Neonatal myocardial oxygen consumption during ventricular fibrillation, hypothermia, and potassium arrest

Neonatal Myocardial Oxygen Consumption During Ventricular Fibrillation, Hypothermia, and Potassium Arrest Michael E. Jessen, MD, Anwar S. Abd-Elfattah, PhD, and Andrew S. Wechsler, MD Department of Surgery, Medical College of Virginia, Richmond, Virginia

Background. Many investigators have examined oxygen consumption in adult hearts under conditions that simulate those encountered duria s cardiac operations and those that approximate basal metabolism. Few studies, however, have addressed this issue in neonatal myocardium. Methods. Hearts from 3- to 9-day-old piglets were studied in a blood-perfused ilolated heart preparation in working, empty beating, fi~iliatin~ potassium chloride-arrested (at 37°C and 15°C), and hypothermic (15°O states. Results. Oxygen consumption (expressed in milliliters of 0 2 per 100 g of ventricular tissue per minute; mean ± standard deviation) was 6.69 ± 1.91 for working hearts and fell to 3.19 ± 1.08 for empty-beating hearts, 3.72 ±

0.84 for fibrillating hearts, 1.30 ± 0.34 for potassiumarrested hearts at 37°C, 0.37 ± 0.18 for hypothermic (15°C) hearts, and 0.32 ± 0.10 for potassium-arrested hearts at 15°C. All values were significantly different except the two obtained at 15°C. Conclusions. Vented fibrillating hearts used more oxygen than empty beating hearts. The addition of an arresting concentration of KC1 did not lower oxygen consumption below that observed with hypothermia alone at 15°C. If potassium-based cardioplegia is incrementally beneficial in neonatal myocardial protection over that afforded by hypothermia alone, its effects cannot be explained by reduction in oxygen demand.

hhe basal oxygen consumption of adult myocardium as been determined by several investigators [1, 2], using a variety of techniques to arrest the heart. These studies have provided a basis for myocardial protective techniques that have proved useful in clinical cardiac surgery, where attempts are made to reduce the metabolic requirements of the heart to their lowest level. Similar protective strategies have been applied to corrective cardiac surgical procedures in neonates, yet their metabolic basis has not been fully evaluated in this population. Neonatal myocardium differs from adult myocardium in several important respects, including calcium regulation [3], sarcolemmal permeability to cations [4], and substrate dependence [5]. We hypothesized that oxidative requirements of ne(matal cardiac tissues in the arrested state differed significantly from those observed in adult myocardium. If true, this might alter our concepts of the relative merit of contemporary myocardial protective strategies in this population. Other conditions that relate to myocardial protection are less well studied in neonates. The diminution in basal (arrested) oxygen consumption that is achieved through myocardial cooling requires quantification in the newborn heart, as hypothermia remains one of the major

myocardial preservation methods used in this group. As well, prolonged ventricular fibrillation, even in the totally vented heart, has been demonstrated to have deleterious effects on myocardial oxygen supply and demand [6]. The influence of fibrillation on metabolic demands in the neonatal heart needs to be addressed. We therefore sought to evaluate myocardial oxygen consumption (MVO 2) in intact, blood-perfused, neonatal porcine hearts in working, empty beating, fibrillating, and potassium-arrested states at normothermia and at 15°C.

Accepted for publicationAug 16, 1995. Address reprint requests to Dr Jessen, Divisionof Thoracicand CardiovascularSurgery,Departmentof Surgery,Universityof TexasSouthwestern Medical Center at Dallas,5323Harry Hines BIvd,Dallas,TX 752358879. © 1996 by The Society of Thoracic Surgeons Published by Elsevier Science Inc

(Ann Thorac Surg 1996;61:82-7)

