Onset of blood lactate accumulation exercise capacity, skeletal muscle fibers and metabolism before and after coronary artery bypass grafting

Onset of Blood Lactate Accumulation Exercise Capacity, Skeletal Muscle Fibers

and Metabolism Before and After Coronary Artery Bypass Grafting

Jan Karlsson, PhD

Male patients with effort angina were studied before (n = 7), I week, and 1 and 6 months (n = 6) after coronary artery bypass grafting (CABG) with 2 to 7 grafts. The test battery included graded exercise, which was performed until unbearable leg exertion or chest pain, or both, was present. On- sets of blood lactate accumulation, anginal pain, leg exertion and dyspnea were interpolated for either the lactate concentration 2 mmol X 1-1 or the ratings 2 on the Borg subjective intensity scale. On- sets of blood lactate accumulation and symptom- limited exercise capacity before surgery amounted to 58 and 100 W, respectively. The corresponding figures 6 months later were the same for onset of blood lactate accumulation, whereas symptom- limited exercise capacity had increased by 58%. Blood lactate was the same at rest and mild exercise (~ onset of blood lactate accumulation) but more than doubled at symptom-limited exercise capacity (peak blood lactate concentration). Muscle fl- ber typing showed a low figure for the slow twitch fiber proportion (35%), which was unchanged after 6 months. Fast twitch subtype C was elevated before (7%) but disappeared after surgery, and fast twitch subtype A percent increased corresponding- ly. The major muscle biochemical changes were in the glycogenolytic pathway and the lactate dehydrogenase enzyme system, which appeared to increase in a quantitative manner, but with an unchanged relative lactate dehydrogenase isozyme pattern.

The increased symptom-limited exercise capacity was related to the increased glycogenolytic activity and peak blood lactate (i.e., increased "anaerobic power"). Whether the causative explanation was the relief from chest pain, i.e., a psychophysio- logic feature or the biochemical changes that took place in the muscle could only be speculated on.

(Am J Cardiol 1988;62:108E- I14E)

From the Department of Clinical Physiology, Karolinska Hospital, S-104 01 Stockholm, Sweden.

Address for reprints: Jan Karlsson, MD, Department of Clinical Physiology, Karolinska Hospital, S- 104 01 Stockholm, Sweden.

M ost studies show a marked improvement in exercise performance after coronary artery bypass grafting (CABG) in patients with crip-

pling effort angina. ~ In contrast, catherization scores, e.g., left ventricular power index vs left ventricular end- diastolic pressure, are not elevated to the same extent, z This discrepancy between the catheterization score and the changes in exercise capacity with grafting has led some investigators to suggest denervation and even place- bo ("acupuncture-like") effects as explanatory circum- stances for the obvious improvement in exercise performance and relief from chest pain during physical activity. 3

No or very little interest has been paid to the periphery as a feature of interest with respect to changed exercise capacity in these patients after surgery. In healthy humans, it is well recognized that both central circulatory capacity as well as the periphery ("skeletal muscle") are significant even for endurance performance capacity, which earlier almost exclusively has been considered related to heart and subsequently stroke volumes, cardiac output and oxgyen delivery capacity. 4-6 With these considerations in mind, we thought it would be of interest to study exercise performance in patients with effort angina before and after coronary bypass surgery, and to relate these changes to simultaneous alterations in the metabolic profile of the contracting muscles of these patients with disabling ischemic heart disease with impaired left ventricular function.

METHODS The onset of blood lactate accumulation exercise

stress test protocol was used because it takes into account both central and peripheral features of significance for endurance exercise performance. 7 This test is based on graded exercise, either cycle or treadmill running, and frequent, moderate intensity increments. 8,9 The increments correspond during cycle ergometer exercise to 10 to 40 W × min -t depending on anamnestic information. Guiding for the intensity increment is that the total exercise time shall not supersede 15 minutes to avoid thermo- regulatory problems and heat stress in the contracting musculature and subsequent discomfort.

Graded exercise of this nature leads almost exclusively to lactate formation in and release from the exercising muscles and accumulation in circulating blood, even in patients with severe ischemic heart disease and an ex- tremely low "maximal" exercise capacity (30 to 50 W).l°

108E THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME62

Based on the relation between blood lactate.concentration and exercise intensity, the load eliciting a lactate concentration corresponding to 2 mmol × 1-m is interpolated and referred to as onset of blood lactate accumulation above resting value. The exercise test is terminated when the patient is either leg-muscle exhausted or has unbearable chest pain, or both. This load is defined as symptom-limited exercise capacity.

