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Right arrow Transplantation - heart

Ann Thorac Surg 2006;81:658-664
© 2006 The Society of Thoracic Surgeons

Original article: Cardiovascular

Celsior Preserved Cardiac Mechanoenergetics Better Than Popular Solutions in Canine Hearts

Yu Oshima, MD a , b , Satoshi Mohri, MD, PhD b , * , Juichiro Shimizu, MD, PhD b , Gentaro Iribe, MD b , Takeshi Imaoka, MD, PhD b , Waso Fujinaka, MD b , Takahiko Kiyooka, MD b , Kozo Ishino, MD, PhD a , Shunji Sano, MD, PhD a , Fumihiko Kajiya, MD, PhD b , Hiroyuki Suga, MD, PhD c

a Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
b Department of Cardiovascular Physiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
c National Cardiovascular Center Research Institute, Osaka, Japan

Accepted for publication July 19, 2005.

Abbreviations and Acronyms Emax = end-systolic pressure–volume ratio, a load-independent index of cardiac contractility; LV = left ventricle; PVA = ventricular pressure–volume area, a measure of total mechanical energy; RV = right ventricle; SR = sarcoplasmic reticulum; STH = St. Thomas' Hospital solution No. 2; UWS = University of Wisconsin solution; Vo2 = cardiac oxygen consumption

* Address correspondence to Dr Mohri, Department of Cardiovascular Physiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan (Email: smohri{at}md.okayama-u.ac.jp).


   Abstract
Top
 Abstract
Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
BACKGROUND: Better protective effects of Celsior on cardiac function than the other conventional solutions have been reported in acute experiments and in clinical trials for at-risk patients. However, no study has yet precisely elucidated how these preservation solutions affect cardiac mechanoenergetics. Therefore, we evaluated the effects of St. Thomas' Hospital solution No. 2, University of Wisconsin solution, and Celsior on left ventricular contractility (Emax: end-systolic pressure–volume ratio) and oxygen consumption.

METHODS: We used 32 canine excised cross-circulated hearts. Twenty-three hearts served as donor hearts after hypothermic ischemia with one of the three solutions, and the remaining 9 served as controls. After arrest with each solution, the hearts were preserved for 4 hours at 4°C. Then, we measured left ventricular pressure, volume, and oxygen consumption to obtain Emax and the relation between ventricular pressure–volume area (a measure of total mechanical energy) and oxygen consumption. We also evaluated the oxygen cost of Emax by changing Emax with calcium administration.

RESULTS: Celsior did not significantly affect Emax (6.3 ± 2.4 in control versus 5.3 ± 1.3 mm Hg · mL–1 · 100 g with Celsior) nor the oxygen cost of Emax (1.2 ± 0.6 versus 1.6 ± 0.5 mL O2 · mL · mm Hg–1 · beat–1 · 100 g–2, respectively). In contrast, St. Thomas' Hospital and University of Wisconsin solutions significantly decreased Emax (4.5 ± 1.1 and 3.5 ± 0.9 mm Hg · mL–1 · 100 g, respectively) and increased the oxygen cost of Emax (2.5 ± 0.8 and 2.4 ± 0.9 mL O2 · mL · mm Hg–1 · beat–1 · 100 g–2, respectively) compared with control and Celsior-preserved hearts. The slope and intercept of the oxygen consumption versus pressure–volume area relation showed no significant difference among the four groups.

CONCLUSIONS: Celsior showed better protective effects on cardiac mechanoenergetics than St. Thomas' Hospital and University of Wisconsin solutions in the acute phase of heart transplantation.


   Introduction
Top
 Abstract
 Introduction
Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
In recent cardiac transplantation, many different kinds of preservation solutions have been used to avoid myocardial injury during the ex vivo ischemic situation. Numerous laboratory and clinical studies on the effects of these preservation solutions have been reported to improve the outcome [1–5]. Ischemia–reperfusion injury has been recognized as the result of myocardial cell swelling and interstitial edema [6], sarcoplasmic reticulum (SR) injury and contractile protein dysfunction by calcium overload [7], and myocardial damage by oxygen-derived free radicals [8]. These adverse effects have been avoided by making many preservation solutions hypertonic with mannitol or adding to them other impermeants including radical scavenging agents. In terms of clinical aspects, some multicenter controlled studies of Celsior have shown that the use of Celsior was as safe and effective as conventional solutions [1, 2] and valuable in at-risk patients in the acute phase of heart transplantation [1].

