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Ann Thorac Surg 2000;69:1393-1398
© 2000 The Society of Thoracic Surgeons

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Original articles: Cardiovascular

Cardioplegia-induced cell swelling: prevention by normothermic infusion

^a Section of Cardiothoracic and Vascular Surgery, The Milton S. Hershey Medical Center, Penn State Geisinger Health System, Hershey, Pennsylvania, USA

Address reprint requests to Dr Damiano, Division of Cardiothoracic Surgery, Washington University Medical Center, 1 Barnes-Jewish Hospital Plaza, Suite 3108 Queeny Tower, St Louis, MO 63110
e-mail: damianor{at}msnotes.wustl.edu

	Abstract

Top Abstract Introduction Material and methods Comment References

 
Background. Previous work has shown significant swelling of isolated rabbit myocytes exposed to cold hyperkalemic cardioplegia; however, the effect of warm hyperkalemic cardioplegia on myocyte volume is unknown. This study examined the effect of warm hyperkalemic cardioplegia (St. Thomas’ solution) on myocyte volume.

Methods. Myocytes were enzymatically isolated and placed on an inverted video microscope. Tyrode’s solution (37°C) was infused for 10 minutes to establish baseline cell volumes. Subsequently, either the control Tyrode’s or St. Thomas’ was infused either at 37°C and 9°C respectively (n = 5 for all groups) for 20 minutes, followed by a 30-minute reperfusion with 37°C Tyrode’s. Cell volume was determined from cell images captured every 5 minutes.

Results. Myocyte swelling occurred rapidly on exposure to cold St. Thomas’ solution to a maximum of 9.8 ± 2.1% (p < 0.001). In contrast, myocytes exposed to warm cardioplegia did not show any volume changes during exposure to cardioplegia. However, upon reexposure to Tyrode’s, these cells showed shrinkage below their baseline volume (p < 0.001).

Conclusions. The cell swelling associated with hypothermic cardioplegia is prevented by normothermic infusion.

	Introduction

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Since its introduction over 20 years ago, hypothermic hyperkalemic cardioplegia has been the foundation of most strategies for myocardial protection during cardiac surgery [1]. Despite excellent results, these solutions are far from perfect. Innumerable modifications in both the chemical composition and method of delivery of cardioplegia have been proposed over the last two decades. It is our basic hypothesis that hypothermic hyperkalemic cardioplegia itself can result in significant physiologic derangements in the absence of ischemia. Disturbances in metabolic intermediates and mitochondrial respiration [2–4], depression of left ventricular function [2, 5–7], and rhythm and conduction abnormalities are prevalent [8]. Myocardial edema and cellular swelling has been observed with both crystalloid and blood cardioplegia [4–7, 9, 10]. Cellular edema is thought to play a role in the abnormal left ventricular function [6–8], slowed conduction and arrthymogenesis [8], and decreased coronary flow on reperfusion [7, 11, 12] observed after cardioplegic arrest.

Our laboratory has shown that myocytes exposed to cold hyperkalemic cardioplegia exhibit significant cell swelling in the absence of ischemia [13, 14]. Atrial and ventricular myocytes have been shown to behave in an identical fashion on exposure to hypothermic cardioplegia. During depolarized hypothermic arrest, the Na⁺-K⁺ pump and other transport processes normally responsible for cell volume regulation are inhibited. As a consequence, cell volume is governed by the passive fluxes of ions across the membrane. Because the permeability of the membrane to K⁺ and Cl^- ions is high, the [K⁺] x [Cl^-] product of the cardioplegic solution governs cell volume, as expected for a Donnan equilibrium system. A reduction in the chloride concentration of the cardioplegia has been shown to ameliorate swelling of both rabbit atrial and ventricular tissue and human atrial myocytes [13, 14].

Clinically, warm cardioplegia has been demonstrated to result in better myocardial protection during surgical global ischemia than traditional hypothermic solutions of the same composition [15–17]. Theoretically, myocytes exposed to warm cardioplegia may be able to better regulate their intracellular volume due to the continued activity of active transport processes. Prior studies have focused only on myocardial tissue water and showed no significant changes [15]; however, the effect of normothermic hyperkalemic cardioplegia on myocyte volume is unknown. The present experiments were designed to test the hypothesis that isolated myocytes exposed to hypothermic, hyperkalemic cardioplegia would exhibit significant cellular swelling, and that this swelling would be prevented by normothermic infusion of the identical solution.

