The intra-aortic balloon pump (IABP) is the most widely used and most appropriate assist device for short-term circulatory support. Part of standard care before proceeding with revascularization in patients presenting with acute myocardial infarction and cardiogenic shock or low output state,1 the IABP is also implemented used for weaning from cardiopulmonary bypass (CPB) complicated by postcardiotomy heart failure (HF),2 and as a bridge to cardiac transplantation in presence of cardiac decompensation.3 The nonpulsatile centrifugal pump (CFP), suitable for short-term left ventricular (LV) assistance and apparently as effective as pulsatile devices to restore hemodynamics,4 probably is the second most frequently used device for the management of postcardiotomy HF.
The IABP improves myocardial energetics by 1) decreasing the LV systolic pressure and afterload, and 2) increasing the myocardial perfusion pressure and flow.2 CFP, on the other hand, decreases the preload but not the afterload.5 In profound cardiogenic shock, combining both pumps appears highly effective in restoring hemodynamics and maintaining the proper perfusion of major organs and peripheral tissues.6 In contrast, experimental7,8 and clinical9,10 studies of the effects of the IABP and CFP on myocardial energetics and systemic circulation in moderate and severe HF in absence of severe hypotension have yielded conflicting results. In the present study, we examined the effects of the IABP versus the CFP on LV energetics in a porcine model of rapidly worsening acute heart failure.
The 18 domestic pigs used in this study weighed between 50 and 60 kg, and were treated in compliance with the “Guide for the care and use of Laboratory animals” of the National Institute of Health. After overnight fast, the animals were premedicated by intramuscular administration of midazolam, 0.5 mg/kg, ketamine hydrochloride, 15 mg/kg, and atropine, 1 mg. Once the pig was sedated, the electrocardiogram was recorded, an ear vein was cannulated, the trachea was intubated with a 7.5 or 8.0 mm cuffed endotracheal tube, and anesthesia through the ear vein was induced with thiopental sodium, 8 mg/kg i.v., followed by fentanyl, 10 μg/kg i.v., and pancuronium bromide, 0.1 mg/kg i.v. Mechanical ventilation was delivered by a volume-controlled, time-cycled ventilator (Soxitronic, Soxil S.P.A., Torino, Italy) with a 10–12 ml/kg tidal volume, a respiratory rate of 12–16 breaths per min, and a 40% inspired O2 concentration, to maintain normal arterial blood gases. Anesthesia, analgesia, and neuromuscular blockade were maintained by continuous infusions of thiopental, 3 mg/kg/h i.v., fentanyl, 0.03 mg/kg/h i.v., and pancuronium bromide, 0.5 mg/kg/min i.v.
A 3-lumen catheter was introduced into the right atrium via the right external jugular vein for monitoring of the right atrial pressure. After median sternotomy, a 6F multipurpose catheter was advanced into the left internal mammary artery for recording of the aortic pressure. The pericardial sac was opened and after systemic anticoagulation with 5,000 U of heparin, i.v., 1) a 40F wired basket cannula connected to the inflow of the CFP (Sarns Centrifugal System, Terumo Corporation, Tokyo, Japan) was introduced into the left atrium, and 2) a 14F cannula connected to the outflow of the CFP was placed into the right carotid artery. Positioning of CFP inflow cannula into the left atrium aimed at partial unloading of LV, simulating the mode of function of other easily applicable percutaneous assist devices already used in clinical practice (i.e., Tandem Heart). Both cannulas and the pump head were connected with 3/8 inches PVC tubings, prefilled with 300 ml of normal saline solution.
A 6F multipurpose catheter was then inserted directly into the left ventricle through the LV apical wall, and a 40-ml intra-aortic balloon catheter was advanced into the descending aorta via the left common carotid artery. The IABP (Datascope 96, Datascope Corp., Montrale, NJ) was synchronized to the electrocardiogram with a view to achieve maximal unloading of the left ventricle. Finally, one 2-mm, ring-shaped flow probe of a transit time ultrasound flowmeter (Medistim AS, Oslo, Norway) was placed around the left anterior descending (LAD) artery for measurements of the LAD flow, and another, 18-mm probe was placed around the pulmonary artery for measurements of the cardiac output (CO). The final configuration of the experimental model is shown in Figure 1.
