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Ann Thorac Surg 1998;66:1527-1532
© 1998 The Society of Thoracic Surgeons

Neonatal piglet model of intraaortic balloon pumping: Improved efficacy using echocardiographic timing

^a Division of Cardiology, Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA
^b Division of Cardiothoracic Surgery, Department of Surgery, University of Utah, Salt Lake City, Utah, USA

Address reprint requests to Dr Hawkins, Department of Surgery, 100 N. Medical Dr, Suite 2550, Salt Lake City, UT 84113
e-mail: jhawkins{at}med.utah.edu

Presented at the Thirty-fourth Annual Meeting of The Society of Thoracic Surgeons, New Orleans, LA, Jan 26–28, 1998.

	Abstract

Top Footnotes Abstract Introduction Material and methods Results Comment References

 
Background. Pediatric intraaortic balloon pumping (IABP) has met with little success because of technical difficulty in tracking rapid heart rates. This study was designed to evaluate the efficacy of M-mode echocardiography for IABP timing in a neonatal piglet model.

Methods. Two groups of piglets underwent mitral valve avulsion to create a model of shock. Group 1 (n = 8; mean weight, 7.7 ± 1.8 kg) underwent IABP timed with both the ascending aortic pressure and M-mode echocardiogram. Group 2 (n = 6; mean weight, 7.5 ± 1.4 kg) underwent two separate periods of IABP: one with echocardiographic timing and the second using standard timing points from the femoral arterial pressure tracing and electrocardiogram. Measurements included ascending aortic flow, left anterior descending arterial flow, ascending aortic pressure, left atrial pressure, and heart rate.

Results. Mitral valve avulsion produced a shock model with a significant decrease in mean aortic pressure and aortic flow and a significant increase in left atrial pressure and heart rate. Compared with the shock state, IABP in group 1 animals resulted in a significant increase in aortic flow (353 ± 152 versus 454 ± 109 mL/min; p < 0.05) and a significant decrease in left atrial pressure (23 ± 6 versus 17 ± 7 mm Hg; p < 0.05). Group 2 animals with echocardiogram-timed IABP had significantly increased aortic flow (365 ± 106 versus 458 ± 107 mL/min; p < 0.05) and mean aortic pressure (43 ± 11 versus 52 ± 8 mm Hg; p < 0.05). However, standard-timed IABP failed to show any improvement.

Conclusions. In piglets with rapid heart rates, echocardiogram-timed IABP results in increased aortic flow and pressure and decreased left atrial pressure compared with standard-timed IABP.

	Introduction

Top Footnotes Abstract Introduction Material and methods Results Comment References

 
Since it was first introduced in 1967, intraaortic balloon pumping (IABP) has become a standard therapeutic tool for managing acute left ventricular failure in the adult patient [1–4]. Theoretically, IABP should also be valuable for reducing cardiac workload and improving contractility of the injured pediatric heart [5–7]. Despite the technical ability to place balloon catheters in pediatric patients, including small infants, IABP has not had widespread use in this population [5–12]. In fact, IABP in pediatric patients is often thought to be ineffective, largely because of the inability to track the rapid heart rates and narrow pulse pressures of children in shock [12, 13].

Recently, we reported the use of M-mode echocardiography to time aortic valve opening and closing during IABP in children [11]. The purposes of the present study were to evaluate the efficacy of IABP in a neonatal piglet model of shock and to compare the hemodynamic effects of timing with M-mode echocardiographic markers with those of timing with standard markers from the peripheral arterial pressure tracing and electrocardiogram in this model.

	Material and methods

Top Footnotes Abstract Introduction Material and methods Results Comment References

 
Animal selection and preparation
Immature piglets weighing approximately 5 to 10 kg were selected to correspond with the smallest group of pediatric patients in whom IABP is technically possible. This group would be expected to have the fastest heart rates and thus be the most challenging in terms of timing balloon inflation and deflation. Group 1 consisted of 8 piglets weighing 5.3 to 10.8 kg (mean, 7.7 ± 1.8 kg). Group 2 consisted of 6 piglets weighing 6.1 to 9.0 kg (mean, 7.5 ± 1.4 kg). The experimental protocol was reviewed by the Institutional Animal Care and Use Committee of the University of Utah, and all animals received humane care in compliance with the "Guide for the Care and Use of Laboratory Animals" published by the National Institutes of Health (NIH publication 85-23, revised 1985).

