Post-transplant conversion from cyclosporin to azathioprine: effect on cardiovascular risk profile

The benefits of long-term cyclosporin (CyA) therapy are not yet established and must be weighed against its toxicity. We studied cardiovascular risk factors in 25 patients who received a kidney transplant between 1985 and 1989 and in whom CyA was discontinued. The protocol for discontinuing CyA involved starting azathioprine (Aza) and then weaning CyA over 6 weeks without changing the prednisone dose. Parameters collected from the patients' charts 3 months before (pre) and 3 months after conversion (post) and at the most current follow-up (cur) included serum creatinine, cholesterol, blood pressure, and anti-hypertensive medication. The severity of the hypertension was graded, based on a hypertension index reflecting the nature and dose of the anti-hypertensive medication. Of the 25 patients in whom CyA was discontinued, 2 experienced a rejection episode during conversion and were switched back to CyA; 1 patient had a rejection episode after conversion but remained on Aza. Converted patients demonstrated improved renal function (1/Cr pre 0.69±0.20, post 0.84±0.23, P<0.05), lower serum cholesterol levels (pre 6.8±1.0, post 5.8±1.2, P<0.05), lower mean arterial pressure (pre 111±14, post 102±8, P<0.05) and a lower hypertension index (pre 2.45±2.77, curr 1.62±1.70, P<0.05). Although conversion may carry some risk of acute rejection, it improves graft function and the cardiovascular risk profile significantly.     

Renal allograft artery stenosis: results of medical treatment and intervention. A retrospective analysis

In a retrospective analysis of 1165 renal transplantations in our center, 65 cases of renal allograft artery stenosis were diagnosed angiographically (prevalence 5.5%). Hypertension was present in all case; a bruit over the allograft and an increase in serum creatinine level were additional reasons for angiography. Shortly after diagnosis of the stenosis, two patients died and two others lost their grafts due to thrombosis. In 24 patients the decision was made not to correct the stenosis. One of these grafts was lost because the stenosis could not be corrected. Medical management of hypertension in these patients resulted in a decrease in diastolic blood pressure from 109±22 to 96±12 mm Hg (P<0.01) 3 months after diagnosis with the use of almost twice as many antihypertensive drugs as at the time of diagnosis (P<0.01). The stenosis was corrected if the angiography showed it to be so severe that it jeopardized renal allograft function or caused uncontrollable hypertension. Only three of nine percutaneous transluminal angioplasty (PTA) procedures resulted in a definitive correction of the stenosis. Surgical intervention was performed in 30 patients, including two patients whose PTAs had proved unsuccessful. Surgery led to graft loss due to thrombosis in 6 of 30 operations (20%), whereas restenosis occurred twice (7%). In three other case (10%), the correction was not successful due to local anatomical variations or concomitant rejection. Successful correction of the stenosis by either PTA or surgical intervention (n=22) resulted in a significant decrease in systolic (171±31 vs 145±27 mm Hg; P<0.01) and diastolic (103±15 vs 89±14 mm Hg; P<0.05) blood pressures 3 months after correction. Concomitantly, a decrease in the number of antihypertensive drugs from 2.1±1.0 to 1.5±1.0 (P<0.01) was achieved. In conclusion, renal allograft artery stenosis could successfully be managed pharmacologically, provided that allograft perfusion was not jeopardized. Successful surgical correction of a stenosis with effective control of hypertension was achieved in 63% of the cases. PTA was less frequently successful but did not cause any graft loss.     

