to allow the muscle to be wrapped around the aorta. After resection of a 4-cm portion of the second rib, the LDM was transposed into the chest. With the “wringer wrap” configuration developed in our laboratory (Figure 1), the LDM was divided longitudinally, with the oblique-transverse portion wrapped clockwise around the proximal part of the descending thoracic aorta and the lateral portion of the muscle wrapped counterclockwise distally.
      • Cmolik BL
      • Thompson DR
      • Sherwood JT
      • Rovner AL
      • Geha AS
      • George DT
      Optimizing muscle wrap configuration for aortomyoplasty.
      Figure thumbnail gr1
      Fig. 1Aortomyoplasty wringer wrap configuration: LDM wrapped around descending thoracic aorta.
      The muscle was then secured to itself.

      Microembolization

      Several months after aortomyoplasty, serial coronary microembolizations were performed. General anesthesia was induced with diazepam (0.165 mg/kg intravenously), pentobarbital (10 mg/kg intravenously), and hydromorphone (0.29 mg/kg intravenously). After endotracheal intubation, prophylactic cefazolin (1 g) and fluids were administered intravenously. Animals were monitored throughout the procedure with a continuous ECG and pulse oximetry. After isolation of the femoral artery to catheterize the left heart, heparin (1500 units intravenously) was administered. A Judkins preformed coronary catheter (JL-4) was positioned in the left anterior descending or circumflex coronary artery under fluoroscopic guidance. Subsequently, a mixture consisting of 0.5-mL Polybead (Polysciences Inc, Warrington, Pa) polystyrene microspheres (90 μm in diameter, approximately 40,000 particles/[mL · injection]) with 0.5-mL radiographic contrast suspension (iothalamate meglumine; Mallinckrodt Inc, St Louis, Mo) was delivered by bolus injection into the artery.
      During each session, an average of three injections were delivered at 15-minute intervals. The ECG was monitored for ischemic changes and arrhythmias. After embolization, propranolol (1 mg) to minimize catecholamine surge and protamine (15 mg) to reverse heparin were administered intravenously. The femoral artery was then primarily repaired, and the incision was closed. Each animal underwent approximately 9 to 14 weekly sessions of microembolization. The left ventricular ejection fraction was measured with contrast ventriculography digital analysis (Simpson method). Once ejection fraction had decreased to approximately 35% (from baseline of 63.5% ± 6.0% to 36.5% ± 3.6%, P <.05), the microembolization sessions were discontinued. Six dogs survived the microembolization procedures.

      Muscle conditioning

      Two weeks after the final microembolization, long-term muscle conditioning was initiated and was continued for approximately 4 months. A fitted jacket securing a portable stimulator was attached to the muscle pacing electrodes that exited between the scapulae. The stimulator was programmed to supply a pulse frequency of 2 Hz (24 h/d) with an amplitude of 3 to 4 V and a pulse width of 210 μs, sufficient to twitch the LDM.
      • Cheever EA
      • Thompson DR
      • Cmolik BL
      • Santamore WP
      • George DT
      A versatile microprocessor-based multichannel stimulator for muscle cardiac assist.
      The twitch was detected by palpation of the left axillary region. The 2-Hz frequency protocol is well documented for developing a fatigue-resistant LDM by converting the type II (fast twitch) muscle fibers to type I (slow twitch) muscle fibers.
      • Mannion JD
      • Bitto T
      • Hammond RL
      • Rubinstein NA
      • Stephenson LW
      Histochemical and fatigue characteristics of conditioned canine latissimus dorsi muscle.
      • Ianuzzo CD
      • Hamilton N
      • O'Brien PJ
      • Desrosiers C
      • Chiu R
      Biochemical transformation of canine skeletal muscle for use in cardiac-assist devices.

