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Biomedical subjects

M J Jacobs

Publications and source records attributed to M J Jacobs.

At least 55 records · Page 3Linked to original sources
PubMed1999

Influence of repetitive finger puncturing on skin perfusion and capillary blood analysis in patients with diabetes mellitus.

BACKGROUND: Frequent puncturing of fingers to check blood glucose in patients with type 1 diabetes might alter skin perfusion and, hence, influence the representativeness of the blood sample. We investigated the influence of repetitive puncturing on skin microcirculatory perfusion using laser Doppler fluxmetry and on the preanalytical phase of capillary blood analysis for small molecules (glucose) and large particles (cholesterol). METHODS: In 49 patients with long-standing (mean, 21 years) type 1 diabetes, with a mean puncture frequency of three times daily for a mean duration of 13 years, laser Doppler skin perfusion was measured in a finger at a frequently punctured site and compared with a similar site of another finger of the same hand, which was never punctured. In the supine position with the hand level with the heart, resting flux (RF), peak flux (PF), and the microcirculatory reserve capacity (MRC; PF - RF) were assessed. Subsequently, blood samples for capillary whole blood glucose and cholesterol analyses were taken from the same sites. RESULTS: No significant differences were found between the puncture and control sites in mean RF (2.3 vs 2.0 V; P = 0.14, paired-samples t-test), PF (3.3 vs 3.1 V; P = 0.24), MRC (1.0 vs 1.0 V; P = 0.65), glucose (10.2 vs 10.2 mmol/L; P = 0.69), or cholesterol (5.1 vs 5.2 mmol/L; P = 0.26). Power calculation for a RF of 2.0 V and the SD and n of this study indicate a power (beta) of 80% to detect a 25% change in RF at P <0.05. CONCLUSIONS: Repetitive finger puncturing in diabetics appears not to injure local skin microcirculatory perfusion nor to influence results of capillary blood analysis for glucose and cholesterol.

Adult↗
PubMed1998

Reduced renal failure following thoracoabdominal aortic aneurysm repair by selective perfusion.

OBJECTIVES: Renal failure and visceral ischemia are feared complications following thoracoabdominal aortic aneurysm (TAAA) repair, significantly contributing to mortality. This prospective study describes volume- and pressure-controlled perfusion of the renal and visceral arteries during TAAA surgery. METHODS: In 73 consecutive patients (mean age 59 years), TAAA repair (27 type I, 28 type II, 8 type III and 10 type IV) was performed, using retrograde and selective organ perfusion. Sixteen patients had impaired renal function with blood creatinine higher than 100 mmol/l. During the thoracic part of the procedure, the mean distal aortic pressure was kept above 60 mm Hg by means of left-heart bypass. After opening the abdominal aorta, the renal and visceral arteries were individually perfused by means of perfusion catheters (9 French) in the first 33 patients (group I). Volume flow through each catheter was assessed with ultrasound flow meters and maintained at least at 60 ml/min. In addition to volume flow measurements, catheters with pressure sensors were used in the last 40 patients (group II), allowing pressure-controlled selective perfusion. The extent of the aneurysm was comparable in both groups. RESULTS: Mean cross-clamp time for the thoracic part was 46 min, including proximal anastomosis and reattachment of intercostal arteries. Mean cross-clamp time for the abdominal part was 74 min, including re-implantation of intestinal and renal arteries and selective dacron grafts to the celiac-axis arteries (n = 5), superior mesenteric arteries (n = 8) and renal arteries (n = 25), through which the catheters guaranteed continuous perfusion during the time the anastomosis was performed. Urine output was uninterrupted in all patients, irrespective of cross-clamp time. In group I, one patient (3%) developed renal failure and three patients (9%) required temporary peritoneal dialysis. In group II, no patients developed renal failure and two patients (5%) required temporary peritoneal dialysis. Thirteen patients with pre-existing renal impairment did not deteriorate. No patients developed visceral ischemia or multiple-organ failure. Total in-hospital mortality was 6/73 (8%) and was related to cardiopulmonary complications. CONCLUSIONS: Renal and visceral ischemia can be reduced significantly by continuous perfusion during cross-clamping in TAAA repair. Not only sufficient volume flow but also adequate arterial pressure appears to be essential in maintaining renal function.

