Tissue Perfusion: Discovery, Measurement, Physiology, Drug Optimization, Regulation and Therapy

The word is derived from the French verb “perfuser” which means “to pour over or to pass through.” All animal tissues require an adequate blood supply for health and life.

Infusion

Perfusion is the passage of fluid through the circulatory or lymphatic system into an organ or tissue, which generally refers to the supply of blood to a capillary bed in the tissue.

Perfusion is measured as the rate at which blood is delivered to the tissue, or the volume of blood per unit time (blood flow) per unit mass of tissue. The international system of unit is m3 / (s · kg), although for human organs perfusion is generally reported in ml / min / g.

Poor perfusion (malperfusion), that is, ischemia, causes health problems, as seen in cardiovascular disease, including coronary artery disease, cerebrovascular disease, peripheral arterial disease, and many other conditions.

Testing for adequate perfusion is part of the patient assessment process performed by medical or emergency personnel. The most common methods include assessing the body’s skin color, temperature, condition (dry / soft / firm / swollen / sunken / etc.), And capillary filling.

During major surgery, especially cardiothoracic surgery, the perfusion must be maintained and managed by the healthcare professionals involved, rather than leaving it alone in the homeostasis of the body .

As lead surgeons are often too busy to handle all hemodynamic control on their own, specialists called perfusionists handle this issue. There are more than one hundred thousand infusion procedures a year.

Discovery

In 1920, August Krogh was awarded the Nobel Prize in Physiology or Medicine for his discovery of the mechanism of regulation of capillaries in skeletal muscle.

Krogh was the first to describe the adaptation of blood perfusion in muscles and other organs according to demands through the opening and closing of arterioles and capillaries.

Malperfusion

Malperfusion can refer to any type of incorrect perfusion, although it generally refers to hypoperfusion. The meaning of the terms “hyperfusion” and “insufficient infusion” is relative to the average level of perfusion that exists in all tissues of an individual body. The following examples:

The tissues of the heart are considered overperfused because they normally receive more blood than the rest of the body’s tissues; they need this blood because they are constantly working. In the case of skin cells, the extra flow of blood in them is used for thermoregulation of a body.

In addition to supplying oxygen, blood flow helps dissipate heat in a physical body by redirecting warm blood closer to its surface where it can help cool the body through sweating and heat dissipation.

Many types of tumors, and especially certain types, have been described as “hot and bloody” due to their hyperfusion relative to the body as a whole.

Overperfusion and underperfusion should not be confused with hypoperfusion and hyperperfusion, which are related to the level of perfusion in relation to the current need for a tissue to meet its metabolic needs.

For example, hypoperfusion can be caused when an artery or arteriole supplying blood to a volume of tissue becomes blocked by an embolus, causing either no blood or at least not enough blood reaching the tissue.

Hyperperfusion can be caused by inflammation, producing hyperemia of a part of the body. Malperfusion, also called poor perfusion, is any type of incorrect perfusion.

There is no official or formal dividing line between hypoperfusion and ischemia ; Sometimes the last term refers to zero perfusion, but often it refers to any hypoperfusion that is severe enough to cause necrosis.

Measurement

In equations, the symbol Q is sometimes used to represent perfusion when referring to cardiac output.

However, this terminology can be a source of confusion as both cardiac output and the symbol Q refer to flow (volume per unit time, for example L / min), while perfusion is measured as flow per unit. tissue mass (ml / (min · gram)).

Microspheres

Microspheres that are labeled with radioactive isotopes have been widely used since the 1960s. Radioactively labeled particles are injected into the test subject and a radiation detector measures the radioactivity in the tissues of interest.

The application of this process is used to develop radionuclide angiography, a method of diagnosing heart problems.

In the 1990s, methods of using fluorescent microspheres became a common substitute for radioactive particles.

Nuclear medicine

The perfusion of various tissues can be easily measured in vivo with nuclear medicine methods that are primarily positron emission tomography (PET) and single photon emission computed tomography (SPECT). Several organ-targeted radiopharmaceuticals are also available, some of the most common being:

  • 99mTc labeled hexamethylpropyleneamine oxime or HMPAO and ethylene cysteine ​​dimer for cerebral perfusion (regional cerebral blood flow) studied with single photon emission computed tomography.
  • 99mTc labeled Tetrofosmin and Sestamibi for myocardial perfusion imaging with single photon emission computed tomography.
  • 133 Xe-gas for the absolute quantification of cerebral perfusion (regional cerebral blood flow) with single photon emission computed tomography.
  • 15O labeled water for cerebral perfusion (regional cerebral blood flow) with positron emission tomography (absolute quantification is possible when arterial radioactivity concentration is measured).
  • 82Rb-chloride to measure myocardial perfusion with positron emission tomography (absolute quantification possible).

Magnetic resonance imaging

Two main categories of magnetic resonance imaging (MRI) techniques can be used to measure tissue perfusion in vivo.

The first is based on the use of an injected contrast agent that changes the magnetic susceptibility of the blood and therefore the MR signal that is repeatedly measured during the bolus passage.

The other category is based on arterial spin labeling (ASL), where arterial blood is magnetically marked before entering the tissue under examination and the amount of marking that is measured and compared to a control record obtained without labeling. .

Computed tomography

Brain perfusion (more correct transit times) can be estimated with a contrast-enhanced CT scan.

Thermal diffusion

Perfusion can be determined by measuring total thermal diffusion and then separating it into thermal conductivity and perfusion components. Regional cerebral blood flow is generally measured continuously over time. It is necessary to stop the measurement periodically to cool down and re-evaluate the thermal conductivity.

Physiology of tissue perfusion

Sufficient tissue perfusion and oxygenation are vital for all metabolic processes in cells and the main factor influencing tissue repair and resistance to infectious organisms.

