Analysis of low-speed rotational atherectomy for the reduction of platelet aggregation.

Platelet activation is an important determinant of acute outcomes of percutaneous intervention. The objective of this study was to assess the effect of rotational atherectomy on platelet activation in an in vitro model. Freshly collected heparinized porcine blood was exposed to a 2.0-mm Rotablator burr rotating at one of three speeds: 180,000, 140,000, or 0 rpm. The specimens were analyzed immediately for concentration and size of platelet aggregates and plasma-free hemoglobin. There were significantly more platelet aggregates of >20-microm diameter at higher speeds (7,434+/-2,193 at 180,000, vs. 2,269+/-627 at 140,000, vs. 633+/-258 aggregates/ml at 0 rpm; P < 0.001). Plasma-free hemoglobin, a simple measure of cell damage, decreased with decreasing rotational speed (429+/-168 mg/dl at 180,000, vs. 88+/-44 mg/dl at 140,000, vs. 9+/-9 mg/dl at 0 rpm; P < 0.0001). In vitro, platelet activation decreases with decreasing burr speed, suggesting that the use of the Rotablator system at its minimum approved speed (140,000 rpm) could prove clinically beneficial.

Analysis of heat generation during rotational atherectomy using different operational techniques.

Rotational atherectomy can generate heat from the friction of the burr as it ablates atherosclerotic plaque. The objective of this study is to correlate Rotablator technique and heat generation using two experimental models. First, 2.0 mm burrs were advanced through a lesion model derived from bovine bone implanted with thermal probes. Intermittent ablation with minimal decelerations resulted in a smaller temperature increase than continuous ablation with maximal decelerations (2.6 +/- 1.3 vs. 13.9 +/- 1.0 degrees C, respectively, P < 0.01). The second model used porcine femoral arteries cradled in constricting polyethylene grafts with thermal probes in contact with the adventitia. As the burr advanced through the segment, RPM decreases of 5-7 k resulted in a temperature rise of 4.1 +/- 1.2 degrees C, whereas decelerations of 10-20 k resulted in a 11.3 +/- 6.2 degrees C temperature increase. We conclude that excessive drops in speed and aggressive advancement of the burr are related to significant increases in temperature and potential thermal injury.

Quantitative angiography of coronary artery dimensions 24 hours after rotational atherectomy.

Rotational atherectomy results in platelet activation and heat generation, which may impact artery size immediately after treatment. In addition, arteries treated with balloon angioplasty may exhibit recoil within 24 hours. In this study, arteries treated with rotational atherectomy, with and without adjunctive balloon angioplasty, were analyzed by quantitative coronary angiography to determine the effect of rotational atherectomy on the dynamic behavior of the arterial wall within 24 hours after the procedure. Quantitative coronary angiography was performed at a core laboratory. Coronary angiogram acquisitions were preceded by intracoronary nitroglycerin injections and were repeated using identical angles of projection. Proximal and distal reference vessel diameters were 2.55 +/- 0.60 and 2.28 +/- 0.51 mm, respectively, and did not change from pre- to postprocedure. Both were larger the following day increasing to 2.72 +/- 0.65 and 2.52 +/- 0.52 mm, respectively, (p <0.001). Minimum luminal diameter (MLD) increased from 0.70 +/- 0.28 mm before to 1.49 +/- 0.34 mm after the procedure and to 1.72 +/- 0.37 mm at 24-hour follow-up (p <0.001). Subset analysis of patients treated with rotational atherectomy alone or rotational atherectomy with adjunctive balloon angioplasty revealed that the increase in luminal diameters occurred in both subsets. Patients treated with adjunctive angioplasty had a smaller initial MLD, a larger postprocedure MLD, and no difference in MLD at 24-hour follow-up compared with stand-alone rotational atherectomy. Subset analysis of 100 patients who had 6-month follow-up angiography revealed that both a calculated acute gain and chronic late loss, based on a 24-hour film, differed significantly from values using a film acquired immediately after the procedure. However, the slope of the linear regression between acute gain and chronic late loss did not differ. Coronary arteries treated with rotational atherectomy with or without adjunctive balloon angioplasty increase significantly in size during the first 24 hours after the procedure. This phenomenon has implications for the calculation of absolute gain and chronic late loss, but not for the linear relation between the 2 quantitative outcomes.

Comparison of patients with either < 70% diameter narrowing or > or = 70% narrowing of the right coronary artery when performing rotational atherectomy on > or = 1 narrowing in the left coronary arteries.