      Hemodynamic studies

      Four months after the final microembolization session (1 year after aortomyoplasty), peak left ventricular pressure, mean diastolic aortic pressure, and endocardial viability ratio were measured for assisted and unassisted beats during 1 hour of aortomyoplasty and 1 hour of IABP counterpulsation. Endocardial viability ratio is the ratio of the diastolic pressure time index to systolic tension-time index, which correlates to the myocardial oxygen supply-to-demand ratio and is an index of the extent of counterpulsation.
      • Cabrera Fischer EI
      • Christen AI
      • de Forteza E
      • Risk MR
      Dynamic abdominal and thoracic aortomyoplasty in heart failure: assessment of counterpulsation.
      General anesthesia was induced as for the aortomyoplasty surgery. A 7.5F Swan-Ganz catheter (Baxter Healthcare Corp, Edwards Division, Santa Ana, Calif) was positioned to measure pressures, cardiac output (CO), and stroke volume. Under fluoroscopic guidance, a combination pressure and conductance catheter (Millar Instruments, Inc, Houston, Tex) was advanced through the carotid artery into the left ventricle. The conductance catheter was attached to a signal conditioner and processor for calculation of an uncalibrated volume signal (Leycom Sigma 5; Cardiodynamics, Zoetermeer, The Netherlands). Stroke volume and ejection fraction were used to calibrate the volume signal. Analog signals were continuously monitored (Gould Electronics Inc, Eastlake, Ohio) and were recorded digitally by computer during a respiratory pause.
      The left ventricular pressure and volume data were used to plot pressure-volume loops during 1:2 aortomyoplasty and 1:2 IABP counterpulsation. For each sampling of the waveforms, the cardiac cycles were separated into assisted and unassisted beats to compare the extent of augmentation. The following indices were derived from the pressure-volume loops: maximal elastance (Emax), the slope of the end-systolic pressure and volume relationship or the index of contractility; effective arterial elastance (Ea), the ratio of the end-systolic pressure to stroke volume or the index of afterload; preload recruitable stroke work (PRSW), the ratio of stroke work to end-diastolic volume; and the ventriculoarterial (VA) coupling index (Ea/Emax), the relationship between the ventricular elastance and the arterial afterload. A VA coupling index value of 1 indicates optimal cardiac performance.
      During 1 hour of aortomyoplasty counterpulsation, the LDM was stimulated by a bench-top stimulator (AstroMed, Inc, Grass Instrument Division, West Warwick, RI) connected to a customized computer program designed in our laboratory incorporating Labview (National Instruments Corporation, Austin, Tex). This software provided the timing and duration of the impulse relative to the ECG waveform. The LDM was stimulated with a pulse frequency of 30 Hz, amplitude of 4 to 10 V, and pulse width of 210 μs duration during every other cardiac cycle, initiated at the dicrotic notch and terminated during isovolumic contraction.
      Finally, each animal underwent 1 hour of IABP counterpulsation while hemodynamic measurements were recorded. A 9.5F IABP catheter (System 98 Pump; Datascope Corp, Montvale, NJ) with a 25-mL balloon was introduced through the femoral artery, and its position was confirmed under fluoroscopy. The IABP activation was set at a 1:2 ratio, and conventional timing was employed such that the balloon was inflated at the dicrotic notch and deflated to yield a presystolic dip (minimal aortic pressure).

      Statistical analysis

      Comparisons of the hemodynamic indices between the assisted and unassisted beats and the cardiac function indices during unassisted beats at the start and the end of 1 hour of counterpulsation were analyzed with paired t tests. All results are expressed as mean ± SD.

      Results

      Outcomes and adverse events

      Ten healthy male mongrel dogs successfully underwent aortomyoplasty without neurologic sequelae. Skin infection at the exit site of the muscle pacing electrodes was noted in 5 animals. The infections were treated with an antibiotic (cephalexin, 1 g orally twice daily) and local wound care. Procainamide (500 mg) was administered intravenously to treat arrhythmias associated with the microembolization procedure. Each animal received a diuretic (furosemide, 10-20 mg orally twice daily) as needed for evidence of pulmonary edema. Four dogs died of arrhythmia during the microembolization procedures, before long-term muscle conditioning. Six dogs successfully completed serial coronary microembolization, long-term muscle conditioning, and hemodynamic studies.

