Vascular Function and Structure in the Rat Aorta
By Keith Wan Kee Ng
Vascular Function and Structure in the Rat Aorta, by Keith Wan Kee Ng
This book first published 2013
Cambridge Scholars Publishing
12 Back Chapman Street, Newcastle upon Tyne, NE6 2XX, UK
British Library Cataloguing in Publication Data
A catalogue record for this book is available from the British Library
Copyright © 2013 by Keith Wan Kee Ng
All rights for this book reserved. No part of this book may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission of the copyright owner.
ISBN (10): 1-4438-4823-9, ISBN (13): 978-1-4438-4823-7
To My parents My best friends
TABLE OF CONTENTS
Chapter One .................................................................................................
Chapter Two ................................................................................................
Arterial Function and Structure
2.1 Historical perspectives
2.2 Large artery wall structure
2.3 Mechanical properties of arteries: evolutionary perspectives
2.4 The behaviour of the large arteries under a distending pressure
2.5 Experimental investigation of aortic wall properties
2.6 Essential non-linear and pressure-dependent properties of aortic stiffness
2.7 The relation between arterial stiffness and hypertension
2.8 Pathophysiological mechanisms associated with arterial stiffening
2.9 Animal models of arterial stiffness
2.10 Measurement of arterial stiffness
Chapter Three ............................................................................................
Logical Treatments of Arterial Hypertension
3.1 Nitric oxide
3.2 Angiotensin-converting enzyme inhibition
3.3 Diuretics
3.4 Angiotensin II type 1 receptor and calcium channel blockers
3.5 Other interventions
3.6 Conclusion
Chapter Four ..............................................................................................
41
Common Methodology Used in the Investigation of Arterial Function and Structure
4.1 Measurements of body weight, body length and conscious tail-cuff systolic blood pressure
4.2 Haemodynamic measurements
4.3 Aortic calcium quantification
4.5 Statistical analysis
4.4 Histomorphometry
Chapter Five ..............................................................................................
53
Regional Aortic Wall Stiffness: Comparison in Normotensive, Hypertensive and Aortic Calcification Rat Models
5.1 Introduction
5.2 Methods
5.3 Results
5.4 Discussion
5.5 Conclusion
5.6 Perspectives
Chapter Six ................................................................................................
71
Aortic Stiffness is Associated with Vascular Calcification and Remodelling in a Chronic Kidney Disease Rat Model
6.1 Introduction
6.2 Materials and Methods
6.3 Results
6.3 Discussion
6.4 Conclusion
Chapter Seven ............................................................................................
83
Brief Antihypertensive Treatment with ACE Inhibition (perindopril) Improves Aortic Distensibility in Spontaneously Hypertensive Rats
7.1 Introduction
7.2 Methods
7.3 Results
7.4 Discussion
7.5 Conclusion
7.6 Perspectives
Chapter Eight ...........................................................................................
Withdrawal of Chronic Antihypertensive Treatment with Perindopril Offsets Aortic Distensibility by a Non-pressor Mechanism in Lewis Polycystic Kidney Disease Rats
8.1 Introduction
8.2 Methods
8.3 Results
8.4 Discussion
8.5 Conclusion
8.6 Perspectives Chapter
LIST OF FIGURES
Figure 2.1 An example of photomicrographs of cross sections of a WKY rat thoracic (left) and abdominal (right) aorta.
Figure 2.2 Collagen (left) and elastin (right) content (mean±SD) in the ascending (A), descending (B) thoracic aorta and abdominal supraceliac (C), suprarenal (D), and midinfrarenal (E) aorta.
Figure 2.3 (A) Stress–strain inflation curves for the aortae of four different species at 10 °C, showing increased slope (modulus) with increased stress.
Figure 2.4 Einc versus external radius for a dog femoral artery.
Figure 2.5 Einc versus MAP of the thoracic aorta (squares), abdominal aorta (triangles), femoral artery (crosses) and carotid artery (circles)
Figure 2.6 The contribution of elastin and collagen fibres to the tensionradius response of human iliac arteries.
Figure 2.7 Plot of the relationship between tension and expansion of an artery (A) and balloon (B) during inflation.
Figure 2.8 Microscopic difference between atherosclerosis and arteriosclerosis.
