Inotropic Effect of Triiodothvronine Following Myoc&dial Ischemia and C&diopulmonary B-flass: An Experimental Study in Pigs Dimitri Novitzky, M.D., F.C.S.(SA), Paul A. Human, M.Sc., and David K. C. Cooper, M.D., Ph.D., F.R.C.S.

ABSTRACT A significant reduction ( p < 0.0001) in plasma-free triiodothyronine (T3), which is known to have an inotropic effect, has been documented in patients undergoing open-heart procedures. To investigate the ef- fect of this observation, 22 pigs underwent 2 hours (Group 1, r = 10) or 3 hours (Group 2, r = 12) of myocardial ischemia during cardiopulmonary bypass (CPB) at 26°C; the myocardium was protected by cardioplegic solution and cold saline solution at 30-minute intervals. After the pig was rewarmed to 37T, CPB was discontinued, and measurements of hemodynamic function were made 10 and 70 minutes later. Half of the pigs (Subgroup B) re- ceived 6 kg of T3 intravenously immediately after removal of the aortic cross-clamp; the remainder (Subgroup A) re- ceived no T3. After 2 hours of ischemia, untreated pigs showed significantly reduced myocardial function 10 min- utes after discontinuation of CPB. By 70 minutes after the end of CPB, 2 of 5 untreated pigs (Subgroup A) had died of low cardiac output, but all 5 treated pigs (Subgroup B) survived. After 3 hours of ischemia, both groups showed some reduced function at 10 minutes, though the reduction was more marked in untreated animals. By 70 minutes, 4 of 6 untreated pigs had died of myocardial failure and all treated pigs remained alive ( p < 0.03). Surviving pigs in both groups still demonstrated some reduced function compared with values obtained before CPB. When all pigs are considered together, overall survival of those that did not receive T3 was significantly less than those that did ( p < 0.006). T3 clearly has a significant beneficial inotropic effect when administered after a period of myocardial isch- emia and CPB; its administration may be indicated in pa- tients undergoing open-heart operations.

We* have documented a significant reduction (p < 0.0001) in plasma-free triiodothyronine (T3), though not of thyroxine or thyroid-stimulating hormone, in patients

‘Novitzky D, Cooper DKC, Swanepoel A Inotropic effect of triiodothy- ronine (T3) following myocardial ischemia and cardiopulmonary bypass: Initial experience in patients undergoing open-heart surgery (submitted for publication, 1987).

From the Department of Cardiothoradc Surgery, University of Cape Town Medical School, Cape Town, South Africa.

Accepted for publication Aug 24, 1987.

Address reprint requests to Dr. Novitzky, Oklahoma Transplantation Institute, Baptist Medical Center, Oklahoma City, OK 73112.

undergoing an open-heart operation.* Similar observa- tions have been made by others [l, 21. The T3 level falls within 15 minutes of the onset of cardiopulmonary by- pass (CPB) and does not return to normal levels until 24 to 48 hours have elapsed after operation. The low level does not appear to be solely related to hemodilution [l, 21. Others [3] have documented an increase in myo- cardial contractility in patients with increased circulating T3 levels.

It occurred to us that patients depleted of T3 at the end of an open-heart operation might benefit from the ino- tropic effect of this hormone. To investigate the inotro- pic effect of T3 under the conditions of an open-heart operation, we carried out a series of experiments in pigs subjected to a period of myocardial ischemia while sup- ported by CPB.

Material and Methods Anesthesia and Monitoring Twenty-two white Landrace pigs weighing between 20 and 30 kg were sedated with intramuscular administra- tion of ketamine hydrochloride (5 mg per kilogram of body weight), and anesthetized with intravenous ad- ministration of sodium thiopental (2.5 mgkg) and mor- phine (1.5 mgkg). Muscle relaxation was brought about with intravenously administered alcuronium chloride (0.5 mgkg), which was repeated in smaller doses subse- quently if necessary. Endotracheal intubation was car- ried out, and ventilation was maintained on a Bird Mark 2 ventilator with a closed circuit, which recycled oxygen (4 literdmin) and nitrous oxide (6 literdmin).