	Material and methods

Top Abstract Introduction Material and methods Comment References

 
Adult New Zealand white rabbits of either gender, weighing 2.8 to 3.1 kg, were used in the study. All animals received humane care in Association for Assessment and Acreditation of Laboratory Animal Care (AAALAC), USDA-registered (#23-R-02) facilities in compliance with the "Principles of Laboratory Animal Care," formulated by the National Society for Medical Research and the "Guide for the Care and Use of Laboratory Animals," prepared by the Institute of Laboratory Animal Resources and published by the National Institutes of Health (NIH Publication No. 86-23, revised 1985).

Experimental preparation
Rabbits were anesthetized using zylazine (23.3 mg/kg), acepromazine maleate (1.3 mg/kg), and ketamine (83.3 mg/kg), and the hearts were rapidly excised. Left atrial samples, 5 to 10 mm in size, were placed in a flask containing an oxygenated, 37°C Hepes-buffered salt solution containing (in mM): 120 NaCl, 5.4 KCl, 0.5 MgSO₄, 5.0 sodium pyruvate, 20 glucose, 20 taurine, 30 2,3-butanedione monoxime (BDM), 10 Hepes, and 6 nitrilotriacetic acid (NTA) (Sigma, St. Louis, MO). The pH of the solution was measured (Nova UltraC; Nova Biomedical, Waltham, MA) and adjusted to 7.35 to 7.45 with 1 mol/L NaOH.

The tissue was rinsed in the same Hepes-buffered salt solution without NTA, and sliced into 0.5- to 1.0-mm pieces using a No. 10 scalpel blade. The tissue was then dissociated into isolated myocytes in a 37°C shaker bath (Precision Scientific 25; Precision Scientific, Chicago, IL) using a three-step enzymatic digestion procedure: (1) protease type XIV (Sigma), 4 U/mL, for 15 minutes; (2) collagenase (Worthington Biomedical Corporation; Freehold, NJ), 1 mg/mL, and hyaluronidase (Sigma), 0.5 mg/mL, for 15 minutes; and (3) collagenase, 1.5 mg/mL, for 20 minutes. The enzyme media contained the same Hepes-buffered salt solution with the omission of the NTA and the addition of 50 µmol/L CaCl₂. The enzyme media was oxygenated before each digestion step and during gentle agitation in the shaker bath. After digestion, large debris was manually removed, and the cells were centrifuged for 2 minutes at 100 g. The cells were washed three times with the Hepes-buffered salt solution increasing the CaCl₂ sequentially to 1.4 mmol/L. and were stored in a 37°C oxygenated environment for up to 4 hours until used for imaging.

Imaging
The isolated myocytes were placed in a custom-made chamber constructed from a cover slip and Lucite sidewalls. The myocytes were allowed to settle for 5 minutes, and the chamber was perfused with the control Tyrode’s solution consisting of (in mmol/L): 130 NaCl, 5 KCl, 2.5 CaCl₂, 1.75 NaKHPO₄, 1.2 MgSO₄, 24 NaHCO₃, and 10 glucose. Before infusion, the solution was equilibrated with 95% O₂/5% CO₂, and the pH was adjusted to 7.4 using NaOH. The temperature of the perfusate was monitored during the experiment with a thermistor (Model Bat 8; Bailey Instruments, Saddle Brook, NJ).

The chamber was placed on an inverted microscope (Diavert; Leitz, Wetzlar, Germany) equipped with Hoffman modulation optics. The cell images were displayed on a video monitor with 800-line resolution (VM-1220; Hitachi, Tokyo, Japan) by a high-resolution television camera (HP-101A; Hitachi). The total magnification of the video-optical system was 1,912x, with a 40x objective. Cells were inspected for viability, clear striations, and sharp boarders. Cell volumes were determined by the method described by Baumgarten and coworkers [13, 18]. The myocyte images were captured using custom software and a video frame grabber (Targa 16/32; Truevision, Indianapolis, IN) by a Pentium 120-MHz personal computer. The resolution of the digitization was 0.24 µm/pixel. The cell borders were traced using JAVA image analysis software (SPSS, Chicago, IL). Contrast enhancement, image magnification, and an edge tracing algorithm identified the borders of the cell with the assistance of the operator. Cell volume was determined using a custom ASYST program (Keithley, Cleveland, OH).

Assuming that the changes in cell width and thickness were proportional, relative cell volume was determined as:

Based on repeated measurements of single images and measurements of multiple images of a cell, the estimates of cell volume have been shown to be reproducible to less than 1% [18, 19].

