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Ann Thorac Surg 1998;65:115-124
© 1998 The Society of Thoracic Surgeons

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Original Articles: Cardiovascular

Effect of Pressure on Myocardial Function After 6-Hour Preservation With Blood Cardioplegia

Department of Cardiovascular Surgery, Dalhousie University, and The Queen Elizabeth II Health Science Center, Halifax, Nova Scotia, Canada
Department of Anaesthesiology, Dalhousie University, and The Queen Elizabeth II Health Science Center, Halifax, Nova Scotia, Canada
Department of Pharmacology, Dalhousie University, and The Queen Elizabeth II Health Science Center, Halifax, Nova Scotia, Canada

Accepted for publication July 12, 1997.

Dr Sullivan, Division of Cardiovascular Surgery, Department of Surgery, The New Infirmary Hospital, Room 2269, Queen Elizabeth II Health Science Centre, 1796 Summer St, Halifax, NS, Canada B3H 3A7.

	Abstract

Top Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Background. This study examined the return of cardiac function in pig hearts after 6 hours’ preservation by continuous perfusion with blood cardioplegia at two perfusion pressures compared with preservation with crystalloid solutions.

Methods. Isolated pig hearts were randomly divided into five groups (n = 8 per group) according to the following treatments: group 1 = fresh hearts (control); group 2 = hearts arrested with Queen’s cocktail cardioplegia and then immersion in 0°C saline solution (QS group); group 3 = hearts arrested with (5°C) and simple immersion in 0°C University of Wisconsin solution (UW group); and groups 4 and 5 = hearts arrested with blood cardioplegia at 10°C and then continuously perfused at a pressure of 80 cm H₂O or 40 cm H₂O, respectively (groups BC80 and BC40). After preservation for 6 hours, donor hearts were reperfused by a cross-circulation support pig. Thereafter, cardiac function and metabolism were examined every half hour for 2 hours. A three-way mixed general linear model was used to analyze data with repeated measures. Bonferroni test was used to determine differences (p 0.05) between groups.

Results. Only 4 hearts recovered electric activity in the BC80 group (p 0.05 versus other groups). There was poor recovery of left ventricular work in the BC80 group compared with the other groups (p < 0.001). Left ventricular work in the QS and UW groups was also lower than in the control and BC40 groups. Left ventricular work in the BC40 group fully recovered. Maximum elastance did not differ between groups. Compliance was reduced in the QS, BC80, and BC40 groups versus controls after preservation (p < 0.006). Coronary flow decreased and coronary vascular resistance increased in the BC80 group versus the other groups (p 0.001). Coronary flow in the QS, UW, and BC40 groups was lower than in the control group (p < 0.001). The magnitude of lactate release was much higher in the BC80 group than in the other groups (p 0.001).

Conclusions. Continuous perfusion with 10°C blood cardioplegia at 40 cm H₂O pressure for 6 hours provided adequate preservation of systolic function in this model. University of Wisconsin solution provided the best protection of diastolic function.

	Introduction

Top Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
The ideal method for donor heart preservation is unknown. Numerous crystalloid preservative solutions, including University of Wisconsin storage solution (UW) and St. Thomas’ Hospital cardioplegic solution, have been developed to protect donor graft function [1][2][3][4]. One of the problems with crystalloid solutions is that they do not carry oxygen, and hence they are often used with hypothermia to reduce graft oxygen requirements. Profound hypothermia can produce deleterious effects such as edema, direct tissue injury, dysfunction of membrane-bound enzymes, and metabolic abnormalities that may lead to impairment of myocardial function [5][6]. Blood cardioplegia has been shown to effectively protect the myocardium from ischemic damage and has been used successfully during cardiac operations [7][8][9][10][11][12][13][14][15]. Laboratory and clinical studies have shown that blood cardioplegia may have advantages over crystalloid cardioplegia for preservation of function during cardiac operation [7][8][9][10]. These advantages include better oxygen delivery and utilization, warmer temperature [11][12], supply of substrates [9], antioxidant effects [13], buffering potential [14], and oncotic effects [9].

