Pharmacological criteria for ventricular assist device insertion following postcardiotomy shock: experience with the Abiomed BVS system

BACKGROUND/AIM: The traditional approach to postcardiotomy shock includes inotropic support followed by the application of an intra-aortic balloon pump (IABP). Consideration toward insertion of a ventricular assist device (VAD) becomes necessary when these maneuvers fail to restore hemodynamic stability. The definition of maximal inotropic support, however, is lacking such that a standard formula for VAD insertion remains problematic. The purpose of this paper is to define the pharmacological thresholds for VAD implantation in the setting of postcardiotomy cardiogenic shock. METHODS: The medical records of all adult open-heart operations performed at Hahnemann University Hospital, Philadelphia, PA, from 1 July 1996 through 1 July 1999 were reviewed. Specific data were collected on the hemodynamics and inotrope levels upon separation from cardiopulmonary bypass (CPB). The hospital course was reviewed with attention toward documenting hospital mortality. Cardiogenic shock was defined as systolic blood pressure (SBP) < 100 mmHg, mean pulmonary artery blood pressure (mPAP) > 25 mmHg, central venous pressure (CVP) > 15 mmHg, and cardiac index (CI) < 2.0 L/min/per m2. Inotrope dosages were defined as low, moderate, and high according to assigned values. A formula for VAD insertion was established if cardiogenic shock parameters were present in the setting of two or more high dose inotropes. Early VAD insertion was defined as implantation within three hours of the first attempt to wean from CPB. The VAD recipients were divided into two groups. Group A were VADs placed in conjunction with the formula. Group B was VADs placed in violation (excess) of the formula. The results of these two groups were compared. [table: see text] RESULTS: From 1 July 1996 to 1 July 1999, there were 3462 adult open-heart operations performed at Hahnemann University Hospital, Philadelphia, Pa. The hospital mortality for patients successfully separating from CPB on no inotropes, low-dose, moderate-dose, one high-dose, two high-dose, and three high-dose inotropes were approximately 2.0%, 3.0%, 7.5%, 21%, 42%, and 80% respectively. During this time there were 29 patients supported with the Abiomed BVS (Danvers, Mass) system for postcardiotomy cardiogenic shock. For the entire group of VAD recipients, there were 18 (62%) who were successfully weaned and 8 (28%) who were discharged from the hospital. For the 20 VAD recipients in group A, there were 16 (80%) who were successfully weaned and 8 (40%) who were discharged from the hospital. For the nine VAD recipients in group B, there were two (22%) who were successfully weaned and zero (0%) who were discharged from the hospital. Multiple organ system failure occurred in three (15%) in group A versus seven (78%) in group B patients, respectively. Early VAD insertion was accomplished in 17 (85%) group A patients and 2 (22%) group B patients. CONCLUSIONS: Hospital mortality correlates with the number and level of inotropic support necessary to separate from CPB following adult open heart surgery. The application of a standard pharmacological formula together with hemodynamic criteria for VAD insertion after postcardiotomy cardiogenic shock results in earlier insertion, lower incidence of postoperative MOSF, and improved wean and discharge rates.     

Inhibition of injury induced intimal hyperplasia by saralasin in rats.

Increasing evidence points toward local production of renin and angiotensinogen in the artery wall. Because angiotensin converting enzyme (ACE) inhibitors have been shown to block intimal hyperplasia after arterial injury in the rat, it has been suggested that angiotensin II is an important mediator of the proliferative response to vascular injury. To prove that previous observations with use of ACE inhibitors are a result of effects on local angiotensin levels versus nonspecific drug effects, we tested the ability of an unrelated drug, the angiotensin II receptor antagonist saralasin, to similarly block intimal hyperplasia after aortic injury in the rat. Balloon catheter aortic denudation was performed in 28 rats pharmacologically treated for 14 days after surgery and split into four groups: group 1, saralasin 360 micrograms/kg/hr intravenously; group two, normal saline 0.5 mm3/hr intravenously; group 3, captopril 100 mg/kg/day orally; and group 4, heparin 50 U/kg/hr intravenously. Animals were killed and aortas were perfusion fixed at physiologic pressure 14 days after denudation. Cross-sectional intima-to-media ratios were calculated by computerized planimetry. Compared with saline controls, saralasin inhibited intimal hyperplasia 45% (p less than 0.001), captopril 59% (p less than 0.001), and heparin 68% (p less than 0.001). A reduction in total intimal area was also evident in animals treated with saralasin (p less than 0.01). Blood pressure in the group treated with captopril decreased from 107.4 +/- 3.9 to 96.3 +/- 4.3 mm Hg (p less than 0.01) after 6 days, whereas saralasin and heparin had no effect on blood pressure. Weight gain during the study was reduced in groups treated with captopril and heparin but not in the group treated with saralasin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Elective intraaortic balloon counterpulsation in high-risk off-pump coronary artery bypass grafting

