Inhaled iloprost to control residual pulmonary hypertension following pulmonary endarterectomy

Objective: Pulmonary endarterectomy (PEA) is the standard therapy for patients with chronic thromboembolic pulmonary hypertension (CTEPH). In the immediate postoperative period, persistent pulmonary hypertension increases the risk of acute respiratory or right heart failure. In pulmonary arterial hypertension, prostanoid inhalation has been found to improve pulmonary hemodynamics, right ventricular function, gas exchange, and clinical outcome. We report the results of a double-blinded randomized trial with the aerosolized prostacyclin analogue iloprost in patients with residual pulmonary hypertension after PEA. Methods: Twenty-two patients (age, 55 ± 13 years; 8 females; propofol- and sufentanil-based anesthesia; pressure-controlled mechanical ventilation) were randomized to receive either a single dose of 25 μg aerosolized iloprost (iloprost group; n = 11) or normal saline (placebo group; n = 11) immediately after postoperative ICU admission. Primary endpoints were changes in gas exchange, pulmonary and systemic hemodynamics, and clinical outcome. Results: Iloprost significantly enhanced cardiac index (CI) and reduced mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance [PVR (dyn s cm⁻⁵)] in contrast to placebo. Placebo: pre-inhalation 413 ± 195 versus post-inhalation 404 ± 196 at 30 min (p = 0.051), 415 ± 189 at 90 min (p = 0.929). Iloprost: pre-inhalation 503 ± 238 versus post-inhalation 328 ± 215 at 30 min (p = 0.001), 353 ± 156 at 90 min (p = 0.003). Blood oxygenation remained unchanged. Conclusion: In addition to the effect of PEA, iloprost reduces residual postoperative pulmonary hypertension, decreases right ventricular afterload and may facilitate the early postoperative management after PEA.     

吸入伊洛前列素和一氧化氮治疗先天性心脏病术后肺动脉高压

目的 探讨吸入伊洛前列素对先天性心脏病(CHD)术后早期机械通气和持续吸入一氧化氮(NO)的基础上,仍合并肺动脉高压(PH)病儿的疗效及对预后的影响,并初步探讨其作用机制.方法 30例CHD根治手术后在机械通气和持续一氧化氮(NO)吸入的基础上仍合并PAH的病儿,随机分为试验(T)组和对照(C)组.在原治疗基础上,T组给予伊洛前列素100 ng·kg-1·min-1,吸入10 min,C组给予0.9%NaCl 4ml吸入.每4h一次,连续治疗48 h.超声和心电监测观察病儿的血流动力学和呼吸机条件的改变.对比首次吸药前后血浆环磷酸腺苷(cAMP)和环磷酸鸟苷(cGMP)浓度变化.结果 T组停止吸入伊洛前列素后20min,肺动脉收缩压(sPAP)和肺动脉收缩压/主动脉收缩压(sPAP/sBP)明显下降,分别为:(43.23±11.72)mm Hg(1 mm Hg=0.133 kPa)和0.48±0.13,均小于C组(53.13±13.60)mm Hg和0.60 ±0.15,P<0.05.停止吸药120 min,T组sPAP/sBP仍然小于C组(0.48±0.09对0.59±0.14,P<0.05).连续治疗24 h和48 h,T组sPAP和sPAP/sBP继续下降,均明显小于C组(P<0.01).停止首次吸药后20 min,T组cAMP(578.68±193.05)pg/dl较治疗前(406.64±179.18)pg/dl明显升高(P<0.01),也明显大于C组(392.26±94.46)pg/dl(P<0.01).C组2例因肺高压危象(PHC)死亡,T组无死亡.结论 CHD双心室矫正术后早期机械通气和持续吸入NO仍合并PH病儿,吸入伊洛前列素后可明显降低sPAP和sPAP/sBP.伊洛前列素可能减少肺高压危象(PHC)导致的死亡.其扩血管作用可能与血浆cAMP浓度升高有关.     

