Artificial Heart
HUMAN contains an artificial heart that allows user control of the volume pumped per unit time (within the limits set by venous return). Activating the artificial heart requires setting at least one and at most 2 parameters. They are (consult Help_variables or List of Variables )

• ARTHRT - the artificial heart switch. Set ARTHRT = 1.0 to turn the heart pump on and back to ARTHRT = 0.0 (the default) to turn it off.
• ARTFLOW - the artifical heart pump's flow rate. The default is the normal average cardiac output of 5500 ml./min..

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Artificial respirator
HUMAN allows user control of respiration volume and frequency. To set the respirator up requires setting 3 parameters. They are (consult Help_variables or List of Variables )

• ARTRES - the artificial respirator switch. Set ARTRES = 1.0 to turn the respirator on and back to ARTRES = 0 (the default) to turn it off.
• ARRT - the respirator rate (analogous to frequency of breaths). Set to desired value. The default is 15.0 per min.)
• ARVOL - the respirator volume (analogous to tidal volume). Set to desired value. The default is 500 ml. per breath.

A common user error is set ARRT & ARVOL but forget to throw the respirator switch on!

Exercise
Human allows control of the level of 'endurance' exercise through the use of two user-selectable parameters. There are

• EXER - the level of exercise in Liters of O2 consumed per minute above the basal O2 consumption level. The level may be set between EXER = 0.0 (the default) and 10.0. Levels of 0.75 are moderate and sustainable, 2.0 is more aggressive and 3.0 L/min. is quite high.
  note: The model ceases exercising (i.e. EXER is reset to 0.0) if it sustains a total of 10 Liters or more of oxygen debt (O2DEBT).
• XERMIN - the duration time of the exercise bout set up in EXER. The default value is 10 minutes. One must raise this value if one wishes to observe the physiology of the response to any long term exercise bout as exercise will terminate at only 10 minutes if not reset.

Some additional useful variables/parameters when working in exercise include but are not limited to

02DEBT Muscle Oxygen Debt (0.0 ml)
FO2AT Fractional 02 in Atmosphere ( 0.21 ) - raising this to 1.0 allows administration of 100% O2.
FCO2AT Fractional C02 in Atmosphere (0.0)
LHSB Basic Left Heart Strength (1.0 X Normal) & RHSB Basic Right Heart Strength (1.0 X Normal)
- the combination of these heart strength controls allow for the simulation of cardiac endurance exercise conditioning (try 1.3 for each, a 30% stronger heart; see the effect on muscle O2 flow delivery). Remember to set BOTH sides upward and equally.

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Infusions
HUMAN allows for the infusion of a user selectable volume, rate and composition of infusate. Infusion involves setting at least one parameter, the volume and up to six parameters totally. They are (consult Help_variables or List of Variables )

• IFVOL - the volume of infusate in ml. This must be set above its default value (=0) to activate any infusion.
• IFMIN - the total time in minutes (default = 10 min.) over which the infusion is delivered and after which the infusion is terminated. Thus, IFVOL = 600 & IFMIN = 30 will deliver the infusate at the rate of 20 ml./min. for 30 minutes and then terminate.
• IFBIC - Sets infusion bicarbonate concentration (mMol/L). Default values for all infusion composition values are near those of normal plasma. Thus the default for IFBIC = 24 mMol/L, very near the resting HUMAN value of 23.69 (mMol/L).
• IFK - Sets infusion Potassium concentration (default = 4.5 mEq/L).
• IFNA - Sets infusion Sodium concentration (mEq/L). The default value is virtually isotonic (145 mEq/L).
• IFPR - Sets infusate Protein concentration (default = 7.3 g/dl).

Infusions can be put to a wide variety of uses. Some examples follow

• raising IFBIC will create a metabolic alkalosis
• IFNA can be manipulated to create hyper and hypotonic infusions
• manipulating IFPR allows for the creation of osmotic problems
• infusions can be used (with some success) to support hypovolemic situations (e.g. see patient #1).

Pathology Inducers
Physiologically pathologic states are normally induced in HUMAN by simply resetting parameters to create the pathology and running the model for an amount of time suitable to allowing the pathology to fully develop. Thus changing TEMSET, the hypothalamic temperature set point, to 39 deg. C from its default value of 37 deg. C will induce a fever state with all of its associated symptoms and problems. Prospective pathology induction variables may be viewed by simply scanning the list of changeable variables (parameters) for useful forcing variables.

HUMAN also contains certain specific parameters who sole purpose is to induce a specific pathology. These, and some particularly useful other inducers are listed immediately below.

ALDOP - induces primary aldosteronism on a user adjustable scale of severity from 0.0 to 10.0.
This simulates a a tumor of the zona glomerulosa of the adrenals that over secretes the mineralocorticoid, aldosterone (ALDO) with all of its sequella including hypertension, hypokalemia and Na+ retention plus extracellular fluid (ECFV) and blood volume (BV) expansion.

