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Ann Thorac Surg 1997;64:1718-1723
© 1997 The Society of Thoracic Surgeons
Department of Anaesthesia and Division of Cardiovascular Surgery, London Health Sciences Centre, London, Ontario, Canada
Accepted for publication June 26, 1997.
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Abstract |
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 TopFootnotes Abstract IntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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Methods. In 10 anesthetized sheep, RV failure was induced using a pulmonary artery constrictor. Baseline measurements included mean systemic blood pressure, RV peak systolic pressure, cardiac index, and RV ejection fraction. Myocardial and organ perfusion were measured using radioactive microspheres.
Results. After pulmonary artery constriction, there was an increase in RV peak systolic pressure (32 ± 2 to 60 ± 3 mm Hg; p < 0.01) and a decrease in mean systemic blood pressure (68 ± 4 to 49 ± 2 mm Hg; p < 0.01), RV ejection fraction (0.51 ± 0.04 to 0.16 ± 0.02; p < 0.01), and cardiac index (2.48 ± 0.04 to 1.02 ± 0.11; p < 0.01). Blood flow to the RV did not change significantly, but there was a significant reduction in blood flow to the left ventricle. The initiation of intraaortic balloon counterpulsation (1:1) using a 40-mL intraaortic balloon inserted through the left femoral artery resulted in an increase in mean systemic blood pressure (49 ± 2 to 61 ± 3 mm Hg; p < 0.01), cardiac index (1.02 ± 0.11 to 1.45 ± 0.14; p < 0.05), RV ejection fraction (0.16 ± 0.02 to 0.23 ± 0.02; p < 0.01), and blood flow to the left ventricle.
Conclusions. In a model of right heart failure, the institution of intraaortic balloon counterpulsation caused a significant improvement in cardiac function. Although RV ischemia was not demonstrated, the augmentation of left coronary artery blood flow by intraaortic balloon counterpulsation and subsequent improvement in left ventricular function suggest that left ventricular ischemia contributes to RV dysfunction, presumably through a ventricular interdependence mechanism. Therefore, study of the safety and efficacy of intraaortic balloon counterpulsation in the management of patients with acute right heart dysfunction is warranted.
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Introduction |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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Right ventricular (RV) dysfunction is a frequent consequence of orthotopic heart transplantation as a result of preexisting recipient pulmonary hypertension. The presence of pulmonary hypertension more than doubles the risk of death associated with transplantation and may precipitate acute RV failure postoperatively because of pressure overload of the donor RV [1]. Several mechanisms have been hypothesized to account for RV failure in the setting of acute RV overload, including RV subendocardial ischemia, left ventricular (LV) free wall ischemia, and RV dysfunction secondary to compromised LV–RV systolic interaction [2–13].
A case report demonstrated an improvement in RV function with intraaortic balloon counterpulsation (IABP) after conventional management of isolated right heart dysfunction had failed [14]. We therefore hypothesized that IABP would improve RV function in the setting of acute RV pressure overload by augmenting right and left coronary artery blood flow. The objective of this study was to produce a steady-state model of moderate RV pressure overload with compromised systemic hemodynamics. With this model, by measuring regional blood flow, we sought to examine the role of myocardial perfusion in the development of RV dysfunction and to determine whether subsequent IABP would have any beneficial effect on ventricular perfusion or function.
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Material and Methods |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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A left thoracotomy was performed to place a fluid-filled silicone elastomer catheter (0.125-in outer diameter) (Dow Corning, Midland, MI) into the left atrial appendage. The catheter was secured with a pursestring suture and exteriorized through a stab incision in the lateral chest wall. The main pulmonary artery was isolated and then encircled with a vascular occlusion device. Vascular access to the right femoral artery, right femoral vein, and left carotid artery was established using similar catheters inserted by direct vascular cutdown. An 8F introducer sheath (Cordis Corp, Miami, FL) was inserted similarly into the left external jugular vein, and a thermodilution pulmonary artery catheter (REF Volumetric TD catheter, model 93A-439H; American Edwards Laboratories, Santa Ana, CA) was flow-directed into the pulmonary artery using pressure tracings to confirm placement.
A standard 40-mL intraaortic balloon (PERCOR-DLII; Datascope Corp, Paramus, NJ) was inserted through a cutdown on the left femoral artery. Palpation of the inflated balloon confirmed its position in the proximal descending thoracic aorta. A three-lead electrocardiogram (ECG) (lead II) was placed using needle electrodes for continuous ECG monitoring. After completion of the preparatory operation, no further interventions were undertaken to allow stabilization of the preparation. After demonstration of both hemodynamic stability and stable anesthetic requirements, the control study was performed.
