Changes of ghrelin and brain natriuretic peptide levels in systemic vascular resistance after cardiopulmonary bypass

The application of cardiopulmonary bypass (CPB) using a heart-lung machine in open heart surgery is associated with numerous pathophysiological changes in the vascular system and the neurohormonal environment. In this study our purpose was to investigate whether the hormones brain natriuretic peptide (BNP) and ghrelin are involved in changes in the systemic vascular resistance index (SVRI) after CPB, using data from 20 patients who had undergone coronary artery by pass grafting accompanied by CPB. Hemodynamic measurements were obtained using a thermodilution catheter and included cardiac index and systemic vascular resistance index. Blood samples were taken before CPB, after CPB, and at 0 and 24 h postoperatively. The blood levels of total and acylated ghrelin were quantified by radioimmunoassay. Blood levels of BNP were measured by a fluorescence immunoassay kit. The SVRI was significantly higher at the end of CPB and at 0 h postoperatively than before CPB (end of CPB: 4282±1035 dyne·s·cm^?5·m^?2, 0 h postoperatively: 3239±635 dyne·s·cm^?5·m^?2 vs. before CPB: 2289±330 dyne·s·cm^?5·m^?2, p<0.05). Total and acylated ghrelin levels decreased until 0 h postoperatively but the change was not statistically significant. However, at 24 h after surgery, they showed a statistically significant increase over the initial ghrelin values (total before CPB: 1413.71±287.93 pg/ml vs. 24 h postoperatively: 1736.85±236.89 pg/ml; acylated ghrelin before CPB: 55.85±25.53 pg/ml vs. 24 h postoperatively: 106.28±30.86 pg/ml; p<0.05 for both). BNP values were markedly lower after than before CPB (before CPB: 69.07±48 pg/ml vs. after CPB: 21.96±13 pg/ml, p<0.05) and reached a maximum value 24 h postoperatively (before CPB: 56.3±42 vs. after CPB: 454.7±229 pg/ml, p<0.05). There was a weak negative correlation between the changes in SVRI and total and acylated ghrelin levels after the CPB period, but this was not statistically significant. However, there was a statistically significant negative correlation between SVRI and BNP after CPB and at 24 h postoperatively (r:?0.709, p<0.01 and r:?0.649, p<0.03, respectively). Taken together, our results show that the observed initial increases in ghrelin and/or BNP in the postoperative period (at 24 h) might be causally related to the decrease in the SVRI in the same period. However, further investigations are needed to clarify the significance of this observation with respect to that of SVRI.     

Ventilatory responses to partial cardiopulmonary bypass at rest and exercise in dogs

We determined the role of blood flow-induced changes in CO2 load to the lungs on ventilatory control, at rest and in the steady-state of electrically induced exercise, in the anesthetized dog. A portion of the vena caval blood was diverted to the descending aorta following "arterialization" through an extracorporeal gas exchanger. Ventilation typically decreased, both at rest and during exercise (i.e., at 2 different levels of mixed venous CO2), in proportion to the CO2 loss; arterial PCO2 was consequently regulated. There were concomitant increases of the pulmonary and peripheral vascular resistance. Bilateral cervical vagosympathectomy markedly attenuated the ventilatory response at rest, thus disrupting arterial PCO2 homeostasis, but not so during exercise. The results therefore provide evidence for and support the suggestion of CO2 flow-related hyperpnea both at rest and during muscular exercise.     

Plasma vasopressin levels during and after cardiopulmonary bypass in man

The effect of cardiopulmonary bypass (CPB) using high dose fentanyl anaesthesia on the concentrations of plasma arginine vasopressin (pAVP), serum electrolytes and osmolality was studied in 12 patients by repeated sampling up to 4th postoperative day. These values were also followed in another 20 patients for the first postoperative day. Fentanyl abolished the pAVP response often seen in major operations but not that produced by CBP. The pAVP concentration 4.8 +/- 0.8 pg/ml immediately after sternotomy increased to 27.2 +/- 1.5 pg/ml (P less than 0.001) after 5-10 minutes on CPB. By the 4th postoperative day the pAVP levels had reached normal values. The main reason for the elevated pAVP concentrations seems to be the onset of CPB, which provokes a fall in mean arterial pressure leading to pAVP release.     