Experimental protocol
The perfusates were placed in temperature-controlled water jackets before infusion, and all perfusates were delivered at 4 to 5 mL/min. Myocytes were perfused with the control Tyrode’s solution for 10 minutes at 37°C to establish baseline cell volume and then with either the study solution, St. Thomas’ solution (Plegisol; Abbott Laboratories, North Chicago, IL), or the control Tyrode’s solution for 20 minutes. St. Thomas’ solution and Tyrode’s solution were studied at both 37°C and 9°C. Five myocytes, each from a different animal, were studied in each group. St. Thomas’ solution consisted of (in mmol/L): 110 NaCl, 10 NaHCO₃, 16 KCl, 16 MgCl₂ (pH 7.3 at 9°C, equilibrated with 95% O₂/5% CO₂, 299 ± 3 mosmol/L). After the 20-minute test period, the myocytes were once again perfused with control Tyrode’s solution at 37°C for 30 minutes. Relative cell volume was measured every 5 minutes throughout the study.

Another group of myocytes (n = 5) was studied to examine the effect of blocking the Na⁺-K⁺ pump with 10 µmol/L ouabain during the final reperfusion with control Tyrode’s solution. The protocol for these experiments was identical to that previously described, except that 30 mmol/L 2,3-butane, dione monoxide (BDM) was added to all solutions. BDM is a membrane-permeant chemical phosphatase and was employed to prevent contracture in ouabain.

Statistics
Data are reported as mean ± standard error. Analysis of variance was conducted using a repeated measures design (SigmaStat; SPSS). Because the variance tended to vary with the treatment mean, a logarithmic transform was applied to the data before analysis; the variance of the transformed data was more appropriate for the analytical model. Comparisons of treatment with a control were done using the Student-Newman-Keuls method. Statistical significance was defined as p less than 0.05.

Results
The width, length, and volume of rabbit atrial myocytes were measured after the cells were equilibrated at 37°C in control Tyrode’s solution for 10 minutes. Under control conditions, the dimensions of the rabbit atrial myocytes were: width, 15.6 ± 0.5 µm; length, 139.2 ± 3.0 µm; volume, 35.5 ± 2.1 pl (n = 20). These calculations of volume assumed that the cross section of the myocytes was square. If the cross section was instead cylindrical, the absolute cell volumes were overestimated by a factor of 4/ (1.27). To avoid this uncertainty in the remaining results, cell volumes were expressed relative to control. Relative cell volumes are independent of the assumed cross-sectional shape.

Effect of cold St. Thomas cardioplegia on cell volume
To determine whether hypothermic St. Thomas’ solution induced cellular edema in the absence of ischemia, rabbit atrial cell volumes were measured under control conditions and during exposure to cold (9°C) St. Thomas’ solution. Rabbit atrial myocytes quickly swelled after the exposure to hypothermic St. Thomas’ solution (Fig 1A). Cell swelling was significant at 1 minute with an increase in relative cell volume of 4.8% ± 0.8% (p < 0.001), and the maximum volume increase during cold cardioplegia was 9.8% ± 2.1% (p < 0.001). The observed changes were the result of changes in cell width while cell length remained unchanged.

View larger version (20K): [in this window] [in a new window]   Fig 1. (A) Relative cell volumes of atrial myocytes (n = 5) during a 20-minute exposure to 9°C St. Thomas’ solution and 30 minute of reperfusion in 37°C physiologic solution (Tyrode’s). In this and subsequent figures, cell volume is expressed relative to that of control conditions in 37°C physiologic solution. *A statistically significant change from control (p < 0.001). (B) Relative cell volume of atrial myocytes (n = 5) during 20 minutes in 9°C physiologic solution and 30 minutes of reperfusion at 37°C in the same solution. (Tyr = Tyrode’s.)

To assure that the observed volume changes were due to the exposure of the myocytes to St. Thomas’ solution, and not to hypothermia alone, a group of rabbit atrial myocytes were exposed to hypothermic Tyrode’s solution. Neither hypothermia nor reperfusion with 37°C Tyrode’s solution significantly altered relative cell volume (Fig 1B).

Effect of warm St. Thomas’ cardioplegia on cell volume
Under normothermic conditions, transport processes responsible for cell volume regulation are active and should enable cells to maintain a constant volume despite a changing extracellular milieu. To test this hypothesis, cells were perfused with normothermic St. Thomas’ solution. Isolated myocytes did not show significant volume changes during a 20-minute exposure to warm (37°C) St. Thomas’ cardioplegia. However, statistically significant shrinkage was observed on reperfusion with 37°C Tyrode’s solution (Fig 2A). Relative cell volume decreased by a maximum of -5.1% ± 1.7% (p < 0.001) and remained less than control throughout the reperfusion period. In contrast, relative cell volume remained constant, as expected, when atrial myocytes were perfused with 37°C Tyrode’s solution throughout the study period (Fig. 2B).

