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Biomedical subjects

L M Messina

Publications and source records attributed to L M Messina.

At least 55 records · Page 3Linked to original sources

Retroviral-mediated transduction of endothelial cells with the lac Z gene impairs cellular proliferation in vitro and graft endothelialization in vivo.

PURPOSE: An endothelialized lumen within a synthetic graft that expresses recombinant proteins with anticoagulant or antiproliferative activity has the potential to improve graft function. However, preliminary data suggest that genetic modification of endothelial cells (ECs) impairs their proliferation. The purpose of this investigation was to test the hypothesis that retroviral transduction of cultured ECs with the lac Z gene encoding for beta-galactosidase would decrease EC proliferation in vitro and graft endothelialization in vivo. METHODS: In vitro studies compared canine EC proliferation over a 14-day period among early-passage ECs (two and three) and late-passage ECs (six and nine) transduced with the BAG vector (containing the lac Z gene and the neomycin resistance gene), ECs transduced with the neomycin resistance gene only, the nontransduced ECs. In vivo canine studies assessed endothelialization of expanded polytetrafluoroethylene thoracoabdominal grafts seeded with autologous lac Z-transduced ECs (n = 7) or nontransduced ECs (n = 3) compared with that of nonseeded grafts (n = 3). Histochemical staining and DNA polymerase chain reaction was used 6 weeks after implantation to detect the presence of the lac Z gene in the grafts' cellular linings and perigraft tissues. Endothelialization was assessed by light microscopy and electron microscopy. RESULTS: Proliferation of late-passage lac Z-transduced ECs in vitro was significantly decreased compared with neomycin resistance-transduced ECs or nontransduced ECs. Among early-passage ECs smaller but significant decreases in proliferation were noted among lac Z-transduced cells compared with nontransduced cells. Six of seven expanded polytetrafluoroethylene grafts seeded with transduced ECs showed lac Z gene expression. Lac Z gene expression was not found on grafts seeded with nontransduced ECs or nonseeded grafts. The endothelialized luminal surface area was significantly less in grafts seeded with lac Z-transduced ECs compared with grafts seeded with nontransduced ECs. CONCLUSIONS: Retroviral-mediated transduction of canine ECs with the lac Z gene encoding for beta-galactosidase impairs EC proliferation in vitro and the ability of transduced ECs to form a confluent EC monolayer on the luminal surface of synthetic grafts in vivo.

Animals↗

Inhibition of aortic aneurysm development in blotchy mice by beta adrenergic blockade independent of altered lysyl oxidase activity.

PURPOSE: This study was designed to define the effects of beta-adrenergic blockade on aortic lysyl oxidase (LO), an enzyme responsible for elastin and collagen cross-linking, and aneurysm formation in the blotchy mouse. It was hypothesized that beta-blockade would inhibit the development of aneurysms because of its hemodynamic effect rather than a direct effect on LO activity. METHODS: Three groups of mice were studied: group I--normal littermates of blotchy mice; group II--untreated blotchy mice; group III--blotchy mice given either propranolol, atenolol, or nadolol. Data from the three different beta blocker-treated animals, group III, were statistically identical and were combined for analysis. The study was concluded when the mice were 4 months of age. At that time systolic blood pressure, heart rate, and aortic diameters were measured, and the entire aorta from each mouse was subjected to a bioassay for LO activity. RESULTS: Group I normal mice had an aortic arch diameter of 0.10 +/- 0.02 cm. Group II blotchy mice developed aortic arch aneurysms with a diameter of 0.21 +/- 0.03 cm. In Group III, beta blockade reduced the aortic arch diameter in blotchy mice to 0.11 +/- 0.03 cm. Mean heart rate in group III beta-blocked mice was reduced 25% compared with group I normal mice, and 18% compared with group II untreated blotchy mice. Blood pressures were similar in all three groups. Group II blotchy mice exhibited approximately half of the aortic LO activity (2.43 +/- 0.57 cpm/micrograms protein) noted in group I normal mice (5.82 +/- 1.06 cpm/micrograms protein). Aortic LO activity in group III blotchy mice remained low (2.09 +/- 0.85 cpm/micrograms protein) despite administration of beta-blockers. CONCLUSIONS: This is the first study to document an actual decrease in the level of aortic LO activity in blotchy mouse. beta-Blockade inhibits development of aortic aneurysms in blotchy mice. This is associated with a reduction in heart rate, but not by alterations in LO activity.