This study compares the complication rates of patients undergoing rotational atherectomy of the left coronary system who had either minimal or significant narrowing of the right coronary artery (RCA). A series of 1,872 patients from a multicenter registry who were treated for left coronary artery disease were divided into <70% diameter stenosis (mild) and > or = 70% stenosis (severe) of the RCA. The patient demographics, lesion characteristics, and frequency of procedural complications for each group were compared. Of the 1,872 patients undergoing rotational atherectomy of the left coronary system, 86.3% (n = 1,616) had mild RCA disease and 13.7% (n = 256) had severe RCA disease. Comparing the mild and severe groups, death (0.8% vs 3.1%, p <0.005), non-Q-wave myocardial infarction (5.1% vs 8.6%, p <0.04), and bypass surgery (2.7% vs 5.8%, p <0.02) were increased in the severe group. Within the severe group, 7 of 8 deaths were in the 128 patients with total occlusion of the RCA. Multivariate analysis demonstrated that RCA stenosis increases the risk of death by 4.9, bypass surgery by 2.6, and non-Q-wave myocardial infarction by 1.8. Patients treated for left coronary disease who have > or = 70% stenosis of the RCA have increased complications during rotational atherectomy.

Comparison of early and recent results with rotational atherectomy.

OBJECTIVES: We compared an early registry of rotational atherectomy with a recent registry to examine the evolution of patient profiles, lesion characteristics and procedural outcomes for patients treated with rotational atherectomy. BACKGROUND: With increased experience, the selection of patients and lesions treated with a device matures. This study documents the changes in the application of rotational atherectomy. METHODS: The patient characteristics and procedural outcomes from two multicenter patient registries-Registry I: 2,953 procedures, 3,717 lesions from 1988 to 1993; and Registry II: 200 procedures, 268 lesions from 1994-were analyzed and compared. RESULTS: There was an increase in the average age of the patients (63 vs. 65 years, p < 0.02) and the proportion of patients with unstable angina (42.9% vs. 56.5%, p < 0.01) or previous coronary artery bypass graft surgery (18.8% vs. 24.5%, p < 0.05) in Registry II. Registry II included fewer left anterior descending coronary lesions (46.5% vs. 32.8%, p < 0.01), more type B and C lesions (83.1% vs. 91.8%, p < 0.01), more eccentric lesions (69.0% vs. 79.5%, p < 0.01) and more calcified lesions (50.3% vs. 69.4%, p < 0.01). Complications, including urgent bypass surgery, Q and non-Q wave myocardial infarction, dissection, acute occlusion and perforation, were similar in the two groups. However, mortality increased from 1.0% to 3.0% (p < 0.05) in Registry II. CONCLUSIONS: Comparison of recent and early patients treated with rotational atherectomy revealed an increase in the complexity of patients and lesions. Although the rate of death was increased, the overall rate of major complications was not significantly changed (4.7% vs. 6.0%, p = NS).

Guidewire bias: potential source of complications with rotational atherectomy.

The guidewire in rotational atherectomy is an integral component in the ablative process. It functions not only to deliver the device but sets the cutting vector when the burr advances. Since the guidewire is a stiff stainless steel monofilament and the vessels are frequently tortuous and angulated, the guidewire may not be centrally oriented, but may bias preferentially to one side of the arterial wall. This may result in tangential or radial cutting. The following cases illustrate the dependence of the ablative process on the lie of the guidewire and the importance of integrating this factor in proper use of the Rotablator system.

Patch testing in actinic prurigo.

42 out of 93 Saskatchewan Indians (32 female (F) and 10 male (M] with actinic prurigo were patch tested to standard series allergens between 1983 and 1987. Positive reactions were most frequently seen with nickel (3F:2M) and colophony. All 3 positive patch tests to colophony were in males. The same patients were also patch tested to extracts of 21 Saskatchewan plants and 3 Hollister-Stier plant extracts. Only 1 male and 2 females had positive patch tests. None of these 3 had rashes on the eyelids, behind the ears or under the chin. We conclude that plant contact dermatitis is unlikely to be mistaken for actinic prurigo in Saskatchewan.

The prognostic value of response to the first cycle of chemotherapy in small cell lung cancer. Results of a multicenter German trial.

The prognostic significance of evaluation of response according to chest X-ray after only one cycle of treatment was investigated in patients with small cell lung cancer (SCLC). Three hundred and six patients entered a multicenter randomized German trial testing alternating vs. sequential chemotherapy. Decrease of tumor size after the first cycle was seen to be 78% in the alternating group and 70% in the sequential group. Stable disease occurred in 25% of the sequentially treated and 19% of the alternatingly treated patients. No substantial differences in pretreatment characteristics were noticed between patients with stable disease in sequential and alternating treatment. In sequential therapy, median survival was 323 days for patients with decrease of tumor size after the first cycle and 219 days for patients with no change. Only five out of 21 patients with no change after one cycle responded to continuous administration of this regimen including one complete remission. In alternating therapy, median survival was 347 days for patients with decrease in tumor size after the first cycle and 378 days for patients with no change indicating no difference in prognosis. Twelve out of 18 patients with no change responded to continuous administration of alternating treatment including six complete remissions. We concluded that response to the first cycle according to chest X-ray is a reliable and prognostically valid response criterion if sequential therapy is used. In this treatment modality no change in tumor size after the first cycle indicates poor prognosis, and improvement of the patients' outcome may be achieved by a switch to a second non-cross resistant drug combination.

Fenoterol depot and fenoterol in premature uterine contractions--a multicentric double-blind comparative study.