View larger version (20K): [in this window] [in a new window]   Fig 2. (A) Relative cell volume of atrial myocytes (n = 5) during a 20-minute exposure to 37°C St. Thomas’ solution and 30 minutes of reperfusion in 37°C physiologic solution (Tyrode’s). *A significant change from control (p < 0.001). (B) Relative cell volume of atrial myocytes (n = 5) during 50 minutes in 37°C physiologic solution. (Tyr = Tyrode’s.)

View larger version (19K): [in this window] [in a new window]   Fig 3. Relative cell volume of atrial myocytes (n = 5) during a 20-minute exposure to 37°C St. Thomas’ solution and 30 minutes of reperfusion in 37°C physiologic solution (Tyrode’s) with the addition of 10 µmol/L ouabain. (Tyr = Tyrode’s.)

	Comment

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Under hypothermic conditions, the transport processes responsible for normothermic cell volume regulation are depressed. As a result, cell volume is regulated by passive fluxes of ions according to a Donnan equilibrium. In a Donnan equilibrium system, the membrane potential (E_m) and the Nernst equilibrium potentials for K⁺ and Cl^- are equal. Writing this relationship and simplifying gives:

where the bracketed chemical symbols refer to the intracellular, i, and the extracellular, o, concentrations, R is the gas constant, T is the temperature (⁰K), and F is Faraday’s constant. As a consequence of these relationships, increasing the [K⁺] x [Cl^-] product of the extracellular solution leads to accumulation of K⁺ and Cl^- within the cell, and water follows osmotically [20].

St. Thomas’ cardioplegia contains a high potassium and normal chloride concentration, resulting in a high [K⁺] x [Cl^-] product (2,566.4 mmol/L²), when compared with blood (350 to 550 mmol/L²) and Tyrode’s solution (700 mmol/L). Previous work has demonstrated that isolated myocytes swell in both blood and crystalloid cardioplegic solutions [10].

Amelioration of cell swelling by normothermic cardioplegia
Cell volume regulation under normothermic conditions is more complex than that observed during hypothermia. Multiple transport systems, including the Na⁺/K⁺/2Cl^- and Na⁺/Cl^- cotransport systems [18, 19], contribute to normothermic volume regulation. These redundant systems allow the cell to closely regulate its volume under a wide variety of extracellular ionic conditions. As opposed to hypothermic cardioplegia, normothermic cardioplegia did not cause cell swelling in our study. This is most likely due to the ability of these various transport systems to compensate for the altered external ionic milieu. Previous work in our laboratory has demonstrated that the cell swelling occurring with hypothermic cardioplegia has detrimental functional and electrophysiological consequences on reperfusion [21]. Prevention of cell swelling by lowering the [K⁺] x [Cl^-] product of the cardioplegia ameliorated myocardial stunning and postreperfusion conduction delays. The lack of cell swelling with normothermic infusion may partly explain the clinical benefits attributed to warm cardioplegia.

The physiologic significance of cell shrinkage upon reperfusion after warm cardioplegia is unclear. We hypothesized that the observed cell shrinkage was due to the activation of the Na⁺-K⁺ pump. During hyperkalemic cardioplegia arrest, membrane depolarization to near -50 mV occurs, which causes an increase in Na⁺ influx, most likely via the Na⁺ "window" current [22], and an increase in intracellular Na⁺ [23]. Upon reexposure to physiologic solutions, the membrane repolarizes, and the Na⁺-K⁺ pump actively extrudes 3 Na⁺ and takes up 2 K⁺ in order to compensate for the increase in intracellular Na⁺ [20]. Because this is equivalent to an efflux of osmoles, cellular volume would be expected to decrease. We hypothesized that inhibition of the Na⁺-K⁺ with ouabain would prevent this net efflux of osmoles and, therefore prevent the decrease in cell volume on reperfusion with physiologic solutions.

To test this hypothesis, a group of myocytes was reperfused with 37°C Tyrode’s solution containing 10 µmol/L ouabain, an inhibitor of the Na⁺-K⁺ pump, after exposure to warm St. Thomas’ solution. With the addition of ouabain, cell shrinkage during reperfusion was eliminated, indicating that activity of the Na⁺-K⁺ pump was responsible for cell shrinkage and plays an important role in the cellular response to increased intracellular Na⁺ after cardioplegic arrest.

