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Ann Thorac Surg 1996;62:143-150
© 1996 The Society of Thoracic Surgeons

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Original Articles: Cardiovascular

Cardiac Surgical Conditions Induced by ß-Blockade: Effect on Myocardial Fluid Balance

Center for Microvascular and Lymphatic Studies, Department of Anesthesiology, The University of Texas–Houston Medical School, Houston, Texas

Accepted for publication March 3, 1996.

	Abstract

Top Footnotes Abstract Introduction Material and Methods Left Ventricular Function... Myocardial Fluid Balance... Cardiopulmonary Bypass Biventricular Assist Device Maintenance of Minimal... Experimental Protocol Statistical Analysis Results Comment Minimal Myocardial Contraction... Minimal Myocardial Contraction... Limitations of the Study Conclusion Acknowledgments References

 
Background. Both crystalloid and blood cardioplegia result in cardiac dysfunction associated with myocardial edema. This edema is partially due to the lack of myocardial contraction during cardioplegia, which stops myocardial lymph flow. As an alternative, acceptable surgical conditions have been created in patients undergoing coronary artery bypass operations with esmolol-induced minimal myocardial contraction. We hypothezised that minimal myocardial contraction during circulatory support using either standard cardiopulmonary bypass (CPB) or a biventricular assist device would prevent myocardial edema by maintaining cardiac lymphatic function and thus prevent cardiac dysfunction.

Methods. We placed 6 dogs on CPB and 6 dogs on a biventricular assist device and serially measured myocardial lymph flow rate and myocardial water content in both groups and preload recruitable stroke work only in the CPB dogs. In all dogs we minimized heart rate with esmolol for 1 hour during total circulatory support.

Results. Although myocardial lymph flow remained at baseline level during CPB and increased during biventricular assistance, myocardial water accumulation still occurred during circulatory support. However, as edema resolved rapidly after separation from circulatory support, myocardial water content was only slightly increased after CPB and biventricular assistance, and preload recruitable stroke work was normal.

Conclusions. Our data suggest that minimal myocardial contraction during both CPB and biventricular assistance supports myocardial lymphatic function, resulting in minimal myocardial edema formation associated with normal left ventricular performance after circulatory support. The concept of minimal myocardial contraction may be a useful alternative for myocardial protection, especially in high-risk patients with compromised left ventricular function.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Left Ventricular Function... Myocardial Fluid Balance... Cardiopulmonary Bypass Biventricular Assist Device Maintenance of Minimal... Experimental Protocol Statistical Analysis Results Comment Minimal Myocardial Contraction... Minimal Myocardial Contraction... Limitations of the Study Conclusion Acknowledgments References

 
The objective for cardioplegia-induced cardiac arrest is to protect the myocardium while providing a flaccid heart, which facilitates surgical treatment. Using conventional hypothermic crystalloid cardioplegia, the myocardium is primarily protected by hypothermia, which prolongs the myocytes' ischemia tolerance. However, several studies have demonstrated that hypothermic crystalloid cardioplegia is still associated with myocardial ischemia and interstitial myocardial edema, both of which impair cardiac function [1–6]. Thus, conventional crystalloid cardioplegia does not completely protect the myocardium.

In contrast to crystalloid cardioplegia, use of blood cardioplegia can avoid myocardial ischemia during cardiac operations [7–9]. However, both intermittent hypothermic blood cardioplegia and continuous normothermic blood cardioplegia have been shown to result in impaired left ventricular (LV) systolic performance [10, 11], decreased LV compliance [9], and prolonged contractility recovery [12] in patients and animal models. We have previously demonstrated that despite ischemia avoidance, normothermic continuous antegrade blood cardioplegia resulted in significant cardiac dysfunction that was directly related to myocardial edema [13].

Cardioplegia-induced myocardial edema is due to an imbalance between fluid flux out of the myocardial microvasculature and its subsequent removal via myocardial lymphatics [6, 13, 14]. Thus, edema could be due to increased fluid filtration rate, decreased myocardial lymph flow rate, or both. As we have shown that cardiac paralysis causes myocardial lymph flow to cease, decreased interstitial fluid removal is at least partially responsible for myocardial edema formation [6, 13]. These data suggest that both ischemic and nonischemic cardioplegia techniques predispose to myocardial edema by depressing myocardial lymphatic function.

