Departments of 1 Heart and Lung Medicine, 2 Internal Medicine, and 3 Anatomy and Cell Biology, University of Göteborg, SE-413 45, Goteborg, Sweden; and 4 Department of Heart Surgery, University of Varese, 21100 Varese, Italy
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ABSTRACT |
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The interstitial fluid of the human myocardium was monitored in 13 patients undergoing aortic valve and/or bypass surgery before, during, and after hypothermic potassium cardioplegia. The regulation of glucose and lactate was studied after sampling with microdialysis. The following questions were addressed. 1) Is the rate of transcapillary diffusion the limiting step for myocardial uptake of glucose before or after cardioplegia? 2) Does cold potassium cardioplegia induce a critical deprivation of glucose and/or accumulation of lactate in the myocardium? Before cardioplegia, interstitial glucose was ~50% of the plasma level (P < 0.001). Interstitial glucose decreased significantly immediately after induction of cardioplegia and remained low (1.25 ± 0.25 mM) throughout cardioplegia. It was restored to precardioplegic levels 1 h after release of the aortic clamp. Interstitial glucose then decreased again at 25 and 35 h postoperatively to the levels observed during cardioplegia. Interstitial lactate decreased immediately after induction of cardioplegia but returned to basal level during the clamping period. At 25 and 35 h, interstitial lactate was significantly lower than before and during cardioplegia. Glucose transport over the capillary endothelium is considered rate limiting for its uptake in the working heart but not during cold potassium cardioplegia despite the glucose deprivation following perfusion of glucose-free cardioplegic solution. Lactate accumulated during cardioplegia but never reached exceedingly high interstitial levels. We conclude that microdialysis provides information that may be relevant for myocardial protection during open-heart surgery.
myocardium; ischemia; microdialysis; surgery
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INTRODUCTION |
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A BETTER UNDERSTANDING of the regulation of delivery and uptake of nutrients in the heart is required to optimize myocardial metabolic balance during cardioplegia. Research in this area has focused mainly on the pre- and immediately postoperative situations, and various studies on plasma sampling techniques have been published (1, 5, 17), including single- and multiple-isotope balance studies (24, 38, 44). Some (5, 36, 37, 39), but not all (31), investigators have demonstrated decreased cardiac uptake and oxidation of glucose and lactate in the initial postoperative period.
However, a more detailed knowledge is required of how the concentration of nutrients is regulated in the myocardium, where interstitial fluid shifts are brought about by perfusion of cardioplegic solutions. A key issue is the monitoring of the myocardial metabolism during the cardioplegic period during which relevant plasma sampling cannot be carried out. Sampling of the interstitial fluid of the myocardium by means of microdialysis before, during, and after open-heart surgery is now used also in the clinical situation (18, 19). When properly calibrated, the approach offers high-precision data from the myocardial interstitium (26). The technique has previously been used for metabolic balance measurements in other organs (14, 15, 29). Myocardial microdialysis has been performed in experimental setups of both the calibrated (25) and the noncalibrated type (20). Noncalibrated microdialysis sampling of the human heart during cardioplegia was recently reported from two different centers (9, 18, 19).
In the present study, we used internal reference calibration for measurement of interstitial glucose and lactate in the myocardium. Glucose and lactate were chosen as both being important nutrients for the myocardium during normal conditions. Increased lactate production serves as a marker for ischemia in the heart. Thirteen patients were monitored before, during, and after open-heart surgery, including hypothermic cardiopulmonary bypass and cold potassium cardioplegia, in an attempt to establish whether 1) the transcapillary diffusion is a rate-limiting step for myocardial glucose uptake before or after cardioplegia; and 2) glucose is lowered and/or lactate increased to a critical extent during cold cardioplegia.
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PATIENTS, MATERIALS, AND METHODS |
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Patients.