Limitations
Studying isolated myocytes has the advantage of allowing repeated measurements of cell volume in response to differing solutions in the absence of ischemia. However, isolated myocytes in a flowing solution do not reflect the complex geometry of the intact arrested heart wherein extracellular volume is limited. Initially, cellular edema during cardioplegic arrest results from fluid transfer from the interstitial space to the cellular compartment [24]. During cardioplegic arrest, ions and metabolites accumulate, increasing the osmolarity of both the intracellular and extracellular compartment [25]. Washout of the extracellular space during reperfusion creates an osmotic gradient favoring further cell swelling and, in severe cases, cell membrane rupture. Also, in the isolated myocyte model, the role of vascular, neural and interstitial elements are ignored. For example, myocardial edema increases coronary vascular resistance and limits or prevents effective reperfusion [11, 12]. The high K⁺ in cardioplegic solution may directly damage vascular endothelium. Great care must be taken in applying these findings to the clinical situation.

The present study considered one of the many factors involved in myocyte edema, and utilized a relatively short period of exposure to cardioplegia. The length of exposure in this preparation is limited by the need to maintain viable myocytes and does not reproduce the prolonged exposure times employed clinically. Additionally, there is no adequate method for simulating clinical ischemic/reperfusion in the isolated myocyte model. Furthermore, the use of high magnification and repeated measurements of the same myocyte preclude the use of blood cardioplegia in the model. However, this model is well accepted in the literature for its utility in providing insights into the mechanisms of cardioplegic injury at the cellular level [10, 13].

Clinical implications
The physiologic effects of warm cardioplegia are not completely understood. However, it has been shown clinically that warm cardioplegia may have potential benefits, such as protection from ischemia/reperfusion injury [17], improved ventricular function [15–17], and decreased arrhythmogenesis [15–17]. Under hypothermic conditions, cellular edema is thought to contribute to the mechanical dysfunction [6, 7, 21], arrhythmogenesis [8], and decreased coronary flow on reperfusion [7, 11, 12]. Our data demonstrated that warm cardioplegia prevented the myocyte swelling previously reported during cold cardioplegia [10, 13, 14], and suggests that temperature may be an important factor in controlling myocyte edema during cardioplegia. The absence of myocyte edema during exposure to warm cardioplegia may explain the observed clinical benefit of warm hyperkalemic cardiac arrest.

	Acknowledgments

 
This study was supported by National Institutes of Health grants HL-51032 (Ralph J. Damiano, Jr, MD) and HL-46764 (Clive M. Baumgarten).

	References

Top Abstract Introduction Material and methods Comment References

 