To integrate the numerous findings obtained from basic research and understand these clinical results, it is important to investigate the effects of the preservation solutions on either cardiac mechanics or energetics or both in whole hearts [3, 4]. However, no study has yet shown the effects of the preservation solutions on cardiac mechanoenergetics.

We therefore performed the present study to compare the cardioprotective effects of the three representative solutions, St. Thomas' Hospital solution No. 2 (STH), University of Wisconsin solution (UWS) [5], and a commercially available Celsior solution [1] on left ventricular (LV) mechanoenergetics after hypothermic ischemia (4°C, 4 hours) using the excised, denervated cross-circulated (blood-perfused) canine heart of our expertise [9]. We used an index of cardiac contractility (Emax: end-systolic pressure–volume ratio), practically independent of ventricular loading conditions [10]. To assess the cardiac energetic effects of each solution, we used the relationship between cardiac oxygen consumption (Vo2) and ventricular pressure–volume area (PVA; a measure of total mechanical energy) of the LV [9].


   Material and Methods
Top
 Abstract
 Introduction
 Material and Methods
Results
 Comment
 Acknowledgments
 References
 
Preservation Solutions
We selected STH, UWS, and Celsior as the three representative preservation solutions as follows. Although 147 heart transplant centers in the United States used 167 kinds of solutions [5], STH was used most commonly for 20.1% of 9,401 transplanted hearts, and UWS was used next most commonly for 16.7% of them. Celsior is a commercially available solution (Sang Stat Medical Corporation, Menlo Park, CA), which has recently been reported to be clinically beneficial [1].

Table 1 lists the compositions of the three solutions. Briefly, STH contains extracellular composition of electrolytes except the relatively high calcium (1.2 mmol/L). University of Wisconsin solution contains no calcium, high potassium, and radical scavengers allopurinol and glutathione. Celsior also contains extracellular composition of electrolytes, low concentration calcium (0.25 mmol/L), high molecular weight compounds, and radical scavengers.


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  		Table 1. Composition of STH (St. Thomas' Hospital solution No. 2), UWS (University of Wisconsin solution), and Celsior
 
Surgical Preparation
All procedures in this study conformed to the animal care guidelines of our institution and the US National Institutes of Health. Experiments were performed in the excised, cross-circulated (blood-circulated) canine heart preparation [11–13]. During anesthesia and mechanical ventilation, the larger dog of each pair was used as the metabolic supporter (Fig 1). Its common carotid arteries and right external jugular vein were cannulated and connected to the arterial and venous cross-circulation tubes, respectively. We performed a total of 32 experiments consisting of 23 preservation experiments (STH, n = 8; UWS, n = 7; Celsior, n = 8) and 9 control experiments.


Figure 1
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  		Fig 1. Schematic illustration of a canine cross-circulated heart preparation. (AVO2D = arteriovenous oxygen content difference; CF = coronary flow; ECG = electrocardiogram; LV = left ventricle; LVP = LV pressure.)

 
In the control group, the arterial and venous cross-circulation tubes from the support dog were cannulated into the left subclavian artery and the right ventricle (RV), respectively, of the smaller heart donor dog. Then, the beating heart, supported by cross-circulation, was excised from the chest without interruption of the coronary circulation.

In the three preservation groups, donor dogs were instrumented in the same way as in the control group except connecting cross-circulation. The heart was perfused with one of the three preservation solutions (300 mL) through the left subclavian artery with a coronary perfusion pressure of approximately 80 mm Hg to induce electromechanical arrest, and then kept at 4°C. Three hours later, the preserved hearts were left for 1 hour at 25°C until the myocardial temperature reached approximately 10°C. Then, the heart was perfused with moderately hypothermic (25°C) oxygenated arterial blood of the support dog at 40 mm Hg for 10 minutes by the controlled aortic reperfusion technique. All hearts started ventricular fibrillation during rewarming to 36°C, and direct current cardioversion had to be performed at approximately 30°C.

A latex thin balloon was inserted into the LV of the isolated donor heart connected to a volume-servo pump (AR Brown, Tokyo, Japan) to control and measure LV volume. A pressure gauge (model P-7, Konigsberg Instruments, Pasadena, CA) was placed inside the apical end of the balloon to measure LV pressure. Complete atrioventricular block was made by chemical (injection of 36% formaldehyde solution) ablation of the bundle of His. Para-Hisian pacing from the LV septum was performed at 120 beats/min. The epicardial electrocardiogram was recorded to trigger data acquisition.

