Endothelium-independent Vasoconstricting and Vasodilating Actions of Halothane on Rat Mesenteric Resistance Blood Vessels

Background: Whether volatile anesthetics produce changes in vascular resistance and blood flow because of direct effects on vascular tissue is unclear. Direct vasoconstricting and vasodilating actions have been demonstrated in isolated conductance arteries in vitro, but there is little information regarding direct effects on the small vessels that mediate resistance and flow changes in vivo.

Methods: We investigated the actions of halothane on 50-200 micro Meter branches of the rat mesenteric artery that were cannulated and studied in vitro. The vessels were pressurized to 60 mmHg, and vascular dimensions were continuously monitored using a computer-based real-time image analysis system. The vessel bath was perfused with HCO3 -buffered saline (37 degrees Celsius) equilibrated with 95% Oxygen2 /5% CO2 (plus/minus halothane). The vascular endothelium was mechanically removed before cannulation in some vessels.

Results: In unstimulated vessels, halothane had a concentration-dependent vasoconstricting action (EC50 = 0.45 mM = 1.5 vol% at 37 degrees Celsius) that was largely transient and was similar to that produced by caffeine. Both halothane and caffeine constrictions were unaffected by bath [Calcium2+], nifedipine (1 micro Meter) or Cadmium2+ (100 micro Meter) and were abolished by ryanodine (10 micro Meter). In addition, caffeine responses were attenuated by halothane in a concentration-dependent manner (EC50 - 1.6 mM). In vessels preconstricted with KCl (40 mM) or phenylephrine (10 sup -6 M), halothane produced transient constriction followed by concentration-dependent vasodilation. Ryanodine, which abolished halothane constrictions, had little effect on the amplitude of KCl- or phenylephrine-induced constrictions or the vasodilating action of halothane. Removal of the endothelium likewise had little effect on the vasoconstricting or the vasodilating actions of halothane in unstimulated, KCl- or phenylephrine-constricted vessels. Halothane completely relaxed KCl and phenylephrine constrictions with EC50 values of 0.36 mM (1.2% at 37 degrees Celsius) and 0.75 mM (2.5%), respectively, in intact vessels before ryanodine; 0.25 mM (0.8%) and 0.59 mM (1.9%) in intact vessels after ryanodine; and 0.52 mM (1.7%) and 0.67 mM (2.2%) in endothelium-denuded vessels.     

Is There an Advantage to Repairing Infected Mitral Valves?

Background. The therapy for native mitral valve endocarditis is in evolution. Antibiotics have significantly improved survival rates, but patients with complications of endocarditis may require surgical treatment.

Methods. Between January 1985 and December 1995, 146 patients underwent surgical therapy (repair or replacement) for native mitral valve endocarditis. All patients had documented bacterial endocarditis. Univariate and multivariate analyses were performed to determine predictors of hospital death, long-term event-free survival, and probability of repair. Patients were evaluated in three groups: all patients, patients with acute endocarditis, and patients with chronic endocarditis.

Results. There were ten hospital deaths (6.8%). Patients undergoing repair had a lower hospital mortality rate (p = 0.008) then those having replacement. Event-free survival was improved after mitral valve repair in the overall group (p = 0.02) and in the group with healed (chronic) endocarditis (p = 0.05). Although the acute endocarditis group demonstrated an improved event-free survival rate after mitral valve repair versus replacement (74% versus 20% at 6 years), this did not reach statistical significance.

Conclusions. We conclude that mitral valve repair is preferable to mitral valve replacement when possible, in patients with complications of endocarditis, as repair results in a lower hospital mortality and an improved long-term survival.     

Histology of a lengthened human tibia.

We describe the histology of a specimen taken from an amputated leg seven months after a 15 cm bone gap in the tibia had been closed by bone transport. Lengthening appeared to have occurred by repeated minor trauma to the bone, with the fractured trabeculae in sufficiently close contact for the repair process to proceed. Osteogenesis did not occur through a cartilage phase, but the fracture gaps were bridged by collagen fibres, around which new bone formed. Microfractures had repaired by primary healing with woven bone and with no microcallus. Small regions of bone were necrotic. Resorption of the necrotic bone and remodelling of the immature bundle and woven bone were still at an early stage, suggesting that complete remodelling in man may take years rather than months.     

