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Biomedical subjects

M J Curtis

Publications and source records attributed to M J Curtis.

At least 55 records · Page 3Linked to original sources
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

Endogenous chemical mediators of ventricular arrhythmias in ischaemic heart disease.

The causes of ventricular arrhythmias in the acute setting of coronary artery disease (myocardial ischaemia and reperfusion) may be approached using two paradigms. One, the electrophysiological paradigm (disturbance of ionic homeostasis, electrogenesis, and conduction) has not been addressed in detail here. Instead, we have focused on the concept of a chemical paradigm of arrhythmogenesis. Many endogenous chemical substances (derived from the myocardium, nerves, blood plasma, platelets, leucocytes, and endothelium) accumulate in the ischaemic tissue or are produced during reperfusion and many of these have been suggested to modulate ventricular arrhythmias. Some substances may be arrhythmogenic and others may be antiarrhythmic. Together they determine whether or not arrhythmias occur. Potentially arrhythmogenic substances include potassium, catecholamines, cAMP, histamine, 5-HT, lysophosphatidylcholine, palmitylcarnitine, platelet activating factor, prostaglandins, leukotrienes, thromboxane A2, angiotensin II, endothelin, opioids, protons, calcium, and free radicals. We have considered each of these, with the objective of evaluating which are important in arrhythmogenesis in acute ischaemia and reperfusion. Two alternative models of arrhythmogenesis are possible in the context of the chemical paradigm: a series model (where one substance or its effects determines the arrhythmogenicity of another) and a parallel model (where numerous substances operate independently to cause ventricular arrhythmias). It is not yet clear which model is most appropriate; a combination of the two is possible, so a working prototype has been constructed which accommodates both. A set of criteria (hitherto lacking) for establishing whether a substance is sufficient and necessary for arrhythmogenesis is proposed. Some generalisations are given on approaches to establishment of these criteria for putative arrhythmogenic substances. Finally, we have considered how arrhythmogenic drug development may be influenced by using the chemical paradigm as an alternative to the electrophysiological paradigm of arrhythmogenesis.

Acute Disease↗
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↗
PubMed1993

Arthrodesis of the first metatarsophalangeal joint: a biomechanical study of internal fixation techniques.

This study compares the strength and rigidity of four methods of internal fixation for arthrodesis of the first metatarsophalangeal joint. Ten matched pairs of cadaveric first rays were harvested and arthrodesis performed by one of four techniques: (1) planar excision of joint surfaces and fixation with crossed Kirschner wires, (2) planar excision of joint surfaces and internal fixation with a dorsal plate and screws, (3) planar excision of joint surfaces and internal fixation with an interfragmentary screw, or (4) excision of the joint surfaces using powered conical reamers and fixation with an interfragmentary lag screw. Biomechanical testing with a Bionix 858 materials testing machine was carried out, applying a plantar force utilizing principles of cantilever loading. Force applied and displacement of the arthrodesis were recorded. Of the four methods tested, bony preparation with power conical reamers and supplementary interfragmentary screw fixation was the most stable.

Arthrodesis↗
PubMed1993

Factors related to susceptibility and recruitment by cults.

Unprecedented escalation of secular and religious cults has necessitated further inquiry into more precise conditions under which individuals develop vulnerability and become converted by these groups. The present discussion focuses on a number of factors which seem to influence individuals' susceptibility and recruitment by cults. These variables include (a) generalized ego-weakness and emotional vulnerability, (b) propensities toward dissociative states, (c) tenuous, deteriorated, or nonexistent family relations and support systems, (d) inadequate means of dealing with exigencies of survival, (e) history of severe child abuse or neglect, (f) exposure to idiosyncratic or eccentric family patterns, (g) proclivities toward or abuse of controlled substances, (h) unmanageable and debilitating situational stress and crises, and (i) intolerable socioeconomic conditions. Also presented are methods utilized by cults, e.g., intimidation, coercion, and indoctrination, for systematically recruiting, initiating, and influencing inductees. More careful attention to these factors might help health care providers, educators, clergy, and concerned family and friends determine more precisely individuals at greater risk for recruitment into cults.

Adolescent↗
PubMed1992

Musculoskeletal injuries in the Afghan war.