After completion of the surgical preparation and instrumentation, 15 min were allowed for hemodynamic stabilization before recording the baseline data. A total of 60 to 70 minutes were normally required from anesthesia induction to baseline phase. Acute HF was then induced by ligation of multiple branches of the LAD coronary artery, consecutive doses of propranolol, 0.5 mg i.v., up to a total of 0.5 mg/kg, and an infusion of crystalloid fluid, as described previously.6 Amiodarone, 5 mg/kg i.v., was administered over 5 min to prevent the development of sustained ventricular tachyarrhythmias. Acute HF was defined as a) moderate when the LV end-diastolic pressure (EDP) was >12 mm Hg and systolic arterial pressure was ≥100 mm Hg, or b) severe when LVEDP was >12 mm Hg and systolic arterial pressure ranged between 80 and 99 mm Hg.
When the moderate stage of acute HF was reached, mechanical assistance with each of the devices was initiated for 5 min in a random order and withheld afterwards. The CFP speed was adjusted to generate the maximum output without evoking left atrial collapse (partial support). To induce severe HF, additional LAD and LCX artery branches were ligated and further doses of propranolol were administered. Although we intended to induce a gradual deterioration of LV function, in some experiments, once severe HF was induced, the hemodynamic status continued to deteriorate rapidly, ending with electromechanical dissociation unless mechanical support was readily implemented.
Hemodynamic measurements, including LVEDP, peak LV systolic pressure (SP), end-diastolic aortic pressure (EDAP), mean right atrial pressure (RAP), heart rate (HR), LAD flow, double product (DP) calculated as LVSP × HR, total tension time index (TTI), mean arterial pressure (MAP), and CO, were made after 5 min of support with IABP or CFP.
Because of the indistinct dicrotic notch of the aortic pressure (AP) tracing during the CFP function, the area corresponding to the TTI could not be precisely measured. Therefore, we utilized total TTI to approximate the myocardial oxygen demand. Total TTI was calculated by planimetry of the area under the LV pressure curve during systole (isovolumic systolic and ejection phase) and isovolumic relaxation (Figure 2). Total TTI is a close approximation of TTI and is closely related to myocardial oxygen consumption (Figure 3).
Student’s t test for paired observations was used for comparisons between variables. Data are presented as mean values ± standard deviation. Statistical significance was assumed when the p value was ≤0.05.
The LV and AP recordings with and without mechanical support by the IABP or CFP are shown in Figure 4.
In the experimentally induced moderate HF, CO decreased by 24% and LVEDP increased by 122%, compared with before the induction of HF (baseline). When HF had reached a severe stage, CO was decreased by 49%, LVSP by 22%, and LVEDP was increased by 111% compared with baseline (Table 1).
The effects of the IABP versus the CFP in moderate HF are shown in Table 2. Total TTI decreased significantly during application of IABP and during CFP. In contrast, DP was significantly decreased by the IABP (p = 0.003), though was little changed by the CFP (Figure 5). Similarly, LVSP was significantly decreased by the IABP (p = 0.002) and nonsignificantly by the CFP (p = 0.137). Furthermore, EDAP was decreased from 77 ± 8 mm Hg to 70 ± 6 mm Hg by the IABP (p = 0.005) and increased to 86 ± 6 mm Hg by the CFP (p = 0.009). Finally, LVEDP was significantly decreased by the CFP (p = 0.002), whereas the change in LVEDP caused by the IABP did not reach statistical significance (p = 0.069).
The effects of the IABP versus the CFP in severe heart failure are shown in Table 3. LVSP was decreased by both the IABP and the CFP, though the decrease associated with the latter was not statistically significant (p = 0.075). In contrast, EDAP was significantly decreased by the IABP (p = 0.044) and significantly increased by the CFP (p = 0.004). MAP, however, was significantly increased from 73 ± 7 mm Hg to 77 ± 7 mm Hg by the IABP (p = 0.032), and to 78 ± 9 mm Hg (p = 0.086) by the CFP. Similarly, CO was increased significantly by the IABP (p = 0.04), whereas the increase achieved by the CFP was not statistically significant (p = 0.106). Finally, LVEDP was markedly decreased by the CFP (p = 0.002), and only moderately decreased by the IABP (p = 0.075). The effects of the IABP versus the CFR in total TTI and DP are shown in Figure 6.
