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Biomedical subjects

J J Lynch

Publications and source records attributed to J J Lynch.

At least 109 records · Page 6Linked to original sources
PubMed1990

Failure of lidocaine to suppress lethal ischemic ventricular arrhythmias in a canine model of previous myocardial infarction.

The antiarrhythmic actions of high-dose intravenous (i.v.) lidocaine infusions were assessed in conscious dogs with spontaneous ventricular ectopy subacutely (48 h) after anterior myocardial infarction and in anesthetized dogs with ventricular tachyarrhythmias inducible by programmed ventricular stimulation at 4-11 days after anterior myocardial infarction. In conscious dogs administered cumulative doses of lidocaine at 48 h after myocardial infarction, a significant reduction in the frequency of spontaneous ventricular ectopic complexes (from 61 +/- 12 to 11 +/- 9% of total complexes) occurred only after administration of 10 mg/kg i.v. lidocaine. In anesthetized postinfarction dogs responding to baseline programmed stimulation with ventricular tachyarrhythmias, lidocaine administration (6 mg/kg i.v. loading dose + 100 micrograms/kg/min i.v. maintenance infusion) resulted in a selective increase in infarct zone conduction time (53.0 +/- 5.6 to 60.5 +/- 6.2 msec; p less than 0.05), increases in infarct zone relative refractory periods (RRPs 182 +/- 5 to 193 +/- 5 ms; p less than 0.05), and effective refractory periods (ERPs 156 +/- 4 to 165 +/- 3 ms; p less than 0.05), and an increase in noninfarct zone ERP (154 +/- 5 to 166 +/- 8 ms; p less than 0.05). The induction of ventricular arrhythmias by programmed stimulation was suppressed by lidocaine (6 mg/kg + 100 micrograms/kg/min i.v.) in 5 of 10 postinfarction animals tested, with an additional 3 animals displaying favorable stabilizations of induced arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1990

The intensity of resistance by mature Merino ewes against Haemonchus contortus and Trichostrongylus colubriformis in single-species and combined-species infection.

Three-year-old, non-lactating and non-pregnant Merino ewes, raised on pasture under a program of strategic treatment with anthelmintic and found to be extremely resistant to "trickle" infection with Haemonchus contortus, were given single-dose infections with either H. contortus or Trichostrongylus colubriformis or both species together. The purpose was to ascertain the intensity of protective immunity against the 2 parasites in sheep with immunity acquired from a presumably slight exposure to infection. To provide a criterion, some infected ewes were immunosuppressed with corticosteroid, dexamethasone. Untreated ewes were extremely resistant to challenge infection with either 15,000 or 150,000 H. contortus or 15,000 T. colubriformis. Surprisingly, when mixed infection was given, egg counts for H. contortus were significantly elevated compared with infection by that species alone. Antibody to antigens from infective larval and adult H. contortus was measured in serum by enzyme-linked-immunosorbent assay (ELISA) during the course of infection. Serum titres against larval antigens were significantly depressed when infections with either H. contortus or T. colubriformis were permitted by immunosuppression with dexamethasone, whereas those against adult antigen were depressed when infection with T. colubriformis was permitted.

Animals↗
PubMed1990

Increased endothelial albumin permeability mediated by protein kinase C activation.