      Hemodynamic effects

      One hour of counterpulsation during every other cardiac cycle with aortomyoplasty and the IABP produced similar hemodynamic improvements. The myocardial oxygen supply-to-demand ratio, endocardial viability ratio, increased by 23.8% ± 7.9% (P =.001) during assisted beats with aortomyoplasty and by 22.7% ± 12.9% (P =.021) with the IABP (Table 1).
      Table 1Indices of hemodynamic augmentation: Aortomyoplasty counterpulsation versus the IABP in an ischemic heart failure model
      StartEnd
      NonaugmentedAugmentedP value% IncreaseNonaugmentedAugmentedP value% Increase
      Aortomyoplasty
       Endocardial viability ratio1.205 ± 0.4101.487 ± 0.483.00123.8 ± 7.91.177 ± 0.2851.404 ± 0.303.00119.9 ± 7.8
       Mean diastolic aortic pressure (mm Hg)98.5 ± 24.0114.0 ± 27.3.00115.8 ± 3.996.4 ± 23.5108.0 ± 26.0.00112.1 ± 207
       Peak left ventricular pressure (mm Hg)120.8 ± 27.4118.0 ± 26.6.001−2.3 ± 0.3120.0 ± 26.7116.8 ± 25.4.02−2.6 ± 1.6
      IABP
       Endocardial viability ratio1.234 ± 0.1621.526 ± 0.358.02122.7 ± 12.91.247 ± 0.1811.525 ± 0.378.02121.0 ± 11.7
       Mean diastolic aortic pressure (mm Hg)89.2 ± 22.9104.5 ± 26.9.00617.5 ± 9.589.1 ± 21.6103.8 ± 25.0.00516.8 ± 8.9
       Peak left ventricular pressure (mm Hg)112.2 ± 25.5109.7 ± 24.9.009−2.2 ± 1.3112.2 ± 24.6110.0 ± 24.1.004−2.0 ± 0.9
      Values are mean ± SD. Start represents mean value of the first 10 minutes of augmentation; End represents mean value of the final 10 minutes of augmentation.
      Both aortomyoplasty and the IABP significantly increased mean diastolic aortic pressure and reduced peak left ventricular pressure. Furthermore, the mean value of the hemodynamic improvements at the start of the hour did not differ significantly from the values at the end of the hour.

      Effects on cardiac performance

      To further evaluate the efficacy of counterpulsation, the average cardiac function indices for the unassisted beats during the first 10 minutes of augmentation were compared with the values during the final 10 minutes. Neither aortomyoplasty nor the IABP significantly changed the heart rate throughout the hour of counterpulsation (Table 2).
      Table 2Indices of cardiac performance: Aortomyoplasty counterpulsation versus the IABP in an ischemic heart failure model
      AortomyoplastyIABP
      StartEndP valueStartEndP value
      Heart rate (beats/min)114.7 ± 22.7117.5 ± 25.9.429111.3 ± 23.3114.0 ± 22.4.323
      Emax (mm Hg/mL)2.9 ± 1.33.1 ± 1.4.6103.2 ± 1.63.4 ± 1.8.393
      Ea (mm Hg/mL)5.4 ± 1.44.8 ± 1.4.0065.1 ± 2.04.8 ± 1.6.431
      Ea/Emax2.1 ± 0.71.8 ± 0.8.2621.8 ± 0.91.7 ± 0.8.140
      PRSW (mm Hg)38.1 ± 15.941.6 ± 16.6.35739.7 ± 18.441.4 ± 18.8.068
      Stroke volume (mL)24.3 ± 8.326.4 ± 7.6.13425.2 ± 8.325.6 ± 8.0.751
      CO (L/min)2.61 ± 0.883.07 ± 1.06.0202.81 ± 0.742.86 ± 0.95.813
      Values are mean of unassisted beats ± SD. Start represents mean value of the first 10 minutes of augmentation; End represents mean value of the final 10 minutes of augmentation.
      Although Emax, an index of contractility, increased with both aortomyoplasty (2.9 ± 1.3 to 3.1 ± 1.4 mm Hg/mL) and the IABP (3.2 ± 1.6 to 3.4 ± 1.8 mm Hg/mL), the difference did not reach statistical significance. During aortomyoplasty counterpulsation, Ea decreased from 5.4 ± 1.4 to 4.8 ± 1.4 mm Hg/mL (P =.006), indicating a reduced afterload. The IABP also decreased Ea (5.1 ± 2.0 to 4.8 ± 1.6 mm Hg/mL), but this decrease did not achieve statistical significance. PRSW increased with both methods, indicating an increase in stroke work throughout the hour, a decrease in end-diastolic volume throughout the hour, or both. Stroke volume increased with aortomyoplasty (24.3 ± 8.3 to 26.4 ± 7.6 mL) but not with the IABP (25.2 ± 8.3 to 25.6 ± 8.0 mL). This in turn was reflected in a statistically significant increase in CO during aortomyoplasty, from 2.61 ± 0.88 to 3.07 ± 1.06 L/min (P =.02). The VA coupling index (Ea/Emax) decreased from 2.1 ± 0.7 to 1.8 ± 0.8 during aortomyoplasty and from 1.8 ± 0.9 to 1.7 ± 0.8 during IABP counterpulsation.
      A pressure-volume analysis for the averaged unassisted beats, comparing the start with the end of 1 hour of aortomyoplasty counterpulsation for a single animal, is presented in Figure 2.
      Figure thumbnail gr2
      Fig. 2Pressure-volume analysis during aortomyoplasty counterpulsation. Averaged unassisted pressure-volume loop of single animal at start (solid line) and end (dashed line) of 1 hour of aortomyoplasty counterpulsation. P, Pressure in millimeters of mercury; V, volume in milliliters.
      The leftward shift of the pressure-volume loop from the start to the end of the hour represents improved cardiac performance, with an increase in Emax (contractility) and a decrease in Ea (afterload). Figure 3 represents the trends in the indices of cardiac function during aortomyoplasty counterpulsation.
      Figure thumbnail gr3
      Fig. 3One hour of aortomyoplasty counterpulsation in ischemic heart failure model. Values are percentage of baseline ± SEM. Stim On, Start of counterpulsation; Stim Off, end of counterpulsation. Small squares, Stroke volume; circles, CO; triangles, PRSW; diamonds, Emax; large squares, Ea.
      The values are percentage changes relative to the baseline. With the onset of counterpulsation, there were gradual increases in stroke volume, CO, Emax, and PRSW and a decrease in Ea as the hour progressed. When the LDM stimulation was turned off, all values approached baseline.

