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Biomedical subjects

R M Donaldson

Publications and source records attributed to R M Donaldson.

At least 55 records · Page 3Linked to original sources

Study of the electrophysiological effects of early or subendocardial ischaemia with intracavitary electrodes in the dog.

The early electrophysiological patterns of regional subendocardial ischaemia were studied by using the paced endocardial evoked response and simultaneous endocardial monophasic action potential recordings in 16 experiments in open chested dogs. Ischaemia was produced by transient (1-3 min) coronary artery occlusion. Regional subendocardial isochaemia caused asynchronous activation due to differential conduction delay and shortened repolarization as evaluated by the duration of the paced evoked response from 175 +/- (SD) 18.7 ms to 167 +/- 16 ms (P less than 0.001). These changes occurred within 60 s of occlusion and reversed rapidly after release of the occlusion. In simultaneous endocardial monophasic action potentials there was a decrease in plateau amplitude and the duration of repolarization shortened from 180 +/- (SD) 21.2 ms to 167 +/- 20.4 ms (P less than 0.001). The delay in endocardial activation after 2 min ischaemia was 5.5 ms, which is considerably shorter than the conduction delay previously reported in the subepicardial layers. The calcium-channel blocking drug verapamil (infused at 0.4 mg/kg) altered the rate at which shortening of repolarization and asynchronous activation occurred during ischaemia in six experiments. These experiments suggest that intracavitary electrodes could provide earlier and more sensitive detection of regional subendocardial ischaemia and may permit the assessment of therapy on the early electrical changes in the intact heart.

Action Potentials↗

The ventricular endocardial paced evoked response.

The endocardial ventricular evoked response which follows delivery of a unipolar stimulus down the sensing electrode is remarkably uniform, and is of slightly longer duration at the base than at the apex of the heart. As the same lead is used for both pacing and sensing, it is possible to record the evoked T wave representing dominantly local repolarization which follows a pacing-induced depolarization from the same site. Studies of the pacing evoked response following administration of drugs with class 3 mode of action are similar to those obtained by monophasic action potential recordings, and suggest that myocardial repolarization can be accurately assessed by this technique. The stimulus to evoked T wave timing has been used to design a pacing system which offers the advantage of physiological control of pacing rate, independent of atrial activity, using a conventional endocardial electrode lead system. The potential advantages of this system are reviewed.

Amiodarone↗

The use of QT interval to determine pacing rate: early clinical experience.

Despite the current availability of physiologic pacing systems, there remain distinct disadvantages associated with their operation. Although in theory the atrial synchronous pacemaker (VDD or DDD) is the ideal system, in practice it performs satisfactorily over a very limited range of heart rates in a limited number of individuals. We describe the TX system which incorporates ventricular pacing and is driven by T wave sensing determined by the QT interval. This pacemaker can distinguish between physiologic and pathologic tachycardias while providing an almost unlimited rate response even in the presence of an unresponsive atrium.

Bradycardia↗

Rate responsive pacing using the evoked QT principle. A physiological alternative to atrial synchronous pacemakers.

We have evaluated clinically a rate-responsive pacemaker which uses the evoked QT principle as indicator of physiological demand. This pacemaker is microprocessor-based and fully programmable noninvasively through radiofrequency coupling to an external microcomputer. To date this system has been implanted in 15 patients. With this QT sensing pacemaker the rate response to exercise was smooth and progressive, and gradually returned to the basic paced rate after termination of activity. Physiologic rate responsive pacing resulted in significant improvement in exercise tolerance and a 40% increase in cardiac output when compared to fixed-rate pacing in 8 patients. This initial experience confirms the possibility of obtaining a physiological response to exercise using a pacing system dependent only on a unipolar electrode which is independent of the problems of atrial activity and sensing. Rate responsive pacing might prove to be a useful alternative to atrial synchronous systems, and particularly advantageous in those patients whose sinoatrial function is abnormal or who suffer from atrial arrhythmias.

Adult↗

Intracardiac electrode detection of early ischaemia in man.

We have evaluated an intracardiac technique for the study of the electrophysiological patterns of early or subendocardial ischaemia in man. Simultaneous recordings of the paced endocardial evoked response and monophasic action potentials were obtained during pacing stress testing in 10 patients with reversible myocardial ischaemia. Early patterns of change occurred in both these recordings in response to regional ischaemia. Abnormal rate corrected shortening of the local repolarisation time in the paced endocardial evoked response from the left ventricular ischaemic zone diverging from control non-ischaemic values by a mean of 10.6% was paralleled by decreases in the simultaneous paced monophasic action potentials duration. A differential delay in the local activation time and conduction was also documented by the paced endocardial evoked response and monophasic action potential electrodes. Non-ischaemic control zones showed no changes in the pattern of activation and repolarisation. Disparate repolarisation times and asynchronous activation within the myocardium were thus consistently demonstrated during regional ischaemia. These changes in the endocardial paced evoked response and monophasic action potentials always preceded the appearance and regression of the clinical ischaemia. Intracavitary recordings may thus provide earlier and more sensitive detection of regional ischaemia during cardiac catheterisation or coronary artery surgery. The study of the patterns of activation and response could permit the assessment of interventions on the early electrical changes of ischaemia, and may bridge the gap between in vitro studies and the electrophysiological studies performed upon the intact heart.

Action Potentials↗

Intrinsic factor-mediated absorption of cobalamin by guinea pig ileal cells.