Animals↗

Effects of retroviral-mediated tissue plasminogen activator gene transfer and expression on adherence and proliferation of canine endothelial cells seeded onto expanded polytetrafluoroethylene.

PURPOSE: Seeding prosthetic arterial grafts with genetically modified endothelial cells (ECs) has the potential to substantially improve graft function. However, preliminary applications suggest that grafts seeded with retrovirally transduced ECs yield a significantly lower percent surface coverage than those seeded with nontransduced ECs. The objective of this study was to test the hypothesis that canine ECs transduced with the human tissue plasminogen activator (tPA) gene would have a lower rate of adherence to pretreated expanded polytetrafluoroethylene (ePTFE) both in vitro and in vivo and that they would proliferate at a slower rate on pretreated ePTFE in vitro. METHODS: Early passage ECs derived from canine external jugular vein were transduced with the retroviral MFG vector containing the gene for human tPA. ECs exposed to media alone served as controls. Iodine 125-labeled ECs were seeded in vitro onto ePTFE graft segments pretreated with canine whole blood, fibronectin (50 micrograms/ml), or media alone, and the percent of ECs adherent at 1 hour were determined (n = 3). Additional tPA-transduced and -nontransduced ECs were grown for 10 days on either fibronectin (50 micrograms/ml)-pretreated ePTFE wafers or tissue culture plastic pretreated with gelatin (1%) or fibronectin (50 micrograms/ml), and the EC proliferation rates were determined (n = 3). Furthermore, 125I-labeled ECs were seeded onto fibronectin (50 micrograms/ml)-pretreated ePTFE graft segments implanted as carotid and femoral artery interposition grafts (n = 3). The grafts were harvested after 1 hour, and the percent of ECs adherent was determined. RESULTS: Human tPA was detected by immunohistochemical staining in 61% +/- 5% of the transduced ECs and was expressed at 35.4 +/- 12.9 ng/hr/10(6) cells. Fibronectin and whole blood pretreatment of the ePTFE grafts led to greater EC adherence in vitro than did media alone (90.9% +/- 5.3% vs 77.8% +/- 5.8% vs 4.7% +/- 1.1%, p < or = 0.05). No significant difference in the rates of adherence or proliferation was seen in vitro between the transduced and nontransduced ECs. No significant difference in proliferation was found for the transduced ECs on the three matrices tested in vitro. In contrast, adherence of the transduced ECs in vivo was significantly lower than that of nontransduced ECs (64.7% +/- 2.1% vs 73.7% +/- 4.1%, p < or = 0.05) 1 hour after implantation. CONCLUSIONS: Lower rates of surface endothelialization by genetically modified ECs in vivo do not appear to be due to an impaired capacity to initially adhere or proliferate on the synthetic graft but may result from decreased adherence after exposure to in vivo hemodynamic forces.

Animals↗

Gadolinium-enhanced magnetic resonance angiography of abdominal aortic aneurysms.