Thirteen patients of Caucasian origin, 3 females and 10 males, mean age
62 yr (range 33-77 yr; Table 1) gave
their informed consent to participate in the study, which was approved
by the local ethics committee. No high-risk patients (i.e., patients with cerebral lesions, renal insufficiency, or recent myocardial infarction) were included in the study. The ejection fraction (EF) was
evaluated with echocardiography and/or angiography, and patients with
an EF of <35% were excluded from the study, as were known cases of
diabetes mellitus. Four patients (all males) underwent coronary artery
bypass surgery (CABG), including one to four distal anastomoses. Three
of these received a left internal mammary artery graft to the left
anterior descending coronary artery. One of the CABG patients also
underwent aortic valve replacement. In another patient, the CABG was an
elective reoperation. Nine patients (3 females, 6 males) received valve
prosthesis because of aortic valve disease. Acetylsalicylic acid,
warfarin, and digoxin medications were discontinued preoperatively. In
the patients from the CABG group, the dose of selective -blockers
was reduced by 50% postoperatively, and antiangina medication was
discontinued. In the valve group, diuretics were reduced or
discontinued postoperatively.
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Protocol. Food and fluid intake was discontinued no later than at 12:00 midnight on the day preceding surgery. No intravenous infusions (including glucose substitution) were given preoperatively. Before surgery, the patients were sedated with 10 mg of morphine hydrochloride and 0.4 mg of hyoscine hydrobromide (morphine-scopolamine, Pharmacia) and 1 mg of flunitrazepam (Rohypnol, Roche). One or more indwelling catheters were established in the radial and/or femoral arteries for blood pressure measurements and blood sampling. Central and peripheral venous indwelling catheters were established. Anesthesia was induced with thiopental sodium (Pentothal, Abbott), fentanyl (Fentanyl, Dumex-Alpharma) and pancuronium bromide (Pavulon, Organon Teknika) and maintained with fentanyl, droperidol (Dridol, Janssen-Cilag), halothane (Fluothane, Zeneca), or enflurane (Efrane, Abbott) and midazolam (Dormicum, Roche). Before sternotomy, a sinus coronary catheter (Wilton-Webster, Baldwin Park, CA) was introduced through the right external jugular vein and placed with its tip in the great cardiac vein with fluoroscopic guidance.
The microdialysis probes were inserted into the region between the left anterior descending artery and the second diagonal artery immediately after a full median sternotomy (18-20). Care was taken to avoid vessels and to place the probes at equal depth (i.e., 2-3 mm). The patients were heparinized (300 U/kg body wt + 7,500 U heparin) before bypass was instituted. Anticoagulation was reversed with protamine (1 mg/100 U heparin) when patients had been weaned from bypass. The hearts were cannulated, either with a two-stage venous cannula in the right atrium (CABG group) or via bicaval cannulation (valve group). After aortic cross-clamping, the hearts were arrested with cold (2-4°C), crystalloid, glucose-free cardioplegic solution (Plegisol; Abbott). The electrolyte composition was (in meq) 110 Na+, 160 ClMicrodialysis. The microdialysis probes were developed and manufactured in our laboratory (18-20). Two types of probe were used, identical except for the length of the outflow tubing. The length of probes used for perioperative measurements was 30 mm to minimize the dead space. Sampling periods were 10 min. Probes for postoperative measurements had an outflow tubing of 470 mm. This permitted tunneling of the probes under the lower left rib for collection of extrathoracic samples. Sampling periods were 60 min. A vial adapter for sample collection was connected to the outlet tubing, and the inlet tubing was connected to an infusion pump (CMA 100; CMA, Stockholm, Sweden). The inlet tubing was ~2,000 mm long, allowing the pump to be placed outside the sterile field.
The permeable membrane (0.6 mm OD, 0.1-µm pores; CPC/PE; Gambro, Lund, Sweden) allowed passage of molecules exceeding the size of the markers used. The probes were perfused with sterile, isotonic NaCl solution at room temperature at 2.5 µl/min. Priming of the probes to evacuate the air began not later than 20 min before implantation. Sampling was done before cardioplegia, at 10-min intervals during cardioplegia and reperfusion, and thereafter at 60-min intervals. Samples were stored atBlood samples.
Arterial blood was drawn from the radial or femoral artery and venous
blood from the coronary sinus, both in the middle of microdialysis
sampling periods (corrected for dead-space delay). The blood
samples were centrifuged, and the plasma was decanted and stored at
80°C.