      Discussion

      The IABP benefitted 155,000 patients globally in 1999 (Datascope Corp, personal communication). As the criterion standard of diastolic counterpulsation, the IABP has assisted patients with cardiogenic shock, unstable angina, and myocardial infarction; however, its long-term use remains limited by such complications as thromboembolic events and infection.
      • Quaal SJ
      Indications.
      • Torchiana DF
      • Hirsch G
      • Buckley MJ
      • Hahn C
      • Allyn JW
      • Akins CW
      • et al.
      Intraaortic balloon pumping for cardiac support: trends in practice and outcome, 1968 to 1995.
      • Eltchaninoff H
      • Dimas AP
      • Whitlow PL
      Complications associated with percutaneous placement and use of intraaortic balloon counterpulsation.
      Aortomyoplasty is a surgical procedure that can provide autologous and hemocompatible counterpulsation. Because it is not limited by the complications of the IABP, its potential to benefit the ischemic heart on a long-term basis as an adjunct to current therapies needs to be explored.
      Successful diastolic counterpulsation enhances coronary perfusion by diastolic augmentation and reduces left ventricular work by afterload reduction.
      • Frazier OH
      New technologies in the treatment of severe cardiac failure: the Texas Heart Institute experience.
      In this model of ischemic heart failure, we demonstrated improved cardiac function through sustained diastolic augmentation and afterload reduction during 1 hour of aortomyoplasty counterpulsation. Equally important was the observation that the hemodynamic augmentation during aortomyoplasty was comparable to that seen with the IABP.
      Pressure-volume analysis of cardiac performance showed similar improvements after 1 hour of counterpulsation with aortomyoplasty and the IABP. Although the changes in such indices as Emax, PRSW, and CO did not reach statistical significance, there was an overall improvement in cardiac function during aortomyoplasty, as demonstrated in Figure 3. With the onset of counterpulsation, Emax, CO, and PRSW gradually increased, followed by a return to baseline after the LDM stimulation was turned off. The overall decrease in the VA coupling index during 1 hour of counterpulsation supports the contention that both interventions were able to decrease afterload, increase ventricular contractility, or both. We speculate that the small number of animals in the study (n = 6) and the moderate degree of ischemic damage could explain why certain values of cardiac performance did not reach statistical significance. Furthermore, a longer period of diastolic augmentation may be necessary for complete recovery of cardiac function.
      Although heart failure models such as rapid ventricular pacing and propranolol administration have been used to demonstrate the effects of aortomyoplasty counterpulsation,
      • Lazzara RR
      • Trumble DR
      • Magovern JA
      Dynamic descending thoracic aortomyoplasty: comparison with intraaortic balloon pump in a model of heart failure.
      • Mannion JD
      • Bitto T
      • Hammond RL
      • Rubinstein NA
      • Stephenson LW
      Histochemical and fatigue characteristics of conditioned canine latissimus dorsi muscle.
      • Cabrera Fischer EI
      • Christen AI
      • de Forteza E
      • Risk MR
      Dynamic abdominal and thoracic aortomyoplasty in heart failure: assessment of counterpulsation.
      we chose the sequential coronary microembolization model for several reasons. Coronary microembolization leads to reduced ejection fraction, increased left ventricular end-diastolic pressure, and elevated plasma norepinephrine levels.
      • Sabbah HN
      • Stein PD
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      • et al.
      A canine model of chronic heart failure produced by multiple sequential coronary microembolizations.
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      • et al.
      Characteristics of chronic left ventricular dysfunction induced by coronary embolization in a canine model.
      The chronic changes of this model support the argument that multiple embolizations will exhaust the compensatory mechanisms of the myocardium, leading to left ventricular dysfunction
      • Sabbah HN
      • Stein PD
      • Kono T
      • Gheorghiade M
      • Levine TB
      • Jafri S
      • et al.
      A canine model of chronic heart failure produced by multiple sequential coronary microembolizations.
      and compromised coronary flow reserve.
      • Blaustein AS
      • Hoit BD
      • Wexler LF
      • Ashraf M
      • Ramrakhyani K
      • Matoba R
      • et al.
      Characteristics of chronic left ventricular dysfunction induced by coronary embolization in a canine model.
      A model of ischemic cardiac dysfunction can benefit the most from diastolic counterpulsation. This is the first study to our knowledge to examine aortomyoplasty in a chronic ischemic heart failure model.
