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Biomedical subjects

M B Simson

Publications and source records attributed to M B Simson.

54 records · Page 3Linked to original sources
PubMed1981

Early ischemia after complete coronary ligation in the rabbit, dog, pig, and monkey.

The character and extent of the myocardial ischemic "borderzone" was assessed in the rabbit, dog, pig, and monkey. A fluorophotographic technique permitting high resolution (+/- 50 micrometers) display of myocardial ischemia has been developed. Reduced intracellular NADH (ischemia) fluoresces and may be photographed while oxidized NAD (perfused tissue) does not. A coronary artery was ligated for 5 min in open-chest rabbits, dogs, pigs, and monkeys. A fluorescent dye was injected into the left atrium as a coronary vascular marker, and the tissue was quick-frozen. The ischemic margin was well seen and was jagged in all species. The distance from anoxic to perfused tissue (borderzone) was less than 50 micrometers in all species. A narrow "oxygen-diffusion zone" of nonperfused non-anoxic tissue is visible in isolated heart perfused with blood-free solution. The width of this zone is inversely related to myocardial oxygen consumption and is less than 50 micrometers in a working blood-perfused heart. We have not yet correlated the oxygen diffusion zone with the clinically defined salvageable borderzone. In dogs, collateral vessels provide a heterogeneous border to the ischemic region so that the canine ischemic pattern differs from that of pigs, rabbits, and monkeys.

Animals↗
PubMed1981

Detection of delayed ventricular activation on the body surface in dogs.

This study describes a noninvasive method for detecting delayed ventricular activation, caused by ischemia, on the body surface. Signal averaging and a newly developed high-pass digital filter were used. The filter has the property that it does not create an artifact or ring after the QRS complex ends, thereby allowing the detection of microvolt-level potentials that occur immediately after the QRS complex. Eleven dogs were studied before and during acute ischemia induced by coronary artery ligation and latex embolization. The ischemic region was mapped with bipolar electrodes and, after the chest was rapidly closed, signal-averaged recordings were made from the body surface. Repeated cycles of ventricular mapping and signal averaging were performed. In each dog, delayed and fractionated electrograms were recorded directly from the ischemic epicardium that lasted a maximum of 118 +/- 18 ms after QRS onset. The duration of the ventricular electrograms varied with time. Whenever delayed epicardial electrograms were recorded, filtered signal-averaged leads showed microvolt-level potentials early in the S-T segment that were continuous with the QRS complex. The duration of ventricular activation, as measured from the bipolar electrograms and from the filtered signal-averaged leads, correlated well (r = 0.93, P less than 0.001). Because of the absence of filter ringing, low-level potentials could be detected less than 40 ms after the QRS complex ended. This study demonstrates that microvolt-level potentials arising from delayed ventricular activation can be reliably detected on the body surface, even when they occur just after the QRS complex.

Animals↗
PubMed1981

Use of signals in the terminal QRS complex to identify patients with ventricular tachycardia after myocardial infarction.

Small, high-frequency electrocardiographic signals were recorded from the body surface in 39 patients with and 27 patients without ventricular tachycardia (VT). All patients were in normal sinus rhythm, had a previous myocardial infarction, were not taking antiarrhythmic drugs, and did not have bundle branch block. Bipolar X, Y, Z leads were signal averaged and processed by a bidirectional digital filter that allowed low-amplitude signals to be detected in the terminal QRS complex and ST segment. The high-pass filter frequency was 25 Hz. Patients with VT had a lower amplitude of high-frequency signal in the late QRS complex. In the last 40 msec of the filtered QRS complex, the patients with VT had 14.9 +/- 14.4 microV of high-frequency signal; patients without VT had 73.8 +/- 47.7 microV (p less than 0.0001). Ninety-two percent of the patients with VT had less than 25 microV of high-frequency voltage; only 7% of patients without VT had less than 25 microV (p less than 0.0001). Patients with VT had a longer QRS duration than those without VT, 139 +/- 26 vs 95 +/- 10 msec (p less than 0.0001). The QRS duration was longer than 120 msec in 72% of the patients with VT but in none of the patients without VT (p less than 0.0001). In all patients there was no separate and discrete high-frequency signal in the ST segment. Advanced signal processing of the ECG accurately identified the patients in the study with VT after myocardial infarction.

Electrocardiography↗
PubMed1981

Surgical therapy of variant angina associated with nonobstructive coronary disease.