The ECG was continuously monitored and heart rate (HR), recorded. Cannulas were inserted for continuous monitoring of mean arterial pressure (MAP) and central venous (CVP) pressure. Arterial blood gases were mea- sured at least every 30 minutes throughout the experi- ment; ventilation and acid-base imbalance were cor- rected as necessary. A Swan-Ganz catheter was inserted for measurement of cardiac output (CO); stroke volume (SV) was calculated.

After exposure of the heart, a left ventricular catheter was inserted through the apex for measurement of left ventricular peak systolic pressure, left ventricular end- diastolic pressure (LVEDP), and maximum rate of rise of left ventricular pressure (dP/dt,,,). In some hearts, a left

‘T3 and thyroxine were measured by radioimmunoassay, and thyroid- stimulating hormone was measured by monoclonal antibody assay (Amersham). Statistical comparisons were by analysis of variance.

50 Ann Thorac Surg 4550-55, Jan 1988. Copyright 0 1988 by The Society of Thoracic Surgeons

51 Novitzky et al: Inotropic Effect of Triiodothyronine in Pigs

atrial catheter was also inserted for direct measurement of left atrial pressure (LAP). All hemodynamic variables were recorded immediately before initiation of CPB (control) and at 10 and 70 minutes after discontinuation of CPB. The measurements made 10 minutes after CPB were always approximately 1 hour after reperfusion of the myocardium had begun, as rewarming to 37°C after release of the aortic cross-clamp took 50 minutes (? 10 minutes).

Blood was taken for estimation of plasma-free T3 be- fore initiation of CPB and at 10 and 70 minutes after discontinuation of CPB.

CPB and Cardioplegic Arrest The heart was exposed through a median stemotomy. CPB was initiated through cannulas inserted into the right atrium and ascending aorta; the heart was vented through the pulmonary artery. A standard CPB tech- nique was used incorporating Sarns roller pumps and an infant Polystan bubble oxygenator. A prime of 500 ml of blood and 1,500 nil of electrolyte solution (Plasmalyte B) was used in each pig, and as we did not wish to add further blood at later intervals (because it might have contained T3), additional fluid was given in the form of mannitol or albumin. A flow rate ranging between 50 and 80 mykg/min and an MAP of 60 to 70 mm Hg were maintained. Since no further blood was administered, the hematocrit of the pig fell from a control value of approximately 34% to a value of 20% (range, 18 to 24%) by the end of the period of CPB. Systemic temperature was reduced as rapidly as possible and maintained at 26°C throughout the period of cardioplegic arrest.

After cross-clamping of the ascending aorta, cardio- plegic arrest was obtained using the Groote Schuur Hos- pital solution, a solution that is used routinely with good results in our clinical cardiac surgery program. The com- position of the solution is as follows:

NaHC03 1.275 gm/L 15 mM KC1 1.5 gm/L 20 mM CaC12-2H20 0.15 gm/L 1.35 mM MgS04-7H20 3.0 gm/L, 24.92 mM Mannitol25% 2.5 gm/L 13.72 mM

It is made up in 1 liter of 5% dextrose. The initial dose was 15 ml/kg, and further doses of 5 mykg were given at 30-minute intervals for a period of 2 or 3 hours. Whenever cardioplegic solution was infused, the pericardial cavity was flushed with cold (4°C) saline so- lution. This combination brought about satisfactory ar- rest of myocardial activity as evidenced by the ECG.

After 2 or 3 hours of myocardial ischemia, the aortic cross-clamp was removed and the heart was reperfused. Systemic rewarming was initiated until rectal and naso- pharyngeal temperatures of 37°C were obtained; re- warming took 50 (* 10) minutes. At a nasopharyngeal temperature of 32"C, the heart was electrically de- fibrillated. At 37T, CPB was discontinued.