Figure 2.9 Osteogenesis regulation of aortic calcification.
Figure 4.1 An example of a tail-cuff recording of SBP using the IITC Life Science blood pressure system
Figure 4.2 In-vivo experimental set up.
Figure 4.3 An example of beat-to-beat recording and calculation of transit time from second derivatives of blood pressure waveforms.
Figure 4.4 Blood pressure, PWV and HR beat-to-beat signal recordings during PE and SNP infusions in one WKY rat.
Figure 4.5 Flame atomic absorption spectrometer used for determination of aortic calcium content.
Figure 4.6 An example of a 4μm section stained with Shitaka’s Orcein. 50
Figure 4.7 Force equilibrium in two equal halves of vessel.
Table 5.1 In vivo mechanical characteristics
Figure 5.1 Sample experimental recording.
Figure 5.2 PWV-MAP relationship.
Figure 5.3 Thoracic PWV-MAP of WKY, VDN and SHR.
Figure 5.4 Abdominal PWV-MAP of WKY, VDN and SHR.
List
of Figures
Figure 5.5 Calculated elastic modulus and wall stress of the aortic segments.
Figure 6.1 PWV-MAP curves are averaged over 5mmHg pressure steps in Lewis (open triangles) and LPK (closed triangles) ±SEM.
Figure 6.2 Aortic calcium content of LPK showed a 6.5-fold increase compared with Lewis (Lewis: 66.8±5.7 μmol·g-1; LPK: 434.0±118.3 μmol·g-1, *P<0.001).
Figure 6.3 Typical histological sections stained with Shitaka’s Orcein (top) and M.S.B. (bottom), showing a longitudinal section of the thoracic descending aorta
Figure 7.1 Body weight during the 5 months following ACE inhibition with perindopril at 3mg/kg/day in all strains of rats.
Figure 7.2 PWV–MAP curves for all four groups of rats (n=6 in each group) in the whole (top panel), thoracic (middle panel) and abdominal (bottom panel) aorta.
Figure 7.3 Typical 4μm cross sections of the thoracic aorta.
Figure 7.4 MCSA (μm2) of the thoracic and abdominal aorta in untreated SHR,
Figure 7.5 Total calcium levels (μmols.g-1) in the thoracic (white bar) and abdominal (black bar) aorta in 25-week-old WKY, untreated SHR, SHR(Tx)y and SHR(Tx)o rats.
Figure 8.1 Effect of chronic ACE inhibition with perindopril (3mg/kg) in the Lewis (A) and LPK (B) from 6 weeks of age on SBP.
Figure 8.2 Isobaric PWV-MAP curves in the Lewis (A) and LPK (A).
Figure 8.3 Aortic calcium content.
Figure 8.4 MCSA of the thoracic aorta in all groups of rats.
Figure 8.5 Elastic modulus/wall stress ratio of the thoracic aorta in all groups of rats.
LIST OF TABLES
Table 5.2 Relationship between PWV and MAP of WKY, SHR, and VDN rats.
Table 5.3 Morphometric parameters of the descending thoracic aorta.
Table 6.1 Basal haemodynamic parameters in the Lewis and LPK.
Table 6.3 Morphometric parameters of the descending thoracic aorta.
Table 7.1 ACE inhibition and haemodynamic parameters from control, SHR(Tx)y, SHR(Tx)o and control SHR rats.
Table 8.1 Haemodynamic parameters in anaesthetised 6-week-old, 12week-old untreated and 12-week-old perindopril-treated LPK and Lewis rats.
Table 8.2 Morphometric parameters of the descending thoracic aorta.
ARTERIAL FUNCTION AND STRUCTURE
2.1 Historical perspectives
The arterial pulse has been an important feature in clinical examination in ancient Chinese, Indian, and Greek medicine (37). Diagnosis involved the patient being placed on a cushion, with the physician placing his index, ring and middle fingers at three sites of the wrist to elicit the superficial and deep pulses. The working principle was that each organ palpated at particular “normal” pulse amplitude and rate, and these pulses prevailed themselves at different seasons. If a particular pulse appeared at the wrong place or in the wrong season, a serious disequilibrium of the system (or a disease) was indicated. The physician also studied the patient's features and complexion and, sometimes, they inspected the urine and faeces for a more complete diagnosis. However, the patient’s pulse was all that was required, and the physician did not necessarily need to interrogate the patient, collect medical history or symptoms as the entire prognosis would have been available through feeling the texture of the pulse. Chinese sphygmology was a carefully guarded secret. Pulse diagnosis was extremely difficult to learn and even if they could, few physicians were willing to devote 5-10 years of supervision under an experienced master to master the technique (38).