Among the 1274 patients admitted to a Pakistan border hospital from 1985 to 1987, the distribution and outcome of musculoskeletal war injuries differed from those seen in other conflicts. Serious complications from injuries were found in approximately 50 per cent of patients, of which most were wound infections, chronic osteomyelitis, and restriction of joint motion. Guerrillas in the Afghan war had no access to acute medical treatment in the field. Many patients died before reaching the hospital, as reflected in the low proportion of paraxial injuries; very high complication rates were noted for all injuries. Although some complications, such as soft tissue infection and foreign body retention are not site specific, other complications such as contracture, non-union, loss of range of motion, and chronic osteomyelitis are highly related to the region injured. Early surgical management and evacuation of those with musculoskeletal war injuries can greatly improve the outcome from war trauma and reduce the subsequent disability. However, the increasing use of hand-held anti-aircraft missiles may prevent the rapid evacuation of the wounded in future conflicts, and may make the situation seen in Afghanistan more common.

Adolescent↗
PubMed1992

Computerized templating in uncemented total hip arthroplasty to assess component fit and fill.

The aim of the uncemented femoral component in total hip arthroplasty is to achieve a stable bone-prosthesis interface without the use of polymethyl methacrylate (PMMA). Maximal fill of the femoral canal by the prosthesis promotes initial stability and long-term optimal stress transfer to the bone. The percentage "fit and fill" of the proximal femur by three prostheses, the porous coated anatomic, anatomic medullary locking, and the Harris-Galante, was compared by use of a computerized templating model to assess preoperative radiographs of 20 patients. Results showed that overall percentage fit and fill was similar and satisfactory (greater than 60%) in 17 of 20 patients. If a satisfactory fill was not achieved with one prosthesis, another prosthesis did not significantly improve fill. Lack of bony contact in the proximomedial femur was the most common deficiency noted.

Computer-Aided Design↗
PubMed1992

A modified model of global ischaemia: application to the study of syncytial mechanisms of arrhythmogenesis.

OBJECTIVE: The aim was to develop a simple modified global ischaemia preparation to study the relation between ischaemic zone size and the incidence of ischaemia induced and reperfusion induced arrhythmias, to test the hypothesis that arrhythmias are initiated by flow of injury current between the ischaemic zone and the uninvolved myocardium. The new model was used to examine whether injury current suppression is involved in the mechanism of action of a new antiarrhythmic intervention, substitution of chloride anion by nitrate. METHODS: Isolated perfused (Langendorff mode) rat hearts (n = 12 per group) were subjected to 30 min global or regional ischaemia. Ventricular arrhythmia incidence during ischaemia and during reperfusion were related to the size of the involved region. The modified model of global ischaemia employed right intra-atrial superfusion to maintain normal sinus rate and 1:1 atrioventricular (AV) conduction. RESULTS: Sham ligation, low left coronary ligation, high left coronary ligation, and global ischaemia produced, as a percentage of total ventricular weight, 0%, 21.0(SEM 0.8)%, 47.0(1.0)%, and 100% regions of ischaemia (occluded zones). Heart rates were similar in each group and AV block did not occur. The incidences of ischaemia induced ventricular fibrillation (VF) were 0, 17, 75, and 17% with increasing occluded zone sizes. Incidences of reperfusion induced VF were 0, 8, 92, and 92% respectively. The antiarrhythmic action of substitution of extracellular chloride by nitrate, previously shown using models of regional ischaemia, was confirmed in the modified global ischaemia model. CONCLUSIONS: These findings strongly support the theory that current of injury between ischaemia and adjacent non-ischaemic zones is necessary for initiation of ischaemia induced VF, since susceptibility was maximal when ischaemic and uninvolved regions were equivalent in size (and the scope for injury current was maximal) whereas susceptibility was negligible when scope was minimal. In contrast, reperfusion induced VF appears to depend only on the presence and amount of reperfused tissue, indicating that flow of injury current between involved and uninvolved tissue is unnecessary for its initiation. Discrimination of the mechanism of action of antiarrhythmic interventions may be possible since drugs effective solely via amelioration of flow of injury current (or incrementation of collateral flow) will not influence arrhythmias in this model. Modification of injury current and collateral flow do not appear to contribute to the antiarrhythmic action of substitution of extracellular chloride by nitrate.

