Asian Cardiovasc Thorac Ann 1999;7:18-22
© 1999 Asia Publishing EXchange Pte Ltd
Effects on the Endocrine System of Pulsatile and Nonpulsatile Perfusion in Heart Surgery
Erdem Silistreli, MD,
Hüdai Çatalyürek, MD,
Nejat Sariosmano
lu, MD,
Ünal Açikel, MD,
Eyüp Hazan, MD,
Öztekin Oto, MD
Department of Thoracic & Cardiovascular Surgery Dokuz Eylul Medical Faculty  zmir, Turkey
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For reprint information contact: Erdem Silistreli, MD Tel: 90 232 277 5867 Fax: 90 232 277 2165 email: silistre{at}cs.med.deu.edu.tr Mithatpasa Cad. No. 257/5, Balcova, zmir 35340, Turkey.
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Abstract
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The effects of cardiopulmonary bypass on the endocrine system were investigated in 10 patients who had pulsatile perfusion and in another 10 who had nonpulsatile perfusion during coronary bypass or valve replacement surgery. Measurements were made of thyroid-stimulating hormone, free and total triiodothyronine, free and total tetraiodothyronine, adrenocorticotropic hormone, cortisol, aldosterone, growth hormone, insulin, and glucose at 5 fixed time intervals up to 24 hours postoperatively. In the perfusion period, free and total triiodothyronine levels were less depressed in the pulsatile group. The mean level of growth hormone was significantly higher in the pulsatile group after 60 minutes of perfusion. The mean levels of insulin and glucose were significantly lower in the pulsatile group after 60 minutes of perfusion. Other changes were not statistically significant. We concluded that pulsatile perfusion was of benefit in stabilizing glucose and some hormone levels.
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Introduction
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Many modifications of the cardiopulmonary bypass (CPB) technique have been developed over the years to reduce complications. Whereas circulation in the human body has a pulsatile character, CPB by the standard technique supplies nonpulsatile flow. Thus, one means of achieving more physiological conditions during CPB has been to provide perfusion in a pulsatile manner.1–7 The benefits of this method are controversial and a number of authors have claimed that pulsatile flow has no advantage in terms of organ perfusion or myocardial function and has adverse consequences in terms of hemolysis.3 On the other hand, better preservation of blood cells has been achieved by technical improvements in pulsatile perfusion instrumentation.4–7 Other studies have demonstrated that pulsatile perfusion improves the microcirculation with better organ perfusion and preservation, diminished fluid retention in the lungs and brain, and prevention of the increase in systemic vascular resistance by maintaining reflex vasomotor control at near normal levels.2,5,6,8–11 Additional beneficial effects on the central nervous system, gastrointestinal system, and the complement system have been reported.10–13
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Patients and Methods
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Twenty patients undergoing open-heart surgery in our institution between September 1997 and December 1997, were included in the study. Nonpulsatile perfusion was used in 10 patients, 7 of whom underwent coronary revascularization and 3 had valve replacement procedures. Pulsatile perfusion was used in the other 10 patients, 6 of whom had coronary revascularization and 4 had valve replacements.
All the patients were operated on with the same anesthetic protocol. Conventional atrial-aortic CPB was used with moderate hypothermia and control of acid-base balance. The lowest temperature during the bypass period was 28°C. The equipment used for extracorporeal circulation comprised 24F to 32F venous cannulae, 1/2 x 3/32 inch (venous) and 3/8 x 3/32 inch (arterial) Bentley custom tubing (Bentley Laboratories Europe BV, Uden, The Netherlands), a Bentley Univox membrane oxygenator (Baxter Healthcare Corp., Irvine, CA, USA), and a Bentley 200 mL arterial filter system with no. 4.5 to 5.2 arterial cannulae (Baxter Healthcare Corp., Irvine, CA, USA). Sarns roller pumps and pump heads (3M Healthcare, Ann Arbor, MI, USA) were used in both groups.