HF refractory to standard medical treatment is an indication for mechanical support with a view to unload the heart and maintain the blood pressure and organ perfusion, and prevent the development of multiple organ failure.11 The failing heart is exquisitely sensitive to afterload reduction and relatively insensitive to preload reduction.11 In patients presenting with HF, Kameyama et al.12 found that afterload reduction (with nitroprusside) was superior to preload reduction (with lower body negative pressure), in restoring optimal ventricular load coupling and improving the work efficiency of the heart.
Similarly, afterload reduction after aortic valve replacement for severe aortic stenosis was associated with more favorable LV systolic13 and diastolic function14 and sustained regression of LV remodeling13 during the early postoperative period, compared with a “predominant” preload reduction achieved after aortic valve replacement for severe aortic regurgitation. Yet, there is still controversy on this issue.15,16
In experimental17 and clinical studies,18,19 mechanical assistance with the IABP improved all components of arterial impedance, including aortic compliance, systemic vascular resistance, and peripheral pulse wave reflection. Salutary effects conferred by the IABP on preload, myocardial wall stress, and myocardial oxygen consumption have also been reported by various recent investigations17,20,21 and studies conducted in the 1960s and 1970s.22,23 The main limitation of the IABP is the need for some residual LV function to propel a sufficient blood volume forward and backward.9 When the IABP fails to provide sufficient circulatory support, CFP or other LV assist devices are implemented.11
The CFP decreases LV end-diastolic volume and pressure and LV wall stress.5,24,25 However, the latter seems to depend on the amount of unloading and on the contractility of the left ventricle. The cannulation of the left atrium probably does not sufficiently unload the left ventricle. However, partial unloading of the heart (≈60%) with CFP results in 50% reduction of myocardial oxygen demand. To accomplish a significant higher reduction of myocardial oxygen demand, 100% unloading of the heart (total bypass) is needed.24 Furthermore, in clinical practice, it is more convenient and safe to implement a percutaneous left ventricular assist device despite its potential limitation of partial LV unloading, especially in cases with acute heart failure either as a bridge to recovery or as a bridge to chronic mechanical assistance.
Conflicting results have been reported with regard to the ability of CFP to increase CO and MAP.7,25–29 In this experimental study, the benefits conferred by the IABP on LVSP, EDAP, and DP in moderate HF were superior to CFPs. The equivalent effects of both pumps on total TTI indicated that partial bypass of the left ventricle with the CFP resulted in significant unloading of that cardiac chamber.
However, CFP confers its benefit on LV mechanics primarily by decreasing LVEDP (preload reduction). This also decreases the afterload by decreasing the in LV end-diastolic volume that is directly associated with the decrease in LVEDP. No significant change in CO and MAP was observed with either pump in moderate HF, which might be explained by the fact that, without mechanical assistance, CO and MAP were nearly normal, to meet the needs of the peripheral organs. Furthermore, neither pump influenced the LAD flow. This observation seems to be due to the autoregulation of the coronary arterial bed. The most prominent effects of the IABP were on LVSP and EDAP, while the most pronounced effects of the support by the CFP were on LVEDP.
In severe heart failure, the IABP increased significantly the CO and MAP. The nonsignificant effect of the CFP on CO was most likely due to the small blood volume drained into the left atrium, which predisposed to “chunking” of the inlet tubing of the CFP and a transient collapse of the left atrium, preventing further increases in CO and MAP. The trend toward a decrease in LAD flow during CFP support in severe heart failure, might have been related to the absent pulsatility of the systemic flow.6 In contrast to our study, Hata et al.7 observed similar increases in MAP and LAD flow produced by both pumps, and a greater decrease in LVEDP associated with the CFP. In a previous study, we found that the para-aortic pump, a counterpulsatory device implanted on the ascending aorta with an 80-ml stroke volume, unloaded the left ventricle more effectively than the CFP.29 Other investigators observed, in a HF model, that only the CFP increased significantly the MAP and maintained cardiac index.8 Bavaria et al.30 reported a significant decrease in end-systolic volume and LVEDP, and an increase in LAD flow with the IABP.
