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Ann Thorac Surg 2007;83:1751-1758
© 2007 The Society of Thoracic Surgeons

Original Articles: Cardiovascular

Does Normothermic Normokalemic Simultaneous Antegrade/Retrograde Perfusion Improve Myocardial Oxygenation and Energy Metabolism for Hypertrophied Hearts?

Jian Wang, MDa,b, Hongyu Liu, MD, PhDb, Tomas A. Salerno, MDc, Bo Xiang, DDSa, Gang Li, MD, PhDa,b, Marco Gruwel, PhDa, Michael Jackson, PhDa, Darren Manley, PhDa, Boguslaw Tomanek, PhDa, Roxanne Deslauriers, PhDa, Ganghong Tian, MD, PhDa,*

a Institute for Biodiagnostics, National Research Council, Winnipeg, Manitoba, Canada
b Department of Cardiac Surgery, First Affiliated Hospital, Harbin Medical University, Harbin, China
c Division of Cardiothoracic Surgery, Jackson Memorial Hospital, Miller School of Medicine, University of Miami, Miami, Florida

Accepted for publication January 15, 2007.

Abbreviations and Acronyms ATP = adenosine triphosphate; Hb = hemoglobin; LAD = left anterior descending coronary artery; LV = left ventricle; Mb = myoglobin; MR = magnetic resonance; NIR = near infrared; NNSP = normothermic normokalemic simultaneous antegrade/retrograde perfusion; NNAP = normothermic normokalemic antegrade perfusion; PCr = phosphocreatine; Pi = inorganic phosphate; RV = right ventricle

* Address correspondence to Dr Tian, Institute for Biodiagnostics, 435 Ellice Ave, Winnipeg, Manitoba, Canada R3B 1Y6 (Email: hong.tian{at}nrc-cnrc.gc.ca).


   Abstract
Top
 Abstract
Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
Background: Beating-heart valve surgery appears to be a promising technique for protection of hypertrophied hearts. Normothermic normokalemic simultaneous antegrade/retrograde perfusion (NNSP) may improve myocardial perfusion. However, its effects on myocardial oxygenation and energy metabolism remain unclear. The present study was to determine whether NNSP improved myocardial oxygenation and energy metabolism of hypertrophied hearts relative to normothermic normokalemic antegrade perfusion (NNAP).

Methods: Twelve hypertrophied pig hearts underwent a protocol consisting of three 20-minute perfusion episodes (10 minutes NNAP and 10 minutes NNSP in a random order) with each conducted at a different blood flow in the left anterior descending coronary artery (LAD [100%, 50%, and 20% of its initial control]). Myocardial oxygenation was assessed using near-infrared spectroscopic imaging. Myocardial energy metabolism was monitored using localized phosphorus-31 magnetic resonance spectroscopy.

Results: With 100% LAD flow, both NNAP and NNSP maintained myocardial oxygenation, adenosine triphosphate, phosphocreatine, and inorganic phosphate at normal levels. When LAD flow was reduced to 50% of its control level, NNSP resulted in a small but significant decrease in myocardial oxygenation and phosphocreatine, whereas those measurements did not change significantly during NNAP. With LAD flow further reduced to 20% of its control level, both NNAP and NNSP caused a substantial decrease in myocardial oxygenation, adenosine triphosphate, and phosphocreatine with an increase in inorganic phosphate. However, the changes were significantly greater during NNSP than during NNAP.

Conclusions: Normothermic normokalemic simultaneous antegrade/retrograde perfusion did not improve, but slightly impaired myocardial oxygenation and energy metabolism of beating hypertrophied hearts relative to NNAP. Therefore, NNSP for protection of beating hypertrophied hearts during valve surgery should be used with extra caution.


