Halothane constricts bovine pulmonary arteries by release of intracellular calcium.

In the canine lung, when compared with the conscious state, halothane causes vasoconstriction that is independent of blood flow. However, traditionally inhalational anesthetics have been shown to attenuate hypoxic pulmonary vasoconstriction and have therefore been considered pulmonary vasodilators. We have shown, in isolated bovine pulmonary artery, that halothane produces a transient contractile response. A variety of smooth muscle cellular mechanisms could be responsible for the vasoconstriction produced by halothane. The purpose of this study was to test the hypothesis that the halothane-induced contraction was caused by the release of sarcoplasmic reticular Ca++. Isometric tension was measured in isolated rings of bovine pulmonary artery with intact endothelium. Three protocols were followed. Rings were exposed to cyclopiazonic acid or ryanodine (modulators of sarcoplasmic reticular Ca++) (protocol 1), caffeine (protocol 2) verapamil or nicardipine (protocol 3). Halothane-induced contraction was measured before, during and after exposure to drug. In nominally Ca(++)-free buffer cyclopiazonic acid and ryanodine attenuated the halothane-induced contraction. Similar responses were seen with cyclopiazonic acid and ryanodine treatment when caffeine was substituted for halothane. The calcium channel blockers nicardipine and verapamil did not significantly alter the halothane-induced contraction. Our data in bovine pulmonary artery segments are consistent with halothane effects seen in vascular smooth muscle from several other tissues and species. The results of our experiments support the conclusion that the release of intracellular Ca++ from sarcoplasmic reticular stores is responsible for the halothane-induced vasoconstriction that has been observed in this tissue.

Potassium channel blockade and halothane vasodilation in conducting and resistance coronary arteries.

On the basis of reports that volatile anesthetics, such as halothane, open membrane potassium channels in several tissues, it was investigated whether coronary vasodilation by halothane is mediated by a similar mechanism. The ability of glyburide, a blocker of ATP-sensitive K+ (KATP) channels, and tetraethylammonium (TEA+), a blocker of Ca(2+)-activated K+ channels, to modify halothane-induced vasodilation was assessed in two vascular preparations. First, coronary resistance vessel tone was measured in isolated rat hearts arrested with tetrodotoxin and, second, conducting vessel responsiveness was evaluated in ring segments of the porcine epicardial coronary artery contracted with prostaglandin F2 alpha. Halothane alone markedly vasodilated the perfused hearts and attenuated the agonist contraction of the coronary rings. Blockade of KATP channels with glyburide alone did not affect the base-line vascular tone or responsiveness but it inhibited cromakalim vasodilation. TEA+ alone caused vasoconstriction. In hearts perfused at constant pressure, glyburide significantly attenuated the halothane-induced increase in coronary flow by 56% and perfusion with a high K+ buffer reduced the halothane-induced vasodilation response by 94%. In endothelium-denuded coronary rings, glyburide did not affect halothane-induced relaxation but KATP channel blockade potentiated halothane-caused relaxation in endothelium-intact rings. The attenuation of halothane-induced vasodilation by TEA+ seen in the perfused hearts did not achieve statistical significance and no halothane/TEA+ interaction was evident in the coronary rings. Thus, the data from the perfused heart experiments suggest that halothane relaxes rat coronary resistance vessels, in part, by opening K+ channels.

Cardiovascular and respiratory effects of tiletamine-zolazepam.

The combination of tiletamine and zolazepam is an important dissociative anesthetic-tranquilizer. However, little is known about the effects of this combination on the heart and respiration in rats. Adult, male rats anesthetized with tiletamine-zolazepam alone or tiletamine-zolazepam combined with xylazine or butorphanol were evaluated for changes in heart rate, mean arterial blood pressure, arterial blood pH, and blood gases during a 75-min period of anesthesia. Rats anesthetized with tiletamine-zolazepam had increased mean arterial blood pressure and less respiratory depression than did rats anesthetized with sodium pentobarbital. Tiletamine-zolazepam combined with xylazine at either dose produced bradycardia and a marked hypotension that persisted throughout the 75-min period. This combination produced respiratory depression comparable to tiletamine-zolazepam alone. The addition of butorphanol to tiletamine-zolazepam caused a transient hypotension and bradycardia. Tiletamine-zolazepam plus butorphanol produced a mild to severe respiratory depression that was dose and time dependent. These results demonstrate that: a) Tiletamine-zolazepam is cardiostimulatory, a property consistent with the known cardiovascular effects of other dissociative anesthetics; b) xylazine plus tiletamine-zolazepam is a potent cardiovascular depressant combination; and c) tiletamine-zolazepam plus butorphanol at specific doses is an anesthetic-analgesic combination with minimal effects on cardiovascular and respiratory function.