Finally, in two recent randomized clinical studies which included patients with cardiogenic shock refractory to medical treatment, improvements in MAP, CO, and pulmonary capillary wedge pressure were improved more with the Tandem Heart (a percutaneous support system that incorporates a centrifugal pump) than with the IABP, though the mortality rate was similar in both groups.9,10 The better hemodynamics accomplished by Tandem Heart did not translate to a survival benefit, probably because of its minimal effects conferred by the former on afterload.
Preload reduction with CFP should not be considered “optimal” because of partial LV bypass and its performance should be contemplated as “intent to treat.” Myocardial oxygen consumption assessment and pressure–volume loops recordings if available, could have provided a more precise approach of myocardial energy requirements. Medications used for anesthesia and heart failure induction (propranolol) might have had an impact on our findings.
IABP, an inexpensive, easily and rapidly inserted device, was at least equivalent to partial bypass with the radial-flow CFP for cardiac unloading and systemic circulatory support at different levels of rapidly worsening acute HF. Further studies are needed to examine the pathophysiological changes in myocardial and peripheral tissues that occur during mechanical assistance with either device. However, the afterload reduction offered by the IABP seems preferable for the recovery of the acutely failing heart, since it plays the most pivotal role in myocardial oxygen consumption reduction.
1. Antman EM, Anbe DT, Armstrong PW, et al
: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of patients with acute myocardial infarction). J Am Coll Cardiol
44: E1–E211, 2004.
2. Santa-Cruz RA, Cohen MG, Ohman EM: Aortic counterpulsation: A review of the hemodynamic effects and indications for use. Cathet Cardiovasc Interv
67: 68–77, 2006.
3. Rosenbaum AM, Murali S, Uretsky BF: Intra-aortic balloon counterpulsation as a ‘bridge’ to cardiac transplantation. Effects in nonischemic and ischemic cardiomyopathy. Chest
106: 1683–1688, 1994.
4. Pae WE Jr, Miller CA, Matthews Y, Pierce WS: Ventricular assist devices for postcardiotomy cardiogenic shock: A combined registry experience. J Thorac Cardiovasc Surg
104: 541–553, 1992.
5. Ratcliffe MB, Bavaria JE, Wenger RK, et al
: Left ventricular mechanics of ejecting, postischemic hearts during left ventricular circulatory assistance. J Thorac Cardiovasc Surg
101: 245–255, 1991.
6. Drakos SG, Charitos CE, Ntalianis A, et al
: Comparison of pulsatile with nonpulsatile mechanical support in a porcine model of profound cardiogenic shock. ASAIO J
51: 26–29, 2005.
7. Hata M, Shiono M, Orime Y, et al
: Coronary microcirculation during left heart bypass with a centrifugal pump. Artif Organs
20: 678–680, 1996.
8. Zobel G, Dacar D, Kuttnig M, et al
: Mechanical support of the left ventricle in ischemia induced left ventricular failure: an experimental study. Int J Artif Organs
15: 114–119, 1992.
9. Holger T, Sick P, Boudriot E, et al
: Randomized comparison of intra-aortic balloon support with a percutaneous left ventricular assist device in patients with revascularized acute myocardial infarction complicated by cardiogenic shock. Eur Heart J
26: 1276–1283, 2005.
10. Burkhoff D, Cohen H, Brunckhorst C, O’Neil W: A randomized multicenter clinical study to evaluate the safety and efficacy of the Tandem Heart percutaneous ventricular assist device versus conventional therapy with intra-aortic balloon pumping for treatment of cardiogenic shock. Am Heart J
152: 469 e1–e8, 2006.
11. Boehmer JP, Popjes E: Cardiac failure: Mechanical support strategies. Crit Care Med
34(suppl): S268–S277, 2006.
12. Kameyama T, Asanoi H, Ishizaka S, Sasayama S: Ventricular load optimization by unloading therapy in patients with heart failure. J Am Coll Cardiol
17: 199–207, 1991.
