IN the 19th century there were two major hypotheses to explain the pathogenesis of atherosclerosis: the "incrustation" hypothesis and the "lipid" hypothesis. The incrustation hypothesis of von Rokitansky,1 proposed in 1852 and modified by Duguid,2 suggested that intimal thickening resulted from fibrin deposition, with subsequent organization by fibroblasts and secondary lipid accumulation. The lipid hypothesis, proposed by Virchow3 in 1856, suggested that lipid in the arterial wall represented a transduction of blood lipid, which subsequently formed complexes with acid mucopolysaccharides; lipid accumulated in arterial walls because mechanisms of lipid deposition predominated over those of removal. The two hypotheses are now . . .

https://www.nejm.org/doi/pdf/10.1056/NEJM199201233260406?articleTools=true

The pathogenesis of coronary artery disease and the acute coronary syndromes (1).

This report is the continuation of two earlier reports that defined human arterial intima and precursors of advanced atherosclerotic lesions in humans. This report describes the characteristic components and pathogenic mechanisms of the various advanced atherosclerotic lesions. These, with the earlier definitions of precursor lesions, led to the histological classification of human atherosclerotic lesions found in the second part of this report. The Committee on Vascular Lesions also attempted to correlate the appearance of lesions noted in clinical imaging studies with histological lesion types and corresponding clinical syndromes. In the histological classification, lesions are designated by Roman numerals, which indicate the usual sequence of lesions progression. The initial (type I) lesion contains enough atherogenic lipoprotein to elicit an increase in macrophages and formation of scattered macrophage foam cells. As in subsequent lesion types, the changes are more marked in locations of arteries with adaptive intimal thickening. (Adaptive thickenings, which are present at constant locations in everyone from birth, do not obstruct the lumen and represent adaptations to local mechanical forces). Type II lesions consist primarily of layers of macrophage foam cells and lipid-laden smooth muscle cells and include lesions grossly designated as fatty streaks. Type III is the intermediate stage between type II and type IV (atheroma, a lesion that is potentially symptom-producing). In addition to the lipid-laden cells of type II, type III lesions contain scattered collections of extracellular lipid droplets and particles that disrupt the coherence of some intimal smooth muscle cells. This extracellular lipid is the immediate precursor of the larger, confluent, and more disruptive core of extracellular lipid that characterizes type IV lesions. Beginning around the fourth decade of life, lesions that usually have a lipid core may also contain thick layers of fibrous connective tissue (type V lesion) and/or fissure, hematoma, and thrombus (type VI lesion). Some type V lesions are largely calcified (type Vb), and some consist mainly of fibrous connective tissue and little or no accumulated lipid or calcium (type Vc).

A Definition of Advanced Types of Atherosclerotic Lesions and a Histological Classification of Atherosclerosis A Report From the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association

When a molecule absorbs a photon of appropriate energy, a chain of photophysical events ensues, such as internal conversion or vibrational relaxation (loss of energy in the absence of light emission), fluorescence, intersystem crossing (from singlet state to a triplet state) and phosphorescence, as shown in the Jablonski diagram for organic molecules (Fig. 1). Each of the processes occurs with a certain probability, characterized by decay rate constants (k). It can be shown that the average length of time τ for the set of molecules to decay from one state to another is reciprocally proportional to the rate of decay: τ = 1/k. This average length of time is called the mean lifetime, or simply lifetime. It can also be shown that the lifetime of a photophysical process is the time required by a population of N electronically excited molecules to be reduced by a factor of e. Correspondingly, the fluorescence lifetime is the time required by a population of excited fluorophores to decrease exponentially to N/e via the loss of energy through fluorescence and other non-radiative processes. The lifetime of photophycal processes vary significantly from tens of femotoseconds for internal conversion1,2 to nanoseconds for fluorescence and microseconds or seconds for phosphorescence.1






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Figure 1


Jablonski diagram and a timescale of photophysical processes for organic molecules.

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Fluorescence Lifetime Measurements and Biological Imaging

In an electrosurgical generator for generating radio frequency power, the generator includes a radio frequency output stage having two or more output connections, and a power supply coupled to the output stage for supplying power to the output stage. A controller is operable to cause the generator to supply a blended output signal alternating constantly between a first output signal across the output connections in which the radio frequency output voltage developed across the output connections is limited to at least a first predetermined threshold value for cutting or vaporisation of tissue, and a second output signal across the output connections in which the radio frequency output voltage developed across the output connections is limited to a second threshold value for coagulation. There is also provided adjustment means, operable by a user of the electrosurgical generator, for changing between various preset settings for the blended signal, the preset settings each having a predetermined duty cycle of the blended signal that is limited to the first threshold value for cutting or vaporisation, and a predetermined duty cycle of the blended signal that is limited to the second threshold value for coagulation.

Electrosurgical generator and system

To help determine if coronary angiography can predict the site of a future coronary occlusion that will produce a myocardial infarction, the coronary angiograms of 42 consecutive patients who had undergone coronary angiography both before and up to a month after suffering an acute myocardial infarction were evaluated. Twenty-nine patients had a newly occluded coronary artery. Twenty-five of these 29 patients had at least one artery with a greater than 50% stenosis on the initial angiogram. However, in 19 of 29 (66%) patients, the artery that subsequently occluded had less than a 50% stenosis on the first angiogram, and in 28 of 29 (97%), the stenosis was less than 70%. In every patient, at least some irregularity of the coronary wall was present on the first angiogram at the site of the subsequent coronary obstruction. In only 10 of the 29 (34%) did the infarction occur due to occlusion of the artery that previously contained the most severe stenosis. Furthermore, no correlation existed between the severity of the initial coronary stenosis and the time from the first catheterization until the infarction (r2 = 0.0005, p = NS). These data suggest that assessment of the angiographic severity of coronary stenosis may be inadequate to accurately predict the time or location of a subsequent coronary occlusion that will produce a myocardial infarction.

Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease?

To visualize intracoronary lesions in patients with different clinical expressions of coronary disease, we performed coronary angioscopy during coronary-artery bypass surgery in 10 patients with unstable angina and 10 patients with stable coronary disease. We examined a total of 32 vessels, using flexible fiberoptic angioscopes. Twenty-two vessels had no acute intimal lesion; three had complex plaques, six had thrombi, and one had both. Coronary angiography correctly identified the absence of complex plaque and thrombus in 22 vessels, but it detected only one of four complex plaques and one of seven thrombi. On angioscopy, none of the 17 arteries in the patients with stable coronary disease had either a complex plaque or thrombus. In the "offending" arteries of the patients with unstable angina, all three patients with accelerated angina had complex plaques and all seven with angina at rest had thrombi. We conclude that angioscopy frequently reveals complex plaques or thrombi not detected by coro...

Coronary Angioscopy in Patients with Unstable Angina Pectoris

A glucose monitor, and related method, determines the concentration of glucose in a sample by monitoring fluorescent light produced directly by any glucose present in the sample. The glucose monitor illuminates the sample with ultraviolet excitation light (16) that induces any glucose present in the sample to fluoresce, with the fluorescent light being monitored and processed to determine the concentration of glucose in the sample. A sensor (18) monitors the return light, which includes fluorescent light (20) produced by any glucose in the sample, and generates first and second electrical signals indicative of the intensity of light in two wavelength bands. One wavelength band includes a characteristic spectral peak of glucose fluorescence, and the other wavelength band is a reference band having known spectral characteristics. A processor (22) then processes the first and second electrical signals to determine the concentration of glucose in the sample. A fiber-optic waveguide is used to guide the excitation light from the laser light source to the sample and the return light from the sample to the sensor. The fiber-optic waveguide is housed in a catheter or probe that is adapted to monitor the concentration of glucose percutaneously in the oral cavity tissues of a person's mouth such as the gums.

Glucose fluorescence monitor and method

The Laser Induced Fluorescence Attenuation Spectroscopy (LIFAS) method and apparatus preferably include a source adapted to emit radiation that is directed at a sample volume in a sample to produce return light from the sample, such return light including modulated return light resulting from modulation by the sample, a first sensor, displaced by a first distance from the sample volume for monitoring the return light and generating a first signal indicative of the intensity of return light, a second sensor, displaced by a second distance from the sample volume, for monitoring the return light and generating a second signal indicative of the intensity of return light, and a processor associated with the first sensor and the second sensor and adapted to process the first and second signals so as to determine the modulation of the sample. The methods and devices of the inventions are particularly well-suited for determining the wavelength-dependent attenuation of a sample and using the attenuation to restore the intrinsic laser induced fluorescence of the sample. In turn, the attenuation and intrinsic laser induced fluorescence can be used to determined a characteristic of interest, such as the ischemic or hypoxic condition of biological tissue.

Method and devices for laser induced fluorescence attenuation spectroscopy

A method is disclosed for determining the biodistribution of substances using fluorescence spectroscopy. A photosensitizing agent or other intrinsically fluorescent agent, or an agent labeled with an extrinsic fluorophor is administered to a subject. A fiberoptic probe integrated with an excitation light source illuminates the examined tissue and causes fluorescence. The fluorescence is recorded by a spectrograph and plotted as a spectral curve. The intensity ratio (S1/S2) for the fluorescence from the photosensitizing agent (S1) and autofluorescence (S2) for the examined tissue is used as an index for drug presence and compared with the intensity ratio at the same wavelengths for various tissues.

Method for determining the biodistribution of substances using fluorescence spectroscopy

A medical monitor, and related method, determines a pre-existing physiological property of an organ of a patient by monitoring fluorescent light produced by constituents associated with the metabolic and structural condition of the organ. The monitor illuminates the organ with ultraviolet excitation light that induces some constituents of the organ to fluoresce, with the fluorescent light being monitored and processed to determine pre-existing physiological properties of the organ. A sensor monitors the return light, which includes fluorescent light produced by the fluorescent constituents of the organ, and generates first and second electrical signals indicative of the intensity of light at two wavelength. One wavelength is associated with the fluorescence of collagen, a constituent associated with organ's structural properties, and the other wavelength is a associated with the fluorescence of NADH, a constituent associated with the organ's metabolism. A processor then processes the first and second electrical signals to determine the localized pH of the organ. A fiber-optic waveguide is used to guide the excitation light from the laser light source to the organ and the return light from the organ to the sensor. In another aspect of the invention, the sensor generates a third electrical signal associated with the fluorescence of elastin, a constituent associated with the organ's structural properties. The processor processes the first, second and third electrical signals to determine the perfusion or oxygenation of the organ.

Warren S. Grundfest

Papers

Coronary Angioscopy in Patients with Unstable Angina Pectoris

Glucose fluorescence monitor and method

Method and devices for laser induced fluorescence attenuation spectroscopy

Method for determining the biodistribution of substances using fluorescence spectroscopy

Induced fluorescence spectroscopy blood perfusion and pH monitor and method