Cardioembolic stroke due to papillary fibroelastoma.

Papillary fibroelastoma (PFE) is a rare primary benign cardiac tumor with significant embolic potential. Diagnosis and requisite surgical treatment may be neglected unless transesophageal echocardiography (TEE) is performed. A 72-year-old man with hypertension and diabetes had a right middle cerebral artery stroke of unclear cause after standard work-up. Subsequent TEE indicated an aortic valve PFE. The TEE may be the only diagnostic modality to identify embolic lesions such as PFE and must be strongly considered in cryptogenic large vessel stroke.

Effect of K+ channel blockade with tetraethylammonium on anesthetic-induced relaxation in canine cerebral and coronary arteries.

The mechanism by which volatile anesthetics produce their direct effects on vascular smooth muscle remains unknown. The authors previously reported that volatile anesthetics decrease both Ca2+ and K+ currents, however the role of Ca(2+)-activated K+ channels during the vasorelaxation by anesthetics has not been investigated. The purpose of this study was to determine whether blockade of the K+ channel alters the response to volatile anesthetics. Responses were studied in canine middle cerebral arteries and proximal and distal canine coronary arteries. Vascular rings (2-mm length) were suspended in tissue baths, and isometric tension was recorded. Rings were constricted with 40 mM KCl and prostaglandin F2 alpha (middle cerebral arteries only) and subsequently exposed to enflurane (3.25%), halothane (1.35%), and isoflurane (2.1%). Volatile anesthetics produced vasorelaxation with relative potency in order: enflurane > halothane > isoflurane. The procedure was repeated in the presence of the K+ channel blocker tetraethylammonium chloride (TEA, 20 mM). In all groups of vessels TEA alone elicited either no increase or only a transient increase in tension, however constrictions to both agonists were augmented in the presence of TEA. The presence of TEA significantly augmented anesthetic-induced vasorelaxation in small and large coronary vessels and in middle cerebral arteries. However, this effect was more pronounced in the cerebral as compared to coronary arteries. Constrictions produced in cerebral vessels by 15 microM prostaglandin F2 alpha were comparable with constrictions produced by 5 microM prostaglandin F2 alpha in the presence of TEA. The subsequent relaxant response of these vessels to enflurane was also comparable in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of halothane and isoflurane on calcium and potassium channel currents in canine coronary arterial cells.

The effects of halothane (0.75% and 1.5%) and isoflurane (2.6%) on macroscopic Ca2+ and K+ channel currents (ICa and IK, respectively) were investigated in voltage-clamped vascular muscle cells from the canine coronary artery. Single coronary arterial cells were dialyzed with K+ glutamate solution and superfused with Tyrode's solution for measurement of IK (n = 45). Stepwise depolarization from a holding potential of -60 mV to beyond -30 mV elicited an outward, slowly inactivating IK that had a macroscopic slope conductance of 18 nS. IK was reduced 75% by 10 mM 4-aminopyridine, a K+ channel antagonist. Compared to 4-aminopyridine, halothane at 0.75% and 1.5% reduced peak IK amplitude only by 14 +/- 2% and 36 +/- 3%, respectively. At approximately equianesthetic concentrations, 2.6% isoflurane suppressed IK less than did 1.5% halothane, reducing peak amplitude by 15 +/- 3%. In other sets of experiments, cells were dialyzed with 120 Cs(+)-glutamate solution and superfused with 10 mM BaCl2 or CaCl2 solutions to isolate ICa (n = 39) pharmacologically. Under these conditions, progressive depolarizing steps from -60 mV elicited a small inward current, which was potentiated 3.4-fold by equimolar substitution of Ba2+ for Ca2+ in the external solution and was blocked by 1 microM nifedipine. This inward current, which resembled L-type ICa, was blocked 37 +/- 4% and 70 +/- 4% in the presence of 0.75% and 1.5% halothane, respectively. Isoflurane (2.6%) also decreased ICa by 55 +/- 5%. It appears that while halothane and isoflurane suppress both IK and ICa, these anesthetics preferentially reduce ICa.(ABSTRACT TRUNCATED AT 250 WORDS)

Interactive effects of volatile anesthetics, verapamil, and ryanodine on contractility and calcium homeostasis of isolated pregnant rat myometrium.