Selective endothelial dysfunction in conscious dogs after cardiopulmonary bypass

Zanaboni, Paul, Paul A. Murray, Brett A. Simon, Kenton Zehr,Kirk Fleischer, Elaine Tseng, and Daniel P. Nyhan. Selective endothelial dysfunction in conscious dogs after cardiopulmonary bypass.J. Appl. Physiol. 82(6):1776-1784, 1997.It has previously been demonstrated thatcardiopulmonary bypass (CPB) causes prolonged pulmonary vascularhyperreactivity (D. P. Nyhan, J. M. Redmond, A. M. Gillinov, K. Nishiwaki, and P. A. Murray. J. Appl.Physiol. 77: 1584-1590, 1994). Thisstudy investigated the effects of CPB on endothelium-dependent(acetylcholine and bradykinin) and endothelium-independent (sodiumnitroprusside) pulmonary vasodilation in conscious dogs. Continuousleft pulmonary vascular pressure-flow (LP-) plots were generated in conscious dogs before CPB and again in the same animals 3-4 days post-CPB. The dose of U-46619 used to acutely preconstrict the pulmonary circulation to similar levels pre- andpost-CPB was decreased (0.13 ± 0.01 vs. 0.10 ± 0.01 mg · kg¹ · min¹,P < 0.01) after CPB. Acetylcholine,bradykinin, and sodium nitroprusside all caused dose-dependentpulmonary vasodilation pre-CPB. The pulmonary vasodilator response toacetylcholine was completely abolished post-CPB. For example, at leftpulmonary blood flow of 80 ml · kg¹ · min¹acetylcholine (10 µg · kg¹ · min¹)resulted in 72 ± 15% reversal (P < 0.01) of U-46619 preconstriction pre-CPB but caused no changepost-CPB. However, the responses to bradykinin and sodium nitroprussidewere unchanged post-CPB. The impaired pulmonary vasodilator response toacetylcholine, but not to bradykinin, suggests a selective endothelialdefect post-CPB. The normal response to sodium nitroprusside indicates that cGMP-mediated vasodilation is unchanged post-CPB.

     

Urinary soluble IL-6 receptor levels after cardiopulmonary bypass

To investigate the possible role of soluble interleukin 6 receptor (sIL-6r) in the inflammatory response to cardiopulmonary bypass (CPB) with extracorporeal circulation (ECC), we examined the levels of sIL-6r in the urine of 50 patients undergoing coronary artery bypass surgery. The presence of sIL-6r in urine was confirmed in these patients, with levels rising from 6 pg/ml preoperatively to 19.5 pg/ml at 6 h and 41 pg/ml at 24 h after the start of cardiopulmonary bypass. Cardiopulmonary bypass leads to a rise in sIL-6r in urine that has not returned to normal after 24 h, suggesting a role for sIL-6r and IL-6 in the inflammatory response to such surgery. Determination of cytokine receptor presence in urine offers a non-invasive approach to the monitoring of the immune and inflammatory response to the stress of surgical and traumatic injury.     

Reflex cardiorespiratory responses to pulmonary vascular congestion

The purpose of these studies was to determine the reflex responses of the cardiovascular system and central inspiratory activity caused by pulmonary vascular congestion. We used a canine preparation in which the left lung was isolated in situ and could be exposed to a variety of stimuli, including distension of the pulmonary capillaries with blood, without direct mechanical or chemical alterations on the circulation. We found that lung expansion to 30 cmH2O and stimulation of nerve endings of the left lung with capsaicin caused pronounced transient reflex bradycardia (-30 to -50 beats/min) and hypotension (-25 to -40 mmHg) and caused reflex cessation of inspiratory activity. Pressurizing the left pulmonary vessels by injecting blood in volumes sufficient to raise pulmonary transcapillary pressures to 30 mmHg caused no changes in heart rate, systemic arterial pressure, or inspiratory muscle activity. These results lead us to conclude that pulmonary vascular congestion does not stimulate pulmonary C-fibers or any other nerve endings to such a degree as to cause detectable changes in blood pressure, heart rate, or central inspiratory activity. Morphometric analysis revealed distended capillaries engorged with blood, but the alveolar wall surface area was not increased which raises the possibility that expansion of the alveolar membrane may be needed to mechanically initiate the C-fiber reflex.     

Autoregulation of the coronary vascular resistance after beta-adrenergic receptor blockade

It was previously observed that at the beginning of a 10 sec multiple arterial haemorrhage, vascular elasticity induces an increase of coronary vascular resistance, which in the late part of the haemorrhage is counteracted by the relaxation of the vascular smooth muscle fibres. In the present study the effect of multiple arterial haemorrhage on the coronary vascular resistance was studied after beta-adrenergic receptor blockade. The results suggest that also in these circumstances an elastic mechanism precedes a myogenic mechanism in the regulation of coronary vascular resistance.     