The experiment was terminated if myocardial activity

Table 1 . Experimental Groups and Outcome

Sub- Myocardial Group group No. Ischemia (hr) T3 Therapy Deaths Survivors

1 A 5 2 No 2 3 B 5 2 Yes 0 5

2 A 6 3 No 4 2 B 6 3 Yes 0 6

ceased, or was terminated electively 90 minutes after discontinuation of CPB (i.e., 140 [ ? 101 minutes) after reperfusion of the myocardium had begun).

Experimental Groups Pigs underwent either 2 hours (Group 1, r = 10) or 3 hours (Group 2, r = 12) of myocardial ischemia (Table 1). No animal received any form of recognized inotropic support (e.g., dobutamine hydrochloride, epinephrine, calcium). Half of the animals in each group received 6 p,g of T3 immediately after removal of the aortic cross- clamp. There were no other differences in protocol be- tween the T3-treated (Subgroup B) and untreated (Sub- group A) animals.

Statistical Methods Comparison of survival was made using Fisher's exact test and comparison of plasma-free T3 levels, by Stu- dent's t test for paired and unpaired data. Comparison of hemodynamic data was by two-way analysis of vari- ance with log transformation of the data.

Results Plasma-free T3 Levels There proved to be considerable variation in the control level of plasma-free T3 in the pigs. The mean T3 level before CPB was 1.16 (standard error, 0.29) pmoVL in untreated pigs (Groups 1A and 2A) and 1.11 (0.34) pmoY L in pigs subsequently treated with T3 (Groups 1B and 2B). There was no significant difference in T3 levels be- tween the untreated and treated groups before CPB.

Ten minutes after removal of the aortic cross-clamp, the plasma-free T3 level in the untreated pigs (Groups 1A and 2A) had fallen to 0.89 (0.30) pmol/L, and the level in the treated pigs (Groups 1B and 2B) had risen to 6.19 (1.19) pmol/L. This level in the treated animals was significantly higher than both the control (before CPB) level ( p < 0.0005) and the level in the untreated group 10 minutes after CPB ( p < 0.0005). Seventy minutes after removal of the aortic cross-clamp, the T3 level in the treated animals had fallen to 3.14 (0.65) pmol/L, but this remained significantly higher than the control level ( p < 0.008) and significantly higher ( p < 0.02) than the level in the untreated animals, which had risen slightly to 1.27 (0.39) pmoVL.

Myocardial Function GROUP 1 (2 HOURS OF MYOCARDIAL ISCHEMIA). Left atrial pressure was not measured in this group. Ten minutes

52 The Annals of Thoracic Surgery Vol 45 No 1 January 1988

Table 2 . Hemodynamic Function in Group 2 Pigs Before and After 2 Hours of Myocardial

Hemodynamic Before CPB Variable Subgroup No. (Control) 10 Minutes After CPB 70 Minutes After CPB

CO (Llmin) A B

HR @eats/min) A B

SV (ml) A B

dP/dt,,, A B

LVEDP (mm Hg) A B

B MAP (mm Hg) A

CVP (mm Hg) A B

5 5

5 5

5 5 5 5

5 5 5 5

5 5

2.7 (0.35) 3.2 (0.67)

116 (7.8) 118 (14.4)

23 (7.7) 19 (6.0) 928 (144.4) 921 (168.8)

6.2 (2.95 7.6 (1.82) 73.4 (13.37) 64.6 (9.32)

5.4 (2.07) 4.0 (2.45) (N = 4)

1.6 (1.13) ( p < 0.05') 2.9 (0.48) ( p < 0.05d) 118 (14.7) 145 (15.4) ( p < 0.05') ( p < 0.05d) 13 (9.2) ( p < 0.05') 20 (1.7) 942 (456.5) 1,412 (201.6) ( p < 0.05') ( p < 0.05d) 9.0 (4.06) 11.4 (5.46) 44.0 (17.15) ( p < 0.01') 67.2 (9.47)