Patients with variant angina refractory to medical therapy pose a difficult management problem. We report two patients with variant angina who had focal spasm in coronary arteries with fixed obstructions of less than 20% of the luminal diameter. Ischemic episodes were accompanied by malignant ventricular arrhythmias and third degree atrioventricular block. Symptoms were refractory to intensive medical management with nitrates and calcium blocking agents in one patient and with nitrates in the other who was treated before calcium blockers were available. Surgery was done; a bypass graft was placed distal to the area of focal spasm and the native artery was ligated proximally. Both patients are asymptomatic 24 and 66 months after surgery and neither takes anginal medication regularly. The surgical procedure outlined should be considered only if therapy to control life threatening ischemic symptoms with nitrates and calcium blocking agents fails.

Angina Pectoris↗
PubMed1980

Heterogeneity of the coronary microcirculation during low-flow ischemia: a model for the heart in shock.

The etiology of myocardial damage in shock is multifactorial. Poor perfusion of the coronary bed during shock may result in areas of cellular anoxia. This study examines the response of isolated perfused rabbit hearts to low-flow ischemia utilizing a high resolution assay of ischemia, NADH fluorescence photography. The hearts were made ischemic by reducing coronary perfusion pressure to 50% for 60 seconds. Islands of ischemic anoxia appear over the surface of the ventricle. The intensity of the ischemic response increased with successive ischemic insults (P less than 0.01). The number of anoxic islands can be reduced by pretreatment with papaverine (P less than 0.01). Anoxic islands are stable up to 20 minutes of ischemic time and are not stained by fluorescein angiography. The data suggest that an intrinsic inequality exists in the perfusion of the coronary microcirculation during low-flow ischemia.

Animals↗
PubMed1979

Temporal relation between onset of cell anoxia and ischemic contractile failure. Myocardial ischemia and left ventricular failure in the isolated, perfused rabbit heart.

Contractile dysfunction is characteristic of the acutely ischemic myocardium. This study was undertaken to assess the temporal relations between the onset of cell anoxia and ischemic contractile failure in isolated, isovolumetric contracting rabbit hearts. High speed epicardial fluorescence photography using reduced nicotinamide adenosine nucleotide (NADH) was used to identify areas of cell anoxia. The onset of ischemia was correlated with deterioration of pressure generation over the course of sequential 60 second coronary arterial occlusions. In the isovolumetric contracting rabbit heart, areas of ischemia were detected 2 seconds after coronary occlusion. Significant reduction in peak systolic pressure occurred at 6 seconds of ischemic time and pressure continued to decrease throughout the 60 second period of coronary occlusion. NADH accumulation indicates imbalance of myocardial oxygen supply and demand and the cessation of oxygen utilization by the mitochondria. The results of this study indicate that ischemia is detectable within 1 to 2 seconds after coronary occlusion and that ischemic ventricular dysfunction occurs several seconds thereafter. Myocardial oxygen reserve is negligible.

Animals↗
PubMed1979

Epicardial ischemia as delineated with epicardial S-T segment mapping andnicotinamide adenine dinucleotide (NADH) fluorescence photography.

In isolated rabbit hearts with an experimental coronary arterial occlusion, epicardial ischemia was identified by reduced nicotinamide adenine dinucleotide (NADH) fluorescence photography, a technique that detects areas of myocardial anoxia. Epicardial S-T segment mapping was performed to evaluate the S-T segment changes across an ischemic border defined by NADH fluorescence. After S-T segment mapping and perfusion with a fluorescein dye, serial selections of the hearts revealed that the ischemic area was transmural and and the border was nearly perpendicular to the epicardial surface. As the epicardial ischemic border was approached, S-T segment elevation was first detected 3.3 mm outside the ischemic border, and increased over a transition zone 7 mm wide. S-T segment negativity was not detected immediately outside the ischemic border. It is concluded from these studies that S-T segment changes give relatively imprecise definition of an ischemic border, and that S-T segment changes across an ischemic border are not consistent with those predicted by solid angle analysis.

Animals↗
PubMed1979

Fluorescence mapping of mitochondrial redox changes in heart and brain.