Inhaled but not intravenous milrinone prevents pulmonary endothelial dysfunction after cardiopulmonary bypass

OBJECTIVE: Cardiopulmonary bypass triggers a systemic inflammatory response that alters pulmonary endothelial function, which can contribute to pulmonary hypertension. Milrinone is a type III phosphodiesterase inhibitor. The objective of this study was to compare the effects of inhaled and intravenous milrinone on the pulmonary endothelium-dependent relaxations and hemodynamic and oxygenation parameters after cardiopulmonary bypass in a porcine model. METHODS: Five groups of Landrace swine were compared: (1) control group, no cardiopulmonary bypass; (2) bypass group, 90 minutes of normothermic bypass and 60 minutes of reperfusion; (3) inhaled milrinone group, bypass preceded by a 1.8-mg bolus of inhaled milrinone followed by a continuous milrinone nebulization; (4) intravenous milrinone group, bypass preceded by 2 mg of intravenous milrinone; and (5) inhaled NaCl group, bypass preceded by inhaled saline solution. After sacrifice, pulmonary arterial endothelium-dependent relaxations to acetylcholine and bradykinin were studied in organ chambers. RESULTS: Inhaled milrinone caused less hypotension ( P < .05), a lesser decrease in peripheral vascular resistances ( P < .01), and a lower heart rate ( P < .05) than intravenous milrinone. Inhaled milrinone prevented the alterations in relaxations of pulmonary arteries to acetylcholine caused by cardiopulmonary bypass, and relaxations to bradykinin were improved in the inhaled milrinone group ( P < .05) compared with the cardiopulmonary bypass and control groups. CONCLUSIONS: Inhaled milrinone prevents the occurrence of the pulmonary endothelial dysfunction seen after cardiopulmonary bypass. The hemodynamic and oxygenation profiles obtained with inhaled milrinone are safer than with intravenous milrinone. These strategies might be useful in preventing pulmonary hypertension after cardiac surgery.     

Inhaled iloprost in patients with chronic thromboembolic pulmonary hypertension: effects before and after pulmonary thromboendarterectomy

BACKGROUND: In primary pulmonary hypertension, aerosolized prostanoids selectively reduce pulmonary vascular resistance and improve right ventricular function. In this study, hemodynamic effects of inhaled iloprost, a stable prostacyclin analogue, were evaluated in patients with chronic thromboembolic pulmonary hypertension (CTEPH) before and early after pulmonary thromboendarterctomy (PTE). METHODS: Ten patients (mean age 49 years old [32 to 70 years old], New York Heart Association functional class III and IV) received a dose of 33 micro g aerosolized iloprost immediately before surgery (T1), after intensive care unit admission (T2), and 12-hours postoperatively (T3). Effects on pulmonary and systemic hemodynamics and gas exchange were recorded and compared with preinhalation baseline values. RESULTS: Preoperatively, inhaled iloprost did not significantly change mean pulmonary artery pressure (mPAP), cardiac index (CI), or pulmonary vascular resistance (PVR). Postoperatively, inhaled iloprost induced a significant reduction of mPAP and PVR and a significant increase of CI at T2 and T3. Preinhalation versus postinhalation PVR was as follows: at T1, 847 versus 729 dynes. s. cm(-5), p = 0.45; at T2, 502 versus 316 dynes. s. cm(-5), p = 0.008; and at T3, 299 versus 227 dynes. s. cm(-5), p = 0.004. CONCLUSIONS: In patients with CTEPH, inhalation of iloprost elicits no significant pulmonary vasodilation before surgery, and may have detrimental effects on systemic hemodynamics. Postoperatively, it significantly reduces mPAP and PVR, and enhances CI. Following PTE, inhalation of iloprost is useful to improve early postoperative hemodynamics.     

吸入伊洛前列素对先天性心脏病矫治术患者体外循环后肺动脉高压的影响

目的 评价吸入伊洛前列素对先天性心脏病矫治术患者体外循环后肺动脉高压的影响.方法 选择体外循环下先天性心脏病矫治术患者58例,年龄14～60岁,气管插管后右颈内静脉置漂浮导管监测肺动脉压.体外循环下行先天性心脏病矫治术,体外循环结束后平均肺动脉压仍>25mm Hg,此时通过压缩式雾化器吸入伊洛前列素10μg,于吸药前即刻(T_0)、吸药完毕后即刻,吸药完毕后5、15、30和60min时监测心率、右房压、肺小动脉楔压、平均肺动脉压、平均桡动脉压、肺血管阻力和体循环阻力、心输出量及混合静脉血氧饱和度.结果 先天性心脏病矫治术患者体外循环后存在肺动脉高压患者28例.与吸药前即刻比较,吸药完毕后各时点患者平均肺动脉压和肺血管阻力明显降低,心输出量和吸药完毕后即刻、5 min时混合静脉血氧饱和度明显升高(P<0.05或0.01).结论 体外循环结束后吸入伊洛前列素可有效降低先天性心脏病矫治术患者肺动脉压和肺血管阻力,有助于患者安全、顺利地脱离体外循环.     