Systemic and renal effects of dopamine in the infant pig

Dopamine is commonly employed in the management of hypotensive patients. Although this medication increases cardiac index (CI) and renal artery (RA) flow in adults, its effect in infants has not been adequately studied. In 13 infant pigs (mean wt 3.05 ± 0.75 kg; age 3–4 weeks) CI, RA flow and systemic blood pressure (BP) were measured at varying renal artery perfusion pressures before and after the administration of dopamine. Pigs were anesthetized with ketamine, intubated, and maintained on a ventilator with succinylcholine. Jugular vein, pulmonary (Swan-Ganz), carotid, and femoral artery catheters were placed. Laparotomy was performed and RA flow was measured with an electromagnetic flow probe. A Blalock clamp was placed around the suprarenal aorta to obtain graded aortic occlusions to pressures of 80 and 50 mm Hg. Dopamine had no significant effect on the CI vs control at 5, 10, 15, 20, 25, or 50 μg/kg/min. BP increased 25 mm Hg on Dopamine (10 μg/kg/min) P > 0.05). RA flow remained stable (318 ± 74 vs 300 ± 68 ml/min) despite reduction in perfusion pressure to 80 mm Hg, suggesting an autoregulatory flow mechanism. At 50 mm Hg perfusion pressure however, RA flow decreased significantly to 220 ± 54 ml/min (P < 0.05) indicating a loss of autoregulation at lower perfusion pressures.Dopamine (10 μg/kg/min) did not change RA flow at control BP (335 ± 76 vs 318 ± 74 ml/min). At 80 mm Hg perfusion pressure however, RA flow fell from 335 ± 74 to 175 ± 50 ml/min (P < 0.001) demonstrating a suppression of renal autoregulation by dopamine. At 50 mm Hg, RA flow was markedly reduced to 22 ± 31 ml/min (P < 0.001). These data suggest: (1) dopamine has no significant effect on CI in infant pigs, (2) an RA flow mechanism is present in infant pigs which protects the kidney at reduced perfusion pressures, and (3) dopamine interferes with autoregulation and may be harmful to the infant kidney in hypotensive states.     

Cyclosporin A in fat emulsion carriers: studies on the immunosuppressive potential,using the heterotopic heart transplant model in rats

Cyclosporin A (CyA) is an extremely lipophilic drug that needs a solubilizing agent to become soluble in water. In the commercially available intravenous formulation-Sandimmun-Cremophor EL is used for this purpose. It is likely that Cremophor EL contributes to some of the side effects produced by i. v. Sandimmun. We have recently shown that if Cremophor EL is replaced by a soybean oil (SBO)-based fat emulsion carrier, the acute renal side effects following i. v. administration of CyA are avoided in a rat model. It is then important to ascertain whether the use of a fat emulsion carrier alters the immunosuppressive effect of CyA. Moreover, fatty acids can themselves influence the immune system, and both omega-3 and omega-6 fatty acids have been reported to possess immunosuppressive properties. In the present study, the effect on graft survival of i. v. CyA administered in five different formulations, using fat emulsions or liposomes as carriers, was compared to that of conventional Sandimmun infusion substance in the heterotopic heart transplant model in rats. The new formulations tested did not reduce the immunosuppressive effect of CyA. On the contrary, a small but significant increase in graft survival was noted in the groups given CyA in the SBO-based fat emulsion carrier (17.0±0.82 days) and CyA in liposomes (16.0±0.63 days) as compared to the results in the Sandimmun-treated group (15.0±0.58 days: P<0.01 and P<0.05, respectively).     

Reduction of aneurysm pressure and wall stress after endovascular repair of abdominal aortic aneurysm in a canine model

A canine model was designed to evaluate the changes in abdominal aortic aneurysm (AAA) pressure and wall stress after endovascular repair. Eight canines underwent laparotomy and creation of an AAA. The aneurysm was then excluded with a transluminally placed endovascular graft (TPEG) inserted through the right femoral artery and deployed across the AAA to exclude the infrarenal aortic branches from aortic perfusion. Blood pressure and flow data were recorded for 6 hours. The AAA blood pressure decreased from 135 ± 9.3 mm Hg before exclusion to 45 ± 17.6 mm Hg at 10 minutes after exclusion (p < 0.001). At 6 hours, AAA blood pressure had declined further to 26 ± 12.5 mm Hg. Blood flow in the excluded iliac artery decreased from a baseline of 242 ± 58 ml/min to 41 ± 29 ml/min 10 minutes after TPEG placement (p < 0.001). At 6 hours, flow was reduced to 12 ± 3.5 ml/min (p < 0.05 compared with that at 10 minutes). Aortic wall stress was significantly reduced by TPEG placement but was only slightly lower than baseline aortic wall stress before AAA creation. The lumbar arteries were patent with retrograde flow in all cases and were found to be the major contributors to postexclusion aneurysm pressure. Endovascular AAA exclusion results in an immediate decrease in blood pressure and wall stress within the excluded aneurysm, but the aneurysm remains perfused by retrograde flow through the lumbar arteries, which resulted in near-baseline levels of aneurysm wall stress in this canine model. Embolization of patent lumbar vessels at prosthesis placement may further reduce the risk of late rupture.Presented at the Twentieth Annual Meeting of the Peripheral Vascular Surgery Society, New Orleans, La., June 10, 1995.     