Recently, an alternative to cardioplegic arrest for myocardial protection has been applied in high-risk patients undergoing coronary artery bypass operations [15]. Avoiding both aortic cross-clamping and cardioplegia administration, Sweeney and Frazier [15] provided surgical conditions during circulatory support by suppressing myocardial chronotropy and inotropy with high doses of the ultra-short-acting ß-blocker esmolol. In contrast to cardioplegic arrest, minimal myocardial contraction (MMC) is maintained. Using this technique, the myocardium is protected against ischemia by reduced oxygen demands and antegrade coronary blood flow. In addition, maintenance of MMC could also protect the myocardium against edema by avoiding myocardial lymph flow cessation.

We hypothesized that maintaining MMC while avoiding myocardial ischemia would prevent myocardial edema by maintaining cardiac lymph drainage, and thus prevent myocardial dysfunction after circulatory support. To investigate if oxygenator use contributes to myocardial edema formation during circulatory support, we compared the impact of two clinically established systems on myocardial water content and myocardial lymph flow. We subjected animals either to conventional cardiopulmonary bypass (CPB) using roller pumps and membrane oxygenator, or to a biventricular assist device (BiVAD) using vortex pumps. In contrast to CPB, the lungs are perfused and ventilated with BiVAD use and no oxygenator is required.

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Left Ventricular Function... Myocardial Fluid Balance... Cardiopulmonary Bypass Biventricular Assist Device Maintenance of Minimal... Experimental Protocol Statistical Analysis Results Comment Minimal Myocardial Contraction... Minimal Myocardial Contraction... Limitations of the Study Conclusion Acknowledgments References

 
Animal Preparation
All procedures were approved by the University of Texas Animal Welfare Committee and were consistent with the National Institutes of Health "Guide for the Care and Use of Laboratory Animals" (NIH publication 85-23, revised 1985). We used 6 conditioned mongrel dogs of either sex (25.8 ± 2.0 kg) for the CPB experiments and 6 dogs (27.0 ± 5.3 kg) for the BiVAD experiments. The dogs were anesthetized with intravenous administration of 25 mg/kg thiopental sodium (Pentothal; Abbott Laboratories, North Chicago, IL), intubated and mechanically ventilated with 100% oxygen using a volume-cycled respirator (Siemens-Elema AB, Solna, Sweden). We maintained anesthesia with intravenous infusion of 1% thiopental sodium in Ringer's solution.

Subcutaneous needle electrodes were used to monitor the heart rate. We placed fluid-filled catheters into the left femoral artery and vein for mean arterial pressure monitoring and arterial blood sampling and for fluid administration, respectively. We inserted a 7F Swan-Ganz thermodilution catheter into the pulmonary artery via the left jugular vein for central venous pressure, pulmonary artery pressure, and cardiac output determination. In 11 dogs, a 5F catheter was introduced via the right jugular vein into the coronary sinus for coronary sinus blood sampling. We then exposed the right femoral artery for subsequent CPB or BiVAD cannulation. After median sternotomy, we incised the pericardium and introduced a micromanometer-tipped pressure transducer (Millar Instruments Inc, Houston, TX) into the left ventricular cavity through the apex of the left ventricle. In the 6 CPB dogs, we placed a snare around the inferior vena cava for cardiac preload manipulation. Sonomicrometry crystals (5 MHz; Triton Technology Inc, San Diego, CA) were placed into the LV subendocardium across the septum/free-wall axis of the LV in the CPB dogs.

	Left Ventricular Function Parameters

Top Footnotes Abstract Introduction Material and Methods Left Ventricular Function... Myocardial Fluid Balance... Cardiopulmonary Bypass Biventricular Assist Device Maintenance of Minimal... Experimental Protocol Statistical Analysis Results Comment Minimal Myocardial Contraction... Minimal Myocardial Contraction... Limitations of the Study Conclusion Acknowledgments References

 
Left ventricular pressure was measured with the micromanometer, and LV septum/free-wall diameter was obtained with a sonomicrometer (Triton Technology Inc). These data were recorded at a frequency of 200 Hz during 15 seconds of inferior vena cava occlusion (MacLab; World Precision Instruments Inc, Sarasota, FL). In the CPB experiments we derived the following LV function parameters as previously described [6, 13, 16, 17]: preload recruitable stroke work, time constant of isovolumic relaxation, unstressed diastolic volume, maximum pressure, and end-diastolic pressure. We did not use sonomicrometry in the BiVAD experiments, and thus only determined the time constant of isovolumic relaxation, maximum LV pressure, and LV end-diastolic pressure with the LV micromanometer in these animals.