When retrograde coronary sinus perfusion is used to deliver cardioplegic solution [12], a high perfusion pressure has generally been considered to have a damaging effect during continuous cardioplegia. This has resulted in the use of a low perfusion pressure (<40 mm Hg) during clinical cardiac operations [10][16]. However, for antegrade perfusion through the aortic root, the optimal perfusion pressure has not been fully defined. Studies [15][17] using cold blood cardioplegia for organ preservation for transplantation have shown that this type of cardioplegia may have a role in this arena.

The purpose of this study was to determine the effect on preservation of myocardial function of continuous perfusion with blood cardioplegia for 6 hours in a large animal (pig) model and the differential effect, if any, of altering the perfusion pressure compared with a standard preservation technique using crystalloid solutions.

	Material and Methods

Top Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
The study protocol followed the standards formulated by the Canadian Council of Animal Care and was approved by the Dalhousie University Animal Care and Use Committee. Each experiment involved the use of 2 adult pigs. For each experiment, the heart of 1 animal was used as the ex vivo preparation (Fig 1). The second animal provided hemodynamic support by cross-circulation to the donor heart during the ex vivo reperfusion period (Fig 2). Donor hearts were obtained from HDC pigs (white, large) of either sex and weighing between 20 and 30 kg. The support pigs were male and weighed between 50 and 60 kg. All animals received only water beginning on the night before the experiment.

View larger version (26K): [in this window] [in a new window]   Preservation model for donor heart with continuous blood cardioplegia. (P = pressure transducer; T = thermometer.)

View larger version (28K): [in this window] [in a new window]   Pig cross-circulation support model for donor heart reperfusion. (HE = heat exchanger; P = pressure transducer; T = thermometer.)

The donor hearts were removed from the preservation device after 6 hours. The aortic cannula was connected to arterial tubing coming from the support pig’s femoral artery. The heart was reperfused with warm oxygenated blood from the support pig for 30 minutes before any measurements were begun. All blood samples were taken and associated measurements done before functional measurements every 30 minutes for 2 hours. If the donor heart failed to return to spontaneous rhythm after 15 minutes of reperfusion, resuscitation attempts were undertaken.

Cardioplegia and Solutions
The following four cardioplegic solutions were used: (1) 0.9% normal saline solution (Baxter, Canada); (2) Queen’s cocktail (NaHCO₃, 25 mmol/L; KCl, 20 mmol/L; heparin, 2,000 IU; insulin, 4 IU; hydrocortisone, 40 mg, in Ringer’s solution, 800 mL; dextran 40 10% in dextrose 10%, 180 mL); (3) Belzer cold storage solution (Na⁺, 20.0 mmol/L; K⁺, 140.0 mmol/L; Mg²⁺, 5 mmol/L; H₂PO₄, 25 mmol/L; SO₄, 5 mmol/L; lactobionate, 100 mmol/L; adenosine 5 mmol/L; allopurinol, 1 mmol/L; Pentastarch, 5 mmol/L; raffinose, 30 mmol/L; glutathione, 3 mmol/L in 1 L (Du Pont Canada); and (4) blood cardiologic solution (KCl, 44 mmol/L; NaHCO₃, 50 mmol/L in Plasmalyte-A, 1 L [Baxter, Canada]; citrate-phosphate-dextrose [CPDA-1; Travenol], 50 mL) mixed with heparinized blood to give a total K⁺ concentration of 19.86 ± 0.88 mmol/L and a hemoglobin level of 5.55 ± 0.28 mg/dL. During the 6-hour preservation period, a blood gas analysis was done and serum electrolyte concentrations were measured to monitor the stability of the blood cardioplegic solution at 30 minutes and 330 minutes of preservation.

Donor Operative Procedure and Preparation
Donor pigs were anesthetized with intramuscularly administered ketamine hydrochloride (20 mg/kg), and anesthesia was maintained with halothane (1.5% to 2.5% in oxygen). After intubation, ventilation was maintained with a volume-limited ventilator (anesthesia ventilator AV500; Penlon, Bear Medical System Inc, Riverside, CA). Body temperature was maintained at 37°C by a recirculating water blanket (K-THERMIA; Baxter). The electrocardiogram was continuously monitored. An arterial catheter was inserted into a femoral artery for continuous monitoring of systemic blood pressure. An 18-gauge catheter was inserted into the pig’s ear vein for fluid and drug administration. The mediastinum was exposed through a median sternotomy. The pulmonary artery, aortic arch, innominate artery, left subclavian artery, and venae cavae were isolated and surrounded by 0 silk sutures. The animal was then systemically heparinized (400 U/kg intravenously).