   Introduction
Top
 Abstract
 Introduction
Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
Cardiac surgery is still the most effective treatment for valve diseases. However, it is not uncommon to encounter postoperative heart dysfunction or heart failure, particularly in patients with severe myocardial hypertrophy [1, 2]. That is because the hypertrophied heart has less tolerance to the detrimental effects of cardioplegia, such as myocardial edema and overload of potassium and chloride. Thus, beating-heart valve surgery has been adopted in several centers to improve preservation of hypertrophied hearts. Clinical experiences showed that the visualization of the operative field during beating-heart valve surgery was comparable to that of cardioplegia-assisted valve surgery [3, 4]. Keeping the heart beating did not compromise surgical precision [3, 4]. Moreover, maintenance of dynamic three-dimensional architecture of a beating heart facilitates intraoperative examination of the aortic and mitral valves [5, 6]. The results from some studies suggested that beating-heart valve surgery improved postoperative recovery of the high-risk patients [3–6].

Sufficient homogeneous myocardial perfusion is obviously a prerequisite for adequate protection of hypertrophied hearts during beating-heart valve surgery. Myocardial hypertrophy is associated with a reduction in capillary and mitochondrial density and an increase in interstitial collagen [7–9]. The pathologic changes reduce oxygen supply to the myocytes and interfere with myocardial energy metabolism, rendering the hypertrophied hearts more vulnerable to an ischemic insult. In addition, myocardial hypertrophy is often associated with coronary stenosis, which impairs myocardial perfusion. Thus, it is critical to develop an effective perfusion technique to improve preservation of hypertrophied hearts during beating-heart valve surgery.

Antegrade perfusion, a physiologic perfusion modality, provides sufficient and homogeneous perfusion to a heart with a normal coronary system. In the presence of critical coronary stenosis and myocardial hypertrophy, antegrade perfusion alone may not be able to deliver enough blood to the entire region of the heart. Because atherosclerosis does not occur in the coronary venous system, retrograde perfusion has been proposed as an alternative perfusion technique [10, 11]. However, because retrograde perfusion is associated with heterogeneous perfusion and poor protection of the right ventricular wall [12], retrograde perfusion alone could not provide sufficient protection to a hypertrophied beating heart, either. The combination of antegrade and retrograde perfusion may therefore be a rational perfusion technique to protect a hypertrophied beating heart. The present study was designed to assess the effects of normothermic normokalemic simultaneous antegrade/retrograde perfusion (NNSP) on myocardial oxygenation and energy metabolism relative to normothermic normokalemic antegrade perfusion (NNAP).

It is clear that not all blood flowing through the coronary system is nutritive (delivering oxygen to the myocytes). Some of antegradely delivered blood bypasses the capillaries and venous plexus, where the exchange process takes place, through arteriovenous anastomosis. Some of retrogradely delivered blood may empty into ventricular chambers through the venous connection to the Thebesian veins without flowing through the capillaries [12, 13]. Thus, measurement of myocardial blood flow alone is not adequate to compare the efficacy of the two perfusion techniques (NNAP and NNSP). Radioactive and color micropheres are often used to study regional blood flow. This technique, however, is not suitable for assessment of simultaneous antegrade/retrograde perfusion because microspheres delivered from one end could be dislodged by the flow from the opposite end. Moreover, not all microspheres trapped in the microvasculature represent nutritive blood flow. Thus, in comparison with microsphere-derived blood flow, myocardial oxygenation and energy metabolism are more reliable indicators of tissue perfusion, and were used in this study to assess the perfusion efficacy of NNSP and NNAP.


   Material and Methods
Top
 Abstract
 Introduction
 Material and Methods
Results
 Comment
 Acknowledgments
 References
 
The animals in this study received humane care in compliance with "Guide to the Care and Use of Experimental Animals" formulated by the Canadian Council on Animal Care. The Animal Care Committee of our institute approved the experimental protocols of this study.

