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T A Johnson

Publications and source records attributed to T A Johnson.

At least 55 records · Page 3Linked to original sources
PubMed1994

Substance P nerve terminals synapse upon negative chronotropic vagal motoneurons.

Previous data indicate that there are anatomically segregated and physiologically independent parasympathetic ganglia on the surface of the heart which are capable of selective control of sino-atrial rate, atrio-ventricular conduction, and atrial contractility. We have injected a retrograde tracer into the cardiac ganglion which selectively regulates heart rate (the SA ganglion). Medullary tissues were processed for the histochemical visualization of retrogradely labeled neurons and for the immunohistochemical detection of the neurotransmitter substance P (SP) by dual labeling light and electron microscopic methods. Negative chronotropic retrogradely labeled cells were found in a long slender column in the ventrolateral nucleus ambiguous (NA-VL) which enlarged somewhat at the level of the area postrema. These cells were found bilaterally, but they were asymmetrically distributed. Half the animals showed a pronounced right side predominance in retrograde labeling, while the other half of the animals showed a lesser left side predominance. These observations may help to explain some of the controversy in the literature concerning the relative influence of the right and left vagus nerves on sinus rate. Ultrastructural examination demonstrated axo-somatic and axo-dendritic contacts between SP nerve terminals and retrogradely labeled negative chronotropic NA-VL neurons. SP immunoreactivity was often associated with large dense-core vesicles in terminals forming either symmetric or asymmetric synapses. These observations provide a potential anatomical substrate for the centrally mediated bradycardia elicited by microinjections of SP into the NA. SP immunoreactive terminals were also observed to make axo-somatic, axo-dendritic, and axo-axonic synapses with unlabeled neurons in NA-VL.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Anti-B cell autoantibodies encoded by VH 4-21 genes in human fetal spleen do not require in vivo somatic selection.

We isolated immunoglobulin (Ig) VH4 genes that were rearranged in the genomic DNA of 160 day human fetal spleen. Productively rearranged VH 4-21 genes were cloned into pRTM1, a human IgM expression vector. This allowed us to generate IgM kappa-expressing transfectomas by co-transfecting each of these constructs with pSVG-V kappa 3, an Ig kappa light-chain expression vector that has a variable region encoded Humkv325, a conserved V kappa gene that is frequently expressed early B cell ontogeny. We find that all transfectomas expressing IgM kappa encoded by VH 4-21 make IgM autoantibodies reactive with i, a linear poly-N-acetyllactosamine determinant present on neonatal red blood cells and a B cell-restricted isoform of the CD45 surface molecule. In contrast, a transfectoma expressing pSVG-V kappa 3 and pRTM1 containing a rearranged VH4-59 (V71-4) gene isolated from a chronic lymphocytic leukemia B cell population, designated WIL, produced IgM kappa antibodies that had no detectable anti-i binding activity. However, transfectomas expressing VH 4-21 fused onto the Ig heavy-chain third complementarity determining region (CDR3) of WIL are found to make anti-B cell autoantibodies with anti-i activity. These studies indicate that VH 4-21 genes rearranged in human fetal B cell ontogeny can encode anti-B cell autoantibodies with a binding specificity that does not require in vivo somatic selection.

Agglutinins↗
PubMed1994

Marked activation delay caused by ischemia initiated after regional K+ elevation in in situ pig hearts.