Analyses. Glucose and lactate concentrations in plasma and dialysates were determined enzymatically using 10-µl samples for simultaneous analysis of glucose and lactate (YSI 2700 select biochemical analyzer; Yellow Springs Instruments, Yellow Springs, OH). Radioactivity was counted in a liquid scintillation counter with a quench-corrected (external standards) double-isotope program (1900 CA, TRI-CARB; Packard Instruments, Meriden, CT).
Statistics. The results are expressed as means ± SE. Significance of differences was tested with ANOVA and, when appropriate, Student's t-test for paired and unpaired observations. A difference of P < 0.05 was considered statistically significant.
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RESULTS |
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There were no infections, infarctions, local bleeding, or other
complications related to the study. The microdialysis probes were
implanted and extracted without inducing arrhythmias or other side
effects. Blood glucose increased ~1 h after surgery, since infusions containing glucose were given perioperatively (Fig. 1A). Glucose infusions
were also given postoperatively. Consequently, the high blood glucose
levels at 25 and 35 h postoperatively were postprandial, in
contrast to the levels recorded before cardioplegia (Fig.
1A).
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The relative recovery (dialysate concentration/interstitial concentration) of interstitial glucose and lactate before induction of cardioplegia was 28 ± 7 and 31 ± 7%, respectively. The recovery declined during cardioplegia to 20 ± 2 and 16 ± 6%, respectively, but increased 25 h postoperatively to 43 ± 7 and 45 ± 6%, respectively.
Interstitial glucose decreased immediately and significantly after coronary instillation of glucose-free cardioplegic solution and remained low throughout cardioplegia (Fig. 1A). It was then restored to precardioplegic levels at 1 h after release of the aortic clamp. Interstitial glucose decreased again, at 25 and 35 h after surgery, to levels similar to those recorded during cardioplegia (Fig. 1A).
Plasma lactate increased slightly postoperatively (Fig. 1B). A statistically nonsignificant decrease in interstitial lactate was registered immediately at induction of cardioplegia, followed by a significant increase throughout the clamping period (Fig. 1B). The lowest levels of interstitial lactate were recorded 25 and 35 h after surgery.
The uptake and release of glucose and lactate in the myocardium were
calculated from the differences between the arterial-coronary sinus
(a-v) and arterial-interstitial (a-i) concentrations. There was a significant uptake of glucose before cardioplegia (Table 2). Both the a-v and the a-i
concentration differences for glucose increased significantly
postoperatively. Throughout the recording period, interstitial glucose
was lower than both arterial and venous blood glucose (Fig.
1A); therefore, the a-i concentration differences of glucose
exceeded the corresponding a-v differences (Table 2).
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Before cardioplegia, a small, but statistically significant, a-v difference was recorded for lactate, indicating a myocardial uptake (Table 2). This switched to a significant negative lactate balance 1 h after cardioplegia. The a-i difference for lactate increased significantly 25 h after surgery, indicating a significant rate of lactate utilization by the myocardium.
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DISCUSSION |
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To our knowledge, this is the first study in which calibrated microdialysis has been used for direct measurement of nutrient concentrations in the interstitium of the human heart. The results show that 1) there are significant differences in a-i concentration for both glucose and lactate in the beating heart, indicating that transcapillary diffusion is a rate-limiting step for both the uptake and the release of glucose and lactate; and 2) interstitial glucose and lactate levels change during cardioplegia but never reach nonphysiological concentrations.
Before cardioplegia. Interstitial glucose in the myocardium was only ~50% of that in arterial plasma, indicating that the entry of glucose into the interstitial fluid does not balance its rate of elimination. Consequently, transcapillary diffusion of glucose in addition to the myocellular glucose transporter is a rate-limiting step for myocardial glucose uptake. This is in agreement with findings in skeletal muscle in resting subjects, in which the glucose uptake rate correlates negatively with interstitial glucose concentration (12, 13). In working skeletal muscle, blood flow and capillary permeability increase to reduce the concentration difference between arterial and interstitial glucose. The interstitial glucose concentration was surprisingly low, since the blood flow in the myocardium is much higher than in skeletal muscle, which, in turn, indicates that the cellular uptake of glucose in the myocardium is extremely efficient (5, 10, 41).