Pig Model of Pressure-Overloaded Left Ventricular Hypertrophy
Twelve 6- to 8-week-old piglets were sedated with an intramuscular injection of diazepam (0.4 mg/kg body weight) and ketamine (20 mg/kg body weight). After the induction of anesthesia, piglets were intubated and mechanically ventilated with gas anesthesia. A left lateral thoracotomy was performed in the third intercostal space. A piece of suture inside a silicone tube was placed to circle the ascending aorta. The ends of the suture were tied to allow for overlap of the tube ends to create a peak systolic pressure gradient of 10 to 20 mm Hg between the left ventricle (LV) and aorta distal to the stenosis. The chests were then closed, and the animals were allowed to recover for 12 weeks while LV hypertrophy developed.

Isolated Pig Heart Preparation
Twelve weeks after aortic banding, the animal chests were reopened under a general anesthesia. A heparinized polyethylene catheter was inserted into the LV chamber to measure the intraventricular pressure. After animal heparinization (3,000 IU heparin into a peripheral vein), the aorta, pulmonary artery, and inferior and superior vena cava were dissected and clamped. A cold (approximately 4°C) cardioplegia was infused into the aortic root to arrest the heart. The heart was quickly excised and immersed in cold saline solution for instrumentation. A catheter with a flow adjuster was inserted into the origin of the left anterior descending artery (LAD) to control its blood flow. The ascending aorta was cannulated for antegrade perfusion of the right coronary artery and left circumflex artery. A 17F retrograde cannula was secured into the coronary sinus for retrograde perfusion. The instrumentation of hearts usually took less than 15 minutes. A short polyethylene tubing was inserted into the LV through the apex to keep the LV empty.

Because pig blood collected from each animal was insufficient to prime our perfusion apparatus, Krebs-Henseleit (K-H) solution was added to the pig blood in 1:1 ratio. The mixture was used to perfuse isolated hearts in this study. Krebs-Henseleit solution is widely accepted as a physiologic perfusion medium and has been used for many years for heart perfusion. The K-H solution contained 118 mmol/L NaCl, 1.2 mmol/L MgSO4, 0.5 mmol/L ethylenediamine-tereaacetic acid, 11 mmol/L glucose, 25 mmol/L NaHCO3, 1.75 mmol/L CaCl2, and 0.625% bovine serum albumin. Potassium concentration of the mixture was adjusted to 3.4 mmol/L to keep the hypertrophied hearts beating throughout the protocol. The hemoglobin concentration in the pig blood and the mixture were 9.7 ± 0.5 and 5.1 ± 0.1 g/dL, respectively. The temperature of the heart was maintained at 36.5° to 37°C.

Experimental Protocol
Twelve hypertrophied hearts were divided into two groups. Hearts in group 1 (n = 6) were used to evaluate the effect of NNAP and NNSP on myocardial oxygenation. Hearts in group 2 (n = 6) were used to assess the effect of the two perfusion techniques on myocardial energy metabolism. All the hypertrophied hearts underwent a protocol consisting of three 20-minute nonpulsatile perfusion episodes (10 minutes NNAP and 10 minutes NNSP in a random order). The three 20-minute perfusion episodes were conducted with LAD flow set at 100%, 50%, and 20% of its initial control, respectively. The two reduced LAD flows were used to simulate coronary stenosis. The LAD flow obtained at a perfusion pressure of 60 mm Hg was considered as initial control (100% LAD flow). The three perfusion periods was interrupted by two 5-minute NNAP with 100% LAD flow to recover ischemic myocardium. During each 10-minute NNSP or NNAP, myocardial oxygenation and energy metabolism were continuously monitored. The NNSP was conducted with perfusion pressure of the aorta and coronary sinus at 60 ± 5 mm Hg and 40 ± 5 mm Hg, respectively. Corresponding total antegrade flow was 221 ± 12 mL/min, and retrograde flow was 45 ± 4 mL/min. The NNAP was performed at an antegrade pressure of 60 ± 5 mm Hg.