      Atherosclerotic plaque rupture and mural thrombus, followed by embolization in the coronary vessels, may be responsible for ischemic heart disease in human beings.
      • Erbel R
      • Heusch G
      Coronary microembolization.
      • Erbel R
      • Heusch G
      Coronary microembolization—its role in acute coronary syndromes and interventions.
      The compromised coronary flow in response to coronary microembolization leads to reduced myocardial contractile function and a new steady state of perfusion-contraction matching to preserve energy and prevent progressive ischemia.
      • Erbel R
      • Heusch G
      Coronary microembolization.
      • Ross Jr, J
      Myocardial perfusion-contraction matching: implications for coronary heart disease and hibernation.
      It has been argued that downward regulation of energy requirement occurs with moderate myocardial ischemia.
      • Bristow JD
      • Arai AE
      • Anselone CG
      • Pantley GA
      Response to myocardial ischemia as a regulated process.
      This perfusion-contraction matching has been proposed to be a physiologic effect of the hibernating myocardium.
      • Erbel R
      • Heusch G
      Coronary microembolization.
      Myocardial function can be restored partially or completely if the supply and demand of oxygen is favorably changed by improving the blood supply,
      • Conversano A
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      • Perez JE
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      • Gropler RJ
      Delineation of myocardial stunning and hibernation by positron emission tomography in advanced coronary artery disease.
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      Repeated stunning precedes myocardial hibernation in progressive multiple coronary artery obstruction.
      as occurs with revascularization. Our results suggest that aortomyoplasty counterpulsation may also benefit a hibernating myocardium by enhancing myocardial oxygen supply and reducing myocardial demand.
      The length of our study supports the long-term potential of aortomyoplasty. The LDM did not fatigue during the hour of counterpulsation, which confirms the adequate conditioning and the viability of the muscle 1 year after the operation. We have previously examined muscle viability 1 year after wringer wrap aortomyoplasty, demonstrating that biopsy samples of short-term-stimulated LDM revealed no evidence of necrosis, fibrosis, or fatty infiltration relative to the contralateral LDM (unpublished data). Studies involving 12 to 24 months of long-term LDM stimulation after aortomyoplasty have also demonstrated no evidence of fibrosis, atrophy, or fatty infiltration of the wrapped muscle.
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      • Camishion RC
      Biotransformation of skeletal muscle used for long-term dynamic aortomyoplasty.
      Limitations of our study include the sole use of ejection fraction to quantify the extent of ischemic heart damage. Additional methods, such as the dobutamine stress test, might better evaluate the ischemic changes after serial coronary microembolization and subsequent improvement with counterpulsation. Furthermore, cardiac benefits of aortomyoplasty counterpulsation were evaluated mainly by pressure-volume analysis. Measurement of coronary blood flow and myocardial oxygen consumption could further demonstrate the benefits of counterpulsation.
      In summary, aortomyoplasty can provide hemodynamic augmentation comparable to that of the IABP, but without the attendant complications.
      • Cmolik BL
      • Thompson DR
      • Sherwood JT
      • Geha AS
      • George DT
      Increased coronary artery blood flow with aortomyoplasty in chronic heart failure.
      • Bolotin G
      • Wolf T
      • Shachner R
      • van der Veen FH
      • Shofti R
      • Lorusso R
      • et al.
      Hemodynamic evaluation of descending aortomyoplasty versus intra-aortic balloon pump performed in normal animals: an acute study.
      • Lazzara RR
      • Trumble DR
      • Magovern JA
      Dynamic descending thoracic aortomyoplasty: comparison with intraaortic balloon pump in a model of heart failure.
      We have demonstrated that acute aortomyoplasty counterpulsation improves cardiac function in a chronic ischemic heart failure model. Future studies should establish the ability of aortomyoplasty to provide long-term counterpulsation capable of attenuating the symptoms of ischemic heart disease. Evidence that long-term counterpulsation by means such as enhanced external counterpulsation devices can benefit patients with angina
      • Lawson WE
      • Hui JCK
      • Cohn PF
      Long-term prognosis of patients with angina treated with enhanced external counterpulsation: five-year follow-up study.
      supports the potential of long-term counterpulsation devices in the clinical setting. For patients with ischemic heart disease that is refractory to current therapies, aortomyoplasty may provide long-term relief through diastolic augmentation and systolic unloading.