	Myocardial Fluid Balance Parameters

Top Footnotes Abstract Introduction Material and Methods Left Ventricular Function... Myocardial Fluid Balance... Cardiopulmonary Bypass Biventricular Assist Device Maintenance of Minimal... Experimental Protocol Statistical Analysis Results Comment Minimal Myocardial Contraction... Minimal Myocardial Contraction... Limitations of the Study Conclusion Acknowledgments References

 
We determined myocardial tissue water content using a microgravimetric technique as previously described [13, 18]. We introduced a biopsy forceps (Cordis Corporation, Miami, FL) transapically into the LV and collected endomyocardial samples [13]. The specific density of these myocardial biopsy samples was measured in a linear density gradient consisting of bromobenzene and kerosene [13]. Knowing myocardial specific density, the gram water per gram tissue or myocardial water content (MWC) can be calculated using the following equation [13, 18]: MWC = {1 - [(SG_myo - 1)/(1 - 1/SG_dry)•SG_myo]}•100, where SG_myo and SG_dry are the specific gravities of the myocardial sample and of dry myocardium, respectively. As changes in myocardial density are linearly related to changes in myocardial water content, serial myocardial density determinations allow measurement of myocardial water content changes over time [13]. At the end of the experiment a last myocardial density measurement was performed. We euthanized the dog with intravenous pentothal overdose and saturated potassium chloride, and rapidly excised the heart. Both ventricles were weighed and then dried to a constant weight at 60°C. We calculated SG_dry using the following equation [13, 18]: SG_dry = 1/{1 - [(SG_myo - 1)•W/(D•SG_myo)]}, where W and D are wet and dry weights of both ventricles, respectively. We assumed that SG_dry did not change over the experimental period. We performed all myocardial water content measurements in duplicate.

For myocardial lymph flow rate determination we cannulated the prenodal major left cardiac lymph trunk as previously described [4, 6, 13, 19]. We measured myocardial lymph flow rate (in microliters per minute) using a calibrated pipette held at heart level. The resistance of this lymph cannula system was 4.11 x 10^-3 mm Hg•min•µL^-1 [13].

	Cardiopulmonary Bypass

Top Footnotes Abstract Introduction Material and Methods Left Ventricular Function... Myocardial Fluid Balance... Cardiopulmonary Bypass Biventricular Assist Device Maintenance of Minimal... Experimental Protocol Statistical Analysis Results Comment Minimal Myocardial Contraction... Minimal Myocardial Contraction... Limitations of the Study Conclusion Acknowledgments References

 
After preparation, heparin (250 IU•kg^-1) was given intravenously for systemic anticoagulation. Additional doses of 100 IU•kg^-1 heparin were administered every 60 minutes throughout the experiment. We introduced a 14F arterial perfusion cannula into the prepared right femoral artery. A two-stage (34/38F) venous cannula (model TAC2; DLP Inc, Grand Rapids, MI) was placed into the right atrium/inferior vena cava. The LV was vented with a 12F catheter inserted via the left atrium. Cardiopulmonary bypass was performed using three roller pumps for extracorporeal circulation, LV drainage, and suction, respectively. We primed the extracorporeal circuit and the membrane oxygenator (Monolyth M2; Sorin Biomedical Inc, Irvine, CA) with 800 mL of Ringer's solution and 1,000 IU of heparin. A rectal temperature probe was placed and the body temperature was kept at 37°C using a heat exchanger. We maintained CPB flow between 70 and 90 mL•kg^-1•min^-1 and systemic perfusion pressure greater than 50 mm Hg.

	Biventricular Assist Device

Top Footnotes Abstract Introduction Material and Methods Left Ventricular Function... Myocardial Fluid Balance... Cardiopulmonary Bypass Biventricular Assist Device Maintenance of Minimal... Experimental Protocol Statistical Analysis Results Comment Minimal Myocardial Contraction... Minimal Myocardial Contraction... Limitations of the Study Conclusion Acknowledgments References