11.8 (5.17) 8.5 (4.80) (N = 4)

( p < 0.01d)

2.3 (1.48) (N = 3) 2.8 (0.52)

121 (8.1) (N = 3) 150 (25.2) ( p < 0.01') ( p < 0.05d) 20 (13.1) (N = 3) 19 (3.9) 856 (133.6) (N = 3) 1,454 (309.5) ( p < 0.05')

13.0 (4.24) ( p < 0.05') (N = 3) 10.4 (6.23) 62.7 (8.62) (N = 3) 58.4 (8.08)

( p < 0.01d)

7.0 (1.73) (N = 3) 6.0 (3.16) (N = 4)

"If difference was not significant, no p value is shown. bNumbers in parentheses (other than p values or numbers of pigs) are standard deviation. 'This represents a significant difference versus control. dThis represents a significant difference between the two subgroups.

CPB = cardiopulmonary bypass; CO = cardiac output; HR = heart rate; SV = stroke volume; dP/dt,,, = maximum rate of rise of left ventricular pressure; LVEDP = left ventricular end-diastolic pressure; MAP = mean arterial pressure; CVP = central venous pressure.

after discontinuation of CPB, there was a significant re- duction in MAP, SV, and CP in untreated pigs (Group 1A) (Table 2). In treated animals (Group lB), HR and dP/ dt,,, were significantly increased and SV was un- changed compared with control readings. When myo- cardial function in the two subgroups (A and B) was compared at this time interval, the untreated pigs showed significantly worse function in terms of MAP, CO, and dP/dt,,,; HR was also significantly lower.

By 70 minutes after discontinuation of CPB, 2 of the 5 untreated pigs (Group 1A) had died of low-output myo- cardial failure; all 5 treated pigs (Group 18) remained alive. At this time interval, however, the 3 surviving untreated pigs showed a significant increase in LVEDP; the 5 treated pigs showed an increase in HR and dP/ dt,,, compared with control levels. HR and dP/dt,,, re- mained significantly higher in Group 1B than in Group 1A.

GROUP 2 (3 HOURS OF MYOCARDIAL ISCHEMIA). In Group 2A, there was significantly diminished function 10 min- utes after CPB compared with control levels in regard to MAP, SV, and CO (Table 3). CVP and LAP were signifi- cantly elevated in both Group 2A and Group 2B. Un- treated pigs (Group 2A) showed a significantly reduced MAP compared with treated pigs (Group 2B).

By 70 minutes after discontinuation of CPB, 4 of the 6 untreated pigs (Group 2A) had died of low-output myo- cardial failure, whereas all 6 T3-treated pigs (Group 2B) remained alive. This difference in survival is significant (p < 0.03).

When the hemodynamic function at 70 minutes of the 2 surviving untreated pigs was compared with control measurements, a reduction in myocardial function was seen to persist with respect to SV and CO. At the same time interval, the 6 treated pigs showed no significant differences from control values except in regard to LAP, which was still elevated. There were, however, no significant differences in function between the 2 surviv- ing untreated pigs and the 6 treated animals.

Overall Survival If the 2-hour experiments (Group 1) and the 3-hour ex- periments (Group 2) are considered as a single study, then 6 (55%) of 11 untreated pigs died of myocardial failure within 70 minutes of discontinuation of CPB; all 11 T3-treated pigs survived. This difference in overall survival is significant (p < 0.006).

Comment In the pig, there does not appear to be a marked fall in plasma-free T3 levels during CPB, a finding that con- trasts with that observed in patients.* In the treated ani- mals in the present study, the 50% fall (over 60 minutes) in the level of T3 after its administration suggests a rapid

*Novitzky D, Cooper DKC, Swanepoel A Inotropic effect of triiodothy- ronine (T3) following myocardial ischemia and cardiopulmonary bypass: 11. Initial experience in patients undergoing open heart surgery (sub- mitted for publication, 1987).