In group 1 (controls), excised hearts were directly connected to the support circuit and then reperfused for 2 hours. Measurements were taken every 30 minutes during this period. In group 2 (QS), hearts were arrested with Queen’s cocktail through an 18-gauge catheter inserted into the aortic root, excised, and then stored in cold saline solution for 6 hours. In group 3 (UW), the procedure was the same as for group 2, except hearts were arrested with and preserved in UW solution.

For groups 4 and 5 (BC80 and BC40, respectively), a specially designed circuit was employed. The circuit consisted of a bubble oxygenator combined with a heat exchanger (H-100; Shiley Inc, Irvine, CA) and a roller arterial pump using -inch (6.25-mm) Tygon tubing. Cannulas were inserted into the right atrium and the aorta through the proximal innominate artery, the distal end of which was clamped and tied off with a suture. The cannulas were connected separately to arterial and venous tubing in a manner that permitted continuous perfusion during the preservation stage (see Fig 1). Approximately half of the animal’s blood was slowly returned to the oxygenator through the venous line with simultaneous infusion of lactated Ringer’s solution to maintain a mean arterial pressure of 50 mm Hg before arrest of the heart through the aortic cannula. After this procedure, blood cardioplegia (10°C) was infused into the aorta. To accomplish arrest, in rapid sequential order, the arteries and venae cavae were tied so as to empty the heart, the aortic arch was cross-clamped distal to the innominate artery, and blood cardioplegia was infused under a pressure of 80 cm H₂O (BC80 group) or 40 cm H₂O (BC40 group) and a total volume of up to 25 mL/kg or until the heart was fully arrested, as demonstrated by visual inspection, palpation, and lack of electric activity on the electrocardiographic monitor. Cardioplegic solution was vented through a venotomy in the proximal superior vena cava and right pulmonary vein to decompress the left ventricle. All blood cardioplegia was returned to the cardiotomy reservoir for later continuous perfusion. The heart was harvested and suspended in a plastic container. The donor hearts were then continuously perfused with the same blood cardioplegic solution and pressure at 10°C for 6 hours. Myocardial temperature was maintained at 14.2° ± 1.0°C.

For all hearts, a pulmonary artery catheter connected to transducers was inserted into the aorta by way of the left subclavian artery to continuously monitor perfusion pressure and temperature. The left atrium was opened and the mitral valve, removed. A custom-made latex balloon with a plastic annulus was sutured to the mitral annulus. The balloon in the left ventricular chamber permitted measurement of left ventricular pressure at a specified volume level during analysis. The balloon was connected to a transducer through a three-way stopcock, and warm (37°C) 0.9% saline solution was injected to fill the balloon to the desired volume. To eliminate dead volume in the balloon, warm saline solution was slowly injected into the balloon to evacuate air until pressure was 5 mm Hg higher than baseline, at which point the stopcock was opened to air to allow the transducer to be balanced and calibrated at 0 mm Hg. At the end point of preservation, the heart was moved to the cross-circulated ex vivo heart support preparation.

Support Animal and Circuit Preparation
Support pigs were anesthetized using intramuscularly administered ketamine (20 mg/kg), and anesthesia was maintained with halothane (1.5% to 2.5% in oxygen). After intubation, ventilation was maintained using a volume-limited ventilator. Body temperature was maintained at 37°C by a recirculating water blanket (K-THERMIA). The electrocardiogram was continuously monitored. A 16-gauge catheter was inserted into the right femoral artery for continuous monitoring of systemic blood pressure. Two 18-gauge venous catheters were inserted into the ear veins for fluid and drug administration. The pig was heparinized (400 U/kg intravenously), and the activated clotting time was monitored before heparinization and every half hour thereafter. Additional heparin was added whenever the activated clotting time was less then 600 seconds to maintain an appropriate level of anticoagulation during the reperfusion period. The support pig’s electrocardiogram, arterial blood pressure, and temperature were monitored throughout the experiment.