Fluorescence techniques may be utilized to map changes in the distribution of mitochondrial redox states in heart and brain during ischemic or hypoxic stress. The basis of these techniques is the intrinsic fluorescence of reduced NADH and oxidized flavoprotein in mitochondria which respond to changes in critical oxygen supply. Ischemic areas in rabbit hearts induced by coronary ligation were detected and mapped based on the increase in NADH fluorescence in the ischemic zone. The width of the jeopardized normoxic tissue surrounding the ischemic area (less than 50--350 mu) was measured by combination of fluorescein angiography and NADH fluorescence. Areas of increased NADH fluorescence in gerbil brains after carotid artery ligation or induction of spreading depression were mapped in a similar manner. Intraoperative monitoring of flavoprotein fluorescence from human cerebral cortex after superficial temporal artery middle cerebral artery (STA-MCA) anastomoses demonstrated increased rates of cortical oxidative metabolism after the surgical procedures.

Animals↗
PubMed1979

The mechanism of apparent right bundle branch block after transatrial repair of tetralogy of Fallot.

The electrocardiographic pattern of right bundle branch block (RBBB) is routinely observed after transatrial repair of tetralogy of Fallot even though no ventriculotomy has been performed. The mechanism of this conduction disturbance was studied in 16 patients with tetralogy of Fallot and one patient with infundibular pulmonic stenosis. Preoperative ECGs and vectorcardiograms showed right ventricular hypertrophy and no RBBB. Epicardial activation maps were obtained before and after total surgical repair in all patients and after infundibular resection but before closure of ventricular septal defect (VSD) in four of these patients. After infundibular resection, RBBB appeared and activation was markedly delayed (greater than 30 msec) over the pulmonary outflow tract, but was unchanged over the body of the right ventricle. No further changes in ventricular activation occurred after closure of the VSD. This study shows that RBBB after transatrial repair of tetralogy of Fallot is usually produced by infundibular resection, but not by VSD closure, and is associated with delayed activation of the pulmonary outflow tract and base of the right ventricle which results from damage to portions of the right ventricular conduction system.

Adolescent↗
PubMed1979

Visualization of the distance between perfusion and anoxia along an ischemic border.

The distance between perfusion and anoxia was measured on the border of an experimental ischemic area in the rabbit heart. Reduced nicotinamide adenine dinucleotide (NADH) fluorescence photography was used to detect myocardial anoxia. Fluorescein angiography marked areas of myocardial perfusion. The hearts were isolated, perfused with a hemoglobin-free solution and performed no external work. In all hearts there was a narrow band between areas of perfusion and anoxia that measured 329 +/- 42 mu (mean +/- SD). The transition from minimal to full NADH fluorescence was abrupt, less than 80 mu. We conclude that the normoxic/anoxic transition is sharp, and the gap between perfusion and anoxia is narrow along an ischemic border in the isolated heart performing no external work. These data suggest that in the vivo working heart the gap between perfusion and anoxia would be even narrower.

Animals↗
PubMed1979

The relationship between atrioventricular nodal refractoriness and the functional refractory period in the dog.

We studied the relationship between the atrioventricular nodal functional refractory period (FRP) and refractoriness by mathematical analysis and by measurement during antegrade Wenckebach cycles in 16 dogs. The FRP relates directly to the conduction time of the control beat, and inversely to the coordinates of the point on the A'-H' vs. A-A refractory curve where the slope is -1. The FRP can vary without any change in refractoriness as measured by the effective refractory period (ERP) or the refractory curve. In 16 dogs the ERP and the FRP were measured during 4:3 Wenckebach cycles. Because of changes in the control conduction times, the FRP declined and did not reflect the progressive increase in refractoriness recorded during Wenckebach cycles. The FRP is a complex parameter and does not reliably measure refractoriness.

Analog-Digital Conversion↗
PubMed1978

Electrophysiologic studies on atrioventricular nodal Wenckebach cycles.

Wenckebach cycles with a 4:3 ratio, produced by rapid atrial pacing, were studied in 27 anesthetized denervated dogs using programmed stimulation. A test stimulus (S') could be inserted after any preselected beat of the Wenckebach cycle. An on-line computer measured the atrial (A) to His bundle (H) intervals. In all dogs a progressive increase in atrioventricular (A-V) nodal refractoriness was seen in the effective refractory period for each beat and a rightward shift of the A'-H' relative to the A-A' refractory curves. Atypical Wenckebach cycles could be produced by small changes in the basic cycle length. No evidence for reentry was found from the refractory curves of Wenckebach cycles and by interruption of stimulation after the third stimulus of a 4:3 Wenckebach cycle. Analysis of the A'-H' relative to the H-A' refractory curves did not confirm a positive feedback mechanism. In order to mimic a Wenckebach cycle, a blocked premature beat was inserted during stressed 1:1 conduction. The changes in the refractory curves for successive beats after the premature beat were rate-dependent and similar to those in Wenckebach cycles but smaller in magnitude. In Wenckebach cycles there is a progressive increase in refractoriness, caused by cumulative effect similar to that seen after a blocked beat during stressed 1:1 conduction, until block occurs and the cycle resets.

