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.     

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     

The arthroscopic monopolar radiofrequency treatment of chronic anterior cruciate ligament instability

The Holmium:YAG (Ho:YAG) laser is the arthroscopic laser of choice. The arthroscopic surgeon can ablate, coagulate, or shrink periarticular soft tissues by manipulating Ho:YAG laser power settings. The ability to ablate soft tissue in a hemostatic fashion greatly facilitates the treatment of labral tear, synovitis, subacromial arch decompression, and distal clavicle arthritis. The nonablative application of Ho:YAG laser energy has been used successfully to treat glenohumeral instability. The laser-assisted capsular shift (LACS) procedure, in conjunction with standard labral repair techniques, successfully treats unidirectional and multidirectional shoulder instability Neuromuscular rehabilitation is accelerated. Excellent clinical results may be achieved with appropriate surgical technique and postoperative rehabilitation.     

Effect of Renal Impairment on the Pharmacokinetics and Tolerability of Tiagabine

Summary: Purpose: We wished to determine the effect of renal impairment on the pharmacokinetics and tolerability of the new antiepileptic drug tiagabine (TGB).
Methods: We assessed TGB pharmacokinetics and tolerability in 25 subjects with various degrees of renal function (based on creatinine clearance, n = 4–6 per group) from healthy (group I) to requiring hemodialysis (group V) in a single and multiple dose (every 12h), one-period (groups I-IV) or a single dose, two-period (group V) study (4-mg oral doses of TGB · HCl). Blood samples were collected after the first dose (both periods for group V) and after the last dose on day 5 (groups I-IV). TGB plasma concentrations and plasma protein binding were determined by high-performance liquid chromatography (HPLC) and ultrafiltration, respectively.
Results: TGB was well tolerated by all study subjects. The pharmacokinetics of TGB were similar in all subjects; no pharmacokinetic parameter (based on either total or unbound concentrations) was statistically correlated with creatinine clearance. For total TGB in plasma, single-dose mean values of the maximum plasma concentration, clearance, and half-life (t1/2) ranged from 52 to 108 ng/ml, from 7.14 to 11.02 I/h, and from 6.4 to 8.4 h, respectively.
Conclusions: TGB pharmacokinetics and tolerability were independent of renal function; therefore, dosage adjustment is unnecessary for epilepsy patients with renal impairment.