Aortic Aneurysm, Abdominal↗
PubMed1998

Spinal cord monitoring with myogenic motor evoked potentials: early detection of spinal cord ischemia as an integral part of spinal cord protective strategies during thoracoabdominal aneurysm surgery.

Spinal cord ischemia during resection of thoracoabdominal aortic aneurysms (TAA) can result in lower limb neurological deficits. Spinal cord monitoring can only improve outcome if ischemia is detected before irreversible damage has occurred and protective measures are readily available. Monitorin( spinal cord function with motor evoked potentials (MEPs) is a relatively new technique. With MEP. recorded from the muscle (myogenic MEPs), the vulnerable spinal motoneuronal system is exclusively monitored and ischemia is detected within minutes. Using a strategy aimed at maintaining and restoring spinal cord blood supply (distal aortic perfusion, sequential aortic clamping, and selective segmental artery reattachment), early detection of ischemia allows protective measures to be applied and adjusted immediately, ie, reattaching or safely ligating intercostal arteries, increasing proximal o distal aortic pressures as required, or inducing hypothermia. Recent improvements in the technique fo eliciting myogenic MEPs include multi-pulse stimulation paradigms and the use of a circumferentia cathode. This results in robust and reproducible signals, which are less susceptible to anesthetic interference and allow the use of a constant level of neuromuscular blockade. In conclusion, monitoring myogenic MEPs during a TAA repair has become clinically feasible. The fast detection of spinal cord ischemia allows timely guidance of protective measures.

Animals↗
PubMed1998

Aortoiliac reconstructive surgery based upon the results of duplex scanning.

OBJECTIVE: To evaluate whether duplex scanning can replace angiography in patients operated for aortoiliac obstructive disease. DESIGN: Retrospective. MATERIALS AND METHODS: Between January 1995 and October 1996, 44 patients underwent vascular surgery of the aortoiliac tract. The study population was divided into two groups; patients operated upon the results of duplex scanning only and patients who also underwent angiography prior to surgery. The additional value of angiography and the differences between both groups concerning unexpected peroperative findings, early postoperative failures and the need for additional radiological or surgical interventions in the first three postoperative months were studied. RESULTS: Duplex scan group: 22 patients were operated upon the results of duplex scanning only. In two patients surgical strategy had to be changed. Early postoperative graft occlusion occurred in one case. A haemodynamically significant graft stenosis within 3 months of surgery occurred in one patient. Duplex/angiography group: 22 patients underwent both duplex scanning and angiography. Six patients underwent diagnostic angiography after failed duplex scanning. In 10 patients angiography was part of percutaneous transluminal angioplasty prior to surgery. In six patients angiograms were performed after successful duplex scanning. Angiography failed in two patients and added information in four of 16 patients. Unexpected findings at operation occurred in four patients. Graft stenosis within 3 months was detected in three patients. CONCLUSION: After successful duplex scanning information obtained by angiography has only a limited impact on therapeutic decision-making. In the majority of patients vascular reconstructive surgery of aortoiliac arteries can be planned based on duplex scanning only.

Adult↗
PubMed1998

Can cruropedal colour duplex scanning and pulse generated run-off replace angiography in candidates for distal bypass surgery.