At each work load and before intensity increment, the patients are interviewed about their chest pain (anginal pain), leg exertion and dyspnea according to the Borg scale ranging from I to 10. 7 The rating 2 or "weak" according to the worded anchor and the corresponding exercise intensity is used to determine onsets of anginal pain, leg exertion and dyspnea, respectively.

Needle muscle biopsy specimens were obtained after local anesthesia from the lateral portion of the thigh muscle (m. vastus lateralis), frozen in liquid nitrogen- precooled isopentane and stored at -80°C until further analysis.11,12 An analytic program was undertaken with respect to histologic and biochemical properties as well.

It is well recognized from a neuromotoric point of view that human skeletal muscle tissue is innervated by 2 major types of motor neuron: fast and slow, although a continuum existsJ 3 This pattern also has its correspon- dence in the composition of muscle cells or rather fibers. The fast motor neuron recruits fast twitch (Type II or "white") fibers, whereas the slow motor neuron recruits slow twitch (Type I or "red") fibers. Undergroups of both fiber types are documented, but only the fast twitch subgroups have been found to have physiologic signficance. 6

The fiber typing is based on different iso(en)zyme patterns for myosin and their resistance to incubation at different pH. This isozyme difference has its counterpart in other protein structure differences, which have their impact on the metabolic profile of the 2 major fiber types.6.14 The different metabolic profiles have their bearing on metabolism in general and adenosine triphosphatase resynthesis in particular. The fast twitch fiber has a more profound glycogenolytic profile but a subsequently higher degree of susceptibility to fatiguing processes resulting from lactic acid formation and accumulation. 6,]4.]5 The slow twitch fiber, on the other hand, is more dependent on combusting processes and then, by definition, the availability of molecular oxygen. The lat- ter property is also, from a teleologic point of view, related to the fact that the 2 major fiber types appear to be differently innervated concerning afferents involved in

TABLE I Mean Value and Range for Physical Characteristics in Seven Men with Effort Angina

Age Weight Height WSL WOBLA

(yr) (kg) (cm) (W) (W)

Effort 54=t=6.5 82=1=10 1774-4 100=1=42 78:1=36 angina (48-62) (68-103) (174-183) (40-160) (14-170) patients

WSL = symptom-limited exercise capacity; Woo~ = exercise intensity eliciting a blood lactate concentration of 2 mmol X 1-L

regulation of central circulation. 16,m 7 Shepherd et al,16 in 1981, introduced the term ergoreceptor to count for these physiologically and pharmacologically well-defined properties. It appears reasonable to relate the lower peripheral resistance both at rest and during exercise in subjects with many slow twitch fibers in their contracting muscles, and the overall more smooth regulation of heart rate and blood pressure during exercise to this entity. Is

The higher combustive potential of the slow twitch fiber, the higher capillary intensity and the larger maximal cardiac output make this fiber type more susceptible to formation of different free radical species, especially free oxygen radicals. 19,20 The slow twitch fiber also has a larger orchestra of antioxidant activities than the fast twitch fiber to cope with this threat to cellular integrity. This includes higher enzyme activities for superoxide dis- mutase, glutathione peroxidase and reductase, catalase,

e

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e

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i J i

020 40 SO 80

i Q B

i

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i i i t

30 40 50 80 2O

Muscle fiber composition expressed as percent slow twiLch fibers, t

FIGURE 1. Muscle ubiquinone, coenzyme qlO, Coqto or "vi- tamin q" content in the lateral portion of the thigh skeletal muscle (m. vasltus lateralis) in healthy volunteers (upper panel) and the present paUents with effort angina (lower panel) vs the corresponding slow twitch fiber proporUon. 2z

THE AMERICAN JOURNAL OF CARDIOLOGY SEPTEMBER9, 1988 1 0 9 Ir

A SYMPOSIUM: REGIONAL BLOOD FLOW IN CONGESTIVE HEART FAILURE

etc. In addition, the slow twitch fiber contains more of the mitochondrial electron shuttler ubiquinone, coenzyme Qlo or CoQIo, which especially in its reduced form is a potent trapper and scavenger of the 2 radical species: the superoxide and hydroxyl ions. 2]

