Abnormal wall strain at distal end-to-side anastomoses

Cyclic stretch has been demonstrated to induce proliferative and secretory activities by cultured arterial endothelial and smooth muscle cells, cellular processes that contribute to the development of intimal hyperplasia. A model of an end-to-side anastomosis was developed to examine the hypothesis that regions of the artery at such anastomoses are subjected to facally increased cyclic stretch, which may stimulate the development of intimal hyperplasia. Polytetrafluoroethylene grafts were anastomosed end to side to latex rubber tubes that have elastic properties similar to those of the human femoral artery. Pulse waves with physiologic pressure, rate, and contour were applied, and systolic and diastolic diameters were measured in two planes at longitudinal intervals. Circumferential strain imposed on the latex artery was calculated at each interval. Strain imposed perpendicular to the suture line was also measured. Circumferential strain was consistently maximal at a distinct region of the artery along the proximal third of the anatomosis (6.0±1.1% vs. 3.3±0.5% at other regions of the artery). The maximal strain across the suture line was found at precisely the same region (3.9±0.3% vs. 2.0±0.4%). The anastomotic region of the recipient artery in a distal end-to-side anastomosis is subjected to cyclic circumferential strains two times greater than those experienced by the remainder of the artery. This corresponds to a common location of intimal hyperplasia. Such strains may be a stimulus for intimal hyperplasia.Presented at the Seventeenth Annual Meeting of the Peripheral Vascular Surgery Society, June 7, 1992, Chicago, Ill.     

Interleukin-3-dependent potentiation of IgE responsiveness in mouse basophils

Basophils produce interleukins (IL)-4 in response to various stimuli and may contribute to type 2 immune responses to various infections and allergens. We found that resting basophils freshly isolated from mice produce IL-4 in response to IL-3 but not to high-affinity Fc receptor (FcεRI) cross-linking (CL), yet both required the immunoreceptor tyrosine-based activation motif (ITAM) containing adaptor Fc receptor γ-chain (FcRγ), while basophils activated in vitro by IL-3 become responsive to FcεRI CL. Acquisition of responsiveness to FcεRI CL occurred upon infection with Trichinella spiralis or administration of superantigen. Because cultured basophils return to a quiescent state upon starvation with IL-3 with surface FcεRI levels unchanged, this acquisition is reversible and probably reflects intracellular events requiring protein synthesis. Interestingly, similar activation-associated acquisition was observed for responsiveness to other stimuli, including CD200R3 CL, which is known to signal via DAP-12, and the allergen protease papain. This acquisition of responsiveness to FcεRI CL was inhibited by Jak inhibitor. Thus, the IL-3 signal bifurcates downstream of Jak, into two distinct pathway, one leading to IL-4 production and the other to render basophils competent to respond to stimuli dependent on ITAM-containing adaptors DAP12 and FcRγ for IL-4 production.     

Low serum cholesterol increases the risk of noncardiovascular events: An antagonist viewpoint

Summary Considerable debate concerning the apparent association of low serum cholesterol levels with enhanced noncardiovascular disease mortality has been aired in both scientific and lay publications within the past year. This debate has resulted in some medical experts calling for a moratorium on efforts to reduce serum cholesterol, particularly with drugs, and for a more conservative approach to screening and modifying cholesterol levels for the primary prevention of coronary heart disease (CHD). Observational studies, including the Framingham Heart Study, the Multiple Risk Factor Intervention Trial, the Whitehall Study, and the International Collaborative Group, have not substantiated a cause and effect relationship between naturally occurring low serum cholesterol and noncardiovascular disease mortality, such as cancer. Intervention trials designed to lower high serum cholesterol levels by diet and drugs have also not been conclusively shown to produce excess harm that offsets the benefit of reduced CHD events. Several primary and secondary CHD prevention trials, with sufficient numbers of subjects to provide the statistical power to detect potential detrimental effects of lowering cholesterol levels, are currently in progress and will be very helpful in resolving the concern about noncardiovascular disease mortality.     

Adrenergic,purinergic, and endothelial mediators and modulators of norepinephrine-induced mesenteric autoregulatory escape

We evaluated the effects of potential factors in autoregulatory escape from norepinephrine-induced vasoconstriction in rat anterior mesenteric artery. We determined mesenteric artery blood flow velocity with a pulsed Doppler, sonic flowmeter, and systemic arterial blood pressure with a transducer. A 4-min norepinephrine infusion (0.125–1.0 × 10^–8 M/min) intravenously evoked a dose-dependent, initial vasoconstriction that was followed by rapid escape of blood flow toward or above the control value during sustained norepinephrine administration. Neonatal capsaicin treatment enhanced vasoconstrictor responses to norepinephrine but failed to affect escape parameters. Propranolol decreased norepinephrine-induced escape dose dependently. Adenosine deaminase attenuated escape, and the combination of this enzyme plus propranolol nearly abolished escape from norepinephrine-induced vasoconstriction. Methylene blue also diminished autoregulatory escape. These findings suggest that norepinephrine-induced autoregulatory escape involves simultaneous -adrenoceptor, purinergic, and endothelial mediation. Norepinephrine-evoked mesenteric vasoconstriction appears to involve predominantly ₂-adrenoceptors and is modulated by peptidergic sensory nerves and adenosine.NIH grant number supporting these studies: USPHS # DK37050.     