The effect of cyclosporin on lower limb blood flow in renal transplant recipients

We investigated the effect of electively converting stable renal allograft recipients from cyclosporin A (CyA) to prednisolone and azathioprine on limb blood. We used a non-invasive method designed to measure the hyperaemic blood flow to the lower limb following a standard ischaemic insult. The hyperaemic blood flow was greater during CyA therapy-median 14 ml/100 ml tissue per minute (95% confidence limits 10.5–16.5)-than that after conversion-median 11 ml/100 ml tissue per minute (8.3–13.8;P<0.01). By increasing peripheral vascular resistance and reducing limb blood flow, CyA may have caused an increase in the degree of ischaemia, so resulting in a greater hyperaemic response.     

Systemic and regional hemodynamics in cyclosporin A hypertension in the rat

SUMMARY: This study examined the hemodynamic effects of 21 days oral administration of cyclosporin A (CyA) in the male Wistar rat. Forty rats were randomly divided into four groups ( n =10). Group 1: Sham (olive oil 1 mL/kg/day by gavage ) with cardiac output (CO) measurement. Group 2: CyA (CyA 15 mg/kg/day in olive oil by gavage ) with CO measurement. Group 3: Sham as for group 1 with regional flow measurements. Group 4: CyA as for group 2 with regional flow measurements. Systolic blood pressure was measured every fourth day. After 21 days mean arterial blood pressure was measured by intra-arterial cannulation, and CO, and renal, mesenteric, and hindquarter blood flows (RBF, MBF, and HBF) were determined using transonic small animal flowmeters. Total peripheral resistance (TPR) and regional resistances were calculated. Oral CyA produced a sustained rise in systolic blood pressure. Olive oil did not affect blood pressure. CyA increased TPR ( P <0.05), renal vascular resistance (RVR, P <0.01) and MBF ( P <0.01), decreased RBF ( P <0.01), but did not change CO, HBF, mesenteric or hindquarter vascular resistance. We conclude that chronic oral administration of CyA produces hypertension with a hemodynamic profile characterized by rises in TPR and RVR without changes in CO or mesenteric or hindquarter vascular resistances in the Wistar rat.     

Assessment of hemodynamic changes in human kidney grafts induced by cyclosporin infusion

Cyclosporin A (CyA) nephrotoxicity is at least partly caused by the vasoconstrictive action of the drug. In this study we set out to assess this hemodynamic effect of CyA on Doppler spectra obtained in arteries of human renal allografts Doppler spectra of renal arteries were obtained shortly before and after the start of CyA infusion in renal transplant recipients. Doppler spectrum analysis revealed a significant change in several spectrum-derived parameters. T_max (acceleration time of the systolic frequency peak), in particular, showed a decrease after 4 h of CyA administration (106±58 ms vs 76±36 ms in segmental arteries; P<0.05). On day 2 the T_max returned to its original value (117±57 ms). Thus, Doppler spectrum analysis enables one to detect temporary hemodynamic changes in the transplanted kidney following CyA administration. These observations may be useful in differentiating causes of renal dysfunction by Doppler spectrum analysis in clinical transplantation.     