The coronary pressure of the excised heart was maintained stable at around 100 mm Hg by infusing hydroxyethyl starch solution or methoxamine to the support dog as needed. Arterial pH and partial pressures of oxygen and carbon dioxide of the support dog were maintained within their physiologic ranges. Left ventricular pressure and volume data were sampled at 2-ms intervals.

Contractility and Oxygen Consumption
Figure 2 shows the schema of the Emax–PVA–Vo2 framework [9]. Left ventricular contractility was assessed by Emax, which was determined as the maximum ratio of P(t)/[V(t) – V0] [9], where V0 was determined as the LV volume at which peak isovolumic pressure and PVA were zero (Fig 2A). Left ventricular contractility was normalized for 100 g LV weight and presented as mm Hg · mL–1 · 100 g [9]. Total coronary blood flow was continuously measured with an electromagnetic flowmeter (MFV-3200, Nihon Koden, Tokyo, Japan) in the coronary venous drainage tube from the RV. We neglected LV Thebesian flow because of its small fraction (<3%) in the coronary blood flow. Coronary arteriovenous oxygen content difference was continuously measured with a custom-made inline oximeter (PWA-200S, Shoe Technica Inc, Chiba, Japan). The oximeter was calibrated against a blood oxygen content analyzer (IL-382 CO-oximeter, Instrumentation Laboratory Inc, Lexington, MA) in each experiment. Cardiac oxygen consumption per minute was obtained as the product of coronary blood flow and arteriovenous oxygen content difference. It was divided by heart rate to obtain total cardiac oxygen consumption per beat. The RV oxygen consumption was kept minimized to reach the RV unloaded oxygen consumption by collapsing the RV with continuous hydrostatic drainage of the coronary venous return. The RV unloaded oxygen consumption per beat was subtracted from this total cardiac oxygen consumption per beat to yield Vo2 by calculation of the following formula (LVW and RVW mean the weights of the LV and RV): Vo2 = total cardiac oxygen consumption per beat – total unloaded oxygen consumption per beat x [RVW/(LVW + RVW)]. At the end of each experiment, the LV, including the septum, and the RV free wall were separately weighed. Oxygen consumption was normalized for 100 g of LV and divided by heart rate. Its unit of measurement was milliliters of oxygen per beat per 100 g.


Figure 2
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  		Fig 2. Schematic illustration of the framework of the left ventricular Emax (a contractility index)–PVA (systolic pressure–volume area, a measure of total mechanical energy)–Vo2 (myocardial oxygen consumption per beat) relation fully used in the present study. The left ventricular Emax is the slope of the end-systolic pressure–volume relation, which sensitively reflects ventricular contractility, practically independent of ventricular loading conditions (A). The ventricular pressure–volume area consists of the mechanical potential energy alone in an isovolumic contraction, which we used exclusively in the present study. Ventricular pressure–volume area correlates linearly with Vo2 in a load-independent manner in a stable contractile state (B). The slope (a) of the Vo2–PVA relation at a constant Emax represents the oxygen cost of PVA. Oxygen consumption can be divided at the Vo2 intercept (b) of the Vo2–PVA relation into the PVA-independent and the PVA-dependent Vo2 components (B). The PVA-dependent Vo2 is considered to be related to crossbridge cycling. The PVA-independent Vo2 is considered to be primarily related to the total calcium handling in the excitation–contraction coupling (E–C coupling) and basal metabolism (C). The Vo2–PVA data point from a data point of the baseline Vo2–PVA relation with changes in Emax at a constant left ventricular volume is induced by positive or negative inotropic intervention. This steeper relation traversed multiple volume-loaded Vo2–PVA relations for different contractility levels (D). We called this steeper relation the composite Vo2–PVA relation. In this relation, the PVA-independent Vo2 of the data point increases or decreases in proportion to an increase or decrease in Emax, respectively. The slope (c) of the relation between PVA-independent Vo2 and Emax represents the oxygen cost of Emax, and the y intercept (d) of this relation indicates the PVA-independent Vo2 at zero Emax nearly equal to basal metabolism. See Suga [9] for more details.

 
Ventricular pressure–volume area of each beat was calculated as the area in the pressure–volume diagram surrounded by the end-systolic and end-diastolic pressure–volume relations, and the systolic pressure–volume trajectory, as schematically shown in Figure 2 [9]. Ventricular pressure–volume area was normalized for 100 g of LV and its unit of measurement was millimeters of mercury per beat per 100 g [9].