The femoral vessels were isolated through a groin incision and surrounded by sutures. A 14F arterial cannula for the femoral artery and an 18F venous cannula for the femoral vein were inserted and then connected to the tubing of the support pig for cross-circulation. A double-head linear roller pump (Masterflex; Cole-parmer, Chicago, IL) was used to maintain the same constant arterial and venous blood flow. The circuit consisted of a heat exchanger/bubble trap on the arterial side. The mean perfusion pressure was controlled at 80 mm Hg through flow adjustment for all groups (see Fig 2). The total circuit volume approximated 500 mL. Plasmalyte-A solution was the prime. Hemodynamic stability was maintained by blood and fluids. Calcium chloride was used as an inotropic agent to support the donor heart if needed. It was necessary in all hearts (3.5 to 7.0 mmol) that recovered in the BC80 group but not in hearts in the other groups. Similar donor and support models have been reported [18]. During the preservation period, perfusion flow, pressure, and blood gases were monitored.

Analysis of Left Ventricular Function and Pressure–Volume Relationship
Left ventricular end-systolic and end-diastolic pressures were recorded through the left ventricular balloon. In donor hearts, analysis of left ventricular performance was derived from the measured left ventricular end-systolic pressure and left ventricular end-diastolic pressure data. The volume in the balloon was increased using warm saline solution in 5-mL increments to a maximum volume of 45 mL. A linear regression analysis of end-systolic pressure on volume was performed to estimate the left ventricular end-systolic pressure–volume relationship, and the slope of the regression was expressed as maximum elastance of the left ventricle (Emax). To estimate left ventricular work (LVW), we calculated cumulative areas under the systolic pressure/volume curve (SWA) and diastolic pressure/volume curve (DWA) and inserted them into the formula for LVW: LVW (mm Hg/mL) = SWA - DWA.

Diastolic compliance (1/slope) of the left ventricle was derived from the linear regression analysis of end-diastolic pressure on volume, ie, end-diastolic pressure–volume relationship. Coronary flow (milliliters per minute) was measured by counting the number of revolutions of the roller pump and multiplying by the volume (milliliters) of solution displaced per revolution and then standardized by heart weight. Coronary vascular resistance (CVR) was standardized by heart weight and derived from coronary flow (COF) and mean blood pressure (MAP) with the formula:

Myocardial Energetics and Metabolism
All blood samples were collected under the same conditions, ie, no preload was present (volume in the balloon = 0 mm Hg), and afterload was 80 mm Hg. Blood samples were collected and stored in ice, and measurements for blood gas analysis and lactate concentration were completed within 30 minutes. Arterial and coronary sinus oxygen tension (PO₂), (millimeters of mercury) oxygen saturation of hemoglobin (SO₂) (volume/100 mL), carbon dioxide tension (PCO₂) (millimeters of mercury), pH (units), and hemoglobin (Hgb) (grams per liter) were measured by a CIBA-Corning 278 blood gas analyzer. Myocardial oxygen consumption (MVO₂) per cardiac cycle was calculated as

where CaO₂ and CvO₂ denote arterial and venous oxygen content, respectively.

Lactate concentration (micromoles per liter) in arterial (CaLac) and venous plasma (CvLac) was measured. Myocardial lactate extraction (MVlac) was determined by the formula

Myocardial Tissue Water Content
At the end of the reperfusion period, a piece of myocardial tissue (200 to 400 mg) was taken from the left ventricle and placed in an oven at 110°C until dry to measure tissue water content. Tissue water content was calculated from the formula

Data Analysis
Linear regression analysis was used to derive values for pressure–volume relationships [19]. When missing observations might have caused the data matrix to be unbalanced, a three-way mixed general linear model with subject (pig) nested in the treatment (group) factor, introduced by Milliken and Johnson [20], was used for data with repeated measurements to compare overall differences between groups. Expected mean square and type III sum of square were estimated from the SAS statistics program (SAS V6.09; SAS Institute Inc, Cary, NC), and further, means of square were adjusted using the calculation equation for unbalanced data recommended by Milliken and Johnson [20]. If an overall difference was determined to be significant (p 0.05), a Bonferroni test was used to determine significance for multiple comparisons. A ² test was used for categoric data. Significance was assumed if the value of p was 0.05 or less. Values are given as the mean ± the standard error of the mean where appropriate.