Material and Methods

Perfusion System Twelve newborn piglets, 3 to 9 days old (mean - standard deviation, 5.3 -+ 0.5 days) weighing between 1,200 and 2,600 grams (mean, 1,825 + 386 g) were used in these studies. All animals received humane care 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 85-23, revised 1985). Animals were anesthetized with intravenous pentobarbital (30 mg/kg) and administered intravenous heparin (400 U/kg). A tracheostomy tube (4-mm inner diameter) was rapidly inserted and the piglets were ventilated with 100% oxygen. Through a median sternotomy, the heart was excised and immersed in ice-cold heparinized saline 0003-4975/96/$15.00 SSDI 0003-4975(95)00905-1

Ann Thorac Surg 1996;61:82-7

Aortic flow - - ~

JESSEN ET AL NEONATAL MYOCARDIAL OXYGEN CONSUMPTION

- Afterload column Chart recorder •Elasticity chamber

t

, R. ventricle

the left atrial cannula from a continuously replenished reservoir at a pressure of 15 cm H20. The heart was allowed to eject blood across the aortic valve, through the aortic cannula, and into an elasticity chamber. Aortic flow then passed through silicone tubing to a height of 70 cm, permitting measurement of aortic flow by timed collection. Pressure developed in the aortic cannula was monitored and recorded.

Pressure

transducer

L. atrium

t

83

saturation

catheter

Coronary' J

Oxygenator

Fig 1. Isolated heart preparation used to evaluate myocardial oxygen consumption. A heart in the working mode is shown. (L. = left; P.A. = pulmonary artery; R. = fight.)

solution to achieve immediate arrest. The ascending aorta was perfused with adult pig blood, obtained earlier from a donor animal and oxygenated with a membrane oxygenator. An overflow system regulated perfusion pressure at 50 mm Hg during stabilization. Perfusion pressure in the aortic cannula was continuously monitored. A metal cannula connected to a blood-filled reservoir 15 cm above atrial level was inserted into the left atrium via a pulmonary vein, and remaining pulmonary veins were ligated. The pulmonary artery was cannulated with a plastic cannula that directed right ventricular (RV) outflow (coronary sinus return) past a branch point, where it was exposed to the tip of a saturation catheter (Oximetrix; Abbott Critical Care Systems, Mountain View, CA). The venous blood then exited the cannula and flow was measured by timed collection. The saturation catheter connected to a computer, which provided continuous oxygen saturation readouts (Oximetrix). All venous effluent and overflow blood was filtered and returned to the oxygenator for reuse. Arterial blood samples from the aortic cannula and from the PA cannula were collected under anaerobic conditions for blood gas determinations. The perfusion system is depicted in Figure 1. E x p e r i m e n t a l Protocol

Each heart was studied under up to six different conditions for determination of myocardial oxygen consumption. These states are described below: WORKINGHEART.A system based on modifications of the working isolated heart of Neely and associates [7] was used. In brief, oxygenated porcine blood was supplied via

EMPTYBEATINGSTATE.In this state, oxygenated blood was supplied retrograde through the aortic cannula at a constant pressure of 50 mm Hg. The left atrial cannula w a s clamped. A small polyethylene catheter with multiple side holes was inserted via an incision in the left atrial appendage, passed across the mitral valve, and secured i n position with a ligature. This assured venting of the left ventricle (LV) by gravity drainage to a level below the heart. The vent was opened for this and all subsequent states. A stab electrode was inserted into the left ventricle and connected to an electrocardiographic transducer to record the electrocardiogram. FIBRILLATINGHEART, The apparatus used in the empty beating state was used in an identical manner with the exception that an alternating current fibrillator was used to provide a continuous current to the heart via the electrocardiographic lead and a ground lead on the aortic cannula. The minimal current that would achieve fibrillation was applied (usually less than 1 V). As removing the stimulus often led to resumption of sinus rhythm, the stimulus was applied continuously during the measurements of this state. A perfusion pressure of 50 mm Hg was maintained. If fibrillation persisted after myocardial oxygen consumption measurements, hearts were deftbrillated electrically before switching to the next state. HYPOTHERMIA.The empty beating configuration was used at a perfusion pressure of 50 mm Hg. Arterial blood was cooled to 15°C in the oxygenator reservoir and via a modified Buckberg-Shiley blood cardioplegia reservoir (Sorin Biomedical, Irvine, CA). The bath around the heart was also cooled by water jacketing, and a temperature probe was inserted into the apex of the LV to monitor LV temperature, which was regulated at 15° --- 0.5°C. POTASSIUM CHLORIDEARREST.The empty beating configuration was used at a peffusion pressure of 50 mm Hg. Measured aliquots of potassium chloride (KC1) were added to the oxygenator reservoir until complete mechanical and electrical arrest was achieved. Measurements were made from the arrested heart at normothermia (37°C) and hypothermia (15°C) by the cooling techniques described above. M e a s u r e m e n t of O x y g e n C o n s u m p t i o n Myocardial oxygen consumption was calculated as the product of arteriovenous oxygen content difference and coronary flow. Blood oxygen content was calculated from the following formula: 0 2 content = [(1.39 × hemoglobin × %0 2 saturation) + (0.003 × oxygen tension)]. Hemo-