Myocardial oxygenation was monitored in group 1 by measuring the ratio of the sum of oxygenated hemoglobin (oxy-Hb) and oxygenated myoglobin (oxy-Mb) versus the sum of total Hb and total Mb using near-infrared (NIR) spectroscopic imaging. The ratio can be expressed mathematically as follows: [oxy-Hb + oxy-Mb]/[total Hb + total Mb]. Levels of myocardial adenosine triphosphate (ATP), phosphocreatine (PCr), and inorganic phosphate (Pi) were monitored using localized 31P magnetic resonance (MR) spectroscopy in group 2.

At the end of experiment, heart weight, LV weight (LV free wall and septum), and LV wall thickness were measured. Corresponding data of normal hearts were obtained from the animals in our other studies and used as control for this study. Experimental protocols are illustrated in Figure 1.


Figure 1
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  		Fig 1. Schematic illustration of experimental protocols. (LAD = left anterior descending coronary artery; NNAP = normothermic normokalemic antegrade perfusion; NNSP = normothermic normokalemic simultaneous antegrade/retrograde perfusion.)

 
Near-Infrared Spectroscopic Imaging
Both hemoglobin and myoglobin have two states, oxy and deoxy ones. Oxy-hemoglobin and oxy-Mb have the same wavelength of light absorbance (760 nm), which is different from that (920 nm) of deoxy-Hb and deoxy-Mb [14]. Thus, the two proteins in either oxy or deoxy state can be readily distinguished and quantified using NIR spectroscopy. The ratio of (oxy-Hb + oxy-Mb) to (total Hb + total Mb) can be then calculated and used as a measurement of myocardial oxygenation.

Myocardial oxygenation of the anterior surface of the heart, including left and right ventricular free walls, was monitored using NIR spectroscopic imaging, which was performed with an infrared-sensitive charge-coupled device (CCD) camera equipped with a liquid crystal tunable filter. Near-infrared spectroscopic images were acquired with a field of view of 12 x 16 cm2, covering the entire anterior surface of a pig heart.

31P Magnetic Resonance Spectroscopy
Myocardial high-energy phosphates (PCr, ATP, and Pi) were measured using localized 31P MR spectroscopy on a 7 Tesla magnet equipped with a Biospec spectrometer (Bruker, Karlsruhe, Germany). The 31P MR spectra were acquired only from the LAD-supported region using a 1.5-cm diameter MR coil.

The observed phosphorus compounds included Pi, PCr, and three peaks of ATP ({alpha}, ß, and {gamma}). The ß peak was used for quantifying ATP.

Data Analysis
Near-infrared spectroscopic images were processed with Matlab (version 5.3; The Mathworks, Natick, Massachusetts). The 31P MR spectra were analyzed using 1D-Winner (Bruker, Karlsruhe, Germany).

Statistical analyses were performed using software Statistica (Statsoft, Tulsa, Oklahoma). All numerical results were expressed as the mean ± SD of the mean. Paired Student’s t test was used to compare myocardial oxygenation level and levels of myocardial PCr, Pi, and ATP between NNAP and NNSP at any given LAD blood flow. One-way analysis of variance was used to compare myocardial oxygenation and levels of myocardial PCr, Pi, and ATP among different LAD blood flow within NNSP or NNAP. A value of p less than 0.05 indicates significant difference.


   Results
Top
 Abstract
 Introduction
 Material and Methods
 Results
Comment
 Acknowledgments
 References
 
Myocardial Hypertrophy
Left ventricular end-diastolic pressure was significantly (p = 0.0001) higher in the hypertrophied hearts (13.1 ± 3.4 mm Hg) than in the normal hearts (5.1 ± 1.3 mm Hg). The ratio of LV weight to heart weight was also significantly (p = 0.0008) higher in hypertrophied hearts (0.53 ± 0.04) than in the normal hearts (0.46 ± 0.03). The index of heart weight to body weight was also significantly (p = 0.006) higher in the hypertrophied hearts (6.59 ± 0.79) than in the normal hearts (5.93 ± 0.57). The LV wall of the hypertrophied hearts was significantly (p = 0.0007) thicker (2.37 ± 0.15 cm) than that of the normal hearts (2.02 ± 0.22 cm). The results indicate that 12-week aortic banding resulted in significant LV hypertrophy.