Animals↗
PubMed1992

Anion manipulation: a new antiarrhythmic approach. Action of substitution of chloride with nitrate on ischemia- and reperfusion-induced ventricular fibrillation and contractile function.

The role of anions in the initiation of ischemia- and reperfusion-induced arrhythmias is unknown. We examined the antiarrhythmic effects of isotonic substitution of extracellular Cl- with NO3- by using the rat Langendorff preparation (n = 12 per group). During 30 minutes of regional ischemia, the incidence of ventricular fibrillation (VF) was reduced from 50% in hearts perfused with control solution (containing a Cl-:NO3- ratio of 100:0) to 25%, 0% (p less than 0.05), 0% (p less than 0.05), and 0% (p less than 0.05) by perfusion with solution containing Cl-:NO3- ratios of 75:25, 50:50, 25:75, and 0:100, respectively. The incidence of reperfusion-induced VF was also reduced from 58% to 25%, 8% (p less than 0.05), 8% (p less than 0.05), and 0% (p less than 0.05), respectively. Similar effects were produced in hearts reperfused after briefer durations of ischemia (10 or 15 minutes). Substitution of NO3- for Cl- also facilitated spontaneous termination of VF. Heart rate and occluded zone size were not affected by anion manipulation. Coronary flow was affected by NO3-, but changes did not correlate with arrhythmias. During ischemia, electrocardiographic changes indicative of class III activity (widening of the ventricular complex) were produced by anion substitution. These changes occurred selectively in the ischemic tissue with no significant influence before ischemia onset. However, the relation between this effect and arrhythmia reduction was not linear and a cause-effect relation is therefore unlikely. In separate groups of hearts (n = 12 per group), switching from 100:0 to 0:100 Cl-:NO3- solution or vice versa 10 seconds after coronary occlusion or just before reperfusion demonstrated that 1) protection against ischemia-induced VF resulted partly from an action in the ischemic zone and partly from an action in the nonischemic zone, and 2) protection against reperfusion-induced VF resulted principally from an action occurring during reperfusion and within the reperfused tissue. To assess whether benefit was offset by deleterious effects on contractile function in nonischemic tissue, we constructed Starling curves in isolated rate hearts. The 0:100 Cl-:NO3- solution had no effect on compliance or contractility at physiological end-diastolic pressures but reduced the slope of the peak systolic pressure-volume relation by approximately 20% as end-diastolic pressure was increased above 10 mm Hg. In conclusion, anions appear to play a hitherto unrecognized role in arrhythmogenesis in ischemia and reperfusion. Manipulation of anion homeostasis may represent a novel target for antiarrhythmic drug development.

Animals↗
PubMed1992

The initial stability of uncemented acetabular components.

The osseo-integration of an uncemented acetabular component depends on its initial stability. This is usually provided by under-reaming of the acetabulum. We have assessed the fixation of 52 mm porous-coated hemispherical prostheses inserted into cadaveric acetabula under-reamed by 1, 2, 3 and 4 mm. We tested the torsional stability of fixation, after preloading with 686 N in compression, by measuring the torque required to produce 1 degree and 2 degrees of rotation. Under-reaming by 2 mm and 3 mm gave significantly better fixation than 1 mm (p less than 0.01, p less than 0.02). Insertion after under-reaming of 4 mm caused some fractures. To obtain maximum interference fit and optimal implant stability, we recommend the use of an implant 2 mm or 3 mm larger than the last reamer.

Acetabulum↗
PubMed1992

Tibiotalar contact and fibular malunion in ankle fractures. A cadaver study.

Six cadaveric ankles were dissected, preserving medial and lateral ligaments; an axial load of 455N was applied to the tibia supported by the foot and ankle. The unconstrained tibia was moved through 20 degrees of flexion and extension to simulate walking. The tibiotalar contact area was defined using carbon black suspension, recorded photographically, and measured using computerized area analysis. Osteotomy of the distal fibula was performed and fixed with a specially modified plate; a selection of plates provided fixation with 0 degrees or 30 degrees of external rotation in combination with 0 or 2 mm of shortening. The contact area was measured for each of the plates and after division of the deltoid ligament. There were greater than 30 percent decreases in tibiotalar contact with both fibular shortening and external rotation, doubled with a divided deltoid ligament. Anatomic restoration of both fibular length and rotation is essential for normal ankle mechanics. The deltoid ligament has crucial effects on the stability of the ankle mortise.