液体复苏对严重脓毒症及脓毒性休克患者的治疗作用研究

目的评价液体复苏手段对严重脓毒症或脓毒性休克的治疗作用。方法通过液体复苏使20例严重脓毒症或脓毒性休克患者达到如下治疗目标：中心静脉压8—12mmHg（机械通气者12—15mmHg）、平均动脉压65～90mmHg、混合静脉血氧饱和度〉70％。测定达标前后血流动力学、组织灌注、血管内皮细胞功能的变化。结果液体复苏达标后,肺动脉楔压明显升高（P〈0．01）,心指数及体循环阻力指数增加（P〈0．01）,肺循环阻力指数下降（P〈0．01）,左心室做功指数上升（P〈0．01）;组织灌注指标中动脉血乳酸（ABL）在复苏后下降（P〈0．01）,胃黏膜二氧化碳分压与动脉血二氧化碳分压差（Pg—aCO2）在复苏后明显下降（P〈0．01）,血管内皮细胞功能中内皮素及血管性假血友病因子在液体复苏后下降（P〈0．05）。结论液体复苏早期达标可改善严重脓毒症或脓毒性休克患者血流动力学和组织灌注并可减轻血管内皮细胞的损伤,是一种有效的治疗方式。     

Comparison of perfusion values after percutaneous transluminal angioplasty according to the severity of ischaemia in the diabetic foot

Percutaneous transluminal angioplasty (PTA) is now more frequently used to improve tissue perfusion in ischemic diabetic feet. However, there are concerns about its feasibility and effectiveness in severely ischaemic feet. This study aimed to compare the perfusion values after PTA according to the ischaemic degree of diabetic feet. This study included 133 ischaemic diabetic feet. The foot transcutaneous oxygen pressure (TcPO₂) and toe pressure were measured before the procedure and every second postoperative week for 6 weeks. The patients were divided into three groups according to ischaemic severity on the basis of TcPO₂ and toe pressures. In the “severely ischaemic” group, the TcPO₂ increased from 7.5 ± 4.9 to 40.3 ± 11.3 mm Hg (5.4‐fold) 6 weeks after the PTA (P < 0.001). The toe pressure increased from 8.5 ± 8.8 to 42.2 ± 19.3 mm Hg (5.0‐fold, P < 0.001). In the “mild” group, the TcPO₂ increased from 35.4 ± 2.5 to 41.8 ± 12.4 mm Hg (1.2‐fold, P = 0.003), and the toe pressure increased from 45.7 ± 12.3 to 54.3 ± 31.3 mm Hg (1.2‐fold, P > 0.05). Results of the “intermediate” group were in between. The most severely ischaemic group had the most dramatic increase of tissue perfusion after PTA. As such, PTA can be an effective method for increasing tissue perfusion even in the severely ischaemic diabetic feet.     

Bipolar impedance-controlled sealing of the pulmonary artery with SealSafe G3 electric current: determination of bursting pressures in an ex vivo model

Background

In every anatomic lung resection operation, the pulmonary artery itself or its branches must be sealed. This involves either stapling or ligating the vessels. Based on the positive results with the bipolar vessel sealing ≤7 mm in abdominal surgery the present study aimed to evaluate burst pressures of the pulmonary artery after sealing with the sealing instrument SealSafe G3 (Gebrüder Martin & CoKG, Tuttlingen, Germany).

Material and methods

The whole pulmonary artery above the pulmonary valve was exposed up to the periphery of the left lung in freshly removed pig heart–lung blocks. A pressure-measuring cylinder was then implanted in the prepared vessel on the side at the main trunk of the pulmonary artery to determine the pressure in the vessel. After either ligation or bipolar sealing of the pulmonary artery, the pneumatic burst pressure (millimeters of mercury) was determined in a water bath. Three groups (n = 12 for each seal type) with different vessel diameters were examined: group 1: 0–6 mm, group 2: 7–12 mm, and group 3: >12 mm. In all cases, vessel sealing was performed with a MARSEAL 5 instrument (Gebrüder Martin & Co KG, Tuttlingen, Germany) and the SealSafe G3 current. The mean burst pressures of the individual groups (ligature and bipolar sealing) were compared using two-tailed, nonparametric Mann–Whitney U test. Significance was defined as P < 0.05.

Results

The mean burst pressures in group 1 were measured by 340 ± 13.4 mm Hg with ligature and 205 ± 44.4 mm Hg with bipolar sealing (P < 0.001). In group 2, the mean values obtained were 270 ± 28.2 mm Hg for ligature and 162 ± 36.0 mm Hg for bipolar sealing (P < 0.001). In group 3, the mean burst pressures for bipolar sealing were only 52.1 ± 15.1 mm Hg, whereas those for ligated vessels were 253 ± 46.9 mm Hg (P < 0.001). For this size of vessel the burst pressure was also determined after stapling. The mean value in this case was 230 ± 21.8 mm Hg.

