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G Sanford

Publications and source records attributed to G Sanford.

5 recordsLinked to original sources
PubMed2000

The relationship between acute rejection and chronic rejection is highly dependent on specific MHC matching: a multi-strain rat heterotopic heart transplant study.

BACKGROUND: The impact of acute rejection, immunosuppression, and infection, specifically cytomegalovirus infection, on the development of chronic rejection in the cardiac allograft, has been the subject of a large number of investigations. One of the difficulties in finding associations has been the marked immunologic heterogeneity of the patient population coupled with the lack of the ability to HLA match. Furthermore, the ideal animal model, which duplicates as well as controls for this immunologic heterogeneity, is lacking. METHODS: To try to simulate differences in HLA matching, immunosuppression regiments and cytomegalovirus infection, heterotopic heart transplantation was performed in two separate, complete MHC mismatch, rat strain combinations (WF-LEW, BN-LEW) requiring chronic immunosuppression and employing four separate immunosuppression/infection protocols. Animals were followed for 6 months, killed, and rejection and vascular changes were scored blinded to the group. RESULTS: The mean vascular and acute rejection scores were not significantly different between treatment regiments for either specific strain combination. There was a trend for the subtherapeutic groups to have higher vascular scores. Overall, there were no significant differences in vascular scores between the WF-LEW and BN-LEW groups (1.25+/-0.18 vs. 1.13+/-0.20, P=NS). Similar numbers of WF-LEW and BN-LEW exhibited cellular infiltration and necrosis of the allograft, but the intensity of the response (rejection score) was more severe in the WF-LEW combination (4.54+/-0.22 vs. 3.92+/-0.21, P=0.052) when limiting the analysis to those with myocyte necrosis. There was no significant correlation between acute rejection and vascular lesion severity in the WF-LEW combination (r=0.22, P=NS) but a high correlation between these parameters in the BN-LEW combination (r=0.74, P<0.0001). CONCLUSIONS: These data suggest that, although acute rejection and chronic rejection are related, MHC matching may influence their interdependence. These data also may explain why the clinical association between acute and chronic rejection is difficult to demonstrate.

Acute Disease↗
PubMed1999

Enhanced nitric oxide synthesis reverses salt-induced alterations in blood flow and cGMP levels.

To understand the role of nitric oxide in salt-induced hypertension, we evaluated cardiovascular, hemodynamic and biochemical parameters in Dahl salt-sensitive rats fed low (0.3%) and high (8.0%) sodium diets. Two high salt groups received 1.25 and 2.5 g/L l-arginine in their drinking water. After three weeks of treatment, blood pressure was greater in the high salt groups. l-arginine did not modify salt-induced hypertension. Eicosapentaenoic acid (EPA) caused a smaller depressor response compared to normotensive rats. The increase in blood pressure was associated with decreases in aortic and renal blood flows. In renal artery, the reduction was counteracted by both l-arginine doses; whereas in the aorta, only the higher l-arginine one restored blood flow. The salt-induced reduction in aortic cyclic GMP level was only overcome by the higher l-arginine treatment. These data suggest that at the dose levels tested, nitric oxide reverses the reduction in cGMP and blood flow, but not the blood pressure changes associated with salt-induced hypertension.

Animals↗
PubMed1998

Possible mechanisms of salt-induced hypertension in Dahl salt-sensitive rats.

Genetic factors, diet, and salt sensitivity have all been implicated in hypertension. To further understand the mechanisms involved in salt-induced hypertension, cardiovascular, hemodynamics, and biochemical parameters in Dahl salt-sensitive rats were evaluated in animals on high- and low-sodium diets. During a 4-week treatment period, blood pressure was significantly elevated in the high (8.0%) salt group compared to the low (0.3%) salt group (p< or =0.05 for weeks 2 and 4, respectively). No significant changes were observed in heart rate. The increase in blood pressure was associated with significant increases in lower abdominal aortic and renal vascular resistance, along with a reduction in blood flow. A fourfold increase in arginine vasopressin was observed in animals on the high-salt diet. In contrast, there was no effect on plasma sodium, potassium, or aldosterone levels during the treatment period. As measured in isolated aortic rings, the high-salt diet also caused a significant elevation in stimulated norepinephrine release and a reduction in cyclic GMP levels. These data suggest that salt-induced elevation in blood pressure is due to activation of both the sympathetic and arginine vasopressin systems via mechanisms involving decreased cyclic GMP generation in vascular smooth muscle.

Aldosterone↗