OBJECTIVE: Both volatile anesthetics and Ca2+ antagonists decrease uterine contractility. The interactive effects of anesthetics, verapamil, and ryanodine on myometrial muscular activity and on intracellular Ca2+ availability were examined. STUDY DESIGN: The effects of minimum alveolar concentrations of 0.5, 1.0, and 2.0 of halothane, enflurane, and isoflurane on electrically stimulated isometric mechanical activity of isolated longitudinal myometrium strips from 45 pregnant rats (15 to 21 days), superfused with Krebs' solution with or without 5.0 mmol/L Ca2+, 10(-7) and 10(-6) mol/L verapamil, and 10(-6) mol/L ryanodine, were compared. Analysis was performed by analysis of variance and Duncan test. RESULTS: All three anesthetics and verapamil produced dose-dependent depression of contractility. Increasing the Ca2+ concentration from 2.5 to 5.0 mmol/L in the superfusate partly reversed the depression. An additive effect of verapamil and anesthetics, especially enflurane, on contractile force was observed. Ryanodine had no effect on contractility, but it could partly counteract the depressant effect of anesthetics. CONCLUSION: Clinically used concentrations of volatile anesthetics modify Ca2+ availability and depress uterine contractility. General anesthesia, especially by enflurane, in patients being treated with calcium antagonists may represent a higher risk.

Atrial pacing thresholds measured in anesthetized patients with the use of an esophageal stethoscope modified for pacing.

Transesophageal atrial pacing (TAP) with the use of standard, thermistor-equipped, esophageal stethoscopes, modified for pacing by incorporation of a 4-French, bipolar TAP probe (pacing esophageal stethoscope [PES]), was evaluated in 100 adult patients under general anesthesia. A commercially available TAP pulse generator supplied 10-ms pulses with current variable between 0 and 40 mA. Pacing distances (in centimeters) were measured from the infraalveolar ridge to midway between PES electrodes (1.5-cm interelectrode distance). Pacing thresholds (milliamperes) were measured at the point of a maximum-amplitude P-wave (PMAX) in the bipolar esophageal electrogram and points 1 cm proximal or 1, 2, or 3 cm distal to PMAX. TAP (70-100 beats per min) was used for sinus bradycardia less than or equal to 60 beats per min (36 patients) or atrioventricular (AV) junctional rhythm (2 patients) and blood pressure changes with TAP documented. In male patients (n = 49), PMAX was 32.7 +/- 0.3 cm (mean +/- SE) and minimum pacing threshold 5.1 +/- 0.4 mA (range, 1-13 mA) at 33.6 +/- 0.3 cm (range, 30-37 cm). In female patients (n = 51), PMAX was 30.4 +/- 0.4 cm and minimum pacing threshold 4.4 +/- 0.4 mA (range, 2-14 mA) at 31.1 +/- 0.4 cm (range, 26-40 cm). TAP produced an average 13-16 mmHg increase in systolic, diastolic, or mean arterial pressure in patients with sinus bradycardia or AV junctional rhythm. There were no subjective patient complaints (epigastric discomfort, dysphagia) that could be attributed to TAP; objective evaluation (esophagoscopy) was not performed.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium-sensitive potassium current in isolated canine coronary smooth muscle cells.