Small hydrophilic molecules exchange via passive diffusion through intercellular clefts in continuous capillaries (4). Thus the extraction fraction (ExF) for glucose and lactate can be calculated according to the formula: ExF = (ADuring cardioplegia. It is notable that mean interstitial glucose, which was low throughout the cardioplegic period, was never lower than 1 mmol/l, despite repeated administration of glucose-free cardioplegic solution. Apparently, glucose was not totally depleted despite low or abolished glucose uptake under low temperature. Interstitial lactate also decreased initially and accumulated slowly during heart arrest, despite the intermittent perfusion with cardioplegic solution. The mean interstitial lactate levels did not exceed the precardioplegia levels during this period. Because the glucose uptake was very low, we conclude that the interstitial lactate is probably derived more from glycogen breakdown. Clearly, in our study this did not lead to exceedingly high interstitial levels of lactate (Fig. 1B).
Finally, it should be noted that, because diffusion over the microdialysis membrane was reduced at lower temperatures, subsequent recalibrations were performed.After cardioplegia. Interstitial glucose increased significantly immediately after release of the aortic cross-clamp, whereas interstitial lactate remained high. Both a-i and a-v differences for glucose increased significantly, indicating enhanced glucose consumption. In contrast, lactate a-i was negative as a result of net myocardial release of lactate. The elimination and oxidation of glucose, as well as of lactate, were low during the early postoperative phase, as reported previously (36). Very high interstitial lactate concentrations were registered in two (patients 6 and 9) of the four patients with coronary heart disease immediately after release of the cross-clamp (4 and 12 mmol/l, respectively; data not shown). This may be due to a previous upregulation of the glycolytic capacity.
At 25 and 35 h after release of the cross-clamp, all patients displayed very low interstitial glucose and lactate, indicating high elimination and oxidation rates. This is in agreement with previous studies at 4 h (5) and 8 h (39) after surgery. In this late phase, patients with coronary heart disease had equally low interstitial glucose and lactate levels, as did the other patients. It should be noted that the 25- and 35-h samples were collected postprandially; hence, blood glucose as well as plasma lactate were high (Fig. 1). The low interstitial levels therefore indicate a rapid elimination of glucose and lactate from the interstitial fluid into the myocardial cells. Markers for ischemia accumulate in the interstitial fluid early during cardioplegia (9, 19) and are steadily released during reperfusion (9). The present data do not indicate that the poor delivery of glucose or the lactate accumulation in the myocardium potentiates the trauma of cold cardioplegia (8). Accordingly, the addition of glucose and/or lactate to cardioplegic solutions has no convincing cardioprotective effect (2, 11, 33, 34). Protection by other compounds such as ![]() |
ACKNOWLEDGEMENTS |
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We are grateful to the surgeons who skillfully and patiently helped implant the microdialysis probes and to Dr. Klaus Kirnö for expertly inserting the coronary sinus probes. We also thank Gudrun Jonson for skillful secretarial aid.
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FOOTNOTES |
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This study was supported by grants from the Swedish Research Council (Project nos. 10864, 11330, and 12206), the Swedish Diabetes Association, Novo Nordisk Foundation, the Magn. Bergvalls Foundation, and the Inga-Britt and Arne Lundberg Foundation.
Address for reprint requests and other correspondence: C. Kennergren, Institute of Heart and Lung Diseases, Sahlgrenska Univ. Hospital, SE-413 45 Göteborg, Sweden (E-mail: kennergren{at}vgregion.se).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
First published August 20, 2002;10.1152/ajpendo.00522.2001
Received 21 November 2001; accepted in final form 31 July 2002.
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REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Ando, H,
Tanaka J,
Hisahara M,
Nagano I,
and
Shimizu I.
Implication of myocardial lactate metabolism during coronary artery by-pass grafting.