13. Sutton M, Plappert T, Spiegel A, et al
: Early postoperative changes in left ventricular chamber size, architecture, and function in aortic stenosis and aortic regurgitation and their relation to intraoperative changes in afterload: A prospective two- dimensional echocardiographic study. Circulation
76: 77–89, 1987.
14. Lamb H, Beyerbacht H, de Roos Albert, et al
: Left ventricular remodelling early after aortic valve replacement: Differential effects on diastolic function in aortic valve stenosis and aortic regurgitation. J Am Coll Cardiol
40: 2182–2188, 2002.
15. Rothenburger M, Drebber K, Tjan T, et al
: Aortic valve replacement for aortic regurgitation and stenosis, in patients with severe left ventricular dysfunction. Eur J Cardio Thorac Surg
23: 703–709, 2003.
16. Chukwuemeka A, Rao V, Armstrong S, et al:
Aortic valve replacement: A safe and durable option in patients with impaired left ventricular systolic function. Eur J Cardio Thorac Surg
29: 133–138, 2006.
17. Kawaguchi O, Pae WE, Daily BB, Pierce WS: Ventriculoarterial coupling with intra-aortic balloon pump in acute ischemic heart failure. J Thorac Cardiovasc Surg
117: 164–171, 1999.
18. Stefanadis C, Dernellis J, Tsiamis E, et al:
Aortic function in patients during intra-aortic balloon pumping determined by the pressure-diameter relation. J Thorac Cardiovasc Surg
116: 1052–1059, 1998.
19. Marchionni N, Fumagalli S, Baldereschi G, et al:
Effective arterial elastance and the hemodynamic effects of intra-aortic balloon counterpulsation in patients with coronary heart disease. Am Heart J
135: 855–861, 1998.
20. Sakamoto T, Suzuki A, Kazama S, et al:
Effects of timing on ventriculoarterial coupling and mechanical efficiency during intra-aortic balloon pumping. ASAIO J
41: M580–M583, 1995.
21. Nanas JN, Nanas SN, Kontoyannis DA, et al
: Myocardial salvage by the use of reperfusion and intra-aortic balloon pump: Experimental study. Ann Thorac Surg
61: 629–634, 1996.
22. Powell WJ Jr, Daggett WM, Magro AE, et al
: Effects of intra-aortic balloon counterpulsation on cardiac performance, oxygen consumption, and coronary blood flow in dogs. Circ Res
26: 753–764, 1970.
23. Nanas JN, Moulopoulos SD: Counterpulsation: Historical background, technical improvements, hemodynamic and metabolic effects. Cardiology
84: 156–167, 1994.
24. Goldstein AH, Pacella JJ, Clark RE: Predictable reduction in left ventricular stroke work and oxygen utilization with an implantable centrifugal pump. Ann Thorac Surg
58: 1018–1024, 1994.
25. Rose EA, Marrin CA, Bregman D, Spotnitz HM: Left ventricular mechanics of counterpulsation and left heart bypass, individually and in combination. J Thorac Cardiovasc Surg
77: 127–137, 1979.
26. Cohen DJ, Kress DC, Swanson DK, et al:
Effect of cannulation site on the primary determinants of myocardial oxygen consumption during left heart bypass. J Surg Res
47: 159–165, 1989.
27. Pego-Fernandes PM, Stolf NA, Moreira LF, et al
: Influence of biopump with and without intra-aortic balloon on the coronary and carotid flow. Ann Thorac Surg
69: 536–540, 2000.
28. Sukehiro S, Flameng W: Effects of left ventricular assist for cardiogenic shock on cardiac function and organ blood flow distribution. Ann Thorac Surg
50: 374–383, 1990.
29. Nanas SN, Nanas JN, Charitos CE, et al
: High stroke volume para-aortic counterpulsation device versus centrifugal pump in cardiogenic shock: Experimental study. World J Surg
21: 318–322, 1997.
30. Bavaria JE, Furukawa S, Kreiner G, et al
: Effect of circulatory assist devices on stunned myocardium. Ann Thorac Surg
49: 123–128, 1990.