This study characterizes K+ current in canine coronary artery and investigates its role in regulation of vascular smooth muscle tone during the resting and activated state. Isolated rings and whole-cell K+ current as well as single K+ channels were studied. Tetraethylammonium (< 3 mM) did not increase the resting tension in isolated rings; however, 0.3 mM tetraethylammonium increased tension in vessels that were precontracted by elevated [K+]o or 5-hydroxytryptamine (5-HT). The whole-cell K+ current showed voltage and Ca2+ dependency and sensitivity to tetraethylammonium (31 +/- 7, 72 +/- 2, and 83 +/- 4% depression by 1, 10, and 30 mM tetraethylammonium, respectively). A large-conductance (100 pS) K+ channel was identified in cell-attached patches with open-time distribution fitted with two exponentials. Calcium ionophore A23187 (10 microM) increased the probability of opening, mean open time, and amplitude of this channel in cell-attached patches, suggesting Ca2+ dependency. A23187 shifted the plot of unitary current as a function of pipette potential to the right, suggesting A23187-induced cell hyperpolarization. In inside-out patches, increase in cytoplasmic-side [Ca2+] from 10(-7) to 10(-6) M increased both the frequency of channel opening and duration of the open state, without changing its conductance. Tetraethylammonium (1 mM) on the cytoplasmic side caused a reversible decrease in the current amplitude. Charybdotoxin (100 nM) decreased the probability of opening and mean open time and increased mean closed time, while apamin (100 nM) did not significantly affect channel kinetics. In summary, this study demonstrates the existence and important functional role of a large-conductance, Ca(2+)-sensitive K+ channel in regulation of membrane potential and cell excitability, as well as some aspects of regulation and kinetics of this channel in canine coronary arterial cells.

Direct comparative effects of isoflurane and desflurane in isolated guinea pig hearts.

The aim of this study was to test if myocardial and coronary vascular effects of desflurane and isoflurane were similar in the isolated heart. The cardiac effects of these anesthetics were examined in 12 guinea pig hearts perfused in a retrograde manner. Spontaneous heart rate, atrioventricular (AV) conduction time, systolic left ventricular pressure and coronary flow were measured. To differentiate direct vasodilatory effects of these anesthetics from an indirect metabolic effect due to autoregulation of coronary flow, O2 delivery (DO2), myocardial O2 consumption (MVO2) and percent O2 extraction were also monitored. Isoflurane and desflurane were injected directly into sealed bottles containing oxygenated perfusate solution. Each heart was perfused randomly with these anesthetics. Anesthetic concentrations in the perfusate were 0.28 +/- 0.02 and 0.52 +/- 0.02 mM for isoflurane and 0.59 +/- 0.01 and 1.02 +/- 0.09 mM for desflurane (mean +/- standard error of the mean). Calculated vapor concentrations were 1.3 and 2.5 vol % for isoflurane and 6.8 and 11.8 vol % for desflurane which correspond to approximately 1 and 2 MAC in vivo. Each anesthetic similarly decreased heart rate and prolonged AV conduction time in a concentration-dependent manner. Left ventricular pressure (control 93 +/- 4 mmHg) decreased by 11 +/- 1% and 24 +/- 2% with isoflurane and by 15 +/- 1% and 30 +/- 2% with desflurane. The decreases in heart rate and pressure were accompanied by decreases in MVO2 of 12 +/- 2% and 30 +/- 3% with isoflurane and of 19 +/- 3% and 40 +/- 4% with desflurane from a control of 57 +/- 2 microliters.g-1.min-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Halothane reduces dysrhythmias and improves contractile function after global hypoperfusion in isolated hearts.