Anesthesia was induced in the prefasted pig with 30 mg/kg of intraperitoneal pentobarbital, and the pig was then endotracheally intubated and ventilated with an O₂ mixture to maintain appropriate arterial blood gases and oxygen saturation. General anesthesia was maintained with a continuous infusion of pentobarbital at a rate of 3 mg · kg^-1 · h^-1. All subsequent manipulations were done with local infiltration of 1% lidocaine to augment the intravenous anesthesia.

Vascular catheters were placed in both a femoral artery for pressure measurements and a femoral vein for intravenous infusions (Fig 1). An incision was performed on the left neck, and the left carotid artery and left jugular vein were isolated. A vascular catheter was inserted into the jugular vein and advanced into the right atrium for pressure monitoring. A high-fidelity catheter-tip pressure sensor (Millar Instruments, Houston, TX) was inserted into the left carotid artery and advanced to the aortic root for central arterial pressure measurements. Limb-lead electrocardiographic electrodes were placed, and the cardiac rhythm was monitored continuously. A left lateral thoracotomy was performed, allowing visualization of the heart and aorta. A left atrial line was inserted, and a transit-time ultrasonic flow probe (Transonic Systems, Ithaca, NY) was placed around both the left anterior descending coronary artery and the ascending aorta. The intraaortic balloon catheter was inserted through a femoral artery incision with the tip positioned just below the origin of the left subclavian artery. Proper positioning of the balloon catheter was verified with echocardiography. A cutting hook was introduced through the left atrial appendage, and the chordae or mitral valve leaflets were cut to produce acute mitral regurgitation, thereby reducing cardiac output and creating a shock state [5].

View larger version (29K): [in this window] [in a new window]   Fig 1. Schematic representation of the animal preparation. (IAB = intraaortic balloon.)

Echocardiography
Through a surgically created sternal window, direct precordial echocardiograms were performed with either an ATL Ultramark 8 (ATL, Bellevue, WA) or Acuson 128 XP system (Acuson, Mountain View, CA) and a 7.0-MHz transducer. The aortic valve and balloon were identified with two-dimensional echocardiography, and the transducer position was adjusted so both were imaged simultaneously. The M-mode cursor was positioned to pass through both structures simultaneously, allowing visualization of the aortic valve as well as balloon motion. This permitted direct adjustment of balloon deflation to correspond with aortic valve opening and of balloon inflation to correspond with aortic valve closing, as previously described [11].

Assessment of hemodynamic parameters
The following baseline measurements were recorded before inducing a shock state: ascending aortic forward flow, mean left anterior descending arterial blood flow, mean ascending aortic pressure, mean left atrial pressure, and heart rate. These hemodynamic measurements were selected because they are the indices used to track the clinical response of the pediatric patient in shock. For the first experimental group, the same measurements were then recorded after creating acute mitral regurgitation but before the initiation of IABP (shock state) and subsequently after establishing IABP. For the second experimental group, hemodynamic measurements were made at baseline, during shock state, and during each of two separate periods of IABP: one with echocardiographic timing and one with standard timing. To insure that the model did not deteriorate hemodynamically with time, shock state measurements were also obtained before each of the two periods of IABP.

Experimental protocol
To evaluate the efficacy of IABP, the first experimental group of piglets underwent a 30-minute period of IABP with balloon timing by both the aortic pressure signal from the Millar catheter and the M-mode echocardiogram. To validate the animal model as an adequate model of shock, comparisons were made between baseline (premitral valve avulsion) and shock state (postavulsion). Because it is unrealistic to expect IABP to return the model to its preavulsion state, IABP was only compared with the shock state.