Conclusions

In all groups, the mean burst pressures after bipolar sealing were significantly lower than those achieved with ligation, but they were sufficient for a save closure of the pulmonary artery with diameters up to 12 mm.     

Splanchnic perfusion pressure: a better predictor of safe primary closure than intraabdominal pressure in neonatal gastroschisis

Background/Purpose

Both measured intraabdominal pressure (IAP) and calculated splanchnic perfusion pressure (SPP) have been advocated for use in operative management of gastroschisis. We directly compared these 2 clinical indices.

Methods

Institutional review board-approved multi-institutional retrospective review from 3 centers with 112 subjects. Splanchnic perfusion pressure was recorded as mean arterial pressure-IAP. We compared the clinical utility of IAP and SPP using univariate and multivariate regression analyses.

Results

Calculated mean SPP was higher among neonates requiring silo placement compared to those without (39.0 ± 1.9 vs 33.7 mm Hg, P < .01). Measured IAP levels were similar between groups (11.5 ± 1.1 vs 10.0 ± 0.5, mm Hg, P < .4). On a receiver operating characteristic curve, the inflection point for more than 90% specificity for silo placement was at an SPP of 44. In multivariate regression analysis adjusting for all factors below, SPP was independently associated with silo placement (odds ratio 1.2, 95% confidence interval 1.1-1.3, P < .01), and IAP was not (odds ratio 1.2, 95% confidence interval <1.0-1.5, P < .1).

Conclusions

These data suggest that SPP is a stronger predictor than IAP for the ability to achieve primary closure in the management of neonatal gastroschisis. We infer from these data that intraoperative SPP of more than 43 mm Hg may obviate the need for silo placement.     

Renal and systemic effects of atenolol and tertatolol in renal transplant recipients on cyclosporine A

Background. Hypertension and nephrotoxicity are well-known side-effects of cyclosporine A (CsA). CsA-induced vasoconstriction of the afferent glomerular arteriole probably plays a role in at least the nephrotoxicity. Frequently renal transplant recipients on CsA have to be treated with antihypertensive drugs and for this purpose also {beta}-blockers are used. Tertatolol is a new {beta}-blocker with specific vasodilatory properties, and thus might be particularly useful in CsA-treated transplant recipients. Methods. We studied the systemic and renal haemodynamic effects of atenolol and tertatolol in 12 hypertensive renal transplant recipients on cyclosporine A (CsA). In a cross-over way, all patients were treated with atenolol and tertatolol for 4 weeks each, separated by a wash-out period also of 4 weeks. At the end of each period, the mean arterial pressure (MAP), heart rate, glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured. Results. The mean arterial pressure was lower (P<0.05) during atenolol (124±2 mm Hg) and tertatolol (125±2 mm Hg) treatment compared with wash out (132±4 mm Hg). Also the heart rate was lower (P<0.01) during atenolol and tertatolol (54±3 and 55±2 beats/min respectively) than in the wash-out period (65±3 beats/min). GFR and RPF were not changed by either {beta}-blocker. Conclusion. In CsA treated renal transplant recipients both atenolol and tertatolol effectively reduced blood pressure. In these patients we found no evidence of a specific vasodilatory effect of tertatolol. Both {beta}-blockers had no negative influence on renal function. Hence, these cardioprotective agents are an attractive and safe choice for the treatment of hypertension in such patients.     

Treatment of transplant renal artery stenosis by percutaneous transluminal angioplasty and/or stenting: study in 63 patients in a single institution

Objective

Our aim was a retrospective evaluation of technical procedures, clinical success, and follow-up of renal transplant patients with stenosis in the transplant renal artery (TRAS) after endovascular treatment.

Methods

From January 1981 to September 2009, 2,150 allograft renal transplants included 62 patients who underwent endovascular procedures for TRAS >75%. Parameters included technical success, arterial blood pressure, antihypertensive drugs, and creatinine level before and after the intervention.