Baseline Measurements
Baseline measurements of systemic (BP) and pulmonary artery (PAP) pressures, pulmonary artery occlusion pressure (PAoP), right ventricular peak systolic pressure (PRV), and right atrial pressure (PRA) were obtained. Simultaneously, thermodilution cardiac output and right ventricular end-diastolic (EDVRV) and end-systolic (ESVRV) volumes and ejection fraction (RVEF) were determined in triplicate, using the thermodilution catheter. All measurements were repeated over a 15-minute period to ensure a steady state and then were averaged. Samples of ECG recordings were documented for each measurement period. Baseline myocardial and organ blood flow were measured according to the technique described by Heymann and colleagues [15] and Buckberg and associates [16], and as outlined later.
Acute Right Ventricular Pressure Overload
The pulmonary artery constrictor was tightened in a slow and graded manner to produce pressure overload of the RV, such that RV pressure increased and the cardiac index (CI) decreased at least by 50%, which also allowed hemodynamic stability for at least 10 minutes before hemodynamic measurements were taken. Further pulmonary artery constriction resulted in a rapid decline in BP and a progressive rise in PRA and EDVRV that necessitated release of the constrictor to allow the hemodynamic parameters to return to baseline levels. During moderate RV pressure overload and steady-state BP, hemodynamic measurements, RV volumes and pressures, and myocardial blood flows were evaluated again.
Institution of Intraaortic Balloon Counterpulsation
After the completion of measurements during acute RV pressure overload, IABP was initiated. Intraaortic balloon counterpulsation (Datascope Intra-aortic Balloon Pulsation-System 83; Datascope Corp) was commenced at a ratio of 1:1 (using T-wave ECG triggering) and adjusted to produce maximal pressure augmentation of the left carotid pressure waveform. After a period of 20 minutes to ascertain steady-state conditions, repeated measurements of hemodynamic parameters; RVEF, EDVRV, and ESVRV; and myocardial blood flow were performed.
After the completion of these measurements, the animals were euthanized by a lethal injection of sodium pentobarbital, 240 mg/mL, and propylene glycol, 20% (Euthanol; MTC Pharmaceuticals, Toronto, Ont, Canada). The heart, brain, kidneys, liver, pancreas, and spleen were excised in total, and constant segments of the small bowel (20 cm of the jejunum) and the large bowel (20 cm of the proximal right colon) were collected for microsphere determination of organ blood flow.
Specific Methodology
Pressures were recorded using strain-gauge pressure transducers (Hewlett-Packard models 7830A, 78901A, and 7154B; Hewlett-Packard, Wertheim, MA), referenced to the animal's humeral tuberosity, for the level of the left atrium. Thermodilution cardiac output and RVEF were determined using a portable cardiac output computer (model 9520A; American Edwards Laboratories) with 10 mL of iced 0.9% saline solution.
The averaged cardiac outputs (three to five determinations) were indexed (CI) to BSA, as were the EDVRV (EDVIRV = EDVRV ÷ BSA), ESVRV (ESVIRV = ESVRV ÷ BSA), and stroke volume index (SI; mL/M2). The right and left ventricular SIs were calculated using the following formulas: [1.36 x (PAP - PRA) • SI]/100 and [1.36 x (BP - PPAoP) • SI]/100, respectively. Calculation of the BSA for sheep was performed according to Maynard [17]: BSA = (70 x body weight in kg 0.75/1,000).
Myocardial and organ blood flow were determined using radioactive microspheres [15, 16]. Carbonized microspheres with an average diameter of 15 ± 3 µm suspended in 10% dextran and 0.5% polysorbate 80 (Tween 80; 3M Medical Products, St. Paul, MN) were used. Three radioactive labels (46Sc, 141Ce, and 85Sr) were used and their order of administration was randomized. Samples of microspheres were withdrawn, diluted in 2.5 mL of heparinized blood, and agitated vigorously for 5 minutes using a vortex mixer (model 58223, Scientific Products, Evansville, IN). The microspheres then were injected through the indwelling left atrial catheter. Dual reference samples were withdrawn simultaneously from the femoral and carotid arterial lines at a rate of 9.89 mL/min (Harvard pump model 942; Harvard Apparatus Company, Mills, MA). Withdrawal of the samples was commenced before the microsphere injection and continued for 90 seconds after completion of the injection. After hemolysis with water, the reference samples were decanted into counting tubes to a maximum depth of 3 cm.
On completion of the study, organs and tissues were removed, cleaned of excess fat, and weighed. After cleaning, each organ was cut into small sections, dried, and placed in counting tubes. The heart was sectioned into the constituent ventricles. The RV free wall was dissected from the interventricular septum and LV. The LV was sectioned further into three layers, the endocardium, epicardium, and midsection, and the RV free wall and interventricular septum were divided into two layers. The tissue was packed into each tube to maximum height of 3 cm, because this was found to provide a uniform counting column, with count accuracy in excess of 90%. A total of between 350 and 460 counting tubes were required for each animal.