Antithrombin reduces pulmonary hypertension during reperfusion after cardiopulmonary bypass in a pig

BACKGROUND: Antithrombin (AT) may alleviate many cardiopulmonary bypass (CPB) and ischemia-reperfusion (I/R)-related adverse effects. Using a porcine model of clinical cardiac surgery on CPB, we tested the effects of supplementary AT on myocardial and lung I/R injury. METHODS: Twenty pigs undergoing 60-min aortic clamping and 75-min normothermic perfusion were randomized in a blinded setting to receive an intravenous (i.v.) bolus of AT (250 IU/kg) (AT group, n = 10) or placebo (n = 10) 15 min before aortic declamping. An additional group of five animals received 500 IU/kg AT in an open-label setting (AT+). Thrombin-antithrombin complexes (TAT), activated clotting times (ACT), AT and myeloperoxidase (MPO) activities, troponin T, and several hemodynamic parameters were measured before CPB and after weaning from CPB up to 120 min after aortic declamping. After 120 min of reperfusion, myocardial and lung biopsies were taken for histological examination. RESULTS: AT effectively inhibited coagulation as assessed by ACT. In the AT and AT+ groups only, cardiac output (CO) and stroke volume (SV) showed a trend of post-ischemic recovery during the first 15 min after CPB. AT-attenuated reperfusion induced an increase in pulmonary arterial diastolic pressure (PAPD) but did not have significant effects on systemic or pulmonary vascular resistance. The effects of AT on SV, CO, and PAPD were fortified in the AT+ group. AT did not show effects on inflammatory changes in either myocardial or pulmonary tissue specimens. AT did not reduce post-ischemic troponin T release. CONCLUSION: Supplementary AT, in doses with significant anticoagulant effect, did not alleviate myocardial I/R injury in terms of histological inflammatory changes or post-ischemic troponin T release. Instead, however, AT-attenuated reperfusion induced an increase in pulmonary pressure after CPB. Mechanisms and clinical implications of these effects remain to be explored.     

Sildenafil citrate alleviates pulmonary hypertension after hypoxia and reoxygenation with cardiopulmonary bypass

BACKGROUND: Sudden reoxygenation of hypoxic neonates undergoing cardiac operation exacerbates the systemic inflammatory response to cardiopulmonary bypass secondary to reoxygenation injury, worsening cardiopulmonary dysfunction. Reports suggest sildenafil decreases pulmonary hypertension and may affect myocardial function. Sildenafil's efficacy for treating postbypass cardiopulmonary dysfunction remains unknown. STUDY DESIGN: Fourteen neonatal piglets (5 to 7 kg) underwent 90 minutes of hypoxia, 60 minutes of reoxygenation with cardiopulmonary bypass, and 120 minutes of recovery. Six animals received 50 mg oral sildenafil and eight received saline at hypoxia. Data are presented as mean +/- SD. RESULTS: Sildenafil prevented the high pulmonary vascular resistance observed in controls (controls baseline 81 +/- 37 dynes. s/cm(5) versus recovery 230 +/- 93 dynes. s/cm(5), p = 0.004; sildenafil baseline 38 +/- 17 dynes. s/cm(5) versus recovery 101 +/- 60 dynes. s/cm(5), p = 0.003). Despite lower pulmonary vascular resistance after sildenafil, arterial endothelin-1 (ET-1) was increased in both groups (control baseline 1.3 +/- 0.5 pg/mL versus recovery 4.5 +/- 3.7 pg/mL, p = 0.01; sildenafil baseline 1.3 +/- 0.3 pg/mL versus recovery 9.8 +/- 4.9 pg/mL, p = 0.003). Intravenous nitric oxide (NO) levels were preserved after sildenafil treatment (sildenafil baseline 340 +/- 77 nM versus recovery 394 +/- 85 nM). IV NO levels in controls were decreased when compared with baseline (control baseline 364 +/- 83 nM versus recovery 257 +/- 97 nM, p = 0.028). Although levels of exhaled NO decreased in both groups, the sildenafil-treated animals had higher levels of exhaled NO when compared with controls at the end of recovery (0.6 +/- 0.4 parts per billion versus 1.8 +/- 0.9 parts per billion, respectively, p = 0.029). CONCLUSIONS: Sildenafil alleviated pulmonary hypertension after reoxygenation with cardiopulmonary bypass. Despite increased ET-1 levels, pulmonary vascular resistance was lower with sildenafil treatment, suggesting sildenafil's effect on the pulmonary vasculature is capable of countering vasoconstriction by ET-1. Further study into the role of sildenafil in perioperative therapy and its interactions with ET-1 are warranted.     

