MYOCARDIAL LACTATE AND PYRUVATE METABOLISM Norman Krasnow, … , Joseph V. Messer, Richard Gorlin J Clin Invest. 1962;41(11):2075-2085. https://doi.org/10.1172/JCI104665. Research Article Find the latest version: https://jci.me/104665/pdf Journal of Clinical Investigation Vol. 41, No. 11, 1962 MYOCARDIAL LACTATE AND PYRUVATE METABOLISM * By NORMAN KRASNOW, WILLIAM A. NEILL, JOSEPH V. MESSER, AND RICHARD GORLIN t (From the Medical Clinics, Peter Bent Brigham Hospital, and Department of Medicine, Harvard Medical School, Boston 15, Mass.) (Submitted for publication May 23, 1962; accepted August 1, 1962) Although the heart has been considered pri- myocardial lactate extraction. Excess lactate has marily an aerobic organ, recent work (1) has re- not been found in normal or diseased human sub- emphasized the possibility that measurement of jects (10-15) at rest except in a few patients oxygen consumption alone may not 1)e adequate with progressive muscular dystrophy (16). None to define the total energy utilization under all con- has been subjected to exercise. ditions. The role of anaerobic metabolism must The purposes of this report are to describe 1) be reviewed. the effects of the stresses of physical exercise and Methods of defining as well as quantifying ischemia on myocardial lactate and pyruvate me- anaerobiosis are currently in dispute. When oxi- tabolism in man and dogs and 2) the role of dation and glycolysis proceed at the same rate, anaerobiosis during these stresses. carbohydrate is oxidized to CO2 and H20. Lac- tate arises whenever the rate of glycolysis exceeds MATERIALS AND METHODS the rate of oxidation. Net production of lactate Thirty-four fasting, subjects were studied by cardiac by an organ, as evidenced for example by venous and coronary sinus catheterization. Diagnoses are listed concentration greater than arterial, has been con- in Table I. Left ventricular failure was defined as an end-diastolic pressure greater than 10 mm Hg at rest, sidered to represent anaerobic metabolism due to or a pulmonary wedge pressure greater than 12 mm Hg cellular hypoxia (2). More recent work (3) has at rest or 17 on exercise. Coronary insufficiency (in- demonstrated that large changes in lactate pro- cluding angina pectoris alone) was defined as described duction can occur unassociated with hypoxia, but elsewhere (17). No patients had diabetes mellitus, ele- related instead to increased pyruvate production. vated fasting blood sugar,' or severe nutritional depriva- tion. Cardiac medications included digitalis and thiazides; Huckabee introduced the concept of "excess lac- the latter have been reported to raise blood pyruvate tate" in order to distinguish between pyruvate- levels (18). Blain, Eddleman, Siegel, and Bing (19) induced changes in lactate and those related solely indicated that digitalization had no effect on lactate and to a shift in DPN: DPNH redox potential. This pyruvate metabolism. In most cases no premedication was inferred from alterations in arterial lactate- was necessary; in a few, 1 ml of a mixture of meperidine (25 mg per ml), Phenergan (6.25 mg per ml), and pyruvate ratio and the relative arteriovenous dif- chlorpromazine (6.25 mg per ml) was given intramus- ferences of the two substrates. "Excess lactate," cularly. Special care was taken to place the catheter so defined, was considered an indicator of cellular deep in the proximal coronary sinus where homogeneity oxygenation and was used quantitatively as a of sampling has been observed (17), and maximal repre- measure of anaerobic metabolic rate. sentation of left ventricular events may be expected (20). Measurements of blood oxygen content were made im- Anaerobic metabolism in cardiac muscle has mediately prior to and at least 3 minutes after onset of been considered to occur only under extreme con- supine leg-raising; exercise was sufficient to raise mean ditions. Whereas earlier work (4-9) showed lac- myocardial oxygen consumption by 42 per cent (11.2 to tate production only sporadically with stresses of 15.9 ml per 100 g per minute) and total body oxygen con- hypoxia, shock, or myocardial emboli, Huckabee sumption by 112 per cent (145 to 307 ml per minute per m2). Samples for lactate and pyruvate were taken si- (1) found that in dogs the stress of either 10 per multaneously from systemic artery and coronary vein im- cent oxygen breathing or leg exercise would re- mediately prior to and between the fifth and sixth min- sult in myocardial excess lactate despite positive utes of exercise, when a steady state of hemodynamics (21) and arterial blood lactate (22) has been observed. *This was from the U. S. work supported by grants were taken in and transferred Public Health Service (NIH-H-2637). Samples dry syringes t Investigator, Howard Hughes Medical Institute. 