Experimental Protocols
We used the isovolumic mode of contraction, which did not affect the Vo2–PVA relation in the previous study [9, 13]. In each experiment, a baseline volume run, a calcium inotropism run, and a potassium chloride arrest run were performed in this order to obtain Emax, the Vo2–PVA relation, the oxygen cost of Emax, and Vo2 for basal metabolism. First, we obtained a volume-loaded Vo2–PVA relation (Fig 2B) of steady-state isovolumic contractions produced at four to seven different LV volumes between 6 and 28 mL. After this baseline volume run, the calcium inotropism run was performed to obtain different types of the Vo2–PVA relation at a single, fixed LV volume. Calcium chloride (1%) was infused into the coronary artery to vary Emax, Vo2, and PVA at a preset constant LV volume (21 ± 6.6 mL). The infusion rate of calcium chloride was increased in steps every 3 to 5 minutes. Left ventricular contractility was increased to twice the baseline in steps by increasing the calcium infusion rate. We used calcium rather than a catecholamine as a positive inotropic agent because calcium administration increases cardiac contractility without primarily involving phosphorylation processes of contractile proteins [14].

Finally, a potassium chloride arrest run was performed after stopping the calcium infusion. The heart was arrested at V0 by a continuous infusion of 0.3 mol/L KCl solution at 1 to 2.5 mL/min into the coronary artery. When coronary blood flow and arteriovenous oxygen content difference reached steady-state during potassium chloride arrest, Vo2 was measured as basal metabolic Vo2. In all experiments, the measurements were started from approximately 10 minutes after completion of surgical preparation and finished within 3 hours. We used no immunosuppressor to exclude its inotropic effects and evaluate the cardiac protective effects of the three solutions themselves. We randomized the solutions within the protocol to avoid the influence of technical maturity of preparation on the results.

Data Analysis
Ventricular pressure–volume area and Vo2 data in the baseline volume run in each heart were subjected to linear regression analysis to obtain a volume-loaded Vo2–PVA relation (Fig 2B): Vo2 = aPVA + b, where a is the slope of the regression line, and b is the Vo2 intercept. The term aPVA represents PVA-dependent Vo2, and intercept b represents PVA-independent Vo2. Coefficient a represents the oxygen cost of PVA [9]. The reciprocal of the oxygen cost of PVA, 1/a, represents contractile efficiency [9].

Ventricular pressure–volume area-independent Vo2 at each Emax level during the calcium inotropism run was calculated as Vo2 minus PVA-dependent Vo2 for the respective PVA. The PVA-dependent Vo2 was calculated as the product of the same slope value a as the baseline a and PVA of this contraction. Thus, the PVA-independent Vo2 at each Emax level was calculated as Vo2 minus aPVA. In this calculation, we assumed that slope a remained constant at each Emax level, on the basis of the strictly confirmed parallelism of the Vo2–PVA relation [9].

The relation between PVA-independent Vo2 values and the corresponding Emax values in the calcium inotropism run was obtained by regression analysis in each heart (Fig 2D). The slope c of the regression line was identified as the oxygen cost of Emax and its dimension is milliliters of oxygen times milliliters per millimeter of mercury per beat per 100 g. To evaluate the diastolic function, end-diastolic pressure–volume relationship was obtained by fitting a cubic equation (end-diastolic pressure = {alpha} + ß volume3) with the variable ß as an index of chamber compliance [15].

Data are expressed as mean ± standard deviation. Analysis of variance was applied to compare all cariables. When analysis of variance showed statistical significance by the F test, the difference in mean values among the groups were tested by the Fisher's protected least significant difference method (StatView version 5.0J, SAS Institute Inc, Cary, NC). Values of p less than 0.05 were considered statistically significant.


   Results
Top
 Abstract
 Introduction
 Material and Methods
 Results
Comment
 Acknowledgments
 References
 
Figure 3A shows Vo2–PVA data points obtained in a baseline volume run (larger open circles), a calcium volume run (solid circles), and a calcium inotropism run (smaller open circles) in a representative case of the STH preservation group. Oxygen consumption increased linearly with PVA in both baseline and calcium volume runs. The Vo2-PVA relation in the calcium volume run shifted upward in a parallel manner from that of the baseline volume run. The slope of the Vo2-PVA relation of the calcium inotropism run was steeper than that of either baseline or the calcium volume run. During the calcium inotropism run, calcium chloride infusion was increased from 0 to 0.045 mmol/min by steps, and Emax was increased from 3.8 to 7.9 mm Hg · mL–1 · 100 g. Therefore, the Vo2–PVA relation during the calcium inotropism run is a composite line between the two Vo2–PVA relation lines in the baseline and calcium volume runs. Similar results were obtained in all four groups.