PURPOSE: The objective of this study was to assess the usefulness of gadolinum-enhanced magnetic resonance angiography (MRA) for defining anatomic features relevant to performing aortic surgery for aneurysmal disease. METHODS: Anatomic data defined by MRA, including abdominal aortic aneurysm (AAA) size and character, as well as the status of the celiac, mesenteric, renal, and iliac arteries, were correlated with angiography, ultrasonography, computed tomography, or operative data in 43 patients. Five MRA sequences were obtained in an hour-long examination optimized for aortoiliac, splanchnic, and renal artery imaging at 1.5 T in a body coil. Four of the sequences were performed during or after infusion of gadolinium to improve image quality. RESULTS: MRA correctly defined the maximum aneurysm diameter, as well as its proximal and distal extent in all patients. MRA detected 33 of 35 significant stenoses among 153 splanchnic, renal, or iliac branches examined (sensitivity = 94% and specificity = 98%). MRA did not resolve the degree of aortic branch stenotic disease sufficiently to precisely grade its severity. MRA did not reliably define the status of the inferior mesenteric artery, lumbar arteries or internal iliac arteries. One ruptured AAA and one inflammatory AAA were correctly diagnosed by MRA. No patient had a contrast reaction or contrast-induced renal toxicity related to administration of gadolinium. CONCLUSION: Gadolinium-enhanced MRA of AAA provides appropriate, essential anatomic information for aortic reconstructive surgery in a 1-hour examination devoid of contrast-related renal toxicity or catheterization-related complications attending conventional arteriography.

Adult↗

Variability in measurement of abdominal aortic aneurysms. Abdominal Aortic Aneurysm Detection and Management Veterans Administration Cooperative Study Group.

PURPOSE: The purpose of this study was to report interobserver and intraobserver variability of computed tomography (CT) measurements of abdominal aortic aneurysm (AAA) diameter and agreement between CT and ultrasonography observed in the course of a large, multicenter, randomized trial on the management of small AAAs. METHODS: CT measurements of AAA diameter from participating centers were compared with measurements made from the same scan by a central laboratory. Blinded central remeasurement of a randomly selected subset of these CT scans was used to assess intraobserver variability. Agreement between AAA measurements by CT and ultrasonography done within 30 days of each other was also assessed. RESULTS: For interobserver pairs of local and central CT measurements of AAA diameter (n = 806), the difference was 0.2 cm or less in 65% of pairs, but 17% differed by at least 0.5 cm. For intraobserver pairs of central CT remeasurements (n = 70), 90% differed by 0.2 cm or less, 70% were within 0.1 cm, and only one differed by 0.5 cm. Of 258 ultrasound-measured and central CT pairs, the difference was 0.2 cm or less in 44% and at least 0.5 cm in 33%. Ultrasound measurements were smaller than central CT measurements by an average of 0.27 cm (p < 0.0001). Local CT and ultrasound measurements showed a marked preference for recording by half centimeter. CONCLUSIONS: A high degree of precision is possible in CT measurement of AAA diameter, but this precision may not be obtained in practice because of differences in measurement techniques. Differences between imaging modalities increase variability further. Variations in AAA measurement of 0.5 cm or more are not uncommon, and this should be taken into account in management decisions. Efforts to reduce variation in measurement are warranted and might include (1) seeking agreement between surgeons and radiologists on a precise definition of AAA diameter, (2) limiting the number of radiologists who measure AAAs, and (3) use of calipers and magnifying glass for CT measurements.

Aged↗

Pediatric renovascular hypertension: a thirty-year experience of operative treatment.