We examined the effects of activation of endothelial protein kinase C (PKC) of the endothelial barrier function. Exposure of confluent bovine pulmonary artery endothelial cell monolayers to phorbol 12-myristate 13-acetate (PMA) resulted in concentration-dependent (10(-8)-10(-6) M) increases in PKC activity and in the transendothelial flux of 125I-albumin. Exposure of the endothelium to 1-oleoyl 2-acetyl glycerol (OAG) also increased the transendothelial flux of 125I-albumin in a concentration-dependent manner. Neither 4 alpha-phorbol didecanoate nor 1-mono-oleoyl glycerol, which do not activate PKC, altered permeability. The increase in 125I-albumin permeability induced by PMA was inhibited by 25 microM H7 (a PKC inhibitor), but not by the control compound HA1004 (25 microM). After 16 h of exposure to PMA, 125I-albumin permeability returned to baseline and a significant reduction in cytosolic PKC activity was noted. Further challenge with PMA at this time resulted in no significant increase in PKC activity indicating downregulation of the enzyme; moreover, this PMA challenge did not increase endothelial permeability. Exposure of endothelial monolayers to phospholipase C (PLC), which increases membrane phosphatidylinositide turnover, or to alpha-thrombin also induced concentration-dependent activation of PKC and increases in 125I-albumin endothelial permeability. The thrombin- and PLC-induced permeability increases were inhibited by H7, but not by HA1004. The activation of endothelial PKC directly by PMA or OAG and by PLC and alpha-thrombin increases the transendothelial albumin permeability, indicating that PKC activation is an important signal transduction pathway by which extracellular mediators increase endothelial macromolecular transport.

Animals↗
PubMed1990

Portrayal of adrenergic denervation in the presence of myocardial infarction: a feasibility study.

Myocardial infarction interrupts adrenergic neurons beyond the region of necrosis to give peri-infarct denervation. A method to define the regions of denervation would be a valuable aid in determining the role that loss of adrenergic neurons plays in myocardial infarction and particularly in causing arrhythmias. [123I] meta-iodobenzylguanidine (MIBG) was used to portray scintigraphically the intact neurons in dog hearts. Occlusion of the left circumflex (LCX) or the left anterior descending coronary artery (LAD) produced defects that appeared to be regularly larger in the [123I]MIBG images than in the [201T1]images of the same heart; the differences were considered to be the regions of denervation which were relatively larger after LCX than LAD infarcts. Ex vivo measurements of endogenous norepinephrine and residual [125I]MIBG concentrations gave confirmation of neuronal injury. A computer program to quantify the regions of denervation appeared imprecise, but gave some promise. Scintigraphy of [123I]MIBG offers a method to define patterns of denervation in the living animal and man.

3-Iodobenzylguanidine↗
PubMed1989

Selective degeneration of the parvocellular-projecting retinal ganglion cells in a New World monkey, Saimiri sciureus.

Selective degeneration of retinal ganglion cells projecting to parvocellular layers of the dorsal lateral geniculate nucleus (LGN) was observed in squirrel monkeys (Saimiri sciureus) exposed to a range of doses of acrylamide monomer. Similar acrylamide-induced neuronal loss has previously been reported in parvocellular-projecting ganglion cells of macaques, but no such selective degeneration has been found in acrylamide-dosed rats, squirrels, rabbits or cats. The extent of ganglion cell loss observed in the present study suggests that in the squirrel monkey, as in the macaque, a majority of ganglion cells project to parvocellular layers of the LGN. The locus of optic tract degeneration suggests that the squirrel monkey parvocellular pathway passes in dorsolateral optic tract, as does that of the macaque. Patterns of decreases in cytochrome oxidase activity confirm that, in both of these primates, geniculocortical pathways driven by these vulnerable neurons project to cortical layers 4A and 4C beta. These results suggest close parallels in the neuroanatomical projections and toxic vulnerability of the parvocellular-projecting pathway in New and Old World monkeys. They indicate that acrylamide intoxication can be used to selectively damage this pathway in order to study the functional roles of parallel visual pathways in both New and Old World monkeys.

Animals↗
PubMed1989

Subchronic dosing of macaques with 2,5-hexanedione causes long-lasting motor dysfunction but reversible visual loss.

