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Biomedical subjects

W R Harden

Publications and source records attributed to W R Harden.

10 recordsLinked 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↗
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.

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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↗
PubMed1978

Two and three dimensional display of myocardial ischemic "border zone" in dogs.

It is intuitively apparent that the ultimate fate of reversibly damaged, peri-ischemic "border zone" tissue should relate to individual patient survival. The purpose of this study was: (1) to describe a technique of assessing the adequacy of epicardial and myocardial oxygenation, and (2) to examine the extent and character of the peri-ischemic "border zone" in the dog after coronary arterial ligation. A diagonal branch of the left anterior descending coronary artery was ligated in four anesthetized open chest, neurohormonally intact dogs. The same diagonal coronary artery was ligated in six isolated perfused canine heart preparations in which coronary partial pressures of oxygen and carbon dioxide, pH, blood flow and temperature were fixed. The ischemic zones were rapidly frozen and reduced nicotinamide adenine dinucleotide (NADH) fluorescence photographs were taken of the epicardium and at 0.5 mm depths into the myocardium. The distinction between perfused and ischemic myocardium is not apparent with the naked eye or natural light photography. Epicardial and myocardial oxidation-reduction status is well seen with NADH fluorophotography. In both the intact and perfused heart preparations the NADH-fluorescent (ischemic) border is jagged along all edges. Islands of perfused nonfluorescent tissue appear within the ischemic border. The transition between NADH-fluorescent ischemic cells and adjacent non-fluorescent tissue is less than 0.1 mm. The ischemic border is narrow. The distance between homogeneously NADH-fluorescent tissue and homogeneously nonfluorescent tissue (across the zone of island normoxia or microheterogeneity) may be as wide as 6 to 8 mm.

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.

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