Asian Cardiovasc Thorac Ann 1999;7:13-17
© 1999 Asia Publishing EXchange Pte Ltd
Thyroid Hormone and Myocardial Metabolism After Heart Surgery in Dogs
Noriyuki Murai, MD,
Yasushi Katayama, MD,
Takashi Yamada, MD,
Takao Imazeki, MD,
Yoshihito Irie, MD,
Hiroshi Kiyama, MD,
Yasuhiro Sato, MD,
Ikkoku Hata, MD,
Hirotugu Yoshida, MD,
Mikaya Mukouyama
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Department of Cardiovascular & Thoracic Surgery Dokkyo University School of Medicine Koshigaya Hospital Saitama, Japan
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For reprint information contact: Noriyuki Murai, MD Tel: 81 489 65 1111 Fax: 81 489 60 1506 email: shinpais{at}po.iijnet.or.jp Department of Cardiovascular & Thoracic Surgery, Dokkyo University School of Medicine, Koshigaya Hospital, 2-1-50 Minamikoshigaya, Koshigaya, Saitama 343-8555, Japan.
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Abstract
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Recent studies have demonstrated that thyroid hormone improves hemodynamics following open-heart surgery, through unknown mechanisms. The effect of triiodothyronine on myocardial metabolism was studied in dogs undergoing normothermic crystalloid cardioplegic arrest. Seven animals in group 0 served as controls, 8 in group 1 received 0.1µg•kg–1•min–1 triiodothyronine intravenously after aortic cross-clamping, and 3 dogs in group 2 received triiodothyronine 150 µg per day orally for 7 days preoperatively and intravenously (0.1 µg•kg–1•min–1) after aortic cross-clamping. Myocardial carbon dioxide production and the uptake of oxygen, lactate, glucose, and free fatty acids were determined before aortic cross-clamping and at 10, 30, 60, and 120 minutes after declamping. After aortic cross-clamping, increased myocardial uptake of oxygen, lactate, and glucose were observed in group 1 compared with group 0. Myocardial free fatty acid uptake decreased in all groups. Carbon dioxide production correlated with myocardial oxygen uptake. These findings suggest that intraoperative triiodothyronine supplementation improves myocardial metabolism but preoperative administration is ineffective.
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Introduction
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Although the operative mortality is less than 2% for elective coronary artery bypass grafting, postoperative left ventricular dysfunction remains a challenging complication. The cause of transient postoperative left ventricular dysfunction is usually attributed to either inadequate intraoperative myocardial protection or reperfusion injury. However, it has been suggested that a perioperative decrease in thyroid hormone metabolism may contribute to cardiac dysfunction and a significant reduction in plasma triiodothyronine (T3) has been documented in patients undergoing open-heart procedures.1,2 Recent studies have suggested that this transient decrease in T3 levels after cardiopulmonary bypass contributes to postoperative myocardial dysfunction and that T3 supplementation can improve ventricular systolic performance in the immediate postoperative period.3,4 The mechanism by which T3 supplementation enhances postischemic function is not clear. We hypothesized that T3 administration might increase myocardial metabolism and thereby improve contractile function. The purpose of this experimental study was to determine the effect of thyroid hormone on myocardial metabolism following cardiac surgery.
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Materials and Methods
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Eighteen mongrel dogs weighing 14.5 to 28 kg were used in these experiments. All studies were performed in accordance with the Guide for the Care and Use of Laboratory Animals (NIH publication no. 85–23, revised 1985). The animals were divided into 3 experimental groups: 7 dogs in group 0 served as controls; 8 in group 1 had 0.1 µg•kg–1•min–1 triiodothyronine intravenously after aortic cross-clamping; and 3 in group 2 received triiodothyronine 150 µg per day orally for 7 days preoperatively and intravenously (0.1 µg•kg–1•min–1) after aortic cross-clamping. After induction of anesthesia with intravenous thiopental sodium (30 mg•kg–1), paralysis was achieved with an intramuscular injection of succinylcholine (20 mg•kg–1), repeated as necessary. Endotracheal intubation was carried out and mechanical ventilation was performed with a Harvard Dual Phase Control Respirator (Harvard Corp., South Natick, MA, USA). The electrocardiogram was monitored continuously and the heart rate was recorded. Cannulae were inserted to monitor arterial and left atrial pressures. Arterial blood gases were measured at least every 30 minutes throughout the experiment and ventilatory or acid-base imbalances were corrected. After exposure of the heart, a two-channel flowmeter (Transonic System Corp., Ithaca, NY, USA) was placed on the ascending aorta to measure cardiac output and stroke volume. A Gundry retrograde coronary sinus perfusion cannula (Medtronic, Inc., Grand Rapids, MI, USA) was inserted for the measurement of coronary flow by balloon inflation.