Ankle Joint↗
PubMed1992

Left main coronary artery dissection during cardiac catheterization.

A 70-year-old man with a downward sloping origin of the left main coronary artery developed left main dissection at coronary angiography and died despite emergency coronary by-pass surgery. Autopsy showed that the left main coronary artery had an acute angle take off and dissection had originated at the junction of the superior wall of the left main and the aorta. The combination of left main stenosis secondary to dissection and severe right coronary atherosclerosis had caused circumferential subendocardial left ventricular infarction. The left main coronary artery had mild atherosclerosis and lacked cystic medial necrosis. An angulated left main coronary artery may be a risk factor for dissection at angiography.

Aged↗
PubMed1992

The Ring total knee replacement--a comparison of survivorship.

Long term results of joint replacement are frequently expressed as survivorship; it therefore becomes increasingly important to have the ability to make valid comparisons between survivorship tables in order to determine accurately the statistical significance of published differences. We present a statistical method for direct comparison of survivorship tables. We have applied this technique to evaluate the survivorship of the unconstrained, uncemented Ring total knee replacement first implanted in 1975 and compare this to contemporaneous constrained prostheses. There is a significant improvement in survival, which suggests a beneficial long-term effect on the bone/implant interface of this changing design concept.

Aged↗
PubMed1991

Torsades de pointes: arrhythmia, syndrome, or chimera? A perspective in the light of the Lambeth Conventions.

What is torsades de pointes? Is it an arrhythmia or a syndrome? The distinction is critical. In this article I have attempted to explain why this is so. Both from the clinical and nonclinical standpoint, it is of overriding importance that torsades de pointes be amenable to measurement and quantification. This is the fundamental prerequisite for any variable to be of value as an endpoint in an investigation. Measurement and quantification require that a variable has an objective definition that is both inclusive and exclusive. In his seminal work, Dessertenne coined the term torsades de pointes to describe an arrhythmia with unusual features. However, torsades de pointes has been reinterpreted and redefined by Dessertenne's successors. It was originally described as occurring in certain settings (e.g., hypokalemia). However, this has been reinterpreted to mean that a specific set of antecedent conditions (such as hypokalemia) are part of the definition of torsades de pointes. If this is the case, then torsades de pointes is a syndrome, not an arrhythmia. For those more concerned with arrhythmias than with syndromes, the key issue to be determined is what to call the arrhythmia that is part of the syndrome. I have put forward some suggestions with the objective of answering this question, using the Lambeth Conventions as a guide. I believe that there is strong case for ventricular tachyarrhythmias to be classified simply as tachycardia or fibrillation, with the optional use of the term delayed repolarization syndrome in cases where a long QT interval is present. The latter term should be used as one might use the term acute myocardial ischemia, i.e., to denote an underlying condition; it should not be used to define the arrhythmia itself. Twenty-four years after its introduction, the term torsades de pointes has now become a chimera and is best abandoned.

Animals↗
PubMed1991

Evaluation of acetabular stability in uncemented prostheses.

The stability of two commonly used uncemented acetabular prostheses fixed with either pegs or screws has been established by evaluating the torque strengths in ten cadaveric acetabulae. The initial stability of implants to simulated frictional loads was satisfactory compared to previous estimations of the frictional torques in polyethylene-on-metal and metal-on-metal articulations. Testing of the torque required to produce 2 degrees of rotation at the bone-implant interface showed that the peg fixation required significantly greater loads than did the screw fixation (P less than .03). Testing the prostheses to failure gave good results, although lower than previous cemented arthroplasty estimations. The margin of stability over the frictional torques that can be generated is such that it may affect the bony ingrowth into these prostheses. This may account for the common finding of fibrous ingrowth in these prostheses.

Acetabulum↗