 
The BiVAD consisted of two Biomedicus vortex pumps (Medtronic BioMedicus, Eden Prairie, MN) serving as left and right ventricular assist devices, -inch heparin-coated tubing (BioActive Surface, CBAS; Carmeda, Stockholm, Sweden), two flowmeters, and heat exchanger (Fig 1). We administered 150 IU•kg^-1 heparin before cannulation and 75 IU•kg^-1 every 60 minutes throughout the experiment. Inflow into the right ventricular assist device was accomplished by standard right atrial cannulation with a two-stage (34/38F) venous cannula (model TAC2; DLP Inc). Blood was returned from the right ventricular assist device to the main pulmonary artery using a right-angled 20F cannula (model 67320; DLP Inc). Inflow into the LV assist device was achieved by LV apex cannulation [15] with a 28F wire-reinforced cannula (model TF028L-90; Research Medical Inc, Midville, UT), and blood was returned to the dog via the right femoral artery using a 14F cannula (model 26032; Biomedicus, Minneapolis, MN) (see Fig 1). In contrast to cardiopulmonary bypass, the dog's lungs are perfused and ventilated on BiVAD; thus, no oxygenator is required. We primed both the LV assist device and right ventricular assist device circuits with Ringer's lactate (200 mL each). A rectal temperature probe was placed and body temperature was maintained at 37°C on BiVAD using the heat exchanger. We adjusted LV assist device and right ventricular assist device flows in such a manner as to maximally unload both ventricles, and we kept arterial perfusion pressure greater than 50 mm Hg.

View larger version (26K): [in this window] [in a new window]   Fig 1. . The biventricular assist device consisted of two vortex pumps serving as left (LVAD) and right (RVAD) ventricular assist devices, two flowmeters (FM), and a heat exchanger (HE). (FA = femoral artery; LV = left ventricle; PA = pulmonary artery; RA = right atrium; RV = right ventricle.)

	Maintenance of Minimal Myocardial Contraction During Circulatory Support

Top Footnotes Abstract Introduction Material and Methods Left Ventricular Function... Myocardial Fluid Balance... Cardiopulmonary Bypass Biventricular Assist Device Maintenance of Minimal... Experimental Protocol Statistical Analysis Results Comment Minimal Myocardial Contraction... Minimal Myocardial Contraction... Limitations of the Study Conclusion Acknowledgments References

	Experimental Protocol

Top Footnotes Abstract Introduction Material and Methods Left Ventricular Function... Myocardial Fluid Balance... Cardiopulmonary Bypass Biventricular Assist Device Maintenance of Minimal... Experimental Protocol Statistical Analysis Results Comment Minimal Myocardial Contraction... Minimal Myocardial Contraction... Limitations of the Study Conclusion Acknowledgments References

 
After instrumentation we recorded baseline measurements of all parameters. We determined total protein concentrations in plasma and myocardial lymph using a refractometer (American Optical, Buffalo, NY). Arterial and coronary sinus plasma samples were frozen at -20°C for later lactate quantification using an enzymatic test (Sigma Diagnostics, St. Louis, MO). We then initiated circulatory support with CPB or BiVAD and induced MMC with esmolol for 60 minutes as described above. The aorta was not cross-clamped, and no cardioplegia was given. Measurements of all parameters were repeated at 10, 30, and 50 minutes of MMC during CPB or BiVAD use. After cessation of the esmolol infusion, we maintained circulatory support for 30 minutes until the heart rate had returned to baseline levels. Thereafter, we weaned the dogs from circulatory support, removed all cannulas, and repeated measurements at 30 and 120 minutes after separation from CPB or BiVAD, respectively.

In our previous study in which we used the same CPB technique, crystalloid CPB priming-induced hemodilution alone caused a 0.9% increase in myocardial water content [13]. To determine the effect of crystalloid BiVAD priming-induced hemodilution on myocardial water content, we performed myocardial biopsy at 10 to 15 minutes after BiVAD initiation before esmolol administration in 4 of the BiVAD dogs.

	Statistical Analysis

Top Footnotes Abstract Introduction Material and Methods Left Ventricular Function... Myocardial Fluid Balance... Cardiopulmonary Bypass Biventricular Assist Device Maintenance of Minimal... Experimental Protocol Statistical Analysis Results Comment Minimal Myocardial Contraction... Minimal Myocardial Contraction... Limitations of the Study Conclusion Acknowledgments References

 
All data presented are mean ± standard error. To examine our data for changes over time and differences between CPB versus BiVAD we used a two-way analysis of variance for repeated measures. Post hoc comparisons were performed using Student's t test with Bonferroni correction for multiple comparisons. A value of p less than 0.05 was considered significant.