These recently appreciated properties of muscle metabolism have to be included in the discussion of peripheral changes in patients with cardiovascular diseases, adaptation mechanisms and effects of pharmacologic treat- ments. Coenzyme Qt0 determinations were also included in the test battery in addition to the glycogenolytic and combustive markers, phosphofructokinase, lactate dehydrogenase and citrate synth(et)ase enzyme activities. 21

Seven men (mean age 54 years) (Table I), who were referred to the clinic as candidates for CABG and preoperative evaluation, were recruited for the project. Their preoperative ejection fraction at rest was 46 4- 7 (stan- dard deviation). They had 2 to 7 grafts, and no postoperative ejection fraction data were obtained. The patients were studied with exercise stress tests the day before surgery, 1 week, and I and 6 months after surgery (n = 6). Muscle biopsy specimens were obtained before, and 1

and 6 months after surgery. The study was approved by the Ethical Committee of the Karolinska Hospital.

RESULTS Characteristics in effort angina (before surgery):

Onset of blood lactate accumulation and symptom-limited exercise capacity averaged 78 to 100 W, respectively (Table I) (i.e., they represented a moderate to medium exercise capacity for patients with effort angina)J ° On- sets of anginal pain, dyspnea and leg exertion corresponded to approximately 50 W. Their muscle fiber composition corresponded to 35% of slow twitch fibers. An age-matched control group of healthy men would have 55% slow twitch fibers. 2z Whether the difference depends on endowment or adaptation is only speculative.

Other markers of muscle combustive metabolism also appeared to be down-regulated, such as citrate synthase activity and CoQto content. On an individual basis, both citrate synthase activity and CoQ]o content tended to decrease with percent slow twitch fibers. This is significantly different from healthy male volunteers (as de- scribed for CoQ[0 in Figure 1). The first derivative of this

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.002 20 40 60 60 SO0

I~scle fiber composition expressed as percenL slov tviLch fibers, |

F IGURE 2. The first derivative of the relations in Figure 1. The ratio muscle CoQso content over s low tw i t ch fiber percent (ST %) has been suggested to represent a metabolic lesion index.2S

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Huscle iiber composilion expressed as pe[cenl slov lwiLch fibe[s, |

F IGURE 3. Exerc ise capac i ty in patients with effort angina (preoperative values) expressed as either onset of blood lac- ta te accumulation (WosLA) or WOeLA as the fraction of symptom-limited exercise capacity (WsL) VS muscle fiber compos i - t ion in the vastus lateralis muscle expressed as the fraction (%) s low tw i t ch muscle fibers (% ST).

1 1 0 Ir THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 62

relation showed a faster decrease in patients than in healthy volunteers, which suggests a larger radical stress to the skeletal muscles in patients relatively rich in slow twitch fibers (Fig. 2). The data could also be interpreted as a sign of fast twitch fiber-related protection confined to less capillary density around and mitochondria in this fiber type. This means less exposure to free radical formation.

The ratio muscle CoQlo content over percent slow twitch has been suggested as an indication of metabolic lesion, which would then be more dominant in slow than in fast twitch fibers./I This circumstance was further supported when the fast twitch subgroups were exam- ined, showing a depressed fast twitch subtype A (the "intermediate fiber type") but enhanced fast twitch subtype C proportion (22 and 7%).

The indication of a larger metabolic stress to the slow twitch fiber population was also present when exercise performance criteria were related to skeletal muscle characteristics. Thus, onset of blood lactate accumulation, in itself, or expressed as a fraction of symptom-limited exercise capacity (onset of blood lactate accumulation percent) increased the higher the percent slow twitch fibers (Fig. 3).

Effects of coronary artery bypass grafting: CABG caused a marked increase in symptom-limited exercise capacity, while onset of blood lactate accumulation remained virtually unchanged (Fig. 4). Mean symptom- limited exercise capacity increased by 58%. Also leg exertion and dyspnea increased significantly (Fig. 4). No patient reported chest pain in any of the postoperative tests. The changes appeared to have been already estab- lished after 1 month as illustrated by the individual values for onset of blood lactate accumulation and symptom- limited exercise capacity (Fig. 5).

