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3.
Ann N Y Acad Sci ; 800: 89-96, 1996 Nov 18.
Article in English | MEDLINE | ID: mdl-8958985

ABSTRACT

Propranolol has been suggested to slow aortic aneurysm (AAA) expansion by a mechanism independent of simple blood pressure (BP) reduction. To investigate this hypothesis, we designed a series of experiments to examine the effects of hypertension and propranolol upon AAA expansion. Using an established animal model, we induced AAA in normotensive and genetically hypertensive rats by perfusion of the isolated infrarenal aorta with elastase for two hours. Systolic tail BP was monitored with a plethysmograph. AAA size was measured directly with a micrometer on postoperative days 7 and 14. All data are expressed as the mean +/- standard deviation (SD). BP (mmHg) was significantly higher in hypertensive rats: 164 +/- 15 versus 119 +/- 7 (p < 0.001). AAA were also significantly larger in hypertensive rats with a mean expansion rate (mm/day) nearly twice that of normotensive animals: 0.13 +/- 0.09 versus 0.07 +/- 0.03. In a second series of animals, propranolol treatment was compared to placebo. In those animals, hypertensive propranolol-treated rats had significantly smaller AAA than placebo-treated controls (p < 0.05). There was no difference in normotensive animals but these rats had an unexplained paradoxical rise in BP with treatment. In this model, hypertension increases the expansion rate of AAA. Propranolol reduced the size of AAA in hypertensive animals, at least in part because of a decrease in BP. Other possible mechanisms of propranolol's action may be operative and require further study.


Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Antihypertensive Agents/therapeutic use , Aortic Aneurysm, Abdominal/pathology , Hypertension/complications , Propranolol/therapeutic use , Aged , Animals , Aortic Aneurysm, Abdominal/complications , Aortic Aneurysm, Abdominal/drug therapy , Aortic Rupture/etiology , Aortic Rupture/prevention & control , Humans , Hypertension/drug therapy , Middle Aged , Rats , Rats, Inbred WKY , Rats, Mutant Strains
4.
Ann N Y Acad Sci ; 800: 121-30, 1996 Nov 18.
Article in English | MEDLINE | ID: mdl-8958987

ABSTRACT

This study was designed to characterize the hemodynamic and biochemical properties of the abdominal aorta in four genetically related inbred rat strains that express genetic hypertension and hyperactive behavior in varying combinations. These include (1) the spontaneously hypertensive rat (SHR), which is hypertensive, hyperactive, and hyperreactive to stress; (2) Wistar-Kyoto (WKY) rats, which express none of these traits; (3) WKHT rats, which are hypertensive but not hyperactive; and (4) WKHA rats, which are hyperactive and hyperreactive to stress, but normotensive. Together, these four strains allowed us to examine the structural and functional changes in the aorta in the hypertensive SHR, the most widely used animal model of genetic hypertension, while controlling for the variables of hyperactivity and hyperreactivity that are also expressed in the SHR. Four groups of animals of both sexes were studied: (1) WKY, n = 101, (2) WKHA, n = 33, (3) WKHT, n = 91, and (4) SHR, n = 28. Blood pressure (BP) was determined by tail plethysmography as well as direct intraarterial monitoring under anesthesia. Fixed specimens were prepared for histologic analysis and the wall thickness determined morphometrically. Quantification of soluble tissue protein, elastin, and collagen in the aortic tissue was determined by measuring leucine (leu), hydroxyproline (HP/leu), and desmosine (DES/leu). The hypertensive strains (SHR and WKHT) had significantly higher tail BP than the normotensive strains (WKY and WKHA)-WKY: 128.7 +/- 22.3; WKHA: 126.7 +/- 14.6; WKHT: 162.8 +/- 21.2; SHR: 164.2 +/- 36.1 (p < 0.0001). Additionally, intraaortic diastolic BP and mean BP were higher in SHR rats than in WKHT. Morphometric studies showed the media thickness in the SHR rats was significantly greater than in the WKY and WKHA rats and no different than in the WKHT rats. Significantly less of the aortic wall protein was present as elastin in the hypertensive rats (SHR and WKHT), as well as the hyperactive rats (WKHA), compared to rats that had neither trait (WKY). These studies provide new information regarding aortic structure and function in genetic hypertension using inbred strains to control for the hyperactivity/hyperreactivity traits that coexist with hypertension in the SHR. They reveal that hypertensive aortas have altered matrix proteins that cannot be explained simply on the basis of blood pressure alone.