84

JESSENET AL NEONATALMYOCARDIALOXYGENCONSUMPTION

Ann Thorac Surg 1996;61:82-7

Table 1. Hemodynamic Parameters in the Isolated Working Heart~

Table 2. Wet Weight of Cardiac Chambers at the Conclusion of the Study~

Parameter

Chamber

Weight (g)

Left ventricle Right ventricle Total ventricles Total heart

9.3 + 1.5 4.1 -+ 0.8 13.4 -+ 2.3 16.8 +- 2.8

Systolic pressure Diastolic pressure Mean aortic pressure Aortic flow Coronary flow Cardiac output Heart rate

Value 109 _+13 mm Hg 39 -+ 6 mm Hg 62 -+ 4 mm Hg 72 _+21 mL/min 22 _+8 mL/min 94 _+24 mL/min 168 _+29 beats/min

a Data are expressed as mean _+standard deviation. globin m e a s u r e m e n t s were made for each state for each heart, a n d oxygen tension values were m e a s u r e d by blood gas analysis. Arterial saturation values were ass u m e d to be 100% as the arterial oxygen tension was never less than 190 m m Hg. Venous saturation values were m e a s u r e d directly from the Oximetrix saturation computer. Arterial pH was m a i n t a i n e d in the range of 7.35 to 7.45 by the addition of sodium bicarbonate w h e n needed, a n d arterial carbon dioxide tension was m a i n tained in the range of 35 to 40 m m Hg by regulation of gas flow to the oxygenator. U n d e r hypothermic conditions, oxygen tension values were corrected for temperature by the technique described by Hedly-Whyte a n d Laver [8]. Blood pH a n d carbon dioxide tension values were temp e r a t u r e - c o r r e c t e d u s i n g n o m o g r a m s d e v e l o p e d by Kelman a n d N u n n [9] to assure constant conditions d u r i n g each state. At the conclusion of the experiment, the isolated heart was cleared of blood a n d weighed in total. Separate LV a n d RV portions were also weighed. The MVO 2 was divided by the sum of LV a n d RV weights a n d expressed as milliliters of oxygen per m i n u t e per 100 g of c o m b i n e d ventricular weight.

Statistical Analysis Calculated oxygen c o n s u m p t i o n values were compared b e t w e e n conditions by a paired t test using commercially available software (SAS Institute Inc, Cary, NC).