An unchanged onset of blood lactate accumulation means the same blood lactate concentration at submaximal exercise intensities before and after operation. Rest- ing blood lactate was also unchanged (1.2 to 1.3 mmol × l-S), whereas peak blood lactate concentration, i.e., lactate at symptom-limited exercise capacity, was markedly increased from 3.6 to 7.4 mmol X 1-L Blood lactate concentration integrates for both release and uptake phe- nomena. An increased peak blood lactate concentration could reflect changed allocation properties such as improved release due to an enhanced local blood flow in the contracting muscles and a subsequently increased lactate efflux. However, the present increase was out of proportion to what a similar redistribution could maximally account for. One could suggest an increased lactate formation indicative of an increased adenosine triphosphatase formation through the glycogenolytic pathway ("anaerobic metabolism and capacity"). 6

The combustive profile of the leg muscles appeared unchanged after CABG, whereas changes occurred with- in the fast twitch fiber population and the glycogenolytic profile in line with the observed increased symptom-limited exercise capacity and lactate formation (Fig. 6 and 7). The increased lactate dehydrogenase activity covaried with the activity of 1 of the 2 proteins constituting

the lactate dehydrogenase molecule--the muscle-specific subunit M. Thus, straight individual relations existed between lactate dehydrogenase and the isozyme lactate de- hydrogenase5 (with exclusively M units) (before: r -- 0.90, p <0.01; after 6 months: r = 0.98, p <0.001) and between M unit activity and lactate dehydrogenase5 isozyme activity (before: r = 0.99, p <0.001; after 6 months: r = 0.97, p <0.001). The regression lines did not indicate any qualitative changes between lactate dehydrogenase subunits, isozyme and total enzyme activities. Conse- quently, lactate dehydrogenase3%, lactate dehydroge- nase4% and lactate dehydrogenase5% were the same before and after surgery.

An increased contribution from "anaerobic sources" means by definition that the "aerobic performance" ac- counts for a smaller fraction of the total energy output. In this study, this resulted in a postoperatively decreased onset of blood lactate accumulation percent. On an indi-

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p ( .001 150 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

loo 'p~-:Ot .............. p _ L ~ ................................. ~ . . . .

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FIGURE 4. Mean values for onset of leg exertion 0NoLE), dyspnea (WoD), Mood lactate accumulation 0NosLA) and symptom- limited exercise capacity (WsL) during the graded cycle ergometer exercise stress test the day before coronary bypass surgery (b) and 6 months later (a).

1 2 5 "

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25-

o o + w

p< .Ol / ° //" : / +//

WSL, W

FIGURE S. Individual values for onset of blood lactate accumulation (WoBLA) VS symptom-limited exercise capacity (Wu.) before, and 1 and 6 months after coronary bypass surgery.

THE AMERICAN JOURNAL OF CARDIOLOGY SEPTEMBER 9, 1988 111 I¢

A SYMPOSIUM: REGIONAL BLOOD FLOW IN CONGESTIVE HEART FAILURE

vidual basis, such a relation was already present preoperatively (Fig. 8). The postoperative relation, although not statistically significant, appeared to follow the same function.

DISCUSSION The major findings in this study on the effect of

CABG in patients with ischemic heart disease and disabling effort angina were: (1) confirmed increased exercise capacity expressed as symptom-limited och "maximal" work load; (2) markedly increased peak lactate concentrations at symptom-limited exercise, whereas concentrations at rest and mild exercise intensities were the same (i.e., that onset of blood lactate accumulation was the same before and 6 months after operation); (3)

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a b a b a b a

FT A FT B FT C

FIGURE 6. The fraction of fast twitch (F'r) muscle fibers in the lhigh muscle before (b) and 6 months after (a) coronary bypass surgery. FT A - C represent the subgroups. FT A the "intermediate" fiber, FT B the "true" glycogenolytic fiber and FT C a fiber in transformation, decomposition and cell death, s

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LD ACTIVITY LD-M SUBUNIT ACTIVITY

FIGURE 7. The giycogenolytic potential of the thigh muscle (m. vastus lateralis) as represented by phosphofructokinase (PFK), total lactate dehydrogenase (LD) and the LD-M subunit activities before (b) and 6 months after (a) coronary bypass surgery.

increased up-regulation of skeletal muscle lactate dehydrogenase activity as a result of absolute but not relative increases in lactate dehydrogenase isozymes (lactate de- hydrogenase3-1actate dehydrogenases); (4) unchanged total muscle fast twitch fiber composition, but a disap- pearance of the subgroup fast twitch C (this fiber-type subgroup reflects fiber trauma and decomposition before and recovery after operation); and (5) no chest pain, less leg exertion and dyspnea during mild exercise, but the same leg exertion and dyspnea ratings at symptom-limited exercise.

