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J Thorac Cardiovasc Surg 1997;114:243-253
© 1997 Mosby, Inc.
CARDIOPULMONARY BYPASS, |
Received for publication July 19, 1996 Revisions requested Sept. 3, 1996; revisions received Feb. 12, 1997 Accepted for publication Feb. 13, 1997. Address for reprints: Willem Flameng, MD, PhD, Department of Cardiac Surgery, KU Leuven, Herestraat 49, 3000 Leuven, Belgium.
Abstract
Objective: Our objective was to analyze the potential advantage of combining an intraaortic balloon pump with a transthoracic Hemopump device (Medtronic, Inc., Minneapolis, Minn.) (Nimbus Medical, Inc., Rancho Cordova, Calif.). Methods: Twelve sheep underwent implantation of a transthoracic Hemopump device and an intraaortic balloon pump. In the first series (n = 6), we analyzed the influence of the counterpulsation on the performance of the Hemopump device. In the second group (n = 6), hemodynamic changes, myocardial wall thickening, organ perfusion, and myocardial perfusion (determined with colored microspheres) were analyzed under the following conditions: (1) control situation, (2) during application of coronary stenosis, (3) during support with the Hemopump device, and (4) during support with the Hemopump device combined with intraaortic balloon pump support. Results: In the first series, we found that addition of counterpulsation reduced output with the Hemopump device by 11.1% ± 6%. In the second series, it was shown that coronary stenosis significantly reduced contractility (rate of pressure change and wall thickening) but did not cause hemodynamic collapse. Myocardial blood flow was significantly reduced in the poststenotic subendocardial regions (mean subendocardial blood flow dropped from 78 ± 33 to 24 ± 17 ml/min/100 gm; p = 0.0486). Support with the Hemopump device alone improved the ratio of subendocardial to subepicardial blood flow, but endocardial underperfusion remained (analysis of variance, p < 0.001). The Hemopump device with an intraaortic balloon pump completely restored perfusion in poststenotic regions. Peripheral organ perfusion did not change during ischemia or mechanical support. Conclusions: The association of balloon counterpulsation with the Hemopump device reduces the Hemopump output by 11% and increases myocardial blood flow to ischemic regions. Perfusion to peripheral organs remains unaltered. The transthoracic Hemopump device combined with an intraaortic balloon pump is an ideal support system for the ischemic, failing heart.
Intraaortic balloon pumping is an established method of supporting the failing heart. Intraaortic balloon pump (IABP) devices have been continuously improved since Moulopoulos, Topaz, and Kolff
1 introduced counterpulsation by means of an intraaortic balloon in 1962. Experimental work has shown that balloon counterpulsation reduces left ventricular work and increases myocardial perfusion.
2-4 The concept of the Hemopump device (Medtronic, Inc., Minneapolis, Minn.) is completely different. This device is a miniature rotary blood pump introduced into the left ventricular cavity through the aortic valve. It aspirates the blood from the left ventricular cavity and expels it in the ascending aorta. The most frequently used and most reliable cannula is the transthoracic cannula, which is introduced through a graft sutured on the ascending aorta. This transthoracic Hemopump device is a powerful pump, with a rotational speed of 26,000 rpm producing a maximum pump flow of 5.1 L/min. The performance of this nonpulsatile blood pump, however, is dependent on the actual pressure differences between inflow and outflow of this pump. With a mean aortic pressure of 70 mm Hg in the clinical situation, the pump thus produces approximately 4 L/min. The Hemopump device increases myocardial blood flow by decreasing ventricular end-diastolic pressure and by increasing mean aortic blood pressure.
5 Most clinicians prefer the less invasive IABP as the first choice for mechanical support in cases of low cardiac output because the use of the transthoracic Hemopump device requires a sternotomy for both insertion and removal. The transthoracic Hemopump device is considered a "second-line" mechanical support device for patients who do not recover despite the use of an IABP. An IABP is thus often already in place when the Hemopump device is introduced. The transthoracic Hemopump device and the IABP inserted through the groin can easily be combined, so we studied whether the combination of these devices could be beneficial.