	Results

Top Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
All donor hearts in the control, QS, UW, and BC40 groups had return of spontaneous electric activity after 6 hours’ storage, and cardiac function could be examined throughout the reperfusion period. Only 4 of 8 hearts in the BC80 group recovered electric activity (p 0.05).

Left Ventricular Function
Left ventricular work calculated from the area under the systolic and diastolic pressure/volume curves is shown in Fig 3. There was poor recovery of LVW in hearts stored in BC80 compared with the control, QS, UW, and BC40 groups (p < 0.001, p < 0.001, p < 0.026, and p < 0.001, respectively). Recovery of LVW in the QS and UW groups was also lower than in the control and BC40 groups (p < 0.001). No significant difference was found between the controls and the BC40 group. Examination of the left ventricular systolic pressure–volume relationship data determined that Emax did not significantly differ between groups during reperfusion (Table 1). Examination of the compliance data, however, revealed a reduction in diastolic compliance in the QS, BC80, and BC40 groups versus the control and UW groups (p 0.006 to 0.001) throughout the reperfusion period. The left ventricular end-diastolic pressure–end-diastolic volume multiple linear regression analysis indicated a significantly increased left ventricular end-diastolic pressure (increased slope) during preservation in the BC80 group (Fig 4). Although the slope in the BC40 group was much better than that in the BC80 group, it was still higher than that in the control and UW groups.

View larger version (41K): [in this window] [in a new window]   Left ventricular (LV) work for experimental groups during reperfusion after 6 hours’ preservation. Group 1 = controls; group 2 = hearts arrested with cold Queen’s cocktail; group 3 = hearts arrested with cold University of Wisconsin solution; and groups 4 and 5 = hearts arrested with cold blood cardioplegia and then continuously perfused at a pressure of 80 cm H2O or 40 cm H2O, respectively, for 6 hours. * = p < 0.001 versus groups 1 and 5; ** = p < 0.026 versus all other groups.)

View larger version (33K): [in this window] [in a new window]   Left ventricular end-diastolic pressure–left ventricular end-diastolic volume relationship at varying intervals of reperfusion. Symbols represent the means at each end-diastolic volume level for every individual treatment group. The solid line demonstrates linear regression, and the dotted line shows 95% confidence interval. (A) Thirty minutes of reperfusion. The slope of the BC80 group differed from slopes of all other groups (p < 0.001). The BC40 slope was higher than slopes of control (p < 0.023) and UW groups (p < 0.001), significantly lower than that of BC80 group (p < 0.001), and not different from that of QS group. (B) Sixty minutes of reperfusion. The slope of the BC80 group is significantly higher than slopes of the control and UW groups (p < 0.001 and p < 0.011, respectively). The BC40 slope is significantly different from that of the UW group (p < 0.001). (C) Ninety minutes of reperfusion. The slope of the BC80 group is the highest (p < 0.001). (BC40 versus UW, p = 0.041.) (D) One hundred twenty minutes of reperfusion. The BC80 slope is higher than slopes of controls, QS group, UW group, or BC40 group (p = 0.001, p = 0.004, p = 0.001, and p = 0.02, respectively). The slope of the BC40 group differs from slopes of control (p = 0.033) and UW groups (p = 0.046). (BC80 and BC40 = hearts arrested with cold blood cardioplegia and then continuously perfused at pressures of 80 cm H2O and 40 cm H2O, respectively; QS = hearts arrested with cold Queen’s cocktail followed by 6 hours’ cold storage; UW = hearts arrested with cold University of Wisconsin solution followed by 6 hours’ cold storage;

View larger version (35K): [in this window] [in a new window]   Coronary blood flow (COF) for all groups at 30, 60, 90, and 120 minutes of reperfusion. (*, ** = p < 0.001 versus other groups; see Fig 4 legend for groups.)