Cardiovasc Surg
5:
210-215,
1997[Medline].
2.
Barratt-Boyes, BG,
Harris EA,
Kenyon AM,
Lindop CA,
and
Seelye ER.
Coronary perfusion and myocardial metabolism during open-heart surgery in man.
J Thorac Cardiovasc Surg
72:
133-141,
1976[Abstract].
3.
Baxter, GF.
Ischaemic preconditioning of myocardium.
Ann Med
29:
345-352,
1997[ISI][Medline].
4.
Crone, C,
and
Levitt D.
Capillary permeability to small solutes.
In: Handbook of Physiology. The Cardiovascular System. Microcirculation. Bethesda, MD: Am. Physiol. Soc, 1984, sect. 2, vol. IV, pt. 1, chapt. 10, p. 411-466.
5.
Fremes, SE,
Weisel RD,
Mickle DA,
Ivanov J,
Madonik MM,
Seawright SJ,
Houle S,
McLaughlin PR,
and
Baird RJ.
Myocardial metabolism and ventricular function following cold potassium cardioplegia.
J Thorac Cardiovasc Surg
89:
531-546,
1985[Abstract].
6.
Gertz, EW,
Wisneski JA,
Neese RA,
Bristow JD,
Searle GL,
and
Hanlon JT.
Myocardial lactate metabolism: evidence of lactate release during net chemical extraction in man.
Circulation
63:
1273-1279,
1981[Abstract].
7.
Gertz, EW,
Wisneski JA,
Neese R,
Houser A,
Korte R,
and
Bristow JD.
Myocardial lactate extraction: multi-determined metabolic function.
Circulation
61:
256-261,
1980[Abstract].
8.
Griesmacher, A,
Grimm M,
Schreiner W,
and
Muller MM.
Diagnosis of perioperative myocardial infarction by considering relationship of postoperative electrocardiogram changes and enzyme increases after coronary by-pass operation.
Clin Chem
36:
883-887,
1990
9.
Habicht, JM,
Wolff T,
Langemann H,
and
Stulz P.
[Intraoperative and postoperative microdialysis measurement of the human heartfeasibility and initial results].
Swiss Surg Suppl
2:
26-30,
1998.
10.
Hamada, M,
Kuwahara T,
Shigematsu Y,
Kodama K,
Hara Y,
Hashida H,
Ikeda S,
Ohtsuka T,
Nakata S,
and
Hiwada K.
Relation between coronary blood flow and left ventricular mass in hypertension: noninvasive quantification of coronary blood flow by thallium-201 myocardial scintigraphy.
Hypertens Res
21:
227-234,
1998[Medline].
11.
Hearse, DJ,
Stewart DA,
and
Braimbridge MV.
Myocardial protection during ischemic cardiac arrest. Possible deleterious effects of glucose and mannitol in coronary infusates.
J Thorac Cardiovasc Surg
76:
16-23,
1978[Abstract].
12.
Holmang, A,
Mimura K,
Bjorntorp P,
and
Lönnroth P.
Interstitial muscle insulin and glucose levels in normal and insulin-resistant Zucker rats.
Diabetes
46:
1799-1804,
1997[Abstract].
13.
Holmang, A,
Muller M,
Andersson OK,
and
Lönnroth P.
Minimal influence of blood flow on interstitial glucose and lactate-normal and insulin-resistant muscle.
Am J Physiol Endocrinol Metab
274:
E446-E452,
1998
14.
Jansson, PA,
Krogstad AL,
and
Lönnroth P.
Microdialysis measurements in skin: evidence for significant lactate release in healthy humans.
Am J Physiol Endocrinol Metab
271:
E138-E142,
1996
15.
Jansson, PA,
Larsson A,
Smith U,
and
Lönnroth P.
Glycerol production in subcutaneous adipose tissue in lean and obese humans.
J Clin Invest
89:
1610-1617,
1992[ISI][Medline].
16.
Kammermeier, H,
and
Wendtland B.
Interstitial fluid of isolated perfused rat hearts: glucose and lactate concentration.
J Mol Cell Cardiol
19:
167-175,
1987[ISI][Medline].
