Impact of Intraaortic Balloon Counterpulsation on Arterial Blood Flow in Juvenile Pigs with Heart Failure

ABSTRACT: Objectives. To assess the impact of intraaortic balloon counterpulsation on coronary, renal and aortic blood flow in an animal heart failure model. Background. Heart failure exacerbations are still often treated with inotropic medications despite a lack of evidence demonstrating any benefit with these drugs. Intraaortic balloon counterpulsation may be considered in certain cases a bridge to recovery. Methods. Four juvenile pigs underwent pacemaker implantation to induce a rapid-pacing mediated dilated cardiomyopathy. After approximately 4 weeks of rapid pacing, the mean ejection fraction was reduced to 28.8 ± 9.5% with a mean systolic blood pressure of 64/44 mmHg. The pigs then underwent surgical placement of flow probes around the circumflex coronary artery, renal artery and infrarenal aorta. A Millar catheter was used to calculate Dp/Dt and a Swan-Ganz to calculate cardiac output. Data were recorded at baseline and after 10 minutes of balloon pumping. The pigs were euthanized post-procedure. Results. Coronary blood flow was increased 9.7% by balloon counterpulsation from 38.3 ± 12.0 to 42.0 ± 11.4 ml/s (p = NS). Renal blood flow was reduced 11.9% by counterpulsation from 130.0 ± 88.6 ml/s to 114.5 ± 76.6 ml/s (p = NS). Infrarenal aortic blood flow was not changed (mean of 900 ml/s with and without counterpulsation); blood pressure, cardiac output and Dp/Dt were not changed after 10 minutes of pumping. There was little impact observed by changing the position of the balloon closer to or farther away from the apex of the aortic arch. Conclusion. Intraaortic balloon counterpulsation did not significantly improve hemodynamics in the pig heart failure model. This may be attributed to the high compliance of the juvenile pig’s aorta, thus attenuating the pressure wave generated by counterpulsation. A larger volume balloon would merit investigation for this application. J INVAS CARDIOL 2004;16:181–183 Key words: heart failure, intraaortic balloon pump, pig model, rapid-pacing Patients suffering heart failure exacerbations refractory to standard medical treatment have historically been treated with inotropic medications, despite the lack of evidence to show any benefit with this modality of care.¹ That there continues to be interest in inotropic therapy is a reflection of the fact that other therapeutic options are lacking for patients who are refractory to conventional medical treatments. Intuitively, mechanical assistance to relieve the pumping burden would be preferable to drugs that exacerbate the sympathetic overload that the failing myocardium is subject to in this setting. In addition, inotropes may hemodynamically stabilize a patient, while end-organ perfusion remains compromised. There have been several studies with left ventricular assist devices to show that mechanical unloading of the heart in transplant candidates results in symptomatic improvement and reverse remodeling. While the intraaortic balloon pump (IABP) is not a standard therapeutic modality in the treatment of heart failure exacerbations, ambulatory IABP counterpulsation has been utilized as a bridge to transplant.² This study was conducted to evaluate the capability of IABP counterpulsation to acutely augment arterial circulation using a pig congestive heart failure model. Methods Four juvenile farm pigs underwent pacemaker implantation in order to raise their heart rate from a baseline of 120 bpm to 180 bpm and induce a tachycardic cardiomyopathy. Under general anesthesia and sterile surgical conditions, a St. Jude Medical (Affinity™) pacemaker with a single right ventricle lead was implanted using fluoroscopic guidance. All devices captured effectively post-procedure except one, which required reprogramming secondary to a higher stimulation threshold and then functioned well. A baseline echocardiogram was performed on the first 3 pigs, and showed a mean ejection fraction (EF) of 51.7% with normal valvular function. The pigs were then recovered for approximately 4–8 weeks depending on the overall health and activity level of the individual pig. The pigs were then brought back to the operating room and anesthetized. After the pacer was turned off, a follow-up echocardiogram was performed. Cut-downs were performed to expose the right femoral artery, carotid artery and jugular vein. The right carotid artery was accessed for placement of a Millar catheter to assess Dp/Dt, central arterial pressure and arterial waveforms. The jugular vein was used for either placement of a Swan-Ganz catheter for cardiac output measurements (2 pigs) or for a central venous line. A lateral thoracotomy was performed to expose the left circumflex coronary artery and permit placement of a 2.5–3 mm Transonic flow probe. A left lateral abdominal incision was made in order to permit dissection to the left renal artery and infrarenal aorta. A 4 mm flow probe was placed around the renal artery and a 20 mm probe around the aorta. Access of the aorta was not possible in 1 pig due to its deeply posterior anatomical position. A 20–34 cc IABP catheter was placed via the femoral artery and attached to a Datascope 98XT machine. The catheter tip was placed approximately 2 inches from the apex of the aortic arch and above the renal arteries. Baseline data were recorded and measurements were then re-recorded after the balloon pump had been functioning for approximately 10 minutes. In 2 pigs, data were recorded with the balloon pump positioned high near the aortic arch and low (approximately 10 inches below the aortic arch apex). If fluids or medications had to be administered before a complete set of data was obtained, a new set of baseline data was recorded and the entire process was repeated. The pigs were then euthanized while under general anesthesia. This experiment was approved by the ACRI Institute for Animal Care and Utilization Committee, and all animal handling and procedures were done according to the principles of The Guide for the Care and Use of Laboratory Animals. Results Tachycardic cardiomyopathy was successfully induced in all of the pigs studied, with a resultant mean EF of 28.8 ± 9.5%. The mean blood pressure at the initiation