AVFIST - induces an arterial -> venous fistula specified as a fraction of the total cardiac output (COL). Resulting values of fistula flow can be read out by the variable AVFLOW (ml/min.). A-V fistulas, direct communications between the arterial and venous circulation, provide a direct shunt pathway bypassing the vascular bed resistances. They thereby cause initial drops in total peripheral resistance (TPR) and concomitant initial decreases in arterial pressure (AP).

 

CAD - No Lipator®, balloon angioplasty or stents here but HUMAN can get coronary artery disease. Resetting CAD induces coronary artery disease of a severity varying between none (0.0, the default) to severe (=1.0) selectable by the user. Affects both coronary flow and cardiac function levels. Try nitroglycerine and vasodilators to relieve.

 

CLAMP - places a resistive clamp on the renal arteries whose effectiveness is measured in mmHg reduction of the arterial pressure perfusing the kidneys. Thus, with an arterial pressure (AP) of 100 mmHg, a renal artery CLAMP = 40 (mmHg) will reduce the pressure perfusing the kidneys (RENPP) to 60 mm Hg. This mimics sclerosis of the renal arteries (classic Goldblatt hypertension) and tends to initiate renally-induced systemic hypertension.

 

EXPRB - specifies basic protein loss via the kidney which has a normal value of 0.00035 gram/min.. Raising renal protein loss can be used to simulate aspects of glomerular nephritis and manipulate plasma osmolarity (POSM).

 

Hemorrhage - can be induced of a selectable volume and duration. The parameters to adjust follow.

• HEMVOL - specifies the total volume of the blood loss in ml..
• HEMMIN - specifies the timespan over which the hemorrhage of size HEMVOL takes place.

Thus, HEMVOL = 500 (ml.) and HEMMIN = 50 (min.) yields a 10 ml/min. blood loss that terminates at 50 min.. Replacement strategies should consider both volume and red cell replacement.

 

MSA - mean pulmonary surface area available for diffusion specified as a %-age. The default is 100 (%) and diffusion problems of varying severity can be simulated by reductions (MSA < 100%). Try MSA = 20 to simulate lung diffusive surface reductions such as in some types of severe emphysema and follow the effects on arterial oxygen (PO2A) over time.

 

Myocardial infarction(MI) - Yes, HUMAN can also have a heart attack! MI is inducible in HUMAN on either the left (LMIB) or the right (RMIB) side of the heart or bilaterally (set both LMIB & RMIB).

• LMIB or RMIB can each be set at any value from 0.0 (no MI) to 1.0 (complete MI).

-The value selected indicates the fraction of cardiac function lost due to the infarct.
- Partial recovery of up to 30% can occur within several days.
- Be aware that response to MI may differ depending on the work levels placed on the heart.

 

PHEO - a pheochromocytoma, a tumor of the adrenal medulla that oversecretes adrenergic neurohumors, can be induced in HUMAN.

• Set the severity of PHEO from non-existent (0.0) to severe (3.0) to mimic a pheochromocytoma.

REMASS - Anatomical nephrectomy, the removal of a fraction of working kidney, can be studied by reducing the working renal mass from its normal full value (REMASS = 1.0) anywhere down to total nephrectomy (REMASS = 0.0). The later will yield full-blown classic uremic syndrome symptoms in HUMAN.

 

RENDIS - simulates renal disease as a reduction of functional renal mass ranging from none (RENDIS =0.0) to severe (RENDIS=4.0). Larger values of renal disease settings tend to induce a progressive deepening of its severity.

 

Finally, a reminder. The list above is by no means exhaustive of the routes of inducing physiologic pathology in HUMAN but rather covers only some of the more explicitly pathologic inducers.

Pharmacy
This version of HUMAN contains a limited pharmacy (but no co-pays!) the contents of which (see below) can be viewed via selecting the <Patient Charts> option and rolling down to the Pharmacy choice.

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Use of each drug is turned on via changing the variable corresponding to it via the <Change Variable> option from zero to the desired dosage. Note that doses are either one time or continuous as indicated.

A list of pharmacy drugs and some additional 'hidden' drugs follows.

