The hemodynamic and embolizing forces acting on thrombi--II. The effect of pulsatile blood flow

A previous analysis (Basmadjian, J. Biomechanics 17, 287-298, 1984) of the embolizing forces acting on thrombi in steady Poiseuille flow has been extended to pulsatile blood flow conditions in the major blood vessels. We show that for incipient and small compact thrombi up to 0.1 mm height, the maximum embolizing stresses can be calculated from the corresponding 'quasi-steady' viscous drag forces and measured maximum wall shear. Their magnitude is from 5 to 30 times (tau w)Max, the maximum wall shear stress during the cardiac cycle in the absence of thrombi. For larger thrombi, inertial and 'history' effects have to be taken into account, leading to embolizing stresses in excess of 100 Pa (1000 dyn cm-2).     

Carotid sinus, aortic and subclavian baroreceptor activities during cardiopulmonary bypass in rabbits.

10Carotid sinus (SIN), aortic (AO) and subclavian (SUB) baroreceptor activities were recorded from intact nerves during experiments using cardiopulmonary bypass in 11 rabbits. These activities (number of impulses/second) were expressed as a percentage of basal activity observed before artificial circulation (AC). The preparation remained in a relative, "stable period" for up to 45 minutes. Then, a progressive decrease occurred in maximal arterial pressure (AP max) in the 11 experiments (fig. 2,4). 20 According to the level of arterial pressure the "stable period", our experiments can be divided into two groups: a) Group I (6 rabbits) with AP max greater than or equal 90 mm Hg; in this group, the correlation coefficients between pressure levels and nervous activities calculated during the period 0-70 min after the onset of AC, were positive (fig. 3) and statistically significant, as we could expect (AO, p less than 0.02; SIN, p less than 0.01; SUB, p less than 0.01). b) Group II (5 rabbits) with AP max less than 90 mm Hg; surprisingly, in this group no positive correlation was found between levels and nervous activities, which were generally very high (fig. 5). 30 Experiments were performed in 18 other rabbits in order to check the nature of the higher activities recorded in group II. These high activities were not of chemoreceptor or efferent origin, and, thus, were thought to be indeed really from baroreceptive fibres. 40 Ten experiments under AC were carried out to test the reactivity of baroreceptors in response to induced increase and decrease of pressure. The responses were qualitatively normal (i.e. an increase of pressure produced an increase in the nervous discharge), but in group II, the operative point was set at a higher level (fig. 6). 50 A possible, time-dependent, shift in the baroreceptor response curve under AC can account for these findings by giving, in some cases the illusion of a negative correlation between baroreceptor activity and arterial pressure (fig. 8). 60 The above mentioned shift in the baroreceptor response curve could be related to a change in sympathetic control of baroreceptors,resulting in a higher activity, and initiating and/or maintaining hypotension.     

Normalization of nitric oxide flux improves physiological parameters of porcine kidneys maintained on pulsatile perfusion.

Early endothelial damage and resultant reduction in the beneficial production of nitric oxide (NO) derived from the endothelial NO synthase (eNOS) are phenomena associated with the functional degradation of transplanted kidneys. In contrast, the inflammation characteristic of kidney preservation leads to the later, detrimental expression of the inducible NO synthase (iNOS). We reasoned that provision of low-level NO (to compensate for lack of eNOS) using the chemical NO donor S-nitrosoglutathione (GSNO), along with an iNOS inhibitor (N-omega iminoethyl-L-lysine; L-NIL), might "normalize" NO levels and therefore be beneficial in maintenance of flow. Non-heartbeating donor porcine kidneys were subjected to 30-45 min warm ischemic time and stored from 3 to 30 h, simulating the time required for national sharing. The kidneys were then machine preserved with Belzer MPS (BMP) at a set systolic pressure of 40 mmHg. Eight kidneys were perfused for 5h with BMP only (Group 1 control), 8 kidneys with BMP+GSNO only (Group 2), and 8 kidneys with BMP+GSNO+L-NIL (Group 3). Lower vascular resistance (VR) is a predictor of improved end-organ function. Both Group 2 and 3 kidneys demonstrated statistically significant reduction in VR as compared to Group 1 kidneys, with Group 3 kidneys demonstrating a greater drop in VR than Group 2. Reduced oxygen saturation suggests a higher metabolic rate. Only Group 3 had lower oxygen saturation as compared to Group 1. Increased Ca2+ concentration in the perfusate is a predictor of worse end-organ function. Group 2, but not Group 3, had a higher perfusate Ca2+ concentration than Group 1. The combination of suppression of harmful amounts of NO, while supplying a constant low-level amount of NO, may improve pulsatile kidney preservation.     