Results

Percutaneous transluminal angioplasty (PTA)/stent placement success was 90.3%. Seventy-nine PTAs with 11 stents were primary interventions with 6 PTAs and 4 stent procedures subsequently performed due to restenosis (mean time to event, 1.5 months). The median follow-up was 39 months (range, 1-236). The mean preprocedure creatinine level was 2.8 ± 1.7 mg/dL, and the 1-month postprocedure value was decreased to 2.1 ± 1.2 mg/dL (P < .001). Systolic arterial blood pressure fell from 147.2 ± 18.7 mm Hg to 131.6 ± 14.2 mm Hg (P < .001) and diastolic blood pressure from 84.4 ± 9.8 mm Hg to 76 ± 9.4 mm Hg (P < .001). Postprocedure number of antihypertensive drugs was reduced from 2.3 ± 1.1 to 1.6 ± 1 (P < .0001). The patency rates were: 95 ± 2.8% at 1 month, 87.9 ± 4.3% at 3 months, and 85 ± 4.7% at 12 months. Secondary patency was 100% with no restenosis on follow-up. Allograft survival after primary and secondary PTA/stenting was 97% at 1, 93% at 3.89% at 5, and 85% at 10 years. The complication included 2 renal artery thromboses, a dissection treated with stents, and a late arterial graft pseudoaneurysm.

Conclusions

TRAS, a problem after kidney transplantation, is detected to be a significant stenosis through the use of Doppler ultrasound. Revascularization is recommended to improve hypertension and graft function. PTA should be primarily planned with stenting for patients with a restenosis or after a lack of response to PTA.     

A pharmacokinetic comparison of the corn oil versus microemulsion gelcap formulation of cyclosporin used de novo after renal transplantation

The initial poor absorption of the corn oil-based, gel capsule oral formulation of cyclosporin (CyA) greatly limits its use for inception of immunosuppressive therapy. Insufficient drug concentrations during the early post-transplant period predispose to renal allograft rejection. The present study served to compare the time required to achieve therapeutic CyA concentrations after de novo administration of the corn oil-based gel capsule (CyA-GC; n = 11) versus the microemulsion (CyA-ME; n = 11) formulation of CyA. During the 1st month after renal transplantation, patients underwent serial pharmacokinetic profiling from which we obtained observed and dose-corrected values of several parameters. Although patients in neither the CyA-GC nor the CyA-ME group adequately absorbed the drug during days 0–2, from day 3 to 4 patients in the CyA-ME group showed significantly greater absorption than those in the CyA-GC group (P = 0.041). Patients in the CyA-ME group reached the 1st month target average concentration (C_av) values ( ≥ 550 ng/ml) earlier than those in the CyA-GC group and required significantly lower daily CyA doses (P = 0.018). We conclude that therapeutic CyA levels can be achieved more rapidly and with lower doses of the drug after de novo administration of CyA-ME than with CyA-GC. Received: 13 September 1996 Accepted: 7 January 1997     

Intima-media thickness and arterial elasticity in hypertensive children: controlled study

The objective of this cross-sectional controlled study was to evaluate the intima-media thickness (IMT) of the common carotid artery (cIMT) and superficial femoral artery (fIMT), as well as the elastic properties of the common carotid artery, in children with essential arterial hypertension. The study included 49 children with newly detected essential hypertension [mean age 14.5 (range 6–20) years] and 61 healthy normotensive children [mean age 13.5 (range 6–20) years]. The cIMT and fIMT were evaluated by ultrasonography. The elastic properties of the carotid artery were calculated from actual blood pressure values, arterial dimensions, and carotid wall thickness. Hypertensive children had greater values of both cIMT (0.45±0.05 mm) (P=0.0001) and fIMT (0.37±0.05 mm) (P=0.005) than controls (0.41±0.04 and 0.33±0.06 mm, respectively). The internal systolic and diastolic diameters of the common carotid artery were also significantly greater in hypertensive patients. The distensibility and elasticity of the common carotid artery were significantly decreased in hypertensive patients, while arterial compliance was significantly greater than in controls. cIMT and fIMT correlated with systolic and pulse pressure values, body mass index (BMI), homocysteine, low high-density lipoprotein, and apolipoprotein AI. After subdividing the control group and patients according to BMI below or above the 95th percentile for age and sex, there were differences only between normal-weight normotensive children and the two groups of hypertensive children. The stepwise regression analysis showed that the predictive factor for cIMT was pulse pressure and for fIMT body mass and homocysteine. Hence, in newly diagnosed children with essential hypertension, functional and anatomical changes in elastic and muscular arteries are observed. Pulse pressure and biochemical risk factors for cardiovascular damage were predictors of vessel wall injury, even if it remained within the normal range. BMI is an important factor influencing IMT values.     