Materials and methods
Animal instrumentation
Twelve sheep (mean weight 69.8 ± 15 kg) were anesthetized with intravenous pentobarbital (3 mg/kg), intubated, and mechanically ventilated with 60% oxygen. Anesthesia was maintained with 0.5% to 2% halothane, and 0.2 mg/kg piritramide was administered every 40 minutes. All animals received humane care in compliance with the "Guide for the Care of and Use of Laboratory Animals" prepared by the Institute of Laboratory Animal Resources and published by the National Institutes of Health NIH Publication No. 86-23, revised 1985.
A triple-lumen central venous line was inserted into the jugular vein, and a fluid-filled pressure catheter was placed in the carotid artery. Both were placed through a cutdown in the left side of the neck. Left thoracotomy was performed through the fifth intercostal space. Heparin was administered at 300 U/kg. When the pericardium was opened, 100 mg lidocaine (Xylocaine) was administered. The left groin was incised and a 40 ml intraaortic balloon (Datascope Inc., Paramus, N.J.) was introduced through the femoral artery. The balloon was positioned in the descending thoracic aorta. A fluid-filled pressure line was inserted in the left atrium and a Mikro-Tip catheter transducer (Millar Instruments, Inc., Houston, Tex.) was placed in the left ventricle through the apex. All pressure transducers were connected to a Triton pressure module (Triton, San Diego, Calif.). Two different instrumentation procedures were performed: one group of six animals was implanted with instruments for accurate measurements of flow through the Hemopump device (protocol 1); the other group of six animals was implanted with instruments for hemodynamic and organ perfusion analysis (protocol 2).
Protocol 1
In the first group of six animals, the ascending aorta was encircled and a 12 mm Dacron polyester fabric Y-graft was sutured to the aorta. A second graft of the same size was sutured to the descending aorta, and the grafts were interconnected with an inflow electromagnetic flowmeter of 3/8 inch (Cliniflow II, model FM 701 D; Carolina Medical Electronics, Inc., N.C.; Fig. 1). A transthoracic Hemopump cannula was transvalvularly placed in the left ventricle through the side arm of the Y-graft. The side arm was occluded by the occluders provided with the Hemopump device, diverting the produced Hemopump flow through the flowmeter back to the descending aorta (Fig. 1). The metal outflow part of the Hemopump device was positioned in the graft, and a suture around the graft secured the pump in this position and prevented leakage of flow along the Hemopump device into the ascending aorta.
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Experimental protocols
In the first protocol (n = 6), we wanted to analyze the effect of the IABP on the flow production by the Hemopump device. The flow through the graft (Hemopump flow) was measured for the seven different rotational speeds provided by the Hemopump console. Flow and pressure measurements were analyzed from beat to beat and flows were expressed in relation to pressure. Aortic pressure, left ventricular pressure, first derivative of the left ventricular pressure, electrocardiograph tracing, aortic flow, and Hemopump flow were recorded on a Nyhon Kohden chart recorder. Aortic flow, left ventricular pressure, first derivative of the left ventricular pressure, Hemopump flow and aortic flow were on-line registered on computer by means of Labview software (National Instruments, Austin, Texas). These curves were analyzed and stored in their numeric form. Measurements were repeated with the balloon pump working in an electrocardiographically triggered 1-to-1 mode. At the end of the experiment, the heart was opened to confirm the intraventricular position of the Hemopump.
In the second protocol (n = 6), we focused on hemodynamic changes, organ perfusion, and myocardial perfusion during Hemopump support alone and with IABP support. Myocardial wall thickening, left ventricular pressure, first derivative of the left ventricular pressure, arterial blood pressure, coronary flow, cardiac output, and left atrial pressure were continuously recorded on an eight-channel chart recorder (Nyhon Kohden). After stabilization, a first set of colored microspheres was injected into the left atrium (Fig. 2).
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Myocardial and organ flow measurement with colored microspheres
Nine million 15 mm diameter polystyrene microspheres of five different colors (white, red, yellow, blue, and violet) were injected on five different occasions during the experiment. The microspheres were injected in a volume of 3 ml over 30 seconds. Arterial reference blood was withdrawn during 90 seconds from the aorta at a flow rate of 10 ml/min. On termination of the experiment, 1 gm tissue samples were isolated from lungs, cerebrum, cerebellum, spleen, liver, pancreas, stomach, small bowel, large bowel, renal cortex, renal medulla, skin, and muscles.