a Data are expressed as mean -+ standard deviation. quantified d u r i n g fibrillation a n d was zero d u r i n g KC1 arrest. In the e m p t y beating hypothermic state (15°C, no KC1 arrest) slow atrial activity was noted (rate, 14 -+ 12 beatstmin), b u t ventricular contractions were not observed except in 1 heart. For KCl-arrested hearts, complete electrical arrest was achieved only at high s e r u m potassium levels. Measured values were 49 --- 18 mEq/L at 15°C a n d 51 --- 16 mEq/L at 37°C. Of the fibrillated hearts (n = 11) only 4 required electrical defibrillation after removal of the alternating current. The others r e t u r n e d to sinus rhythm spontaneously. As the neonatal heart is highly d e p e n d e n t on glucose as substrate a n d the preparation is typically in use for about 3 hours for each study, we m e a s u r e d blood glucose levels at the conclusion of 5 experiments. These values ranged from 57 to 165 mg/dL, with a m e a n of 94 + 43 mgldL. A d e q u a t e substrate appeared present throughout this experiment. Heart weight varied from 12.2 to 22.2 g (mean, 16.8 --2.8 g). C h a m b e r weights are presented in Table 2. As the right ventricle was never vented, b u t used to deliver coronary flow through the system, it was p r e s u m e d to make a contribution to MVO 2 in all states. As a result MVO 2 values are expressed in milliliters of oxygen per m i n u t e per 100 g of c o m b i n e d RV a n d LV weight, although RV work was probably minimal. M e a n MVO2, coronary flow, a n d arteriovenous oxygen difference values for each state are presented in Table 3. Oxygen utilization in the empty beating state fell significantly from that seen in the working state to a level representing nearly half of the working requirements.

Results The working mode could not be well established in 3 hearts, a n d MVO2 data were not collected for this state in these. In 1 heart, the preparation deteriorated after only the working a n d empty beating states h a d b e e n evaluated. M e a s u r e m e n t s of MVO2 were not m a d e at hypothermia in the e m p t y beating heart in 2 other studies. H e m o d y n a m i c m e a s u r e m e n t s in the working mode are presented in Table 1. The pressures generated were greater than those m e a s u r e d in 4 piglets in vivo before extraction of the heart, where systolic a n d diastolic arterial pressures averaged 67 ___ 5 a n d 44 + 9 m m Hg, respectively. The isolated heart was free of any depressant effects of anesthetics a n d appeared to be stressed to a greater work-load than the anesthetized piglet. In the e m p t y beating state, heart rate was slightly lower (151 + 31 beats/min), although this was not significantly different from the working mode. Heart rate could not be

Table 3. Arteriovenous Oxygen Content Differences, Coronary Blood Flow, and Myocardial Oxygen Consumption in the Neonatal Heart Under Each Experimental Condition a

Condi~on Working (n = 9) Empty beating (n = 12) Fibrillating (n = 11) Hypothermia (n = 9) KCI arrest (n = 11) Arrest-hypothermia (n = 11)

A-V 02 Difference (vol %)

Coronary Flow (mL/min)

MVO2 (mL • min -1 • 100 g-l)

5.00 -+ 2.57 20.5 -+ 6.8 1.70 + 1.00 29.3 -+ 11.9

6.69 + 1.91 3.19 + 1.08

1.82-+ 1.47 37.6 -+ 18.1 0.28 -+ 0.11 18.3 -+ 7.4

3.72 _+0.84 0.37 _+0.18

3.17+ 2.13 10.8_+12.6 0.36+ 0~6 16.5 -+ 8.6

1.30 + 0.34 0.32 _+0.10

a Data are expressed as mean + standard deviation. A-V = arteriovenous; MVO2 = myocardialoxygen consumption.

Ann Thorac Surg 1996;61:82-7

Ventricular fibrillation consistently increased oxygen utilization from the empty beating state, but only by about 15%. Although small in magnitude, this difference was statistically significant by paired t test. Potassiuminduced arrest caused a significant decline in MVO 2 (to a level of 1.30 + 0.34 mL of oxygen per minute per 100 g). However, hypothermia (15°C) led to a greater reduction (0.37 - 0.18 mL of oxygen per minute per 100 g). At this temperature, the addition of an arresting concentration of KCI to the perfusate did not significantly alter oxygen consumption.