Preoperative glucocorticoids decrease pulmonary hypertension in piglets after cardiopulmonary bypass and circulatory arrest

BACKGROUND: Glucocorticoids during cardiopulmonary bypass benefit pediatric patients undergoing repair of congenital heart defects and are routine therapy, but underlying mechanisms have not been fully examined. The hypothesis was that glucocorticoids could improve cardiopulmonary recovery after cardiopulmonary bypass and deep hypothermic circulatory arrest. METHODS: Crossbred piglets (5 to 7 kg) were cooled with cardiopulmonary bypass, followed by 120-min deep hypothermic circulatory arrest. Animals were then warmed to 38 degrees C, removed from bypass, and maintained for 120 min. Methylprednisolone (60 mg/kg) was administered in the cardiopulmonary bypass pump prime (intraoperative glucocorticoids) or 6 hours before bypass (30 mg/kg) in addition to the intraoperative dose (30 mg/kg; preoperative and intraoperative glucocorticoids). Controls (no glucocorticoids) received saline. RESULTS: Pulmonary vascular resistance in controls increased from a baseline of 152 +/- 40 to 364 +/- 29 dynes. s/cm(5) at 2 hours of recovery (p < 0.001). Intraoperative glucocorticoids did not alleviate the increase in pulmonary vascular resistance (301 +/- 55 dynes. s/cm(5) at 2 hours of recovery, p < 0.001). However, animals receiving pre and intraoperative glucocorticoids had no increase in pulmonary vascular resistance (155 +/- 54 dynes. s/cm(5)). Plasma endothelin-1 in controls increased from 1.3 +/- 0.2 at baseline to 9.9 +/- 2.0 pg/mL at 2 hours recovery (p < 0.01), whereas glucocorticoid-treated animals had lower endothelin-1 levels (4.5 +/- 2.1 pg/ml, preoperative and intraoperative glucocorticoids; 4.9 +/- 1.7 pg/mL, intraoperative glucocorticoids) at the end of recovery (p < 0.05). Intracellular adhesion molecule-1 in lung tissue was lower in animals receiving pre and intraoperative glucocorticoids (p < 0.05). Myeloperoxidase activity was elevated in control lungs at 2 hours of recovery compared with glucocorticoid-treated groups (p < 0.05). Inhibitor kappaBalpha, the inhibitor of nuclear factor-kappaB, was higher in lungs of animals receiving glucocorticoids compared with controls (p < 0.05). CONCLUSIONS: Glucocorticoids prevented pulmonary hypertension after cardiopulmonary bypass and deep hypothermic circulatory arrest, which was associated with reduced plasma endothelin-1. Glucocorticoids also reduced pulmonary intercellular adhesion molecule-1 and myeloperoxidase activity. Inhibition of nuclear factor-kappaB, along with reduced neutrophil activation, contributed to glucocorticoid alleviation of pulmonary hypertension after cardiopulmonary bypass and deep hypothermic circulatory arrest.     

Acute pulmonary hypertension after cardiopulmonary bypass in pig: the role of endogenous endothelin.