BACKGROUND: Conduction mediated by the slow inward (Ca2+) current occurs in vitro under specific experimental conditions but has not been documented in ventricular muscle in vivo during regional myocardial ischemia, perhaps because certain constituents of ischemia (including hypoxia and acidosis) may inhibit the Ca2+ current in this setting. We hypothesized that slow conduction mediated by the Ca2+ current could occur during acute ischemia in situations in which the extracellular K+ rise was more marked relative to the degree of acidosis, as may occur at ischemic boundaries. METHODS AND RESULTS: In open-chest, anesthetized swine, an arterial shunt from the carotid artery to the mid-left anterior descending coronary artery was created through which a solution of KCl was infused to raise extracellular K+ ([K+]e) to approximately 9.4 mmol/L before the initiation of ischemia, which we termed "K(+)-modified ischemia." Ischemia initiated at a normal [K+]e ("unmodified ischemia") resulted in a mean activation delay in the center of the ischemic zone of 55 +/- 26 milliseconds after 5 minutes of ischemia and a decrease in epicardial longitudinal conduction velocity from 53 to 21 cm/s before the onset of conduction block. K(+)-modified ischemia resulted in a mean activation delay in the center of the ischemic zone of 181 +/- 8 milliseconds and a decrease in epicardial longitudinal conduction to less than 10 cm/s. K(+)-modified ischemia was associated with ventricular fibrillation in 85% of episodes compared with 28% of episodes of unmodified ischemia (P < .01). Verapamil prevented the occurrence of marked activation delay during K(+)-modified ischemia, producing local activation block following a maximum activation delay of 74 +/- 25 milliseconds. In two experiments, responses mediated by the slow inward current were produced by regional K+ elevation to 15 to 16 mmol/L, followed by concomitant regional administration of epinephrine (10(-7) mol/L). Regional [K+]e elevation alone to this level resulted in local activation block following a maximum activity delay of 70 to 80 milliseconds, whereas administration of epinephrine in combination with high [K+]e resulted in return of local activation with an activation delay of 160 to 180 milliseconds (ie, similar to that during K(+)-modified ischemia). CONCLUSIONS: Compared with unmodified ischemia, K(+)-modified ischemia resulted in marked activation delay and a high incidence of ventricular fibrillation. Based on measurements of longitudinal conduction velocity, the inhibitory effect of verapamil, and the results of experiments with high [K+]e plus epinephrine, we conclude that the marked activation delay during K(+)-modified ischemia represents conduction mediated by the slow inward current. Because the conditions produced by K(+)-modified ischemia (high [K+]e with minimal acidosis) are similar to conditions in and near ischemic border regions, we hypothesize that responses mediated by the slow inward current may occur in such regions during unmodified ischemia and may participate in the development of reentrant arrhythmias.

Animals↗
PubMed1993

Effect of rate on changes in conduction velocity and extracellular potassium concentration during acute ischemia in the in situ pig heart.

INTRODUCTION: The purpose of our study was to determine if the slowing of longitudinal intraventricular conduction in the in situ porcine heart during acute regional no-flow ischemia was rate dependent. Further, we investigated whether any rate dependence could be correlated to a rate-dependent component of the ischemia-induced rise in extracellular potassium concentration, [K+]e. METHODS AND RESULTS: We studied in situ hearts in nine anesthetized open chest pigs in which acute no-flow ischemia was induced by occlusion of the left anterior descending coronary artery. To determine the effects of steady-state rate on the slowing of conduction and rise in [K+]e during ischemia, we varied the rate of stimulation during sequential occlusions from 90 to 150 beats/min. Longitudinal conduction velocity was determined by unipolar electrodes embedded in a plaque that was sutured to the epicardial surface in the center of the ischemic zone. Myocardial [K+]e was determined simultaneously by potassium-sensitive electrodes placed at or within 1 to 2 mm of the epicardium in close proximity to the activation recording electrodes. Conduction velocity decreased more rapidly at the more rapid rates of stimulation although the reduction in conduction velocity occurring prior to the onset of conduction block was similar at both rates. The potassium change was not rate dependent and rose at the same rate regardless of the rate of stimulation. CONCLUSION: Our study demonstrates that the steady-state rate-dependent component of the slowing of intraventricular conduction induced by acute ischemia in the in situ porcine heart occurs in the absence of a rate-dependent component in the rise of [K+]e. Between rates of 90 and 150 beats/min, the rate dependence of the conduction slowing may be attributed to one or more potassium-independent factors such as the rate-dependent changes in resting membrane potential, in Vmax of the action potential upstroke, and in cell-to-cell uncoupling, which have been observed in other models of acute ischemia.