Visual sensitivity and neurological status were monitored in four female macaque monkeys dosed orally with 2.5-hexanedione (0.64 mM/kg, 5 days per week) for 15 or 17 weeks. The first sign of toxicity was intention tremor seen after 3 months of dosing. This was followed, a week later, by a moderate decrease in visual contrast sensitivity, which returned to baseline 6 to 11 weeks after the end of dosing. Acuity and flicker resolution were not disrupted. A progressive general weakness ensued for 5 to 7 weeks after dosing had ended. Some slow recovery was seen, although the animals remained severely disabled 20 weeks after dosing was discontinued. Pathologic changes were examined 3 weeks (one monkey) and 20 weeks (three monkeys) after dosing. Soon after the end of dosing, axonal swellings were present throughout the distal optic tracts, peripheral nerves, and long tracts of the spinal cord. Twenty weeks after dosing, there was no indication of degeneration in the retinocortical pathway. Peripheral nerves showed widespread axonal loss, residual ongoing degeneration, and only slight regeneration. Axon loss and gliosis were evident in distal dorsal columns, and to a lesser extent, dorsal spinocerebellar and corticospinal tracts. These effects of 2,5-hexanedione on the macaque differ from those found previously for two other axonotoxic compounds, acrylamide monomer and carbon disulfide, which caused marked permanent degeneration that was most prominent in the visual system.

Animals↗
PubMed1989

Electrophysiologic actions and antifibrillatory efficacy of subacute left stellectomy in a conscious, post-infarction canine model of ischemic ventricular fibrillation.

The autonomic nervous system appears to modulate ventricular arrhythmias associated with acute myocardial ischemia. This study investigated the electrophysiologic effects and antifibrillatory actions of subacute left stellectomy in a conscious, post-infarction canine model of sudden cardiac death. Twenty-two dogs with a previous anterior wall myocardial infarction and inducible ventricular arrhythmias were randomized to undergo either left stellectomy (n = 12) or remain as sham-denervated controls (n = 10). Five to 7 days post left stellectomy, there were no significant changes in heart rate, electrocardiographic intervals or ventricular refractoriness compared to sham-denervated controls. Acute posterolateral ischemia was produced in left stellectomy and sham-denervated dogs by anodal current-induced thrombosis via a previously positioned electrode in the left circumflex coronary artery. Ventricular fibrillation developed within 1 hour of the onset of ischemia (early ventricular fibrillation) in 3/12 (25%) left stellectomy dogs versus 8/10 (80%) sham-denervated controls (P less than 0.05). However, 24-hour mortality rate was 5/12 (42%) after left stellectomy versus 8/10 (80%) after sham denervation (P = 0.072). Small differences in regional myocardial norepinephrine content, which is a marker for neuronal integrity, occurred in the mid-posterolateral and mid-anteroseptal regions of the left ventricle after left stellectomy. Overall norepinephrine concentration after left stellectomy was 409.70 +/- 9.90 ng/g vs 428.07 +/- 10.84 ng/g in sham controls (P = NS). In summary, subacute left stellectomy significantly reduces the incidence of ventricular fibrillation occurring within 1 hour of the onset of acute posterolateral ischemia at a distance to a previous myocardial infarction in conscious dogs, and tends to reduce the ischemic post-infarction mortality at 24 hours after the onset of ischemia. This protective effect of left stellectomy is not due to any alteration in cardiac electrophysiologic parameters measured prior to the development of acute posterolateral ischemia, nor is it related to regional denervation as determined by myocardial tissue concentration of residual norepinephrine.

Animals↗
PubMed1989

Alinidine reduces the incidence of ischemic ventricular fibrillation in a conscious canine model, a protective effect antagonized by overdrive atrial pacing.

