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S A Rees

Publications and source records attributed to S A Rees.

26 records · Page 2Linked to original sources
PubMed1995

Pharmacological analysis in rat of the role of the ATP-sensitive potassium channel as a potential target for antifibrillatory intervention in acute myocardial ischaemia.

We tested the hypothesis that blockade of the ATP-sensitive K+ channel (IK(ATP)) is an antiarrhythmic mechanism in acute myocardial ischaemia, using an opener of the channel (10 microM RP 49356, RP) and a blocker of the channel (10 microM glibenclamide, GL) and a combination of the two drugs (GL+RP, 10 microM each) in a randomised blinded study. Isolated rat hearts (n = 8 per group) were subjected to 30-min left regional ischaemia. GL and GL+RP widened QT interval after 10-min ischaemia (197 +/- 39 and 203 +/- 20 ms, respectively vs. 154 +/- 12 ms in controls), whereas RP significantly shortened QT interval (123 +/- 6 ms). GL and GL+RP decreased coronary flow (p < 0.05). RP caused slight increase in flow during ischaemia. These effects are all consistent with modulation of vascular and cardiac IK(ATP). RP alone had no effect on ischaemia-induced arrhythmias. Neither did GL have any effect on the incidence of ventricular fibrillation (VF: 88 vs. 100% in controls). However, GL reduced the incidence of sustained VF (VF lasting continuously for > 2 min) to 14% vs. 88% in controls (p < 0.05). Therefore, GL had defibrillatory activity. Surprisingly, in view of these findings, the GL+RP combination significantly reduced the incidence of VF to 25% (from 100% in control hearts, p < 0.05) i.e., had an antifibrillatory effect. So, two agents that produce pharmacological effects attributable to block and opening of IK(ATP) when administered singly had no effects on the incidence of ischaemia-induced VF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1993

Tacrine inhibits ventricular fibrillation induced by ischaemia and reperfusion and widens QT interval in rat.

OBJECTIVE: Tacrine was used as a tool to examine whether block of inward rectifying potassium current (IK1) represents a mechanism for suppression of arrhythmias induced by ischaemia and reperfusion. METHODS: Isolated rat hearts (n = 10-12 per group) were subjected to 30 min left regional ischaemia followed by reperfusion with and without tacrine. Rat heart was used to permit delayed rectifier (IK) block to be disregarded in interpretation of results (rat ventricle is deficient in functional IK). RESULTS: The incidence of ischaemia-induced ventricular fibrillation was reduced from 70% to 42%, 17% (p < 0.05), and 0% (p < 0.05) in hearts perfused with 0, 0.1, 1.0, and 10.0 microM tacrine. Likewise, the incidence of reperfusion induced ventricular fibrillation was reduced from 100% to 90%, 75%, and 50% (p < 0.05), respectively. Indirect evidence of repolarisation delay by tacrine was provided by QT widening; for example, 15 min after the onset of ischaemia, QT (at 100% repolarisation) was increased from 194(SEM 6) to 231(17), 235(13) (p < 0.05), and 341(24) ms (p < 0.05) by increasing concentrations of drug. QT interval measured in individual hearts during ischaemia correlated inversely with arrhythmia score (r2 = 0.392; p < 0.001). Tacrine had no effect on RR interval, coronary flow, recovery of flow during reperfusion, or occluded zone size. Tacrine caused bradycardia (significant at the 1.0 and 10.0 microM concentrations). In additional hearts (n = 12 per group), reversal of 10.0 microM tacrine-induced sinus bradycardia by left atrial pacing (5 Hz) significantly reduced tacrine induced QT widening (p < 0.05), and increased the incidence of ventricular fibrillation from 0% to 42% (although significant antiarrhythmic and QT widening effects were still present); 10.0 microM tacrine failed to reduce the incidence of reperfusion induced ventricular fibrillation in paced hearts (92% incidence v 100% in controls). CONCLUSIONS: The novel antiarrhythmic effects of tacrine, a drug with established blocking action on IK, IK1, and slow inward current, appear to result from QT widening in the rat (dependent partly on IK1 blockade in the ventricles and partly on drug induced sinus bradycardia).

Animals↗
PubMed1993

Combined administration of an IK(ATP) activator and Ito blocker increases coronary flow independently of effects on heart rate, QT interval, and ischaemia-induced ventricular fibrillation in rats.

The effects of combined administration of the ATP-dependent K+ channel opener cromakalim and the transient outward K+ current (Ito) blocker tedisamil on ventricular tachyarrhythmias, QT interval, and coronary flow were investigated in isolated rat heart (n = 12/group) subjected to 30-min regional ischaemia. When administered alone, beginning 5 min before onset of ischaemia and continuously thereafter, neither cromakalim (10 microM) nor tedisamil (3 microM) had any significant influence on the incidence of VF, although tedisamil abolished sustained VF (SVF, defined as VF lasting > 2 min). Cromakalim did not affect tedisamil's ability to abolish SVF when administered concurrently with tedisamil and had no effect on SVF when administered alone; incidences of SVF were 64, 0 (p < 0.05), 66, and 0% (p < 0.05) in control, tedisamil, cromakalim, and combined treatment groups, respectively. Occurrence of SVF was related to the width of the ventricular complex at 50% of repolarisation (QT50). Pretreatment with tedisamil widened QT50 (p < 0.05), and this effect was not attenuated by combined treatment with cromakalim. Cromakalim increased coronary flow (14 +/- 0.4 in controls versus 21 +/- 0.6 ml/min/g in cromakalim-treated hearts, p < 0.05). This effect was not reduced by coadministration of tedisamil (20 +/- 0.9 ml/min/g in hearts cotreated with both drugs). Tedisamil alone had no significant effect on coronary flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Selective IK blockade as an antiarrhythmic mechanism: effects of UK66,914 on ischaemia and reperfusion arrhythmias in rat and rabbit hearts.