Observations on the arterial baroreflex in neurally mediated vasodepressor syncope

The arterial baroreflex was studied in subjects who had recently had an episode of vasodepressor syncope. This was determined using 2–3 mcg/kg intravenous boluses of phenylephrine and assessing the bradycardic response. The values were measured in ms/mmHg and expressed as the angular coefficient of the regression line between the increase in R—R interval on the electrocardiograph and the systolic arterial pressure. In subjects examined immediately after the vasodepressor syncope episode the bradycardic response was much more marked than in controls (p < 0.01) and in the subjects themselves 6 months after the episode, provided that they were symptom-free (p < 0.01). It is concluded that in vasodepressor syncope there is a phase in which the baroreflex is highly sensitive and that this is due not to a lowering of the stimulation threshold but to a gain in the efferent arc, which explains a vagotonic response.     

Interaction of technetium 99m-labeled teboroxime with red blood cells reduces the compound’s extraction and increases apparent cardiac washout

Background

^99mTc-labeled teboroxime shows high myocardial extraction in both in vivo animal and in vitro cell culture and isolated heart studies. Whereas in vivo studies show rapid myocardial clearance of teboroxime, in vitro cell culture and isolated heart studies show slower washout comparable to that of²⁰¹Tl. Binding of teboroxime to blood components may contribute to these conflicting results.

Methods and Results

We measured teboroxime extraction in the isolated blood-perfused rabbit heart after injection in saline solution, brief incubation in red blood cell perfusate, or 4-hour incubation with human red blood cells. Teboroxime in saline solution showed high extraction (E_max=0.89±0.02; E_net=0.69±0.02), whereas brief incubation in perfusate (E_max=0.60±0.06; E_net=0.48±0.05) or prolonged incubation with human red blood cells (E_max=0.43±0.09; E_ne=0.38±0.07) resulted in reduced extraction. Teboroxime clearance was similar for all groups and was slower than²⁰¹Tl clearance. Analysis of total residual cardiac teboroxime (comparable to external imaging) showed that teboroxime clearance was biexponential. Reduced extraction of teboroxime in red blood cells resulted in an increased size of the rapidly clearing (unextracted) fraction, giving the appearance of rapid myocardial washout.

Conclusions

Teboroxime has a high myocardial extraction. Binding to blood components reduces teboroxime extraction and increases the rate of cardiac teboroxime clearance.     

Intraoperative measurement of javid shunt flow with transit-time ultrasound

Transit-time ultrasound methods were used to measure blood flow in 37 patients undergoing carotid endarterectomy. Internal carotid flow before (ICF^bef) and after (ICF^aft) endarterectomy was measured with a 6 mm perivascular probe, and Javid shunt flow (SF) was measured with a clamp-on probe. For the entire group ICF^bef averaged 117±67 ml/min and ICF^aft was 173±67 ml/min. Shunt flow averaged 123±51 ml/min. The differences between ICF^bet and ICF^aft and between SF and ICF^aft were significant (ANOVA,p<0.01) but the difference between ICF^bef and SF was not. The relationship between ICF^bef and SF appeared to define two groups of patients. Those in whom SF was greater than ICF^bef (SF > ICF^bef) had more stenosis evident on preoperative arteriograms (64.7%±14.55% maximum single diameter stenosis) and a greater average increase in ICF (151%±159%) than those with SF ICF^bef (43.3%±20.9% stenosis and 34%±54% increase in ICF), suggesting that the relationship between SF and ICF^bef defines groups with different hemodynamic responses. The similarity between SF and ICF^bef indicates that Javid shunt flow offers adequate protection from cerebral ischemia. A practical benefit of the shunt clamp-on flow probe is the ability afforded to recognize shunt occlusions.Presented at the Twelfth Annual Meeting of the Southern California Vascular Surgical Society, Coronado, Calif., September 17–19, 1993.     

Motility Disorders after Roux-en-Y Gastrojejunostomy

About 30% of patients who have a Roux-en-Y gastrojejunostomy after gastrectomy suffer from abdominal pain, nausea, vomiting of food and bloating made worse by eating. This syndrome, called the Roux stasis syndrome, is caused, in part, by a motility disorder of the Roux limb. Transection of the jejunum during the construction of the limb separates the limb from the natural small intestinal pacemaker located in the duodenum. Ectopic pacemakers then appear in the limb and trigger retrograde contractions in its proximal portion. These contractions slow transit through the limb and result in Roux stasis. Current nonsurgical treatment of the syndrome includes the use of prokinetic agents and intestinal pacing, neither of which has demonstrated long-term benefits. A near-total gastrectomy may speed upper gastrointestinal transit somewhat, but stasis in the Roux limb often persists. Our current approach aims at preventing the syndrome by the use of an ‘uncut’ Roux limb, an operation which preserves myoneural continuity between the duodenal pacemaker and the Roux limb and so prevents the appearance of ectopic pacemakers and stasis in the limb.