Action Potentials↗
PubMed1992

Fine mapping of monoclonal antibody epitopes on human von Willebrand factor using a recombinant peptide library.

A recombinant human von Willebrand factor (vWF) cDNA fragment library was constructed in lambda gt11 for the localization of anti-vWF monoclonal antibody epitopes. Twelve of 21 monoclonal antibodies screened identified epitopes expressed in lambda gt11 as beta-galactosidase fusion proteins. By sequence analysis, these antigenic determinants were localized to segments ranging from 17 to 105 amino acids in length. Four epitopes apparently shared by more than one antibody were identified, suggesting the presence of immuno-dominant epitopes within vWF. Monoclonal antibody C3, which blocks factor VIII (FVIII) binding to vWF, bound to the same epitope previously identified by a second monoclonal antibody which also blocks this function, suggesting that this region may be at or near the vWF/FVIII binding domain. Three antibodies recognize the same region within the vWF A2 repeat. Mutations near this region appear to be responsible for Type IIA von Willebrand's disease. The co-localization of these antibodies suggests that this domain might be exposed on the surface of vWF, consistent with its apparent increased sensitivity to plasma proteases.

Antibodies, Monoclonal↗
PubMed1992

A secondary lingual casting for removable partial dentures.

This article describes a technique for constructing a nickel chromium alloy lingual casting that reinforces a removable partial denture against heavy anterior occlusion. The metal can be cast into a thin secondary casting, and it is easily etched and bonded to the resin anterior teeth and associated base. This type of lingual casting has the potential to provide a simple and effective solution to the problem of repeated fracture or displacement of anterior teeth in many restorations.

Cementation↗
PubMed1992

The effect of pH on release of PGE2 from vaginal and endocervical preparations for induction of labour: an in-vitro study.

OBJECTIVE: To study the effect of pH and precoating with obstetric cream on the release of prostaglandin E2 (PGE2) from commercially available triacetin and starch based gels, lactose based vaginal tablets and sustained release hydrogel polymer pessaries in-vitro. DESIGN: A prospective observational study. METHODS: PGE2 preparations held in dialysis bags were placed in Ringers lactate buffer and release of PGE2 into the buffer was measured over 8-12 h by radioimmunoassay. The hydrogel polymer pessary was also assessed after precoating with obstetric cream. MAIN OUTCOME MEASURES: In-vitro PGE2 release at pH 7.4, pH 5.4 and pH 3.4. RESULTS The gel preparations provided rapid and reliable release, while the lactose based vaginal tablet provided much lower release of PGE2 with sudden and variable release occurring after 5-8 h, an effect which was enhanced at low pH. With the triacetin gel preparation, release of PGE2 was reduced at lower pH, while the starch based gel appeared to provide optimal release at pH 5.4. The hydrogel polymer pessaries provided linear release in-vitro and this was reduced at pH 3.4. In addition, precoating the sustained release hydrogel polymer pessaries with obstetric cream virtually abolished release of PGE2. CONCLUSIONS: As the vagina is normally acid, these results suggest that vaginal pH could influence PGE2 release and this may result in variable clinical responses. In view of this, pH should be taken into account in the development of preparations for clinical use. Furthermore, the use of obstetric cream should be avoided when administering PGE2 preparations for induction of labour.

Cells↗
PubMed1991

Magnitude and time course of extracellular potassium inhomogeneities during acute ischemia in pigs. Effect of verapamil.