The beneficial effects of intraaortic balloon pump (IABP) in CABG with cardiopulmonary bypass (CPB) have been reported. However, the benefits of insertion of IABP electively in high-risk off-pump coronary artery bypass grafting (OPCAB) have not been established. Six hundred and twenty-five patients who underwent OPCAB form the study group. High-risk patients fulfilling two or more of the following: left main stem stenosis >70%, unstable angina, and poor left ventricular function, who had elective insertion of IABP preoperatively by the open technique (group I; n = 20) were compared with a similar high-risk group that did not (group II; n = 25). There were no significant differences in risk factors between the two groups (Euroscore 5.68). The mean number of grafts was similar. Postoperatively, there were no significant differences in the need for inotropes, duration of ventilation, arrhythmias, cerebrovascular, gastrointestinal, and infective complications (p = NS). There were no IABP-related complications. Acute renal failure requiring hemofiltration was higher in group II (n = 5; p < 0.05). Four patients (16%) in group II required postoperative IABP. Although intensive care stay was longer in group I (27.6 +/- 15.3 vs. 18.6 +/- 9.1 hours; p < 0.05), patients in group I were discharged earlier from hospital. There was no difference in mortality between the two groups (n = 1 in each group). In high-risk patients undergoing OPCAB, routine preoperative insertion of IABP electively reduces the incidence of acute renal failure. In addition it avoids the need for emergency insertion postoperatively and may result in earlier discharge.     

Prognostic indices for survival during postcardiotomy intra-aortic balloon pumping. Methods of scoring and classification, with implications for left ventricular assist device utilization.

To define more clearly a salvageable patient for possible utilization of a left ventricular assist device prior to multiple organ failure and irretrievability during postcardiotomy intra-aortic balloon pumping (IABP), we made prospective and retrospective analyses to determine prognostic indices for survival. Serial left ventricular function curves (IABP on-off), scoring methods, hemodynamic and renal function tracking trajectories, survival versus nonsurvival data envelopes, and classification methods were developed and used. All patients requiring postcardiotomy IABP support who were in Class A survived; 80 percent of the patients in Class B survived. All patients who remained in Class C for 12 hours or more following operation with IABP support died. These preliminary analyses suggest that the postcardiotomy IABP-supported patient with a score of less than 6 who remains in Class C for 12 hours or more is at the highest possible risk and is a probably candidate for more effective support with a left ventricular assist device.     

Intraaortic balloon pumping in patients undergoing coronary artery bypass grafting

Beneficial effect of preoperative intraaortic balloon pumping (IABP) treatment in high-risk patients who had open heart surgery have been demonstrated. The purpose of this study is to determine the impact of preoperative IABP use on survival in high-risk patients undergoing coronary artery bypass grafting (CABG). METHODS: Two hundred seventy-seven consecutive patients having CABG at our institution were reviewed. Patients having an IABP were identified retrospectively and grouped into one of 3 groups as follows. Group A (n = 14): preoperative IABP for high-risk urgent or elective cases. Group B (n = 26): preoperative IABP for emergency cases. Group C (n = 6): unplanned intraoperative or postoperative IABP. RESULTS: Forty-six patients had an IABP (16.6% of total). Parsonnet score in group B was significantly higher (p < 0.05). Length of operation for group C was significantly longer (p < 0.05). Overall hospital mortality in the total group of 277 cases was 4.2%. Hospital mortality was 7.1% in group A, 7.7% in group B, and 50% in group C. Hospital mortality in group C was significantly higher (p < 0.01). CONCLUSIONS: The beneficial effect of preoperative treatment with IABP in high-risk patients undergoing CABG was confirmed. This approach resulted in a significantly lower hospital mortality.     