All samples then were analyzed in a multichannel well-counter (Automatic Gamma Counting System, series 1185; Scarle Analytic Inc., Des Plaines, IL) and each tube was counted for 3 minutes at the four appropriate energy window settings. Arithmetic correction for scatter from high- and lower-energy isotopes into the window settings was achieved through the solution of a series of simultaneous equations. The adequacy of intravascular mixing of the microspheres was assessed by comparison of flows to the kidneys and cerebral hemispheres. Variations exceeding 10% resulted in rejection of that individual study from the subsequent analysis. The resultant data from tissues were related to the counts in the reference samples, with blood flow to each organ (Q-organ) calculated using the following formula: Q-organ = (arterial reference flow x organ nuclide activity)/arterial reference nuclide activity expressed as mL • 100 g of tissue-1 • min-1.
Data Analysis
Data are reported as mean plus or minus standard deviation. A repeated-measures analysis of variance (multivariate analysis of variance–Statistical Package for the Social Sciences/personal computer) was used to detect significant changes in hemodynamic parameters and measures of regional blood flow between control and RV pressure overload with and without IABP.
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Results |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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. Tightening of the pulmonary artery constrictor produced an acute RV pressure overload with a significant increase in PRV, PRA, EDVIRV, ESVIRV, and heart rate, and a significant decrease in mean BP, RVEF, SI, and CI, whereas no change occurred in PAP.
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All animals demonstrated ECG evidence of LV ischemia (ST segment depression) during severe pulmonary artery constriction. This usually led to significant hemodynamic deterioration requiring release of the pulmonary artery constrictor. However, in 5 animals, despite ST segment depression, we were able to achieve a hemodynamic steady state, allowing us to proceed with our physiologic measurements during ST segment depression. With the institution of IABP, the ischemic changes immediately returned to baseline (Fig 1).
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, respectively. With pulmonary artery constriction, there was a tendency for RV blood flow to increase and for the endocardial-to-epicardial ratio to decrease, but these changes did not attain statistical significance (Table 2). After the institution of IABP, these values did not change. In the LV, after pulmonary artery constriction, there was a 46% fall in total perfusion of the LV, concomitant with a decrease in perfusion of the LV endocardium and epicardium, with redistribution of transmural blood flow from the endocardium to the epicardium as the LV endocardial-to-epicardial ratio declined from 1.29 ± 0.07 to 1.09 ± 0.03 (Table 3). Intervention with IABP significantly improved perfusion of both the LV endocardium and epicardium without modifying transmural distribution.
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). Although the greatest reduction in septal blood flow affected perfusion of the LV septum compared with the RV septum, no redistribution of flow between the left and right sides occurred. The institution of IABP did not alter septal blood flow significantly, although flow increased in all animals. Organ blood flow to the rest of the body was compromised by the fall in cardiac output and BP that accompanied pulmonary artery constriction (Table 5). Although organ blood flow tended to improve with IABP, perfusion to the spleen was the only significant increase observed.
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Comment |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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In attempting to re-create the clinical scenario of RV dysfunction after orthotopic heart transplantation, we used an animal model with an open pericardium consisting of pulmonary artery banding, because this technique presents the RV with maximal dynamic afterload [18]. With a fixed obstruction, any improvement in RV function would result from the institution of IABP, and not from spontaneous changes in the obstruction. Such criticism has been levied against models using embolization of the pulmonary vasculature, whereby the pulmonary and systemic responses to pulmonary microembolization not only represent the effects of mechanical obstruction within the pulmonary microvasculature, but also the release of inflammatory mediators that follows. As a result, these models are unpredictable and produce spontaneous variations in pulmonary resistance over time.
Hemodynamic Effects of Pulmonary Artery Occlusion
Constriction of the pulmonary artery by banding resulted in hemodynamic changes consistent with RV dysfunction, as demonstrated by a significant reduction in RVEF, SI, CI, and BP, whereas PRV, heart rate, EDVI, and ESVI increased; previous models of RV failure demonstrated similar consequences [3, 4, 6, 19]. The increase in EDVI and ESVI observed in this study correlates with an increase in RV end-diastolic length and has been demonstrated to be a physiologic compensatory mechanism to counteract the acute pressure overload to which the RV is subjected [2].