We investigated the effects of halothane on changes in cardiac function during hypoperfusion and recovery of function after reperfusion in the isolated perfused guinea pig heart. Heart rate, atrioventricular (AV) conduction time, the incidence and severity of dysrhythmias, and isovolumetric left ventricular systolic pressure (LVSP) and its derivative were measured. Hearts (n = 85) were divided into three groups for 30 min of perfusion at 0% (no flow), 10%, and 25% of the control perfusion pressure (PP, 55 mm Hg). These groups were subdivided and exposed to 0%, 0.74% (0.23 +/- 0.01 mM), or 1.65% (0.51 +/- 0.01 mM) halothane 10 min before, during, and 10 min after hypoperfusion. Hypoperfusion was followed by 40 min of reperfusion at control PP. Exposure to 0.74% and 1.65% halothane before hypoperfusion produced a 9% and 13% decrease in heart rate, a 2% and 30% increase in AV conduction time, and a 25% and 51% decrease in LVSP and dLVP/dtmax, respectively. During the 30 min of hypoperfusion, heart rate decreased and AV conduction time increased; second- and third-degree AV block occurred in all hearts in the 0% and 10% PP groups, but only in some hearts in the 25% PP groups. Left ventricular systolic pressure rapidly decreased during hypoperfusion in all groups. During early reperfusion ventricular fibrillation and ventricular tachycardia occurred in the 0% and 10% PP groups but not in the 25% PP groups. During reperfusion 0.74% and 1.65% halothane greatly reduced the duration of ventricular fibrillation from 8.1 +/- 3.3 min to 1.5 +/- 0.8 and 1.9 +/- 1.2 min in the 0% and 10% PP groups, respectively. A concentration of 0.74% halothane increased the incidence of supraventricular tachycardia on reperfusion in the 10% group (from a control of 20% to 65%), and 1.65% halothane increased the duration (2.6 +/- 2.5 min) and incidence (38%) of supraventricular tachycardia on reperfusion in the 0% PP group. A concentration of 1.65% halothane facilitated recovery of LVSP after hypoperfusion in the 25% group but not in the 0% and 10% PP groups. These results indicate that halothane, in some instances, can have protective cardiac effects after graded hypoperfusion as assessed by improved contractility and by reduced severity of some dysrhythmias during reperfusion; however halothane may also increase the incidence of supraventricular tachycardia. The cardiac protection by halothane could be a result of reduced cardiac work before, during, and after hypoperfusion, or of some other direct protective cellular effects.

Isoflurane produces endothelium-independent relaxation in canine middle cerebral arteries.

Although it is generally accepted that isoflurane can cause cerebral vasodilation, the sensitivity of the cerebral vessels to this anesthetic agent remains controversial. Furthermore, the mechanism by which isoflurane produces its direct effects on the cerebral vasculature remains unknown. The purpose of this study was to determine if isoflurane-induced relaxation of canine middle cerebral arteries is dose-dependent and/or endothelium-dependent. In an additional series of experiments, isoflurane-induced relaxation was studied in the presence of indomethacin to inhibit prostacyclin release, and endothelium-independent relaxation was examined with sodium nitroprusside. The response to isoflurane was examined in middle cerebral arteries prior to and following pretreatment with 300 microM NG-monomethyl-L-arginine (LnMMA), an inhibitor of endothelium-dependent vasodilation. Vascular rings (2.5 mm in length and 600-800 microns in diameter) were suspended in tissue baths and isometric tension recorded. The rings were constricted with either 0.2 microM 5-hydroxytryptamine or 5 microM prostaglandin F2 alpha and subsequently exposed to increasing concentrations of isoflurane (0.65-4.9%). In separate experiments the procedure was repeated in vessels with and without endothelium. Isoflurane produced a dose-dependent relaxation in all vessels. This relaxation was not inhibited by LnMMA and was unaffected by the absence of endothelium. The isoflurane response was independent of cyclooxygenase inhibition. These results demonstrate that isoflurane-induced relaxation of canine middle cerebral arteries: 1) is dose-dependent; 2) is not mediated by modulation of endothelium-derived relaxing factor or a release of prostacyclin; and 3) is endothelium-independent.

Effects of isoflurane on K+ and Ca2+ conductance in isolated smooth muscle cells of canine cerebral arteries.