BACKGROUND: Acute pulmonary hypertension occurring after cardiopulmonary bypass can be a cause of post-operative morbidity and mortality. The purpose of this study was to investigate whether bosentan, a non-peptidic mixed endothelin antagonist affected the pulmonary hypertension induced by experimental cardiopulmonary bypass. METHODS: Pigs were anesthetized and instrumented to determine hemodynamic measurements. Pigs were randomized to receive either 3 mg/kg bolus + 7 mg/kg per h bosentan (n = 8) or saline (n = 7). All pigs underwent 90 min of cardiopulmonary bypass and were further observed for a 120-min period. RESULTS: In the control group, cardiopulmonary bypass induced a dramatic pulmonary hypertension (+78 +/- 13%, P < 0.005) and accompanied an increase of pulmonary vascular resistance (+228 +/- 50%, P < 0.005), whereas, in the treated group, bosentan completely prevented these deleterious effects of cardiopulmonary bypass with only a moderate decrease of systemic vascular resistance (-19 +/- 14.6%, P < 0.05). CONCLUSIONS: The present findings support the hypothesis that endogenous endothelin is a mediator of acute pulmonary hypertension occurring after cardiopulmonary bypass. Bosentan, a mixed endothelin antagonist completely prevented pulmonary hypertension after cardiopulmonary bypass and may, therefore, have therapeutic applications in the management of patients following cardiac surgery.     

Effects of ischemia on pulmonary dysfunction after cardiopulmonary bypass

BACKGROUND: Pulmonary hypertension and lung injury secondary to cardiopulmonary bypass (CPB) are probably caused by a combination of ischemia and inflammation. This study was undertaken to investigate the potential ischemic effects of cessation of pulmonary arterial flow during CPB on pulmonary injury. METHODS: Twenty neonatal piglets (2.5 to 3.1 kg) were randomly assigned to two groups. Group A (n = 10) underwent 90 minutes of CPB at full flow (100 mL x kg(-1) x min(-1)) and clamping of the main pulmonary artery (PA). Group B (n = 10) underwent 90 minutes of partial CPB (66 mL x kg(-1) x min(-1)) with continued mechanical ventilation and without clamping of the PA. All hearts were instrumented with micromanometers and a PA ultrasonic flow probe. Endothelial function was assessed by measuring endothelial-dependent relaxation (measured by change in pulmonary vascular resistance after PA infusion of acetylcholine) and endothelial-independent relaxation (measured by change in pulmonary vascular resistance after ventilator infusion of nitric oxide and PA infusion of sodium nitroprusside). RESULTS: All groups exhibited signs of pulmonary injury after CPB as evidenced by significantly increased pulmonary vascular resistance, increased alveolar-arterial O2 gradients, and decreased pulmonary compliance (p<0.05); however, pulmonary injury was significantly worse in group A (p<0.05). CONCLUSIONS: This study suggests that although exposure to CPB alone is enough to cause pulmonary injury, cessation of PA flow during CPB contributes significantly to this pulmonary dysfunction.     

Antihypertensive mechanism of ketanserin in postoperative hypertension after cardiopulmonary bypass

The effect of ketanserin (0.15 mg/kg followed by an infusion at 6 mg/hr) was studied in 13 patients who developed hypertension (blood pressure greater than 150/90 mm Hg) after cardiopulmonary bypass (CPB) for coronary artery bypass grafting. Eleven patients responded to ketanserin with a decrease of arterial pressure from 159 +/- 15/83 +/- 10 mm Hg to 131 +/- 9/70 +/- 12 mm Hg (P less than 0.01), which was sustained during the subsequent infusion of ketanserin. Mean plasma ketanserin concentrations were maintained at 187 micrograms/L (range 118-525). No significant changes in plasma levels of 5-hydroxyindoles or in platelet 5-hydroxytryptamine content were observed during or after CPB, or after administration of ketanserin. Plasma epinephrine (398 +/- 124 pg/ml) and norepinephrine (1161 +/- 673 pg/ml) concentrations were markedly increased during the hypertensive period after CPB. Plasma epinephrine concentrations decreased (P less than 0.01) during ketanserin infusion to 213 +/- 101 pg/ml, whereas plasma norepinephrine concentrations did not change. The pressor response to three graded doses of phenylephrine was decreased during CPB (P less than 0.01), and a further decrease (P less than 0.05) occurred during infusion of ketanserin. The hypotensive effect of ketanserin after CPB may be attributable to alpha 1-adrenoceptor blockade rather than to its antiserotoninergic effect. Serotonin does not appear to be involved in the short-term disturbances of arterial pressure during or after CPB.     

Inhaled nitric oxide for pulmonary hypertension after heart transplantation.