As in Chinese medicine, the art of feeling the pulse was also highly developed amongst ancient Hindu physicians (37). The pulse was felt at the wrist, on the right side in males and on the left side in females. The various pulses were likened to the motions of animals such as the serpent, the frog, the swan, and the peacock. Diseases were attributed to the eccentricity of the three humours, namely air, bile, and phlegm, which were duly reflected in the pulse.
It was not until Hippocrates and other Greek physicians that a scientific basis of the pulse was founded. Various features of the pulse were recognised and named in the fourth century BC (39). The arteries were thought to dilate actively, thus drawing in vital spirits from the airway.
Herophilos later described a relation between the heart and the arteries and invented the first sphygmograph that could measure the number of pulses in the time domain. Erasistratos was the first to note a delay in the travel of the pulse from central to peripheral, but he did not measure the delay or relate it to the stiffness of the arterial path travelled by the pulse. Galen (AD 130-200) later discovered the relationship among the heart, arteries, and veins and he was the first to point out that the arteries contained blood, not air. Galen’s approach dominated medicine for over 14 centuries (40).
The beginning of modern cardiovascular medicine was in the sixteenth century. William Harvey (1578-1657) proved the circulation of blood and noted for the first time that the pulse was a consequence of cardiac contraction (40, 41). Harvey’s attempt to explain a physical phenomenon from a modern scientific approach rather than from “natural philosophy” might have been influenced by his contemporary Galileo Galilei (15641642). Harvey’s work laid the foundation for the physiological understanding of the mechanism of the arterial pulse and later its clinical applications. The implication was highly significant. The pulse was established as a manifestation of cardiac contraction and thus would be altered by abnormalities in the function of the heart and blood vessels.
Reverend Stephen Hales (1677-1761) was the first to use experimental animals to study the circulatory system (42, 43). Hales formulated the concept of peripheral resistance by demonstrating in a simple yet elegant experiment that greater resistance to flow resides in the smaller blood vessels. Hales also conceptualised the elastic arterial system as the airfilled chamber of the contemporary fire engine, which later translated into German as “Windkessel”, and this word has been used since. The Windkessel model describes the conduit and cushioning function of the arteries and has been widely used to model the circulatory system, despite being simplistic and limited (44).
The inability of the Windkessel model to address the substantial issue of pressure wave propagation led to the establishment of the wave transmission model in the nineteenth century. Thomas Young (1773-1829) investigated and established the relationship between the elasticity of the artery and the speed of propagation of the arterial pulse (45, 46). In 1828, Jean Poiseuille (1797-1869) measured blood pressure with a mercuryfilled column and determined the factors responsible for resistance to flow in tubes of capillary dimensions. This was further developed into a series of sphygmographs by Étienne-Jules Marey (1830-1904) (47). Frederick Akbar Mohamed later established the foundation of pulse wave analysis.
He described normal levels of blood pressure and the effect of high blood pressure on the radial pressure waveform, and used the waveform to chart the natural history of essential hypertension even before the invention of the sphygmomanometer. He also described the effects of arterial degeneration with ageing on the arterial pulse (48, 49), which was then used in the life insurance studies of the late nineteenth century (50).
Mohamed’s sphygmogram was succeeded by the introduction and acceptance of the sphygmomanometer of Scipione Riva-Rocci (1896) (51) and Nicolai Korotkoff (1905) (52). Although the sphygmomanometer enabled pressure to be recorded reasonably accurately, quickly and noninvasively, the sphygmomanometer disoriented the biological significance in the pulse wave shape by giving only a simplistic notion of two extremes of pressure waveform. Nevertheless, these two figures, systolic and diastolic pressures, were still of great importance as the former is a manifestation of left ventricular ejection and the latter a manifestation of the arteriolar tone (peripheral resistance). The sphygmomanometer has been widely used in clinical settings despite its limitation in predicting the central blood pressure (45).