To compare M-mode echocardiographic timing with standard arterial pressure and electrocardiographic timing, a second experimental group of piglets underwent two separate 20-minute periods of IABP: one with echocardiographic timing and one with standard timing. Again, the shock state was compared with the preavulsion (baseline) state to validate the model. To evaluate the superiority of a specified timing method, comparisons were made during four conditions: shock state, echocardiogram-timed IABP, repeat shock state, and standard-timed IABP. Percent changes were calculated for both timing methods and compared.

Statistical analysis
Hemodynamic values to validate the model (shock state versus baseline) and the percent change between the timing methods were compared using paired Student’s t tests. The hemodynamic data for multiple experimental conditions were analyzed by a one-factor analysis of variance for repeated measures with Fisher’s post hoc comparison of pairs. Data are expressed as mean ± standard deviation. A p value less than 0.05 indicated a significant difference.

	Results

Top Footnotes Abstract Introduction Material and methods Results Comment References

 
The first experimental group of animals was studied to evaluate the efficacy of IABP, and their hemodynamic measurements are summarized in Table 1. Compared with baseline measurements, there was a significant decrease in ascending aortic flow and mean aortic pressures and a significant increase in heart rate in the shock state. These hemodynamic alterations validate this animal model of shock. The mean flow in the left anterior descending artery was not significantly different between the baseline and shock states (19 ± 6 versus 17 ± 13 mL/min).

View larger version (75K): [in this window] [in a new window]   Fig 2. Simultaneous recording of electrocardiogram and ascending aortic pressure. Millar and M-mode echocardiogram demonstrating that the upstroke of the arterial pressure curve (U) coincides with the aortic valve (Ao) opening (O) from the M-mode recording and the dicrotic notch (D) coincides with aortic valve closure (C).

	Comment

Top Footnotes Abstract Introduction Material and methods Results Comment References

 
This report shows the effectiveness of properly timed IABP in a neonatal piglet model of shock. The theory underlying IABP emphasizes the importance of balloon timing. According to this theory, placing a balloon in the aorta and synchronizing its deflation with left ventricular ejection results in afterload reduction, whereas synchronizing its inflation with ventricular diastole results in diastolic augmentation and increased instantaneous coronary artery blood flow. With optimal afterload reduction and diastolic augmentation, cardiac workload is decreased, and myocardial contractility and cardiac output are improved [14–16]. For IABP to provide maximal left ventricular afterload reduction and diastolic augmentation, inflation and deflation must be synchronized precisely, but 180 degrees out of phase with the cardiac cycle. Inappropriate timing has been shown to result in either minimal clinical improvement or even deterioration of the patient’s hemodynamic status [15, 16]. Adult animal experiments have shown that an error of 20 ms in deflation time could reduce coronary augmentation by as much as 50% [14]. Several timing errors may occur: (1) early inflation (before aortic valve closure), increasing afterload and decreasing left ventricular emptying; (2) late inflation (after aortic valve closure), shortening the period of diastolic augmentation; (3) early deflation (before isovolumetric contraction), shortening the period of diastolic augmentation; and (4) late deflation extending into systole, increasing afterload and decreasing left ventricular emptying. Most IABP consoles allow operator adjustment of both inflation and deflation points, and balloon timing is accomplished by electronic tracking of arterial pressure and electrocardiographic signals. The balloon is inflated at the dicrotic notch on the aortic blood pressure waveform or at the end of the T wave on the electrocardiogram and deflated just before the upstroke on the arterial waveform or with the R wave [17–22]. Subtle adjustments are then made to maximize the resulting changes of the arterial waveform [5, 7, 9]. Arterial pressure and electrocardiographic signals, however, provide only rough estimates of aortic valve opening and closing and are inherently associated with errors. One source of error is the variable delay in transmission time between aortic valve closure and the appearance of the systolic signal of the arterial tracing on the oscilloscope. The time lag increases as the arterial waveform travels downstream [19]. The quality of the arterial pressure tracing may provide another source of error. When the patient is in shock, the tracing often has a low amplitude and a narrow pulse pressure, making it difficult to track with current IABP equipment [23, 24]. An additional problem is that neither the arterial pressure tracing nor the electrocardiogram has an exact marker for deflating the balloon; rather, attempts are made to deflate before the next arterial upstroke or R wave on the electrocardiogram.