Preoperative intraaortic balloon pumps in high-risk patients undergoing open heart surgery

BACKGROUND: The use of the preoperative intraaortic balloon pump (IABP) in patients with severe left ventricular dysfunction or unstable angina with critical coronary anatomy is becoming more frequent as surgical casemix changes. The aim of this study was to determine the impact of preoperative IABP use on survival in high-risk patients having open heart surgery. METHODS: Prospectively collected data for 645 consecutive patients were reviewed. Patients receiving an IABP were identified and grouped as follows: group A (preoperative IABP for high-risk nonemergent cases), group B (preoperative IABP for emergent cases), and group C (intra/postoperative IABP). Risk-adjusted hospital mortality rates in these three groups was compared using the modified Parsonnet score for preoperative risk stratification. RESULTS: IABPs were used in 101 cases (16%). The predicted versus actual hospital mortality rate was 20% versus 5.7% in group A, 32.1% versus 47.6% in group B, and 12.6% versus 22.2% in group C (group A vs group B, p = 0.0014; group A vs group C, p = 0.012). IABP-related morbidity occurred in 3% of cases (all in group C). CONCLUSIONS: Risk-adjusted mortality was significantly lower in high-risk cases with preoperative IABPs compared with emergent cases and intraoperative/postoperative IABPs. We encourage the use of preoperative IABPs in selected high-risk patients.     

Urinary angiotensin-converting enzyme 2 in patients with CKD

Aim: Angiotensin‐converting enzyme 2 (ACE2) is a type I membrane protein that antagonizes the action of angiotensin II. Because of the need for invasive kidney biopsy, little is known about the role of renal ACE2 in human kidney diseases. The authors studied if urinary ACE2 could provide a novel clue to renal ACE2 in chronic kidney disease (CKD). Methods: Subjects were 190 patients with CKD including 38 patients with diabetic nephropathy and 36 healthy subjects. Parameters were urinary ACE2 by enzyme‐linked immunosorbent assay, blood pressure, casual plasma glucose, proteinuria, microalbuminuria, serum creatinine and estimated glomerular filtration rate. Urine and serum samples were also subjected to western blotting of ACE2. Results: Western blotting confirmed increased urinary ACE2 levels in patients with CKD. Urinary ACE2 was significantly higher in patients with CKD than healthy subjects (median 9.64 (interquartile range, 4.41–16.89) vs 1.50 (0.40–2.33) mg/g·creatinine, P < 0.001) and in patients with diabetic nephropathy than patients without diabetic nephropathy (median 13.16 (interquartile range 6.81–18.70) vs 8.90 (4.19–16.67) mg/g·creatinine, P < 0.05). No significant difference in urinary ACE2 was observed by the use of angiotensin‐converting enzyme inhibitor and angiotensin receptor blocker. Conclusion: Urinary ACE2 could be used as a non‐invasive marker to understand the role of renal ACE2 in CKD.     

Diagnosis of unilateral renovascular hypertension: comparative effect of intravenous enalaprilat and oral captopril

The effectiveness of 2 angiotensin converting enzyme inhibitors, intravenous enalaprilat and oral captopril, in stimulating renin secretion was compared in 47 hypertensive patients with suspected renovascular hypertension. Both inhibitors were more effective stimuli to renin secretion than head-up tilting of the patient. In patients with unilateral renovascular hypertension single doses of angiotensin converting enzyme inhibitors increased the renal venous renin ratio compared to the recumbent ratio. This therapy reduced the number of false negative studies more effectively than head-up tilting and was tolerated better. Contralateral suppression of renin in the unaffected kidney, an important ancillary diagnostic marker of unilateral renovascular hypertension, was preserved. No false positive studies owing to the use of angiotensin converting enzyme inhibitors acutely were apparent. Mean arterial pressure decreased by 5 minutes with intravenous enalaprilat and by 20 minutes with oral captopril, and it continued to decrease gradually for at least 2 hours. No significant syncopal symptoms were observed with either inhibitor. Plasma renin activity increased by 5 and 15 minutes with enalaprilat and captopril, respectively. Plasma aldosterone levels decreased by 10 minutes with enalaprilat and by 30 minutes with captopril, and these changes increased in magnitude during the 2 hours of observation. To achieve the maximum diagnostic effectiveness from the renal venous renin ratio, single dose angiotensin converting enzyme inhibitors warrant consideration for routine use. Intravenous enalaprilat may be preferable because of certain achievement of an effective blood level.     