1. Hearse D.J., Baimbridge M.V., Jynge P. Protection of ischemic myocardium. New York: Raven Press, 1981.
2. Fremes S.E., Weisel R.D., Mickle D.A.G., et al. Myocardial metabolism and ventricular function following cold potassium cardioplegia. J Thorac Cardiovasc Surg 1987;89:531-546.[Abstract]
3. Engelman R.M., Rousou J.H., Lemeshow S., Dobbs W.A. The metabolic consequences of blood and crystalloid cardioplegia. Circulation 1981;64(Suppl II):67-74.
4. Sunamori M., Harrison C.E. Myocardial respiration and edema following hypothermic cardioplegia and anoxic arrest. J Thorac Cardiovasc Surg 1979;78:208-216.[Abstract]
5. Kay H.R., Levine F.H., Fallon J.T., et al. Effect of cross-clamp time, temperature, and cardioplegic agents on myocardial function after induced arrest. J Thorac Cardiovasc Surg 1978;76:590-603.[Abstract]
6. Foglia R.O., Steed D.L., Follette D.M., Deland E., Buckberg G.D. Iatrogenic myocardial edema with potassium cardioplegia. J Thorac Cardiovasc Surg 1979;78:217-222.[Abstract]
7. Wang Z.C., Nicolosi A.C., Detwiler P.W., et al. Effects of crystalloid, blood, and University of Wisconsin perfusates on weight, water content, and left ventricular compliance in an edema-prone, isolated porcine heart model. J Thorac Cardiovasc Surg 1992;103:504-513.[Abstract]
8. Cohen N.M., Allen C.A., Belz M.K., Nixon T.E., Wise R.M., Damiano R.J., Jr Electrophysiological consequences of hypothermic hyperkalemic elective cardiac arrest. J Card Surg 1993;8:156-160.[Medline]
9. Schaper J., Scheld H.H., Schmidt U., Hehrlein F. Ultrastructural study comparing the efficacy of five different methods of intraoperative myocardial protection in the human heart. J Thorac Cardiovasc Surg 1986;92:47-55.[Abstract]
10. Handy J.R., Jr, Dorman B.H., Cavallo M.J., et al. Direct effects of oxygenated crystalloid or blood cardioplegia on isolated myocyte contractile function. J Thorac Cardiovasc Surg 1996;112:1064-1072.[Abstract/Free Full Text]
11. Kloner R.A., Ganote C.E., Jennings R.B. The "no-reflow" phenomenon after temporary coronary occlusion in the dog. J Clin Invest 1974;54:1496-1508.
12. Rubboli A., Sobotka P.A., Euler D.E. Effect of acute edema on left ventricular function and coronary vascular resistance in the isolated rat heart. Am J Physiol 1994;267:H1054-H1061.[Abstract/Free Full Text]
13. Drewnowska K., Clemo H.F., Baumgarten C.M. Prevention of myocardial intracellular edema induced by St. Thomas’ Hospital cardioplegic solution. J Mol Cell Cardiol 1991;23:1215-1221.[Medline]
14. Shaffer R.F., Baumgarten C.M., Damiano R.J., Jr Prevention of cellular edema directly caused by hypothermic cardioplegia. J Thorac Cardiovasc Surg 1998;115:1189-1195.[Abstract/Free Full Text]
15. Brown W.M., III, Jay J.L., Gott J.P., et al. Warm blood cardioplegia. Ann Thorac Surg 1993;55:32-42.
16. Lichtenstein S.V., Ashe K.A., El Dalati H., Cusimano R.J., Panos A., Slutsky A.S. Warm heart surgery. J Thorac Cardiovasc Surg 1991;101:269-274.[Abstract]
17. Mezzetti A., Calafiore A.M., Lapenna D., et al. Intermittent antegrade warm cardioplegia reduces oxidative stress and improves metabolism of the ischemic-reperfused human myocardium. J Thorac Cardiovasc Surg 1995;109:787-795.[Abstract/Free Full Text]
18. Clemo H.F., Baumgarten C.M. Atrial natriuretic factor decreases cell volume of rabbit atrial and ventricular myocytes. Am J Physiol 1991;260:C681-C90.[Abstract/Free Full Text]
19. Drewnowska K., Baumgarten C.M. Regulation of cellular volume in rabbit ventricular myocytes. Am J Physiol 1991;260:C122-C31.[Abstract/Free Full Text]
20. Baumgarten C.M., Feher J.J. Osmosis and the regulation of cell volume. In: Sperelakis N., ed. Cell physiology source book, 2nd ed. New York: Academic Press, 1998:253-293.
21. Jayawant A.M., Stephenson E.R., Jr, Baumgarten C.M., Damiano R.J., Jr Prevention of cell swelling with low chloride St. Thomas’ solution improves post-ischemic myocardial recovery. J Thorac Cardiovasc Surg 1998;115:1196-1202.[Abstract/Free Full Text]
22. Attwell D., Cohen I., Eisner D., Oheba D., Ojeda C. The steady state TTx-sensitive (window) sodium current in cardiac Purkinje fibers. Pflugers Arch 1979;379:137-142.[Medline]
23. Skinner B., Krohn E., Gebhard M.M., Bretschneider H.J. Intracellular pH, Na⁺- and K⁺ activities at the onset of St. Thomas’ cardioplegia. Thorac Cardiovasc Surgeon 1988;36:247-253.[Medline]
24. Schmiedl A., Haasis G., Schnabel P.A., Gebhard N.M., Richter J. Morphometric evaluation of volume shifts between intra- and extra-cellular space before and during global ischemia. Anat Rec 1995;241:319-327.[Medline]
25. Tranum-Jensen J., Janse M.J., Fiolet J.W.T., Krieger W.J.G., D’Alnoncourt C.N., Durrer D. Tissue osmolarity, cell swelling, and reperfusion in acute regional myocardial ischemia in the isolated porcine heart. Circ Res 1981;49:364-381.[Free Full Text]

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Ralph J. Damiano, Jr Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stephenson, E. R. Articles by Damiano, R. J. Search for Related Content PubMed PubMed Citation Articles by Stephenson, E. R., Jr Articles by Damiano, R. J., Jr