In children, arterial pressure and electrocardiographic markers are even more inaccurate [11, 14]. In fact, in clinical practice, most operators of pediatric consoles use the arterial pressure tracing and electrocardiogram only as rough guidelines and arbitrarily adjust timing to produce an arterial waveform that correlates best with diastolic augmentation [5, 7–9, 18]. Another common maneuver is to go to 2:1 timing in which hemodynamics are compromised by the loss of IABP assistance for every other beat [12, 19, 20, 23].

Because synchronization of the balloon to aortic valve opening and closing is so important, precise markers of the onset of systole and diastole are needed. M-mode echocardiography is ideal for providing accurate markers because its rapid sampling rate (>1,000/min) can demonstrate precise aortic valve opening and closing even at rapid pediatric heart rates.

In the first experimental group of piglets, we demonstrated that properly timed IABP effectively increased cardiac output. Timing of aortic valve opening and closing was identical with the use of M-mode echocardiography and the arterial pressure tracings obtained with the Millar catheter in the ascending aorta. Because it is not practical to place this catheter in the ascending aorta of a child and the M-mode echocardiogram has the advantage of being noninvasive, it was selected as the more clinically useful technique for timing IABP. Therefore, in group 2, we used the M-mode method alone for IABP and compared the results with standard methods of balloon timing with arterial pressure and electrocardiographic tracings. Standard timing of IABP failed to change any hemodynamic parameter significantly, but echocardiogram-timed IABP resulted in significant increases in both ascending aortic flow and mean arterial pressure (Table 2). It is interesting that the mean flow in the left anterior descending artery did not change significantly from baseline measurements during any condition. This is consistent with previous studies that have shown normal coronary arteries respond with maximal dilation to shock and IABP does not increase their flow [25, 26]. Because most pediatric patients undergoing IABP have normal coronary arteries, they are likely to benefit more from afterload reduction than diastolic augmentation, as shown in this model.

Although avulsion of the mitral valve apparatus in this neonatal piglet model resulted in low cardiac output and the hemodynamic consequences of the shock, it had some limitations. The amount of valve disruption and the degree of shock could not be reliably controlled, nor could the anatomic derangement be reversed. Attempts were made to overcome these effects by obtaining complete hemodynamic data with the piglet in the shock state before IABP regardless of the method used for timing. All hemodynamic measurements were similar for the two pre-IABP periods.

The variability of the shock state may also explain the differences in significantly lowering the left atrial pressure in only the first experimental group and significantly increasing the mean aortic pressure only in the second experimental group. It is encouraging, however, that ascending aortic flow increased significantly in both experimental groups with Millar- or echocardiogram-timed IABP.

Immature piglets weighing 5 to 10 kg were chosen to simulate the infant size and heart rates in which the technical demands of IABP are greatest. However, the piglet model may not mimic the human infant entirely in other characteristics (for example, aortic compliance and autonomic response to stress) that may affect IABP efficacy. Despite this, the ability to pump this animal model effectively with the M-mode technique and the failure to pump effectively with standard techniques still suggest that properly timed IABP would be efficacious in pediatric patients. Further studies with M-mode echocardiogram-timed IABP in a pediatric population are needed to determine whether outcomes actually improve.

Thus, properly timed IABP increases ascending aortic flow and mean aortic pressure and decreases left atrial pressure in a neonatal piglet model of shock. M-mode echocardiographic markers of aortic valve motion are comparable to pressure markers from a Millar catheter placed in the ascending aorta and are superior to standard peripheral arterial pressure and electrocardiographic timing markers. In fact, unlike IABP with M-mode echocardiographic markers, IABP with the standard timing markers does not result in improvement of shock hemodynamics in this neonatal piglet model.

	Footnotes

Top Footnotes Abstract Introduction Material and methods Results Comment References

 
A grant was received for this work from the Primary Children’s Medical Center Foundation and from Datascope, Inc, Paramus, NJ. The grant from Datascope was only given to Dr Minich and none of the other coauthors.

	References

Top Footnotes Abstract Introduction Material and methods Results Comment References

 

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