Subject(s)
Aorta/physiology , Rats, Inbred Strains/anatomy & histology , Rats, Mutant Strains/anatomy & histology , Amino Acids/analysis , Animals , Aorta/physiopathology , Aorta, Abdominal/chemistry , Aorta, Abdominal/pathology , Blood Pressure , Collagen/analysis , Elastin/analysis , Female , Hyperkinesis/metabolism , Hyperkinesis/pathology , Hypertension/genetics , Hypertension/physiopathology , Male , Organ Size , Rats , Rats, Inbred SHR , Rats, Inbred Strains/genetics , Rats, Inbred Strains/physiology , Rats, Inbred WKY , Rats, Mutant Strains/genetics , Rats, Mutant Strains/physiology
5.
J Pediatr Surg ; 31(5): 731-2, 1996 May.
Article in English | MEDLINE | ID: mdl-8861496

ABSTRACT

The use of laparotomy and splenectomy for staging purposes in patients with Hodgkin's disease (HD) gained popularity in the early 1970s. Accurate staging and more effective treatment regimens, including combined chemotherapy and irradiation, have resulted in improved patient survival rates. Similarly, an increased number of late complications have been reported, including the development of thyroid disease, second malignancies, and septic complications related to splenectomy. Partial splenectomy has been proposed as one method of preventing overwhelming postsplenectomy sepsis. The authors present a case of recurrence of HD, which occurred in the splenic remnant 13 years after the initial treatment. This case demonstrates that the spleen is a potential for recurrent intraabdominal Hodgkin's disease after partial splenectomy; thus, the use of partial splenectomy for HD should be discouraged.


Subject(s)
Hodgkin Disease/surgery , Neoplasm Recurrence, Local/surgery , Splenectomy , Splenic Neoplasms/surgery , Chemotherapy, Adjuvant , Child , Combined Modality Therapy , Female , Hodgkin Disease/drug therapy , Hodgkin Disease/pathology , Humans , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Reoperation , Spleen/pathology , Splenic Neoplasms/drug therapy , Splenic Neoplasms/pathology
6.
J Vasc Surg ; 23(2): 301-7, 1996 Feb.
Article in English | MEDLINE | ID: mdl-8637107

ABSTRACT

PURPOSE: Inflammation has been implicated as a contributing factor in the expansion of abdominal aortic aneurysms (AAA). To test this hypothesis, we examined the effects of a monoclonal antibody (MAB) to the leukocyte CD18 adhesion molecule on the expansion of experimental AAA. METHODS: Aneurysms were induced by perfusion of an isolated segment of the infrarenal aorta with elastase in 22 normotensive (WKY) and 17 genetically hypertensive (WKHT) rats. Animals of both strains were randomly allocated to control or MAB-treated groups (MAB, 5 microgram/100 gm body weight intraperitoneally, daily, beginning on the operative day for a total of four doses). The activity of the MAB against rat leukocytes had first been determined by in vitro immunofluorescence flow cytometry. Aortic size was directly measured initially and on day 14. At that time, a segment of aorta was stained with hematoxylin and eosin and mononuclear leukocytes and neutrophils were counted in each of 10 microscopic fields (400X). RESULTS: The initial aortic size in all animals was 1.11+/-0.15 mm. All groups developed aneurysms significantly larger than the initial aortic size (p<0.01). However, the MAB-treated animals had significantly smaller aneurysms than the untreated controls (mm): WKY: 3.63+/-1.26, WKY-MAB: 2.08+/-0.30, WKHT: 4.54+/-1.86, WKHT-MAB: 2.37+/-0.40, p<0.0001. There also were significantly fewer monocytes in the MAB-treated normotensive rats: WKY:35.5+/-29.9, WKHT:40.6+/-28.8, WKY-MAB: 8.9+/-8.5, WKHT-MAB: 32.3+/-25.7, p=0.03. Neutrophil counts did not differ significantly between the groups. CONCLUSIONS: Treatment with anti-CD18 monoclonal antibody slows the expansion of AAA in this experimental model. The associated inflammatory process at day 14, as indicated by monocyte infiltration, is reduced, but this effect may be opposed by the presence of hypertension. Further evaluation of the role of leukocytes and adhesion molecules in the expansion of AAA is warranted.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Aortic Aneurysm, Abdominal/prevention & control , CD18 Antigens/immunology , Animals , Antibodies, Monoclonal/immunology , Aorta, Abdominal/immunology , Aorta, Abdominal/pathology , Aortic Aneurysm, Abdominal/immunology , Aortic Aneurysm, Abdominal/pathology , Disease Models, Animal , Disease Progression , Flow Cytometry , Injections, Intraperitoneal , Leukocyte Count , Leukocytes/immunology , Leukocytes, Mononuclear/immunology , Neutrophils/immunology , Pancreatic Elastase/adverse effects , Rats , Rats, Inbred SHR , Rats, Inbred WKY
7.
J Vasc Surg ; 20(2): 178-83, 1994 Aug.
Article in English | MEDLINE | ID: mdl-8040940