	Results

Top Footnotes Abstract Introduction Material and Methods Left Ventricular Function... Myocardial Fluid Balance... Cardiopulmonary Bypass Biventricular Assist Device Maintenance of Minimal... Experimental Protocol Statistical Analysis Results Comment Minimal Myocardial Contraction... Minimal Myocardial Contraction... Limitations of the Study Conclusion Acknowledgments References

 
Data of 12 dogs are presented. Table 1 provides data on circulatory support duration and flow rates, as well as administered esmolol doses in the CPB and BiVAD groups. Dogs on CPB required more esmolol than dogs on BiVAD to achieve similar heart rate and LV pressure reductions. Because blood esmolol concentrations are not affected by oxygenator use [20], this difference was probably due to the larger CPB priming volume, resulting in a larger circulating volume compared with BiVAD use.

Figure 2 demonstrates the impact of esmolol-induced MMC on myocardial lymph flow rates. We were able to cannulate the major myocardial lymph trunk in 4 of the CPB dogs and in all BiVAD dogs. In the CPB group, myocardial lymph flow rate remained unchanged compared with baseline during esmolol infusion. In the BiVAD group, myocardial lymph flow rate increased significantly during esmolol infusion. After separation from circulatory support, myocardial lymph flow rate increased to three to four times control in both groups. There was no significant difference between both groups.

View larger version (32K): [in this window] [in a new window]   Fig 2. . Impact of esmolol-induced minimal myocardial contraction (MMC) during normothermic cardiopulmonary bypass (CPB; closed circles; n = 4) and biventricular assist device use (BiVAD; open squares; n = 6) on myocardial lymph flow rate (mean ± standard error). (BL = baseline; ' = minutes; *p < 0.05 versus baseline.)

View larger version (31K): [in this window] [in a new window]   Fig 3. . Changes in myocardial water content induced by minimal myocardial contraction (MMC) during normothermic cardiopulmonary bypass (CPB; closed circles; n = 6) and biventricular assist device (BiVAD; open squares; n = 6) (mean ± standard error). (BL = baseline; ' = minutes. *p < 0.05 versus baseline.)

	Comment

Top Footnotes Abstract Introduction Material and Methods Left Ventricular Function... Myocardial Fluid Balance... Cardiopulmonary Bypass Biventricular Assist Device Maintenance of Minimal... Experimental Protocol Statistical Analysis Results Comment Minimal Myocardial Contraction... Minimal Myocardial Contraction... Limitations of the Study Conclusion Acknowledgments References

Although myocardial lymph flow rate did not decrease during MMC, a significant increase in myocardial water content still occurred. Thus, fluid filtration out of the myocardial capillaries into the cardiac interstitium must have been increased during MMC. Myocardial microvascular filtration rate was probably increased for the following reasons. The plasma colloid osmotic pressure decreased due to hemodilution with the crystalloid bypass prime. Using an equation for colloid osmotic pressure estimation [21], the calculated plasma and myocardial interstitial (lymph) colloid osmotic pressure decreased from about 15 and 7 mm Hg at baseline to about 6 and 4 mm Hg, respectively, at 10 minutes of MMC. Thus, the colloid osmotic pressure gradient across the myocardial microvascular exchange barrier decreased by about 6 mm Hg, favoring increased fluid filtration. Fluid filtration was probably also enhanced by the heart rate reduction induced by ß-blockade during MMC. Diastole is the phase during which myocardial perfusion and filtration occur [19]. As ß-blockade prolongs diastole [22], the time for fluid exchange is increased, increasing the myocardial microvascular filtration coefficient [14]. Thus, both crystalloid hemodilution and increased filtration coefficient enhanced microvascular fluid filtration during MMC.