Comment

Work Conditions The use of MVO 2 as an index of metabolic activity of the heart has been well established by previous studies [1, 2]. In the current investigation, MVO2 averaged 6.7 mL of 0 2 per minute per 100 g of tissue in the working state and fell to 3.2 mL per minute per 100 g in the empty beating state. Although significantly less, this still represented 48% of the working requirements. In previously reported studies evaluating this relationship in adult myocardium, this fraction was considerably smaller [1]. Thus it appears that when external work performance is factored out, the energy requirements of the neonatal heart remained proportionately greater. Nonetheless, the actual MVO2, when corrected for tissue weight, is very similar to values others have observed in the adult under empty beating conditions. A greater difference may be present in the working state. Most measurements of MVO2 in adult hearts under working conditions have been higher than observed in this study with the neonate. However, systolic pressures generated are also higher in the adult.

Ventricular Fibrillation The induction and maintenance of electrical ventricular fibrillation led to an increase in oxygen utilization to 3.7 mL per minute per 100 g. Although only a 15% increase from empty beating levels, this increase was observed in virtually all experiments. As a result, by paired t test, the difference was statistically significant. In contrast, work by Hottenrott and associates [10] in 1974 in adult canine hearts found that fibrillating normothermic ventricles consumed more than 50% more oxygen than empty beating hearts. In part, differences in intrinsic heart rates may explain this phenomenon. In Hottenrott and associates' study, hearts were paced at 100 beats/min to establish empty beating MVO 2 levels, whereas the hearts in the present investigation beat at a rate of approximately 160 beats/min. When this group reported a subsequent study comparing ventricular fibrillation with unpaced adult hearts beating at greater than 160 beats/min [11], the increase observed was in the order of 16%. However, other features of neonatal myocardium may contribute to the observation that ventricular fibrillation did not increase MVO 2 by the magnitude reported in adult studies. Neonatal myocardium may have less contractile elements to respond or the immature sarcoplasmic reticulum may be unable to maintain calcium mobilization.

JESSEN ET AL NEONATAL MYOCARDIAL OXYGEN CONSUMPTION

85

Further studies will be required to clarify this phenomenon. Of interest, most studies in adult myocardium allow ventricular fibrillation to be maintained spontaneously after a brief electrical induction. Continuous eledxical fibrillation may have different consequences on energy requirements [10]. In our study, ventricular fibrillation could not be spontaneously maintained in the perfused neonatal heart, likely due to small mass. As a result, a continuous electrical stimulus was applied. Voltages used were very low (less than 1 V), and would be insufficient in larger animals. Most hearts resumed sinus rhythm spontaneously within seconds of discontinuing the current.

Hypothermia and Potassium Arrest This investigation examined interventions predicted to lower the metabolic rate of the heart. Production of depolarized arrest with KCI reduced MVO 2 to 1.3 mL per minute per 100 g. This represents a significant decline from empty beating levels, and is similar to levels observed in adult myocardium with potassium arrest [1]. In all studies, arrest was maintained for at least 20 minutes before measuring MVOa as shorter periods may lead to falsely elevated values [12]. Hypothermia to a myocardial temperature of 15°C offered the greatest reduction in MVO 2 to a level of 0.37 mL per minute per 100 g. At this temperature, no mechanical ventricular activity was observed, although atrial activity continued slowly. The addition of an arresting concentration of KCI to the perfusate did not lead to a significant change in MVO 2 at this temperature (0.32 mL per minute per 100 g). Thus, as evaluated by oxygen cost, hyperkalemic arrest appears to offer no additional protective benefits if myocardial cooling of this magnitude has been achieved.

Relationship Between Oxygen Consumption and Coronary Blood Flow Unlike studies in adult animals on cardiopulmonary bypass [2], arteriovenous O 2 content difference showed considerably more variability between the different states in the present study (see Table 3). As a result, differences in MVO 2 were not directly related to blood flow changes. For example, coronary flow was greater under empty beating conditions compared with the working state, although MVO 2 was lower. Under hypothermic conditions, MVO 2 declined by a much greater degree than the change in blood flow. Several factors may be involved in these observations. First, autoregulatory mechanisms may be altered in the immature heart, and may be further modified in a denervated isolated heart preparation. Second, conditions such as hypothermia may affect regulatory processes in the coronary vasculature of the neonate, reducing the ability to match flow to metabolic demand. Finally, as conditions change, the distribution of coronary blood flow within the myocardial wall may vary. For example, if blood flow was preferentially shunted through regions with low oxygen extraction and low resistance, higher coronary flow values and lower arteriovenous 02 differences would be observed. These autoregulatory issues have implications for myocardial

86

JESSENET AL NEONATALMYOCARDIALOXYGENCONSUMPTION

protective strategies that use similar conditions and deserve further investigation.