Effects of Antegrade and Retrograde Machine Perfusion Preservation on Cardiac Function After Transplantation in Canines

Introduction

Most studies investigating machine perfusion preservation for heart transplantation perfuse through the aortic root (antegrade), but the coronary sinus (retrograde) is a potential option. We hypothesized that retrograde machine perfusion provides better functional protection than static storage, while avoiding the potential irregular perfusion seen when aortic insufficiency occurs with antegrade perfusion.

Materials and Methods

Eighteen canine donor hearts were arrested, procured, and stored in modified Celsior solution for 4 hours by using either static storage at 0°C to 4°C (n = 6) or machine perfusion preservation at 5°C via the aortic root (antegrade, n = 6) or coronary sinus (retrograde, n = 6). Lactate and myocardial oxygen consumption were measured in perfused hearts. Hearts were reimplanted and reperfused for 6 hours with hourly function calculated by using the preload recruitable stroke work (PRSW) relation. Myocardial water content was determined at the end of the experiment.

Results

Storage lactate levels and myocardial oxygen consumption were comparable in both perfused groups. The PRSW was increased immediately after bypass in the antegrade group (120.6 ± 19.1 mm Hg) compared with the retrograde (75.0 ± 11.3 mm Hg) and static (78.1 ± 10.5 mm Hg) storage groups (P < .05). At the end of reperfusion, PRSW was higher in the retrograde group (69.8 ± 7.4 mm Hg) compared with the antegrade (40.1 ± 6.8 mm Hg) and static (39.9 ± 10.9 mm Hg) storage groups (P < .05). Myocardial water content was similar among groups.

Conclusions

Both antegrade and retrograde perfusion demonstrated excellent functional preservation, at least equivalent to static storage. Initial function was superior in the antegrade group, but the retrograde hearts displayed better function late after reperfusion. Neither perfused group developed significant edema. Machine perfusion preservation is a promising technique for improving results of cardiac transplantation.     

Impact of long-term immunosuppression with cyclosporin A on serum lipids in stable renal transplant recipients

To determine the impact of long-term immunosuppression on serum lipids in stable renal graft recipients we measured serum lipids and apolipoprotein B concentrations in 20 patients receiving therapy with cyclosporin (CsA) and low-dose prednisolone (CsA/P) and in 18 patients on therapy with azathioprine and maintenance steroids (Aza/P). The patients were matched for age, body mass index, primary renal disease and dose of prednisolone, but not for the duration in transplantation and serum creatinine concentration. Triglyceride concentrations were significantly higher in the CsA/P group than in Aza/P-treated patients: 2.62±0.35 vs 1.62±0.23 mmol/l (P<0.05). Similarly, total cholesterol (C) levels were significantly more elevated in the CsA/P recipients than in the other group: 7.44±0.32 vs 5.84±0.25 (P<0.02). CsA/P patients had higher serum levels of LDL-C (4.79±0.20 vs 3.43±0.19 mmol/l P<0.001) and apolipoprotein B concentrations (191±13 vs 128±9 mg/dl; P<0.001). CsA/P and Aza/P recipients had similar concentrations of HDL-C (1.73±0.13 vs 1.52±0.09 mmol/l; NS). We conclude that in stable renal graft recipients with good transplant function long-term immunosuppression with CsA/P is associated with a more atherogenic lipid status than therapy with Aza/P.     