Our data show that the excess myocardial water that accumulated during MMC decreased significantly after circulatory support demonstrating rapid edema resolution. Edema resolution rates after circulatory support were about 25% and 27% per hour in the BiVAD and CPB groups, respectively, which is comparable with previously published data [13]. As plasma colloid osmotic pressure did not increase substantially after circulatory support, myocardial edema resolution was probably due to several other factors. Myocardial microvascular filtration most likely decreased after return of normal diastole after MMC. In addition, myocardial lymph flow increased probably due to contractility recovery after esmolol cessation. In the normal contractile heart, edema is prevented by lymphatic removal of excess interstitial fluid [4, 14, 19, 23]. We believe that the contractile state of the heart affects myocardial lymphatic function. In other words, decreased cardiac contractility impairs myocardial lymphatic function and thus removal of excess myocardial fluid. This is supported by our previous work, which showed that recovery of cardiac performance was associated with increased myocardial lymph flow rate, which enhanced myocardial edema resolution [13]. Although MMC maintained myocardial lymph flow rate at or above baseline values, lymph flow rate should have been higher in response to the increased microvascular fluid filtration [4, 23]. Thus, the depressed cardiac contractility during MMC prevented the expected myocardial lymph flow rate increase. However, contractility recovery after esmolol cessation was associated with increased myocardial lymph flow rate, thereby contributing to myocardial edema resolution. This emphasizes the important role of regular cardiac contraction for sufficient myocardial lymphatic function.

	Minimal Myocardial Contraction During Circulatory Support: Cardiopulmonary Bypass Versus Biventricular Assistance

Top Footnotes Abstract Introduction Material and Methods Left Ventricular Function... Myocardial Fluid Balance... Cardiopulmonary Bypass Biventricular Assist Device Maintenance of Minimal... Experimental Protocol Statistical Analysis Results Comment Minimal Myocardial Contraction... Minimal Myocardial Contraction... Limitations of the Study Conclusion Acknowledgments References

 
We studied the effect of avoiding an oxygenator on myocardial fluid balance by providing circulatory support with a BiVAD. Mechanical circulatory support is associated with activation of multiple mediators that are capable of increasing vascular permeability, which may result in tissue edema [24, 25]. We did not find a difference in myocardial water content over time between the groups. To separate myocardial fluid accumulation due to MMC from that due to crystalloid hemodilution, we determined myocardial water content at 15 to 20 minutes after initiation of BiVAD use before esmolol administration in 4 dogs. We found an average myocardial water content increase of 0.5% (from 76.0% ± 1.4% at baseline to 76.5% ± 1.3%; p = 0.04), which is comparable with the 0.9% increase we observed due to CPB priming hemodilution in our previous study using similar prime volume and CPB technique [13]. Thus, the myocardial edema was partially due to crystalloid hemodilution before MMC and was similar between the groups.

We found that compared with baseline, myocardial lymph flow rate increased significantly during MMC on BiVAD, whereas lymph flow remained unchanged during MMC on CPB. Although there was no significant difference between the groups, myocardial lymph flows tended to be higher in the BiVAD group due to increased filtration secondary to higher arterial perfusion pressure [23]. As the crystalloid prime volume was smaller in the BiVAD group, this higher perfusion pressure was probably due to a relatively higher viscosity [26]. Although the lower perfusion pressure in the CPB group may pose a risk for subendocardial ischemia, we believe ischemia probably did not occur as hearts did not produce lactate during CPB and myocardial dysfunction was absent after CPB.

	Minimal Myocardial Contraction Versus Normothermic Continuous Blood Cardioplegia

Top Footnotes Abstract Introduction Material and Methods Left Ventricular Function... Myocardial Fluid Balance... Cardiopulmonary Bypass Biventricular Assist Device Maintenance of Minimal... Experimental Protocol Statistical Analysis Results Comment Minimal Myocardial Contraction... Minimal Myocardial Contraction... Limitations of the Study Conclusion Acknowledgments References

 
Further insights into myocardial fluid balance mechanisms can be gained by comparing the data from the present study with those from our previous study in which we used the same CPB technique and experimental set-up except that we used normothermic continuous antegrade blood cardioplegia [13]. We demonstrated that myocardial lymph flow decreased to less than 30% of baseline during cardioplegia, thereby contributing to myocardial edema formation [13]. Based on myocardial wet and dry weights measured at the end of the experiments, we estimated the amount of accumulated myocardial water corresponding to each myocardial density measurement. Figure 4 shows that 50 minutes of MMC resulted in significantly less myocardial water accumulation compared with 50 minutes of continuous blood cardioplegia. This was probably due to the maintained myocardial lymph flow rate during MMC as compared with the virtual lymph flow cessation during blood cardioplegia perfusion [13]. Excess myocardial water remained significantly lower after MMC compared with blood cardioplegia after circulatory support (see Fig 4). This is important because myocardial edema impairs both systolic and diastolic cardiac function [4, 5, 13, 27, 28]. Figure 5 demonstrates the impact of myocardial edema on preload recruitable stroke work. The graph includes data from two myocardial protection methods: MMC during CPB (n = 6) from the present study and continuous blood cardioplegia on CPB (n = 11) from our previous study [13]. Compared with baseline, myocardial water content after MMC was only slightly increased, resulting in unchanged preload recruitable stroke work after circulatory support. In contrast, the increased myocardial water content after blood cardioplegia was directly related to significantly depressed LV systolic performance [13]. This suggests that MMC improves myocardial protection compared with continuous blood cardioplegia by producing less myocardial edema.