While Mohamed was the first to note the difference between pressure waves in central and peripheral arteries, Donald McDonald and John Womersley were responsible for quantifying and explaining this phenomenon based on wave reflection (46, 53, 54). They also introduced the use of transfer functions between pressure and flow to characterise the properties of vascular beds in the frequency domain, using the technique of Fourier analysis developed by Frank (55). Bramwell and Hill described cardiac function in relation to hydraulic load and more importantly showed that arterial stiffness was an important component in the determination of cardiac load (56). These classic works of McDonald, Womersley, Taylor and their followers have informed the conceptual background and the rationale of research work in this book.
2.2 Large artery wall structure
Arterial tissue can be mechanically described in terms of a long-range elastic element (elastin) arranged in parallel with a system of continuous collagen fibres that set a limit on extension. There are three recognisable layers in an artery: tunica intima, tunica media and tunica adventitia (Figure 2.1).
2.2.1 Tunica intima
The tunica intima is defined as the endothelial cells and subendothelial area on the luminal side of the inter elastic lamina. These endothelial cells are able to produce elastin in vitro, thus contributing to the formation of the inter elastic lamina (57-59). The subendothelial area contains cellular matrix in lower order animals and a population of smooth muscle cell in higher order animals such as humans (60). This layer is particularly important in atherosclerosis (61) but plays no role in the mechanical properties of the normal conducting vessel.
2.2.2 Tunica media
The next layer of the arterial wall is the tunica media, which consists of smooth muscle cells and elastic. Elastin is arranged in fenestrated sheets (lamellae) with collagen fibres, extracellular matrix and smooth muscle cells in between layers. Inter-lamellae elastin connects to the lamellae and smooth muscle cells forming a three-dimensional continuous network (62). Elastin fibres, with high distensibility but low tensile strength, function primarily as an elastic reservoir by distributing stress evenly across the vessel wall and on to collagen fibres, with high tensile strength but low distensibility, at high pressure. Interestingly, the number of elastin lamellae does not change after birth, suggesting that a loss of elastin, such as in the case of elastin fragmentation or degeneration, would translate into a permanent loss of the reservoir function. Elimination of smooth muscle function or disruption of the morphological organisation has also been found to show remarkable alterations which could cause functional impairments and vascular disorders (63-65). Given the unique vascular network, the media layer is a prominent site for aortic calcification, a phenomenon in which deposition of calcium particles obstructs and/or fragments the elastin lamellae. Aortic calcification is studied extensively in this book.
2.2.3 Tunica adventitia
The outermost layer of the vessel wall is the tunica adventitia. The tunica adventitia is defined as the area outside of the external elastic lamina and consists of a collagen-rich extracellular matrix (66). In this layer lie the vasa vasorum, small vessels that supply nutrients and oxygen to the vessel wall. The tunica adventitia is susceptible to vascular inflammation as it is the outermost protective layer and can act as an injury-sensing device for
the vessel wall. An elegant study by Hu et al. showed that resident progenitor cells populate within the adventitia layer contributing to atherosclerosis of vein grafts in ApoE-deficient mice (67, 68).
Figure 2.1 An example of photomicrographs of cross sections of a WKY rat thoracic (left) and abdominal (right) aorta. Fixation was done while distending at 110mmHg and stained with Shitaka’s Orcein stain. The architecture is essentially the same. The abdominal aortic media is narrower than in the thoracic segment. The difference in thickness corresponds to the difference in diameter. Adventitial (A), media (M) and intima (I) layers are shown.
2.2.3 Intrinsic differences in segmental aortic structure
It is well known that the arterial wall structure varies with increasing distance from the heart. These inherent differences in the organisation and content subject the arterial wall to different compliance and integrity of the aorta. This difference in compliance and integrity is related to aortic disease as shown by several classic studies on the thoracic and abdominal aortas of man and other mammalian species (69). The human aorta consists of between 80 to 32 lamellae from the ascending to the midinfrarenal aorta (Figure 2.2a) (70). Similarly, collagen content also decreases from the proximal to the distal aorta (Figure 2.2b), although no difference was found between the suprarenal and midinfrarenal segments (70). The contribution of elastin and collagen to the function and structural integrity of the aorta has been investigated by Dobrin (71). Since the mean arterial pressure is essentially constant throughout the length of the aorta, degradation of the elastin network, as in arterial calcification and chronic kidney disease, could significantly impair the viscoelasticity properties of the wall. Comparing both the thoracic and abdominal aorta, the latter will be affected to a greater extent as more force is applied per gram of elastin in this segment. Collagen, on the other hand, provides tensile strength;
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wholly taken away, if earthly fire and light should be wanting unto us.