The effect of different gas mixtures under increased pressure on the self-stimulation reaction of rabbits]

Self-stimulation of rabbits in heliox at high pressure was decreased. That effect was potentiated by rapid compression. Addition of 2% or 6% nitrogen to heliox exerted no influence on the self-stimulation behavior.     

The effect of nicotine on in vitro placental perfusion pressure

Cigarette smoking throughout pregnancy is associated with several negative outcomes, of which an increased incidence of intra-uterine growth restriction (IUGR) is most pronounced. Gestationally age-matched infants born to smoking mothers are, on average, 200 g lighter at birth, per pack smoked per day. The mechanisms and specific tobacco compounds responsible for the increased risk of IUGR among smokers have yet to be identified; however, it is widely accepted that smoking women have compromised placental perfusion throughout gestation due to the vasoconstricting effect of nicotine on uterine and placental blood vessels. Despite the universal acceptance of this theory, very little work has been completed to date examining the vasoactive properties of nicotine within the human placenta. The objective of this study was to determine the effect of nicotine on placental vascular function. Normal-term human placentae were obtained after elective cesarean sections. An in vitro placental perfusion system was used; increasing doses of nicotine (20-240 ng/mL) were added to either the maternal (n = 5) or fetal (n = 3) circulation. The basal feto-placental perfusion pressure was 39.87 +/- 4.3 mmHg and was not affected by nicotine. This finding supports the hypotheses that nicotine does not directly affect placental microvascular function and that any contribution to fetal growth restriction is likely at the level of placental function (i.e., amino acid transport) and (or) uterine vascular function.     

Effects of essentiale forte on biosynthesis of nucleic acids and several hemodynamic parameters of the damaged myocardium in rabbits

Normalization of heart muscle phospholipid metabolism and reactivation of the activity of membrane-bound enzymes participating in the reactions of biosynthesis of nucleic acids have been studied. These investigations were carried out under the conditions of experimental myocardial infarction. The effects of essential forte have been examined when it was combined with both a tocopherol, and sodium nucleinate. It was pointed out that essential forte using without other reagents leads to the depression of nucleic acids biosynthesis in affected heart muscle, while the combinations of it with a-tocopherol, and especially with sodium nucleinate are accompanied by the significant intensification of reactions of formation of desoxynucleic and ribonucleic acids biosynthesis in necrotic areas as well as in peripheral regions of affected myocardial tissue. These positive changes are accompanied also by the pronounced normalization of haemodynamic activity of infarcted myocardium.     

Use of cardiopulmonary bypass, hypothermic perfusion, and circulatory arrest in the surgical management of basilar artery aneurysm

Two cases of intracranial aneurysm are discussed in relation to surgical management. The superiority of vena cavae/ascending aorta to femoral vein/femoral artery cannulation is indicated, thus minimizing ventricular fibrillation and myocardial damage.     

Changes in alpha-tocopherol and retinol levels during cardiopulmonary bypass correlate with maximal arterial partial pressure of oxygen

Cardiopulmonary bypass (CPB) is associated with oxidative stress. This study examined antioxidant levels in adults undergoing CPB surgery and their correlation with clinical variables. Arterial blood samples were obtained from 27 patients undergoing CPB. The time-course variation of vitamin C (spectrofluorimetry), alpha-tocopherol and retinol (HPLC) levels were determined. Plasma vitamin C rose initially but gradually decayed during reperfusion until 60% reduction of baseline values post-surgery. alpha-Tocopherol and retinol were reduced along CPB with post-operative values approximately 25% lower than baseline. No significant changes were found for selenium and glutathione peroxidase. PaO(2) values rose steadily throughout CPB. A correlation existed for alpha-tocopherol and retinol depletion vs maximal PaO(2) throughout CPB but no correlation was found for antioxidant consumption vs duration of ischaemia and reperfusion and hypothermia level. In conclusion, consumption of arterial blood antioxidant vitamins occurs with CPB in relation with PaO(2) levels but not for other clinical variables measured in this study.     

Induction of aquaporin-1 mRNA following cardiopulmonary bypass and reperfusion.