Oral acetazolamide in the assessment of (urine-blood)PCO2

Urine-blood (U-B)Pco₂ difference in children is usually assessed following urine alkalinization with oral sodium bicarbonate (NaHCO₃). Since oral NaHCO₃ is often poorly tolerated by children, we compared oral acetazolamide with oral NaHCO₃ in a study of (U-B)Pco₂. In the first phase of the study 14 children and adolescents aged 11.1±3.7 years (mean±SD) were studied. Eight participants had normal kidney function and 6 had disturbed distal acidification capacity. Each child was studied twice, once with oral NaHCO₃ (2.5 mEq/kg) and once with acetazolamide (17±2 mg/kg). All studies were performed according to the standard protocol. Acetazolamide administration resulted in a lower blood pH than NaHCO₃ (7.30±0.03 vs 7.38±0.06,P<0.001) and a lower serum bicarbonate (HCO₃ ^–) concentration (25.1±2.2 mEq/l vs 27.5±2.1 mEq/l,P<0.025). Acetazolamide also resulted in a higher urinePco₂ (81.9±26.2 mm Hg vs 71.6±18.2 mm Hg) than NaHCO₃ (P<0.025). No significant differences between acetazolamide and NaHCO₃ were observed with respect to their effects on urinary pH and HCO₃ ^– concentration, plasmaPco₂ and (U-B)Pco₂. Good linear correlations were found between the effects of acetazolamide and NaHCO₃ on urinePco₂ (r=0.878,P<0.001), and on (U-B)Pco₂ (r=0.795,P<0.01). Using either method of urinary alkalization, children with normal kidney function had urinePco₂ greater than or equal to 80 mm Hg and (U-B)Pco₂ greater than or equal to 30 mm Hg, and those with disturbed acidification capacity had urinePco₂ less than or equal to 70 mm Hg and (U-B)Pco₂ less than or equal to 20 mm Hg. Patient satisfaction with the test, on a scale of 1 (worst) to 5 (best), was 2.6±0.8 for NaHCO₃ and 3.9±0.3 for acetazolamide (P<0.001). Tests with NaHCO₃ lasted 150.9±30.5 min versus 115.7±18.1 min for acetazolamide (P<0.01). In the second phase of the study 8 children, 5 with normal and 3 with abnormal acidification capacity were studied twice with oral acetazolamide. Studies were performed 3 weeks apart. The results showed very good reproducibility of (U-B)Pco₂ in all of the subjects. Oral acetazolamide and NaHCO₃ have similar effects on (U-B)Pco₂ but the diuretic agent shortens the testing time and is easier to administer to children. We conclude that oral acetazolamide could be substituted for NaHCO₃ under certain circumstances in the assessment of (U-B)Pco₂.     

Effect of increased compartment pressure on the microcirculation of skeletal muscle

To determine the changes in capillary perfusion, which occur with elevated tissue pressure, and to highlight the relationship between systemic blood pressure and compartment pressure, we designed an experiment that allowed direct observation of the microcirculation of skeletal muscle under normal and increased compartment pressures. In each of 10 anesthetized rats, the cremaster muscle was exposed and suspended in a transparent pressure chamber. In vivo videomicroscopy was then performed and blood pressure was monitored via left carotid artery cannulation. Two sets of data for each animal were obtained: ΔP (mean arterial pressure − compartment pressure) at which the muscle capillary blood flow was completely arrested, and the number of capillaries per 10,000 square micrometers of skeletal muscle with blood flowing at compartment pressures of 0, 15, 30, 45, and 60 mm Hg. Capillary blood flow stopped at a ΔP of 25.5 mm Hg ± 14.3 SD. We found that capillary blood flow, as measured by the number of capillaries with blood flow per 10,000 square micrometers, decreased significantly (P< 0.05) as compartment pressure reached 15, 30, 45, and 60 mm Hg, when compared to 0 mm Hg; there was no vessel collapse at these pressures. These data show that increasing compartment pressure reduces the number of perfused capillaries per unit area, and that there is complete cessation of muscle capillary blood flow when the compartment pressure is within about 25 mm Hg of the mean arterial pressure. © 1998 Wiley-Liss, Inc. MICROSURGERY 18:67-71 1998