PURPOSE: This study was undertaken to characterize the changing operative treatment of pediatric renovascular hypertension and subsequent outcomes in a 30-year experience at a single institution. METHODS: Clinical data were analyzed on 57 pediatric patients, 24 girls and 33 boys, ranging in age from 10 months to 17 years, who underwent operations for renovascular hypertension from 1963 to 1993 at the University of Michigan. Renal artery disease included atypical medial-perimedial dysplasia, often with secondary intimal fibroplasia (88%), and inflammatory mural fibrosis (12%). Abdominal aortic narrowings affected 15 patients. Data were categorized into three chronologic eras (I:1963-1972, II:1973-1980, and III:1981-1993) to allow identification of therapeutic trends. RESULTS: Primary surgical procedures were undertaken 74 times. Ex vivo reconstruction was necessary once. Primary operations included aortorenal bypass with autogenous vein grafts (n = 26) or internal iliac artery grafts (n = 7); iliorenal bypass with vein grafts (n = 2); renal artery resection beyond the stenosis and reimplantation into the aorta (n = 10), the main renal artery (n = 2), an adjacent segmental renal artery (n = 3), or the superior mesenteric artery (n = 3); renal artery resection and reanastomosis (n = 3); focal renal arterioplasty (n = 2); operative dilation (n = 7); splenorenal bypass (n = 2); and primary nephrectomy (n = 7). Among 23 primary operations performed in era I, 56.5% were aortorenal bypasses with vein grafts, but in era III this form of revascularization represented only 3% of 33 primary operations. No reimplantations were performed in era I, whereas reimplantations accounted for 51.5% of era III procedures. Thirteen patients underwent staged or concomitant aortic reconstructions with thoracoabdominal aortoaortic bypass grafts (n = 5) or patch aortoplasty (n = 8). Fourteen patients underwent a total of 20 secondary operations, including seven secondary nephrectomies. Operative therapy benefited 98% of these children: hypertension was cured in 45 (79%), improved in 11 (19%), and unchanged in one (2%). There were no operative deaths. CONCLUSIONS: Contemporary surgical management emphasizes direct reimplantation of main renal arteries into the aorta, reimplantation of segmental arteries into adjacent renal arteries, patch aortoplasty for associated abdominal aortic coarctations, and single-stage revascularizations. Pediatric patients with renovascular hypertension clearly benefit from carefully executed operative therapy.

Adolescent↗

Transplantation of lac-Z-transduced microvascular endothelial cells into the skeletal muscle capillary bed of the rat hindlimb occurs independent of the duration of femoral artery occlusion after injection of cells.

The skeletal muscle capillary bed may be an ideal recipient site for transplantation of genetically modified autologous endothelial cells and thus provide a basis for a technique of somatic gene therapy that would be applicable to a variety of acquired and inherited human diseases. The purpose of this study was to test the hypothesis that adhesion of lac-Z-transduced microvascular endothelial cells (MVEC) in the skeletal muscle capillary bed in vivo is dependent on the duration of arterial occlusion after injection of the transduced MVEC. MVEC derived from the abdominal fat pad of syngeneic rats (Wistar F-455) were transfected with the BAG vector, a replication-incompetent retroviral vector containing the lac-Z gene for beta-galactosidase and the Tn5 gene for selection of the transduced cells by the neomycin analogue, G418. lac-Z-transduced MVEC were radiolabeled with 125I-PKH-95, and, after the femoral artery was occluded for 10 min, these cells (1 to 2 x 10(6)) were injected intraarterially into the rat hindlimb. In the experimental groups the femoral artery clamp was removed at 0, 60, or 120 min after injection. A control group without pre- or postinjection femoral arterial occlusion was also studied. Adhesion of MVEC in the skeletal muscle capillary bed (mean percentage of injected 125I activity) was determined in groups of 4 rats at 1 day, 1 week, and 1 month after injection. Adhesion of the transduced MVEC did not increase as the duration of femoral artery occlusion after injection was increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Design of the abdominal aortic Aneurysm Detection and Management Study. ADAM VA Cooperative Study Group.

PURPOSE: This study describes the design of an ongoing randomized trial intended to determine which of two strategies is superior for managing small abdominal aortic aneurysms (AAA). METHODS: Patients aged 50 to 79 years with AAA 4.0 to 5.4 cm in diameter as determined by computed tomography (CT) who are not at high surgical risk are randomized to either repair of the AAA, called "immediate surgery," or follow-up of the AAA with ultrasonography or CT every 6 months, reserving surgery for those aneurysms that enlarge to 5.5 cm, enlarge rapidly, or become symptomatic, called "selective surgery." RESULTS: The primary outcome measure is all-cause death, and secondary outcome measures are AAA-related death, morbidity, and general health status. The study design calls for 1350 patients to be randomized and monitored for a mean of 5 years. A second objective of the study is to accurately define the prevalence and risk factors for AAA with use of information from the large screening program established to detect AAA for recruitment into the randomized trial. CONCLUSIONS: By the end of 1993, 38,697 patients had been screened with ultrasonography, accounting for about three fourths of new randomizations, and 330 patients had been enrolled (70% of the target rate).