BACKGROUND: Recipient pulmonary hypertension due to chronic congestive heart failure is a major cause of right ventricular (RV) dysfunction after heart transplantation. We hypothesized that inhaled nitric oxide (NO), in the postoperative period, would a) selectively reduce pulmonary vascular resistance and improve RV hemodynamics and b) reduce the incidence of RV dysfunction compared with a matched historical group. METHODS: Sixteen consecutive adult heart transplant recipients with lowest mean pulmonary artery (PA) pressures >25 mmHg were prospectively enrolled. Inhaled NO at 20 parts per million (ppm) was initiated before termination of cardiopulmonary bypass (CPB). At 6 and 12 hours after CPB, NO was stopped for 15 minutes and systemic and pulmonary hemodynamics were measured. RV dysfunction was defined as central venous pressure >15 mmHg and consistent echocardiographic findings. The incidence of RV dysfunction and 30-day survival in this group was compared with a historical cohort of 16 patients matched for pulmonary hypertension. RESULTS: Discontinuation of NO for 15 minutes at 6 hours after transplantation resulted in a significant rise in mean PA pressure, pulmonary vascular resistance (PVR), and RV stroke work index. Systemic hemodynamics were not affected by NO therapy. One patient in the NO-treated group, compared with 6 patients in the historical cohort group, developed RV dysfunction (P< .05). The 30-day survival in the NO-treated group and the historical cohort group were 100% and 81%, respectively (P> .05). CONCLUSION: In heart transplant recipients with pulmonary hypertension, inhaled NO in the postoperative period selectively reduces PVR and enhances RV stroke work. Furthermore, NO reduces the incidence of RV dysfunction in this group of patients when compared with a historical cohort matched for pulmonary hypertension. Inhaled NO is a useful adjunct to the postoperative treatment protocol of heart transplant patients with pulmonary hypertension.     

吸入伊洛前列素行急性肺血管扩张试验在先天性心脏病合并重度肺动脉高压术前评估中的作用

目的 评价吸入伊洛前列素的急性肺血管扩张试验在先天性心脏病(CHD)肺动脉高压(PH)患者心脏外科手术适应证选择中的作用.方法 对2006年6月至2008年12月46例CHD合并重度PH患者的临床资料进行回顾性分析.其中男性15例,女性31例,平均年龄(12±9)岁.所有患者术前均接受心导管检查和吸入伊洛前列索试验,患者平均肺动脉压(mPAP)(80±13)mm Hg(1 mill Hg=0.133 kPa),平均肺小动脉阻力指数(PVRI)(17±10)wood·m2.将吸入伊洛前列素试验肺血管阳性反应定义为在体循环压力不变或上升的情况下,PVRI下降≥20%,并作为选择手术适应证的重要条件.药物试验阳性患者在心脏外科修补术后均放置肺动脉漂浮导管,监测术后肺动脉压力、阻力以及心功能状况.结果 46例患者中,药物试验阳性29例(63.1%),吸药后PVRI由(15±6)wood·m2降至(9-4-4)wood·m2,肺循环体循环阻力比(Rp/Rs)由0.7±0.2降至0.4±0.2(P值均<0.05).药物试验反应阴性者17例(36.9%),吸药后PVRI由(21±10)wood·m2降至(19±9)wood·m2(P<0.05),Rp/Rs由1.0±0.5降至0.9±0.5(P>0.05).23例患者接受了心脏外科手术治疗,全部存活.其中药物试验阳性组21例,术后mPAP降至(27±10)mm Hg.药物试验阴性组仅2例接受外科修补术,术后mPAP均>45 mm Hg.结论 吸入伊洛前列素试验阳性患者术后肺动脉压力和PVRI明显降低,可作为评价合并PH的CHD手术适应证的一种蕈要手段.     

Increased pulmonary artery diastolicpulmonary wedge pressure gradient after cardiopulmonary bypass

In 29 patients undergoing elective coronary artery bypass grafting, the diastolic pulmonary arterial pressurepulmonary capillary wedge pressure gradient (DPAP-PCWP) and related haemodynamic parameters were determined before and after induction of anaesthesia, immediately after cardiopulmonary bypass (CPB) and one and three hours after CPB. The DPAP-PCWP gradient remained unchanged after induction of anaesthesia but was significantly increased after CPB. A gradient of 5 mmHg or greater was observed in 16 patients after CPB, whereas none of the patients showed such a gradient before CPB. A significant correlation was found between the change in DPAP-PCWP and the change in pulmonary vascular resistance (PVR). It is concluded that DPAP should not be used as a substitute of PCWP in the early postbypass period without frequent confirmation of the presence of the normal small DPAP-PCWP gradient. Since an increase of PVR may impair right ventricular ejection, we recommend the routine measurement of DPAP-PCWP gradient in the postbypass period.     