53 Novitzky et al: Inotropic Effect of Triiodothyronine in Pigs

Table 3 . Hemodynamic Function in Group 2 Pips Before and After 3 Hours of Myocardial Ischemiaafb

Hemodynamic Before CPB Variable Subgroup No. (Control) 10 Minutes After CPB 70 Minutes After CPB

CO (Wmin)

HR (beatdmin)

SV (ml)

dPIdt,.,

LVEDP (mm Hg)

MAP (mm Hg)

CVP (mm Hg)

LAP (mm Hg)

~~

A B A B A B A B A B A B

A B A B

~

6 6 6 6 6 6 6 6 6 6 6 6

6 6 6 6

3.1 (0.49) 2.9 (0.71) 128 (21.3) 131 (33.8) 25 (5.0) 23 (7.3) 1,043 (216.5) 1,101 (412.2) 8.2 (3.76) 9.0 (3.10) 82.5 (14.68) 83.5 (17.44)

5.5 (1.87) 6.5 (1.76) 6.5 (1.52) 5.2 (2.93)

1.9 (0.91) (p < 0.01') (N = 3) 2.1 (0.48) 124 (12.9) (N = 3) 128 (16.0) 15 (5.9) (p < 0.05') (N = 3) 17 (5.0) 1,035 (321.86) (N = 3) 1,047 (329.4) 12.0 (1.00) (N = 3) 11.2 (2.23) 39.0 (17.35) (p < 0.01') (N = 3) 57.5 (22.34) (p < 0.05d) 10.3 (2.08) (p 0.01') (N = 3) 10.8 (2.4) (p < 0.05') (13.0) (2.65) (p < 0.05') (N = 3) 9.5 (3.56) (p < 0.05')

2.0 (0.59) (p < 0.05') (N = 2) 2.0 (0.51) 148 (11.3) (N = 2) 133 (17.2) 14 (5.0) (p < 0.05') (N = 2) 15 (5.2) 1,368 (70.7) (N = 2) 1,095 (157.4) 9.0 (1.41) (N = 2) 8.7 (3.08) 55.0 (1.41) (N = 2) 59.2 (21.99)