17.
Kaukoranta, PK,
Lepojarvi MV,
Kiviluoma KT,
Ylitalo KV,
and
Peuhkurinen KJ.
Myocardial protection during antegrade vs. retrograde cardioplegia.
Ann Thorac Surg
66:
755-761,
1998
18.
Kennergren, C,
Mantovani V,
Lönnroth P,
Nyström B,
Berglin E,
and
Hamberger A.
Extracellular amino acids as markers of myocardial ischemia during cardioplegic heart arrest.
Cardiology
91:
31-40,
1999[ISI][Medline].
19.
Kennergren, C,
Mantovani V,
Lönnroth P,
Nyström B,
Berglin E,
and
Hamberger A.
Monitoring of extracellular aspartate aminotransferase and troponin T by microdialysis, during and after cardioplegic heart arrest.
Cardiology
92:
162-170,
2000[ISI].
20.
Kennergren, C,
Nyström B,
Nyström U,
Berglin E,
Larsson G,
Mantovani V,
Lönnroth P,
and
Hamberger A.
In situ detection of myocardial infarction in pig by measurements of aspartate aminotransferase (ASAT) activity in the interstitial fluid.
Scand Cardiovasc J
31:
343-349,
1997[ISI][Medline].
21.
King, LM,
and
Opie LH.
Glucose and glycogen utilisation in myocardial ischemiachanges in metabolism and consequences for the myocyte.
Mol Cell Biochem
180:
3-26,
1998[ISI][Medline].
22.
Kjellman, UW,
Bjork K,
Ekroth R,
Karlsson H,
Jagenburg R,
Nilsson FN,
Svensson G,
and
Wernerman J.
Addition of alpha-ketoglutarate to blood cardioplegia improves cardioprotection.
Ann Thorac Surg
63:
1625-1633,
1997
23.
Larrieu, AJ,
Kao RL,
Yazdanfar S,
Redovan E,
Silver J,
Ghosh S,
and
Magovern GJ.
Preliminary evaluation of cocarboxylase on myocardial protection of the rat heart.
Ann Thorac Surg
43:
168-171,
1987[Abstract].
24.
Larsen, TS,
Irtun O,
Steigen TK,
Andreasen TV,
and
Sorlie D.
Myocardial substrate oxidation during warm continuous blood cardioplegia.
Ann Thorac Surg
62:
762-768,
1996
25.
Lönnroth, P,
Carlsten J,
Johnson L,
and
Smith U.
Measurements by microdialysis of free tissue concentrations of propranolol.
J Chromatogr
568:
419-425,
1991[Medline].
26.
Lönnroth, P,
Jansson PA,
and
Smith U.
A microdialysis method allowing characterization of intercellular water space in humans.
Am J Physiol Endocrinol Metab
253:
E228-E231,
1987
27.
Lönnroth, P,
and
Strindberg L.
Validation of the "internal reference technique" for calibrating microdialysis catheters in situ.
Acta Physiol Scand
153:
375-380,
1995[ISI][Medline].
28.
McCully, JD,
and
Levitsky S.
Alternatives for myocardial protection: adenosine-enhanced ischemic preconditioning.
Ann NY Acad Sci
874:
295-305,
1999
29.
Muller, M,
Holmang A,
Andersson OK,
Eichler HG,
and
Lönnroth P.
Measurement of interstitial muscle glucose and lactate concentrations during an oral glucose tolerance test.
Am J Physiol Endocrinol Metab
271:
E1003-E1007,
1996
30.
Paternostro, G,
Camici PG,
Lammerstma AA,
Marinho N,
Baliga RR,
Kooner JS,
Radda GK,
and
Ferrannini E.
Cardiac and skeletal muscle insulin resistance in patients with coronary heart disease. A study with positron emission tomography.
J Clin Invest
98:
2094-2099,
1996
31.
Pietersen, HG,
Langenberg CJ,
Geskes G,
Kester A,
de Lange S,
van der Vusse GJ,
Wagenmakers AJ,
and
Soeters PB.
Myocardial substrate uptake and oxidation during and after routine cardiac surgery.