The antiarrhythmic and antifibrillatory effects of the specific bradycardic agent alinidine were evaluated in a conscious canine model of myocardial infarction and sudden death, and by determination of ventricular fibrillation thresholds (VFT) in anesthetized dogs. Programmed electrical stimulation (PES) was performed in conscious animals, 3-5 days after a 2-h occlusion/reperfusion of the left anterior descending coronary artery (LAD). Dogs in which PES resulted in a reproducible nonsustained or sustained ventricular tachycardia (VT) were randomized to receive either intravenous alinidine (1 mg/kg, n = 11) or intravenous vehicle (n = 10). Programmed electrical stimulation and measurement of electrophysiologic parameters were repeated after 30 min, and the animals were entered into the sudden death protocol by introducing a 150 microA anodal current to the lumen of the left circumflex coronary artery (LCX) via a surgically implanted silver wire electrode. A second alinidine-treated group (n = 3) had heart rates controlled by atrial pacing during this period. Alinidine failed to prevent the programmed electrical induction of VT in 10 of 11 animals, but significantly reduced both sudden (less than 1 h ischemia) and 24-h mortality as compared to the ventricle group. Infarct sizes were similar in the two groups, but the ischemia-related increase in heart rate was attenuated (p less than 0.05) by alinidine and the onset of ischemia tended to be delayed. All of the atrial-paced animals died acutely. Heart rate decreased after alinidine (p less than 0.01), but apart from a single index of refractoriness, the drug was without electrocardiographic or electrophysiologic effects. Neither alinidine nor vehicle demonstrated any effect upon VFT in two groups of five animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1989

Effects of the positive inotropic agents milrinone and pimobendan on the development of lethal ischemic arrhythmias in conscious dogs with recent myocardial infarction.

The effects of milrinone and pimobendan upon the initiation of programmed ventricular stimulation-induced ventricular tachycardia (VT) and the incidence of lethal ischemic ventricular arrhythmias were assessed in conscious dogs with recent anterior myocardial infarctions. Based upon the results of previous studies, the animals which were entered into this investigation were nonresponsive to baseline programmed stimulation and, therefore, considered to be at "low risk" toward the development of subsequent lethal ischemic arrhythmias. Milrinone (200 micrograms/kg/h continuous i.v. infusion) and pimobendan (300 micrograms/kg i.v.) were administered in dosing regimens shown to produce equivalent and sustained increases in left ventricular (LV) + dP/dt. At the time of repeat electrophysiologic testing, 9 of 9 pimobendan-, 9 of 10 milrinone-, and 12 of 12 concurrent vehicle-treated animals remained nonresponsive to programmed ventricular stimulation. Compared to a total control population of 39 "low risk" postinfarction dogs; however, both milrinone and pimobendan administration increased the incidence of sudden ventricular fibrillation occurring in response to the development of acute posterolateral ischemia (milrinone 4 of 10 [40%] and pimobendan 4 of 10 [40%] versus "low risk" control population 4 of 39 [10.3%]; p = 0.038). The incidence of ischemic mortality at 24 h after the development of posterolateral myocardial ischemia was increased in the milrinone-treated group (6 of 10 [60%]) compared to the "low risk" control population (6 of 39 [15.2%]; p = 0.007), whereas the incidence of 24-h ischemic mortality in the pimobendan-treated group (4 of 10 [40%]) was only of borderline statistical significance when compared to that of the "low risk" control population (p = 0.083). Milrinone, but not pimobendan, delayed the onset of acute posterolateral myocardial ischemia in the postinfarction dogs. The predominant electrophysiologic effects of both milrinone and pimobendan were decreases in ventricular refractoriness in both non-infarct (NZ) and in infarct zones (IZ), as well as reductions in electrocardiographic QTc or QT intervals. These findings suggest that with both positive inotropic agents, including milrinone which may possess protective antithrombotic action, sudden death may be increased via a reduction in ventricular refractoriness in the ischemically injured heart. The enhanced susceptibility toward the development of ischemic ventricular arrhythmias in the presence of the inotropic interventions is not predicted by programmed ventricular stimulation testing prior to the ischemic event.

Animals↗
PubMed1989

Endothelial barrier function.