View larger version (24K): [in this window] [in a new window]   Fig 4. . Minimal myocardial contraction (MMC) results in less myocardial water accumulation (closed circles; n = 12, both MMC groups from present study) compared with the normothermic continuous blood cardioplegia (BC) groups from our previous study [13] (open circles; n = 11) (mean ± standard error). (BL = baseline; ' = minutes; *p < 0.05 MMC versus BC.)

View larger version (27K): [in this window] [in a new window]   Fig 5. . Minimal myocardial contraction (MMC) (closed circles; n = 6, cardiopulmonary bypass [CPB] group from present study) results in less myocardial edema and unchanged preload recruitable stroke work (PRSW) after CPB compared with normothermic continuous blood cardioplegia in our previous study [13] (open circles; n = 11) (mean ± standard error). Regression statistics: y = 1017 - 12.1x; r2 = 0.97. (BL = baseline; ' = minutes; *p < 0.05 versus baseline.)

	Limitations of the Study

Top Footnotes Abstract Introduction Material and Methods Left Ventricular Function... Myocardial Fluid Balance... Cardiopulmonary Bypass Biventricular Assist Device Maintenance of Minimal... Experimental Protocol Statistical Analysis Results Comment Minimal Myocardial Contraction... Minimal Myocardial Contraction... Limitations of the Study Conclusion Acknowledgments References

	Conclusion

Top Footnotes Abstract Introduction Material and Methods Left Ventricular Function... Myocardial Fluid Balance... Cardiopulmonary Bypass Biventricular Assist Device Maintenance of Minimal... Experimental Protocol Statistical Analysis Results Comment Minimal Myocardial Contraction... Minimal Myocardial Contraction... Limitations of the Study Conclusion Acknowledgments References

 
In conclusion, the results of the present study demonstrate that ß-blocker–induced MMC supports myocardial lymphatic function. We found that MMC maintained myocardial lymph flow rate, resulting in minimal myocardial edema formation and normal LV performance after circulatory support. As MMC during both standard CPB and BiVAD had similar impacts on myocardial lymphatic function and myocardial water content, a membrane oxygenator does not appear to significantly affect myocardial fluid balance during circulatory support for up to 2 hours.

	Acknowledgments

Top Footnotes Abstract Introduction Material and Methods Left Ventricular Function... Myocardial Fluid Balance... Cardiopulmonary Bypass Biventricular Assist Device Maintenance of Minimal... Experimental Protocol Statistical Analysis Results Comment Minimal Myocardial Contraction... Minimal Myocardial Contraction... Limitations of the Study Conclusion Acknowledgments References

 
We thank Mark Brown and Ira Lown for their excellent technical assistance.

This project was supported by Ohmeda Pharmaceutical Products Division Inc.

Uwe Mehlhorn is the recipient of a fellowship granted by the German Research Foundation (Deutsche Forschungsgemeinschaft).

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Left Ventricular Function... Myocardial Fluid Balance... Cardiopulmonary Bypass Biventricular Assist Device Maintenance of Minimal... Experimental Protocol Statistical Analysis Results Comment Minimal Myocardial Contraction... Minimal Myocardial Contraction... Limitations of the Study Conclusion Acknowledgments References

 
Address reprint requests to Dr Allen, Department of Anesthesiology, The University of Texas–Houston Medical School, 6431 Fannin, MSMB 5.020, Houston, TX 77030 (E-mail: sallen{at}anes1.med.uth.tmc.edu).

	References

Top Footnotes Abstract Introduction Material and Methods Left Ventricular Function... Myocardial Fluid Balance... Cardiopulmonary Bypass Biventricular Assist Device Maintenance of Minimal... Experimental Protocol Statistical Analysis Results Comment Minimal Myocardial Contraction... Minimal Myocardial Contraction... Limitations of the Study Conclusion Acknowledgments References

 

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