Ability of NNAP and NNSP to Sustain Myocardial Oxygenation
Representative myocardial oxygenation images obtained from a hypertrophied pig heart during NNAP and NNSP are shown in Figure 2. The green represents a well-oxygenated region with myocardial oxygenation above 0.9, whereas the blue represents a less-oxygenated region with myocardial oxygenation approximately 0.75. As blood flow in the LAD decreased during both NNAP and NNSP, the blue area in the LAD-supported region progressively enlarged. More importantly, the blue area of the LV anterior wall was significantly larger during NNSP than during NNAP at the same LAD flow. Myocardial oxygenation levels in the LAD region during NNAP and NNSP are shown in Figure 3. It is clear that NNSP resulted in a small but significant decrease in myocardial oxygenation relative to NNAP when LAD flow was at 50% and 20% of its initial control. Although the difference did not reach statistical significance, myocardial oxygenation was lower during NNSP than during NNAP with 100% LAD flow. Moreover, reduction in LAD flow from 100% to 50% of its initial control did not result in a significant decrease in myocardial oxygenation during NNAP, but did during NNSP. The results demonstrated that NNSP had less ability to sustain myocardial oxygenation for hypertrophied beating hearts in comparison with NNAP.


Figure 2
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  		Fig 2. The left panel shows representative myocardial oxygenation (MO) images with differential left anterior descending artery (LAD) flows during normothermic normokalemic antegrade perfusion (NNAP) and normothermic normokalemic simultaneous antegrade/retrograde perfusion (NNSP). The right panel displays the orientation of hearts receiving myocardial oxygenation examination. The ratio of oxy-(hemoglobin + myoglobin) to total-(hemoglobin + myoglobin) was monitored and used as the myocardial oxygenation determinant. Green and blue areas represent regions of myocardium with high and low myocardial oxygenation, respectively. Note that the blue area was larger during NNSP than during NNAP, especially with 50% and 20% LAD blood flow.

 

Figure 3
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  		Fig 3. Myocardial oxygenation (MO) measured from the myocardium supported by the left anterior descending artery (LAD) during normothermic normokalemic simultaneous antegrade/retrograde perfusion (NNSP [gray bars]) and normothermic normokalemic antegrade perfusion (NNAP [black bars]). Myocardial oxygenation measurements were lower during NNSP than during NNAP with varying LAD flow. Reduction in LAD flow resulted in a significantly larger decline in myocardial oxygenation value during NNSP than during NNAP. (Hb = hemoglobin; Mb = myoglobin.)

 
Figure 4 shows myocardial oxygenation levels measured from the right ventricular (RV) free wall. It is clear that NNSP and reduction in LAD flow did not significantly change myocardial oxygenation of the RV.


Figure 4
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  		Fig 4. Myocardial oxygenation (MO) measured from the right ventricle (RV) free wall. There was no significant difference in myocardial oxygenation of RV between normothermic normokalemic simultaneous antegrade/retrograde perfusion (NNSP [gray bars]) and normothermic normokalemic antegrade perfusion (NNAP [black bars]), suggesting that NNSP did not affect myocardial perfusion of the RV. (Hb = hemoglobin; LAD = left anterior descending artery; Mb = myoglobin.)

 
Ability of NNAP and NNSP to Sustain Myocardial Energy Metabolism
Representative 31P spectra acquired from the LAD region of a beating hypertrophied heart during NNAP and NNSP are shown in Figure 5. Average levels of myocardial PCr, ATP, and Pi are shown in Figure 6. Both perfusion techniques at 100% LAD flow sustained normal levels of myocardial ATP, PCr, and Pi. The NNAP with 50% LAD flow did not result in any significant changes in the levels of the high-energy metabolites. However, NNSP with 50% LAD flow resulted in a marked reduction in PCr and a corresponding increase in Pi, indicating ischemic metabolic changes. At 20% LAD flow, both NNAP and NNSP caused a substantial decrease in PCr and ATP with a significant increase in Pi. However, the ischemic metabolic changes were significantly more severe during NNSP than during NNAP. The results demonstrated that NNSP was not as effective as NNAP in sustaining myocardial energy metabolism of the beating hypertrophied heart.


