Giuseppe Cicco

Microcirculation and Reperfusion Injury in Organ Transplantation

There are many interesting aspects regarding hemorheology and tissue oxygenation in organ transplantation (such as liver, kidney, heart, etc.). The ischemia-reperfusion injury syndrome is a very important problem. Much damage in organs appears to be induced by reperfusion injury syndrome. In fact, not only immunological etiopathogenesis but also biochemically-mediated microcirculation alterations can modulate the organ damage induced by ischemia-reperfusion injury during organ transplantation. During ischemia-reperfusion injury, xanthine oxidase activity, the increase in oxygen free-radicals, and the activation of neuthrophils are all very important. Platelet activating factor (PAT) and LTB4 (promoting neuthrophils adhesiveness), activated by the xanthine oxidase-derived oxidants during reperfusion, activates the final post-ischemia injury. Much research is necessary in order to gain a fuller knowledge of the microcirculation conditions and oxygenation during organ transplantation.

Wound Healing in Diabetes: Hemorheological and Microcirculatory Aspects

Diabetes is associated with many hemorheological alterations. The decrease of RBC deformability, increase of aggregability, vasoconstriction, increase of blood viscosity and decrease of oxygen supply have a significant effect on wound healing, such as in foot ulcers. Basically, there is endothelial dysfunction and alteration of permeability; these impair wound healing in diabetic patients. Microcirculation still functions and there is blood flow, even when there is a decrease in vessel diameter, without anatomical lesions in vessel walls. It is necessary to maintain a good oxygen supply. Analyzing microcirculation and hemorheology in diabetes and considering methodologies to treat diabetic foot ulcers (e.g., hyperbaric oxygen therapy, laser, and vacuum) may help in the treatment of patient pathologies.

The Influence of Oxygen Supply, Hemorheology and Microcirculation in the Heart and Vascular Systems

The microcirculation is an important system, containing resistance arterioles, capillaries and venules, whose main function is to transport oxygen and nutrients to the tissues. Endothelial cells are the main cell types of the microcirculation; their homeostasis is modulated by constant shear stress. Altered hemorheology induces a change in the production of vasodilator and vasoconstrictor agents. The most important pattern inducing endothelium dysfunction is an increase in oxidative stress, which decreases the amount of nitric oxide and favors microvascular phlogosis. In this review we will consider the main scientific reports about the cardiovascular risk factors such as smoking, hypercholesterolemia, hyperviscosity, hypertension, diabetes, stress and increased homocysteine levels, all having as common etiopathogenetic factor alterations in microcirculation and in tissue oxygenation. We also focus on their influence on endothelial cells, inducing endothelial changes and dysfunction related to altered oxygen supply and linked to increased oxidative stress. Also important are endothelial stem cells, that are able to repair vascular endothelial damage, especially in cardiovascular patients, with or without endothelial dysfunction. Under these circumstances the numbers of these stem cells are altered, which means there is a decrease in regeneration capability (post ischaemia modified albumin, etc.). This could be an important negative prognostic factor. Microcirculation and tissue oxygenation are very important factors strongly linked to hemorheology, especially in cardiovascular patients, and their alterations could cause impairment, or initiate cardiovascular pathologies.

Alteration of Brain Oxygenation During “Piggy Back” Liver Transplantation

Relevant changes in cerebral circulation occur during “Piggy Back” liver transplantation. Particularly at the washout-reperfusion time the cerebral perfusion suddenly changes from its lowest to its highest values. Further investigation is required to evaluate whether patients with the greatest change in cerebral oxygenation at this time point will suffer neurological complications after transplantation.

Laser-Assisted Optical Rotational Red Cell Analyzer (LORCA) in Clinical Practice

Relevant hemodynamic changes in arterial hypertension (i.e. vasoconstriction induced by an organic arterial wall thickening or a functionally induced vasospasm) can lead to increased peripheral resistance. In the microvasculature of hypertensive subjects it is often possible to detect decreased peripheral perfusion together with hemorheological alterations (such as the presence of red blood cell aggregates, decreased erythrocyte deformability). These hemorheological changes can raise blood pressure (increasing the resistance of the blood flow in the microvasculature) and may finally induce a reduction in peripheral tissue oxygenation. These conditions are negatively influenced by lipoido-proteinosis, diabetes and smoking, which very important risk factors in hypertensives for acute myocardial infarction, transient ischemic attack, ictus, and peripheral occlusive arterial disease (Cesarone, 1992; Cicco, 1993, 1998). It has been shown that a good pharmacological control of the blood pressure and the lipoidoproteinosis influence the hemorheological patterns in the microvasculature, improving peripheral perfusion and tissue oxygenation (Cicco, 1994, 1995, 1997).