If there were some one man onely in Some whole City or Province, or in a whole Kingdom, who alone could make others partakers of fire and light, would there not be made the greatest concourse of all men unto him? but because it is known to every one, and everyone hath known by an easy manner, how to strike it out of flints, it is had in no esteem, for it is customary not to esteem those things which are made common, although they are pretious. The same thing hath happened to the fire, the which although it ought to be made of greatest account, yet it is reckoned of no worth because it is common and vulgar.
But even as the common fire, and that known to every one, doth by very many most profitable operations bring much good to mortals, who can least of all want the use thereof; so also I affirm that those artificial and hidden fires are to be very much accounted of, because a Phisician can hardly be without them, for the preparations of efficacious Medicines, and a Chymist can never want for the transmutation of the more base metals into better, either of them without the aid of those fires shall perform nothing of any great moment in Chymical Labours.
He that works and is ignorant of such fires, what will he effect in metallick operations? he being conversant in cold and darkness is afflicted with the Same difficulty, as a certain brewer or baker is, who wants wood in the winter season, or who is not able to use water, it being congealed into ice, the one he cannot bake although he hath the best meal, and the other brew drink although he have abundance of the best malt.
So also goes the matter with Alchymical Affairs, the want whereof causeth that we handle not the most noble Alchimy with any profit, but rather receive loss from the same, daily experience being witness, that 100 are wont to be sooner undone than that it happens to any one man to get himself riches thereby. The blame of which discommodity is not to be transferred on an impossibility of
the art, but rather to be imputed to the want of those moist, cold, and ripening fires extracted out of Salts, the which after what sort they ought to be used for the amendment of metals, as also for medicine and other arts, shall be taught partly in this, and partly in the other Centuries.
XXVIII. The general use of our concentred fiery and ripening Spirits, extracted out of Salts, in the amendment and converting of metals into more noble ones; also the preparationofmany excellentmedicaments,andtheincrease and amendment of many other arts, are briefly here demonstrated;thewhich,Godgranting,shallmore largelybe declaredintheirparticularuse.
That I may discourse in few words whether imperfect metals may by the operation of the more common and gross Salts, and of the fire be broken, destroyed, cleansed, and reduced into a better form, it being that which the fifth part of the prosperity of Germany confirmeth by divers experiments.
I affirm that the pure Spirits of Salts, do with a greater efficacy, and far better effect the same, the which, since those simple Spirits are able, better and more easily to perform than gross Salts, why should not also con-centrated Spirits after the best and easiest manner of all perform the same thing?
From a like reason the use of Salts shall not be of so great efficacy in the preparation of medicines, and other arts, as the useing of common Spirits is; the which, notwithstanding being still for the most part clogged with much phlegm, do of necessity not disclose so great virtues, as those con-centred fiery Spirits do which are freed from all phlegm.
The Sun-beams are for an example which do not send forth so great heat, when they are co-mixed with a moist air, as also green and wet Woods do not so vehemently burn with heat, as withered and dry ones are wont to do.
Yea if the hot beams of the Sun are con-centred in or by some hollow glass increasing the fire, or the fires of Coals by a strong blowing of the Bellows, and are as it were constrained into straights or narrow passages, they effect ten times, yea one hundred times more than those which are not centred together after such a sort. But by how much the more strictly those forces of the beams of the Sun, or of other fires are con-centred by so much the greater, stronger, and sharper heat they draw out.
A burning glass of one foot Diameter, onely enflames Wood; but one of two foot Diameter will melt Tin, Lead, and other metallick matters of that sort, which are easie to be melted, as Bismuthum, or the whitest, lightest, and basest kind of Lead, Zink, the nonsplendent metallick dark matter Koboltum, &c. But if you extend the Diameter to four foot, the Sun-beams taking the stronger increase will melt silver and copper, and will render iron it self so bright burning hot, that it may be wrought with a hammer, as if it had been heated with Coals. This effect is to be ascribed unto the con-centring of the Sun-beams by an instrument, and to the constraining of the heat of Coals, by Bellows, or Wind.