The hearts were removed, trimmed of excess fat, and cut in five slices along the short axis. Each slice was then cut and unrolled into a myocardial strip (Fig. 3). Three right ventricular and nine left ventricular regions were identified and biopsy samples were taken from each zone from the subepicardium as well as from the subendocardium. The second slice (counting from the base of the heart) from each animal was processed for quantification of the colored microsphere content. The colored microsphere content was determined by the methods described by Kowallik and coworkers,
6 Rudolph and Heymann,
7 and Wieland and colleagues.
8
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Results
Influence of the IABP on the performance of the Hemopump device
The IABP reduced the performance of the Hemopump device. Fig. 4 shows the mean flow produced at the different rotational speeds by the Hemopump device and by the combination of the Hemopump device with the IABP. In the control situation, with the Hemopump device switched off, a backflow was measured through the cannula (0.39 L/min). This backflow was further increased to 0.49 L/min by the IABP (increase of the backflow by 20%). When the Hemopump device was working, the IABP reduced the flow by 11.1% at all rotational speeds. This reduction of the Hemopump flow by the IABP was only significant in the control situation and at low speed.
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Assistance with the Hemopump device improved myocardial flow to a small extent (Figs. 9, A, 10, A, and 11, A). The mean subendocardial blood flow in the ischemic regions rose from 24 ± 17 to 44 ± 40 ml/min/100 gm (p > 0.2), the subepicardial flow rose from 45 ± 31 to 55 ± 45 ml/min/100 gm, and the ratio rose from 0.48 ± 0.22 to 0.85 ± 0.59 (p > 0.2). For the subendocardial myocardial perfusion, the ANOVA still showed a significant difference from the control situation (p < 0.001; Fig. 9, A).
Support with the combination of the Hemopump device and IABP improved myocardial blood flow to a greater extent (Figs. 9, B, 10, B, and 11, B). Subendocardial blood flow improved from 24 ± 17 to 63 ± 57 ml/min/100 gm (p > 0.2), epicardial blood flow remains unchanged from 57 ± 40 to 57 ± 44 ml/min/100 gm, and the ratio increased from 0.48 ± 0.28 to 1.26 ± 1.23 (p = 0.1750). As a consequence, there was no significant difference from the control situation (ANOVA for subendocardial flow p > 0.2).
Discussion
Clinical practice has led us to the combined use of the transthoracic Hemopump device and the IABP.
9 In cases of postcardiotomy heart failure, the IABP remains the first choice as a mechanical support device. The device is easily introduced through the femoral artery, has an acceptable complication rate,
10,11 and has been shown to be beneficial by increasing myocardial perfusion and reducing left ventricular work.
2-4 In cases of persistent low cardiac output despite pharmacologic support and IABP use, we consider the transthoracic Hemopump device to be the first choice as a left ventricular assist device. This pump is powerful (produces up to 5 L/min), also is easily introduced, and has proved to be technically reliable, as opposed to the femoral cannulas of the Hemopump device. With the IABP already in place, we introduced the transthoracic Hemopump device and thus created the combination of these devices. We suspected a possible beneficial effect on myocardial flow and were intrigued by the gradual weaning possibilities (first weaning from the Hemopump device and then from IABP).
This experimental study proves our theoretic hypothesis to be sound. First, the increase in diastolic blood pressure created by the IABP reduced the Hemopump flow. Second, the higher diastolic perfusion pressure created an increase in myocardial blood flow in ischemic regions. With the colored microsphere technique, we showed that the Hemopump device and IABP combination returned subendocardial flow in ischemic regions to normal.