Animals↗
PubMed1978

Display of epicardial ischemia by reduced nicotamide adenine dinucleotide fluorescence photography, electron microscopy, and ST segment mapping.

Reduced nicotinamide adenine dinucleotide (NADH) fluorescence photography, a technique of assessing myocardial ischemia, was correlated with ischemia as identified by ST segment mapping and electron microscopy (EM) in 25 Langdneorff perfused rabbit hearts following coronary occlusion. Nicotinamide adenine dinucleotide (NAD), a component of the intramitochondrial electron transport chain, becomes reduced during periods of ischemia (NADH). NADH fluoresces when excited by ultraviolet light. NAD does not. All three techniques were compared to assess their resolution of the "border zone" between ischemia and nonischemic myocardium. The border zone defined by NADH fluorescence is 0.1 mm or less. Areas of high NADH fluorescence invariably revealed ST segment elevation, whereas minimally fluorescent areas did not. St segment mapping yields a border zone of approximately 7 mm. Areas of high NADH fluorescence following 1 hour of ischemia displayed severe damage on EM as compared to matched controls. A zone of intermediate ultrastructural damage is identified in a 1 mm biopsy taken between fluorescent and nonfluorescent myocardium. This evidence confirms epicardial NADH fluorescence photography as an assay of myocardial ischemia. This high resolution technique delineates a border zone of narrow dimensions as compared with ST segment mapping.

Animals↗
PubMedDate not supplied

Prevention of sudden death in patients with coronary artery disease: the Multicenter Unsustained Tachycardia Trial (MUSTT).

This trial will significantly advance our understanding of the prognostic and therapeutic usefulness of electrophysiologic studies in patients with coronary artery disease. Several features of this trial are worth emphasizing. First, the protocol for performing programmed stimulation and serial drug testing is designed to mirror those currently in use by many practicing electrophysiologists. While practice patterns vary, the procedures used in the trial reflect what is considered "usual and standard" practice. Second, because half of the patients with inducible sustained ventricular tachycardia will be given no antiarrhythmic therapy, we will be able to ascertain the true risk of sudden death in this patient population without the influence of these agents. Third, this trial will assess the usefulness of a method of guiding antiarrhythmic therapy (electrophysiologic testing) to reduce mortality in this high-risk population. It will not evaluate the efficacy of a specific type of antiarrhythmic therapy.

Amiodarone↗
PubMedDate not supplied

Changes in cardiac excitability and vulnerability in NMR fields.

Alterations in ventricular excitability and vulnerability were assessed in nine isolated perfused rabbit hearts in and out of static external magnetic fields (4.7 tesla) associated with radiofrequency pulsing (5 gauss). Ventricular refractoriness was assessed with the strength interval relationship in and out of the NMR magnet. Strength interval curves were measured at threshold, at the midpoint of the strength interval relationship, and at 10 mA. The refractory period measured at threshold was 193 +/- 24 mS outside the magnet and 195 +/- 24 mS inside the magnet (P = ns). Ventricular refractoriness measured at the midpoint of the strength interval curve was 169 +/- 16 mS outside and 167 +/- 17 mS in the magnet (P = ns). At 10 mA the refractory period outside of the magnet was 162 +/- 16 mS and 161 +/- 17 mS in the magnet (P = ns). To assess ventricular vulnerability the repetitive response threshold and the ventricular fibrillation threshold were also determined in and out of the NMR magnet. The repetitive response threshold was 61 +/- 16 mA out of the magnet and 75 +/- 24 mA inside the magnet. This was significant at the P = 0.04 level. The ventricular fibrillation threshold was 71 +/- 14 mA out of the magnet and 81 +/- 20 mA in the magnet (P = ns). In summary, static magnetic fields associated with radiofrequency pulsing have no measureable effect on the strength interval relationship. There is no increase in ventricular vulnerability as assessed by the repetitive response threshold and the ventricular fibrillation threshold.

Animals↗