The same thing is to be understood concerning our con-centred and moist fires, which ought to be compared, not onely with the common beams of the Sun, or with the heat of Kitchin fire, but also with those Sun-beams which are con-centred by a glass, and with the fiery heat of Coals constrained or forced by windy blasts. Whence they must of necessity be of greater virtues than the common Salts, and watery spirits of them, the which the more quick sighted will sufficiently comprehend and believe. Simple Countrey People do see this thing with their eyes, and handle it with their hands, as well knowing that the subtile, hot, sweet Spirits of Wine and Ale, (and those procuring strength to the heart,) when they are freed from all moisture by Distillation, and con-centred by Rectification; effect ten fold more than if they had still remained with their humidites.
That thou mayest understand the thing more clearly, well weigh thou Grapes, Bread-corn, or the Fruits of Trees, which we eat in that substance as the trees bring them forth unto us: and they afford us a nourishment, but not such a one, as their juice being pressed out, and separated from its dreggs, and by fermentation reduced into a clear and sweet drink.
If necessity compell, Bread corn may be used for nourishment as it is, yet not so well as when it is separated from its husks, being changed into meal, and reduced by water into a mass or lump, and Salt and Leaven added, and by fire concocted or digested into Bread of the best Savour. By the same reason Bread-corn being boiled in fair water yields a potion indeed somewhat better than the water it self, but if it be artificially handled, and boyled up into Ale or Bear, the husks are separated from the more pure juice, the which afterwards by fermentation, separates many dreggs from it, and arrives to a more noble nature, yielding a sweeter and better drink. But if the same juice be after that brought by distillation into a greater purity, and con-centred together by rectifying, that the virtues thereof may come into a narrow compass, (because it is a meer fire) it will exercise far greater virtues, than gross Bread-corn which wants a power of exercising so great virtues.
So also doth it succeed with con-centrated Salts, to wit, when the dreggs are separated from them by the help of art, and the more pure parts converted, and con-centred into a fiery substance, performing effects of great moment in Alchymy. But that Salts do commonly destroy metals, as well by a moist as a dry way, is known to every Barber, and persons of no reputation. But after what manner metals being destroyed may be reduced into more noble bodies than they were before, there hath been none hitherto (who being skilled in that artifice or craft) that have not hid it with the greatest care. Hence it hath come to pass, that nothing of profit hath been perceived from metallick transmutations, and Alchymy it self hath been made a mock of by the most unskilfull rout of ignorant ones, as if it were most false, and at the farthest distance from truth.
That this doubt therefore may be taken away, and the truth it self may be more evidently placed in our view, I have resolved in my mind, by God’s assistance, to place before the eyes of the whole world, a true and profitable transmutation of metals, by a clear description, and to assert the certainty of so many writings set forth by such men, by the most true experiments, so that every one that is seasoned but even with a light or small knowledge of the fire, may by an easy business hereafter obtain some profit from them. But I will first treat of common and crude Salts, and then of the simple Spirits of those, and at length of their con-centred Spirits and Fires, which we have taught to extract out of them.
But before I attempt to describe and assert this kingly and noble art, I have been led first to shew the cause why some places do occur in the description of the same, wherein words are omitted, and signs or blanks reposed instead of the same.
Indeed this was therefore done, that the art may be concealed from the unworthy, and they in all respects to be driven from the same, and may be made known onely to Adeptists, and the Sons of Art.
Besides also that all secrets may not in all places, and without difference be divulged, but that the chief things thereof may be preserved for friends, lest they be trodden under foot, and broken to pieces by the unworthy, but that they may be left to friends as it were a certain secret stroak, and that an unknown one to others, for to fight successfully.
I therefore earnestly require of every one by a friendly Petition that he be not suddenly angry, if he be not able clearly to perceive, by the sharpness of his wit, all those things which I propose, but rather let him consider that they are not written for him, but for others; by whose capacity they can be perceived. Neither is it altogether necessary that all do know all things, neither also would it be of concernment if friends and enemies attain all those things in their understanding alike, without any difference, which I here openly produce by my descriptions; it is sufficient that some onely,
and indeed those that are worthy may clearly and knowingly possess the same, and testifie the truth.