Figure 5
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  		Fig 5. Representative 31P magnetic resonance spectra acquired from the myocardium served by the left anterior descending artery (LAD) during normothermic normokalemic antegrade perfusion (NNAP) and normothermic normokalemic simultaneous antegrade/retrograde perfusion (NNSP). The NNAP with 50% LAD blood flow maintained normal myocardial energy metabolism, whereas the NNSP with 50% LAD blood flow resulted in significant ischemic metabolic changes. With 20% LAD blood flow, NNSP caused a more severe metabolic disturbance than did NNAP. (ATP = adenosine triphosphate; PCr = phosphocreatine; Pi = inorganic phosphate; PPM = parts per million.)

 

Figure 6
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  		Fig 6. Averaged levels of the myocardial high-energy phosphates (top) inorganic phosphate (Pi), (middle) phosphocreatine (PCr), and (bottom) adenosine triphosphate (ATP) and measured during normothermic normokalemic antegrade perfusion (NNAP [black bars]) and normothermic normokalemic simultaneous antegrade/retrograde perfusion (NNSP [gray bars]). Decrease in left anterior descending artery (LAD) blood flow resulted in a significantly greater extent of decline in PCr and ATP level with a larger increase in Pi level during NNSP than during NNAP.

 
Correlation Between Myocardial Oxygenation and Energy Metabolism
Figure 7 shows correlations between myocardial oxygenation and levels of Pi, PCr, and ATP. As expected, PCr levels were positively and linearly correlated with myocardial oxygenation. The Pi levels were inversely associated with myocardial oxygenation. Linear correlation was not observed between myocardial oxygenation and ATP levels for the reasons discussed below.


Figure 7
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  		Fig 7. Correlations of myocardial oxygenation (MO) with the levels of (top) myocardial inorganic phosphate (Pi), (middle) phosphocreatine (PCr), and (bottom) adenosine triphosphate (ATP). Note that both PCr and Pi levels displayed linear relationships with myocardial oxygenation level. (Hb = hemoglobin; LAD = left anterior descending artery; Mb = myoglobin.)

 

   Comment
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
Acknowledgments
 References
 
Beating-heart valve surgery might improve postoperative recovery of patients relative to conventional valvular surgery [3–6]. Use of an effective perfusion method is essential for good protection of hypertrophied hearts during beating-heart valve surgery, especially for patients with coronary artery disease. Our previous studies showed that simultaneous antegrade/retrograde cardioplegia could deliver cardioplegia to myocardium distal to the occluded coronary artery through antegrade and retrograde routes [15, 16]. Other investigators also demonstrated that intermittent occlusion of the coronary sinus in vivo led to a reduction of infarct size and improvement of cardiac function [17, 18]. However, no studies have demonstrated that simultaneous antegrade/retrograde perfusion indeed improves myocardial perfusion for hypertrophied beating hearts in comparison with simple antegrade perfusion during beating-heart valve surgery. The present study was therefore to determine whether NNSP was superior to NNAP in terms of myocardial oxygenation and energy metabolism. With 100% LAD flow, both NNSP and NNAP sustain normal myocardial oxygenation and energy metabolism. As LAD flow was reduced from 100% to 50% or 20% of initial control, NNSP displayed a greater extent of depression in myocardial oxygenation and energy metabolism in comparison with NNAP. The results demonstrated that NNSP did not improve but rather decreased myocardial perfusion.