PURPOSE: To compare the diagnostic accuracy of duplex scanning (DS) and pulse generated run-off (PGR) with ia-DSA for the assessment of cruropedal outflow and explore the reliability of clinical decision making based on a work-up with DS/PGR in candidates for peripheral bypass surgery. METHODS: Popliteal, crural and pedal arteries were evaluated independently with DS and ia-DSA in 126 limbs of 120 consecutive patients for claudication (16%) or critical ischaemia (84%). Arterial segments were graded with DS and ia-DSA as normal, stenosed, or occluded and compared using weighted kappa (kappa) analysis. PGR was used to select the best crural artery for bypass. Proposed management based on DS/PGR and, if applicable, anastomosis site were compared to definitive treatment based on ia-DSA. RESULTS: Overall agreement between DS and ia-DSA for popliteal and crural arteries was moderate (kappa 0.51, 95% CI 0.48-0.55) with good agreement within the popliteal (kappa 0.67) and anterior tibial (kappa 0.61) arteries. Agreement was moderate within the pedal arterieds (kappa 0.32, 95% CI 0.24-0.40). In 74/126 (59%) limbs proposed management with DS/PGR was identical to ia-DSA. In 23/29 (79%) femoropopliteal and 15/37 (41%) femorocrural bypasses DS/PGR agreed perfectly with ia-DSA with regard to acceptor artery and anastomosis site. CONCLUSION: DS can accurately assess the popliteal and anterior tibial arteries. In a substantial number of patients with severe lower limb ischaemia decisions for conservative management, PTA and femoropopliteal bypass can be based on a DS/PGR work-up.

Adult↗
PubMed1998

Effect of mild hypothermia and the 21-aminosteroid U-74389G on neurologic and histopathologic outcome after transient spinal cord ischemia in the rabbit.

Mild hypothermia and the 21-aminosteroids have both been neuroprotective in several models of cerebral ischemia. In this study we compared the effects of mild hypothermia and the 21-aminosteroid U-74389G, alone and in combination on neurologic and histopathologic outcome after temporary spinal cord ischemia. Forty male anesthetized New Zealand white rabbits were randomized to four groups (n = 10): (a) normothermia (control); (b) U-74389G (3 mg/kg intravenously [i.v.] before aortic occlusion, 1.5 mg/kg i.v. and 10 mg/kg intraperitoneally after occlusion); (c) mild hypothermia (4 degrees C epidural temperature decrease); and (d) mild hypothermia combined with U-74389G. Spinal cord ischemia was produced by 40 min of infrarenal aortic balloon occlusion. Forty-eight hours after the procedure, the neurologic status of the animals was assessed (Tarlov score) and the animals were killed for histologic evaluation. In the normothermic control group, eight of 10 animals became paraplegic. There was a significant reduction of the incidence of paraplegia and overall neurologic deficits and a significant improved Tarlov score in the mild hypothermic group (one animal paraplegic) and in the group with both mild hypothermia and U-74389G (two animals with a mild paraparesis). The histopathologic scores showed significantly less damage in both hypothermic groups. In group 2, U-74389G administration did not improve neurologic or histopathologic outcomes. The results of the current study demonstrate that a slight decrease of intraischemic spinal cord temperature significantly improved neurologic and histopathologic outcomes after experimental spinal cord ischemia. Protection by the 21-aminosteroid at normothermic conditions, or additional protection when U-74389G was added to mild hypothermia, could not be demonstrated.

Anesthesia, Intravenous↗
PubMed1997

Skin blood flow abnormalities in a rat model of neuropathic pain: result of decreased sympathetic vasoconstrictor outflow?

Loose ligation of a sciatic nerve in rats provokes signs and symptoms like those observed in human conditions of neuropathic pain. Some of these have been associated with sympathetic dysfunction. Since the skin microcirculation in the rat is strongly influenced by sympathetic tone, abnormalities in skin blood flow may be used as an indirect measure of sympathetic dysfunction. We measured, by means of laser Doppler flowmetry, skin blood flow at the plantar surface of the rat hind paw before and after ipsilateral loose sciatic nerve ligation. We assessed basal skin blood flow as well as the vasoconstrictor response which follows cooling of the rat abdomen. The effectiveness of this response may be used as a measure of sympathetic vasoconstrictor outflow. As compared to the values obtained before ligation (= 100%): (1) the vasoconstrictor response was impaired (65%, P < 0.01) from day 1 onwards, whereas (2) basal skin blood flow was increased (171%; P < 0.01) from day 3 until day 5, and decreased (51%, P < 0.0001) from day 7 until day 28. At day 28, blockade of impulse propagation in the loosely ligated sciatic nerve (by means of lidocaine) did not increase the lowered level of skin blood flow. These findings suggest that in the chronic construction injury model loose ligation of a sciatic nerve reduces sympathetic vasoconstrictor outflow, which, in turn may induce supersensitivity of skin microvessels to catecholamines.