CEREBRAL BLOOD FLOW DURING ANAESTHESIA: INFLUENCE OF PRETREATMENT WITH METOPROLOL OR CAPTOPRIL

We have studied the influence of a beta adrenergic blockingagent and an angiotensin converting enzyme (ACE)-inhibitor oncerebral blood flow (CBF) during general anaesthesia beforesurgery. Nine patients served as controls and received no specialpretreatment. Two other groups were allocated randomly to receiveeither metoprolol 0.07 mg kg^–1 i.v. (nine patients) atthe time of induction or captopril 1 mg kg^–1 by mouth(11 patients) 1.5 h before induction. There was no significantdifference in CBF or CBF values corrected for changes in Pa_co2(CBF_corr.) between the metoprolol group and controls. In thegroup pretreated with captopril, CBF_corr. values were significantlylower compared with the metoprolol group. Low CBF_corr. in associationwith low mean arterial pressure was observed in two patientstreated with captopril. These findings suggest that treatmentwith ACE-inhibitors should be discontinued before anaesthesia.     

Effects of captopril administration on pulmonary haemodynamics and tissue oxygenation during exercise in ACE gene subtypes in patients with COPD: a preliminary study

BACKGROUND: We have previously shown that angiotensin converting enzyme (ACE) DD genotype is associated with exaggerated pulmonary hypertension and disturbance of tissue oxygenation during exercise in patients with chronic obstructive pulmonary disease (COPD). A pilot study was designed to examine the effects of captopril on these exercise related variables in COPD patients categorised according to ACE gene polymorphisms. METHODS: Thirty six patients with COPD (II=13, ID=11, DD=12) received oral captopril (25 mg) or placebo in a randomised, double blind, crossover manner and underwent right heart catheterisation with exercise. RESULTS: Mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), and lactate concentration after exercise with both placebo and captopril were higher in patients with the DD genotype than in those with the II or ID genotypes. In contrast, mixed venous oxygen tension (PvO(2)) was lower in patients with the DD genotype than in those with the other genotypes. Moreover, mPAP, PVR, and lactate concentration after exercise were lower in the captopril group than in the placebo group in patients with the II or ID genotype, but not in those with the DD genotype. PvO(2) after exercise was higher with captopril than with placebo in patients with the II genotype, but not in those with the other genotypes. CONCLUSIONS: These findings suggest that pulmonary haemodynamic variables and state of tissue oxygenation during exercise are dependent on ACE genotypes, and that captopril administration effectively influences these exercise related variables. Although the sample size in this pilot study was limited, it is likely that the improvement in exercise related variables in COPD patients with the II genotype is relatively sensitive to captopril.     

Alterations in angiotensin converting enzyme during rodent aortic aneurysm formation

BACKGROUND: The renin-angiotensin system (RAS) has been implicated in vessel wall remodeling. This investigation tested the hypothesis that the RAS is altered during experimental rodent aneurysm formation. MATERIALS AND METHODS: Rat aortas were perfused with saline (controls, N = 45) or elastase (6 U/ml, N = 45). At 4, 7, and 14 days after aortic perfusion, aortic diameters were measured (n = 15/time point/group) and aortic wall mRNA and protein were extracted. Real time polymerase chain reation (PCR) measured RNA levels of angiotensin, angiotensin converting enzyme (ACE), angiotensin II receptor 1 (AT(1)), and angiotensin II receptor 2 (AT(2)). Western blot analysis measured ACE protein levels. Immunohistochemical studies localized ACE within the aortic wall. Statistical analyses were performed with the unpaired t-test and ANOVA. RESULTS: Elastase perfusion significantly increased aortic diameter (P < 0.01), with no significant changes in saline control aortic diameters. ACE mRNA did not become elevated in elastase-perfused aortas, yet ACE protein levels were elevated on days 4 and 7 of perfusion (P < 0.01) compared to controls, and ACE staining was noted in these aortas. This difference resolved by 14 days. In neither group were there significant alterations in AT(1), AT(2), or An mRNA levels, although ACE mRNA was elevated in controls after 7 days of perfusion compared to elastase perfused aortas (P < 0.005). CONCLUSIONS: Experimental aortic aneurysm formation may be associated with increased aortic wall ACE protein levels. The mechanisms by which these proteins contribute to, or serve as markers of, aneurysm formation in vivo requires further intervention.     