Figure 3
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  		Fig 3. Left ventricular oxygen consumption (Vo2) versus pressure–volume area (PVA) relation in a baseline volume run, a calcium volume run, and a calcium inotropism run (A) and PVA-independent Vo2 versus Emax (a contractility index) relation in the calcium inotropism run (B) in one St. Thomas' Hospital solution–preserved heart. (A) Larger open circles were obtained in the baseline volume run. Solid circles were obtained in the calcium volume run. Solid lines connecting larger open circles and solid circles indicate the baseline Vo2–PVA relation and the Vo2–PVA relation under calcium administration, respectively. Smaller open circles indicate the Vo2–PVA data point moving upward and rightward with enhancement of Emax by calcium administration at constant left ventricular volume. In the calcium inotropism run, PVA-independent Vo2 was increased by calcium administration proportionally to increases in Emax. (B) Ventricular pressure–volume area-independent Vo2–Emax data in the same heart as in A. A solid line connecting the circles indicates the PVA-independent Vo2–Emax relation during gradual enhancement of Emax by calcium administration.

 
Figure 3B shows the relation between PVA-independent Vo2 and Emax obtained from the same data used for the composite Vo2–PVA relation during the calcium inotropism run. The PVA-independent Vo2 increased linearly with Emax. Similar results were obtained in all four groups.

The correlation coefficients of the Vo2–PVA relations during the baseline volume and calcium inotropism runs were always nearly equal to unity. Specifically, they were 0.939 ± 0.048 in control, 0.981 ± 0.021 with STH, 0.953 ± 0.037 with UWS, and 0.983 ± 0.013 with Celsior in baseline volume runs; and 0.949 ± 0.051 in control, 0.991 ± 0.063 with STH, 0.978 ± 0.031 with UWS, and 0.991 ± 0.007 with Celsior in calcium inotropism runs. These results proved it reasonable to apply the Vo2–PVA–Emax framework to the present 4-hour ex vivo hypothermic and ischemic hearts.

Mechanics
Table 2 shows the data of mechanoenergetics in the control and three preservation groups. In the baseline volume run, Emax significantly decreased by 29% with STH and by 44% with UWS as compared with control hearts. However, Emax did not significantly change with Celsior. Left ventricular contractility with UWS was significantly lower than with Celsior. Variable ß values were not significantly different among all four groups, indicating that the ventricular compliances were equally preserved by the three preservation solutions.


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  		Table 2. Slope of End-Systolic Pressure–Volume Relationship, Slope and Oxygen Consumption Intercept of the Oxygen Consumption–Pressure Volume Area Relation, Slope of Pressure–Volume Area-Independent Oxygen Consumption–Cardiac Contractility Relation, and Magnitude of Cubic Equation Describing End-Diastolic Pressure–Volume Relationship (ß)
 
Energetics
Among the control and three preservation groups, neither the slope nor the intercept of the Vo2–PVA relationship (PVA-independent Vo2) showed any significant differences in the baseline volume run (Table 2). The oxygen cost of Emax was significantly higher with either STH or UWS than in control and with Celsior, but was not significantly different between control and Celsior. The basal metabolic Vo2 obtained by potassium chloride arrest did not differ among all four groups.


   Comment
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
Acknowledgments
 References
 
We have shown that cardiac mechanoenergetics after the hypothermic and ischemic ex vivo situation (4 hours, 4°C) was reasonably well preserved with any of the three representative solutions, ie, STH, UWS, and Celsior, in the canine isolated hearts. The main results that we obtained are (1) although LV contractility in hearts preserved with either STH or UWS was significantly lower than control, there was no significant difference in contractility between Celsior-preserved and control hearts; (2) neither the slope nor the intercept of the Vo2–PVA relation showed significant differences among the control and three preservation groups; and (3) the oxygen cost of contractility with either STH or UWS but not with Celsior was significantly higher than control. The better outcome of Celsior in at-risk patients in the acute phase [1] may be related to not only the better-preserved contractility but also the lower oxygen cost of Emax, namely, less oxygen consumption per unit increase in contractility. These cardiac mechanoenergetics characteristics of the donor hearts treated as in clinical settings have never been evaluated integratively in appropriate animal models.