Animals↗
PubMed1997

Role of interleukin-4 and interleukin-10 in murine collagen-induced arthritis. Protective effect of interleukin-4 and interleukin-10 treatment on cartilage destruction.

OBJECTIVE: To examine the role of endogenous interleukin-4 (IL-4) and interleukin-10 (IL-10) and the therapeutic effect of the addition of IL-4 and IL-10 in early and established murine collagen-induced arthritis (CIA). METHODS: Murine recombinant IL-4, IL-10, or the combination was given intraperitoneally twice daily from the day of arthritis onset up to 7-10 days of CIA in DBA/1 mice. Anti-IL-4, anti-IL-10, or both antibodies were given intraperitoneally before or after the onset of CIA. The effect of cytokine or anticytokine treatment was monitored visually by macroscopic scoring. Histology and reverse transcription-polymerase chain reaction (RT-PCR) analyses were performed at the end of the treatment period. RESULTS: IL-4 alone did not provoke any effect, IL-10 slightly suppressed the arthritis, but a more pronounced amelioration was found with the combination. This cooperative effect was noted after early treatment but also occurred when the start of treatment was delayed until 1 week after onset. Apart from suppression of macroscopic signs of inflammation, combined treatment with IL-4/IL-10 also reduced cellular infiltrates in the synovial tissue and caused pronounced protection against cartilage destruction. Moreover, levels of mRNA for tumor necrosis factor alpha (TNF alpha) and IL-1 were highly suppressed both in the synovial tissue and in the articular cartilage. In contrast, levels of IL-1 receptor antagonist (IL-1Ra) mRNA remained elevated, which suggests that the mechanism of protection may be related to suppressed production of TNF alpha and IL-1, with concomitant up-regulation of the IL-1Ra/IL-1 balance. However, accelerated onset of CIA and increased severity could be achieved with neutralizing anti-IL-10 antibodies. This expression could be further optimized with a combination of anti-IL-4 and anti-IL-10 antibodies, although anti-IL-4 alone was without effect. CONCLUSION: Our data are consistent with a dominant role of IL-10 in the natural suppression of arthritis expression, whereas combined treatment with IL-4 and IL-10 appears of potential therapeutic value, not only at the onset, but also in established arthritis.

Animals↗
PubMed1997

Morphology and function of preserved microvascular arterial grafts: an experimental study in rats.