Stunned myocardium and cellular damage in patients undergoing valvular cardiac surgery and pretreated with captopril.

BACKGROUND: Following extracorporeal cardiac surgery, transient myocardial dysfunction (stunning) and cellular damage may develop in relation, among other mechanisms, to the production of free radicals (FR) during reperfusion. The purpose of this study is to evaluate whether captopril (CTP), an angiotensin converting enzyme inhibitor with a thiolic group, which has been shown to be useful as an antioxidant agent both in in vitro and in vivo studies, can prevent emergence of those problems when used as pretreatment within 24 hours in patients undergoing valvular cardiac surgery. METHODS: Experimental design: prospective and randomized study. Comparison of data pre-ischemic (pre-aortic clamping) and post-reperfusion (post-cardiac rewarming) was performed. Ejection fraction was compared pre-surgery, after surgery and after 3 months. Setting: cardiology and cardiovascular surgery services in a general hospital. Patients or participants: thirty patients who had to undergo valvular replacement surgery were randomly allocated to two similar groups, one group pretreated with captopril (CTP group, n = 15) and the other group without it (CON group, n = 15). Exclusion criteria (left ventricular ejection fraction <40%, evidence of angiographic coronary disease or prior myocardial infarction and peroperative myocardial infarction). Intervention: in CTP group, the dose of captopril administered was 12.5 mg every 8 hours orally, from 24 hours before. Measures: using electron microscopy of myocardial biopsies taken prior to aortic clamping and post-reperfusion, a semi-quantitative analysis was performed on the degree of myocytic damage (MD), mitochondrial swelling (MS), sarcoplasmic reticulum swelling (SRS) and content in glycogen granules (GLY). Left ventricular ejection fraction was evaluated isotopically at three timepoints, preoperatively (EF1), at 2-3 days (EF2) and at 3 months (EF3). Also, analytical data were collected from the coronary sinus to determine creatine phosphokinase (CPK) and activity of the angiotensin converting enzyme (ACE). RESULTS: We noted that, in general, cellular damage resulting from valvular surgery is low, the degree of MS and SRS being lower in the CTP group. In the CTP group, however, there is a stunning phenomenon (EF1: 54.9+/-6.9%; EF2: 50.8+/-8.5%; EF3: 57.7+/-7.7%) which does not occur in the CON group (EF1: 58.0+/-8.3%; EF2: 60.8+/-10.9%; EF3: 63.0+/-9.3%). CONCLUSIONS: We conclude that the cellular damage caused during valvular replacement surgery is small, and emphasize that pretreatment with CTP further minimizes both MS and SRS; however, for reasons as yet unknown, CTP pretreatment may induce myocardial stunning, an indication that at these low rates of cellular damage, CTP has no beneficial effect, either because it is ineffective as an antioxidant agent or because FR formation has little repercussion in human beings, pointing out to the likely existence of other mechanisms that may induce an appearance of postsurgical myocardial stunning.     

Angiontensin-converting enzyme activity in dunning rat prostate tumor

A dipeptidyl carboxypeptidase activity in the Dunning rat prostate tumor was characterized. This enzyme demonstrated the most prominent properties of angiotensin converting enzyme (ACE): that is, it was stimulated by NaCl and Co(2+) and was potently inhibited by captopril. The enzyme solubilized by Triton X-100 had a molecular mass of 110 kDa as determined by gel filtration chromatography. The specific activity of ACE did not change with castration, indicating that ACE activities are not controlled by androgen. The role of ACE in the prostate and its tumors is not understood, but the ability of this enzyme to hydrolyze a number of bioactive peptides suggests that it may function in controlling the molecular forms or activity of regulatory peptides.     