      Discussion

      Dr George L. Hicks, Jr (Rochester, NY). This was an elegant long-term study. Clearly, in a chronically ischemic model you need to increase diastolic flow while you are treating heart failure by decreasing cardiac work. So what were your results in terms of the left ventricular dynamics?
      Dr Hedayati. Although the data were not presented, we did measure load-independent and load-dependent variables of cardiac performance with a conductance catheter that measured ventricular volume. Values such as contractility, stroke work, preload recruitable stroke work, and afterload did improve during counterpulsation, with some of the values reaching statistical significance. These are discussed at length in our manuscript.
      Dr Ernst Wolner (Vienna, Austria). I have two comments. Number one, usually patients who use such a device have a calcified and inflexible aorta. That is why we use fresh homografts and a large pericardial patch to obtain similar results.
      Number two, in the early 1970s, as balloon pumping came up, I had used at that time (before the transplant era) in some patients so-called long-term balloon pumping in cardiomyopathy, where we implanted the balloon pump over the iliac artery and had it tunneled under the skin. The long-term effect of this treatment at that time was more or less inefficient, so I have some concern that you can assist patients with cardiomyopathy with such a device. However, it is an elegant study.
      Dr Hedayati. Aortic calcification is a contraindication to aortomyoplasty. With respect to your second comment, our study was based on an ischemic heart failure model in which we compared aortomyoplasty with the IABP, which has been the criterion standard of diastolic counterpulsation. Currently, diastolic augmentation is achieved with lower extremity external compression devices in patients with unstable angina, and this has been effective long-term in clinical practice.
      Dr Paul Kurlansky (Miami Beach, Fla). I congratulate you on an interesting study. I note that from the enhanced external counterpulsation literature we find that 35 weeks of treatment with external counterpulsation can result in increased myocardial perfusion and actually symptomatic benefit that will last 3 years after therapy has stopped. I was just wondering whether you have any long-term experiments which show changes in myocardial perfusion.
      Dr Hedayati. The aortomyoplasty procedure and subsequent muscle stimulation and conditioning were performed during the year before the acute studies. Our long-term plans would be to show the effects of chronic aortomyoplasty counterpulsation and to examine the effects on the myocardium with tests such as stress echocardiography.

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