Hemodynamic effects
We did not intend to cause hemodynamic collapse by the applied coronary stenosis. On the contrary, our intention was to show the specific effects of the assisted circulation on myocardial perfusion. In a model of cardiogenic shock, the simple increase of cardiac output and arterial blood pressure by the Hemopump device should itself influence the myocardial perfusion. We therefore preferred to create a stenosis with 50% flow reduction, rather than a complete occlusion. In consequence we did not study the effects of cardiogenic shock. Total cardiac output and blood pressure did not significantly change during the created "ischemia." The effects of the Hemopump device alone and with IABP support were therefore minimal; there was no change in total cardiac output.
Organ perfusion
We could not identify any effect on peripheral organ perfusion. In this series of experiments, the myocardial stenosis was only applied with the purpose of creating an ischemic subendocardial region. We did not intend to cause myocardial failure and subsequent shock. The so-called "ischemic values" of peripheral organ perfusion thus do not differ from the control values. However, the fact that assistance with the Hemopump device alone and with IABP did not alter this organ perfusion is important. It proves that the organ perfusion in the assisted situation (with the nonpulsatile Hemopump device) is similar to that in the normal or unassisted situation. Associating an IABP and adding to the pulsatility of the flow did not change the organ perfusion. This finding underlines our clinical experience, where several of our patients with nonpulsatile assistance had good organ function.
9
Myocardial perfusion
Several series have shown that myocardial perfusion is increased by support with the Hemopump device.
5,12,13 These experiments in dogs studied myocardial perfusion after occlusion of the left anterior descending coronary artery. Such an occlusion will always impair the hemodynamic status of the animal, and the beneficial effect of the Hemopump device on myocardial perfusion is therefore due in part to the treatment of the cardiac shock. The coronary stenosis used in our experiments did not alter cardiac output or perfusion pressures. The changes in myocardial blood flow in this study were thus due purely to the unloading capacities of the Hemopump device. We caused a significant drop in subendocardial perfusion during ischemia. The Hemopump device improved the ratio of subendocardial to subepicardial blood flow, and this effect was caused by the decreased end-diastolic left ventricular pressure,
3 as also illustrated by the decrease in left atrial pressure (from 12.5 ± 4.8 to 8.4 ± 5 mm Hg). Moreover, the Hemopump device strongly unloaded the heart (decrease in first derivative of pressure from 1089 ± 448 to 505 ± 277; p < 0.001) and therefore reduced myocardial oxygen need. The Hemopump device increased the subendocardial blood flow in the ischemic areas to a small extent (from 24 ± 17 to 44 ± 40 ml/min/100 gm; p > 0.2), and a significant underperfusion compared with the control situation remained (ANOVA, p < 0.001).
Perfusion pressure (and particularly diastolic perfusion pressure) is the most important parameter for coronary flow in the ischemic, vasodilated vascular bed. The association of the IABP with the Hemopump device combined both advantages, unloading and high diastolic pressure, to create an almost ideal situation. Coronary flow in the ischemic subendocardial region was returned completely to normal (no statistically significant difference from the control situation; ANOVA, p > 0.2) and the unloading features of the Hemopump device remain unchanged. In other words, myocardial flow was returned to normal and oxygen need was reduced; one could hardly assist the ischemic heart in a better way.
To validate our experimental results in the clinical situation, the studied animals' weights needed to be similar to those of human beings. Otherwise, the effect of the mechanical support systems could have been overestimated. We therefore chose to use sheep. One anatomic difference between human beings and sheep must be considered in this experimental setup. The ovine descending aorta is relatively small in comparison to the human aorta. This means that the effect on the ovine heart of an IABP in the descending aorta remains rather moderate in comparison with that in the human heart. Taking this into consideration, it is possible that the IABP effect on the heart will be more pronounced in human beings than we were able to demonstrate in these sheep.
This physiologic insight has shown us that the Hemopump device with IABP is an ideal support system in cases of ventricular failure from ischemia. However, the addition of the IABP is not always beneficial. It neither contributes to nor reduces the peripheral organ perfusion, and it reduces the flow produced by the Hemopump device by approximately 10%. In all cases in which the myocardial perfusion is no longer of importance (irreversible damage), the association of an IABP with the Hemopump device is not indicated.
Footnotes
The authors do not have any financial interest in the Hemopump product or its manufacturer, nor in the intraaortic balloon pump used in this study. ![]()
References
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