Aged↗

Clinical significance of routine imaging of iliac and calf veins by color flow duplex scanning in patients suspected of having acute lower extremity deep venous thrombosis.

BACKGROUND: Because duplex ultrasonography is used increasingly to evaluate patients suspected of having acute deep venous thrombosis of the lower extremity, the clinical significance of limiting venous duplex scanning to the common femoral, superficial femoral, and popliteal veins becomes an important question. METHODS: We prospectively studied by venous color flow duplex ultrasonography 181 patients referred for evaluation to rule out acute deep venous thrombosis to determine (1) the frequency with which the iliac and calf veins could be imaged adequately to determine the presence or absence of acute deep venous thrombosis, (2) the frequency of acute venous thrombosis in these venous segments, and (3) the time required to scan these additional segments. RESULTS: In 79% of the patients studied, one segment of the iliac venous system was imaged adequately to determine the presence or absence of venous thrombosis. In the lower extremity, the common femoral vein, the superficial femoral vein, and the popliteal vein were imaged adequately in 94% of the patients. In 76% of the patients all three calf veins were imaged adequately to determine whether acute deep venous thrombosis was present or absent. The anterior tibial vein was the most difficult vein to image consistently and was imaged adequately in 76% of the patients referred. The mean time to scan the affected limb was 8 minutes 37 seconds. Forty-seven patients (26%) of the 180 patients studied had positive venous scans. Twenty-three percent of the patients who had positive scans were found to have iliac vein involvement. Thirty-two percent who had positive venous scans were found to have thrombosis of the calf veins. Fifteen percent of the 47 patients who had positive scans had either an isolated iliac or calf vein thrombosis. CONCLUSIONS: We believe this frequency of isolated iliac or calf vein thrombosis coupled with the frequency of successful imaging of these venous segments and the short additional time required to image these segments justifies the inclusion of routine imaging of the iliac and calf veins in patients undergoing venous duplex scanning to rule out acute deep venous thrombosis.

Acute Disease↗

Adhesion and incorporation of lacZ-transduced endothelial cells into the intact capillary wall in the rat.

Use of the capillary bed of skeletal muscle as an in vivo recipient site to transplant autologous endothelial cells that have undergone gene transfer ex vivo has considerable potential as a technique of somatic gene therapy. Here we document a previously unrecognized capacity of endothelial cells to adhere and incorporate spontaneously into confluent endothelial cell monolayers in vitro and in vivo. This spontaneous adhesion and incorporation of endothelial cells enabled us to seed lacZ-transduced endothelial cells into the wall of skeletal muscle capillaries of the hindlimb of the rat. Certain transduced endothelial cells became incorporated within the capillary wall, whereas others remained within the capillary lumen where they formed focal, electron-dense, contacts with host endothelium. lacZ expression in the capillary bed was documented for up to 1 month after transplantation. Use of the intact capillary bed of skeletal muscle as an in vivo recipient site for transduced, autologous endothelial cells holds promise as a strategy for somatic gene therapy to treat various genetic and acquired human diseases.

Animals↗

Effect of calcium on the vasoactive response of arterioles to light during fluorescent intravital microscopy of the tibialis anterior muscle of the hamster.

