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R Neville

Publications and source records attributed to R Neville.

11 recordsLinked to original sources
PubMed1992

Dose-dependent smooth muscle cell proliferation induced by thermal injury with pulsed infrared lasers.

BACKGROUND: Recently, laser-heated and radio frequency-heated balloon angioplasty techniques have been proposed as a means to treat or minimize dissection and elastic recoil but have been associated with a high rate of clinical restenosis. Similarly, pulsed laser angioplasty techniques proposed to minimize thermal injury while ablating obstructing atheroma have failed to reduce clinical restenosis. Because "hot balloon" and pulsed laser angioplasty create both mechanical and thermal injury, it has been difficult to discern the cause of the smooth muscle cell (SMC) proliferation resulting in restenosis and whether such magnitude of proliferation is predictable and dose related. This study was undertaken to explore these issues. METHODS AND RESULTS: Localized thermal lesions accompanying efficient ablation were created with a pulsed Tm:YAG laser in nine rabbit aortas, which consistently led to a focal proliferation of SMC that filled the ablated region by 4 weeks. Transcutaneous Ho:YAG pulsed laser irradiation at multiple independent sites of 24 central rabbit ear arteries without ablation led to brief approximately 30 degrees C thermal transients and thermal damage to the artery wall resulting in significant neointimal proliferation by 3 weeks and a mean cross-sectional narrowing of 59 +/- 17% at a dose of 390 mJ/mm2. Acute and chronic responses to varying total energy deposition were studied by histology after the rabbits were killed at 2 hours to 4 weeks. Arterial segments midway between laser injuries were unaffected and served as internal controls. Neointimal proliferation at 3 weeks after laser injury exhibited a clear dose dependence. Mean cross-sectional narrowing increased from 34 +/- 10% to 85 +/- 15% as laser fluence increased from 240 mJ/cm2 to 640 mJ/cm2 (r = 0.84). Similarly, cross-sectional narrowing caused by SMC neointimal proliferation increased from 20 +/- 10% to 77 +/- 17% for a fixed surface irradiation as the depth of the most superficial arterial media decreased from 600 microns to 330 microns (r = 0.94). CONCLUSIONS: Thermal injury to the arterial wall is a potent stimulus for SMC proliferation and may necessitate reduction in laser or thermal energy used for angioplasty. Moreover, a dose-response relation exists between the degree of thermal injury and SMC proliferative response. Hence, this technique could be used as a practical model of restenosis suitable for screening therapies for inhibition of SMC proliferation.

Animals↗
PubMed1991

Vascular responsiveness in obstructed gut.

Multiorgan system failure due to hypotension and sepsis is an important cause of death in patients with bowel obstruction. We have investigated the pathophysiology of this entity in an animal model. After 5 days of bowel obstruction, blood flow in the superior mesenteric artery was measured with and without Pitressin and norepinephrine given in separate experiments. In controls, Pitressin in moderate dosages caused a substantial fall in gut blood flow, which was not seen in obstructed animals (blood flow reduction 52 percent vs. 11 percent in sham and obstructed animals respectively, P less than 0.01). Similarly, norepinephrine infusion had less of an effect on gut blood flow in obstructed animals (blood flow reduction 79 percent vs. 58 percent sham vs. obstructed animals (P less than 0.05). Thus, both agents had dose-related effects on gut blood flow, which was maintained at a higher level throughout the drug infusion periods in the bowel of obstructed animals, demonstrating that splanchnic flow is less responsive to vasoactive drug infusion under these experimental conditions. Because splanchnic vasoconstriction is an important feature of normal hemodynamic homeostasis, we suggest that these results may help explain some aspects of the pathophysiology of multiorgan failure caused or worsened by systemic hypotension seen in bowel obstruction.

Animals↗
PubMed1987

Somatostatin and analogs lack splanchnic vasoconstrictive effects in anesthetized pigs.

Due to an apparently selective vasoconstrictive effect on the splanchnic circulation, somatostatin (SRIF) has been advocated for the treatment of variceal hemorrhage. The present study was designed to compare and contrast the systemic and splanchnic hemodynamic effects of SRIF and two of its long-acting analogs (SMS 201,995 and L 363,568) with those of Pitressin. Anesthetized pigs were subjected to laparotomy for placement of an electromagnetic flowmeter on the main trunk of the superior mesenteric artery (SMA). Systemic hemodynamic parameters of arterial blood pressure and cardiac output were monitored with thermodilution catheters. Portal venous blood was collected for measurement of plasma levels of SMS 201,995 and L 363,568 and for determination of gastrin levels during infusion of the latter analog. Experimental drugs were administered via an aortic cannula in a range (5-10 mg/kg bolus and 5-10 mg/kg/min continuous infusion) of dosages. At the higher dosages, SRIF, SMS 201,995, and L 363,568 decreased SMA blood flow (mean% +/- SD) 5.6 +/- 2.2, 1.6 +/- 4.4, and 8.0 +/- 3.8 after 10 min. None of the values achieved significance when compared to variation in baseline determinations. Pitressin (0.25 units, intravenously) produced a consistent and highly significant (P less than 0.001) reduction-in SMA flow after 5 min. Pharmacologic levels of SMS 201,995 and L 363,568 were reliably achieved in portal blood and the latter produced significant reduction (P less than 0.05) in portal venous levels of gastrin. SRIF and its long-acting analogs produced no significant splanchnic nor systemic hemodynamic effects in this model.

Anesthesia↗
PubMedDate not supplied

Pyrolytic carbon, porous implants, and the fibrin adhesive system.

The bone implant interface for Pyrolite and titanium alloy was evaluated. The effects of a fibrin adhesive system (FAS) on the interface was also compared. Fixation of the Pyrolite and porous titanium implants was observed to occur in the 4-week period of the study with minimal fibrous tissue encapsulation. The ultimate interfascial shear strength for bone-Pyrolite interface was attained at 4 weeks. No adverse effect with utilization of the FAS could be identified. Further investigation into the use of Pyrolite and the FAS in foot surgery is anticipated.

Animals↗
PubMedDate not supplied

Role of heparin in reducing skeletal muscle infarction in ischemia-reperfusion.

Heparin continues to be recommended in the clinical management of limb ischemia to prevent extension of distal vascular thrombosis and increased rates of limb loss. However, heparin may also be responsible for reduced skeletal muscle injury. Although its mechanism of action has not been fully evaluated, we have investigated the ability of heparin to minimize skeletal muscle injury associated with the ischemia-reperfusion syndrome in an in vivo canine gracilis muscle model. Our findings demonstrated a significant reduction in the amount of skeletal muscle infarction, microvascular permeability, and H+ ion accumulation cumulation after preischemic heparinization. Diffuse intravascular coagulation also has been observed in observed in this model which may be prevented or reduced by the anticoagulant properties of heparin when administered prior to ischemia. However, heparin's protective effect may be independent of its anticoagulant activity. Heparin is a polycomponent drug with non-anticoagulant properties which may serve to reduce cellular injury during ischemia and reperfusion in several different ways. Microvascular injury is decreased by the restoration of normal intimal negative charge and through the binding and resultant inactivation of histamine, bradykinin and other vasoactive amines. Heparin inhibits the complement cascade which is known to determine ischemic infarct size. Other factors of importance in determining the extent of skeletal injury include neutrophil activation, chemotaxis, enzyme release, and free oxygen radical generation, all of which are decreased or modulated by heparin. Heparin is a complex substance and much more remains to be learned about its anticoagulant and nonanticoagulant properties as well as its protective effects on skeletal muscle injury in ischemia-reperfusion syndrome.

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