Antinociceptive properties of tiletamine-zolazepam improved by addition of xylazine or butorphanol.

A combination of tiletamine HCl and zolazepam HCl is frequently used as an anesthetic, but little is known about the antinociceptive properties of tiletamine-zolazepam. The antinociceptive properties of tiletamine-zolazepam alone or combined with xylazine or butorphanol were determined in the adult male rate using the tail-flick test. Changes in tail-flick latency were determined at 15, 45, and 75 min after IP drug administration of sterile water, sodium pentobarbital, morphine, tiletamine-zolazepam, xylazine, butorphanol, and tiletamine-zolazepam plus xylazine or butorphanol. Tail-flick latency approximated 100% maximum possible effect (MPE) at 15-75 min postinjection in morphine-treated rats. Tiletamine-zolazepam, xylazine, and butorphanol alone, at any dose utilized, produced less than 50% MPE. However, the combination of tiletamine-zolazepam with butorphanol or xylazine increased tail-flick latency approximately three times greater than tiletamine-zolazepam alone. These results demonstrate that: a) consonant with earlier findings, analgesia and anesthesia are independent states; b) tiletamine-zolazepam is not an effective combination with respect to analgesia; but c) in concert with appropriate drugs, it can exhibit potent antinociceptive properties.

The social impact of dental problems and visits.

OBJECTIVES: The purpose of this analysis was to assess selected social consequences of maintaining oral health and treating oral diseases. The associations among socioeconomic and demographic factors with time lost from work or school and reductions in normal activities are explored. METHODS: Data were gathered as part of the 1989 National Health Interview Survey from 50,000 US households (117,000 individuals), representing 240 million persons. The oral health care supplement was analyzed using the software SUDAAN to produce standard errors for estimates based on complex multistage sample designs. RESULTS: Because of dental visits or problems, 148,000 hours of work were lost per 100,000 workers, 117,000 hours of school were lost per 100,000 school-age children, and 17,000 activity days beyond work and school time were restricted per 100,000 individuals in 1989. Exploratory analyses suggest that sociodemographic groups have different patterns of such time loss and of reduced normal activities. CONCLUSIONS: Overall, there is low social impact individually from dental visits and oral conditions. At the societal level, however, such problems and treatments among disadvantaged groups appear to have a greater impact.

Transvalvular left ventricular pressure measurement in the isolated working rat heart.

A method of continuously measuring left ventricular (LV) pressure in an isolated buffer-perfused working rat heart is described. Transvalvular placement of a micromanometer through the aorta is the unique feature of this procedure. Advantages include catheter stability and lack of myocardial trauma. Changes in cardiac function were quantified by exposing hearts to either isoproterenol (10(-9) M) or halothane (1.5% vol/vol). To examine if any obstruction to LV outflow was caused by the micromanometer, cardiac performance was assessed during pullback from the ventricle to the aorta. Complications such as aortic insufficiency and ventricular arrhythmias were also studied. The results indicate that the transvalvular placement of a micromanometer can provide continuous, high-fidelity reproduction of LV pressure in this small-organ preparation. The presence of the micromanometer did not significantly alter cardiac performance, and proper catheter placement was achieved easily in a high percentage (> 90%) of cases.

Heparin resistance after intraoperative platelet-rich plasma harvesting.