The aim of this study is to examine the morphology and function and small-caliber, arterial grafts after preservation in the University of Wisconsin solution (UW). Rat carotid arteries were stored in UW (n = 10) or in phosphate-buffered saline (PBS) (n = 10) for 1, 3, 7, and 14 days and were examined with light microscopy (LM) and scanning electron microscopy (SEM). Rat aortic preparations were stored in UW or PBS for 1 hour, 24 hours, 72 hours, 7 days, and 14 days and assessed for functional responses (stimulated contraction and endothelium-dependent relaxation). Segments (5 mm) of rat carotid arteries were stored in UW or PBS for 3 days, 7 days, and 14 days and orthotopically implanted as autografts and allografts. No immunosuppressive or anticoagulant agents were used. After 28 days of implantation, the grafts were assessed for patency and excised for LM and SEM. In UW, the endothelial layer remained intact up to 9 days of storage. In PBS, the endothelial layer showed deterioration after 1 day and was completely lost after 3 days. Functional responses were demonstrated to exist for as long as 7 days storage in UW. In PBS, no responses could be evoked after 24 hours storage. Autografts preserved in UW for 3 days (n = 6), 7 days (n = 6), and 14 days (n = 6) showed patency rates of 83.3%, 66.6%, and 66.6%, respectively, whereas patency rates of allografts were 66.6%, 33.3%, and 33.3%, respectively. Autografts stored in PBS for 3 days (n = 6), 7 days (n = 6), and 14 days (n = 6) showed patency rates of 33.3%, 33.3%, and 50%, respectively, whereas patency rates of allografts were 16.7%, 0%, and 33.3%, respectively. The UW preserved autografts showed normal morphology. All other groups showed vessel wall degeneration which in the allograft groups, were accompanied by lymphocellular infiltration. In conclusion, the endothelial layer and vessel wall of arteries are adequately preserved in UW. Functional responses are retained up to 14 days storage in UW, but, are lost after 24 hours storage in PBS. Autograft implantation studies accordingly show good performance of arterial segments preserved in UW, whereas allografts are subject to degradation as a result of rejection.

Adenosine↗
PubMed1997

Efficacy of transcranial motor-evoked myogenic potentials to detect spinal cord ischemia during operations for thoracoabdominal aneurysms.

OBJECTIVE: Motor-evoked myogenic potentials after transcranial electrical stimulation monitor the vulnerable motoneuronal system of the spinal cord. This study reports our initial experiences with motor-evoked potentials to assess the adequacy of spinal cord perfusion during operations for thoracoabdominal aneurysms. METHODS: In 20 patients undergoing thoracoabdominal aneurysm operations, myogenic motor-evoked potentials were recorded. In 18 patients retrograde aortic perfusion was used. When spinal cord ischemia was detected, distal flow or mean arterial pressure was increased in an attempt to restore cord perfusion. By means of sequential crossclamping, motor-evoked potentials were also used to identify intercostal or lumbar arteries that needed to be reimplanted. RESULTS: Reproducible motor-evoked potentials could be recorded in all patients. During retrograde perfusion, nine patients showed a rapid decrease in the amplitude of motor-evoked potentials to less than 25% of baseline, indicating spinal cord ischemia. In five patients ischemic changes in motor-evoked potentials could be reversed by increasing distal and proximal blood pressures. In four patients ischemic changes during crossclamping necessitated segmental artery reimplantation. In three of these four patients intercostal or lumbar arteries were reattached. In one patient reimplantation of segmental arteries was not possible; this patient awoke paraplegic. Segmental arteries were ligated after confirmation of intact motor-evoked potentials during aortic clamping in eight patients. None of these patients had a neurologic deficit. The absence of motor-evoked potentials at the end of the procedure always indicated a postoperative motor deficit. CONCLUSION: During operations for thoracoabdominal aneurysms, monitoring of motor-evoked potentials is an effective technique to detect spinal cord ischemia within minutes. This modality can be used to guide the management of distal aortic perfusion techniques and may also help to identify segmental arteries that need to be reattached.

Adult↗
PubMed1997

The value of non-invasive techniques for the assessment of critical limb ischaemia.