In the pulsatile perfusion group, extracorporeal circulation was started in nonpulsatile mode and converted to pulsatile mode after application of the aortic cross-clamp. When the aorta was declamped and left ventricular ejection was restarted, the perfusion was continued in nonpulsatile mode. In the pulsatile perfusion period, the flow rates ranged from 4.0 to 5.2 L•min–1 depending on the body temperature (flow was controlled at 2.4 L•min–1•m–2 but when calculated in terms of body weight, the range was 50 to 75 mL•kg–1•min–1). The mean arterial pressure was 61.1 ± 5.5 mm Hg in the nonpulsatile group and 62.1 ± 5.9 mm Hg in the pulsatile group. The mean difference between systolic and diastolic pressures in the pulsatile group was 18.8 mm Hg. Cold blood high-potassium cardioplegia was used with infusion of warm blood just before declamping the aorta in all cases.
Five blood samples were obtained from each patient: in the preoperative period; after induction of general anesthesia; after 30 and 60 minutes of perfusion; and at 24 hours postoperatively. The samples were analyzed for glucose and the following hormones: thyroid-stimulating hormone (TSH); free and total triiodothyronine (T3); free and total tetraiodothyronine (T4); adrenocorticotropic hormone (ACTH); cortisol; aldosterone; insulin; and growth hormone. The blood samples were preserved under appropriate conditions, glucose levels were measured immediately, and the samples for each hormone measurement were analyzed together with the same test kit. All test kits were produced by DPC (Diagnostic Products Corp., Los Angeles, CA, USA). Free and total T3 and free and total T4 were measured by the Coat-a-Count method, TSH was measured by the IRMA-Count method fluorometrically using a BYK Sangtec analyzor (BYK Sangtec Diagnostica, Deitzenbach, Germany). Growth hormone, ACTH, insulin, cortisol, and aldosterone were measured by radioimmunoassay in a Packard gamma counter (Packard Instruments, Meriden, CT, USA).
The statistical calculations were made with SPSS software (Statistical Package for Social Sciences for Windows, Student Version 6.0; SPSS, Inc., Chicago, IL, USA). A nonparametric test, the two-independent-samples test (Mann-Whitney U test) was used for comparing the groups and the alpha value was accepted as 0.05.
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Results
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There were no statistical differences between the groups in terms of age, weight, body surface area, mean perfusion pressure, flow rate, total CPB time, aortic cross-clamp time, and maximal cooling. No statistically significant differences were noted between the groups for any of the parameters measured in the first and second blood samples (p > 0.05). There were no significant differences in the mean levels of TSH, cortisol, total T4, or free T4 between the two groups of patients during the study period. However, the mean values of T3 decreased in both groups after the start of perfusion and they were significantly lower in the nonpulsatile group after 30 and 60 minutes of perfusion but there was no difference between the two groups at 24 hours postoperatively (Figure 1
). Free T3 was also lower in the nonpulsatile group but the difference was significant only after 30 minutes of perfusion (Figure 2). There was no significant difference in ACTH levels between the two groups during CPB (Figure 3) but the pulsatile perfusion group had higher levels at 24 hours postoperatively (p = 0.03). Aldosterone levels decreased during CPB in both groups with a trend for lower levels in the pulsatile perfusion group but the difference between the two groups was not significant (Figure 4). Growth hormone levels tended to be higher in the pulsatile group with a significant difference (p = 0.03) between the groups after 60 minutes of perfusion (Figure 5).
Insulin levels were lower in the pulsatile group (p = 0.04) after 60 minutes of perfusion (Figure 6). The results of glucose measurements are shown in Figure 7. The levels of glucose rose during CPB in both groups and they were significantly higher in the nonpulsatile group after 30 and 60 minutes of perfusion (p < 0.05).