The concept of tissue perfusion has been affected by blood flow, oxygen supply, or a combination of flow and nutritional supply that includes oxygen.

A concept that encompasses both the delivery of oxygen, the transport of oxygen in the tissue, and the consumption of oxygen by the cells could be called tissue oxygen perfusion. This concept could be useful for clinicians describing tissue perfusion and oxygenation of the patient.

Tissue perfusion should be assessed at the local tissue level. A single fabric that represents the situation in all tissues of the body and is readily available for measurements would be ideal.

Subcutis and mucosa of the gastrointestinal tract are such tissue types. Many monitoring systems are available to measure tissue perfusion and oxygenation.

However, only the measurement of tissue oxygen tension and the pH of the gastrointestinal mucosa meet the criteria for tissue oxygen perfusion. Future evaluation of tissue perfusion will be of critical importance to the outcome of medical treatment.

At present, measurements of oxygen tension in tissues and in intensive care units, also the pH of the gastrointestinal mucosa, appear to be the best clinically available monitoring systems for this purpose.

Pharmacological optimization of tissue perfusion

Optimizing tissue perfusion does not simply mean improving blood pressure, cardiac output, or both, but rather delivering oxygen from the lungs to the mitochondria in adequate amounts to maintain the required metabolism.

However, the wide range of available therapeutic options and hemodynamic end points, as well as a relative paucity of convincing evidence for best practice, generates passionate debate and a variety of management ploys.

Outside of the cardiac arrest / arrhythmia scenario, fluid resuscitation is universally accepted as the usual first step in hemodynamic optimization. However, the choice of liquid remains highly controversial.

The monitoring modality is related to tools that can assess cellular well-being. This is the Holy Grail of tissue perfusion monitoring, however responses in different organ beds do vary.

Specific biochemical markers are released in organ damage, such as troponin or B-type natriuretic peptide for the myocardium, and a variety of biomarkers for the kidney, including urinary interleukin-18, plasma cystatin C, and plasma neutrophil gelatinase-associated lipocalin and urine.

At present, plasma lactate, arterial base deficit, and mixed venous oxygen saturation are the only biomarkers of whole-body tissue perfusion, and these are not particularly specific or, in some situations, sensitive.

For example, hyperlactatemia may represent exaggerated aerobic glycolysis with excessive pyruvate production stimulated by endogenous or exogenous catecholamines.

Therefore, a high lactate level should not automatically be considered an indicator of a tissue oxygen debt requiring an increase in systemic oxygen transport.

Regulation of tissue perfusion by microcirculation

In addition to providing the large surface area necessary for blood-tissue exchange, microcirculation largely controls tissue perfusion in response to varying metabolic requirements.

Microcirculation largely determines local and general peripheral resistance. The precapillary elements of microcirculation also protect fragile capillaries from potentially damaging pressures that occur in larger arteries.

Tissue perfusion in hypertension

A sudden increase in pressure produces a rapid and reversible vasoconstriction of small resistance vessels due to their inherent myogenic tone.

Prolonged elevations in pressure can cause a range of more lasting changes in microcirculation, 2 of which remodeling of small arteries and arterioles and rarefaction of arterioles and capillaries.

In its simplest form, microvascular remodeling and rarefaction could be predicted to reduce tissue perfusion and prevent blood tissue exchange.

Not only does rarefaction reduce the surface area available for exchange, it also increases the distance between capillaries and target cells through which diffusion must occur.

Therefore, one might expect that these processes could lead to inadequate perfusion and tissue hypoxia in situations of high metabolic demand, and modeling studies have confirmed this possibility.

There is experimental evidence that hypertension-related microvascular abnormalities can lead to impaired oxygenation in active skeletal muscle sufficient to reduce muscle performance.

Tissue perfusion in diabetes mellitus

Reducing inflammation and improving tissue perfusion may become important therapeutic targets in preventing disease progression and complications in diabetes.

Organ damage, complications and prognosis

Impaired tissue perfusion due to abnormality of the microvascular system is common among conventional cardiovascular risk factors, including hypertension, diabetes, obesity, and dyslipidemia.

Microvascular abnormalities leading to impaired tissue perfusion appear to represent a generalized condition that affects multiple tissues and organs.

For example, in hypertension, the coronary flow reserve is correlated with the media: the ratio of the lumen of the small arteries in biopsies of subcutaneous fat.

The dilation of the venules in the retina independently predicts the progression of cerebral small vessel disease, and in diabetes, the reduction of the coronary flow reserve predicts the development of retinopathy.

The alteration of tissue perfusion may be related to organ damage and complications involving various vascular beds.

For coronary microcirculation, an obvious example associated with hypertension and diabetes is the occurrence of myocardial ischemia and angina in the presence of angioscopically normal epicardial coronary arteries, also known as cardiac syndrome X.

Impaired myocardial perfusion can also be an important factor in the development of hypertensive heart failure and can lead to localized ischemia and disturbed patterns of electrical activity that constitute a substrate for severe arrhythmias.

In the case of kidney disease, glomerular and peritubular capillary rarefaction has been observed in different animal models and in human progressive kidney disease, and precedes the development of impaired perfusion and chronic hypoxia.

It has been suggested that hypoxia may be the common factor linking many forms of progressive kidney disease.

Combination therapy

The combination whose effects on tissue perfusion have been studied the most extensively is a low-dose combination of the angiotensin converting enzyme inhibitor (ACE inhibitor) perindopril and the diuretic indapamide.

Lifestyle changes can also improve tissue perfusion. Regular exercise reduces the levels of pro-inflammatory mediators, including TNF-α.90, and increases the capillary density of skeletal muscle.