5.5 (2.12) (N = 2) 7.5 (2.59) 7.0 (1.41) (N = 2) 9.0 (2.89) (p < 0.05')

~~~ _____ ~ ~ ~ ~ ~ ~~~~~~~~~ ~ ~ ~ ~ ~ _ _ _ _ _ _ _ _

"If difference was not significant, no p value is shown. bNumbers in parentheses (other than p values or numbers of pigs) are standard deviation. 'This represents a significant difference versus control. dThis represents a significant difference between the two subgroups. CPB = cardiopulmonary bypass; CO = cardiac output; HR = heart rate; SV = stroke volume; dP/dt,,, = maximum rate of rise of left ventricular pressure; LVEDP = left ventricular end-diastolic pressure; MAP = mean arterial pressure; CVP = central venous pressure; LAP = left artrial pressure.

utilization or inactivation of this hormone; the fall in T3 is associated with a comparable increase in reverse T3 [2].*

Though the level of free T3 in the untreated pigs re- mained insignificantly different from the control (before CPB) level, myocardial function after CPB was significantly worse in these animals (Groups 1A and 2A) and mortality from low-output myocardial failure sig- nificantly greater compared with that in the treated ani- mals (Groups 1B and 2B). T3 therapy was associated with improved cardiac function and no deaths.

The high mortality among the untreated pigs is in keeping with our observations on the development of fairly rapid hemodynamic instability and failure in pigs subjected to brain death, where again T3 levels are low, particularly when coupled with a period of myocardial ischemia [4, 51. (In comparison, the baboon remains in relatively hemodynamically stable condition for long pe- riods when subjected to identical conditions of CPB and myocardial ischemiat or brain death [6, 71. It should be emphasized that, in the present study, neither the un- treated nor T3-treated pigs received any form of conven-

'Novitzky D, Human PA, Cooper DKC Effect of triiodothyronine (T3) on myocardial high-energy phosphates and lactate following ischemia during cardiopulmonary bypass: an experimental study in baboons (sub- mitted for publication, 1987). 'Novitzky D, Human PA, Cooper DKC: Effect of hiiodothyronine (T3) on myocardial high-energy phosphates and lactate following ischemia during cardiopulmonary bypass: an experimental study in baboons (sub- mitted for publication, 1987).

tional inotropic support at any time during the ex- periment.

This study was neither a blind nor a randomized study. Nevertheless, following 2 or 3 hours of ischemia, the administration of T3 appears to be associated with a rapid return to normal or near-normal function. It is pos- sible that following 3 hours of ischemia, the dose of T3 administered was insufficient to reverse the functional deterioration completely. This conclusion is supported by the fact that HR was not increased either in compari- son with the control value or in comparison with the untreated pigs at the same time interval (in contrast to the pigs who underwent 2 hours of myocardial isch- emia).

Others [3] have observed an increase in myocardial contractility in patients with raised levels of plasma-free T3, and have shown that this increased contractility is not dependent on changes in preload, afterload, or heart rate. The hemodynamic observations made in the pres- ent study confirm that although some benefit may be obtained from the chronotropic effect of T3, there is also a definite increase in myocardial contractility, as evi- denced by dPidt,,,.

Previous studies [4-91 both in our laboratory and in potential organ donors from our center have demon- strated that following brain death, there is a fall in plasma-free T3 levels, which is associated with dimin- ished aerobic metabolism and an increase in anaerobic metabolism, events leading to a reduction in myocardial energy stores and increasing hemodynamic instability.

54 The Annals of Thoracic Surgery Vol 45 No 1 January 1988

We [7] have postulated an inability of the mitochondria to function adequately. The administration of T3 to brain-dead animals [5, 7, 81 or to brain-dead potential organ donors [9] results in a reversal to aerobic metabo- lism, a replacement of myocardial energy stores, and a return to hemodynamic stability. The need for inotropic support is greatly diminished or entirely eradicated. These observations correlate well with the work of others [lo-151 showing that T3 influences the oxidative activity of the mitochondria. It would seem likely that after a period of myocardial ischemia and CPB, during which the plasma-free T3 level is reduced, a similar se- quence of events takes place.