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Discussion
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It has been well established that CPB causes many physiological changes although most of these are transient. A number of modifications to the technique of CPB have been advocated to lessen these physiological changes but many have proved ineffective. One such modification is to perform the perfusion in a pulsatile manner.1–7 There are conflicting reports of the benefits of pulsatile perfusion in reducing the hemolytic effects of CPB.3,4,7 The advantages in physiological terms are also contro-versial.2,5,6,8–11 Several studies have indicated that there is no physiological advantage with this technique.3 Some early and important research in this area was carried out by Wesolowski and colleagues14,15, which suggested in animal experiments in 1955 that pulsatile perfusion had no advantages even over a period of 6 hours. However, some of these findings were based on high flow rates of between 130 and 200 mL•kg–1•min–1 whereas with flow rates of 100 mL•kg–1•min–1, the difference between the pulsatile and nonpulsatile modes was more evident.1,16–18
Our study investigated the effects of pulsatile and nonpulsatile perfusion on the endocrine system in two groups of 10 patients. Samples were obtained at fixed time intervals for all patients to show the preoperative basal levels, the effect of general anesthesia, and the changes after 30 and 60 minutes off CPB as well as the levels at 24 hours postoperatively. In previous studies, samples were taken at the start and at the end of variable periods of CPB.
TSH is released during the endocrine response to trauma, mediated by stimulation of thyrotropin-releasing hormone. In a similar study, it was reported that this response could be reduced by pulsatile perfusion.5 However, another study showed no difference in TSH levels related to the mode of perfusion, in agreement with our findings.19 T3 has been shown to have inotropic and chronotropic effects on the myocardium and to increase its tolerance to ischemia.19 Our results support previous findings that the level of this hormone declined during CPB irrespective of the mode of perfusion.1,5,19 Hemodilution has been postulated as one explanation of this observation as well as diminished activity of 5'-deiodinase in peripheral tissues, which has a role in the translation of T4 to T3.5 It has been reported that T3 levels were closer to normal during pulsatile perfusion, as we found in our study.5,19 The factors determining the level of free T3 are similar to those for total T3, and higher levels of total T3 have been detected during pulsatile perfusion, which is also in agreement with our data.5,19 We found no significant difference between the two groups in terms of total or free T4, as reported by others.19
ACTH and cortisol have important roles in the response to trauma and they are among the first hormones to show increased levels in the posttraumatic state.20,21 ACTH secretion is stimulated by corticotropin-releasing hormone in the hypothalamo-hypophyses system.20 While the higher levels of ACTH in the pulsatile group did not have statistical significance during the perfusion period in our study, the difference was significant at 24 hours postoperatively. This is compatible with reports that pulsatile perfusion maintains the function of the hypothalamo-hypophyses system in the postoperative period.1,6,20 In some studies, higher cortisol levels were detected in patients with pulsatile perfusion, which were attributed to better protection of adrenocortical function.1,6 Our results revealed no statistically significant difference although there was a trend for higher levels in the pulsatile group. The results of growth hormone measurements were higher in the pulsatile group with significantly higher levels after 60 minutes of perfusion. This was considered to be beneficial because growth hormone plays a role in the posttraumatic phase via its anabolic effects.21
One of the advantages of pulsatile perfusion is more effective renal cortical perfusion. This is associated with higher urine output and lower secretion of renin, angiotensin, and aldosterone.1,3,22,23 Thus, it may reduce fluid retention and the degree of systemic vascular resistance. In comparing aldosterone levels in this study, the mean levels were lower in the pulsatile perfusion group, especially during the perfusion period, although the differences were not statistically significant.
It is claimed that pulsatile perfusion increases insulin secretion via protection of beta-cell function by enhancing perfusion of the pancreas.1,13,24 Our results do not support this; insulin levels were lower in the pulsatile group and consistent with the glucose measurements. In addition, the levels of anti-insulin hormones such as ACTH, cortisol, and growth hormone were higher in the pulsatile group during the perfusion period. In previous studies, both pulsatile and nonpulsatile perfusion during CPB caused a degree of hyperglycemia that was more evident in the nonpulsatile groups.1,13,24 We concluded that glucose levels were more stable during pulsatile perfusion and attribute this to the lower insulin levels.
This study showed that there were benefits in using pulsatile perfusion for CBP. These included potential positive inotropic effects on the myocardium indirectly by maintenance of T3 levels closer to normal and protection of the response to trauma by increasing the growth hormone levels. The glucose levels were more stable and this may be particularly important in diabetic patients. A further study is underway in our institution to assess the specific benefits of this mode of perfusion in diabetic patients.
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Abstract
Introduction