XXIX. An infallible practice of changing the more imperfect MetalsintomoreperfectonesbythehelpofcrudeSalts.
As I have already a little before, and also in other places of my writings, evidently enough demonstrated that Salts, or the spirits of Salts, are in the earth, or out of the earth a universal Agent, promoting the maturation or ripening of metals: So here I again firmly affirm the same thing, and do say, that by Salts the gross bodies of metals are destroyed, and trans-changed into more noble metals, and that indeed after divers manners, and that more easily or difficultly as any one shall be more or less conversant in Chymical labours.
I will hear God willing make manifest all things, yet not to every one, but to the worthy onely; and that indeed after the manner of a Clock or Watch-maker, who taking some Clock or Watch in pieces, do lay up all the parts thereof in some place without any order; the which he that is unskilfull in the art, shall never again compose and reduce into order. But another who before hath handled that art, will by an easie labour again conjoyn all those parts, and reduce them into the former body of a Clock or Watch.
All those therefore who have experienced the foregoing labours to be perfected by the fire, shall by these my descriptions easily dispatch or accommodate themselves in future things, not easie to be understood by the rout of ignorant persons which have made no experiments in the fire; who will in vain look into those things which I have written; no otherwise than as if any one being plainly unskilfull in reading and writing, should behold written letters, and knows not what they signifie, or what argument they may contain: Such a man if he would be angry with the writer, should he not do him much injury, because as being far remote from the fault of that ignorance which hinders him, whereby he cannot read these letters which he had never learned to read.
The same thing must be understood concerning my writings, which are openly published, not for the sake of any one, but onely of those who have first learned to understand those kind of writings.
But that I may set upon the thing it self, and may teach the amendment of metals for the better, and shew the very foundation of the whole business, I say, that a true changing of them is attempted in vain, unless they are first destroyed, and wholly slain. A grain of Wheat, as Christ himself saith, will never increase or multiply, unless it first putrifies in the earth. If therefore metals ought to be destroyed by Putrefaction, that must needs be done by the help of Salts, according to the truth of the Philosophers Maxim: the corruption of one thing, is the generation of another. The death of one thing, is the life of another. Since therefore metals must die, it must needs be that death be brought on them by enemies, or contrary things, because nothing in natural or artificial things dieth, unless it be slain by its own enemy.
Since metals therefore ought to be destroyed, and killed by their enemies; it is of necessity that they are invaded, tortured, and so long vexed by the same, untill the Agent as the stronger part, be overcome by the Patient as the weaker part; that it be slain by it, [or rather the Patient be overcome by the Agent,] and be translated into a better nature, in which action the Patient ought not to depart from the Agent, but to be tortured with an un-intermitting torment.
Whosoever seeing his enemy and conceives himself of the weaker force, indeavours as much as in him lies to decline him, by retreating, but all occasions of running away and slipping aside being taken away, he is constrained to deliver his life to his enemy, who handles the Patient or suffering party according to his own pleasure, and doth whatsoever he will, therefore after the same manner is the melioration of metals, the which although they should be melted together with Salts their enemies, yet would they make little account of them, but would separate themselves from the same; so that every part of them being unhurt, would keep its own nature and essence. But if the Salts do take away the occasion of
flight from metals, and do inclose them in their Prisons, that they have no way of escaping, but remain, suffer, and die, then they obtain victory over the Salt, and of slain metals are made more pure and better.
This thing is done in the fire by the moist and dry way, of which enough hath been spoken already.
This is the whole and intire art, and there needs no other superfluous teachings; yet he whom these things doth not Suffice, let him read the following operations thorough, wherein he shall find truth, and see with his eyes, and handle with his hand; those things which have been heretofore impossible to him, and very many more.
XXX. After what manner Metals may be slain by their enemies andbetransmutedintobetter .
Unto Metals not one but many enemies are adverse; and part of those enemies are enemies to some and friends to others, but the other part is friendly to some, and at enmity with others. For example sake.