of the procedure was 64/44 mmHg. Coronary blood flow increased 9.7% above baseline by balloon counterpulsation from 38.3 ± 12.0 ml/s to 42.0 ± 11.4 ml/s (p = NS). Renal blood flow was reduced 11.9% by counterpulsation from 130.0 ± 88.6 ml/s to 114.5 ± 76.6 ml/s (p = NS). Infrarenal aortic blood flow was not changed (mean of 900 ml/s with and without counterpulsation), but lacked the sensitivity to detect alterations less than 50 ml/s. Blood pressure recorded for the carotid artery was unchanged by pumping. Dp/Dt was not changed after 10 minutes of pumping (911.3 ± 263.9 to 900.8 ± 243.5). Cardiac output was measured in 2 pigs and was also unchanged after 10 minutes of pumping (mean of 4.9 L/minute to 4.6 L/minute). Balloon positioning closer or farther from the apex of the aortic arch did not have a significant impact on coronary blood flow. In 1 animal with the balloon positioned low, the coronary blood flow was 59 ml/s at a blood pressure of 60/31 mmHg (48). With the balloon positioned high (2 inches below the apex of the arch), the coronary flow was 61 ml/s at a blood pressure of 63/31 (53). The variation in the amount of renal flow to aortic flow is related to difference in the size of the renal artery studied with respect to the aorta. The renal artery varied in size between 3 mm and 6 mm, while the aortic diameter varied in size as well (average of approximately 15 mm in diameter). Discussion Balloon counterpulsation has previously been determined to have little or no impact on renal blood flow, and this animal study confirms that point. Coronary blood flow was augmented slightly, however, this experiment did not have the power to distinguish a 10% or less difference in flow as being significant. The diminished ability of balloon pumping to favorably impact the hemodynamics can potentially be attributed to several factors. First, the compliance of the aorta in a juvenile pig is more similar to a younger human aorta than the typical older, atherosclerotic, calcified, adult human patient in which these balloons are most often implemented. While there is not a significant difference in aortic compliance between juvenile and adult pigs due to the absence of age-related atherosclerotic and calcific changes, a cadaver study by Lin, et al. showed dramatic differences in aortic compliance between younger and older human aortas.³ These differences were related to the amount of atherosclerosis present. The aortic compliance of a pig was shown to be similar to that of a young human, particularly that of a woman’s aorta due to its smaller diameter. There has been a study to show that aortic compliance is inversely related to the effectiveness of balloon counterpulsation.⁴ This is due to the observation that the energy of balloon expansion is transferred to the aortic wall, which expands, thus diminishing the impact on the movement of blood within the conduit. While vessel compliance was not directly studied in this experiment, the induction of heart failure has been shown to reduce aortic compliance in the canine model.⁵ Nevertheless, heart failure does not reduce aortic compliance to the degree that is appreciated in human patients with a significant atherosclerotic burden. It is reasonable to extrapolate these results to humans and suggest that the IABP would be less effective in younger patients with more compliant arteries and less atherosclerotic disease than older patients with stiffer vessels. A second issue is balloon volume. The catheters used for this study were 20–34 cc balloons, primarily because the diameter of these catheters ranges from 12–14.7 mm. We have observed that 40 cc balloons, which have a 15 mm diameter, completely occlude the pig aorta during inflation, thus diminishing augmentation and inducing vascular injury. While it was not possible for the investigators to test balloons larger than 34 cc given the above limitations, unpublished industry-sponsored studies with prototypes have shown that larger volumes have a greater hemodynamic impact. Based on this information, it would appear beneficial to utilize even larger volume IAB catheters than are currently available on the market for application in the heart failure setting. The adult male aorta is 24–27 mm in diameter and a 40 cc IAB catheter is 15 mm in diameter. This leaves a substantial amount of room to increase the diameter as well as the length. Given the limitations of inotropes and the established benefit of mechanical assistance to the failing heart, it is possible that balloon pumping may someday have a role in the management of heart failure exacerbations, a setting for which this modality of treatment has thus far not been widely utilized. Based on the results of this animal experiment, the authors feel that new, larger volume balloon catheters (or other types of multi-chamber innovations) would perform better in young patients with compliant aortas. The investigators propose that a 50 or 60 cc balloon would potentially have a greater hemodynamic impact than existing 40 cc catheters when applied to younger patients with heart failure. There are almost 5 million people in the United States living with CHF.⁶ Approximately 550,000 new cases are diagnosed each year with > 200,000 deaths related to heart failure occurring annually.⁶ A significant number of patients experiencing CHF exacerbations are still treated with inotropes — a class of medications that have been shown to be of no benefit (and possibly of detriment). The IABP represents an alternative treatment modality that has not been widely embraced for this indication, primarily due to the invasive nature of the device, and also due to the greater inconvenience when compared to an intravenous drip. If the IABP balloon were to be enlarged so as to enhance its hemodynamic impact, perhaps its benefit could be shown to outweigh these other drawbacks. It is also estimated that 25,000 patients per year would benefit from a heart transplant — far exceeding the 2,500 donor hearts available each year.⁷ Some of these patients are young people being treated with an IABP as a bridge to transplant or recovery. Given the large number of heart failure patients requiring hemodynamic support as a bridge to recovery or transplant, this subject merits further investigation.