Prior studies have demonstrated the presence of inhomogeneities in myocardial [K+]e after serial 10-minute occlusions of the left anterior descending coronary artery in the pig, even within restricted locations of an ischemic zone. These inhomogeneities are thought to underlie the electrophysiological abnormalities responsible for lethal ventricular arrhythmias through reentrant and nonreentrant pathways, but a clear association has not been demonstrated. As a prerequisite to establishing this association, these studies were performed to establish measurement standards for [K+]e inhomogeneity, to quantify the magnitude and time course of these inhomogeneities, to determine whether the inhomogeneities are greater in the ischemic border where lethal ventricular arrhythmias are known to originate, and to assess the effect of a known antifibrillatory drug on [K+]e inhomogeneities. [K+]e (expressed as the change in potassium equilibrium potential, dEK [mV]) was measured in 15 preparations using an average of 17 closely spaced, critically calibrated K(+)-sensitive electrodes having stable response characteristics. A series of four 10-minute occlusions each separated by a 50-minute reperfusion period were performed in each study. In half of the studies, intravenous verapamil (0.2 mg/kg bolus followed by 0.0065 mg/kg/hr) was administered before the fourth occlusion. In nine studies (five control and four verapamil), electrodes were placed in the marginal ischemic zone (from 2 mm outside to 5 mm inside the visible cyanotic border). In six other studies (three control and three verapamil), electrodes were placed in the central ischemic zone (10-20 mm within the ischemic region). We determined that the standard deviation is the best measure of inhomogeneity and that 12 equivalent measurement sites are required to estimate it with a satisfactory degree of statistical confidence. We found that after 10 minutes of ischemia, mean dEK was 1.6 times greater in the central than in the marginal ischemic zone, whereas mean standard deviation at the same time was 1.5 times greater in the marginal than in the central ischemic zone. Verapamil reduced mean dEK and mean standard deviation in both ischemic zones for most of the occlusion by delaying the rise in [K+]e and the inhomogeneity of that rise by 3-5 minutes. Comparisons of mean dEK with mean standard deviation revealed a steep linear relation in the marginal zone and a curvilinear relation in the central zone where higher mean dEK values were not accompanied by higher values for mean standard deviation. Furthermore, we determined that these relations were not altered by verapamil.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Fabrication, evaluation, and use of extracellular K+ and H+ ion-selective electrodes.

Ion-selective mini-electrodes have been widely employed to measure extracellular K+ and H+ during myocardial ischemia. However, the recent availability of this technology has not been accompanied by uniform fabrication, amplification, and calibration standards. In their fabrication, the chloride tips of Teflon-coated silver wires should be covered with a cellulose acetate-titanium dioxide sponge followed by a polyvinyl chloride (PVC)-valinomycin (K+) or PVC-tridodecylamine (H+) ion-selective membrane. Critical analysis of the nonworking electrodes using scanning electron micrographs has revealed membrane holes, membrane and sponge contamination, Teflon plaque, poor membrane-sponge-Teflon adhesion, and improperly applied or torn membrane. We have also found that signal amplification must have variable-gain filtration (0-1 Hz) with 0.5-pA input offset current and 10(12)-omega input resistance. Furthermore, in vitro calibration in 3 and 10 mM KCl (K+) or pH 8 and 6 buffer (H+) should produce a Nernstian slope +/- 5 or 10%, respectively, at 26 degrees C with a response time less than or equal to 50 ms, resistance greater than or equal to 10(12) omega, and drifts less than or equal to 1 mV/h. In vivo performance and calibration criteria (delineated for K+ only) include 1) transient response to bolus injections of KCl (0.12 mM/kg body wt) yielding peak amplitude changes of 2.5-3.0 mM, response times less than or equal to 10 s, and washout time constants less than or equal to 3 min, and 2) in vivo calibration to artificial independently confirmed systemic [K+] producing a Nernstian slope +/- 15% at 38 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Molecular basis of human von Willebrand disease: analysis of platelet von Willebrand factor mRNA.

von Willebrand disease (vWD), the most common inherited bleeding disorder in humans, can result from either a quantitative or a qualitative defect in the adhesive glycoprotein, von Willebrand factor (vWF). Molecular studies of vWD have been limited by the large size of the vWF gene and difficulty in obtaining the vWF mRNA from patients. By use of an adaptation of the polymerase chain reaction, vWF mRNA was amplified and sequenced from peripheral blood platelets. A silent vWF allele was identified, resulting from a cis defect in vWF mRNA transcription or processing. In two type IIA vWD patients, two different but adjacent missense mutations were identified, the locations of which may identify an important vWF functional domain. Expression in heterologous cells of recombinant vWF containing one of these latter mutations reproduced the characteristic structural abnormality seen in type IIA vWD plasma.