Hemodynamic Effects of Intraaortic Balloon Counterpulsation During Pulmonary Artery Occlusion
The institution of IABP produced significant improvement in RVEF, CI, and BP (Table 1). The pathophysiology of right heart failure during acute pressure overload is reported to result from RV subendocardial ischemia. Thus, any therapy designed to augment perfusion of the RV endocardium would improve RV function. Other studies also have shown an improvement in RV function during acute pressure overload, either by increasing BP with phenylephrine or clamping of the descending aorta, or by augmenting right coronary artery vasodilation with adenosine [4, 6, 19]. It was hypothesized that the improvement in RV function was a result of the alleviation of RV myocardial ischemia [4, 6]. In our study, the return of mean aortic pressures with IABP restored coronary artery perfusion pressures to baseline values, which was associated with increases in RVEF and cardiac output of 44% and 50%, respectively.
Effects of Pulmonary Artery Constriction and Intraaortic Balloon Counterpulsation on Myocardial Blood Flow
RIGHT MYOCARDIAL BLOOD FLOW.
Models of RV failure have demonstrated that when increases in pulmonary artery resistance are sufficient to decrease cardiac output by 20%, the RV is performing primarily pressure work as opposed to flow work, causing oxygen requirements to increase dramatically at a time when it usually is coupled with a decrease in right coronary artery perfusion pressure (resulting from decreased BP) [2, 20]. As a result, RV ischemia is inevitable and is reputed to be the cause of right heart failure during acute pressure overload of the RV [2–6].
The initial response to acute pressure overload of the RV is to increase RV myocardial blood flow, with a redistribution to the endocardium (ie, to increase the endocardial-to-epicardial ratio), to meet the increased metabolic demands of the RV endocardium [4–6]. However, during severe pressure overload of the RV, these demands may not be met because right coronary artery perfusion pressure is reduced as a result of systemic hypotension and reduced cardiac output, rendering the RV endocardium ischemic [3–6].
Our study hypothesis was that an improvement in RV endocardial blood flow with IABP would reduce ischemia during acute pressure overload and result in an improvement in RV function. We were unable to demonstrate significant changes in perfusion of the RV, although the possibility of a type II statistical error exists because of the large standard deviations and small sample size in our study. For example, after either pulmonary artery constriction or the institution of IABP, there was a tendency in all animals for perfusion to the RV to increase during RV pressure overload, which would result from the increased oxygen requirements. This occurred at a time when CI and perfusion of the LV were decreased significantly. In addition, a reduction in the RV endocardial-to-epicardial ratio, consistent with subendocardial ischemia, occurred during pulmonary artery constriction, which subsequently returned to baseline values with IABP. However, these parameters also did not reach statistical significance (Table 2).
LEFT MYOCARDIAL BLOOD FLOW.
Several studies have demonstrated the existence of an LV–RV systolic interaction, which suggests that the LV may contribute up to 40% of RV function through a ventricular interdependence mechanism [7–13]. As a result, RV function is subject to changes in LV function or compliance [7, 10, 21]. Santamore and co-workers [10, 11] have shown that LV free wall ischemia alters both the filling characteristics and the pressure development of the RV. Therefore, failure in pressure generation by an ischemic LV would be expected to have a significant impact on RV function.
In our study, we demonstrated a reduction in perfusion of the LV, perfusion of the septum, and the LV endocardial-to-epicardial ratio during acute pressure overload of the RV (Tables 3, 4). The ECG demonstrated evidence of LV ischemia in all animals during severe pulmonary artery constriction, necessitating release of the pulmonary artery constrictor. In 5 animals, during moderate pulmonary artery constriction, we were able to achieve steady-state hemodynamics with concomitant ECG evidence of LV ischemia, which improved after the institution of IABP (Fig 1). Unfortunately, biochemical determinants of myocardial ischemia were not measured in our study, so we were unable to confirm LV ischemia in our animal population. However, such an alteration in total blood flow and regional distribution of LV perfusion during pulmonary artery constriction and an improvement during IABP suggests that LV ischemia contributed to RV dysfunction.
In summary, we defined the characteristics of a steady-state model of acute RV pressure overload and demonstrated significant hemodynamic improvement with IABP. We were unable to implicate RV subendocardial ischemia as the cause of the observed hemodynamics; however, a role for LV ischemia appears to be appropriate. Improved coronary artery perfusion after IABP would account for the improvement in both LV and RV function. As a result, ventricular interdependence as defined by previous work suggests a possible mechanism whereby reversal of LV ischemia/dysfunction with IABP results in an improvement in RV function. Therefore, investigation of the safety and efficacy of IABP in the management of patients with acute right heart dysfunction is warranted.
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Acknowledgments |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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Supported in part by research grants from the Ontario Thoracic Society and the University Hospital Pooled Research Trust Fund.
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Footnotes |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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References |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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