Could dilated cardiomyopathy alter the peripheral microcirculation and blood rheology

Our aim was to perform a preliminary study of blood flow in the peripheral microcirculation in patients with heart failure. Cardiac patients were investigated to establish possible microcirculatory changes due to this pathology. We evaluated 16 patients (non-smokers, dislipidemic with hypercholesterolemia), receiving oral treatment and in NYHA class 2.3 +/- 0.5. A dilated cardiomyopathy (DCM) group was evaluated before cardiac resynchronization therapy (CRT) obtained by biventricular intra-cardiac defibrillator (ICD) implantation, and again 3 months after its implantation. We measured the ejection fraction (EF), peripheral blood flow (using laser Doppler) at the left wrist on the volar side, capillary morphology (using computerized videocapillaroscopy) on the nail bed of the 4th finger of the left hand, rheological status (using the LORCA), as well as hematocrit, hemoglobin concentration, red blood cell (RBC) surface acetylcholinesterase (AchE), and homocysteine. Our data show that in the DCM vs. control group, peripheral flow did not depend only on the heart: throughout the study, blood flow did not change significantly compared to controls and was increased after CRT. There was no decrease in aggregation time. The blood flow did not alter RBC deformability or RBC surface AchE. Due to the lower oxygenation and to a non-significant increase in the number of capillaries after CRT, DCM patients are at higher cardiovascular risk than healthy subjects.

Microcirculation hemorheology and tissue oxygenation in clinical and experimental practice: CEMOT activity in the last two years.

It is obvious from these results that CEMOT has been a driving force in the development and application of haemorheology in research and clinical practice.

The Effect of Losartan on Red Blood Cell Deformability and Tissue Oxygenation in Patients with Arterial Hypertension

Norepinephrine (NE) plays an important vasoconstrictive role (via postsynaptic alpha-receptors). Parasympathetic cholinergic stimulation induces the release of acetylcholine (Ach) which stimulates the muscarine receptors to inhibit the release of NE modulating vasodilatation in the microvasculature. It is known that Angiotensin II formed following renin stimulation from the kidneys or locally formed is an extremely important vasoconstrictive agent. In fact Angiotensin II induces the release of norepinephrine (NE) from the terminal neurones, it acts directly on Angiotensin II receptors (AT,), and enhances calcium current influx and releases endothelin (ET) from the endothelium (1). These systems influence the peripheral vascular system, inducing a predominantly vasoconstrictive action that can increase blood pressure. Therefore increased peripheral vascular resistance is almost always observed in hypertensive patients.

Post ischemic no-reflow after 60 minutes hepatic warm ischemia in pigs

Prolonged liver ischemia is a frequently required condition in liver surgery. During major resection for cancer or in cases of severe trauma, it may be necessary to interrupt blood inflow or outflow, by clamping the pedicle of Glissons capsule (Pringles maneuver), or even resorting to total vascular exclusion, by clamping the supra and subhepatic inferior vena cava, to limit intraoperative blood loss. Although it is universally acknowledged that the organ can tolerate prolonged ischemia for a period of up to 60 minutes, the anatomical and functional variations of the liver parenchyma inevitably induced by the procedure are receiving ever greater attention. Ischemia-reperfusion damage is also an essential factor during liver transplant and the degree of damage suffered will affect the functional efficiency of the graft. In the present experimental study, the alterations of the liver microcirculation induced by warm ischemia lasting 60 minutes were studied by continuous measurement of the microcirculation with an intraparenchymal probe (Periflux).

Effects of preservation solutions on blood

Celsior solution does not aggregate erythrocytes, whereas Wisconsin solution massively does. This feature could make CS preferable to UW during organ procurement.