1 One patient had an abnormal glucose tolerance test. 2075 2076 KRASNOW, NEILL, MESSER, AND GORLIN TABLE I Myocardial lactate-pyruvate Diagnosis Physio- Etiologic logic Rest Exercise 0 > o cd a uaY'Y'Y0a Q Y c a a o ,Eam.f e % " " aoY" :" . Control-normal left ventricle 1 GW 31 F HR 0 0 .59 +.04 .06 -.02 10.6 1.95 +.21 .07 2 CC 64 F N, small ASD 0 0 .92 +.59 .07 0 12.8 1.78 +.72 .11 3 DB 18 M N 0 0 .53 +.20 .06 -.01 9.3 .90 +44 .07 4 JLy 43 M N 0 0 .35 +.11 .11 +.03 3.2 1.21 +.46 .17 5 RA 41 M N 0 0 .59 +.03 .09 +.01 6.6 1.45 +31 .15 6 AH 47 M MS 0 0 .59 +.13 .05 +01 13.1 2.5 +60 .05 Control-diseases involving LV without CI or CHF 7 LT 20 M Myocard 0 0 .63 +.26 .07 -.02 8.6 1.35 +.64 .07 8 RG 25 M Hypervent, Al 0 0 1.06 +.43 .07 -.01 14.9 2.06 +.70 .06 9 WGt 39 M AL 0 0 2.85 +.90 .10 -.04 28.5 3.63 +.88 .13 10 RD1 20 M AI 0 0 .59 +.02 .10 +.05 5.8 .93 +.37 .08 11 JDet 32 M AL 0 0 .54 +.14 .06 +.03 9.1 .65 +.32 .07 12 JWA 26 M Al 0 0 .52 +.29 .11 +.04 4.7 1.03 +.47 13 13 FB1 18 M AL 0 0 .36 +.14 .09 +.03 4.2 .45 +.05 .10 Coronaryinsufficiency 14 PM 33 F AI, mild 0 .59 +.21 .10 +.01 5.8 .77 +.16 .12 15 LY 37 F LVH, CAD (uncertain) + 0 .81 +.37 .06 -.01 14.0 .71 +.35 .08 16 EE 38 M CAD + 0 .85 +.41 .12 +.04 7.2 .99 +.52 .13 +.05 7.9 1.26 +.54 .13 17 JL 53 M CAD + 0 .37 +.20 .09 +.03 4.2 .49 +.27 .09 .59 +.32 .1 1 18 RC 58 M CAD + 0 .63 -.15 .08 +.03 8.0 1.06 +.68 .09 19 JK 29 M AS. AL + 0 .52 +.07 .08 +.01 6.4 20 SBt 36 F CAD + 0 .55 -.06 .07 -.02 8.2 1.15 -.22 .10 21 MC 38 F CAD MS, old my + 0 .50 +.13 .08 -.01 6.3 1.29 +.29 .11 22 JT 54 M CAD, old my + 0 .52 +.07 .06 0 8.1 .90 +.25 .09 23 VW 51 F Hypervent, CAD (uncertain) + 0 .49 -.03 .12 +.02 4.2 .98 -.26 .15 24 AS 36 M AI, CAD, old my + 0 .43 +.12 .05 0 9.0 1.96 +.60 .14 Congestive heart failure 25 JD 57 M AL, AS, MI 0 + .50 +.16 .09 +.02 5.7 .94 +.33 .11 26 HJ 53 M A, MI 0 + .47 +.12 .08 +.02 6.3 1.54 +.37 .12 27 MCi 46 M AL, AS, MS. MI 0 + .75 +.22 .07 -.06 10.3 1.29 +34 .07 Coronary insufficiency and congestive heart failure 28 CM 45 M AS, AL, MI + + 1.01 +.16 .14 +.01 7.5 2.77 +.73 .19 29 JA 56 M AL + + .67 +.20 .09 -.04 7.8 .99 +.40 .11 30 LR 53 M AS + + .81 -.14 .11 +.01 7.2 2.56 +.43 .19 31 JO 36 M AI + + .52126 .2 +.03 4.5 .67 +.21 .13 32 ED 47 M HCVD, old my + + .38 +.03 .09 0 4.2 .82 +.25 .11 33 LM 51 M Al, MI, AS, MS + + 1.06 +.47 .12 +.03 8.9 1.78 +.86 .12 Miscellaneous 34 JM 20 F Tetralogy 0 0 .81 +.15 .21 +.04 3.8 .99 +.40 .20 -.03 5.0 Mean .70 .20 .10 .01 8.1 1.36 .40 .11 Standard deviation .43 .17 .04 .03 4.6 .69 .22 .035 p value p .001 * Abbreviations: HR =heart block; N =normal; ASD =atrial septal defect; MS =mitral stenosis; LV =left ventricle; CL -coronary insuffici- ency (including angina pectoris); CHF =congestive heart failure; myocard =myocardopathy; hypervent hyperventilation; AL =aortic insuffici- ency; LVH =left ventricular hypertrophy; CAD =coronary artery disease; AS =aortic stenosis; old my 7oldmyocardial infarction; ML =mitrsl insufficiency; HCVD =hypertensive cardiovascular disease; PTM =pressure time per minute; Qo =ox4ygenconsumption. t Rest samples taken 16 to 20 minutes after exercise., within 30 seconds to test tubes containing 3 cc of ice- travenously with morphine, chioralose, and urethane, or cold 10 per cent perchioric acid. This was done to ap- with pentobarbital, were studied. They were ventilated proximate as closely as possible the in vivo lactate and through a cuffed endotracheal tube via a Harvard pyruvate concentrations that change rapidly in vitro (23). respiration pump. Catheters were placed in the coronary A constant time interval for transferring samples was sinus and femoral artery.