OBJECTIVE: The European Consensus Document (ECD) defines critical ischaemia (CI) according to clinical (Fontaine) and blood pressure parameters. However, clinical symptoms may be non-specific and CI may exist without severely reduced blood pressures. This study prospectively investigated the additive value of transcutaneous oxygen tension (pO2) and toe blood pressure measurements to assess the presence of CI. METHODS: Forty-nine patients with 65 legs clinically classified as Fontaine stages III (n = 23) and IV (n = 26) were studied. Ankle and toe systolic blood pressure and pO2 were measured to assess the presence of CI (cut-off values were 50, 30 and 30 mmHg, respectively). The surgeon was blinded for the toe pressure and pO2 results. The treatment received within 1 month after presentation was recorded as being either conservative or invasive (vascular surgery or PTA). RESULTS: An ankle pressure of < or = 50 mmHg classified only 17% of the legs as having CI. By adding toe pressure and pO2, significantly more legs (63%; p < 0.0001) were classified as CI, of which 68% received invasive therapy. Forty-nine percent of the legs with an ankle pressure > 50 mmHg were treated invasively, whereas only 32% of the legs classified as not having CI by means of toe pressure and pO2 underwent invasive therapy. If the need for invasive treatment is used as the "gold standard" for the presence of CI, 54% of the legs would accurately be classified on the basis of the ankle blood pressure. The combination of toe pressure and pO2 would have yielded 71% and the ECD criteria 72% and accurately classified legs. The odds ratio for invasive therapy given a pO2 or toe pressure above the cut-off value was 14. CONCLUSION: Ankle blood pressure measurements have limited diagnostic value. Adding toe and/or oxygen pressures enhances the detection of CI requiring invasive therapy.

Aged↗
PubMed1997

Retrograde aortic and selective organ perfusion during thoracoabdominal aortic aneurysm repair.

OBJECTIVES: To evaluate the possible prevention of renal and intestinal ischaemia during surgery of thoracoabdominal aortic aneurysms (TAAA) by use of retrograde and selective organ perfusion. DESIGN: Prospective study. MATERIALS: Thirty-three consecutive patients underwent TAAA repair, six of whom had a previous type B dissection: 14 patients (35%) had type I TAAA, 12 patients type II (32%), three patients type III (15%) and four patients type IV (18%). Mean age was 61 years (range 22-84 years). METHODS: In patients with type I TAAA, retrograde aortic perfusion was performed by means of a left atrium femoral artery bypass or partial cardiopulmonary bypass. In type II, III and IV the same procedure was performed; however, following cross-clamping and opening of the abdominal aorta, the coeliac trunc, superior mesenteric and both renal arteries were selectively perfused with four Pruitt-catheters (9 Fr.), connected as an octopus to the extracorporal circulation. RESULTS: All patients survived the surgical procedure. The minimal volume flow through each octopus catheter was 60 ml/min. Urine output was uninterrupted in all patients, irrespective of the aortic cross-clamp time. Only one patient (3%), who already had renal insufficiency, developed renal failure. Total in-hospital mortality was 15%, paraplegia occurred in 12%. CONCLUSION: Retrograde aortic and selective organ perfusion is a safe technique and can prevent ischaemic renal and intestinal damage during cross-clamping of the aorta in thoracoabdominal aneurysm surgery.

Adult↗
PubMed1997

Diabetes mellitus is not a contra-indication for peripheral vascular intervention in patients with leg ischemia.

BACKGROUND: The effect of diabetes mellitus on the patency of peripheral vascular interventions was investigated in patients with arterial insufficiency of the leg in a retrospective follow-up study performed between 1993 and 1995. METHODS: In 65 patients without and 36 with diabetes 124 vascular reconstructions were performed because of rest pain and/or ulceration. RESULTS: In diabetic patients ulcers were found more frequently and more distal bypasses were performed. No significant differences were observed between diabetics and non-diabetics as to bypass patency, number of re-interventions and amputations. Smoking and age were significant factors influencing bypass patency. CONCLUSION: Diabetes mellitus in patients with critical leg ischaemia appears to be no reason to refrain from vascular surgery.

Aged↗
PubMed1997

Colour duplex scanning and pulse-generated run-off for assessment of popliteal and cruropedal arteries before peripheral bypass surgery.