A previous study using the Vo2–PVA–Emax framework has reported that a 15-minute normothermic global ischemia followed by 60 to 120 minutes of reperfusion significantly decreased Emax by approximately 40%, but this regimen neither significantly decreased the PVA-independent Vo2 nor affected the slope of the Vo2–PVA relation in canine hearts [12]. This indicates a decreased cardiac contractility and an oxygen wasteful mechanoenergetics of the stunned hearts when the oxygen cost of contractility was increased with varying Emax by calcium administration [11]. A similarly increased oxygen cost of contractility has also been observed in postacidotic stunned myocardium in canine hearts [11]. In the present study, STH and UWS produced similar results to stunned hearts [12], but Celsior prevented this deterioration of contractility and the increased oxygen cost of contractility determined by intracoronary calcium administration.

The mechanism of the wasteful mechanoenergetics that we observed with STH and UWS may be explained by the calcium-leaky SR [16], the decreased fraction of total calcium handling by the SR [16], and the decreased calcium sensitivity and responsiveness [16, 17]. Calcium-leaky SR causes some futile calcium cycling by the SR, which does not allow calcium binding to the contractile proteins but wastes adenosine triphosphate to take up the calcium [18]. Hearts with decreased calcium sensitivity and responsiveness need more calcium to develop the same Emax and hence increase the oxygen cost of Emax. The fraction of calcium handled (ie, released and removed) by the SR critically affects cardiac energetics because total calcium handling Vo2 was a significant fraction of LV Vo2, and the internal (by the SR) and external (transsarcolemmal) calcium handling routes have calcium to adenosine triphosphate stoichiometries with a twofold difference [19].

Hypothermic ischemia maintained for 8 hours reduced the P/O ratio due to disturbed mitochondrial oxidative phosphorylation, resulting in a decreased efficiency from Vo2 to adenosine triphosphate in rat hearts [20]. These authors showed that the slope of the Vo2–PVA relation significantly increased [20]. In our present study, however, the slope of the Vo2–PVA relation had no significant difference among the three groups. Therefore, we speculate that all three solutions preserved mitochondrial oxidative phosphorylation.

The three solutions we used had considerably different components (Table 1). Although we recognize the importance of analyzing how each component influences the preservation of cardiac mechanoenergetics, it is difficult to examine the roles of all the individual components and their interactions. However, we speculate that radical scavengers included in Celsior, such as histidine, glutamate, and glutathione, may play an important role for better preservation. For example, histidine scavenges hydroxyl radical caused by ischemia–reperfusion injury that activates the ryanodine receptor on the SR, resulting in increasing calcium release. Therefore, histidine may decrease futile calcium cycling by the SR and contribute to keep oxygen cost of Emax lower in Celsior preservation than with STH despite their similar extracellular compositions of electrolytes.

The purpose of the present study was to compare integrative cardioprotective effects of each solution as a whole in the acute phase, but not to elucidate the mechanism of each individual factor in the respective solutions in the chronic phase. Therefore, the better protective effect of Celsior on cardiac mechanoenergetics does not necessarily guarantee better long-term survival. For analyzing cardiac performance after transplantation, our canine cross-circulated heart preparation has some advantages because the donor heart is perfused with normal blood of another dog, which resembles the clinical setting of heart transplantation. This warrants a chronic study after transplantation.

In conclusion, this study has shown a considerably better cardioprotective effect of Celsior than STH and UWS in the acute setting of heart transplantation, although in a canine heart model. The heart preserved with either STH or UWS showed a lower cardiac contractility and a higher oxygen cost of contractility than with Celsior. The results of the present study support the clinical advantage of Celsior in at-risk patients in terms of cardiac mechanoenergetics.


   Acknowledgments
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
References
 
This study was partly supported by Grants-in-Aid for Scientific Research (13558113, 13770350, 13878185, 13878192, 14380405) from the Ministry of Education, Science, Technology, Sports and Culture, and a Research Grant for Cardiovascular Diseases (14A-1) from the Ministry of Health, Labor and Welfare, all from Japan.


   References
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 

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D. F. Stowe, A. K. S. Camara, J. S. Heisner, M. Aldakkak, and D. R. Harder
Ten-hour preservation of guinea pig isolated hearts perfused at low flow with air-saturated Lifor solution at 26{degrees}C: comparison to ViaSpan solution
Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H895 - H901.
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Yu Oshima
Kozo Ishino
Shunji Sano
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