VASOCONSTRICTION IN THE RENAL VASCULAR BED DURING EXERCISE: STUDIES IN CONTROL AND HEART FAILURE RABBITS

1. The effects of graded treadmill exercise on renal blood flow (RBF) were examined in seven rabbits, in which congestive heart failure (CHF) was produced by the administration of doxorubicin, 1 mg/kg, twice weekly for 8 weeks, and in seven controls. A third group of five rabbits underwent doxorubicin treatment with the addition of surgical section of the left renal sympathetic nerve. 2. During submaximal exercise, there was a small reduction in RBF in controls, which was greatly exaggerated in CHF. 3. In both control and heart failure rabbits, there was a precipitous fall in RBF as exercise fatigue developed. 4. Renal sympathectomy ablated these changes in RBF during exercise. 5. It is concluded that in heart failure there is an exaggerated, sympathetically mediated, diversion of blood flow away from the kidney. The onset of exercise fatigue in both normal and heart failure rabbits is accompanied by a marked intensification of this process.     

Triple lumen venous access for pediatric bone marrow transplantation candidates

Multiple routes of vascular access are required in children undergoing bone marrow transplantation to facilitate total parenteral nutrition (TPN); blood withdrawal; and administration of blood products, antibiotics, fluids, and immunosuppressive drugs. Placement of multiple catheters frequently requires multiple venotomies in separate vessels. We have found that both a Broviac catheter and pediatric dual-lumen Raaf catheter can be placed through separate venotomies in the external jugular vein, which provides sufficient routes of vascular access without complications. This technique places only one vessel at risk while minimizing the chance for infection by utilizing two exit sites. We consider this to be the procedure of choice in young patients requiring multiple routes of vascular access.     

Contribution of the distal tubule to potassium excretion in experimental glomerulonephritis

The renal adaptations that maintain potassium homeostasis in diffuse forms of glomerular disease are not well defined. Thus, handling of potassium by superficial nephron segments was examined in a rat model of antiglomerular basement membrane nephritis. Sampling the same nephron successively from the end and beginning of the distal tubule and the end of the proximal tubule allowed a segmental analysis. Despite a 40% reduction in GFR, potassium excretion in the glomerulonephritis animals was normal due to an increase in FEK. The proximal tubule and loop segment did not contribute to the enhanced FEK seen in these animals. In contrast, potassium entry along the distal tubule was significantly greater in the experimental group averaging 13.7 +/- 4.3 pmol/min compared to 1.2 +/- 1.7 pmol/min in controls (P less than 0.01). Multiple linear regression analysis showed that distal tubule potassium entry at any level of flow was enhanced in glomerulonephritis compared to controls (P less than 0.0001). Plasma aldosterone levels were similar in both groups of animals. Thus, the adaptation to potassium excretion seen in glomerulonephritis is partly achieved by the distal tubule through flow-rate independent mechanisms and appears to be independent of plasma aldosterone levels.     

Antigenic structure of bovine growth hormone: location of a growth enhancing region.

Site-directed antisera generated by peptide immunization have been used to study the antigenicity of bovine growth hormone (bGH). Prediction of sequential antigenic sites has been performed using secondary structure information derived from the 'Protean' prediction routine. The structures predicted by this programme agree closely with the corresponding structure of GH recently derived from crystallographic studies. We have previously shown that the binding of monoclonal antibodies of particular epitope specificity to human or bovine GH results in significant enhancement of hormonal activity in vivo; however, the sites recognized by these antibodies were not known. Here we identify a sequence region, corresponding to a loop structure joining helices 3 and 4, which, is associated with the growth enhancement phenomenon. Antisera raised to either of two overlapping peptides (residues 120-140 and 134-154) significantly increase the biological activity of GH in vivo. Antisera directed to other regions on the GH molecule failed to demonstrate this property. Coincidentally, the sites recognized by the growth-enhancing anti-peptide antisera overlap with the site on GH which is highly susceptible to proteolytic cleavage; such cleavage has been shown in some cases to result in hormone enhancement.     

Periosteal transplantation to the rabbit patella

Autologous periosteal transplantation (without chondrocyte cell transplantation) for treating traumatic articular cartilage defects of the patella gives pain relief in uncontrolled clinical studies. To study the whole transplanted area macroscopically and microscopically, animal studies are motivated. In this pilot study, we reproduce the surgical technique for periosteum transplantation on human patella to a rabbit model. A full-thickness cartilage defect of the whole patella was created in eight adult female rabbits. The defect was treated with autologous periosteal transplantation. After surgery, the rabbits were allowed free activity. This is the difference compared to the treatment in humans, where our group uses CPM for 5 days and non-weight-bearing for 12 weeks. After 21 weeks, there was a diffuse synovitis in all transplanted knees, and in five of eight knees there were signs of osteoarthritis in the patello-femoral joint. Histologically, in three animals, small islands of hyaline cartilage surrounded by fibrocartilage were seen in the transplanted area. In the other five animals, fibrocartilage was the predominant tissue. In contrast to previous experimental studies using a rabbit model, we did not achieve hyaline cartilage resurfacing.     

Arteriosclerotic changes in the myocardium, lung, and kidney in dogs with chronic congestive heart failure and myxomatous mitral valve disease.

BACKGROUND: The occurrence of small vessel arteriosclerosis in the myocardium, kidney, and lung in dogs with naturally occurring myxomatous mitral valve disease has not been previously investigated systematically. METHODS: Twenty-one dogs with naturally occurring congestive heart failure and 21 age-matched, sex-matched, and weight-matched control dogs underwent extensive pathological and histopathological examination. Morphometry and scoring of tissue sections were used to measure arterial narrowing and fibrosis in the myocardium, kidney, and lung; and intimal thickness and plaque formation in the aorta and pulmonary artery. RESULTS: Dogs with congestive heart failure had significantly more arterial narrowing in the left ventricle (P < .003), lung (P < .0001), and kidney (P < .02); intimal-medial thickening in the pulmonary artery (P = .04); and fibrosis in the left ventricle (P < .0001) than control dogs. However, they did not have more plaque formation or intimal-medial thickening in the aorta than controls. There was significantly more arterial narrowing in papillary muscles than in all other locations in dogs with congestive heart failure (P < .002). In control dogs, arterial changes were less pronounced and did not differ in different locations. CONCLUSIONS: Dogs with naturally occurring myxomatous mitral valve disease have significantly more arterial changes in the myocardium, lung, and kidney, and significantly more fibrosis in the myocardium than control dogs. This could have important implications in the management of myxomatous mitral valve disease and raises interesting questions about the occurrence and importance of intramural small vessel disease in humans with primary mitral valve prolapse.