BACKGROUND: Cardiopulmonary bypass (CPB) and hypothermic circulatory arrest (HCA) are important components of congenital cardiac surgery. Ischemia/reperfusion injury and inflammatory cascade activation result in endothelial damage and vascular leak which are clinically manifested as pulmonary edema and low cardiac output postoperatively. Newborns are particularly susceptible. Subtraction cloning is a useful method of isolating induced genes and can be applied to CPB/HCA. MATERIALS AND METHODS: We used a newborn lamb model replicating infant CPB with HCA to obtain tissues during various periods of reperfusion. We utilized subtraction cloning to identify mRNA induced in lung following CPB/HCA and reperfusion. Ribonuclease protection was used to quantify mRNA levels. RESULTS: We isolated a cDNA encoding ovine aquaporin-1 in a subtracted cDNA screen comparing control lung with lung exposed to CPB/HCA and reperfusion. Aquaporin-1 mRNA levels increased 3-fold in lung (p = .006) exposed to CPB/HCA and 6 hr of reperfusion. No induction was observed immediately following bypass or after 3 hr of reperfusion. We found no significant induction of aquaporin-1 mRNA following bypass, arrest, and reperfusion in other tissues surveyed, including ventricle, atrium, skeletal muscle, kidney, brain, and liver. CONCLUSIONS: Our finding that aquaporin-1 mRNA is reproducibly induced in lung following CPB/HCA with 6 hr of reperfusion suggests an important role for the water channel in the setting of pulmonary edema. Induction of Aquaporin-1 is late compared with other inflammatory mediators (ICAM-1, E-selectin, IL-8). Further studies are needed to determine if aquaporin-1 contributes to the disease process or if it is part of the recovery phase.     

Changes in urinary thromboxane level in man during cardiopulmonary bypass: effect of thromboxane on renal tubules

ONO-3708, a thromboxane A2 (TXA2) antagonist, was administered at a dose of 2 micrograms/kg/min by a double blind method as compared with inactive placebo during cardiopulmonary bypass (CPB) procedure to study the changes of thromboxane B2 (TXB2) levels in plasma and urine and N-acetyl-glucosaminidase (NAG) level in urine. TXB2 levels in plasma and urine increased significantly (P less than 0.01) during CPB in the patients given ONO-3708 (ONO-3708 group) and in those given placebo (placebo group). The plasma TXB2 level as expected from the urinary TXB2 level was higher than the measured plasma TXB2 level showing increases in TXB2 originating from the kidney. The urinary NAG level, increased significantly (P less than 0.01) during CPB the NAG level in ONO-3708 group was significantly low as compared to placebo group. The levels of TXB2 in plasma and urine in ONO-3708 group were not different from those of the patients receiving placebo, indicating that ONO-3708 does not have any effect on TXA2 production. We concluded that the elevation of urinary TXB2 level might be due to increased TXA2 production in the kidney under hypoxic condition induced by hypotension and lowered perfusion during CPB. Furthermore, the increased production of TXA2 appears to suppress the functions of the renal proximal tubules.     

The effect of methylprednisolone on cytokine concentration and leukocyte adhesion molecule expression in an isolated cardiopulmonary bypass system

This study examines the effect of methylprednisolone on cytokine balance and adhesion molecule expression within an isolated cardiopulmonary bypass (CPB) system. This isolated CPB system is an in vitro model which simulates the pro-inflammatory immune response. Whole blood from 10 volunteers was obtained in two equal amounts. Heparin and saline were added to the control group while heparin and methylprednisolone were added to the methylprednisolone group. The blood was added to two identical CPB circuits and bypass commenced by a trained perfusionist. Samples were taken at blood donation (Sample 0), 10 min after the addition of drugs (Sample 1) and after 30, 60 and 90 min of CPB (Samples 2, 3 and 4, respectively). Cytokines interleukin-8 (IL-8), interleukin-10 (IL-10), interleukin-1 receptor antagonist (IL-1ra) and tumour necrosis factor soluble receptor 2 (TNFsr2) and the leucocyte adhesion molecules L-selectin, HLA DR, CD18 and CD11b were determined. IL-8 increased in both groups. This increase was significantly less in the methylprednisolone group. Increases in granulocyte CD11b and CD18 expression were less in the methylprednisolone group than in the control group but did not reach statistical significance. These results indicate that methylprednisolone significantly reduces the production of IL-8 in an isolated CPB system. This effect occurs in the absence of IL-10.     