Role of the renin-angiotensin system in ventilator-induced lung injury: an in vivo study in a rat model

BACKGROUND: Injurious mechanical ventilation can cause a pro-inflammatory reaction in the lungs. Recent evidence suggests an association of the renin-angiotensin system (RAS) with lung inflammation. A study was undertaken to investigate the pathogenic role of the RAS in ventilator-induced lung injury (VILI) and to determine whether VILI can be attenuated by angiotensin converting enzyme (ACE) inhibition. METHODS: Male Sprague-Dawley rats were mechanically ventilated for 4 h with low (7 ml/kg) or high (40 ml/kg) tidal volumes; non-ventilated rats were used as controls. Lung injury and inflammation were measured by the lung injury score, protein leakage, myeloperoxidase activity, pro-inflammatory cytokine levels and nuclear factor (NF)-kappaB activity. Expression of the RAS components was also assessed. Some rats were pretreated with the ACE inhibitor captopril (10 mg/kg) for 3 days or received a concomitant infusion with losartan or PD123319 (type 1 or type 2 angiotensin II receptor antagonist) during mechanical ventilation to assess possible protective effects on VILI. RESULTS: In the high-volume group (n=6) the lung injury score, bronchoalveolar lavage fluid protein concentration, pro-inflammatory cytokines and NF-kappaB activities were significantly increased compared with controls (n=6). Lung tissue angiotensin II levels and mRNA levels of angiotensinogen and type 1 and type 2 angiotensin II receptors were also significantly increased in the high-volume group. Pretreatment with captopril or concomitant infusion with losartan or PD123319 in the high-volume group attenuated the lung injury and inflammation (n=6 for each group). CONCLUSIONS: The RAS is involved in the pathogenesis of ventilator-induced lung injury. ACE inhibitor or angiotensin receptor antagonists can attenuate VILI in this rat model.     

Short-term treatment with captopril in hypertension due to acute glomerulonephritis

We report that the inhibition of the angiotensin converting enzyme is an effective short-term treatment of low-renin hypertension in acute glomerulonephritis (AGN). We treated 9 patients who had AGN with moderate to severe hypertension and suppressed plasma renin activity with 25-50 mg of captopril per os every 6-8 hours. Control of blood pressure was achieved in 1-2 hours and maintained thereafter. Captopril therapy was associated with an increase in plasma renin activity, a decrease in plasma aldosterone and an increase in the urinary excretion of prostaglandin E2 and kallikrein, independent of changes in urine output. Creatinine clearance increased 39.6 +/- SE 15.2% with captopril and decreased in the postcaptopril period, suggesting that captopril exerted a reversible effect on glomerular filtration rate, possibly modifying intrarenal vasoconstriction. Our study shows that rapid control of hypertension in AGN may be obtained with oral inhibition of the angiotension converting enzyme. Stimulation of PGE2 and kinins, as well as angiotensin II blockade appear to contribute to the hypotensive effect of the drug; by inference, the suppressed activity of vasodilator systems seems to play a significant role in the hypertension of AGN.     

Expansion of PCI at the Expense of Bypass Surgery Jeopardizes Protection against Premature Death

Prophylactic use of an intraaortic balloon pump (IABP) prior to open-heart surgery in patients with impaired left ventricular function is still under debate. Patients with left ventricular ejection fraction (LVEF) &;lt; 40% were therefore compared according to time of IABP placement, viz. preoperative (n = 56), intraoperative (n = 40) or postoperative (n = 17), and also with patients who did not receive mechanical support despite LVEF &;lt; 40% (n = 78). The main indication for preoperative IABP insertion was severely impaired left ventricular function (80%), while patients with intraoperative or postoperative IABP placement mainly presented with low cardiac-output syndrome (70%/53%). Preoperative IABP was associated with a low mortality rate (8.9%), whereas patients with intraoperative or postoperative IABP placement had a high mortality risk and an increased catecholamine requirement. Of the patients scheduled for surgery without prophylactic IABP, 19% required intra- or postoperative insertion. Prophylactic placement of IABP thus reduced the mortality rate as well as the postoperative need for mechanical and catecholamine support. Need for intraoperative IABP insertion was associated with high mortality, whereas the outcome after postoperative IABP placement depended on the indication for the measure.     