Although isoflurane is a known cerebral vasodilator, the mechanism of isoflurane-induced vasodilation is not clear. The purpose of this study was to investigate the effects of 2.6% isoflurane (1.2 mM) on macroscopic calcium and potassium channel currents in voltage-clamped canine middle cerebral artery cells. Cells were dialyzed with K(+)-glutamate solution and superfused with Tyrode's solution for measurement of potassium current (n = 20). Stepwise depolarization from a holding potential of -60 mV to beyond -30 mV elicited an outward, slowly inactivating potassium current that was reduced 50% +/- 2% and 81% +/- 3% (mean +/- SEM) in the presence of 1 mM 4-aminopyridine and 30 mM tetraethylammonium, respectively. Calcium ionophore (A23187, 10 microM) increased the potassium current by 76% +/- 3%, suggesting calcium dependency. Isoflurane reduced the amplitude of the potassium current by 35% +/- 4%. Calcium current was measured in cells dialyzed with solution containing 130 mM Cs(+)-glutamate and superfused with solution containing 10 mM BaCl2 and 135 mM tetraethylammonium to pharmacologically isolate the calcium current (n = 13). Under these conditions, progressive depolarizing steps from -60 mV elicited an inward current that was maximally activated at +20 mV and essentially eliminated by 1 microM nifedipine. This current, resembling a long-lasting (L-type) Ca2+ channel current, was reduced 40% +/- 4% by isoflurane. The results of this study suggest that isoflurane acts directly at the vascular muscle membrane to suppress transmembrane calcium and potassium currents. The decrease in calcium current would cause vasodilation; however, the concomitant decrease in potassium current may partially antagonize the depressant effect of isoflurane mediated through calcium current reduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative cardiac effects of KT-362 and verapamil in isolated heart--correlation to calcium channel current depression.

Direct cardiac effects of KT-362 (5-[3 [[-2-(3,4-dimethoxyphenyl)-ethyl]amino]-1-oxopropyl]-2,3,4,5- tetrahydro-1,5-benzothiazepine fumarate), a drug that may inhibit intracellular calcium mobilization as well as extracellular calcium influx was compared to verapamil. Guinea pig hearts (n = 19) were used to examine the changes in atrial rate, atrioventricular conduction time (AVCT), coronary flow, myocardial oxygen consumption (MVO2), and isovolumetric left ventricular pressure (LVP). Both drugs concentration-dependently and reversibly decreased atrial rate, contractility, and MVO2; AVCT increased during spontaneous rhythm. The increases in AVCT and the incidence of AV dissociation were accentuated during cardiac pacing. Verapamil significantly increased coronary flow, while KT-362 did not. Median effective concentration (EC50) was about 25 times lower for verapamil in depressing LVP and about three times lower in depressing atrial rate and AV conduction. The changes in calcium channel current in voltage-clamped single canine Purkinje cells (n = 6) were also examined. Verapamil (0.3 microM) and KT-362 (7 microM) decreased peak Ca2+ channel current at maximum activation (+10 mV) by 38.1 +/- 8% and 28.6 +/- 6%, respectively, without shifting the current-voltage relationship. This study indicates that verapamil is more potent than KT-362 in depressing contractile function, heart rate, and AV conduction in isolated hearts and calcium current in isolated cardiac Purkinje cells. Moreover, there was a much greater difference between the EC50 for verapamil and that for KT-362 for the depression of indices of contractility (23-30-fold) than for the depression of sinoatrial and atrioventricular nodal function (2.5-4-fold).

Differential effects of etomidate, propofol, and midazolam on calcium and potassium channel currents in canine myocardial cells.