Pulsatile flow through a constricted tube: effect of stenosis morphology on hemodynamic parameters

In this paper, we investigate pulsatile flow through a constricted tube with the aim of assessing the effect of stenosis morphology on hemodynamic parameters. The fluid-solid interaction of pulsatile flow through a compliant tube with elastic walls was simulated using an arbitrary Lagrangian-Eulerian (ALE) finite-element method. We consider blood flow through various mild stenoses of 25.8% severity in diameter with trapezoidal and bell-like morphologies at a fixed Womersley number of 7.75. The results show that the distribution of the time-averaged wall shear stress (TAWSS), which is the main factor affecting the hemodynamic parameters, strongly depends on the axial stretch of the stenosis; elongation of the stenotic region increases by 41.1% the maximum TAWSS for stenoses of trapezoidal morphology whereas the maximum TAWSS decreases by 14.8% for the corresponding stenoses of bell-like morphology. The present findings indicate that risk factors due to atherosclerosis may vary in a complicated manner as an atheromatous plaque gradually builds up and morphs with time.     

Systemic hemodynamic and regional blood flow changes in response to chronic reductions in uterine perfusion pressure in pregnant rats

Preeclampsia (PE) is associated with increased total peripheral resistance (TPR), reduced cardiac output (CO), and diminished uterine and placental blood flow. We have developed an animal model that employs chronic reductions in uterine perfusion pressure (RUPP) in pregnant rats to generate a "preeclamptic-like" state during late gestation that is characterized by hypertension, proteinuria, and endothelial dysfunction. Although this animal model has many characteristics of human PE, the systemic hemodynamic and regional changes in blood flow that occur in response to chronic RUPP remains unknown. Therefore, we hypothesized that RUPP would decrease uteroplacental blood flow and CO, and increase TPR. Mean arterial pressure (MAP), CO, cardiac index (CI), TPR, and regional blood flow to various tissues were measured using radiolabeled microspheres in the following two groups of conscious rats: normal pregnant rats (NP; n = 8) and RUPP rats (n = 8). MAP was increased (132 +/- 4 vs. 99 +/- 3 mmHg) in the RUPP rats compared with the NP dams. The hypertension in RUPP rats was associated with increased TPR (2.15 +/- 0.02 vs. 0.98 +/- 0.08 mmHg x ml(-1) x min(-1)) and decreased CI (246 +/- 20 vs. 348 +/- 19 ml x min(-1) x kg(-1), P < 0.002) when contrasted with NP dams. Furthermore, uterine (0.16 +/- 0.03 vs. 0.38 +/- 0.09 ml x min(-1) x g tissue(-1)) and placental blood flow (0.30 +/- 0.08 vs. 0.70 +/- 0.10 ml x min(-1) x g tissue(-1)) were decreased in RUPP compared with the NP dams. These data demonstrate that the RUPP model of pregnancy-induced hypertension has systemic hemodynamic and regional blood flow alterations that are strikingly similar to those observed in women with PE.     

The effect of surgery with cardiopulmonary bypass on oxygen transport in elderly patients with ischemic heart disease

In a clinical trial, 103 patients undergoing coronary artery bypass grafting from May, 1999, to December, 2001 with hypothermic cardiopulmonary bypass (CPB) were retrospectively assigned to one of two groups: group I (n = 45)--patients 65 years of age and older (68.0 +/- 0.5), group II (n = 58)--patients 45-50 years of age (48.2 +/- 0.2). The following parameters were recorded: haemodynamic--with thermodilution method (SMU--612, Hellige), blood gases (OMNI-6, Austria). Measurements were performed 7 times: (1) before surgery, (2) before CPB, (3) after CPB, (4, 5, 6, 7)--1, 3, 9, 12 hours after surgery. Indexes of oxygen delivery and consumption, oxygen utilization coefficient and anion gap were calculated. Obtained results were statistically analyzed using appropriate t-test and chi2-test for categorical variables. Data are expressed as mean +/- SE. There were no significant differences between the groups in all stages of examination, p > 0.05. In elderly group both oxygen delivery and consumption were lower then in younger one, thus the coefficient of oxygen utilization did not differ between groups. Therefore the surgery with CPB seems to be inrelated to adverse changes on oxygen transport in elderly patients, and its dynamic was similar in patients over 65 years of age and younger group.