The endothelial barrier in all organ beds allows the free exchange of water, but is restrictive to varying degrees to the transport of solutes such as albumin. For example, in the brain microvessels, the endothelial barrier restricts the transport of protein, whereas in fenestrated and continuous endothelial cells of the renal and lung endothelial cells, the endothelial barrier is semipermeable. The endothelial monolayer demonstrates selectivity, i.e., the permeation of molecules is inversely related to the molecular weight. Although the "pore" theory has been used to describe the transport across the endothelial barrier, the transport of solutes is also dependent on the charge of solutes and the endothelial cell, and the ability of the solute to bind to or be taken up by endothelial cells. Receptor-mediated trancytosis of albumin may contribute to albumin transport in addition to transport by paracellular pathways (i.e., through a so-called pore). Water permeability across the endothelium is determined by the interaction of albumin with glycocalyx and interstitial components of the endothelium (the "fiber matrix"). Ambient concentration of albumin serves to lower endothelial hydraulic conductivity. Increased endothelial permeability to solutes and water in inflammatory states is dependent on the shape and configuration of endothelial cells as determined by alterations in cytoskeletal elements, such as f-actin, and as regulated by intracellular second messengers such as free cytosolic calcium.

Animals↗
PubMed1989

Macrophages activated by fibrin increase albumin permeability across pulmonary artery endothelial monolayers.

We have examined the effects of alveolar macrophages (AM) obtained after challenge with alpha-thrombin on 125I-labeled albumin permeability across ovine pulmonary artery endothelial monolayers. AM were obtained by bronchoalveolar lavage before and after challenging the sheep with alpha-thrombin (80 U/kg). Post-thrombin AM increased 125I-labeled albumin transendothelial permeability, whereas resting AM had no effect (82.7 +/- 7.9% increase versus 17.2 +/- 1.6% increase at the AM:endothelial cell ratio of 1:1; p less than 0.001). The permeability increase was also seen at AM:endothelial cell ratios of 0.2:1 and 5:1. Endothelial permeability to 125I-labeled albumin did not increase after in vitro incubation of macrophages with 10(-8) M thrombin, suggesting that AM are activated as a result of thrombin-induced fibrin microembolism rather than by the alpha-thrombin per se. The increase in permeability was not due to endothelial lysis since macrophages did not cause release of endothelial lactate dehydrogenase. Adherence of AM to the endothelium did not correlate with the ability of AM to increase endothelial permeability. Superoxide anion production was increased when post-thrombin AM were exposed to the endothelial monolayers (30.6 +/- 4.2 nmol/10(6) cells/10 min) compared with production by post-thrombin AM in the absence of endothelial cells (2.5 +/- 0.5 nmol/10(6) cells/10 min). The addition of superoxide dismutase (SOD) blunted the permeability increase induced by AM (32.3 +/- 3.9% increase with SOD versus 84.1 +/- 7.1% increase without SOD; p less than 0.001), indicating that superoxide anion is an important mediator of the macrophage-induced increase in endothelial monolayer permeability.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Blood pressure, heart rate, and heart rhythm changes in patients with heart disease during talking.

Blood pressure and heart rate were recorded in 37 patients with cardiac disease while they were resting quietly and talking. Heart rate, systolic blood pressure, and diastolic blood pressure were all significantly greater while the patients were speaking than while they were resting silently. In addition, ventricular and atrial arrhythmias were more frequent while they were talking than while they were quiet. Higher resting systolic blood pressure levels also were associated with larger blood pressure increases while the patients were speaking. Older patients exhibited significantly greater systolic pressure increases while talking than younger patients. Therapeutic doses of antihypertensive medications, including beta-blockers, calcium channel blockers, and diuretics did not block the heart rate and blood pressure increases while the patients were talking. These findings suggest that more attention needs to be paid to the hemodynamic consequences of communication in patients with coronary heart disease. Coupled with previous research findings, these data also suggest that clinicians need to attend to verbal communications during routine diagnostic procedures for evaluating cardiovascular function.

Adult↗
PubMed1989

Celiprolol does not protect against ventricular tachycardia or sudden death in the conscious canine: a comparison with pindolol in assessing the role of intrinsic sympathomimetic activity.