As mentioned above, not all the blood flowing into the coronary arteries is nutritive. The blood that bypasses the capillaries and intramyocardial venous plexus through the arteriovenous anastomoses plays no nutritive role in myocardial oxygenation and myocardial energy metabolism. Only the portion flowing through the capillaries and intramuscular venous plexus delivers oxygen to the myocytes. Under physiologic conditions (antegrade perfusion), the majority of the coronary blood flows though the exchange sites. Coronary capillary flow depends on coronary arterial pressure, intramyocardial pressure, and coronary venous pressure [19]. Elevated coronary venous pressure during NNSP increases venous resistance, reducing flow velocity in the capillaries and forcing some blood diverting from the capillaries and intramyocardial venous plexus into the nonnutritive pathways [20–23]. Thus, nutritive flow decreases and less oxygen is available to the myocytes, which we believe was the situation taking place during NNSP. As a result, levels of myocardial oxygenation and high-energy metabolites were significantly lower during NNSP than during NNAP.

Under physiologic conditions, the coronary sinus drains approximately 55% of coronary arterial blood flow [24]. It collects blood primarily from the LV, anterior portion of the ventricular septum, and both atria. Blood flowing through the RV wall, which accounts for about 35% of total coronary arterial flow, is drained directly into the RV and right atrium through the epicardial veins of the RV [24]. Thus, retrograde perfusion of NNSP through the coronary sinus does not significantly affect venous pressure of RV free wall. Therefore, NNSP did not change myocardial oxygenation of the RV. It is expected that NNSP will not change myocardial energy metabolism of the RV relative to NNAP; unfortunately, we did not measure myocardial energy metabolism of the RV wall because of technical difficulties.

As discussed above, the measurements of myocardial oxygenation in this study contained contributions from both hemoglobin in blood and myoglobin in the myocytes. Myoglobin has an approximately 10 times higher oxygen affinity than hemoglobin [25, 26]. In other words, myoglobin is almost fully saturated under nonischemic and ischemic conditions. That indicates that the changes in myocardial oxygenation were mostly from hemoglobin oxygen saturation percent. As such, the ratios were predominantly dependent on amount of oxygen delivered to the myocardium, which is defined as myocardial oxygenation. In addition, a normal pig heart contains 0.36 mmol/kg myoglobin and 0.45 mmol/kg hemoglobin [26], indicating that approximately 44% of myocardial oxygenation signals were from myoglobin. Myoglobin was fully saturated under our experimental conditions. Thus, myocardial oxygenation measured during NNAP and NNSP appeared relatively high even during ischemic conditions (0.75 ± 0.03 with LAD blood flow at 20% of its control level). Nevertheless, myocardial oxygenation levels were closely correlated with the levels of myocardial PCr and Pi. This further demonstrates that myocardial oxygenation levels were a true measurement of myocardial oxygenation.

As the initial metabolic response to ischemia is a decrease in PCr with a corresponding increase in Pi, the two metabolites showed a linear relationship with myocardial oxygenation levels. Conversely, ATP remains relatively unchanged during early ischemic insult because PCr is used to replenish ATP storage through creatine kinase reaction (PCr + ADP + H+ {leftrightarrow} ATP + creatine) [27, 28]. Thus, level of ATP was not linearly related to myocardial oxygenation.

Myocardial hypertrophy in this study was created by a 12-week supracoronary banding of the ascending aorta. Its pathologic changes might be somewhat different from those of a patient’s hearts. Moreover, the pig hearts were isolated from the animals. Myocardial perfusion and energy metabolism may also be slightly different from those of in situ hearts. In this study, coronary artery stenosis was simulated simply by reduction of LAD blood flow, which is obviously different from that developed during several decades. Therefore, the efficacy of NNSP in sustaining myocardial oxygenation and energy metabolism found in this study might be slightly different from that to be observed in clinic.

In conclusion, NNSP did not improve, but slightly impaired myocardial oxygenation and energy metabolism in comparison with NNAP. Use of this technique to protect beating hypertrophied hearts should be with caution.


   Acknowledgments
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
References
 
This work is supported by National Research Council Canada, Canadian Institutes of Health Research, and Natural Sciences Foundation of Hei-Long-Jiang (D200520).


   References
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 

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