I. Pharmacy drugs

• ATROP - Administers a single dose Atropine, a parasympathetic post-ganglionic blocker in an intramuscular (I.M.) dose ranging from 0.0 (the default) to 0.5 mg/kg.
• CHLORO - Administers Chlorothiazide, one of the thiazide diuretics, continuously in user specified doses ranging from 0.0 to 1000 mg/day. Note that continuous dosage requires user intervention to be turned off.
• CEI - Administers a converting enzyme (ACE) inhibitor continuously in doses from 0.0 to 600 Mg./day. ACE inhibitors block the conversion of the decapeptide angiotensin I to the octapeptide angiotensin II which occurs in the lung. This blockage will decrease both the vasoconstrictor effect of ANGIO II and its stimulation of adrenal aldosterone (ALDO).
• DIGIT - Administers Digitalis, a cardiotonic cardiac glycoside, continuously in doses from 0.0 to 0.5 mg/day. Try this in HUMAN for decompensated heart disease induced perhaps by coronary artery disease (CAD), myocardial infarction (RMIB, LMIB) or reductions in cardiac strength of contraction (RHSB, LHSB).
• FUROSE - Administers a single dose (range: 0.0 - 80 mg.) of Furosemide, a 'loop' diuretic, intravenously.
• HYDRAL - Administers a continuous dose of Hydralazine in amounts ranging from 0.0 to 75.0 mg/day. Hydralazine (e.g. APRESOLINE) causes direct relaxation of arteriolar smooth muscle. The drug has no direct effect on capacitance vessels.
• NOREPI - Administers Norepinephrine (Noradrenaline) in user selectable doses ranging from 0.0 to 50 mcg/min.. Infusion is neither one time nor continuous but rather is controlled by a second parameter, NORMIN (see directly below).
  NORMIN - Sets the duration of a Norepinephrine (NOREPI) infusion ( in minutes ). Must be set to > 0 min. to activate an infusion.
• NITRO - Administers a single Nitroglycerin dose in amounts up to 1.0 mg as needed. Nitroglycerin is HUMAN's coronary vasodilator and is a reasonable choice in response to a prompt of cardiac angina from the model.
• PHOXY - Administers Phenoxybenzamine, an alpha adrenergic blocker that in the model blocks sympathetic vascular effects, in doses of between 0 to 60.0 mg/day. The dosing is continuous and is therefore administered until PHOXY is reset to 0.0. May be tried as a general anti-hypertensive or in managing specific pathologies such as a pheochromocytoma (PHEO), an adrenal tumor that oversecretes sympathomimetic substances.

II. Additional non-pharmacy "drugs"
This version of HUMAN also contains several additional pharmaceutical-like interventions, as a glance through the variables list reveals. Some of these are noted below.

• A2INF - Angiotensin II Infusion ( 0.0 to 100.0 ng/kg/min. )
• ADHB - the basic level of secretion of posterior pituitary anti-diuretic hormone, ADH (1.0 X Normal).
• ALDOB - the basic level of secretion of the mineralocorticoid Aldosterone ( 8.0 ng/dl ).
• SYMCL - The sympathetic output can be set by the user at desired fixed levels by
  1) Setting the sympathetic switch SYMSW to 1.0 from its default value of 0.0. This activates user control of the sympathetics and abolishes normal model reflex sympathetic responses. For example, expect possible orthostatic hypotension (and fainting) upon changing from prone to upright (see UP) position with SYMSW set to user control.
  2) Setting the sympathetic clamp level SYMCL to the desired level (default clamped sympathetic level = 1.0 x normal).
• THY - Sets the level of Thyroxine Secretion (100.0 ng/min . = default value). [ Note that hypothalmic target temperature (TEMSET) must be set separately to fully simulate a hyperthyroid state].

Transfusions
HUMAN allows for blood transfusions of a user selectable volume delivered over a user selectable period of time. Transfusion hematocrit can also be controlled. The three variables controlling blood transfusion are

• TRNVOL - the total volume of the transfusion in ml.
• TRNMIN - the total transfusion time span (minutes).
• TRNHCT - the hematocrit (%) of the transfusion.

Transfusions offer a wide variety of possibilities. For example

• experiment with blood doping the model by transfusion high HCT blood and then assess the effects of the extra O2 carriage on exercise duration.
• use transfusions to support 'hypovolemic' situations (try patient #1).

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 Urine collection (24 hours or specimen)

A 24 urine collection can be initiated by setting the parameter switch U24 from its default value of 0.0 ( = No) to 1.0 ( = do it). This initiates the collection. Values generated by the collection can then be read out 24+ hours later.

- Under the Patient Charts option, roll down to select the option <24 hr Urine Collection> and values will be shown for the following:

24-Hour Urinary Potassium ( 42.0 mEq/L )
24-Hour Urinary Sodium ( 118.0 mEq/L )
24-Hour Urine Osmolarity ( 760.0 mOs/L )
24-Hour Urinary Protein ( 0.035 g/dl )
24-Hour Urine Volume ( 1440.0 ml )

An on-the-spot urine specimen can be initiated as follows:

- Under the Patient Charts option, roll down to select the option <Urine Specimen > and values will be shown for the following:

Urine Potassium ( 42.0 mEq/L )
Urine Sodium ( 118. mEq/L )
Urine Osmolarity ( 760.0 mOs/L )
Urine pH (7.1 pH Units)
Urine Protein (0.035 g/dl)

(Average normal values are indicated in parenthesis)

References

[ We would like to thank Dr. Coleman for generously releasing the HUMAN code for use in web-HUMAN and Dr. Randall for his kind words of encouragement ].

1) HUMAN - Physiological Basis of A Comprehensive Model For Body Function - 1981 Version. Thomas G. Coleman.

2) HUMAN - FORTRAN Source Code and Comments. Thomas Coleman - 1979 Version.

3) HUMAN - 80 - Microcomputer Version of A Mathematical Model ... (1981-7)

Instructor's Manual Thomas Coleman and James E. Randall

Physiological Basis of A Comprehensive Model For Body Function Thomas Coleman

Student's Manual Thomas Coleman and James E. Randall

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