Neopterin kinetics after cardiac surgery with or without cardiopulmonary bypass

Cardiac surgery (CS) with cardiopulmonary bypass (CPB) induces systemic inflammatory response by activating plasma proteins and blood cells. Activated monocytes/macrophages produce inflammatory marker neopterin (NP). The aim was to explore the NP kinetics in first 24 hours after CS according to the CPB use. Significant difference between groups was found for NP levels 12 and 24 hrs after CS, being higher in on-pump group. Strong association was found between NP levels 12 hrs after CS and the length of ICU stay for on-pump group (r=0.744, p<0.001). Strong association was found between preoperative NP levels and the length of ICU stay for those on-pump patients with elevated preoperative NP (r=0.855, p=0.001; linear regression equation y=0.50x-5.14, p<0.001). Preoperative NP levels higher than 10 nmol/L in on-pump group could predict prolonged ICU stay and outpoint patients at higher risk for developing postoperative complications and, therefore, help to determine the necessary therapeutic interventions.     

Plasma catecholamine responses to exercise after training with beta-adrenergic blockade

Exercise training has been shown to decrease plasma norepinephrine (NE) and epinephrine (EPI) levels during absolute levels of submaximal exercise, which may reflect alterations in sympathetic tone as a result of training. To determine if beta-adrenergic blockade altered these changes in the plasma concentration of catecholamines with exercise conditioning, we studied the effects of beta-adrenergic blockade on NE and EPI at rest and during exercise in 24 healthy, male subjects after a 6-wk exercise training program. The subjects were randomized to placebo (P), atenolol 50 mg twice daily (A), and nadolol 40 mg twice daily (N). There were no changes in resting NE and EPI compared with pretraining values in any subject group. During the same absolute level of submaximal exercise NE decreased in P and A but was unchanged in N, whereas EPI decreased only in P. At maximal exercise all three groups developed significant increases in NE after training that paralleled increases in systolic blood pressure. EPI at maximal exercise increased after training with N but was unchanged with P or A. These training-induced changes in plasma catecholamine levels were masked or blunted when the A and N groups were studied while still on medication after training. Thus beta-adrenergic blockade has important effects on adaptations of the sympathetic nervous system to training, especially during submaximal exercise.     

氨甲环酸对体外循环术后炎症因子的影响

目的观察氨甲环酸(TA)对体外循环(CPB)围术期炎症因子的影响。方法将40例行体外循环心脏手术的患者随机分为实验组(A组)20例和对照组(B组)20例。A组在麻醉诱导后、体外循环结束时、手术结束时3个时段每次给予TA 10mg/kg;B组给予等量生理盐水。观察两组术前(T1),CPB停机时(T2),术后6h(T3)、12h(T4)和24h(T5)血IL-6、IL-8和CRP的计数水平。结果实验组血清中的IL-6和IL-8水平在CPB停机时、术后6h和12h均显著升高,术后24h均呈下降趋势,并显著低于对照组(P<0.05);CRP水平在术后12h显著升高,术后24h对照组较实验组显著升高(P<0.05)。结论氨甲环酸能减少CPB术后炎症因子的释放,减轻全身炎性反应。     

Peroxynitrite does not impair pulmonary and systemic vascular responses.

The effects of peroxynitrite (ONOO-) on vascular responses were investigated in the systemic and hindquarters vascular bed and in the isolated perfused rat lung. Intravenous injections of ONOO- decreased systemic arterial pressure, and injections of ONOO- into the hindquarters decreased perfusion pressure in a dose-related manner. Injections of ONOO- into the lung perfusion circuit increased pulmonary arterial perfusion pressure. Responses to ONOO- were rapid in onset, short in duration, and repeatable without exhibiting tachyphylaxis. Repeated injections of ONOO- did not alter systemic, hindquarters, or pulmonary responses to endothelium-dependent vasodilators or other vasoactive agonists and did not alter the hypoxic pulmonary vasoconstrictor response. Injections of sodium nitrate or nitrite or decomposed ONOO- had little effect on vascular pressures. Pulmonary and hindquarters responses to ONOO- were not altered by a cyclooxygenase inhibitor in a dose that attenuated responses to arachidonic acid. These results demonstrate that ONOO- has significant pulmonary vasoconstrictor, systemic vasodepressor, and vasodilator activity; that short-term repeated exposure does impair vascular responsiveness; and that responses to ONOO- are not dependent on cyclooxygenase product release.