Alleles↗
PubMed1989

Effects of verapamil and propranolol on changes in extracellular K+, pH, and local activation during graded coronary flow in the pig.

The beta-adrenergic and calcium channel blocking agents are known to reduce heart rate and alter myocardial contractility. More recent evidence suggests that both agents affect the metabolic consequences of ischemia, independent of their effects on heart rate and contractility. We used a low-flow model of ischemia in swine with heart rate held constant by atrial pacing. Blood was shunted from the carotid artery to the left anterior descending coronary artery through a controlled-flow roller pump to assess the threshold flow for the rise in extracellular potassium ([K+]e) and fall in extracellular pH (pHe) associated with ischemia during control situations and after the administration of either propranolol or verapamil. We also measured the changes in activation delay and contractility associated with graded flow reductions in the presence and absence of these drugs. We found that when heart rate is held constant, 1) verapamil shifts the threshold flow for [K+]e and pHe to lower levels, but propranolol does not; 2) verapamil lessens activation delay, while propranolol aggravates the delay; and 3) verapamil reduces afterload and selectively depresses contractility in the reperfused ischemic zone. We conclude that the calcium channel blockers and the beta-adrenergic-blocking agents have different effects and possibly different modes of action and should not be considered interchangeable when evaluating therapeutic options for patients with ischemic heart disease.

Adrenergic beta-Antagonists↗
PubMed1989

Metabolic protection by verapamil during graded coronary flow reduction independent of effect on baseline systolic function. Separation of mechanical and ionic markers of ischemia.

Pretreatment with the calcium channel-blocking agent verapamil lowers the coronary flow associated with the first rise in myocardial extracellular potassium [( K+]e). The mechanisms underlying this effect are unclear. It is not known whether this effect is a manifestation of verapamil-induced reduction in baseline cardiac work before the reduction in coronary flow, is dependent on a selective depression of contractility within the low-flow region, or is independent of an effect on myocardial work. This study was performed to determine the relations between changes in regional contractility and [K+]e before and after verapamil (0.2 mg/kg followed by 6.5 micrograms/kg/min) when left anterior descending (LAD) coronary flow is progressively reduced and when verapamil-induced alterations in baseline myocardial work are prevented by atrial pacing and by dobutamine (4.3 +/- 2.2 micrograms/kg/min) to maintain systemic arterial blood pressure and contractility. Before verapamil-dobutamine, myocardial [K+]e rose and regional contractility fell when LAD coronary flow was reduced to 87.7 +/- 9.6% and 83.4 +/- 7.4%, respectively, of the unrestricted control value (p = NS). After verapamil-dobutamine, the threshold flow for rise in [K+]e decreased to 56.4 +/- 13.5% of the unrestricted control flow (p = 0.003), but the threshold flow for regional contractility fall was unchanged (84.8 +/- 11.3%). Our results indicate that the protective effect of verapamil on preventing ischemia-induced [K+]e release is not dependent on a reduction in baseline myocardial work. In this setting, calcium channel blockade by verapamil results in a dissociation between the ionic and mechanical events that occur when coronary flow is reduced.

Animals↗
PubMed1988

Distribution of extracellular potassium and its relation to electrophysiologic changes during acute myocardial ischemia in the isolated perfused porcine heart.