1. UK66,914 is a specific and selective blocker of the delayed rectifying potassium current (IK). The effectiveness of IK block as a mechanism for prevention of ischaemia- and reperfusion-induced arrhythmias was tested by use of UK66,914: its actions in rat, a species deficient in cardiac IK were compared with its actions in rabbit, a species possessing functional cardiac IK. Antiarrhythmic actions in rabbit but none in rat is the only outcome possible if selective IK blockade is responsible for the antiarrhythmic actions of the drug during ischaemia and/or reperfusion. 2. During 30 min regional ischaemia, 0.3 and 1 microM UK66,914 had no influence on the incidence of ventricular fibrillation (VF) in rat (n = 9/group), values being 78% in controls, 100% in 0.3 microM-treated hearts and 78% in 1.0 microM-treated hearts (NS). UK66,914 also had no effect on reperfusion-induced VF incidence (100% in each group), nor on the latency to onset of ischaemia- or reperfusion-induced arrhythmias. In contrast, in rabbit (n = 13/group), similar concentrations of drug reduced the incidence of reperfusion-induced VF from 77% in controls, to 38% and 31% (P < 0.05) respectively. The incidence of ischaemia-induced arrhythmias was too low in controls to permit detection of an antiarrhythmic effect in rabbit; however no drug-induced proarrhythmia was seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Specific IK1 blockade: a new antiarrhythmic mechanism? Effect of RP58866 on ventricular arrhythmias in rat, rabbit, and primate.

BACKGROUND: The effectiveness of blockade of the inwardly rectifying K+ current (IK1) in prevention of arrhythmias is unknown. We have examined the antiarrhythmic potential of a new selective IK1 blocker, RP58866, in rat, rabbit, and primate (marmoset) isolated hearts in the settings of acute ischemia and reperfusion. METHODS AND RESULTS: In concentration-response studies (n = 12 per group), the drug reduced ischemia-induced ventricular fibrillation (VF) in rat from control incidence of 100 to 50%, 17% (p < 0.05), and 0% (p < 0.05) at 1, 3, and 10 mumol/L, respectively. RP58866 produced significant bradycardia at the 3- and 10-mumol/L concentrations and significant QT interval widening at all three concentrations (p < 0.05). When rat hearts (n = 12 per group) were paced (5 Hz) via the left atrium to prevent bradycardia, the antiarrhythmic effects of 10-mumol/L RP58866 were unmodified (ischemia-induced VF incidence was reduced by drug from 83% in control hearts to 8%; p < 0.05). Similarly, pacing did not prevent the drug's QT-widening activity at 90% repolarization (QT90 was 64 +/- 3 msec in control hearts versus 128 +/- 17 msec in the presence of 10 mumol/L of drug after 10 minutes of ischemia; p < 0.05). These values are similar to equivalent values in unpaced hearts (65 +/- 3 msec in control hearts versus 159 +/- 15 msec with 10 mumol/L of drug; p < 0.05). In separate groups of rat hearts (n = 10 per group) subjected to 10 minutes of ischemia, reperfusion-induced VF incidence was reduced from 90% in control hearts to 10% (p < 0.05), 0% (p < 0.05), and 0% (p < 0.05) by 1-, 3-, and 10-mumol/L RP58866. To examine whether drug actions were species-specific, we performed further studies in rabbit and primate using the middle concentration of RP58866 (3 mumol/L). Ischemia-induced VF incidence was too low in these species to assess the effects of the drug. However, RP58866 widened QT interval (p < 0.05), slowed heart rate (p < 0.05), and reduced the incidence of reperfusion-induced VF from 67% to 8% (p < 0.05) in rabbit. Furthermore, in the more clinically relevant primate species (marmoset; n = 9-12 per group), RP58866 (3 mumol/L) abolished ischemia-induced VT (36% incidence in control hearts; p < 0.05) and significantly reduced the incidence of ischemia-induced ventricular premature beats from 91% to 33% (p < 0.05). The drug was also effective against reperfusion VF in primates (incidence reduced from 64% in control hearts to 11%; p < 0.05). As in rat and rabbit, RP58866 significantly widened QT interval in primate and caused bradycardia before and during ischemia. RP58866 had no significant influence on coronary flow in any species. Finally, in further studies on rat, QT widening by RP58866 was found to persist relatively unmodified in nonischemic hearts perfused with solution containing K+ elevated to 8 mmol/L to mimic the early ischemic milieu. CONCLUSIONS: RP58866, a selective IK1 blocker, is a potent and efficacious new antiarrhythmic drug in ischemia and reperfusion in rat, rabbit, and primate. When tested in rat, pharmacological activity was undiminished by cardiac pacing or elevation of extracellular K+.

Animals↗
PubMed1991

A medical college service for computer-generated graphics with DIY aspects.

This paper describes the setting-up and management of a computer graphics service, mainly for producing 2 x 2 inch projection slides, by a department of medical illustration within a medical school. The service has been arranged to provide a limited facility for composing original illustrations by computer and to encourage medical and scientific staff to compose their own illustrations. These are recorded on magnetic disc for review and possible adjustment by medical illustrators. Images are then output as slides or paper prints by the medical illustration department. The range of equipment and apparatus used is described and evaluated briefly. Also described are the effects of the introduction of a computer-generated graphics service on the general work of non-patient slide production in the department.

Computer Graphics↗