BACKGROUND: Intravenous anesthetics etomidate, propofol, and midazolam produce negative inotropic effects of various degrees. The mechanism underlying these differences is largely unknown. METHODS: The effects of intravenous anesthetics on L-type Ca2+, transient outward and inward-rectifier K+ channel currents (ICa, IKto, and IK1) were compared in canine ventricular cells using the whole-cell voltage-clamp technique. ICa and IK were elicited by progressively depolarizing cells from -40 to +40 mV, and from -90 to +60 mV, respectively. The peak amplitude and time-dependent inactivation rate of ICa and IK were measured before, during, and after the administration of equimolar concentrations (5, 30, or 60 microM) of etomidate, propofol, or midazolam. RESULTS: Exposure to etomidate, propofol, and midazolam produced a concentration-dependent inhibition of ICa. Midazolam was the most potent intravenous anesthetic; at 60 microM, etomidate, propofol, and midazolam decreased peak ICa by 16 +/- 4% (mean +/- SEM), 33 +/- 5%, and 47 +/- 5%, respectively. Etomidate, propofol, and midazolam given in a 60-microM concentration decreased IKto by 8 +/- 3%, 9 +/- 2%, and 23 +/- 3%, respectively. IK1 was decreased by 60 microM etomidate and midazolam by 20 +/- 6% and 14% +/- 5%, respectively. Propofol had no effect on IK1. CONCLUSIONS: At equimolar concentrations, intravenous anesthetics decreased the peak ICa, IKto, and IK1 with various degrees of potency. Effects of anesthetics on ICa were significantly greater compared with their effects on K+ currents. These findings suggest that the negative inotropic actions of etomidate, propofol, and midazolam are related, at least in part, to decreased ICa. Some effects, such as IK inhibition, may partially antagonize effects of decreased ICa. Indeed, the final effect of these intravenous anesthetics on myocardium will be the sum of these and other sarcolemmal and intracellular effects.

Opposing effects of diacetyl monoxime on contractility and calcium transients in isolated myocardium.

Isolated, perfused guinea pig hearts were used to determine the effects of diacetyl monoxime (DAM) on atrial rate, atrioventricular conduction time (AVCT), and left ventricular peak systolic pressure (LVSP). Contractile force and calcium transients were also monitored in isolated papillary muscles injected with aequorin in the absence and presence of ryanodine (RYA). In the isolated heart, 0.2-5 mM DAM caused significant dose-dependent decreases in LVSP (up to 51%) without change in atrial rate and AVCT. DAM (10 mM) produced a small slowing of atrial rate, no change in AVCT, and a 76% decrease in LVSP; 20 and 30 mM DAM further reduced LVSP, decreased atrial rate 38%, and produced AV dissociation. In isolated, paced papillary muscles, 2, 10, and 30 mM DAM decreased contractile force 27, 58, and 87%, respectively, while calcium transients increased by -9, 38, and 225%, respectively. All cardiac effects of DAM were readily reversible. RYA (1 microM) alone and with DAM (30 mM) decreased contractile force by 30 and 99%, respectively and decreased calcium transients by 59 and 74%, respectively. This study shows that low concentrations of DAM have little effect on electrical activity but greatly depress contractility and modify intracellular handling of calcium.

Halothane reduces release of adenosine, inosine, and lactate with ischemia and reperfusion in isolated hearts.

We investigated the protective effects of halothane on cardiac function of isolated hearts during global hypoperfusion and reperfusion by examining halothane's effects on altering coronary flow, myocardial oxygen utilization (MVO2), and release of adenosine (ADE), inosine (INO), and lactate (LAC). Isolated perfused guinea pig hearts were divided into three groups of perfusion at 25% (14 mm Hg), 10% (5.5 mm Hg), and 0% (no perfusion) from control perfusion pressure (PP, 55 mm Hg). Each of these PP groups was subdivided into three subgroups and perfused without halothane (control), with 0.23 +/- 0.01 mM (0.74%) halothane, or with 0.51 +/- 0.01 mM (1.65%) halothane. Halothane was present 10 min before reducing PP, during reduced PP (30 min), and for 10 min after reducing PP. Hypoperfusion was followed by 40 min of reperfusion at the control (100%, 55 mm Hg) PP. An additional group of control hearts was followed for the same period without reducing PP or perfusing with halothane. Exposure to 0.74% and 1.65% halothane, before reducing PP, decreased MVO2 and percent oxygen extraction (% O2E), but produced no significant change in coronary flow or release of ADE, ISO, or LAC. During early hypoperfusion (10 min) at 25% PP, 1.65% halothane significantly reduced release of ADE, INO, and LAC. During late hypoperfusion (40 min) the differences in LAC release diminished, but release of ADE and INO remained lower in the 1.65% halothane group. With early reperfusion there was a large increase in release of these metabolites, that was dependent on the decrease in perfusion pressure.(ABSTRACT TRUNCATED AT 250 WORDS)