Records of anticoagulation for cardiopulmonary bypass from 58 patients who underwent elective coronary artery revascularization were analyzed to determine whether the harvesting of autologous platelet-rich plasma produces heparin resistance. The effect of preoperative heparin therapy on anticoagulation for cardiopulmonary bypass after harvesting of platelet-rich plasma was also evaluated. Patients were grouped by presence of preoperative heparin therapy and type of blood component harvested before cardiopulmonary bypass, including platelet-rich plasma, autologous whole blood, both, or neither. The dose of heparin required to initiate and to maintain anticoagulation for cardiopulmonary bypass was determined for each patient, and the groups were compared by two-way analysis of variance. Significantly more heparin was required to maintain anticoagulation for cardiopulmonary bypass in the platelet-rich plasma group than in the groups receiving autologous whole blood or no blood products. More heparin was also required to initiate and to maintain anticoagulation for cardiopulmonary bypass after preoperative heparin therapy. These results reinforce the concept that anticoagulation during cardiopulmonary bypass must be carefully monitored, and increased vigilance may be warranted in patients after harvesting of platelet-rich plasma.

Direct vasodilation by sevoflurane, isoflurane, and halothane alters coronary flow reserve in the isolated rat heart.

Direct vasodilation of coronary resistance vessels by anesthetics may reduce coronary flow reserve and interfere with myocardial flow-metabolism coupling. This study was performed to evaluate the potential for the halogenated anesthetic agents sevoflurane, isoflurane, and halothane to alter the regulation of coronary flow via a direct action on coronary resistance vessels. Coronary flow and flow reserve were measured in the quiescent isolated perfused rat heart at anesthetic concentrations between 0 and 3 x MAC. In order to minimize anesthetic-induced secondary changes in coronary resistance, constant coronary perfusion pressure was maintained; the left ventricular cavity was vented; and tetrodotoxin was used to achieve cardiac arrest. These conditions permitted the dissociation of direct anesthetic actions from indirect regulatory processes affecting coronary vascular resistance (CVR). Coronary flow reserve was defined as the difference between coronary flow prior to and during administration of a maximally vasodilating dose of adenosine. Each anesthetic significantly reduced the magnitude of both CVR and coronary flow reserve in a concentration-dependent manner. Sevoflurane reduced coronary flow reserve significantly less than did halothane and isoflurane. At high concentrations (3.0 x MAC), coronary flow reserve was abolished by halothane and was decreased to near zero by isoflurane; however, flow reserve was reduced only 48% from control by sevoflurane. This difference among anesthetics is explained primarily by variations in the magnitude of direct coronary vasodilation produced by each anesthetic, rather than by effects on maximal vasodilator capacity. These data show that sevoflurane's intrinsic vasodilator action on coronary resistance vessels differs substantially from that of halothane and isoflurane.

The accuracy of Finapres noninvasive mean arterial pressure measurements in anesthetized patients.

The Finapres (FIN) is a new noninvasive blood pressure monitor that provides continuous arterial waveform display with the use of a finger cuff. The authors assessed the accuracy of FIN mean arterial pressure (MAP) measurements relative to simultaneous direct radial arterial pressures in 20 patients undergoing general anesthesia for major elective surgery. Data were collected digitally with the use of RS-232 communications over a total of 16.2 h. The data were processed into 6012 interference-free time samples, each spanning 6 s. The authors determined the difference between FIN and direct MAPs during each time sample. The authors calculated not only the bias of FIN measurements, but also the frequency, magnitude, and duration of discrepancies between simultaneous FIN and direct MAPs. The overall bias of the FIN MAP was -0.5 +/- 1.0 mmHg, which was not significantly different from zero. However, 32.3 +/- 6.2% of all MAP comparisons differed by greater than +/- 10 mmHg, and 5.0 +/- 1.1% differed by greater than +/- 20 mmHg. Moreover, there was an average of one episode every 2 patient-hours when the FIN MAP differed by greater than +/- 20 mmHg for more than 1 min. Although the MAP measured by FIN accurately reflected direct MAPs most of the time, there were occasional discrepancies of different magnitude such that clinical usefulness may be limited in patients in whom continuous accurate blood pressure measurements are essential.

Hemodynamic effects of muscle relaxant drugs during anesthetic induction in patients with mitral or aortic valvular heart disease.