Nothing more prosecutes Gold with an hostile hatred than burning Sulphur and sulphurious Salts, such as are Alcalies, and crude tartar; the cause of this hatred is, because Gold is nothing else, but a fixed Sulphur, and therefore it disagreeth by a capital hatred, with every burning Sulphur; Silver and Lead do love every Sulphur , and all sulphureousSalts,suchasareVitriol,SaltPeter , SaltArmoniack,and thelike, the which they stand in need of for their colour; they have an hatred against Kitching Salt, because it is of a mercurial nature, and therefore not requiring its help, but onely desiring a Sulphur and Tincture, Copper , Iron, and Argent vive, or Quicksilver do possess both natures, to wit, a mercurialandsulphureous one, and for that cause they prosecute all Sulphurs, and any Salts with love.
Tin is an enemy of all Salts, whether they are sulphureous or mercurial ones, when it is slain by Sulphur and Salt, and recalled
unto life, it obtains a more pure and thin or fine body, whether of Gold or Silver, according as it shall be handled.
Moreover, if any should desire to obtain as yet a better essence out of better metals, its necessary that he slay them by their enemies, and raise them up again by their friends; by how much the greater and vehement the enemies are whereby metals are slain, by so much the more those metals do suffer, and with so much the more famous and better bodies do they re-arise.
The whole art therefore consisteth in this, that metals are overwhelmed by their greatest enemies, are slain by them, and after death are separated from them, and that by their best friends, are restored unto a better life.
Thou hast the whole art, neither doth any other thing remain than that thou attempt the matter, and set to thine hand.
For example sake, I will add an operation. Slay a light metallick matter by the sharp Spirits of sulphurious Salts, that it may become a white calx; free this from the Salt Spirits, by water being poured thereon, the which being freed, cannot be reduced into a metallick body by any violence of fire. Likewise slay mercurial metals as are B. by mercurial, Salts their enemies, and change them into white calx’s, the which being freed from their saltness, willbeliquidor flowable; mix those calx’s, to wit, the mercurial and sulphurious being slain, put them into a double vessel of cement, cover the uppermost with a certain plenty of B. fence well the juncture of the cementing vessel with clay, set them into a cementing furnace, and at the beginning administer a gentle fire, that the calx’s may rise up against or assault each other, and the fixed sulphur may bind the fugitive flowable and mercurial calx’s, D. for although in the cement something would depart into smoak, yet that is intercepted by E. and after a certain manner is thus exalted into the degree of F. Too much fire is not presently to be joyned to the cement or plaistering it self, that some time may be granted to the matter that is swift of flight, whereby it may adjoyn it self unto the fixed matter, and may also become fixed and constant with the same for four hours space, therefore the fire
shall be somewhat the more slack, and afterwards for the space of eight or ten hours, it shall be kept in a clear bright burning heat, that G. may not melt: the said time being ended, the fire is to be extinguished, and the cementing vessel to be taken away, in G. a black or brittle body shall be found containing Silver, the easy separation whereof we shall afterwards hear.
The calx of both metals being coagulated into a hard stone, if by grinding it be reduced into powder, and be put into a furnace fit for this thing, a metallick body will be attained, being impregnated, not with a little Gold and Silver, especially if the metals shall be slain, not by the Spirits of common Salts, but with gradatory martial waters. In this cement, H. is rendred aureal or golden, and I. is silvery, by one and the same endeavour. The profit also it self is of no small moment, especially if this operation be exercised with the greater quantity, and the bigger instruments alwaies to supply or afford Silver being pregnant with Gold for separation.
XXXI. A brief and compendious manner of extracting and rendringcorporeal,a volatileGoldoutofcolouredFlints,Red Talck, Granates or Red MarbleStones,Sand, White Clay and thelikemetallickearths.
At the beginning, these mineral or metallick earths are to be made bright burning hot, to be quenched in cold water, and to be broken in a mill, into meal or powder.
After that they are thus broken, thou shalt put them into some Waldenburge, or Cullein Can, and shalt pour so much of Aq; Regis on them, that they may onely be moistened, and let them, together with the Can, be placed in a fire of coals, and incompassed therewith, to be made hot; after that the minerals and Aq; Regis have waxed well hot together, so much hot water is to be poured on those very minerals as shall be necessary for the extracting of the Aq;Regis.
Put the minerals thus moistened with the water into great pots, and those made of the best earth, having many little holes in the