ACE Index in patients with respiratory failure]

To investigate whether ACE Index (ACE.Cardiac output-1) which excludes the influence of pulmonary perfusion volume is more useful than angiotensin converting enzyme (ACE) as an early marker of pulmonary endothelial injury and repair, we measured ACE, ACE index, and PaO2.FIO2-1 ratio several times during the stay in the ICU in two patients with respiratory failure. ACE index had a closer relationship to clinical course of respiratory condition and PaO2.FIO2-1 (r = 0.806, 0.889, respectively), in comparison with ACE. We conclude that ACE index could be more sensitive than ACE as an early marker of pulmonary endothelial injury and repair.     

Loss of captopril-bound Fe by end-stage renal failure patients during hemodialysis

BACKGROUND: Patients on chronic hemodialysis often suffer from severe anemia, the outcome of iron deficiency and inadequate response to erythropoietin. Antihypertensive treatment with captopril worsens anemia, erythropoietin production and iron balance in hemodialysis patients. We investigated the possibility that iron chelation by captopril in the blood may result in elimination of iron-captopril complexes during hemodialysis, thus minimizing the effect of both medications. METHODS: Twelve hypertensive hemodialysis patients (group 1) were treated with 12.5 mg/day captopril, while their 12 counterparts received 1.25 mg/day ramipril. Following two weeks of treatment and two weeks of "washout", captopril in group 1 was substituted with ramipril and ramipril in group 2 was replaced by captopril for an additional two week period. Blood and dialysate samples were procured at the beginning and the end of the dialysis, for iron, aluminum, transferin, ferritin, hemoglobin (Hb) and hematocrit (Htc) determination. RESULTS: Iron, ferritin, transferin, Hb and Htc were decreased in the captopril-treated group 1. They similarly decreased in group 2 following replacement of ramipril by captopril for an additional period of two weeks. Significant amounts of iron were detected in dialysates of captopril, but not ramipril-treated patients. At the end of the dialysis, iron content was further increased in dialysates of the captopril-treated groups. CONCLUSIONS: 1) Captopril-chelated iron is eliminated in dialysis fluid during the dialysis session, apparently contributing to captopril-related anemia in patients on chronic hemodialysis. 2) Antihypertensive treatment with angiotensin converting enzyme (ACE) inhibitors other than captopril might prove advantageous for this patient category.     

血管紧张素Ⅱ对抗吗啡呼吸抑制效应的实验研究

实验研究了中枢神经系统内的内源性抗阿片物质－血管紧张素Ⅱ（ＡⅡ）对吗啡所致吸吸抑制效应的影响。结果显示：侧脑室注射ＡⅡ具有明显呼吸兴奋效应，并可翻转吗啡的呼吸抑制作用；相反，卡托普利可降低脑内ＡⅡ含量后，抑制呼吸运动；酚妥拉明可部分阻断ＡⅡ的呼吸兴奋效应，而普萘洛尔对ＡⅡ的作用无明显影响。     

Kidney Scintigraphy after ACE Inhibition in the Diagnosis of Renovascular Hypertension

Suppression of the renin-angiotensin system (RAS) by angiotensin converting enzyme (ACE) inhibition may induce renal failure in patients with bilateral renal artery stenosis. Recent scintigraphic studies with the glomerular tracer technetium-99m-diethylenetriaminepenta-acetate (^99m-Tc DTPA) indicate that in patients with unilateral renal artery stenosis, glomerular filtration rate (GFR) may be markedly reduced in the affected kidney after inhibition of ACE. This finding reflects the important role of the RAS in maintaining GFR (by increasing postglomerular resistance) in states of low renal perfusion pressure. Preliminary observations suggest that this scintigraphic test might be useful in the detection of renovascular hypertension.