An experimental approach is described to quantitate inhomogeneity in extracellular K concentration ([K+]out) in the presence of ischemia and to relate this inhomogeneity to the electrophysiologic changes. Extracellular potassium concentration and local direct-current electrograms from the same sites were measured in isolated perfused pig hearts with the use of multiple electrodes. Dispersion of [K+]out is described under three conditions: (1) during regional ischemia in the "central zone" and the "borderzone", (2) during global ischemia, and (3) during perfusion of the heart with a high-K perfusate. Inhomogeneity was greatest during regional ischemia, especially in the borderzone, where generally lower concentrations were measured. When during regional ischemia the normal zone was perfused with a high-K perfusate, dispersion in the ischemic borderzone diminished, and higher concentrations than in the central zone were measured. During global ischemia inhomogeneity was slightly larger than during high-K perfusion. Dispersion during the latter was considered due to experimental error. A decrease in [K+]out during regional ischemia after the initial increase was closely correlated with electrical recovery of the electrograms. This decrease occurred earlier in the borderzone than in the central zone. During ischemia [K+]out was not related to the occurrence of monophasic electrograms, which are indicative of the absence of local regenerative responses. For every single electrode position a linear relationship between TQ depression and [K+]out was found, the slope of which varied with the position of the electrode. When all sites were taken together, there was no correlation between TQ depression and [K+]out. We conclude that: (1) inhomogeneity of K+ is largest in the borderzone, (2) potassium flows from the ischemic zone into the normal zone, (3) transient electrical recovery is related to a decrease (after an initial increase) in [K+]out, which is at least partly due to a flow of K+ toward the normal zone, (4) monophasic ("block") electrograms can be recorded from intrinsically excitable tissue, (5) for every single site in the ischemic region there is a linear relationship between local [K+]out and local TQ segment depression, and (6) the degree of TQ depression at a particular site is not a reliable index of the degree of ischemic injury at that site.

Animals↗
PubMed1987

Occurrence of exercise-induced and spontaneous wide complex tachycardia during therapy with flecainide for complex ventricular arrhythmias: a probable proarrhythmic effect.

Flecainide acetate, a new antiarrhythmic agent, possesses favorable pharmacokinetic and hemodynamic properties and demonstrates highly favorable antiarrhythmic activity in patients with ventricular arrhythmias. However, the proarrhythmic potential of flecainide deserves further evaluation. In 7 (13%) of 55 consecutive patients treated with oral flecainide, 200 to 600 mg/day, for complex ventricular arrhythmias (including sustained ventricular tachycardia in 14), we observed the appearance of new or more sustained exercise-induced (five patients) or spontaneous (two patients) wide complex tachycardia. The mechanism of wide complex tachycardia appeared to be ventricular tachycardia in all seven. In our series, episodes were self-remitting or successfully treated. In four patients, wide complex tachycardia did not recur during exercise testing during alternative antiarrhythmic therapy (three patients) or no antiarrhythmic therapy (one patient). These observations raise the possibility of flecainide-related proarrhythmia, manifested as an increased propensity to exercise (activity)-induced wide complex tachycardia, which was not reliably predicted by results of Holter recordings or programmed electrical stimulation. Patients with complex ventricular arrhythmias beginning long-term treatment with oral flecainide should be considered for treadmill exercise testing together with ambulatory monitoring as part of the initial assessment of drug efficacy.

Adult↗
PubMed1987

Relationship between extracellular potassium accumulation and local TQ-segment potential during acute myocardial ischemia in the porcine.