Implications for Myocardial Protection Myocardial protection remains a significant issue in neonatal cardiac surgery. Studies by Bull and associates [13] related 50% of postoperative mortality to problems of inadequate protection during operation. Furthermore, the techniques used clinically have largely been those adapted from use in adult cardiac operations: hypothermia and potassium arrest. As contemporary studies are finding more physiologic and biochemical age-related differences, the use of these techniques must be reevaluated. The use of cardioplegia for neonatal myocardial protection is controversial and serves as an example. Baker and co-workers [14] reported that the use of St. Thomas II solution in addition to hypothermia (14"C) led to lower functional recovery after 2 to 6 hours of ischemia than the use of hypothermia alone. In contrast, Bove and colleagues [15] found that single-dose and multidose crystalloid cardioplegia with hypothermia afforded better protection against 2 hours of ischemia than hypothermia alone. Temperature, however, was 28"C in the latter study. Our results suggest that potassium-based arrest reduces metabolic demand, and may have protective effects on the neonatal heart. However, the addition of potassium cardioplegia when myocardial temperature was 15"C did not lower oxygen demands. This provides a rationale for the differing results in the above-mentioned studies and agrees with work by Corno and associates [16], who found no difference in protection afforded by hypothermia alone and hypothermia with cardioplegia. One must note that variations in cardioplegla composition [17], frequency of administration [18], degree of hypothermia [19], or combinations of these variables [20] can influence recovery of neonatal myocardium after ischemia. As well, the age [21] and species [22] of the experimental animals can affect results, limiting the scope of many experimental Investigations. Further work will be required to define the role of cardioplegla in neonatal cardiac surgery.

Study Limitations The present study was conducted in an isolated heart preparation and carries with it problems inherent in the use of such systems. In particular, denervation of the heart may alter MVO 2 values. Drake and co-workers [23] have reported an increase in MVO 2 levels with cardiac denervation, and our study may be subject to a similar phenomenon. As well, this preparation uses oxygenated blood provided by an oxygenator. No endogenous catecholamines are present in the preparation, nor are any of the normal hepatic or renal mechanisms that regulate waste metabolites in the intact animal. One additional concern is that neonatal hearts contain a lower contractile mass per unit weight, and have a higher water content. As a result, the expression of oxygen per 100 g of wet

Ann ThoracSurg 1996;61:82-7

weight may make comparisons with adult data more difficult. This study demonstrates that MVO2 is different under a variety of conditions. However, it cannot state whether MVO 2 is adequatefor these conditions. If relative myocardial ischemia were present under any condition, coronary resistance would fall, and autoregulation would be affected. It is unknown whether this played a role under the conditions studied here as no measurements of ischemic metabolites or comparisons with baseline function were made. In this study no measurements of MVO 2 of adult hearts were made. Ventricular geometry, wall thickness, perfusion pressure, and heart rate all differ between adult and neonatal hearts. As a result, conditions of perfusion pressure or ventricular stress normal for one age group might be very suboptimal for the other. Therefore, comparisons of metabolic rates must be qualitative at best. These studies suggest that the relationships of M V O 2 in different states in the neonate may have some intrinsic differences to those which have been observed in studies using adult hearts. The effects of fibrillation, hypothermia, and KC1 arrest may all have slightly different consequences to myocardial protective strategies in this age group. Further studies will be needed to define the specific cellular processes that contribute most to oxygen demand and coronary blood flow regulation in the neonate. This may allow the development of optimal myocardial protective strategies for the newborn. This work was supported by National Institutes of Health grant HL 26302.