Development of an isolated, pulsatile blood-perfused rat lung model for evaluating the preserved lung functions

The purpose of this study was to develop an isolated, pulsatile blood-perfused rat lung model that allows us to evaluate the preserved lung functions. Lungs isolated from Sprague-Dawley rats, were perfused with venous whole blood by either a pulsatile or constant flow. The effuent was continuously deoxygenated with a 95% N₂/5% CO₂ gas mixture. Airway resistance, lung compliance, elastic work, flow resistive work, pulmonary vascular resistance, and blood gas analysis were assessed. Pressor responses toN ^G -monomethyl-l-arginine (l-NMMA) were compared between pulsatile and constant blood flow. At a flow of 0.1 ml/g body weight/min, pulsatile perfusion allowed for stable perfusion at least for 2h (mean 162.5±15.1 min) with stable aerodynamic and hemodynamic variables including blood gas tensions, whereas constant perfusion resulted in immediate lung failure. Whenl-NMMA was added to the perfusate, the mean pulmonary artery pressure did not show any change in the constant flow (6.0±2.6% increase), but did show a significant increase in the pulsatile flow (45±11% increase). Pulsatile blood flow reduced the pulmonary vascular resistance relative to the constant flow and allowed for a 2-h perfusion period to evaluate the lung function. The vasorelaxant mechanism in the pulsatile perfusion is related in part to the endothelial-dependent relaxation observed in the nitric oxide pathway. Presented in part at the 79th, Annual Clinical Congress of the American College of Surgeons (ACS) held in San Francisco, CA USA, 1993.     

Leukocyte Depletion of Blood Cardioplegia Attenuates Reperfusion Injury

Background. Leukocytes are associated with myocardial injury during reperfusion after ischemia. Short periods of leukocyte depletion during reperfusion result in persistent attenuation of postischemic myocardial dysfunction.

Methods. Leukocyte depletion was examined in a canine model of regional myocardial ischemia and reperfusion. The extracorporeal circuit and cardioplegia circuits underwent leukocyte depletion by mechanical filtration. Animals were instrumented for baseline global function before 90-minute occlusion of the left anterior descending coronary artery. Global function during ischemia and at 5, 30, 60, and 90 minutes after a 60-minute cardioplegic arrest using continuous blood cardioplegia was assessed in leukocyte-depleted (n = 9) and control (n = 10) groups.

Results. No significant difference between groups was seen for systemic leukocyte counts, global function, or water content. Endothelial function was significantly protected as assessed by response to both calcium ionophore (endothelial-dependent, receptor-independent relaxation: leukocyte-depleted, 72% ± 19% of endothelin-induced constriction versus control, 46% ± 14%; p < 0.05) and acetylcholine (endothelial-dependent, receptor-dependent relaxation: leukocyte-depleted, 83% ± 11% versus control, 44% ± 15%; p < 0.05).

Conclusions. Leukocyte-mediated endothelial reperfusion injury can be attenuated by leukocyte depletion during reperfusion.     

Media Review

E_mergency M_edicine P_rocedures.: By Eric F. Reichman and Robert R. Simon. New York, NY     

Combining Free Flap Reconstruction and Craniofacial Prosthetic Technique for Orbit,Scalp, and Temporal Defects

Objectives: To identify factors leading to successful application of prosthetic techniques following free flap reconstruction of the orbit, scalp, and temporal region. Study Design: Retrospective review. Methods: Twenty-eight patients who underwent free flap reconstruction for defects of these regions between 1989 and 1996 were reviewed for clinical parameters, flap loss, patient survival, and implant loss rate. Prosthetic usage rates were compared before and after introduction of a site-specific reconstructive algorithm. Results: Free flap success rate was 93%, whereas osseointegrated implant loss rate was 11%. In addition to implants, a reconstructive strategy that provided thin, vascular tissue between bone and skin, a flat platform in the temporal region, and preservation of orbital cavity depth led to increased prosthetic usage. Conclusions: Craniofacial prosthetic techniques can significantly augment the results of free flap surgery for the orbit, scalp, and temporal region. Successful combination of these techniques requires a site-specific surgical approach.