Arterioles may undergo a transient vasoactive response when exposed to light during fluorescent intravital microscopy. We hypothesized that the type and frequency of the vasoactive responses by arterioles to light is calcium dependent. In order to test this hypothesis we quantitated the type and frequency of vasoactive responses by arterioles to light in the presence and absence of calcium within the suffusate bathing the muscle. In addition, we determined whether the presence or absence of calcium also influenced the reactivity of these arterioles to adenosine and norepinephrine. In separate experiments, we determined the effect of increases in suffusate calcium concentration on the resting diameter of arterioles. The concentration of calcium in the suffusate significantly influenced the frequency of light-induced vasoactivity of the arterioles of the tibialis anterior muscle: a normal suffusate calcium concentration of 2 x 10(-3) M was associated with an incidence of light-induced vasoreactivity of 77% but decreased significantly to 58% when calcium was removed from the suffusate. Although the frequency of the vasoactive response to light was different for the two experimental conditions, the type of vasoactive response, predominately vasomotion, was similar. The vasoactive responses of arterioles to adenosine and norepinephrine were similar in the presence and absence of calcium in the suffusate. However, the concentration of calcium in the suffusate did significantly influence resting arteriolar diameters: 2 x 10(-3) M calcium CaCl2 caused a mean decrease in the arteriolar diameter of 11.6 (+/- 3.0)%, 4 x 10(-3) M CaCl2 caused a mean decrease of 41.2 (+/- 12)%, and 8 x 10(-3) M CaCl2 caused a mean decrease of 55.4 (+/- 14.4)%. These results show that the concentration of calcium in the suffusate bathing the tibialis anterior muscle during fluorescent intravital microscopy significantly influences the vasoactive response of arterioles to light. Further investigation of the mechanisms of light-induced effects on microcirculation during fluorescent intravital microscopy will become important as this technique is used more widely in the study of the microcirculation of solid tissues and organs.

Adenosine↗

Renal revascularization for recurrent pulmonary edema in patients with poorly controlled hypertension and renal insufficiency: a distinct subgroup of patients with arteriosclerotic renal artery occlusive disease.

Recurrent pulmonary edema in patients with poorly controlled hypertension and renal insufficiency appears to be a marker of bilateral renal artery occlusive disease. The effectiveness of renal revascularization to prevent recurrent pulmonary edema in this distinct subgroup with renal artery occlusive disease was analyzed in 17 consecutive patients treated at the University of Michigan Hospital between 1984 and 1990. Their mean preoperative blood pressure was 207/110 mm Hg, and mean serum creatinine clearance was 3.8 mg/dl. Pulmonary edema occurred despite evidence of normal ventricular function in 65% of these patients. Bilateral renal artery occlusive disease affected 94% of the patients, and 54% had an occluded renal artery. Renal revascularization was accomplished by iliorenal bypass (41%), aortorenal bypass (29%), endarterectomy (24%), and transluminal angioplasty (6%). Contralateral nephrectomy (41%) and concomitant aortic reconstruction (24%) were also required frequently. No postoperative deaths occurred, and no patient had early postoperative pulmonary edema. Control of hypertension was improved in all patients, two of whom were discharged from the hospital on no antihypertensive medications. Two of the three patients requiring dialysis before operation were able to discontinue dialysis after operation. Late follow-up (mean, 2.4 years) revealed hypertension to be cured in one patient (6%), and improved in 16 patients (94%). Pulmonary edema occurred in one patient during late follow-up. Late follow-up showed renal function (mean creatinine, 1.7 mg/dl) to be improved in 77%, stable in 12%, and worse in two patients; one required dialysis. A single episode of pulmonary edema in a patient with poorly controlled hypertension and renal insufficiency should prompt consideration of this clinical syndrome and early diagnostic angiography.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

High-level expression of recombinant human tPA in cultivated canine endothelial cells under varying conditions of retroviral gene transfer.