In healthy humans, leg exertion is well correlated to both blood and muscle lactate) 5 This is also true for anginal pain and leg exertion vs blood lactate in patients with effort angina. 8,t0,~7 After surgery and at symptom- limited exercise, the current data disclosed the same leg exertion but higher blood lactate levels. No data were obtained on local muscle lactate, but the down-regulated slow twitch fiber population and the subsequently lowered capillary density speaks in favor of an enhanced lactate gradient muscle to blood. 17 The possibility is then obvious that one and the same muscle lactate concentration at symptom-limited exercise before surgery corresponded to a lower blood lactate than after surgery, when circulatory capacity was improved) '/ In addition, it is possible that the presence of anginal pain before surgery could have lowered the setting point for leg exertion. This would then imply, hypothetically, a higher leg exertion score for the same muscle lactate before than after surgery, when no anginal pain was experienced. How- ever, there is no experimental evidence to support this hypothesis.

The increased peak lactate concentration can only be related minimally to a changed efflux and redistribution of lactate. The explanation that is left is an increased lactate production, release and accumulation in circulating blood. This is indicative of an increased glycogenolytic activity and enhanced adenosine triphosphatase contribution from "anaerobic" sources.] 2

Assuming a mechanical efficiency corresponding to 23% (10 W increments equals VO2 increments of 0.14 liters × min -t) and a complete "aerobic energy production," the preoperative graded exercise would correspond to a total oxygen use of 7.7 liters. How large was the "anaerobic fraction"? This question can be approached providing some assumptions: (I) a muscle to blood lactate gradient corresponding to 2:1,12,t s (2) a contracting skeletal muscle mass of 10 kg, and (3) blood lactate concentration representing the remaining fluid compartments-- approximately 40 liters.

The total preoperative lactate formation would then correspond to 0.21 mol, which equals a VO2 of 1.2 liters) 2 In relative terms, the preoperative anaerobic fraction would then correspond to approximately 16%.

The corresponding postoperative values 6 months after surgery would be 10.6 liters, assuming a complete aerobic energy production during exercise and a calculat- ed anaerobic fraction of 2.5 liters of oxygen, respectively. In relative terms, this meant 24%. If anything, the anaerobic fractions are underestimated because it can be taken

11121' THE AMERICAN JOURNALOF CARDIOLOGY VOLUME 62

for granted that some lactate has been combusted in the heart, resting and semiactive muscles and even in the working muscles at "no extra cost" during the graded exercise.6, t;

The down-regulated glycogenolysis in effort angina (i.e., preoperative values) appeared then to have a physiologic implication. Down-regulation has earlier been observed in relation to endurance type training. 23 However, in those studies the lowered lactate dehydrogenase activity was accompanied and explained by a lactate dehydrogenase isozyme shift toward lactate dehydrogenase3-1ac- tate dehydrogenaset, i.e., the "heart specific isozymes." The down-regulated glycogenolytic activity corresponded then to an up-regulated combustive potential of the lactate dehydrogenase isozyme system. This is in contrast to the data obtained in the present patients, where no relative isozyme shift was observed.

The reason for the down-regulation is only speculative. In healthy humans, there is a positive venous-arterial difference in the femoral blood for creatine kinase and lactate dehydrogenase activities already at exercise intensities corresponding to onset of blood lactate accumulation, (i.e., 50 to 60% of VO2max). The patients in this study appeared to have traumatized exercising muscles as indicated by the preoperative fast twitch subtype C values. It is then possible that the present down-regulation could be related to a more extended protein leakage in contrast to the lactate dehydrogenase changes seen in endurance-type training, when a qualitatively changed protein synthesis may be the most obvious explanation.6,14,23

Peak blood lactate concentration can vary with a figure of 2 to at the most 5 between patients with ischemic heart disease and different groups of healthy volunteers. 8 This is in contrast to symptom-limited exercise, when the corresponding figure could amount to 10 to 15. The discrepancy is depending on the impact of ischemic heart disease on cardiac performance, perhaps in combination with endowment. 24 Less oxygen transport means, by definition, less aerobic performance.t 2 It is then proposed that patients with effort angina already during normal daily activities operate at intensities, which is referred to in published reports on sports medicine as "anaerobic training." In healthy humans, this results in an up-regulation of lactate dehydrogenase activity and an enhanced glycogenolytic potential. 23 As pointed out previously, the current results indicate the opposite direction with lactate dehydrogenase down-regulation. The question then arises whether the result of surgery is the relief of Chest pain and the ability to attain an even higher exercise intensity and a subsequent up-regulation. Future studies are needed to address that question.