BACKGROUND: This prospective pilot study compared the diagnostic accuracy of duplex scanning and pulse-generated run-off (PGR) with intra-arterial digital subtraction angiography (IADSA) for assessment of popliteal, crural and pedal arteries, and explored the reliability of investigation with the combination of duplex scanning and PGR in patients who needed femorodistal reconstruction. METHODS: In 23 limbs, 345 arterial segments were graded independently with duplex scanning and IADSA as normal, stenosed or occluded and compared using weighted kappa analysis. PGR was rated as good, poor or no run-off and compared with pedal arch patency on IADSA. Based on information derived from duplex scanning and PGR a vascular surgeon proposed treatment and the distal anastomosis site for bypass, which was compared with definitive treatment as determined by IADSA. RESULTS: Overall agreement between duplex scanning and IADSA for popliteal and crural arteries was moderate (kappa 0.47, 95 per cent confidence interval (c.i.) 0.39-0.55) with best agreement within the popliteal and proximal tibial arteries. Agreement within pedal arteries was fair (kappa 0.35, 95 per cent c.i. 0.17-0.53). PGR detected good run-off in five of 21 pedal arteries shown to be occluded on IADSA. In 16 of 23 patients treatment based on duplex scanning and PGR was identical to that based on IADSA. Eight of eleven femoropopliteal bypasses were predicted accurately. CONCLUSION: Operative strategy could have been based on investigation by duplex scanning and PGR in a substantial number of patients scheduled for femoropopliteal bypass surgery. Agreement between duplex scanning and IADSA within very distal arterial segments was fair.

Adult↗
PubMed1997

Use of spiral computed tomographic angiography in monitoring abdominal aortic aneurysms after transfemoral endovascular repair.

Transfemoral endovascular repair of abdominal aortic aneurysms has proved to be technically feasible in a selected group of patients. However, long-term efficacy has not been proved. Graft performance after implantation can be monitored by a single imaging technique: spiral computed tomographic angiography. With this technique, the parameters for continuing clinical success of the procedure-graft patency, endoleaks, graft migration, attachment site diameter, attachment system failure, and aneurysm diameter-can be monitored. Only in selected cases will an additional imaging technique be necessary.

Aortic Aneurysm, Abdominal↗
PubMed1996

Experimental arterial allografting under low and therapeutic dosages of cyclosporine for immunosuppression.

The aim of this study was to investigate performance of preserved arterial allografts under the protection of a high-dose and a low-dose immunosuppressive regimen, with cyclosporine (CsA). Dog carotid arteries were harvested and stored for 14 days at 4 degrees C in University of Wisconsin organ preservation solution. Segments (6 cm) of carotid artery were orthotopically and bilaterally implanted in mongrel dogs (n = 18). CsA was given in two dosage regimens: 25 mg/kg/day (group I, n = 7) and 10 mg/kg/day (group II, n = 7). The control group received no CsA (group III, n=4). After 3 months of implantation, patency was assessed by angiography. The grafts were excised for investigation of vessel wall and endothelial function and morphology. For assessment of function in vitro, slices of arterial segments were connected as ring preparations to an isometric force transducer and immersed in a 5 ml organ bath (37 degrees C) containing Tyrode's solution. The contractile response was examined by adding 40 mM KCl and phenylephrine (100 microM) to the organ bath; endothelium-dependent relaxation was examined by adding methacholine (100 microM). Morphology was assessed semiquantitatively. The functional responses to KCl, phenylephrine (Phe) and methacho- line (Met) after 14 days of storage in UW, were 30.2 +/- 1.2 mN, 26.9 +/- 1.0 and 45 +/- 1.2% (means +/- SEM, n=9), respectively. Patency after three months of implantation for group I was 100% (14/14), for group II 50% (7/14), and for group III 75% (6/8). In vitro functional responses of preserved arteries, after 3 months of implantation in group I were 58.5 +/- 10.6 mN (KCl), 36.5 +/- 5.8 mN (Phe), and 57.4 +/- 9.7% (Met), respectively. Functions in group II were 1.2 +/- 0.1 mN (KCl, 0.0 mN (Phe), and 0.0% (Met). Grafts in group III showed no function. Measurement of medial thickness showed significant thinning (P <0.05) in groups II and III. Patency and function of arterial allografts under a therapeutic dose of CsA were superior to grafts implanted under low-dose CsA or no immunosuppressive treatment.

Animals↗