Successful genetic transduction of endothelial cells (EC) provides a theoretic means of increasing luminal secretion of tissue-type plasminogen activator (tPA) and lessening arterial and venous thrombotic processes. To identify the duration and number of retroviral exposures for an optimal tPA expression, enzymatically derived adult canine jugular venous EC were subjected to different exposure regimens using an amphotropic murine retroviral vector, MFG, containing the human tPA gene. Human tPA antigen secretion and its functional activity were determined at 2 days (subconfluent cells) and 14 days (confluent cells) after retroviral exposure. High-level secretion of human tPA was detected among transduced EC in all experimental groups. No secretion of human tPA occurred in control EC exposed to media alone. At 2 days after transduction, no significant differences in tPA secretion rates occurred among the different exposure regimens. At 14 days, the 12-hour X two-exposure group exhibited higher tPA secretion rates than all other exposure regimens (analysis of variance, p < 0.05). All exposure groups at 14 days exhibited significantly higher tPA secretion compared with those at 2 days (analysis of variance, p < 0.05). The presence of retroviral sequences in the genome of transduced EC was confirmed by Southern blot analysis. At 14 days, increased EC numbers were observed in vector-exposed wells compared with controls. Human tPA functional activity paralleled tPA antigen secretion. Genetically modified canine EC are capable of high levels of constitutive expression of human tPA after relatively short exposures to a retroviral vector containing the reporter gene. Increased cell number of tPA-transduced EC in culture suggests that tPA also may have other biologically important effects. These results support the efficacy of MFG-tPA gene transfer as a means of genetically modifying EC fibrinolytic activity and establishes the potential of this technology in vivo.

Animals↗

Clinical characteristics and surgical management of vascular complications in patients undergoing cardiac catheterization: interventional versus diagnostic procedures.

The purpose of this report is to define the clinical characteristics and outcome of surgical management of vascular complications after interventional cardiac catheterization and to contrast them to those after diagnostic cardiac catheterization. From October 1985 to December 1989, 101 patients were treated for 106 vascular complications after 1866 interventional and 5046 diagnostic cardiac catheterizations at the University of Michigan Medical Center. Interventional catheterizations resulted in 69 vascular complications in 64 patients (frequency 3.4%). The most common interventions included coronary angioplasty (34), of which 10 required percutaneous partial cardiopulmonary bypass, intraaortic balloon pump placement (14), and aortic valvuloplasty (11). Interventional catheter-related complications included hemorrhage (33), arterial thrombosis (18), pseudoaneurysm formation (12), catheter embolization (2), thromboembolism (2), as well as arteriovenous fistula, pseudoaneurysm, and arterial dissection (1 each). Fifteen of these 69 patients (24%) had suffered acute myocardial infarction just before their catheterization. Surgical repair was performed under local anesthesia in 70% of patients. Major vascular reconstructions were required in 9% of patients. Three percent of the involved lower extremities had to be amputated because of complications occurring after arterial puncture. Eight percent of the patients incurring vascular complications after interventional procedures died after operation. Diagnostic catheterizations resulted in 37 vascular complications in 37 patients (frequency 0.7%). In contrast to diagnostic cardiac catheterization, vascular complications after interventional cardiac catheterization occurred more frequently, were most often due to hemorrhage at the vascular access site, and occurred in high-risk, critically ill patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Splanchnic and cerebral vasodilatory effects of calcitonin gene-related peptide I in humans.

The ability of synthetic human calcitonin gene-related peptide (CGRP I) to act as an arterial vasodilator was tested in healthy men by measuring arterial blood flow parameters in carotid, superior mesenteric, celiac, and femoral vessels. Calculated volume flow was significantly increased (140 +/- 21% of basal) in the SMA with a 2-ng/kg/min infusion of CGRP. Carotid artery volume flow increased dose dependently (96 +/- 6%, 122 +/- 15%, 135 +/- 15% of basal, respectively, with 2, 4, or 8 ng/kg/min). With steady-state infusion, carotid and superior mesenteric arterial flow parameters remained significantly elevated for 30 minutes after cessation of peptide administration. Blood pressure was unchanged. Pulse increased dose dependently. Arterial diameters were unchanged, implying activity at the arteriolar level.

Adult↗

Rapid and complete recovery of responsiveness to adenosine and norepinephrine by regenerating arterioles of the tibialis anterior muscle of the hamster after in situ autografting.