The hemodynamic effects of three nondepolarizing skeletal muscle relaxant drug regimens were compared during the induction of general anesthesia in 64 patients with valvular heart disease using a double-blind protocol. Patients were first stratified according to primary valvular defect (aortic stenosis, aortic regurgitation, mitral stenosis, or mitral regurgitation). Next, patients were randomly allocated to a drug group, either group A (atracurium), group V (vecuronium), or group MP (metocurine plus pancuronium). Data were collected during three periods: awake, postanesthetic induction, and posttracheal intubation. Four cardiovascular variables were designated a priori as primary variables of interest. These were heart rate (HR), mean arterial pressure (MAP), cardiac index (CI), and systemic vascular resistance index (SVRI). Patients with mitral stenosis showed two significant hemodynamic differences among muscle relaxant drug groups: (1) CI increased in group A but decreased in group MP between the awake and postinduction measurements (P = 0.032); and (2) SVRI decreased in group A but increased in group MP between the awake and postintubation periods (P = 0.034). In contrast, patients with aortic stenosis, aortic regurgitation, or mitral regurgitation demonstrated no statistically significant difference in cardiovascular responses among drug groups. Further analysis was performed using the following data: (1) other hemodynamic variables; (2) incidence of deviations from cardiovascular stability; and (3) the frequency of cardiovascular drug use. This examination showed no important differences among the muscle relaxant drug groups. The small but significant hemodynamic changes observed in mitral stenosis patients in drug groups A and MP were not noted with vecuronium.(ABSTRACT TRUNCATED AT 250 WORDS)

Direct effects of myocardial depressant drugs on coronary vascular tone: anesthetic vasodilation by halothane and isoflurane.

Because certain vasoactive drugs also possess negative myocardial inotropic properties, it is difficult to determine their direct pharmacological actions on coronary resistance vessels in situ. Thus, a drug's myocardial effects may induce indirect physiological changes in coronary vascular tone that confound measuring its direct action. To separate the direct from indirect drug actions on vascular tone, the authors describe an experimental system utilizing the isolated perfused rat heart arrested with tetrodotoxin. The direct effects of the volatile anesthetics halothane and isoflurane on coronary vascular tone were examined in this preparation, using the concept of minimum alveolar concentration as the measure of potency. Both anesthetics demonstrated a dose-dependent direct coronary vasodilation that was reversible, with the median effective dose being 1.31 +/- 0.08 (mean +/- S.E.) for halothane, and 1.53 +/- 0.12 for isoflurane (P = 0.06; units of measure are the fraction of minimum alveolar concentration for each anesthetic). Further studies indicated that maximal vasodilation by adenosine was diminished after 90 min of perfusion, independent of anesthetic administration. Myocardial oxygen consumption was decreased significantly from the beating state by arrest, but neither anesthetic nor adenosine affected myocardial oxygen consumption further. These data indicate that halothane and isoflurane are equipotent for inducing direct dilation of coronary resistance vessels in the isolated perfused arrested rat heart.

Vascular responses to dopamine and dobutamine in the awake calf during constant aortic flow or constant aortic pressure.

We investigated vascular effects of dopamine and dobutamine infusions in awake calves implanted with the Penn State total artificial heart (TAH). This preparation uniquely permits independent servo-control of cardiac output (CO) and arterial blood pressure (BP). Thirty-two studies (22 with dopamine and 10 with dobutamine) were performed in four juvenile calves from 1 to 4 months after TAH implantation. Studies were performed in one of two TAH operating conditions: (a) constant aortic flow, in which the CO is fixed and aortic BP varies with systemic vascular resistance (SVR), or (b) constant pressure, in which the CO varies to maintain a constant BP when SVR changes. During both constant flow and constant pressure studies, dopamine caused a dose-dependent increase and dobutamine caused a dose-dependent decrease in SVR. There was no difference in the SVR response between constant flow or constant pressure conditions at any dose of dopamine or dobutamine (p greater than 0.05). The infusion doses of dopamine required to raise the SVR 20 and 50% during constant flow studies were 7.2 and 12.4 micrograms.kg-1.min-1, respectively. In constant pressure studies, these doses were 7.7 and 13.5 micrograms.kg-1.min-1. The infusion dose of dobutamine resulting in a 20% reduction in SVR was 27.2 micrograms.kg-1.min-1 in constant flow studies 26.2 micrograms.kg-1.min-1 in constant pressure studies. These data suggest that baroreflex and other indirect mechanisms are less important than direct vascular drug effects in this system.(ABSTRACT TRUNCATED AT 250 WORDS)