The antiarrhythmic and antifibrillatory effects of the beta-1 adrenoceptor antagonist celiprolol were evaluated in a chronic canine model of myocardial infarction and sudden death. Programmed electrical stimulation (PES) was performed in conscious animals 3 to 5 days after a 2-hr occlusion/reperfusion of the left anterior descending coronary artery. Dogs in which PES resulted in a reproducible nonsustaining or sustained ventricular tachycardia (VT) were randomized to receive i.v. celiprolol (3 mg/kg, n = 10) or vehicle (n = 10). PES and measurement of electrophysiologic (parameters were repeated after 30 min and the animals were entered into the sudden death protocol by introducing a 150-microA anodal current to the lumen of the left circumflex coronary artery via a surgically implanted silver wire electrode. Celiprolol failed to prevent the induction of VT, and the outcome of the sudden death protocol did not differ from vehicle with respect to either sudden (within 1 hr of ischemia) or delayed (greater than 1 hr) mortality. VT cycle length and ventricular refractoriness were prolonged (P less than .05) by celiprolol, but other electrophysiologic parameters were unaffected. Heart rate was not altered after drug, but celiprolol antagonized the ischemia-induced increase in rate seen in the vehicle group. Similar electrophysiologic results and mortality data were apparent in a third group of dogs which received pindolol (0.09 mg/kg, n = 8). The failure of both drugs to protect against ischemic ventricular fibrillation in a model in which beta adrenoceptor antagonism has previously proved beneficial may be due in part to related cardiostimulant properties shared by celiprolol and pindolol.

Adrenergic beta-Antagonists↗
PubMed1988

Increase in experimental infarct size with digoxin in a canine model of myocardial ischemia-reperfusion injury.

In the present study, dogs were pretreated with intravenous digoxin, 0.0125 mg/kg/day, for 6 to 7 consecutive days to achieve clinically relevant serum concentrations; untreated animals were used as control subjects. After pretreatment, nine digoxin-pretreated dogs and nine control dogs were anesthetized and subjected to a 60-minute occlusion of the left circumflex coronary artery, followed by 6 hours of reperfusion. Anatomic myocardial infarct size, expressed as a percentage of the areas at risk of infarction and as a percentage of the total left ventricle were: 20.2 +/- 3.3% control vs 35.4 +/- 6.2% digoxin-pretreated (p less than 0.05) and 8.6 +/- 1.3% control vs 14.7 +/- 2.5% digoxin-pretreated (p less than 0.05), respectively (2.04 +/- 0.37 ng/ml serum digoxin). Regional myocardial blood flow in the nonischemic and ischemic zones tended to be lower in digoxin-pretreated than in control animals at baseline testing and were significantly reduced in the anterior subendocardial sites of digoxin-pretreated dogs during ischemia and reperfusion. These data suggest that an exacerbation or enhancement of myocardial ischemia-reperfusion injury may occur in the presence of clinically observable serum digoxin concentrations.

Animals↗
PubMed1988

Scintigraphic detection of regional disruption of adrenergic neurons in the heart.

Experiments were designed to detect regional disruptions of adrenergic neurons in the hearts of living dogs. The neuron disruption was achieved by the application of phenol to the epicardium of the left ventricle. Evidence for denervation was the reduction in endogenous norepinephrine (NE) concentrations in the myocardium beneath the region of phenol treatment and toward the apex. Radiolabeled meta-iodobenzylguanidine (MIBG) acts as an analog of NE and as such is concentrated in adrenergic nerve terminals. Following phenol application, MIBG labeled with 125I was found, 20 hours after injection, to be distributed within myocardium in patterns comparable to those of NE. However, left stellectomy did not alter the distributions of NE or 125I-MIBG in the myocardium and apparently did not disrupt adrenergic innervation. MIBG labeled with 123I enabled scintigraphic images of heart neurons in the living dog 3 and 20 hours after injection; these images portrayed the regions of adrenergic neuron disruption caused by phenol treatment. Concentrations of thallium-201 depicted on scintigraphic image and of triphenyltetrazolium observed on in vitro staining demonstrated no myocardial injury. Thus scintigraphy with 123I-MIBG will display regional adrenergic denervations in the heart.