How does T3 bring about this inotropic effect? It is known that T3 activates various adenosine triphospha- tases (ATPases), for example, Na+-K+, Na+-Ca2+, Ca2+, myosin, and troponin, and may increase the ionized cal- cium concentration within the cytosol [16]. There is evi- dence from other studies [17, ls] that T3 stimulates adenyl cyclase, which is intimately involved in regula- tion of intracellular calcium levels and consequently of myocardial contractility [ 191; calcium activates key en- zymes of the tricarboxylic acid cycle, such as the pyru- vate dehydrogenase system. It has also been shown that as T3 influences the activity of the ATPases [16, 191, it will thus lead to increased usage of ATP. The protein carrier system, adenine nucleotide translocase, which transports adenosine diphosphate into and ATP out of the mitochondria to the cytoplasm to meet the energy requirements of the cell, may be the initiating site for T3 stimulation of the mitochondria [14, 151.

Further studies in our laboratory in baboons undergo- ing identical experimental protocols to the pigs reported here* would suggest that T3 possibly leads to increased synthesis of myocardial high-energy phosphates (per- haps by a similar mechanism to that seen in brain-dead potential organ donors) as well as increased utilization of such stores, thereby resulting in improved myocardial function. The postulated increased rates of ATP produc- tion and utilization would maintain a normal level of energy stores with a more efficient mechanical perform- ance. This suggestion is strongly supported by previous reported studies [20, 211.

In our study in baboons,* after 3 hours of ischemia, ATP and creatine phosphate returned to significantly higher levels (p < 0.002 and p < 0.05, respectively) in T3- treated animals than in untreated animals. Myocardial tissue lactate remained significantly increased (p < 0.01) in untreated baboons compared with treated baboons. It may be that T3 therapy leads to an increased production of energy stores, possibly by increasing aerobic metabo- lism in the myocardium.

In conclusion, T3 clearly has a significant beneficial inotropic effect when administered after a period of

*Novitzky D, Human PA, Cooper DKC: Effect of triiodothyronine (T3) on myocardial high-energy phosphates and lactate following ischemia during cardiopulmonary bypass: an experimental study in baboons. (submitted for publication, 1987)

myocardial ischemia and CPB. Therefore its administra- tion may be indicated in patients undergoing an open- heart operation.

This work was supported by the Christiaan Barnard Fund, the Medical Research Council of South Africa, the Cape Provincial Administration, and the University of Cape Town. We thank Mr. S. Isaacs, 8 . A., M.Sc., F.S.S., for advice regard- ing the statistical analyses, and Mrs. P. Ahrends, Ms. J. Place, F. Barends, Mrs. J. Kloppers, P. Madlingozi, J. Rossouw, and F. Snyders for skilled technical assistance.

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Bremner WF, Taylor KM, Baird S, et al: Hypothalamopitui- tary-thyroid axis function during cardiopulmonary bypass. J Thorac Cardiovasc Surg 75:392, 1978 Robuschi G, Medici D, Fesani F, et al: Cardiopulmonary bypass: “a low T4 and T3 syndrome” with blunted thyro- tropin (TSH) response to thyrotropin-releasing hormone (TRH). Horm Res 23:151, 1986 Feldman T, Borow KM, Same DH, et al: Myocardial me- chanics in hyperthyroidism: importance of left ventricular loading conditions, heart rate and contractile state. J Am Coll Cardiol 7967, 1986 Wicomb WN, Cooper DKC, Lanza RP, et al: The effects of brain death and 24 hours‘ storage by hypothermic perfu- sion on donor heart function in the pig. J Thorac Cardiovasc Surg 919396, 1986 Novitzky D, Wicomb WN, Cooper DKC, Tjaalgard MA: Improved cardiac function following hormonal therapy in brain dead pigs: relevance to organ donation. Cryobiology 241, 1987 Novitzky D, Wicomb WN, Cooper DKC, et al: Electrocar- diographic, haemodynamic and endocrine changes occur- ring during experimental brain death in the chacma ba- boon. J Heart Transplant 4:63, 1984 Novitzky D, Cooper DKC, Morrell D, Isaacs S: Change from aerobic to anaerobic metabolism after brain death, and reversal following triiodothyronine therapy. Transplanta- tion (in press, 1987) Novitzky D, Wicomb WN, Cooper