References 1. Gibbs CL, Papadoyannis DE, Drake AJ, Noble MIM. Oxygen consumption of the nonworking and potassium chloridearrested dog heart. Circ Res 1980;47:408-17. 2. Chitwood WR, Sink JD, Hill RC, Wechsler AS, Sabiston DC Jr. The effects of hypothermia on myocardial oxygen consumption and transmural coronary blood flow in the potassium-arrested heart. Ann Surg 1979;190:106-16. 3. Nakanishi T, Jarmakani JM. Developmental changes in myocardial mechanical function and subcellular organelles. Am J Physiol 1984;246(Heart Circ Physiol 15):H615-25. 4. Seguchi M, Harding JA, Jarmakani JM. Developmental change in the function of sarcoplasmic reticulum. J Mol Cell Cardiol 1986;18:189-95. 5. Hoerter JA, Opie LH. Perinatal changes in glycolytic function in response to hypoxia in the incubated or perfused rat heart. Biol Neonate 1978;33:144-61. 6. Reis RL, Cohn LH, Morrow AG. Effects of induced ventricular fibrillation on ventricular performance and cardiac metabolism. Circulation 1967;36(Suppl 1):234-43. 7. Neely JR, Liebermeister H, Battersby EJ, Morgan HE. Effect of pressure development on oxygen consumption by isolated rat heart. Am J Physiol 1967;212:804-14. 8. Hedley-Whyte J, Laver MB. 02 solubility in blood and temperature correction factors for PO2. J Appl Physiol 1964; 19:901-6. 9. Kelman GR, Nunn JF. Nomograms for correction of blood PO2, PCO2, pH, and base excess for time and temperature. J Appl Physiol 1966;21:1484-90. 10. Hottenrott C, Maloney JV Jr, Buckberg G. Studies of the effects of ventricular fibrillation on the adequacy of regional

Ann Thorac Surg 1996;61:82-7

11.

12.

13. 14. 15.

16.

17.

myocardial flow. I. Electrical vs. spontaneous fibrillation. J Thorac Cardiovasc Surg 1974,~8.~15--25. Buckberg GD, Brazier JR, Nelson RL, Goldstein SM, Mc ConneU DH, Cooper N. Studies of the ~ of hypothermia on regional myocardial blood flow and metabolism during cardiopulmonary bypass. I. The adequately perfnsed beating, fibrillating, and arrested heart. J Thotac Cardiovasc Surg 1977;73:87-93. Sternbergh WC, Brunsting LA, Abd-Elfattah AS, Wechsler AS. Basal metabolic energy requirements of polarized and depolarized arrest in rat heart. Am J Physiol 1989-,256(Heart Circ Physiol 25):H846-51. Bull C, Cooper J, Stark J. Cardioplegic protection of the child's heart. J Thorac Cardiovasc Surg 19~L;88..287--93. Baker JE, Boerboom LE, Olinger GN. Age-related changes in myocardial protection of the isolated rabbit heart. Surg Forum 1986;37~93-5. Bove EL, Stammers AH, Gallagher KP. Protection of the neonatal myocardium during hypothermic ischemia. Elect of cardioplegia on left ventflcul~/unction in the rabbit. J Thorac Cardiovasc Surg 1987,~k115--23. Como AF, Bethencourt DM, Laks H, et al. Myocardial protection in the neonatal heart. A comparison of topical hypothermia and crystalioid and blood carclioplegic solutions. J Thorac Cardiovasc Surg 19ff/,~&.163--72. Kempsford RD, Hearse DJ. Protection of the immature

JESSENET AL NEONATALMYOCARDIALOXYGENCONSUMPTION

18.

19.

20.

21. 22. 23.