View larger version (28K): [in this window] [in a new window]   Coronary vascular resistance (CVR) for all groups at 30, 60, 90, and 120 minutes of reperfusion. (* = p < 0.001 versus other groups; see Fig 4 legend for groups.)

Blood Gas Analysis and Electrolytes of Blood Cardioplegia
Results of blood gas analysis at 30 minutes and 330 minutes during the preservation period are shown in Table 4.

	Comment

Top Abstract Introduction Material and Methods Results Comment Acknowledgments References

The slope of the left ventricular end-systolic pressure–volume relationship or maximum elastance (Emax) has been introduced and used as an index of myocardial contractility [18][19]. It is generally considered to be a better measurement of contractility than other indices such as cardiac output, ejection fraction, or rate of rise of left ventricular pressure because of the linear relationship with ventricular volume and its independence from preload and afterload conditions. In this study, the Emax data did not differ among the five groups despite marked differences in cardiac functional recovery (LVW). Calculated Emax values did not reflect ventricular contractile function, and Emax values were affected by left ventricular end-diastolic pressure–volume relationship changes. In some cases, diastolic compliance decreased significantly, reflecting increased wall stiffness and diastolic dysfunction, whereas high end-systolic pressures were achieved after increased volume even though ventricular performance was poor. Our results demonstrating that Emax is not a sensitive measure of ventricular contractile function in the study of myocardial protection techniques are similar to those reported by other investigators [18][19][21].

The total energy output of the left ventricle is reflected by the area between the end-systolic pressure–volume relationship and the end-diastolic pressure–volume relationship. This area represents external stroke work and potential energy [19]. Therefore, ventricular performance is determined by a reduction or an augmentation in the slope of the end-systolic pressure–volume relationship, or a decrease or an increase in the slope of the end-diastolic pressure–volume relationship, or both. Measurement of this area has been used to investigate ventricular performance after ischemia-reperfusion injury [22] and may be a more sensitive measure of myocardial function or injury versus preservation than Emax alone. In this study Emax did not demonstrate differences between groups, whereas the end-diastolic pressure–volume relationship showed significantly increased slopes on multiple linear regression analyses (see Fig 4) and significantly decreased compliance in the BC80 group. This finding indicated that diastolic dysfunction of the hearts preserved with BC80 was the preponderant functional abnormality.

Theoretically, a continuous blood cardioplegic solution containing a high potassium concentration can not only arrest the heart but also supply oxygen, which can be used to maintain aerobic metabolism during the arrest period. Therefore, blood cardioplegic solutions should, at least in theory, provide better myocardial protection than crystalloid cardioplegic solutions. Our results suggest that in the isolated pig heart model, continuous perfusion with simple cold (10°C) blood cardioplegia at 80 cm H₂O pressure for 6 hours did not provide adequate myocardial preservation, whereas a lower perfusion pressure at 40 cm H₂O dramatically changed the recovery of myocardial function after prolonged preservation.

There are conflicting reports concerning the utility of blood cardioplegia for prolonged storage periods. Cold blood cardioplegic solutions were demonstrated to provide better myocardial protection than crystalloid cardioplegic solutions in earlier experiments [17][23]. Blood cardioplegia (4°C) has been used to protect myocardial function after up to 4 hours of aortic clamp time in normal hearts, provided sufficient doses were administered to counteract washout of cardioplegic solution by noncoronary collateral flow [23]. In a study [24] with intermittent multidose blood cardioplegia (27°C) for up to 6 hours in an in situ canine model, blood cardioplegia provided superior protection of myocardial morphology. A 1993 study [17] using cold blood cardioplegia (8°C) and 24 hours’ cold storage (4°C) demonstrated that myocardial ultrastructural protection by cold blood cardioplegia was poorer than that of UW solution but better than that of St. Thomas’ solution, and protection of pneumonocytes by blood cardioplegic solution was much better than that achieved with UW or Euro-Collins solution. It may be that differences among studies can be explained by differences in perfusion pressures used to initiate and maintain preservation. In this study, systolic function (LVW) after 6 hours of continuous perfusion with blood cardioplegia at 40 cm H₂O was very well preserved and was significantly better than in the other experimental groups. It was the only group with full recovery of myocardial function (101.9% recovery of LVW versus controls [see Fig 3]). The QS and UW treatment groups had acceptable but inferior recovery of myocardial function (75.8% and 66.5% recovery of LVW, respectively, versus controls). The BC80 group had the worst recovery of LVW (22.8% recovery versus controls).