DKC, Reichart B: Evi- dence of myocardial and renal functional recovery follow- ing hormonal treatment after brain death. Transplant Proc 18613, 1986 Novitzky D, Cooper DKC, Reichart 8: Hemodynamic and metabolic responses to hormonal therapy in brain-dead po- tential organ donors. Transplantation (in press, 1987) Bronk J R Thyroid hormone: effects on electron transport. Science 163:638, 1966 Sterling K, Milch PO: Thyroid hormone binding by a com- ponent of mitochondrial membrane. Proc Natl Acad Sci USA 723225, 1975 Sterling K, Milch PO, Brenner MA, Lazarus JH: Thyroid hormone action: the mitochondrial pathway. Science 197996, 1977 Sterling K, Brenner MA, Sakurada T: Rapid effect of triiodothyronine on the mitochondrial pathway in rat liver in vivo. Science 210:340, 1980 Sterling K Direct thyroid hormone activation of mitochon- dria: the role of adenine nucleotide translocase. Endocrinol- ogy 119:292, 1986

55 Novitzky et a1 Inotropic Effect of Triiodothyronine in Pigs

15. Sterling K The molecular mechanisms of thyroid hormone action at the cellular level. In van Middlesworth LC (ed): The Thyroid Gland: Practical Clinical Treatise. Chicago, Year Book, 1986, pp 203-229

16. Marriot ML, McNeill J H Effect of thyroid hormone treat- ment on response of the isolated working rat heart. Can J Physiol Pharmacol61:1382, 1983

17. Epstein SE, Skelton CL, Levey GS, Entman M: Adenyl cy- dase and myocardial contractility. Ann Intern Med 72:561, 1970

18. Levey GS: Catecholamine sensitivity, thyroid hormone and the heart. Am J Med 50413, 1971

19. Kim D, Smith TW: Effects of thyroid hormone on calcium handling in cultured chick ventricular cells. J Physiol (Lond) 364:131, 1985

20. Tata JR, Emster L, Lindenberg 0, et al: The action of thy- roid hormones at the cell level. Biochem J 86:408, 1963

21. Sestolt L Metabolic aspects of the calorigenic effect of thy- roid hormone in mammals. Clin Endocrinol (Oxf) 13:489, 1980

Circulatory Support 1988 Adam’s Mark Hotel, St. Louis, Missouri February 6-7, 1988 (weekend meeting)

Circulatory Support 1988 will be a comprehensive meet- ing on the clinical application of circulatory support de- vices. Surgeons, perfusionists, engineers, and operating room and intensive care unit nurses are encouraged to attend either individually or as a team.

The meeting is sponsored by The Society of Thoracic Surgeons under the direction of its Committee on Circulatory Assist Devices and Artificial Hearts. Com- mittee members are: D. Glenn Pennington, M.D., Chair- man; Jack G. Copeland, M.D.; Charles Hahn, M.D.; J. Donald Hill, M.D.; George J. Magovern, M.D.; Peer M. Portner, Ph.D.; and M. Glenn Rahmoeller.

For this weekend meeting, the Saturday morning seg- ment entitled “Problem Cases” will include panel dis- cussions on such topics as Patient Selection, Intraopera- tive Management, and Bleeding and Anti-Coagulation. Saturday afternoon will be divided in two parts, the first being a unique series of video presentations on the working details of currently available support devices. The second Saturday afternoon session will offer atten- dees break-out meetings divided into concurrent ses- sions for surgeons, perfusionists/engineers, and OWCU nurses on the subjects of (1) Ecmo, Roller, and Cen- trifugal Pumps, (2) External Pulsatile Pumps, and (3)

Internal Pulsatile Pumps. Sunday morning will be de- voted to a state-of-the-art session with discussions focusing on such topics as Resuscitation for Cardiac Shock, Post Cardiotomy Support, Bridging to Trans- plant, Permanent Artificial Hearts, and Devices of the Future.

On Sunday, February 7, from 2:OO to 5:OO P.M. there will be an optional session on regulatory issues. This special meeting will be chaired by The Society of Tho- racic Surgeons’ Committee on Circulatory Assist Devices and Artificial Hearts. Scientists from the Food and Drug Administration will be present. The session is intended to be an open forum for discussion of regulatory issues from the perspective of clinicians, the FDA, and the in- dustry. All registrants are invited to attend at no addi- tional fee.

In addition, there will be commercial exhibits related directly to program topics (by invitation only), and scientific posters will be used to show how circulatory devices are being used throughout the U.S. and else- where.

For registration and other meeting information con- tact: The Society of Thoracic Surgeons, 111 East Wacker Dr, Chicago, IL 60601; tel: (312) 644-6610.