J Thorac Cardiovasc Surg
118:
71-80,
1999
32.
Rinne, T,
Laurikka J,
Penttila I,
and
Kaukinen S.
Adenosine with cold blood cardioplegia during coronary revascularization.
J Cardiothorac Vasc Anesth
14:
18-20,
2000[ISI][Medline].
33.
Robinson, LA,
Braimbridge MV,
and
Hearse DJ.
Comparison of the protective properties of four clinical crystalloid cardioplegic solutions in the rat heart.
Ann Thorac Surg
38:
268-274,
1984[Abstract].
34.
Salerno, TA,
and
Chiong MA.
Cardioplegic arrest in pigs. Effects of glucose-containing solutions.
J Thorac Cardiovasc Surg
80:
929-933,
1980[Abstract].
35.
Stowe, DF.
Understanding the temporal relationship of ATP loss, calcium loading, and rigor contracture during anoxia, and hypercontracture after anoxia in cardiac myocytes.
Cardiovasc Res
43:
285-287,
1999[ISI][Medline].
36.
Svedjeholm, R,
Ekroth R,
Joachimsson PO,
Ronquist G,
Svensson S,
and
Tyden H.
Myocardial uptake of amino acids and other substrates in relation to myocardial oxygen consumption four hours after cardiac operations.
J Thorac Cardiovasc Surg
101:
688-694,
1991[Abstract].
37.
Svensson, S,
Svedjeholm R,
Ekroth R,
Milocco I,
Nilsson F,
Sabel KG,
and
William-Olsson G.
Trauma metabolism and the heart. Uptake of substrates and effects of insulin early after cardiac operations.
J Thorac Cardiovasc Surg
99:
1063-1073,
1990[Abstract].
38.
Teoh, KH,
Mickle DA,
Weisel RD,
Fremes SE,
Christakis GT,
Romaschin AD,
Harding RS,
Madonik MM,
and
Ivanov J.
Decreased postoperative myocardial fatty acid oxidation.
J Surg Res
44:
36-44,
1988[ISI][Medline].
39.
Thorelius, J,
Ekroth R,
Joachimsson PO,
van der Linden J,
Ronquist G,
Tyden H,
and
Wesslen O.
Myocardial metabolism 8 hours after coronary surgery: effects of dopamine.
Scand J Thorac Cardiovasc Surg
28:
135-141,
1994[ISI][Medline].
40.
Thourani, VH,
Nakamura M,
Ronson RS,
Jordan JE,
Zhao ZQ,
Levy JH,
Szlam F,
Guyton RA,
and
Vinten-Johansen J.
Adenosine A3-receptor stimulation attenuates postischemic dysfunction through KATP channels.
Am J Physiol Heart Circ Physiol
277:
H228-H235,
1999
41.
Watanabe, T,
Okazaki O,
Akutsu Y,
Yamanaka H,
Michihata T,
Katagiri T,
and
Harumi K.
Correlation between myocardial blood flow and fasting glucose metabolism in ischemic heart disease. Quantitative assessment by nitrogen-13 ammonia and fluorine-18 fluorodeoxyglucose positron emission tomography.
Jpn Heart J
39:
275-285,
1998[ISI][Medline].
42.
Wisneski, JA,
Gertz EW,
Neese RA,
Gruenke LD,
and
Craig JC.
Dual carbon-labeled isotope experiments using D-[6-14C] glucose and L-[1,2,3-13C3] lactate: a new approach for investigating human myocardial metabolism during ischemia.
J Am Coll Cardiol
5:
1138-1146,
1985[ISI][Medline].
43.
Wisneski, JA,
Gertz EW,
Neese RA,
Gruenke LD,
Morris DL,
and
Craig JC.
Metabolic fate of extracted glucose in normal human myocardium.
J Clin Invest
76:
1819-1827,
1985[ISI][Medline].
44.
Yudilevich, DL.
Blood-tissue transport of substrates in the heart: studies by single circulation tracer dilution.
Int J Microcirc Clin Exp
8:
397-409,
1989[ISI][Medline].