To investigate the fate of intrinsic factor and cobalamin during cobalamin absorption, we incubated enterocytes isolated from guinea pig ileum for periods of up to 30 min with (57)Co-labeled cyano-cobalamin bound either to human intrinsic factor or to rabbit intrinsic factor biosynthetically labeled with [(35)S]methionine. When the labeled complex was incubated for 30 min with isolated ileal cells under conditions that block cellular metabolism, virtually all cellular radioactivity could be removed by washing the cell surface with EDTA or acid. In contrast, washing removed only half the radioactivity from cells incubated at 37 degrees C in O(2). When residual cellular radioactivity was extracted and analyzed by gel filtration, 80-94% of both the (35)S and (57)Co radioactivity eluted in the same fractions as the original complex. The remaining 6-20% eluted as free [(57)Co]cobalamin or [(35)S]methionine. To examine events occurring after 30 min, we instilled into tied-off ileal loops of intact guinea pigs radiolabeled intrinsic factor-cobalamin complex and extracted nondissociable radioactivity 2-4.5 h later. The proportion of extracted (57)Co eluting as free cobalamin increased to 39-46%, that eluting as intrinsic factor-cobalamin complex declined to 22-45%, and 9-34% now eluted as a macromolecule that reacted with antitranscobalamin II antibody but not antiintrinsic factor antibody. Extracted (35)S radioactivity eluted in several peaks in addition to the intrinsic factor peak. These findings suggest that (a) after reversible attachment of intrinsic factor-cobalamin complex to its ileal surface receptor, an energy-dependent process prevents removal of the complex from the cell surface by EDTA or acid; (b) cobalamin dissociates from intrinsic factor and, as suggested by previous workers, binds to a molecule antigenically similar to transcobalamin II; and (c) intrinsic factor is slowly degraded and forms breakdown products that are detectable in ileal extracts.

Animals↗

The role of nitrates on regional subendocardial ischaemia--studies with endocardial monophasic action potentials during pacing-induced angina.

Intracavitary recording of monophasic action potentials (MAP) is a sensitive means of detecting the electrophysiological effects of early or subendocardial ischaemia. The effect of nitroglycerin on the MAP was evaluated during pacing-induced angina in seven patients with localized, reversible ischaemia. Recordings from the ischaemic zone demonstrated a decrease in MAP amplitude and an abnormal rate-corrected shortening of MAP repolarization. The "control" right ventricular MAP showed only the expected rate-dependent decrease in duration throughout the pacing stress test. The ischaemic MAP were unchanged following the intracoronary administration of 100 micrograms nitroglycerin. In contrast, 200-300 micrograms intravenous nitroglycerin produced a normalization of MAP amplitude and duration in spite of continuous pacing at the angina-provoking rate. These changes were preceded by a fall in aortic pressure (from mean 123/84 to 96/62) and subsequent lowering of the rate-pressure product. The major beneficial effects of nitroglycerin on the early electrical changes of pacing-induced ischaemia are thus related to decreased oxygen demand due to cardiac unloading.

Action Potentials↗

Detection of ventricular thrombi by ultrasound.

Left ventricular mural thrombi have certain characteristics in location and accoustical appearance that permit their detection by two dimensional echocardiography. We report our experience in the detection of cardiac thrombus by ultrasound.

Coronary Disease↗

Emission tomography in embolic lung disease: angiographic correlations.

The data from 84 patients with suspected embolic lung disease who underwent radionuclide section scanning of the chest is reported. All underwent additional conventional planar imaging; specific angiographic evidence of embolic disease was available in 12 cases. A good correlation between the section scans and angiography was obtained. Greater sensitivity in lesion detection was obtained by multiplane section imaging, which should reduce the number of diagnostic uncertainties in embolic lung disease.

Humans↗

Effect of intravenous amiodarone on myocardial repolarization and refractoriness: a new method of assessment.

Amiodarone is a benzofuran derivative with depressant effects on all electrically active cardiac tissues and important antiarrhythmic properties after long-term dosing. We evaluated its short-term effects on myocardial repolarization and refractoriness in eight patients. The duration of repolarization was evaluated by a new method, the paced evoked-response system, which records the dominantly local repolarization that follows a controlled (paced) depolarization from the same site. Intravenous amiodarone (5 mg/kg) prolonged the latency of the stimulus peak-evoked T wave interval an average of 39.4 msec (+15% of control) 10 min after infusion. In animal experiments these changes correlated well with simultaneous increases in the paced monophasic action potentials obtained with suction electrode catheters. There was also a lengthening of the effective refractory period of the atrioventricular node from 270 +/- 20 to 295 +/- 25 msec. Atrial and ventricular refractoriness were not altered. Amiodarone early activity at the atrial and ventricular level apparently differs from that long-term therapy and appears to favor changes in action potential duration and not changes in refractoriness.

Action Potentials↗

Hemodynamically significant anomalies of the coronary arteries. Surgical aspects.

In 78 (0.9%) of 8,283 patients without associated congenital heart disease studied by angiography, one or more major elements of the coronary arterial system originated in an ectopic manner. Symptoms attributable to the aberrant vessel more present in 20 of the 78 patients and in 15 patients these anomalies were treated surgically. The hemodynamically significant anomalies which lead to abnormalities of myocardial perfusion are of particular surgical importance. There are 4 major types: 1) aberrant origin of the left anterior descending branch from the pulmonary artery; 2) origin of the left coronary artery from the right aortic sinus; 3) origin of the left coronary artery from the pulmonary artery and 4) severe atherosclerotic occlusive disease in an aberrant vessel. The incidence, angiographic features and surgical aspects of these anomalies are discussed.

Adolescent↗

Rupture of a papillary muscle of the tricuspid valve. Echocardiographic diagnosis.

Abnormal tricuspid valve structure and motion resulting from the rupture of a right ventricular papillary muscle were visualised by two dimensional echocardiography. These findings were confirmed at operation. Two dimensional echocardiography appears to be a satisfactory method for evaluating patients with tricuspid regurgitation of sudden onset with a view to surgery.

Adult↗