3-Iodobenzylguanidine↗
PubMed1988

Reduction in digitalis-associated postinfarction mortality with nadolol in conscious dogs.

Previously, we have demonstrated an increased incidence of lethal ischemic arrhythmias in postinfarction dogs with clinically observable serum digoxin concentrations, and a significant reduction in digitalis-related lethal ischemic arrhythmias after subacute left stellectomy. In the present study, the protective actions of acute beta-adrenoceptor blockade with nadolol, 1.0 mg/kg administered intravenously immediately preceding the induction of posterolateral myocardial ischemia, were assessed in conscious dogs with recent, small anterior myocardial infarctions pretreated with digoxin, 0.0125 mg/kg/day intravenously, for 5 to 7 consecutive days (total n = 11). A cohort of postinfarction dogs pretreated with digoxin alone served as a control group (total n = 26). Pre vs postdigoxin electrophysiologic testing indicated reductions in myocardial refractoriness in ventricular noninfarct and infarct zones in both treatment groups, whereas the administration of nadolol tended to reverse the reductions in ventricular refractoriness. Arrhythmia-related deaths in response to posterolateral myocardial ischemia were reduced from 12 of 20 (60%) in the digoxin control group to 2 of 10 (20%) in the digoxin + nadolol group (p = 0.039). Serum digoxin concentrations (1.29 +/- 0.14 ng/ml vs 1.39 +/- 0.24 ng/ml), underlying anterior myocardial infarct size (6.9 +/- 1.5% vs 4.6 +/- 0.9% of left ventricle), and developing posterolateral myocardial infarct size (22.8 +/- 2.5% vs 17.5 +/- 3.6% of left ventricle) did not differ significantly between the digoxin and digoxin + nadolol groups. Acute beta-adrenoceptor blockade with nadolol appears to reduce digitalis-mediated ischemic postinfarction mortality, possibly because of a salutary increase in ventricular refractoriness.

Animals↗
PubMed1988

Cardiac electrophysiologic interactions of bepridil, a new calcium antagonist, with enflurane, halothane, and isoflurane.

Bepridil is an investigational calcium antagonist that also has fast sodium channel blocking and antidysrhythmic properties. In the present study, the potential interactions of bepridil with volatile anesthetics on cardiac electrophysiologic parameters were evaluated in open-chest dogs. Twenty-four dogs anesthetized with enflurane (n=6), halothane (n=6), isoflurane (n=6), or chloralose (n=6) received 2.5 mg/kg of bepridil intravenously (IV). Twenty-five additional dogs anesthetized with enflurane (n=7), halothane (n=6), isoflurane (n=6), or chloralose (n=6), received bepridil, 5.0 mg/kg, IV. Dogs anesthetized with cloralose served as controls. Cardiac electrophysiologic parameters were measured after the dogs were anesthetized and were repeated 5, 15, 30, 45, and 60 minutes after bepridil infusion. Plasma bepridil concentrations were also determined at the above time points. Synergy between bepridil and enflurane was demonstrated in the following cardiac electrophysiologic parameters: depression of sinus node function as evidenced by severe depression of sinus node automaticity and conduction; depression of atrioventricular function as evidenced by prolongation of the atrial-His bundle interval and the Wenckebach R-R interval; and, prolongation of the atrial effective refractory period. No synergy was demonstrated between bepridil and halothane or isoflurane when compared to bepridil's effects during chloralose anesthesia. It is concluded that significant synergistic cardiac electrophysiologic effects exist between bepridil and enflurane in dogs. It is recommended that caution be used when anesthetizing patients receiving bepridil with enflurane until human data on the use of this combination of pharmacologic agents is available.

Anesthetics, Inhalation↗