The citrate synthase and CoQ]o data before and after surgery are puzzling. There was a marked difference compared with results in healthy volunteers and free oxygen radical trauma was proposed. 2~ Although the fast twitch subtype C fibers had disappeared after surgery, minute changes were seen in citrate synthase activity and CoQ~0 content. Preliminary electronmicroscopic analyses have preoperatively revealed "rugged" fibers, as seen ear-

I00 o

~ 7a

Before After 6 months - "r=-.96 "r:-.SB p ( .OOl p < .5

iO , , ,

0 2 4 6 B

PBK BLOOD LACTATE CONCENTRATION, aol x 1-1

FIGURE 8. Individual values for the onset of Mood lactate accumulation (Worn.A) h'action of symptom-limited exercise capacity (WsL) (Worn.A%) in relation to the corresponding peak blood lactate concentration during graded exercise before and 6 months after coronary bypass surgery.

lier in extreme marathon and ultramarathon runners (un- published observations).

Eldridge et a125 reported similar data to this study with respect to effort angina and exercise capacity. They found in patients with ischemic heart disease with approximately the same ejection fraction (50%) and the same peak blood lactates (4.5 mmol × 1 -l) that onset of blood lactate accumulation (lactate threshold) corresponded to 66% of maximal values compared with 57% for healthy volunteers. As mentioned previously, a high percentage figure means less anaerobic capacity usually seen only in endurance athletes. 8

Sax et a126 recently reported data concerning skeletal muscle "vasodilator reserve" in patients with angina, They found a 21% lower peak forearm blood flow after cuff-induced ischemia than that found in healthy con- trols. They suggested an "...impairment of vasodilator reserve ..." without discussing the biologic background. Zelis and Flaim 2~ suggested that in congestive heart failure, an arteriolar constriction will support systemic blood pressure and maintain flow to vital organs as the heart itself. Assuming that this suggestion has a bearing on ischemic heart disease and effort angina, the present data add some experimental support because the preoperative muscle fiber composition indicated an enhanced peripheral resistance. 28

Physical conditioning has improved exercise tolerance in patients with ischemic heart disease or congestive heart failure in general. 29-31 Providing a very low initial ejection fraction (20 to 25%), blood lactate is lowered or deep vein oxygen saturation is increased during submaximal exercise. This is in contrast to current blood lactate findings. Whether the discrepancy is related to the degree of deterioration of left ventricular function or the etiology of the disease is only hypothetical. Peak exercise capacity and, in most cases, peak blood lactate increased. Likoff 29 strongly advocates a down-regulation of the periphery related to lack of physical inactivity as the explanation. In line with this, Likoff argues for an increased conditioning

THE AMERICAN JOURNAL OF CARDIOLOGY SEPTEMBER9, 1988 11'1131r

A SYMPOSIUM- REGIONAL BLOOD FLOW IN CONGESTIVE HEART FAILURE

program in these patient groups to improve their exercise tolerance and subsequently their "quality of life."

In conclusion, men with effort angina (n -- 7) have been investigated before and after coronary bypass surgery. Previously observed increases in symptom-limited exercise capacity have been confirmed in addition to a complete relief from chest pain. Blood lactate concentration at rest and at mild exercise intensities (~ onset of blood lactate accumulation) were unchanged, whereas peak blood lactate more than doubled. Skeletal muscle studies revealed an increased glycogenolytic potential after surgery (up-regulation), which could have a causative significance for the increased "anaerobic energy production" and an increased "anaerobic" fraction after surgery and recovery. The preoperative data also implied cellular trauma in the muscle both from a histologic and biochemical point of view related to the oxidative, oxygen-depending processes. The postoperative histologic data indicated a recovery in that respect, whereas the biochemical indi- cations of a metabolically down-regulated combustive profile in the contracting muscles remained.

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Onset of blood lactate accumulation exercise capacity, skeletal muscle fibers and metabolism before and after coronary artery bypass grafting