Maintenance of normal mechanical function of the myocardium relies on the high efficiency of aerobic metabolism. In the normal myocardium, the production of adenosine triphosphate is strictly coupled to myocardial oxygen consumption. Therefore, the level of ventricular functional recovery depends mainly on the integrity of the energy production apparatus, as 80% of oxygen utilization is devoted to the contractile activities of the heart. In a canine model, Ko and co-authors [18] showed that the level of oxygen utilization was well maintained throughout an extended period of hypothermic ischemia (6 hours) when preserved with UW solution. In the present study, myocardial oxygen consumption (mL · min^-1 · beat^-1 · 100 g Wt^-1) in all experimental groups was not significantly different from that in the control group over the reperfusion period.

As a measure of substrate utilization by the myocardium and an index of the degree of myocardial ischemia after a prolonged preservation time, lactate extraction was measured. Negative values reflect lactate released rather than used by ischemic myocardium. As seen in the results for lactate extraction (see Table 3), a large amount of lactate was released in the BC80 group during the reperfusion period, and all hearts preserved with BC80 were severely ischemic. With a lower perfusion pressure (40 cm H₂O), lactate release from the myocardium was significantly decreased compared with the BC80 group, and levels gradually recovered after reperfusion.

All experimental groups showed decreased coronary flow after reperfusion compared with the controls, but a significant increase in coronary vascular resistance was found only in the BC80 group (p < 0.001 versus all other groups). This increased resistance cannot be explained by the phenomenon of extravascular compression caused by intracellular and interstitial myocardial edema, as there was no significant difference in extravascular water between groups. It can be speculated that perfusion pressure exerts a considerable influence on the magnitude of the increase in coronary vascular resistance during prolonged reperfusion. A perfusion pressure of less than 40 mm Hg during retrograde perfusion through the coronary sinus has been suggested as preferable by some investigators [10][16]. The optimal perfusion pressure when using the aortic root for delivery of antegrade blood cardioplegia has not been adequately defined [17][18]. Chambers and colleagues [25] reported the best perfusion pressure for a continuous low-flow hypothermic cardioplegic solution (St. Thomas’ solution) to be 10 to 12 cm H₂O in an isolated rat heart model for 8 hours.

Blood cardioplegia consists of a number of components besides red blood cells, and whole blood is not a homogeneous fluid. When whole blood is perfused through the vascular system of an animal’s extremity, no flow is produced until the pressure gradient from arteries to veins reaches 10 mm Hg [26]. Higher perfusion pressures may be necessary to maintain flow, but they can also lead to injury to the coronary artery endothelium with a subsequent increase in coronary resistance. On the other hand, a lower perfusion pressure may cause more sludging because of a reduced flow in the coronary system, especially under hypothermic conditions. In this study, perfusion pressures of 80 cm H₂O and 40 cm H₂O in the aortic root were used, and we measured an increase in coronary artery resistance in the BC80 group.

Our results suggest that although the optimal antegrade perfusion pressure needs to be further defined, a perfusion pressure higher than 40 cm H₂O might be harmful for prolonged preservation of cardiac function. Further, our results imply that high perfusion pressures should be of concern during routine cardiac surgical procedures, especially in those with long perfusion times. Our hypothesis—that higher perfusion pressures cause direct damage to the endothelium of the coronary artery, thus leading to our observations of increased coronary vascular resistance and ischemia—requires further investigation.

In conclusion, continuous perfusion with 10°C blood cardioplegia at 40 cm H₂O pressure for 6 hours provided adequate preservation of myocardial systolic function compared with QS and UW solutions in the isolated pig heart model.

	Acknowledgments

Top Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Supported by Canadian Heart and Stroke Foundation of Nova Scotia and Division of Cardiovascular Surgery, Department of Surgery, Dalhousie University.

	References

Top Abstract Introduction Material and Methods Results Comment Acknowledgments References

 

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