Intravital microscopy studies of small bundles of fibers of the extensor digitorum longus muscle grafted onto the hamster cheek pouch revealed a persistent reduction in the responsiveness of regenerated arterioles to vasoactive agents. We tested the hypothesis that the recovery of responsiveness to vasoactive agents by regenerating arterioles within whole, in situ autografted tibialis anterior muscles occurs earlier and more completely than that reported for regenerating arterioles within bundles of fibers of the extensor digitorum longus muscle grafted ectopically to the hamster cheek pouch. The tibialis anterior muscles of Syrian golden hamsters were excised and soaked in bupivacaine (0.75%) for 10 minutes to ensure uniform degeneration of muscle fibers. The tendons were resutured, and the graft became revascularized spontaneously. Fluorescent intravital microscopy was used to measure the responsiveness of 10-40-microns arterioles to topically applied adenosine and norepinephrine at 7, 14, and 30 days after grafting. Nine to 25 arterioles were studied at each time period. Both intravital and light microscopy were used at each time period to characterize the structural development of the microcirculation. We found that the responsiveness of regenerated arterioles returned to control values for topically applied norepinephrine by 14 days and for adenosine by 30 days. Light microscopy showed regenerated blood vessels in the center of the grafts early in the second week after grafting. The structure of the microcirculation at 7 days was characterized by a plexiform microvascular pattern, long spiderlike capillaries, and arterioles and venules that had irregular walls and an irregular branching pattern. Rhodamine-labeled albumin extravasated spontaneously. The 14-day grafts had a more linear capillary pattern, and the arterioles and venules often contained loops that had circular flow patterns. By 30 days, a parallel capillary structure had developed, no vascular loops were present, and the arteriolar-venular pattern was nearly normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

In vivo assessment of acute microvascular injury after reperfusion of ischemic tibialis anterior muscle of the hamster.

The purposes of this study were to develop an in vivo model of skeletal muscle ischemia--reperfusion to assess the patterns of microvascular injury, to evaluate a scoring system that permits quantitation of this injury, and to determine in vivo the extent of white blood cell adhesion within the microcirculation during the acute postreperfusion period. Syrian golden hamsters underwent 3.0 or 4.5 hr of lower extremity ischemia without anticoagulation. The microcirculation of the tibialis anterior muscle was visualized by fluorescent intravital microscopy (700X). During the first 1.5 hr of reperfusion the microvascular injury was scored by a grading system based upon the extent of extravasation of fluorescein-labeled albumin and the degree and level of microvessel obstruction. To correlate the observed changes in the microcirculation to changes in the whole muscle, in a separate group of animals, pH changes in the tibialis anterior muscle were measured at the same time intervals under identical experimental conditions as the microvascular measurements. White blood cells were transiently fluoresced at 1.5 hr after reperfusion by intravenous acridine red and the number of white blood cells rolling (rollers) or sticking (stickers) to the endothelium during a 30-sec observation period was recorded. Two distinct patterns of microvascular injury were seen: after 3.0 hr of ischemia there was a progressive extravasation, some capillary but no arteriolar or venular obstruction, flow velocities increased over time; after 4.5 hr of ischemia there was a greater heterogeneity of injury, primary "no reflow," extensive capillary, arteriolar, and venular obstruction, as well as a progressive decline in flow velocities. Thrombosis of microvessels was rare. There was no inflow vessel thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Relief of mesenteric ischemia in type III aortic dissection with percutaneous fenestration of the aortic septum.

Subacute mesenteric ischemia developed 2 months after initial presentation in a patient with a type III aortic dissection. Percutaneous transfemoral fenestration of the septum between the true and false lumens resulted in resolution of clinical, angiographic, and manometric signs of ischemia. Continued expansion of the false lumen required aortic resection and graft replacement of the distal thoracic and abdominal aorta 2 months after the fenestration procedure. At operation, the fenestration site appeared as a 2-cm horizontal tear in the aortic septum, free of adherent thrombus and unrelated to expansion of the false lumen.

Aortic Dissection↗