In a double-blind randomized study, the effect of a single dose of a fenoterol preparation with delayed release of active substance (designated as fenoterol depot) was compared with a fenoterol product with undelayed release of active substance (designated as fenoterol) in two groups respectively comprising 66 and 65 female patients with premature uterine contractions. The fenoterol depot was administered p.o. in a single total dose of 21 mg at the beginning of an investigation period of 360 minutes and the fenoterol was administered p.o. within 235 minutes in three identical consecutive doses resulting in a total dose of 22.5 mg. The increased uterine activity present at the beginning was markedly lowered by an initial intravenous infusion of Partusisten. After administration of the two oral preparations, the uterine contractions remained at the low level achieved. The fenoterol depot was slightly superior to fenoterol with regard to the reduction of the duration of contractions: the difference in the inhibition of the duration of the contraction between the two preparations was a maximum of 25.7% in favor of fenoterol depot. The frequency of uterine contraction was substantially reduced by both preparations, but to a greater extent by the depot form. The tocolytic efficacy and the tolerance were rated as "good" in 70% and 75% respectively with fenoterol depot and in 69% and in 71% respectively in the case of fenoterol. The maternal pulse rate remained at the level reached at the end of Partusisten infusion with the two preparation, and the blood pressure fluctuated slightly within the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Preferential binding of vasoactive intestinal polypeptide to basolateral membrane of rat and rabbit enterocytes.

Binding of radioiodinated vasoactive intestinal polypeptide (VIP) to intestinal cell membranes of the rabbit ileum and rat jejunum was investigated. Specific binding of 125I-labeled VIP could be demonstrated only on the basolateral membrane and not on the brush border membrane. This corresponded with the lack of an effect on ion transport when VIP was applied to the mucosal side of an in vitro preparation of rabbit ileum. VIP altered ion transport only when it was applied to the serosal side. The binding of 125I-VIP was specific and dependent upon incubation temperature. There was a close correlation between the potency of VIP for inhibition of 125I-VIP binding and that for increasing adenylate cyclase activity. These observations demonstrate that VIP receptors are located on the basolateral membrane.

Organic and inorganic solute transport in renal and intestinal membrane vesicles preserved in liquid nitrogen.

The transport of organic solutes (sugars, amino acids, and metabolic intermediates) and inorganic solutes (Na+/H+ exchange and Na+-SO = 4 cotransport) in renal brush border and in intestinal brush border and basal lateral membrane vesicles is preserved when the vesicles are stored in liquid nitrogen. The preservation allows comparisons among transport systems of renal and intestinal cells obtained from the same animal.

Transport properties of intestinal basolateral membranes.

Techniques for the isolation and study of basolateral membrane vesicles from the intestinal epithelium have afforded new insights into the mechanisms of intestinal absorption. First, we have confirmed the hypothesis that the second stage of glucose transport involves facilitated diffusion. Second, we have shown that the major system for translocation of neutral amino acids across the basolateral membrane is the classical "L" system. Third, we have established that basolateral membranes contain sodium-dependent transport systems that may be useful in the supply of essential amino acids to the epithelium from the blood. And, finally, our studies of the basolateral (Na + K)-ATPase have clarified the role of this enzyme in sodium absorption.

Some characteristics of Na/K-ATPase from rat intestinal basal lateral membranes.

Basal lateral membrane vesicles were isolated from rat intestinal epithelial cells. The sodium potassium triphosphatase (Na/K-ATPase) of these plasma membranes has been characterized by (1) the molecular weight of the phosphorylated intermediate, (2) the sensitivity of the phosphorylated intermediate to hydroxylamine, (3) its ouabain binding constants, and (4) its susceptibility to digestion by pronase. The phosphorylated intermediate was shown by SDS polyacrylamide gel electrophoresis to be a protein of 100,000 Daltons apparent mol wt. Its extensive hydrolysis in hydroxylamine demonstrated that it was an acyl phosphate. The isolated basal lateral membranes bound ouabain with a dissociation constant, Km (1.5 x 10(5) M), similar to the inhibitory constant KI (3 X 10(-5) M), measured for ouabain inhibition of the Na/K-ATPase activity. The association rate constant measured for ouabaiation rate constants reported for other tissues and species. The high dissociation rate constant 3.6 x 10(-2) sec-1, is consistent with the insensitivity of the rat to ouabain. Digestion of the intact cells by pronase yielded basal lateral membranes in which the Na/K-ATPase had been unaffected. The phosphorylated intermediate ran as a sharp band at 100,000 Daltons on electrophoresis, and the ouabain dissociation constant appeared to be unchanged. In these membranes, protein stains of polyacrylamide gels revealed digestion of the major high mol wt proteins including the major protein at 100,000 Daltons. This suggests that the Na/K-ATPase represents a minor component, less than 1%, of the basal lateral membrane protein. From these characteristics of the phosphorylated intermediate and the ouabain binding constants, we conclude that the Na/K-ATPase of the basal lateral membranes of rat intestinal epithelial cells is similar to that found in other tissues and species. Estimates of the number of pump sites and the turnover number predict rates of Na transport that are consistent with observed values.