Depolarization of resting membrane potential during acute myocardial ischemia is strongly correlated with the accumulation of extracellular potassium ([K+]e). Also, diastolic currents of injury flowing across the ischemic border that occur as a result of local differences in resting membrane potentials cause changes in the TQ-segments of unipolar, DC-coupled, extracellular electrograms. Further, the changes in [K+]e and TQ-segment potentials during acute ischemia and reperfusion follow a similar time course. For these reasons, a predictable relationship between [K+]e and TQ potentials might be expected to exist. If found, easily obtainable local TQ potential measurements could serve as an index of the resting membrane depolarization induced by [K+]e accumulation and, by extension, as an index of ischemic injury. We measured local [K+]e and TQ potentials from 30 mid-myocardial sites in central and marginal ischemic zones in 2 isolated, Langendorff-perfused porcine hearts during a single, 10-min ligation of the left anterior descending coronary artery. In general, we found a linear relationship between [K+]e and TQ potential for both ischemic zones when data was taken as a whole, but the slopes (S) and correlation coefficients (R) were markedly different between the two locations (-2.24 vs -1.28 and -0.73 vs -0.51 for central and marginal zones, respectively). Further, we found a time dependent change in both S and R that was biphasic. Both were low during the first minutes, attained their maximum values at 4 mins, and then fell during the remainder of the occlusion. We conclude, therefore, that local TQ potentials cannot be used as an index of the severity of ischemic changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1987

Effect of graded coronary flow reduction on ionic, electrical, and mechanical indexes of ischemia in the pig.

This study was performed to determine the relative sensitivities of ionic, electrical, and mechanical indexes of myocardial ischemia. We used ion-selective and bipolar plunge electrodes, epicardial unipolar electrodes, a suction electrode, and ultrasonic crystals to determine the changes in intramyocardial extracellular potassium ([K+]e) and extracellular pH (pHe), local activation, epicardial TQ-ST segment, monophasic action potential duration (MAPD), and regional contractility during graded coronary flow reduction in open-chest pigs. A carotid-to-coronary shunt was created to perfuse the left anterior descending coronary artery via a roller pump. The shunted coronary flow was reduced in a stepwise fashion at 5-min intervals. In 25 pigs, the approximate myocardial blood flow associated with the initial changes in each variable was as follows: midmyocardial [K+]e, pHe, and TQ-ST segment, 0.7 to 0.8 ml/min/g; subepicardial [K+]e and TQ-ST segment, 0.6 to 0.7 ml/min/g; segmental shortening, 0.5 to 0.6 ml/min/g; local activation and epicardial TQ-ST segment, 0.3 to 0.4 ml/min/g; epicardial MAPD, 0.15 to 0.2 ml/min/g. Our results indicate that changes in [K+]e, pHe, and TQ-ST segment provide the most sensitive means of detecting myocardial ischemia and of determining the effect of interventions capable of influencing the ischemic process.

Action Potentials↗
PubMed1987

Enhancement of procainamide-induced rate-dependent conduction slowing by elevated myocardial extracellular potassium concentration in vivo.

Procainamide, a type 1A antiarrhythmic drug, blocks sodium channels and reduces the maximum rate of rise of the cardiac action potential (Vmax) in a rate-dependent fashion. In vitro, the magnitude of this rate-dependent reduction in Vmax is greater in tissue that is partially depolarized at rest than in tissue with a normal resting potential. Reductions in Vmax produced by drugs that block sodium channels are also directly related to the reductions in longitudinal conduction velocity of action potential propagation in papillary muscle preparations. We therefore sought to determine whether the rate-dependent conduction slowing induced by procainamide in the intact canine heart is enhanced in myocardial tissue abnormally depolarized by an elevated myocardial extracellular potassium concentration, [K+]o. QRS duration and epicardial activation times were measured as indexes of myocardial conduction. QRS duration and epicardial activation times were measured at control (4.0 mM) and at intermediate (6.5 mM) and high (9.2 mM) myocardial [K+]o in the presence or absence of a clinically relevant procainamide concentration (12.2 +/- 2.6 g/ml) at the longest obtainable interstimulus interval of 440 msec and at 330, 280, and 250 msec. Intermediate and high myocardial [K+]o alone induced rate-dependent conduction slowing as the frequency of stimulation increased (cycle length 440 msec to 330, 280, and 250 msec). In the presence of procainamide, rate-dependent conduction slowing was observed at all levels of myocardial [K+]o, and the amount of rate-dependent change in conduction time increased as the myocardial [K+]o was increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