Cardiopulmonary bypass was initiated through cannulae inserted into the right atrium and right femoral artery and the heart was vented through either the pulmonary artery or the ventricular apex. Standard cardiopulmonary bypass was performed using roller pumps (model 5745; Pemco Inc., Cleveland, OH, USA) and a membrane oxygenator (Monolith; Sorin Biomedica, Saluggia, Italy). The pump was primed with 700 mL of blood. A flow rate of 70 mL•kg–1•min–1 maintained a mean arterial pressure of 60 mm Hg. After cross-clamping the ascending aorta, cardioplegic arrest was induced with a solution containing glucose (38.61 g•L–1), insulin (10 U•L–1), potassium (29.8 mEq•L–1), magnesium (31.8 mEq•L–1), chloride (21.9 mEq•L–1), and D-mannitol (18.02 g•L–1). The cardioplegic solution was infused initially at 30 mL•kg–1 with subsequent infusions of 15 mL•kg–1 at 30-minute intervals. After one hour of myocardial ischemia, the aorta was declamped and the heart was reperfused.
The myocardial uptake of oxygen, lactate, glucose, and free fatty acid (FFA), and myocardial carbon dioxide production were studied before aortic cross-clamping and at 10, 30, 60, and 120 minutes after declamping. Immediately after cardioplegic arrest and 120 minutes after the release of the aortic cross-clamp, biopsies were taken from the apex of the heart. Cardiac output, heart rate, and coronary sinus flow were recorded at the same time as the metabolic measurements. Uptake rates of myocardial oxygen, glucose, lactate, and FFA, as well as production of carbon dioxide (CO2) were calculated from the difference between arterial and coronary sinus concentrations x coronary sinus flow ÷ heart weight.
All data were expressed as the mean ± standard error. Comparisons between the groups were analyzed using the Student t test for unpaired data. Comparisons between CO2 production and oxygen uptake were made with simple regression analysis.
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Results
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There was no difference in the hemodynamic measurements between group 1 and the control group (Figure 1
). One dog in group 2 could not be weaned from cardiopulmonary bypass. Uptake of oxygen, lactate and glucose was significantly greater in group 1 at 10, 30, 60, and 120 minutes after release of the aortic cross-clamp compared to the other groups (Table 1). After reperfusion, FFA uptake was reduced to a similar extent in all three groups (Table 1). There was a strong correlation (r = 0.911, p < 0.0001) between myocardial CO2 production and myocardial oxygen uptake (Figure 2). There was a trend toward an increase in CO2 production in group 1 compared to the control group but the differences were not significant. Electron microscopy in the control showed intact mitochondria and myofibrils. Samples taken from Group 2 showed heterogeneity of the mitochondria and the myofibrils were disrupted (Figure 3). This showed that excessive doses of T3 were harmful to the micro-architecture.
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Figure 1. Hemodynamic parameters in controls (group 0) and group 1 dogs. There were no significant differences between the groups in terms of heart rate or stroke volume.
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Figure 2. Comparison of CO2 production and myocardial O2 uptake in controls (group 0) and group 1. There was a strong correlation between these data (y = 0.009 + 0.396x, r = 0.911, p < 0.0001).
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Discussion
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After cardiopulmonary bypass, thyroid hormone concentrations are reduced.1,2 Further, the concentration of T3 is markedly reduced in low-output syndromes. Previous studies have implicated decreased thyroid hormone reducing factor (iodothyronine 5'-deiodinase activity), hypothalamo-pituitary thyroid function, and dopamine as causing the decrease in T3 following cardiopulmonary bypass.5–7 When the thyroid hormone concentration is low, protein metabolism decreases, myocardial tissue becomes edematous, oxygen supply decreases, and the endocardium becomes ischemic.8 Karlsberg and colleagues9 found that myocardial infarction mediated by hypothyroidism was associated with ultrastructural abnormalities. Recent studies have demonstrated a beneficial effect of T3 administration after myocardial ischemia and cardiopulmonary bypass.3,4 The effects of T3 on hemodynamic function are due to maintenance of cellular ultrastructure and improvement in dilatory and contractile functions as well as improvement in vasodilation and the response to beta-adrenergic agents.10–14
In this study, T3 administration increased myocardial uptake of oxygen, lactate, and glucose. In addition, there was a tendency toward an increase in CO2 production in group 1. However, the myocardial uptake of FFA decreased after ischemia in all groups. Therefore, T3 did not improve FFA metabolism. Another study demonstrated that administration of intravenous glucose-insulin-potassium solution following open-heart surgery caused an increase in CO2 production.15 In our study, there was a strong correlation between myocardial CO2 production and myocardial oxygen uptake. Therefore, CO2 production may be a reliable index of aerobic metabolism. There were no differences observed in this study between the hemodynamic parameters in the three groups. This indicates that the effect of T3 on hemodynamics was minimal and suggests that metabolic improvement does not result in hemodynamic improvement.
While hyperthyroidism increases the incidence of arrhythmias and angina pectoris, T3 therapy after cardiac surgery can reduce the incidence of arrhythmias.16 Therefore, maintaining the T3 concentration within the normal range is important. Naito17 reported that mild hyperthyroidism improved ventricular systolic performance but severe hyperthyroidism caused ventricular dysfunction. Our study confirms the benefit of T3 administration on myocardial metabolism following cardiac surgery. However, it must be kept in mind that excessive doses of T3 are harmful.18
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References
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Abstract
Introduction