Increased pulmonary artery diastolic-pulmonary wedge pressure gradient after cardiopulmonary bypass

In 29 patients undergoing elective coronary artery bypass grafting, the diastolic pulmonary arterial pressure-pulmonary capillary wedge pressure gradient (DPAP-PCWP) and related haemodynamic parameters were determined before and after induction of anaesthesia, immediately after cardiopulmonary bypass (CPB) and one and three hours after CPB. The DPAP-PCWP gradient remained unchanged after induction of anaesthesia but was significantly increased after CPB. A gradient of 5 mmHg or greater was observed in 16 patients after CPB, whereas none of the patients showed such a gradient before CPB. A significant correlation was found between the change in DPAP-PCWP and the change in pulmonary vascular resistance (PVR). It is concluded that DPAP should not be used as a substitute of PCWP in the early postbypass period without frequent confirmation of the presence of the normal small DPAP-PCWP gradient. Since an increase of PVR may impair right ventricular ejection, we recommend the routine measurement of DPAP-PCWP gradient in the postbypass period.     

心肺转流中丙泊酚对鱼精蛋白中和肝素后肺高压的影响

目的观察心肺转流中丙泊酚对鱼精蛋白中和肝素后引起的肺高压反应的影响。方法心肺转流心脏直视手术鱼精蛋白中和肝素5 min内出现肺高压反应患者51例,随机分为研究组(n=27)和对照组(n=24)。研究组在肺高压反应出现后即刻给予丙泊酚1 mg/kg,同时缓慢静脉注射10%葡萄糖酸钙0.02 g/kg,并经主动脉缓慢泵入机血。记录注射鱼精蛋白前(T0)、注射鱼精蛋白后5 min(T1)、注射葡萄糖酸钙后1 min(T2)、5 min(T3)、10 min(T4)、20 min(T5)、30 min(T6)时的CVP、气道压(Paw)、MAP。结果 T1、T2时两组MAP均明显下降,CVP、Paw显著上升(P<0.05)。T3时对照组CVP、Paw仍明显高于T0时(P<0.05),且显著高于研究组(P<0.05)。T4时对照组CVP仍明显高于T0时和研究组(P<0.05)。结论心肺转流中丙泊酚(1 mg/kg)可减轻鱼精蛋白中和肝素后引起的肺高压反应。     

Inhaled carbon monoxide abrogates pulmonary hypertension

Background: Pulmonary hypertension poses a significant clinical challenge. Our current therapies are limited and not efficacious. Carbon monoxide (CO), which is produced endogenously by heme oxygenases, has been shown to possess vasoregulatory properties. Therefore, we hypothesized that inhaled low dose CO would prevent and reverse pulmonary vascular hyperplasia and right ventricular hypertrophy (RVH) in an animal model of pulmonary hypertension. Methods: Monocrotaline (MCT)-treated rats were divided into 4 groups (n = 3-6 per group). Group A received MCT (50 mg/kg, s.c.) alone. Group B was treated with 1 hour daily of inhaled CO (250 ppm) days 1-14 after MCT administration. Group C received CO from days 15-28 and Group D received CO from days 29-42. All animals were sacrificed on day number 43 and their hearts and lungs harvested for morphometric and histologic evaluation. Body weight, right and left ventricular masses, and mean pulmonary arterial pressure (mPAP) were evaluated. Results: MCT caused progressive pulmonary hypertension. By day 42, MCT-treated rats had a mPAP of 35 ± 3.3 compared to untreated controls whose mPAP was 16 ± 2.1 and CO-treated rats which had a mPAP of 20 ± 7.1 (p < 0.05, ANOVA). CO prevented RVH in all treatment groups, even when normalized for body weight (Table) (p < 0.05, Fisher’s Least Significant Difference). Rats treated with MCT alone displayed significant muscularization of the ventricular wall and pulmonary neointimal hyperplasia; CO therapy abrogated these effects. Conclusion: Our data show that low dose inhaled CO decreases mPAP, and prevents RVH and vascular changes in MCT-induced pulmonary hypertension. CO therapy was effective even after the development of cardiac and pulmonary disease. CO may be a useful adjunct in the treatment or prevention of pulmonary hypertension.