ABSTRACT

PURPOSE: It has been suggested that propranolol has unique effects that slow aneurysm expansion by remodeling the structural proteins of the aorta. These effects are believed to be independent of blood pressure reduction, a hypothesis we tested in this investigation with a rat model of abdominal aortic aneurysm (AAA). METHODS: With an established model, AAA were induced in normotensive Wistar-Kyoto (WKY) rats and genetically hypertensive Wistar-Kyoto (WKHT) rats by perfusing an isolated segment of the infrarenal aorta with elastase. A propranolol dose-response was studied for each strain: (1) saline solution controls (n = 18); (2) propranolol, 10 mg/kg subcutaneously (n = 18); (3) propranolol, 30 mg/kg (n = 14). Systolic blood pressure was determined by tail plethysmography before operation and on day 14, as well as by direct recording at surgery and on day 14. Rats were killed at 14 days, and aneurysm diameter was measured. RESULTS: The initial tail BP was 129 +/- 22 mm Hg in WKY animals and 158 +/- 21 mm Hg in WKHT animals (p < 0.0001). Tail BP and intraaortic systolic, diastolic, and mean blood pressure (BP) were not significantly decreased by propranolol treatment in either strain of rats. However, BP tended to rise in WKY rats, whereas it fell slightly in WKHT rats. Initial aortic size in all animals was 1.06 +/- 0.12. The final aortic size in untreated, hypertensive rats was more than twice that of untreated normotensive controls: 1: WKHT, 3.0 +/- 0.73 mm, 1: WKY, 6.9 +/- 3.5 mm (p < 0.01). After treatment with both doses of propranolol, hypertensive aneurysms were significantly smaller than the untreated WKHT group (p < 0.05) and not significantly different from aneurysms in all groups of normotensive animals: 2: WKY, 3.1 +/- 1.13 mm, 2: WKHT, 4.0 +/- 1.81 mm; 3: WKY, 4.1 +/- 0.41 mm, 3: WKHT, 2.9 +/- 1.24 mm. There was no significant difference in aortic size between the three normotensive WKY groups. CONCLUSIONS: Hypertension increases the size of aortic aneurysms in this experimental model. Propranolol significantly reduces the size of experimental AAA in hypertensive animals independently of the dose and by a mechanism that may be unrelated to simple BP reduction.


Subject(s)
Aortic Aneurysm, Abdominal/drug therapy , Hypertension/complications , Propranolol/therapeutic use , Analysis of Variance , Animals , Aortic Aneurysm, Abdominal/complications , Aortic Aneurysm, Abdominal/pathology , Aortic Aneurysm, Abdominal/physiopathology , Dose-Response Relationship, Drug , Female , Hemodynamics/drug effects , Propranolol/pharmacology , Rats , Rats, Inbred WKY
8.
Biochem J ; 227(2): 355-62, 1985 Apr 15.
Article in English | MEDLINE | ID: mdl-3890830

ABSTRACT

The insulin sensitivity of protein synthesis and glucose incorporation into glycogen by the soleus and epitrochlearis muscles from fed rats and 24 h-starved rats was determined in vitro during the first and second hours of incubation after isolation of the muscles. Rates of protein synthesis by both muscles from fed rats in the first hour of incubation were 2-fold higher than in the second hour and were not increased by insulin. Rates of protein synthesis during the first hour in the presence of 6000 microunits of insulin/ml were increased in soleus, but not in epitrochlearis, muscles from starved rats. Rates of protein synthesis in both muscles from fed and starved rats were increased significantly by insulin during the second hour. High concentrations of insulin caused a marked stimulation of the rates of glucose incorporation by both muscles from fed and starved rats in both the first and second hours of incubation. The insulin sensitivity of glucose incorporation during the second hour, defined as the concentration of insulin causing half-maximal stimulation, was increased 10-fold for both muscle types from starved rats (soleus, 65 microunits/ml; epitrochlearis, 45 microunits/ml) relative to muscles from fed rats (soleus, 600 microunits/ml; epitrochlearis, 500 microunits/m). The insulin sensitivity of protein synthesis in the second hour was greater for soleus muscles from starved rats (65 microunits/ml) than from fed rats (500 microunits/ml). In contrast, the insulin sensitivity of protein synthesis in epitrochlearis muscles from starved rats was significantly decreased (225 microunits/ml) compared with fed rats (25 microunits/ml Maximal rates achieved by high concentrations of insulin were not different from those in the same muscle from fed rats. It is suggested that protein synthesis, in distinction to glucose utilization, may be resistant to insulin stimulation during periods of acute starvation in muscles with fibre compositions similar to the epitrochlearis, but not in muscles with fibre compositions similar to the soleus. Partial reversal of the resistance observed in vitro for epitrochlearis muscles from starved rats may be due to the loss of factors which suppress the effect of insulin in vivo.


Subject(s)
Glucose/metabolism , Glycogen/biosynthesis , Insulin/pharmacology , Muscle Proteins/biosynthesis , Muscles/metabolism , Animals , Dose-Response Relationship, Drug , Female , In Vitro Techniques , Muscles/drug effects , Rats , Rats, Inbred Strains , Starvation/metabolism
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