Hg Transmural Pressure Research Articles

Effect of shear stress and of transmural pressure on cAMP-dependent responses of cells adhering to a biomaterial

Biomaterials used in some bioreactors are porous and exposed to normal and tangential flow of physiological fluid. Flow-induced forces may influence the morphological and biochemical responses of cells adhering to these materials. The objective of this work is to examine the capacity of mechanical stress to cause changes in cell morphology via the cAMP pathway (cyclic adenosine monophosphate). This second messenger is known to modulate cell morphology in static conditions. In classical flow devices, cells are submitted to only tangential stresses. We designed a new flow system, a Hele-Shaw cell with a porous bottom wall, in order to take into account the influence of a transmural pressure. This flow chamber allows to follow up continuously the shape changes of cells that are adherent to a porous biomaterial (polyacrylonitrile) and are exposed to controlled levels of shear stress or transmural pressure. Mouse Swiss 3T3 fibroblasts exposed to a 1.1-Pa shear stress, as well as those exposed to a 84-mm Hg transmural pressure, round up (up to 50%) in a few minutes. If the cAMP pathway is inhibited when a mechanical stress is applied, cell rounding is significantly prevented. These observations suggest that flow-induced cell shape changes are cAMP-dependent. This conclusion is supported by an increased cAMP accumulation measured in cells under mechanical stress when compared to static experiments. Our in vitro flow system is thus useful to study the influence of transmural pressure or shear stress on the early morphological and biochemical responses of cells in contact with a biomaterial.

Blockade of angiotensin receptor subtypes in arcuate uterine artery of pregnant and postpartum rats.

During pregnancy, uterine circulation undergoes hypertrophy and hyperplasia. We investigated the effects of angiotensin (Ang) II receptor subtype (AT(1)/AT(2)) blockade on increased responses to the peptide during reversible remodeling of the uterine vasculature in pregnant and postpartum rats. Uterine arcuate arteries were set up in wire myographs for microvessel and submitted to a tension equivalent to 50 mm Hg transmural pressure. Cumulative concentration-response curves to Ang II were measured in the absence and presence of losartan on the same vascular segment. A similar protocol was repeated in the presence of PD 123,319, an AT(2) receptor blocker, again in the absence and presence of losartan. Responses to Ang II on the arcuate artery increased markedly during pregnancy and returned to the prepregnant level within 12 days postpartum. Losartan (10(-7) mol/L) produced a parallel right shift of the concentration-response curve to Ang II in all groups of tissues, but potency of the AT(1) receptor blocker was reduced at the end of pregnancy and in the early postpartum period. PD 123,319 (10(-7) mol/L) significantly increased maximum response to Ang II in arterial segments of the nonpregnant, term-pregnant, and 5 days postpartum rats. AT(1) receptor expression was decreased in arcuate arteries of term-pregnant rats. These results show that contractile responses to Ang II on the uterine arcuate artery of the rat are mediated by the AT(1) receptor and that blockade of AT(2) receptors potentiated responses to the peptide. They also indicate that, in uterine vessels, AT(2) receptor stimulation interferes with Ang II responses, but this effect is decreased in uterine arcuate arteries in the peripartum period.

Endothelium-derived nitric oxide regulates arterial elasticity in human arteries in vivo.

Arterial elasticity is determined by structural characteristics of the artery wall and by vascular smooth muscle tone. The identity of endogenous vasoactive substances that regulate elasticity has not been defined in humans. We hypothesized that NO, a vasodilator released constitutively by the endothelium, augments arterial elasticity. Seven healthy young men were studied. A 20-MHz intravascular ultrasound catheter was introduced through an arterial sheath to measure brachial artery cross-sectional area, wall thickness, and intra-arterial pressure. After control was established, indices of elasticity (pressure-area relationship, instantaneous compliance, and stress-strain, pressure-incremental elastic modulus (E(inc)), and pressure-pulse wave velocity relationships) were examined over 0 to 100 mm Hg transmural pressure obtained by inflation of an external cuff. Thereafter, the basal production of endothelium-derived NO was inhibited by N(G)-monomethyl-L-arginine (L-NMMA) (4 and 8 mg/min). Finally, nitroglycerin (2.5 and 12.5 microgram/min), an exogenous donor of NO, was given to relax the vascular smooth muscle. Elasticity was measured under all of these conditions. L-NMMA (8 mg/min) decreased brachial artery area (P=0.016) and compliance (P<0.0001) and increased E(inc) (P<0.01) and pulse wave velocity (P<0.0001). Nitroglycerin (12.5 microgram/min) increased brachial artery area (P<0.001) and compliance (P<0.001) and decreased pulse wave velocity (P=0.02). NO, an endothelium-derived vasodilator, augments arterial elasticity in the human brachial artery. Loss of constitutively released NO associated with cardiovascular risk factors may adversely affect arterial elasticity in humans.

Theory of the oscillometric maximum and the systolic and diastolic detection ratios.