87

myocardium during global ischemia. A comparison of four clinical cardioplegic solutions in the rabbit heart. J Thorac Cardiovasc Surg 1989;97:856-63. Sawa Y, Matsuda H, Shimazaki Y, et al. Comparison of single dose versus multiple dose crystalloid cardioplegia in neonate. Experimental study with neonatal rabbits from birth to 2 days of age. J Thorac Cardiovasc Surg 1989;97: 229-34. Kempsford RD, Hearse JD. Protection of the immature heart. Temperature-dependent beneficial or detrimental effects of multidose crystalloid cardioplegia in the neonatal rabbit heart. J Thorac Cardiovasc Surg 1990;99:269-79. Murashita T, Hearse DJ. Temperature-response studies of the detrimental effects of multidose versus single-dose cardioplegic solution in the rabbit heart. J Thorac Cardiovasc Surg 1991;102:673--83. Magovern JA, Pae WE Jr, Waldhausen JA. Age-related changes in the etlicacy of crystalloid cardioplegia. J Surg Res 1991",51:229--32. Baker JE, Boerboom LE, Olinger GN. Is protection of ischemic neonatal myocardium by cardioplegia species dependent? J Thorac Cardiovasc Surg 1990;99"~.80-7. Drake AJ, Stubbs J, Noble MIM. Dependence of myocardial blood flow and metabolism on cardiac innervation. Cardiovasc Res 1978;12:69-80.

INVITED COMMENTARY There is perhaps no other subject that elicits such a strong and visceral (and always biased) response from the cardiac surgeon than ventricular fibrillation. The spectrum ranges from those (few) who routinely use intermittent aortic cross-clamping and fibrillation as an intraoperative myocardial m a n a g e m e n t strategy to those who " n e v e r " allow the heart to fibrillate during cardioplegia, and rapidly defibrillate if needed early in reperfusion to prevent myocellular damage. W h o is right? The simple answer to the question is probably both. Why? The metrics used to assess any fibrillation effects often confound determinant variables such as the duration and method of fibrillation induction, internal and external cardiac workload, endocardial wall tension, coronary perfusion pressure and flow, oxygen extraction, left ventricular hypertrophy, and the heart rate in the beating comparison group. It is no surprise that electrically induced and sustained ventricular fibrillation in a hypertrophied, distended ventricle is bioenergetically and mechanically deleterious compared with the electrically quiescent, nondistended heart. Is there a significant difference, however, between the spontaneously fibrillat-

utilization cost of ventricular fibrillation versus the empty beating, vented state is small, about 15%. If the heart were cooled to a myocardial temperature of 15°C, the absolute difference would be predictably less, because the greatest reduction in myocardial oxygen consumption is realized (at least 90%) attendant to empty, nonworking, vented hypothermia whether induced by cold perfusion or cardioplegia. This was the observation of the present study. The central question, however, is what is the postischemic, postfibrillation or reperfusion residual functional capacity, as all of us desire a rapid and successful wean from bypass at the end of the operation. Perhaps differences between cold perfusion alone, cold plus fibrillation, or cold plus cardioplegia would be better assessed by preintervention and posiintervention mechanical indices, where the relative impact of each intervention on depleting adenosine triphosphate stores, altering calcium homeostasis and buffering capacity, and exacerbating transmural flow maldistribution and edema formation are immediately evident. Such data were not reported by Jessen and colleagues for the neonatal heart, but serve as fertile soil for future investigation.

ing, empty, nondistended, nonhypertrophied, well-perfused

Irvin B. Krukenkamp, MD

(high coronary perfusion pressure and flow) heart and one that is in a similar state, but beating? Most well conducted and controlled experimental studies, as well as clinical series, would suggest not. This is not a surprise if one considers that the oxygen cost of electrical activation alone without the resultant mechanical activity has been previously reported at less than 1% of the total working myocardial oxygen consumption per beat [1]. As indicated by this excellent study by Jessen and associates, for the neonatal myocardium, the oxygen

Division of Cardiothoracic Surgery New England Deaconess Hospital 110 Francis St, Suite 2C Boston, MA 02215 Reference 1. Klocke FJ, Braunwald E, Ross J. Oxygen cost of electrical activation of the heart. Circ Res 1966;18:357-65.