It is proposed that the maximum in cuff pressure oscillations during oscillometry is due to the buckling of the brachial artery under a cuff. This theory is investigated by means of a mathematical model of oscillatometry that includes the mechanics of the occlusive arm cuff, the arterial pressure pulse waveform, and the mechanics of the brachial artery. A numerical solution is provided for the oscillations in cuff pressure for one cycle of cuff inflation and deflation. The buckling pressure is determined from actual arterial data and the von Mises buckling criteria. The buckling of an artery under a cuff occurs near -2 to 0 mm Hg transmural pressure. This effect corresponds with a maximum arterial compliance and maximum cuff pressure oscillations when cuff pressure is nearly equal to mean arterial pressure (MAP), in support of the suggested theory. The model was also found to demonstrate the basic characteristics of experimental oscillometry, such as an increasing and decreasing amplitude in oscillations as cuff pressure decreases, the oscillations that occur when cuff pressure is above systolic pressure, maximum oscillation amplitudes in the range of 1 to 4 mm Hg, and an oscillatory maximum at cuff pressure equal to MAP. These findings support the case that the model is representative of oscillometry. Finally, the model predicted values for the systolic and diastolic detection ratios of 0.593 and 0.717, respectively, similar to those found empirically. These ratios alter with blood pressure, but the tightness of the cuff wrap did not change their value.

Pressure-diameter curves of mesometrial arteries of guinea pigs demonstrate a non-muscular, oestrogen-inducible mechanism of lumen regulation

Pressure-diameter curves were determined on mesometrial (uterine radial) arteries obtained from guinea pigs during different stages of ovarian cycle and pregnancy. In order to investigate changes in arterial diameter that are not caused by the vascular musculature, we studied excised arteries that were relaxed by papaverine (40 mg/l). The pressure-diameter curves were found to be shifted toward wider diameters when the arteries studied were obtained from pregnant, oestrous or oestrogen treated animals (oestradiol benzoate, 10 micrograms s.c.): the external diameter at 60 mm Hg transmural pressure on the 14th day of pregnancy exceeded the one during dioestrus by 50%. At term, there was a 7-fold increase. During oestrus and 24 h after oestrogen treatment the diameter was 30-40% wider than during dioestrus. Moreover, we found that the diameter measured on excised vessels in the presence of papaverine is the same as the one observed in situ. We conclude that the mesometrial arteries of guinea pigs possess a muscle-independent mechanism of lumen regulation. The mechanism operates in non-pregnant and pregnant animals. It may be induced by oestrogen and seems to be qualified for long-term lumen regulation during pregnancy. In contrast, dilation by smooth muscle relaxation appears to be of minor importance in mesometrial arteries.

Diastolic ventricular properties in patients during coronary revascularization: Intermittent ischemic arrest versus cardioplegia

Left ventricular diastolic properties were examined in 24 patients undergoing coronary revascularization with either 32 degrees C intermittent ischemic arrest (IA) or 4 degrees C potassium cardioplegia (CP) for myocardial protection. The ages, numbers of grafts, and preoperative cardiac function were similar for the two groups of patients. For compliance data, hearts were filled passively during bypass perfusion to diastolic pressures between 0 and 20 mm Hg by clamping the left ventricular vent. Simultaneously, minor axis dimensions were measured with 8 mm epicardial ultrasonic crystals. End-diastolic lengths (EDL), normalized to a Lagrangian strain definition (epsilon), were compared at each pressure (P) by the nonlinear regression equation, P = alpha(e beta epsilon-1). Both elastic constants, alpha and beta, as well as linear regression slopes (k) of pressure-strain data were compared as indices of ventricular stiffness. Prior to determinations, the EDL at 0 mm Hg transmural pressure was defined as l0. At each filling pressure, a leftward shift in the compliance curve developed following IA but not CP. Moreover, shifts in alpha, beta, and k constants occurred with IA alone, l0 did not change in either group. Therefore, stiffening did not occur when CP was used for protection, despite ischemic durations twice those of IA (31 versus 15 minutes). These data confirm CP to be a superior method of cardiac protection during coronary bypass grafting and show diastolic ventricular properties to be a sensitive indicator of subclinical ischemic injury.

Measurement of global ventricular function in patients during cardiac operations using sonomicrometry

In these studies, we evaluated the applicability of pulse-transit sonomicrometry for measuring changes in global cardiac activity in patients during cardiac operative procedures. In six patients two epicardial ultrasonic crystals (8 mm) were sutured across the left ventricular minor axis. Diastolic pressure-length data were recorded as left ventricles were filled passively to transmural pressures (P) from 0 to 20 mm Hg. Data were collected at the beginning of cardiopulmonary bypass and again 15 minutes following periods of induced global ischemia (29.8 +/- 0.8 minutes). Minor axis length data were normalized to Lagrangian strain (epsilon), and best-fit regression curves were obtained from P-epsilon by computer analysis. Nonlinear elastic constants, alpha and beta, were mathematically derived as additional curve descriptors. Decreases in ventricular compliance were demonstrated as leftward shifts in both computed and measured P-epsilon curves. Global ischemia appeared to effect a decrease in overall ventricular diastolic compliance in all patients studied (p =7E 0.01 at 5, 10, 15, 20 mm Hg). Simultaneously, no statistical change occurred in lo (62.93 +/- 2.80 mm), which represented end-diastolic length (EDL) at 0 mm Hg transmural pressure. Following coronary grafting several patients showed augmented systolic excursion when compared at similar EDL. For those analyses, shortening was compared at specific minor axis EDLs rather than filling pressures. These data indicate that experimentally developed sonomicrometry may safely provide accurate indices of systolic and diastolic ventricular properties during operations necessitating cardiopulmonary bypass. Thus various cardioplegic solutions, ischemic arrest periods, and inotropic agents may be evaluated more objectively.